bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of venous congestion with venous excess ultrasound score in the prognosis of acute heart failure in the emergency department: a prospective study
Authors: Landi Irene , Guerritore Ludovica , Iannaccone Andrea , Ricotti Andrea , Rola Philippe , Garrone Marco
Published: July 2024

Aims

In acute decompensated heart failure (HF), systemic venous congestion contributes to patients’ symptoms and hospital admissions. The purpose of our study is to determine if venous congestion, examined using the venous excess ultrasound (VExUS) score, predicts HF-related hospitalization and mortality in patients admitted to the emergency department (ED) with acute decompensated HF.

Methods and results

Fifty patients admitted for acute HF in ED underwent ultrasound (US) assessment according to the VExUS score within the first 24 and 72 h. All patients were followed up with a telephone call at 30 and 60 days after hospital discharge. On admission, 56% had a VExUS score of 3. After 72 h, 32% had no more signs of congestion at the Doppler VExUS examination (inferior vena cava < 2 cm, VExUS score of 0); a similar percentage still exhibited a VExUS score of 3 despite therapy. Eighty per cent of patients were hospitalized after admission to the ED, while six (15%) died in-hospital; all exhibited a first-assessment VExUS score of 3. No patient with a VExUS score < 3 died during the study. During short-term follow-up, 18 patients were readmitted to the ED for acute decompensated HF. Ninety-four per cent of the readmitted patients had a VExUS score of 3 at the Doppler assessment at the first ED admission.

Conclusion

Severe venous congestion, defined as a VExUS score of 3 at the initial assessment of patients with acute decompensated HF, predicts inpatient mortality, HF-related death, and early readmission.
Assessing Macroeconomic Tail Risk
Authors: Loria Francesca , Matthes Christian , Zhang Donghai
Published: July 2024

Real gross domestic product and industrial production in the United States display substantial asymmetry and tail risk. Is this asymmetry driven by a specific structural shock? Our empirical approach, based on quantile regressions and local projections, suggests otherwise. We find that the tenth percentile of predictive growth distributions responds between three and six times more than the median to monetary policy shocks, financial shocks, uncertainty shocks, and oil price shocks, indicating a common transmission mechanism. We present two data-generating processes that are capable of matching this finding: a threshold vector autoregression model and a non-linear equilibrium model.
Evaluation of custom-made Relay® stent-grafts for aortic arch landing zones 0 and 1: experience from two high-volume aortic centres
Authors: Dabravolskaite Vaiva , Makaloski Vladimir , Hakovirta Harri , Kotelis Drosos , Schoenhoff Florian S , Lescan Mario
Published: July 2024

OBJECTIVES

To report experience with a Relay® stent-graft custom-made platform in treating different aortic arch pathology in 2 high-volume aortic centres.

METHODS

A retrospective analysis of all patients treated between July 2016 and July 2023 with custom-made Relay® stent-graft (custom-made device). Underlying aortic arch pathology was an aneurysm, penetrating aortic ulcer, and dissection. Three custom-made device designs were used: proximal scallop, fenestrations, and inner branches. The endpoints were technical success, perioperative stroke, death, and reintervention rate.

RESULTS

Thirty-five patients (89% males) with a mean age of 70 ± 11 years were treated.

Indication for treatment was penetrating aortic ulcer in 14 patients (40%), aneurysm in 11 patients (31%) and aortic dissection in 10 patients (29%). The technical success rate was 100%. Twenty-eight patients (80%) had proximal sealing in zone 0, and 7 (20%) had proximal sealing in zone 1. Nine patients (25.6%) had proximal scallops, 9 (25.6%) had 1 big fenestration and 17 (48.8%) had a branched device; 1 with single branch, 15 with double branches and 1 with triple branches. Thirty patients (86%) had previous or simultaneous left subclavian artery revascularization. No patient died during 30 days. Two patients (5.7%) had stroke postoperatively; both recovered without disabling deficits. The mean follow-up was 35 ± 26 months. Six patients (17.1%) died during follow-up. One patient required reinforcement of the bridging stent in the left common carotid artery and one additional vascular plugging of the left subclavian artery. Three patients received distal extension.

CONCLUSIONS

The Relay® stent-graft custom-made platform showed a good performance in our study with a high technical success rate, low perioperative stroke and mortality, and low reintervention rates during the follow-up.
Coronary artery disease management in older adults: revascularization and exercise training
Authors: Pavasini Rita , Biscaglia Simone , Kunadian Vijay , Hakeem Abdul , Campo Gianluca
Published: July 2024

The mean age of patients with coronary artery disease (CAD) is steadily increasing. In older patients, there is a tendency to underutilize invasive approach, coronary revascularization, up-to-date pharmacological therapies, and secondary prevention strategies, including cardiac rehabilitation. Older adults with CAD commonly exhibit atypical symptoms, multi-vessel disease involvement, complex coronary anatomy, and a higher presence of risk factors and comorbidities. Although both invasive procedures and medical treatments are characterized by a higher risk of complications, avoidance may result in a suboptimal outcome. Often, overlooked factors, such as coronary microvascular disease, malnutrition, and poor physical performance, play a key role in determining prognosis, yet they are not routinely assessed or addressed in older patients. Historically, clinicians have relied on sub-analyses or observational findings to make clinical decisions, as older adults were frequently excluded or under-represented in clinical studies. Recently, dedicated evidence through randomized clinical trials has become available for older CAD patients. Nevertheless, the management of older CAD patients still raises several important questions. This review aims to comprehensively summarize and critically evaluate this emerging evidence, focusing on invasive management and coronary revascularization. Furthermore, it seeks to contextualize these interventions within the framework of improved risk stratification tools for older CAD patients, through user-friendly scales along with emphasizing the importance of promoting physical activity and exercise training to enhance the outcomes of invasive and medical treatments. This comprehensive approach may represent the key to improving prognosis in the complex and growing patient population of older CAD patients.
Fronts divide diazotroph communities in the Southern Indian Ocean
Authors: Chowdhury Subhadeep , Berthelot Hugo , Baudet Corentin , González-Santana David , Reeder Christian Furbo , L'Helguen Stéphane , Maguer Jean-François , Löscher Carolin R , Singh Arvind , Blain Stéphane , Cassar Nicolas , Bonnet Sophie , Planquette Hélène , Benavides Mar
Published: July 2024

Dinitrogen (N2) fixation represents a key source of reactive nitrogen in marine ecosystems. While the process has been rather well-explored in low latitudes of the Atlantic and Pacific Oceans, other higher latitude regions and particularly the Indian Ocean have been chronically overlooked. Here, we characterize N2 fixation and diazotroph community composition across nutrient and trace metals gradients spanning the multifrontal system separating the oligotrophic waters of the Indian Ocean subtropical gyre from the high nutrient low chlorophyll waters of the Southern Ocean. We found a sharp contrasting distribution of diazotroph groups across the frontal system. Notably, cyanobacterial diazotrophs dominated north of fronts, driving high N2 fixation rates (up to 13.96 nmol N l−1 d−1) with notable peaks near the South African coast. South of the fronts non-cyanobacterial diazotrophs prevailed without significant N2 fixation activity being detected. Our results provide new crucial insights into high latitude diazotrophy in the Indian Ocean, which should contribute to improved climate model parameterization and enhanced constraints on global net primary productivity projections.
What we know about Turkey oak (Quercus cerris L.) — from evolutionary history to species ecology
Authors: Lados Botond B , Benke Attila , Borovics Attila , Köbölkuti Zoltán A , Molnár Csilla É , Nagy László , Tóth Endre Gy , Cseke Klára
Published: July 2024

Turkey oak (Quercus cerris L.) is a deciduous tree species of the genus Quercus section Cerris (Fagaceae), widely distributed in Europe and Asia Minor. Throughout its vast distribution range, the species carries high phenotypic and genetic variability. Due to its high drought tolerance, Turkey oak may have great potential to be a key tree species in Central and Western Europe under climate change conditions. However, more detailed information on its phylogeny, phylogeography, phenotypic, and genetic variability is still needed for a more careful and reliable assessment of the species’ adaptation potential. To this end, based on 41 reviewed articles, we collected detailed information to support the evaluation of Turkey oak’s adaptation potential under climate change. In the reviewed articles, we observed a significantly lower number of genetic studies of the members of the section Cerris (especially the Euro-Mediterranean species) relative to the subgenus Quercus. We also identified research gaps with respect to the functional and population genetics of the species that should be addressed in the future. Nevertheless, the different evolutionary background and adaptation strategies of Turkey oak as compared to Central European white oaks, as well as its high phenotypic and genetic variability, may indeed represent a great potential for this species to support the climate adaptation of forestry in Central and Western Europe.
Dominant suppressor genes of p53-induced apoptosis in Drosophila melanogaster
Authors: Szlanka Tamás , Lukacsovich Tamás , Bálint Éva , Virágh Erika , Szabó Kornélia , Hajdu Ildikó , Molnár Enikő , Lin Yu-Hsien , Zvara Ágnes , Kelemen-Valkony Ildikó , Méhi Orsolya , Török István , Hegedűs Zoltán , Kiss Brigitta , Ramasz Beáta , Magdalena Laura M , Puskás László , Mechler Bernard M , Fónagy Adrien , Asztalos Zoltán , Steinbach Gábor , Žurovec Michal , Boros Imre , Kiss István
Published: July 2024

One of the major functions of programmed cell death (apoptosis) is the removal of cells that suffered oncogenic mutations, thereby preventing cancerous transformation. By making use of a Double-Headed-EP (DEP) transposon, a P element derivative made in our laboratory, we made an insertional mutagenesis screen in Drosophila melanogaster to identify genes that, when overexpressed, suppress the p53-activated apoptosis. The DEP element has Gal4-activatable, outward-directed UAS promoters at both ends, which can be deleted separately in vivo. In the DEP insertion mutants, we used the GMR-Gal4 driver to induce transcription from both UAS promoters and tested the suppression effect on the apoptotic rough eye phenotype generated by an activated UAS-p53 transgene. By DEP insertions, 7 genes were identified, which suppressed the p53-induced apoptosis. In 4 mutants, the suppression effect resulted from single genes activated by 1 UAS promoter (Pka-R2, Rga, crol, and Spt5). In the other 3 (Orct2, Polr2M, and stg), deleting either UAS promoter eliminated the suppression effect. In qPCR experiments, we found that the genes in the vicinity of the DEP insertion also showed an elevated expression level. This suggested an additive effect of the nearby genes on suppressing apoptosis. In the eukaryotic genomes, there are coexpressed gene clusters. Three of the DEP insertion mutants are included, and 2 are in close vicinity of separate coexpressed gene clusters. This raises the possibility that the activity of some of the genes in these clusters may help the suppression of the apoptotic cell death.
The core competencies of a health education teacher
Authors: Paakkari Olli , Kulmala Markus , Lyyra Nelli , Saaranen Terhi , Lindfors Pirjo , Tyrväinen Heli
Published: July 2024

Teachers play a crucial role in students’ learning and in the development of health literacy. Hence, the aim of this study was to identify the core competencies needed for teachers of health education in supporting student learning. A three-round Delphi study was carried out over an 8-week period, through consultation with 25 Finnish experts in health education. An open-ended question was used to identify the core competencies for school health educators. The data were analysed using inductive content analysis. In subsequent rounds, experts were asked to assess the importance of the identified competencies on a 7-point Likert scale, and finally to rank the most important competencies. In total, 52 competencies were identified and categorized into eight core competence domains. Thereafter, 40 competencies were assessed and selected for the third round, in which the experts ranked the 15 most important competencies, encompassing four core domains, i.e. pedagogic and subject-specific didactic, social and emotional, content knowledge and continuous professional development. Other domains of competence identified in the present study were ethical competence, competence in school health promotion, contextual competence and professional well-being competence. The study defines health education teacher core competencies and domains, and the information can be used in teacher education programmes, for developing teaching and for teachers’ self-evaluation.
Joint models reveal genetic architecture of pubertal stage transitions and their association with BMI in admixed Chilean population
Authors: Vicuña Lucas , Barrientos Esteban , Leiva-Yamaguchi Valeria , Alvares Danilo , Mericq Veronica , Pereira Anita , Eyheramendy Susana
Published: July 2024

Early or late pubertal onset can lead to disease in adulthood, including cancer, obesity, type 2 diabetes, metabolic disorders, bone fractures, and psychopathologies. Thus, knowing the age at which puberty is attained is crucial as it can serve as a risk factor for future diseases. Pubertal development is divided into five stages of sexual maturation in boys and girls according to the standardized Tanner scale. We performed genome-wide association studies (GWAS) on the “Growth and Obesity Chilean Cohort Study” cohort composed of admixed children with mainly European and Native American ancestry. Using joint models that integrate time-to-event data with longitudinal trajectories of body mass index (BMI), we identified genetic variants associated with phenotypic transitions between pairs of Tanner stages. We identified $42$ novel significant associations, most of them in boys. The GWAS on Tanner $3\rightarrow 4$ transition in boys captured an association peak around the growth-related genes LARS2 and LIMD1 genes, the former of which causes ovarian dysfunction when mutated. The associated variants are expression and splicing Quantitative Trait Loci regulating gene expression and alternative splicing in multiple tissues. Further, higher individual Native American genetic ancestry proportions predicted a significantly earlier puberty onset in boys but not in girls. Finally, the joint models identified a longitudinal BMI parameter significantly associated with several Tanner stages’ transitions, confirming the association of BMI with pubertal timing.
SlTrxh functions downstream of SlMYB86 and positively regulates nitrate stress tolerance via S-nitrosation in tomato seedling
Authors: Zeng Senlin , Sun Xudong , Zhai Jiali , Li Xixian , Pedro García-Caparrós , Nian Hongjuan , Li Kunzhi , Xu Huini
Published: July 2024

Nitric oxide (NO) is a redox-dependent signaling molecule that plays a crucial role in regulating a wide range of biological processes in plants. It functions by post-translationally modifying proteins, primarily through S-nitrosation. Thioredoxin (Trx), a small and ubiquitous protein with multifunctional properties, plays a pivotal role in the antioxidant defense system. However, the regulatory mechanism governing the response of tomato Trxh (SlTrxh) to excessive nitrate stress remains unknown. In this study, overexpression or silencing of SlTrxh in tomato led to increased or decreased nitrate stress tolerance, respectively. The overexpression of SlTrxh resulted in a reduction in levels of reactive oxygen species (ROS) and an increase in S-nitrosothiol (SNO) contents; conversely, silencing SlTrxh exhibited the opposite trend. The level of S-nitrosated SlTrxh was increased and decreased in SlTrxh overexpression and RNAi plants after nitrate treatment, respectively. SlTrxh was found to be susceptible to S-nitrosation both in vivo and in vitro, with Cysteine 54 potentially being the key site for S-nitrosation. Protein interaction assays revealed that SlTrxh physically interacts with SlGrx9, and this interaction is strengthened by S-nitrosation. Moreover, a combination of yeast one-hybrid (Y1H), electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR), and transient expression assays confirmed the direct binding of SlMYB86 to the SlTrxh promoter, thereby enhancing its expression. SlMYB86 is located in the nucleus and SlMYB86 overexpressed and knockout tomato lines showed enhanced and decreased nitrate stress tolerance, respectively. Our findings indicate that SlTrxh functions downstream of SlMYB86 and highlight the potential significance of S-nitrosation of SlTrxh in modulating its function under nitrate stress.
Development of super-infective ternary vector systems for enhancing the Agrobacterium-mediated plant transformation and genome editing efficiency
Authors: Jeong Jin-hee , Jeon Eun-young , Hwang Min Ki , Song Young Jong , Kim Jae-Yean
Published: July 2024

Agrobacterium-mediated transformation remains a cornerstone of plant biology, fueling advancements in molecular genetics, new genomic techniques (NGTs), and the biotech industry. However, recalcitrant crops and technical hurdles persist as bottlenecks. The goal was to develop super-infective ternary vector systems that integrate a novel salicylic acid-degrading enzyme, GABA, and ethylene-degrading enzymes, targeting the transformation of crops by neutralizing plant defense system on Agrobacterium. Firstly, both the effect and activity of introducing enzymes were validated in EHA105, an important Agrobacterium strain. Our study demonstrates that all ternary vector (Tv) system variants significantly enhance reporter expression in transient assays with Nicotiana benthamiana and Cannabis sativa. Specifically, incorporating a constitutive virG mutation with novel enzyme combinations increased GFP and RUBY expression in C. sativa by >5-fold and 13-fold, respectively. The Tv system, combined with a geminivirus replicon, markedly boosted GUS gene expression in tomato, enhancing genome editing efficiency. Notably, compared to controls, Tv-VS demonstrated up to 18-fold and 4.5-fold increases in genome editing efficiency in C. sativa and tomato, respectively. Additionally, stable transformation rates in tomato and Arabidopsis improved significantly, with Tv-VS showing a remarkable 2.5-fold increase in transformation efficiency compared to control strains. The research marks notable progress in Agrobacterium-mediated plant transformation. The innovative ternary vectors overcome plant defense mechanisms, enabling genetic manipulation in previously challenging plant species. This development is anticipated to broaden the applications of plant genetic engineering, contributing to advancements in crop genome editing.
Single-cell RNA sequencing reveals a high-resolution cell atlas of petals in Prunus mume at different flowering development stages
Authors: Guo Yuhong , Chen Xiling , Li Jinhong , Wang Qi , Zhang Shuangyu , Liu Nuoxuan , Zhang Yanlong , Zhang Tengxun
Published: July 2024

Prunus mume (mei), a traditional ornamental plant in China, is renowned for its fragrant flowers, primarily emitted by its petals. However, the cell types of mei petals and where floral volatile synthesis occurs are rarely reported. The study used single-cell RNA sequencing to characterize the gene expression landscape in petals of P. mume ‘Fenhong Zhusha’ at budding stage (BS) and full-blooming stage (FS). Six major cell types of petals were identified: epidermal cells (ECs), parenchyma cells (PCs), xylem parenchyma cells, phloem parenchyma cells, xylem vessels and fibers, and sieve elements and companion cells complex. Cell-specific marker genes in each cell type were provided. Floral volatiles from mei petals were measured at four flowering development stages, and their emissions increased from BS to FS, and decreased at the withering stage. Fifty-eight differentially expressed genes (DEGs) in benzenoid/phenylpropanoid pathway were screened using bulk RNA-seq data. Twenty-eight DEGs expression increased from BS to FS, indicating that they might play roles in floral volatile synthesis in P. mume, among which PmBAHD3 would participate in benzyl acetate synthesis. ScRNA-seq data showed that 27 DEGs mentioned above were expressed variously in different cell types. In situ hybridization confirmed that PmPAL2, PmCAD1, PmBAHD3,5, and PmEGS1 involved in floral volatile synthesis in mei petals are mainly expressed in EC, PC, and most vascular tissues, consistent with scRNA-seq data. The result indicates that benzyl acetate and eugenol, the characteristic volatiles in mei, are mostly synthesized in these cell types. The first petal single-cell atlas was constructed, offering new insights into the molecular mechanism of floral volatile synthesis.
Association analysis of BSA-seq, BSR-seq, and RNA-seq reveals key genes involved in purple leaf formation in a tea population (Camellia sinensis)
Authors: Wang Yueqi , Jin Ji-Qiang , Zhang Rui , He Mengdi , Wang Liubin , Mao Zhuozhuo , Gan Min , Wu Liyun , Chen Liang , Wang Liyuan , Wei Kang
Published: July 2024

Purple tea, rich in anthocyanins, has a variety of health benefits and is attracting global interest. However, the regulation mechanism of anthocyanin in purple tea populations has not been extensively studied. In this experiment, RNA-seq, BSA-seq, and BSR-seq were performed using 30 individuals with extreme colors (dark-purple and green) in an F1 population of ‘Zijuan’ and ‘Jinxuan’. The results show that 459 genes were differentially expressed in purple and green leaves, among which genes involved in the anthocyanin synthesis and transport pathway, such as CHS, F3H, ANS, MYB75, GST, MATE, and ABCC, were highly expressed in purple leaves. Moreover, there were multiple SNP/InDel variation sites on chromosomes 2 and 14 of the tea plant, as identified by BSA-seq. The integrated analysis identified two highly expressed genes (CsANS and CsMYB75) with SNP/InDel site variations in the purple tea plants. By silencing leaves, we proved that CsMYB75 could positively regulate anthocyanin accumulation and expression of related structural genes in tea plants. A 181-bp InDel in the CsMYB75 promoter was also found to be co-segregating with leaf color. The results of this study provide a theoretical reference for the molecular mechanism of anthocyanin accumulation in purple tea plants and contribute to the creation of new tea cultivars with high anthocyanin content.
Extended remdesivir administration in haematological patients with malignancies and COVID-19 during the Omicron era: safety and outcomes
Authors: Gras Emmanuelle , Aiello Tommaso Francesco , Chumbita Mariana , Gallardo-Pizarro Antonio , Monzó-Gallo Patricia , Teijón-Lumbreras Christian , Suárez-Lledó Maria , Magnano Laura , Tuset Montse , Marcos Maria Ángeles , Soriano Alex , Garcia-Vidal Carolina
Published: July 2024

Objectives

To describe the management of haematological patients experiencing prolonged SARS-CoV-2 viral shedding, as the optimal management strategy for this condition remains undetermined.

Methods

We conducted a retrospective evaluation of our prospectively followed cohort of haematological patients treated with remdesivir for more than 10 days. Starting January 2023, upon COVID-19 diagnosis, the treatment strategy was based on symptoms and PCR cycle threshold (Ct) as follows: (i) when Ct was 25 or less or if the patient had symptoms, a course of remdesivir for at least 10 days, nirmatrelvir/ritonavir for 5 days (whenever possible) and convalescent plasma was administered; and (ii) when the patient was asymptomatic and had a PCR Ct of more than 25, when possible, a course of 5 days of nirmatrelvir/ritonavir was administered. The patient was considered to have achieved viral clearance and, thus, remdesivir was stopped, in either of these cases: (i) PCR negativity, or (ii) subgenomic RNA negativity.

Results

From January to November 2023, 18 patients benefited from a safe extended remdesivir administration, resulting in detection of SARS-CoV-2 viral clearance in a median time of 3.5 weeks (IQR 2.6–3.9) (min–max 1.6–8.0). No clinical or biological side effects were detected. No patient died or needed further treatment for their COVID-19 episode.

Conclusions

The extended course of remdesivir, combined with other active therapies for COVID-19 infection, was well tolerated. Cure and virus negativity were obtained in all these high-risk patients.
The bacterial and fungal profiles of patients hospitalized with non-COVID-19 lower respiratory tract infections in Wuhan, China, 2019–2021
Authors: Li Liangyu , Zhang Haiyue , Liu Chan , Wan Lu , Liu Mengling , Li Ruiyun , Liu Hailing , Yin Jing , Shang Min , Luo Yuchuan , Wang Ming , Wu Xiaojun
Published: July 2024

Aims

A severe lockdown occurred in Wuhan during the COVID-19 pandemic, followed by a remission phase in the pandemic’s aftermath. This study analyzed the bacterial and fungal profiles of respiratory pathogens in patients hospitalized with non-COVID-19 lower respiratory tract infections (LRTIs) during this period to determine the pathogen profile distributions in different age groups and hospital departments in Wuhan.

Methods and results

We collected reports of pathogen testing in the medical records of patients hospitalized with non-COVID-19 LRTI between 2019 and 2021. These cases were tested for bacterial and fungal pathogens using 16S and internal transcribed spacer sequencing methods on bronchoalveolar lavage fluid samples. The study included 1368 cases. The bacteria most commonly identified were Streptococcus pneumoniae (12.50%) and Mycoplasma pneumoniae (8.33%). The most commonly identified fungi were Aspergillus fumigatus (2.49%) and Pneumocystis jirovecii (1.75%). Compared to 2019, the S. pneumoniae detection rates increased significantly in 2021, and those of M. pneumoniae decreased. Streptococcus pneumoniae was detected mainly in children. The detection rates of almost all fungi were greater in the respiratory Intensive Care Unit compared to respiratory medicine. Streptococcus pneumoniae and M. pneumoniae were detected more frequently in the pediatric department.

Conclusions

Before and after the COVID-19 outbreak, a change in the common pathogen spectrum was detected in patients with non-COVID-19 in Wuhan, with the greatest change occurring among children. The major pathogens varied by the patient’s age and the hospital department.
Period circadian regulator 2-mediated steroid hormone synthesis by regulating transcription of steroidogenic acute regulatory protein in porcine granulosa cells
Authors: Zhang Zelin , Cheng Jianyong , Yang Li , Li Xiaoya , Li Qingwang
Published: July 2024

Steroidogenesis is associated with circadian clock genes. However, the regulation of steroid hormone production in sow granulosal cells by Per2, a crucial circadian regulator, remains unexplored. In this study, we have identified the presence of Per2 in ovarian granulosa cells and have observed its circadian expression pattern. Employing siRNA to interfere with Per2 expression, our investigation revealed that Per2 knockdown notably elevated progesterone (P4) levels along with increasing the expression of StAR but interference of Per2 did not alter the rhythm of clock-related gene (Bmal1, Clock, Per1, and Cry1) in granulosa cells. Subsequent mechanistic analysis showed that Per2 formed complexes with PPARγ and interference with Per2 promoted the formation of the PPARγ:RXRα heterodimer. Importantly, we uncovered that PPARγ:RXRα heterodimer could control the expression of StAR via direct peroxisome proliferator response element binding to its promoter to regulate its activity, and knockdown of Per2 promoted the transcription of StAR via increasing the binding of PPARγ:RXRα ligands. Altogether, these findings indicated a noncanonical role of Per2 in controlling PPARγ:RXRα binding to regulate transcription of StAR and progesterone synthesis, thus revealing potential avenues of pharmacological and therapeutic intervention.
Sex chromosome cycle as a mechanism of stable sex determination
Authors: Hayashi Shun , Abe Takuya , Igawa Takeshi , Katsura Yukako , Kazama Yusuke , Nozawa Masafumi
Published: July 2024

Recent advances in DNA sequencing technology have enabled the precise decoding of genomes in non-model organisms, providing a basis for unraveling the patterns and mechanisms of sex chromosome evolution. Studies of different species have yielded conflicting results regarding the traditional theory that sex chromosomes evolve from autosomes via the accumulation of deleterious mutations and degeneration of the Y (or W) chromosome. The concept of the ‘sex chromosome cycle,’ emerging from this context, posits that at any stage of the cycle (i.e., differentiation, degeneration, or loss), sex chromosome turnover can occur while maintaining stable sex determination. Thus, understanding the mechanisms that drive both the persistence and turnover of sex chromosomes at each stage of the cycle is crucial. In this review, we integrate recent findings on the mechanisms underlying maintenance and turnover, with a special focus on several organisms having unique sex chromosomes. Our review suggests that the diversity of sex chromosomes in the maintenance of stable sex determination is underappreciated and emphasizes the need for more research on the sex chromosome cycle.
Utility of the Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) in Pediatric Stevens-Johnson Syndrome Patients
Authors: Gust Nina K B , Adams Rebecca M , Frei Ashley , Coughlin Michelle , Klein Justin , Ridelman Elika , Shanti Christina
Published: July 2024

The Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) is a system that predicts in-hospital mortality for Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). The system is widely utilized in adults but not in pediatrics. We aim to determine the accuracy of the SCORTEN in pediatrics. A retrospective review of pediatric patients admitted to a verified pediatric burn center with SJS/TEN from 2008 to 2022 was performed. Twenty-four patients were analyzed. Ten patients had 0-1 SCORTEN risk factor, 13 had 2 risk factors, and 1 had 3 risk factors. There was no relationship between initial blood urea nitrogen, bicarbonate, glucose, or initial heart rate on the length of an intensive care unit (ICU) stay or ventilator days. Hospital length of stay and feeding tube days were positively related (P < .001) along with length of stay and maximum total body surface areas (P < .05). Hospital length of stay, ICU length of stay, and ventilator days were not statistically significant between those having 0-1 and 2 risk factors. This study suggests that the SCORTEN system is not useful for pediatrics and a different scoring system is needed, as SCORTEN overestimates mortality and does not have a relationship to outcome measures.
Bone turnover biomarkers reflect radiation-induced bone injuries in women with non-metastatic rectal cancer
Authors: Magnusson Per , Sääf Maria , Martling Anna , Svanström Röjvall Annika , Atanasova Diana , Wilamowski Franciszek , Flöter Rådestad Angelique , Buchli Christian , Segelman Josefin
Published: July 2024

Preoperative radiotherapy (RT) for non-metastatic rectal cancer reduces local recurrence rates but can cause pelvic insufficiency fractures. Despite the high morbidity from RT-induced skeletal injuries, predictive and preventive measures are lacking. How these injuries are reflected by bone biomarkers are largely unknown. The aim was to assess longitudinal changes in bone biomarkers and their relation to RT-related bone injuries in women with rectal cancer. This longitudinal cohort study includes 47 women with non-metastatic rectal cancer treated with surgery ± preoperative RT with or without chemotherapy. Sclerostin, bioactive sclerostin, C-terminal telopeptide cross-links of collagen type I (CTX), bone-specific alkaline phosphatase (BALP), and type I procollagen intact N-terminal propeptide (PINP) were measured at baseline, after RT, and 1 yr postoperatively. Pelvic magnetic resonance imaging was used for detection of skeletal injury. Sixteen of 36 (44%) irradiated women had radiation-induced bone injuries and were compared to 11 women (RT–) and 20 women (RT+) without bone injuries. Serum CTX, BALP, and PINP increased during the first year after RT in women with radiation-induced bone injuries. The difference in mean change of CTX (p=.037) and BALP (p=.042) was conferred by longitudinal regression analyses adjusted for serum estradiol. Serum sclerostin and bioactive sclerostin remained stable over time. Taken together, bone markers may be of interest for future research on fracture prediction or preventive measures in women susceptible to radiation-induced bone injury. Due to few measure points, the full pattern cannot be captured regarding the relation over time between bone biomarkers and skeletal injury from irradiation.
Standardization of body composition parameters between GE Lunar iDXA and Hologic Horizon A and their clinical impact
Authors: Vendrami Colin , Gatineau Guillaume , Gonzalez Rodriguez Elena , Lamy Olivier , Hans Didier , Shevroja Enisa
Published: July 2024

Body composition (BC) measured by DXA differs between devices. We aimed to compare regional and total BC measurements assessed by the Hologic Horizon A and the GE Lunar iDXA devices; to determine device-specific calibration equations for each BC parameter; and to assess the impact of this standardization procedure on the assessment of sarcopenia, lipedema, obesity, and cardiovascular risk with DXA. A total of 926 postmenopausal women (aged 72.9 ± 6.9 yr, height 160.3 ± 6.6 cm, weight 66.1 ± 12.7 kg) underwent BC assessment on each device within 1 h, following the ISCD guidelines. The included sample was split into 80% train and 20% test datasets stratified by age, height, and weight. Inter-device differences in BC parameters were assessed with Bland–Altman analysis, Pearson or Spearman correlation coefficients, and t-tests or Wilcoxon tests. The equations were developed in the train dataset using backward stepwise multiple linear regressions and were evaluated in the test dataset with the R-squared and mean absolute error. We compared the abovementioned BC-derived health conditions before and after standardization in the test set with respect to relative risk, accuracy, Kappa score, and McNemar tests. Total and regional body masses were similar (p>.05) between devices. BMC was greater for all regions in the Lunar device (p<.05), while fat and lean masses differed among regions. Regression equations showed high performance metrics in both datasets. The BC assessment from Hologic classified 2.13 times more sarcopenic cases (McNemar: p<.001), 1.39 times more lipedema (p<.001), 0.40 times less high cardiovascular risk (p<.001), and similarly classified obesity (p>.05), compared to Lunar. After standardization, the differences disappeared (p>.05), and the classification metrics improved. This study discusses how hardware and software differences impact BC assessments. The provided standardization equations address these issues and improve the agreement between devices. Future studies and disease definitions should consider these differences.
The usefulness of head computed tomography in patients with known cirrhosis presenting to emergency department with suspected hepatic encephalopathy
Authors: Yang David Yi , Bowron Joel , Ahmed Mohammed , Abraldes Juan G , Veldhuyzen van Zanten Sander
Published: July 2024

Background

Computed tomography of the head (CT head) is frequently used for patients with cirrhosis presenting with suspected hepatic encephalopathy (HE).

Aims

The primary aims of this study were to assess the frequency of CT head usage in this patient population and to determine whether these scans yielded significant findings. Our secondary aims were to identify factors associated with the decision to order CTs and whether patients who received CTs had different outcomes.

Methods

A single-centre, retrospective chart review was performed. Patients presenting to the University of Alberta Hospital with cirrhosis and common liver disease aetiologies over a 27-month period were identified via discharge diagnosis codes. Charts of patients with suspected HE were manually identified. The use of a CT head was documented, as were patient demographics, cirrhosis aetiology, MELD, and outcomes. Comparisons were made between patients with and without CT head.

Results

A total of 119 encounters from 100 patients met our inclusion criteria. In 57% of encounters, a CT scan was performed on presentation. None of these CT scans had significant findings. Patient factors associated with the decision to order CT included older age, more preserved liver function, and longer length of time between patient’s current and previous presentations. Patients who did not receive CT head had higher in-hospital mortality, which was likely reflective of more severe underlying liver dysfunction in this group.

Conclusions

The frequency of CT head usage in the studied patient population was high while the yield was low. This calls into question the usefulness of CT head in this population.
Graphical criteria for the identification of marginal causal effects in continuous-time survival and event-history analyses
Authors: Røysland Kjetil , Ryalen Pål C , Nygård Mari , Didelez Vanessa
Published: July 2024

We consider continuous-time survival and event-history settings, where our aim is to graphically represent causal structures allowing us to characterize when a causal parameter is identified from observational data. This causal parameter is formalized as the effect on an outcome event of a (possibly hypothetical) intervention on the intensity of a treatment process. To establish identifiability, we propose novel graphical rules indicating whether the observed information is sufficient to obtain the desired causal effect by suitable reweighting. This requires a different type of graph than in discrete time. We formally define causal semantics for the corresponding dynamic graphs that represent local independence models for multivariate counting processes. Importantly, our work highlights that causal inference from censored data relies on subtle structural assumptions on the censoring process beyond independent censoring; these can be verified graphically. Put together, our results are the first to establish graphical rules for nonparametric causal identifiability in event processes in this generality for the continuous-time case, not relying on particular parametric survival models. We conclude with a data example on Human papillomavirus (HPV) testing for cervical cancer screening, where the assumptions are illustrated graphically and the desired effect is estimated by reweighted cumulative incidence curves.
Trends in multi-jurisdictional enforcement of anti-corruption in the global petroleum industry
Authors: Randall Scott W , Marques Francisco Paes
Published: July 2024

The global petroleum industry has been much maligned over the past 10–15 years for its involvement in foreign corrupt activities due to well-publicized instances of US-led prosecution for bribery of foreign public officials. Among the high-profile cases include the infamous Technip, Snamprogetti, Kellogg Brown & Root, JGC (TSKJ) conspiracy bribing Nigerian officials of the Bonny Island LNG terminal to the far-reaching Odebrecht/Petrobras Brazilian Lava Jato and more recent global Unaoil bribery scandals. What these cases and others have in common is the incidence of ‘multi-jurisdictional’ prosecution for foreign bribery rather than simply prosecution by US authorities as occurred prior to 2005. Through detailed quantitative analysis, we show how this multi-jurisdictional enforcement is a petroleum industry trend. The financial and reputational risk in terms of both likelihood and impact of a foreign bribery event has increased dramatically over the past 10 years. Despite this increased risk, we found little evidence of a risk-based compliance approach among industry participants. We show that the current practice of limiting liability is not an efficient risk-based approach towards corruption compliance and is not likely to meet new anti-corruption compliance guidelines by international regulators. Our research examines a possible cause-and-effect model behind this heightened corruption risk. We profile and describe the nature of the top 10 petroleum industry multi-jurisdictional bribery cases. We then provide a display of a corruption event’s drivers, consequences, and barriers in the form of a risk-based ‘bow-tie’ diagram. Finally, we recommend ways the industry can move towards a more risk-based corruption compliance approach.
Susceptibility of pESI positive Salmonella to treatment with biocide chemicals approved for use in poultry meat processing as compared to Salmonella without the pESI plasmid
Authors: McMillan Elizabeth A , Adams Eric S , Mitchell Trevor R , Hawkins Jaci A , Read Quentin D , Pokoo-Aikins Anthony , Berrang Mark E , Harris Caitlin E , Hughes Michael D , Glenn Anthony E , Meinersmann Richard J
Published: July 2024

Salmonella is a common cause of human foodborne illness, which is frequently associated with consumption of contaminated or undercooked poultry meat. Serotype Infantis is among the most common serotypes isolated from poultry meat products globally. Isolates of serotype Infantis carrying the pESI plasmid, the most dominant strain of Infantis, have been shown to exhibit oxidizer tolerance. Therefore, 16 strains of Salmonella with and without pESI carriage were investigated for susceptibility to biocide chemical processing aids approved for use in US poultry meat processing: peracetic acid (PAA), cetylpyridinium chloride (CPC), calcium hypochlorite, and sodium hypochlorite. Strains were exposed for 15 s to simulate spray application and 90 min to simulate application in an immersion chiller. All strains tested were susceptible to all concentrations of PAA, CPC, and sodium hypochlorite when applied for 90 min. When CPC, calcium hypochlorite, and sodium hypochlorite were applied for 15 s to simulate spray time, strains responded similarly to each other. However, strains responded variably to exposure to PAA. The variation was not statistically significant and appears unrelated to pESI carriage. Results highlight the necessity of testing biocide susceptibility in the presence of organic material and in relevant in situ applications.
TOI-2447 b / NGTS-29 b: a 69-day Saturn around a Solar analogue
Authors: Gill Samuel , Bayliss Daniel , Ulmer-Moll Solène , Wheatley Peter J , Brahm Rafael , Anderson David R , Armstrong David , Apergis Ioannis , Alves Douglas R , Burleigh Matthew R , Butler R P , Bouchy François , Battley Matthew P , Bryant Edward M , Bieryla Allyson , Crane Jeffrey D , Collins Karen A , Casewell Sarah L , Carleo Ilaria , Claringbold Alastair B , Dalba Paul A , Dragomir Diana , Eigmüller Philipp , Eberhardt Jan , Fausnaugh Michael , Günther Maximilian N , Grieves Nolan , Goad Michael R , Gillen Edward , Hagelberg Janis , Hobson Melissa , Hedges Christina , Henderson Beth A , Hawthorn Faith , Henning Thomas , Jones Matías I , Jordán Andrés , Jenkins James S , Kunimoto Michelle , Krenn Andreas F , Kendall Alicia , Lendl Monika , McCormac James , Moyano Maximiliano , Torres-Miranda Pascal , Nielsen Louise D , Osborn Ares , Otegi Jon , Osborn Hugh , Quinn Samuel N , Rodriguez Joseph E , Ramsay Gavin , Schlecker Martin , Shectman Stephen A , Seager Sara , Tilbrook Rosanna H , Trifonov Trifon , Teske Johanna K , Udry Stephane , Vines Jose I , West Richard R , Wohler Bill , Winn Joshua N , Wang Sharon X , Zhou George , Zivave Tafadzwa
Published: July 2024

Discovering transiting exoplanets with relatively long orbital periods (>10 d) is crucial to facilitate the study of cool exoplanet atmospheres (Teq < 700 K) and to understand exoplanet formation and inward migration further out than typical transiting exoplanets. In order to discover these longer period transiting exoplanets, long-term photometric, and radial velocity campaigns are required. We report the discovery of TOI-2447 b (=NGTS-29 b), a Saturn-mass transiting exoplanet orbiting a bright (T = 10.0) Solar-type star (Teff = 5730 K). TOI-2447 b was identified as a transiting exoplanet candidate from a single transit event of 1.3 per cent depth and 7.29 h duration in TESS Sector 31 and a prior transit event from 2017 in NGTS data. Four further transit events were observed with NGTS photometry which revealed an orbital period of P = 69.34 d. The transit events establish a radius for TOI-2447 b of $0.865 \pm 0.010\, \rm R_{\rm J}$, while radial velocity measurements give a mass of $0.386 \pm 0.025\, \rm M_{\rm J}$. The equilibrium temperature of the planet is 414 K, making it much cooler than the majority of TESS planet discoveries. We also detect a transit signal in NGTS data not caused by TOI-2447 b, along with transit timing variations and evidence for a ∼150 d signal in radial velocity measurements. It is likely that the system hosts additional planets, but further photometry and radial velocity campaigns will be needed to determine their parameters with confidence. TOI-2447 b/NGTS-29 b joins a small but growing population of cool giants that will provide crucial insights into giant planet composition and formation mechanisms.
Offset of M54 from the Sagittarius dwarf spheroidal galaxy
Authors: An Zhaozhou , Walker Matthew G , Pace Andrew B
Published: July 2024

We present results from simultaneous modelling of 2D (projected along the line of sight) position, proper motion, and line-of-sight velocity for Gaia- and Apache Point Observatory Galactic Evolution Experiment (APOGEE)-observed stars near the centre of the Sagittarius (Sgr) dwarf spheroidal galaxy. We use a mixture model that allows for independent sub-populations contributed by the Sgr galaxy, its nuclear star cluster Messier 54 (M54), and the Milky Way foreground. We find an offset of $0.295\pm 0.029$ deg between the inferred centroids of Sgr and M54, corresponding to a (projected) physical separation of $0.135\pm 0.013$ kpc. The detected offset might plausibly be driven by unmodelled asymmetry in Sgr’s stellar configuration; however, standard criteria for model selection favour our symmetric model over an alternative that allows for bilateral asymmetry. We infer an offset between the proper motion centres of Sgr and M54 of $[\Delta \mu _{\alpha }\cos \delta ,\Delta \mu _{\delta }]=[4.9, -19.7] \pm [6.8, 6.2] \ \mu \mathrm{ as}\,\mathrm{ yr}^{-1}$ ($[0.61, -2.46] \pm [0.85, 0.77] \ \mathrm{ km}\,\mathrm{ s}^{-1}$), with magnitude similar to the covariance expected due to spatially correlated systematic error. We infer an offset of $4.1\pm 1.2 \ \mathrm{ km}\,\mathrm{ s}^{-1}$ in line-of-sight velocity. Using inferred values for the systemic positions and motions of Sgr and M54 as initial conditions, we calculate the recent orbital history of a simplified Sgr/M54 system, which we demonstrate to be sensitive to any line-of-sight distance offset between M54 and Sgr, and to the distribution of dark matter within Sgr.