bluuebunny/crossref_metadata_2025 huggingface dataset:
simCAS: an embedding-based method for simulating single-cell chromatin accessibility sequencing data
Authors: Li Chen , Chen Xiaoyang , Chen Shengquan , Jiang Rui , Zhang Xuegong
Published: July 2023

Motivation

Single-cell chromatin accessibility sequencing (scCAS) technology provides an epigenomic perspective to characterize gene regulatory mechanisms at single-cell resolution. With an increasing number of computational methods proposed for analyzing scCAS data, a powerful simulation framework is desirable for evaluation and validation of these methods. However, existing simulators generate synthetic data by sampling reads from real data or mimicking existing cell states, which is inadequate to provide credible ground-truth labels for method evaluation.

Results

We present simCAS, an embedding-based simulator, for generating high-fidelity scCAS data from both cell- and peak-wise embeddings. We demonstrate simCAS outperforms existing simulators in resembling real data and show that simCAS can generate cells of different states with user-defined cell populations and differentiation trajectories. Additionally, simCAS can simulate data from different batches and encode user-specified interactions of chromatin regions in the synthetic data, which provides ground-truth labels more than cell states. We systematically demonstrate that simCAS facilitates the benchmarking of four core tasks in downstream analysis: cell clustering, trajectory inference, data integration, and cis-regulatory interaction inference. We anticipate simCAS will be a reliable and flexible simulator for evaluating the ongoing computational methods applied on scCAS data.

Availability and implementation

simCAS is freely available at https://github.com/Chen-Li-17/simCAS.
Pollution: the new culprit in skin pigmentation
Authors: Afzal Usamah M , Ali Faisal R
Published: July 2023

The noteworthy paper considered in this article has provided compelling evidence that traffic-related air pollution should be considered an environmental factor contributing to skin hyperpigmentation and clinicians should take this into account when counselling patients about skincare routines; for example, use of twice daily facial cleansers especially in urban environments.
Alpha-ketoglutarate supplementation reduces inflammation and thrombosis in type 2 diabetes by suppressing leukocyte and platelet activation
Authors: Agarwal Sakshi , Ghosh Riya , Verma Garima , Khadgawat Rajesh , Guchhait Prasenjit
Published: July 2023

The interplay between platelets and leukocytes contributes to the pathogenesis of inflammation, thrombosis, and cardiovascular diseases (CVDs) in type 2 diabetes (T2D). Our recent studies described alpha-ketoglutarate (αKG), a Krebs cycle intermediate metabolite as an inhibitor to platelets and leukocytes activation by suppressing phosphorylated-Akt (pAkt) through augmentation of prolyl hydroxylase-2 (PHD2). Dietary supplementation with a pharmacological concentration of αKG significantly inhibited lung inflammation in mice with either SARS-CoV-2 infection or exposed to hypoxia treatment. We therefore investigated if αKG supplementation could suppress hyperactivation of these blood cells and reduce thromboinflammatory complications in T2D. Our study describes that dietary supplementation with αKG (8 mg/100 g body wt. daily) for 7 days significantly reduced the activation of platelets and leukocytes (neutrophils and monocytes), and accumulation of IL1β, TNFα, and IL6 in peripheral blood of T2D mice. αKG also reduced the infiltration of platelets and leukocytes, and accumulation of inflammatory cytokines in lungs by suppressing pAkt and pP65 signaling. In a cross-sectional investigation, our study also described the elevated platelet–leukocyte aggregates and pro-inflammatory cytokines in circulation of T2D patients. T2D platelets and leukocytes showed an increased aggregation and thrombus formation in vitro. Interestingly, a pre-incubation of T2D blood samples with octyl αKG significantly suppressed the activation of these blood cells and ameliorated aggregate/thrombus formation in vitro. Thus, suggesting a potential therapeutic role of αKG against inflammation, thrombosis, and CVDs in T2D.
Impact of Concomitant 5-Aminosalicylic Acid Therapy on Vedolizumab Efficacy and Safety in Inflammatory Bowel Disease: Post Hoc Analyses of Clinical Trial Data
Authors: Ungaro Ryan C , Kadali Harisha , Zhang Wenwen , Adsul Shashi , Reinisch Walter
Published: July 2023

Background and Aims

The benefit of continuing 5-aminosalicylic acid [5-ASA] treatment when escalating to advanced therapies in patients with inflammatory bowel disease [IBD] is unclear. Vedolizumab is a gut-selective monoclonal anti-α4β7-integrin antibody used to treat moderate to severe IBD. Clinical trial data were analysed post hoc to assess the impact of 5-ASA co-treatment on vedolizumab efficacy and safety in patients with IBD.

Methods

Data were analysed from patients aged 18–80 years with moderate to severe ulcerative colitis [UC]/Crohn’s disease [CD] receiving intravenous [IV]/subcutaneous [SC] vedolizumab. Efficacy data were from four studies [GEMINI 1 and 2 and VISIBLE 1 and 2]; safety data were from seven studies [GEMINI 1‒3 and long-term, VISIBLE 1, 2, and open-label extension]. The impact of 5-ASA co-treatment on clinical and endoscopic outcomes at Weeks 6 and 52 was assessed using multivariate analysis (adjusted odds ratios [aORs] with 95% confidence intervals [CIs]).

Results

There were no significant differences in UC clinical remission [Mayo score ≤2, no subscore >1] rates with vs without 5-ASA at Week 6 [20.7% vs 20.4%, respectively; aOR 0.77, 95% CI 0.43–1.38] or at Week 52 [45.1% vs 40.6%; aOR 1.14, 0.70–1.86], and in CD clinical remission [CD activity index score ≤150] rates at Week 6 [41.4% vs 35.1%; 1.26, 0.86–1.85] or at Week 52 [49.6% vs 37.8%; 1.35, 0.91–1.99]. The incidence of enteric and all infections in vedolizumab IV/SC-treated patients was low with and without 5-ASA.

Conclusion

Continuation of concomitant oral 5-ASA after starting vedolizumab had no significant impact on clinical and endoscopic outcomes.

Clinical trial identifiers

GEMINI 1: NCT00783718, EudraCT 2008-002782-32; GEMINI 2: NCT00783692, EudraCT 2008-00278-33; GEMINI 3: NCT01224171, EudraCT 2009-016488-12; GEMINI long-term safety study: NCT00790933, EudraCT 2008-002784-14; VISIBLE 1: NCT02611830, EudraCT 2015-000480-14; VISIBLE 2: NCT02611817, EudraCT 2015-000481-58; VISIBLE open-label extension: NCT02620046, EudraCT 2015-000482-31.
Challenges in diagnosing pulmonary embolism in an adult with Fontan physiology: a case report
Authors: Teng Catherine , Shrestha Ribesh , Phillips Jason
Published: July 2023

Background

With the increasing longevity of congenital heart disease patients and limited number of adult congenital heart disease specialists, it is becoming increasingly imperative for general cardiologists to understand not only the unique physiology of Fontan patients but also imaging protocol considerations when treating this group of patients.

Case summary

Here, we present a patient with a history of congenital tricuspid atresia status after the Fontan procedure who presented for gut translocation–related bacteraemia. Importantly, the patient was falsely diagnosed with pulmonary embolism resulting from inaccurate acquisition of computed tomography imaging.

Discussion

This case illustrates the complex intricacies that clinicians should consider when facing the challenge of treating Fontan patients.
Acute pulmonary hypertension due to microthrombus formation following COVID-19 vaccination: a case report
Authors: Nakagawa Akiko , Nakamura Norihito , Torii Sho , Goto Shinya
Published: July 2023

Background

Several side effects have been reported after mRNA COVID-19 vaccinations. Nonetheless, the risk of pulmonary hypertension (PH) is rarely reported. Most cases with acute PH following vaccination were due to macropulmonary embolism secondary to deep vein thrombosis. However, acute PH due to microthrombus formation after COVID-19 vaccination has not been reported before, although a microthrombus has been considered to lead to the dysfunction of multiple organs, particularly in patients infected with COVID-19.

Case summary

A 63-year-old woman without any past medical history presented to our hospital with facial and bilateral pedal oedema and progressive dyspnoea on exertion. Her symptoms began the day after her second COVID-19 vaccination and developed gradually, which prompted her to seek consultation in our hospital 6 weeks later. An echocardiogram revealed substantially elevated right heart pressure, and cardiac catheterization revealed high pulmonary artery pressure (mean PAP, 30 mmHg). Contrast-enhanced computed tomography and venous echography revealed no apparent thrombus, and ventilation/perfusion (V/Q) scintigraphy revealed no V/Q mismatch. However, elevated D-dimer indicated the presence of a coagulation–fibrinolysis system in her body; thus, heparin therapy was initiated intravenously on Day 3 for 4 days, followed by direct oral anticoagulants ended on Day 16. Her symptoms substantially improved as her D-dimer level decreased, and a follow-up cardiac catheterization on Day 14 revealed a decline in mean PAP (15 mmHg).

Discussion

Our case suggests that the presence of acute PH is likely due to microangiopathy. Further studies are required to reveal the relationship between immune responses and microthrombus formation after COVID-19 vaccination.
Lifestyle interventions to change trajectories of obesity-related cardiovascular risk from childhood onset to manifestation in adulthood: a joint scientific statement of the task force for childhood health of the European Association of Preventive Cardiology and the European Childhood Obesity Group
Authors: Hanssen Henner , Moholdt Trine , Bahls Martin , Biffi Alessandro , Siegrist Monika , Lewandowski Adam J , Biondi-Zoccai Giuseppe , Cavarretta Elena , Kokkvoll Ane , Løchen Maja-Lisa , Maestrini Viviana , Pinto Rita Salvador , Palermi Stefano , Thivel David , Wojcik Malgorzata , Hansen Dominique , Van Craenenbroeck Emeline M , Weghuber Daniel , Kraenkel Nicolle , Tiberi Monica
Published: July 2023

There is an immediate need to optimize cardiovascular (CV) risk management and primary prevention of childhood obesity to timely and more effectively combat the health hazard and socioeconomic burden of CV disease from childhood development to adulthood manifestation. Optimizing screening programs and risk management strategies for obesity-related CV risk in childhood has high potential to change disease trajectories into adulthood. Building on a holistic view on the aetiology of childhood obesity, this document reviews current concepts in primary prevention and risk management strategies by lifestyle interventions. As an additional objective, this scientific statement addresses the high potential for reversibility of CV risk in childhood and comments on the use of modern surrogate markers beyond monitoring weight and body composition. This scientific statement also highlights the clinical importance of quantifying CV risk trajectories and discusses the remaining research gaps and challenges to better promote childhood health in a population-based approach. Finally, this document provides an overview on the lessons to be learned from the presented evidence and identifies key barriers to be targeted by researchers, clinicians, and policymakers to put into practice more effective primary prevention strategies for childhood obesity early in life to combat the burden of CV disease later in life.
Interannual dynamics of Tuber melanosporum and fungal communities in productive black truffle orchards amended with truffle nests
Authors: Garcia-Barreda Sergi , Marco Pedro , Bonito Gregory , Parladé Javier , Sánchez Sergio , González Vicente , Larena Inmaculada , Benucci Gian Maria Niccolò
Published: July 2023

Truffle growers devote great efforts to improve black truffle productivity, developing agronomic practices such as ‘truffle nests’ (peat amendments that are supplemented with truffle spore inoculum). It has been hypothesized that improved fruiting associated with nests is linked to stimulation of truffle mycelia previously established in soil or to changes generated in soil fungal community. To assess this, we used real-time PCR to quantify black truffle extraradical mycelium during 2 years after nests installation. We also characterized the fungal community via high-throughput amplicon sequencing of the ITS region of rRNA genes. We found that neither the abundance of truffle mycelium in nests nor in the soil—nest interphase was higher than in the bulk soil, which indicates that nests do not improve mycelial growth. The fungal community in nests showed lower richness and Shannon index and was compositionally different from that of soil, which suggests that nests may act as an open niche for fungal colonization that facilitates truffle fruiting. The ectomycorrhizal fungal community showed lower richness in nests. However, no negative relationships between amount of truffle mycelium and reads of other ectomycorrhizal fungi were found, thus countering the hypothesis that ectomycorrhizal competition plays a role in the nest effect.
The genome sequence of the Champagne Epernay Geisenheim wine yeast reveals its hybrid nature
Authors: Bernardi Beatrice , Michling Florian , Muno-Bender Judith , Matti Katrin , Wendland Jürgen
Published: July 2023

Lager yeasts are hybrids between Saccharomyces cerevisiae and S. eubayanus. Wine yeast biodiversity, however, has only recently been discovered to include besides pure S. cerevisiae strains also hybrids between different Saccharomyces yeasts as well as introgressions from non-Saccharomyces species. Here, we analysed the genome of the Champagne Epernay Geisenheim (CEG) wine yeast. This yeast is an allotetraploid (4n − 1) hybrid of S. cerevisiae harbouring a substantially reduced S. kudriavzevii genome contributing only 1/3 of a full genome equivalent. We identified a novel oligopeptide transporter gene, FOT4, in CEG located on chromosome XVI. FOT genes were originally derived from Torulaspora microellipsoides and FOT4 arose by non-allelic recombination between adjacent FOT1 and FOT2 genes. Fermentations of CEG in Riesling and Müller-Thurgau musts were compared with the S. cerevisiae Geisenheim wine yeast GHM, which does not carry FOT genes. At low temperature (10°C), CEG completed fermentations faster and produced increased levels of higher alcohols (e.g. isoamyl alcohol). At higher temperature (18°C), CEG produced higher amounts of the pineapple-like alkyl esters i-butyric and propionic acid ethyl esters compared to GHM. The hybrid nature of CEG thus provides advantages in grape must fermentations over S. cerevisiae wine yeasts, especially with regard to aroma production.
Gene-by-environment interactions influence the fitness cost of gene copy-number variation in yeast
Authors: Robinson DeElegant , Vanacloig-Pedros Elena , Cai Ruoyi , Place Michael , Hose James , Gasch Audrey P
Published: July 2023

Variation in gene copy number can alter gene expression and influence downstream phenotypes; thus copy-number variation provides a route for rapid evolution if the benefits outweigh the cost. We recently showed that genetic background significantly influences how yeast cells respond to gene overexpression, revealing that the fitness costs of copy-number variation can vary substantially with genetic background in a common-garden environment. But the interplay between copy-number variation tolerance and environment remains unexplored on a genomic scale. Here, we measured the tolerance to gene overexpression in four genetically distinct Saccharomyces cerevisiae strains grown under sodium chloride stress. Overexpressed genes that are commonly deleterious during sodium chloride stress recapitulated those commonly deleterious under standard conditions. However, sodium chloride stress uncovered novel differences in strain responses to gene overexpression. West African strain NCYC3290 and North American oak isolate YPS128 are more sensitive to sodium chloride stress than vineyard BC187 and laboratory strain BY4743. Consistently, NCYC3290 and YPS128 showed the greatest sensitivities to overexpression of specific genes. Although most genes were deleterious, hundreds were beneficial when overexpressed—remarkably, most of these effects were strain specific. Few beneficial genes were shared between the sodium chloride-sensitive isolates, implicating mechanistic differences behind their sodium chloride sensitivity. Transcriptomic analysis suggested underlying vulnerabilities and tolerances across strains, and pointed to natural copy-number variation of a sodium export pump that likely contributes to strain-specific responses to overexpression of other genes. Our results reveal extensive strain-by-environment interactions in the response to gene copy-number variation, raising important implications for the accessibility of copy-number variation-dependent evolutionary routes under times of stress.
Power of neutrality tests for detecting natural selection
Authors: Tanaka Tomotaka , Hayakawa Toshiyuki , Teshima Kosuke M
Published: July 2023

Detection of natural selection is one of the main interests in population genetics. Thus, many tests have been developed for detecting natural selection using genomic data. Although it is recognized that the utility of tests depends on several evolutionary factors, such as the timing of selection, strength of selection, frequency of selected alleles, demographic events, and initial frequency of selected allele when selection started acting (softness of selection), the relationships between such evolutionary factors and the power of tests are not yet entirely clear. In this study, we investigated the power of 4 tests: Tajiama's D, Fay and Wu's H, relative extended haplotype homozygosity (rEHH), and integrated haplotype score (iHS), under ranges of evolutionary parameters and demographic models to quantitatively expand the understanding of approaches for detecting selection. The results show that each test detects selection within a limited parameter range, and there are still wide ranges of parameters for which none of these tests work effectively. In addition, the parameter space in which each test shows the highest power overlaps the empirical results of previous research. These results indicate that our present perspective of adaptation is limited to only a part of actual adaptation.
The Rhodoexplorer Platform for Red Algal Genomics and Whole-Genome Assemblies for Several Gracilaria Species
Authors: Lipinska Agnieszka P , Krueger-Hadfield Stacy A , Godfroy Olivier , Dittami Simon M , Ayres-Ostrock Lígia , Bonthond Guido , Brillet-Guéguen Loraine , Coelho Susana , Corre Erwan , Cossard Guillaume , Destombe Christophe , Epperlein Paul , Faugeron Sylvain , Ficko-Blean Elizabeth , Beltrán Jessica , Lavaut Emma , Le Bars Arthur , Marchi Fabiana , Mauger Stéphane , Michel Gurvan , Potin Philippe , Scornet Delphine , Sotka Erik E , Weinberger Florian , Cabral de Oliveira Mariana , Guillemin Marie-Laure , Plastino Estela M , Valero Myriam
Published: July 2023

Macroalgal (seaweed) genomic resources are generally lacking as compared with other eukaryotic taxa, and this is particularly true in the red algae (Rhodophyta). Understanding red algal genomes is critical to understanding eukaryotic evolution given that red algal genes are spread across eukaryotic lineages from secondary endosymbiosis and red algae diverged early in the Archaeplastids. The Gracilariales is a highly diverse and widely distributed order including species that can serve as ecosystem engineers in intertidal habitats and several notorious introduced species. The genus Gracilaria is cultivated worldwide, in part for its production of agar and other bioactive compounds with downstream pharmaceutical and industrial applications. This genus is also emerging as a model for algal evolutionary ecology. Here, we report new whole-genome assemblies for two species (Gracilaria chilensis and Gracilaria gracilis), a draft genome assembly of Gracilaria caudata, and genome annotation of the previously published Gracilaria vermiculophylla genome. To facilitate accessibility and comparative analysis, we integrated these data in a newly created web-based portal dedicated to red algal genomics (https://rhodoexplorer.sb-roscoff.fr). These genomes will provide a resource for understanding algal biology and, more broadly, eukaryotic evolution.
Efficient and Highly Continuous Chromosome-Level Genome Assembly of the First Chameleon Genome
Authors: Xie Hongxin , Chen Zixuan , Pang Shuai , Du Weiguo
Published: July 2023

Most amniote genomes are diploid and moderate in size (∼1–6 Gbp) and contain a large proportion of repetitive sequences. The development of next-generation sequencing technology, especially the emergence of high-fidelity (HiFi) long-read data, has made it feasible to resolve high-quality genome assembly for nonmodel species efficiently. However, reference genomes for squamate reptiles have lagged behind other amniote lineages. Here, we de novo assembled the first genome from the Chameleonidae family, the panther chameleon (Furcifer pardalis). We obtained telomere-to-telomere contigs using only HiFi data, reaching a contig N50 of 158.72 Mbp. The final chromosome-level assembly is 1.61 Gbp in size, and 100% of primary contigs were placed to pseudochromosomes using Hi-C interaction data. We also found that sequencing depth > 30 folds can ensure both the integrity and accuracy of the genome, whereas insufficient depth led to false increase in genome size and proportion of duplicated genes. We provide a high-quality reference genome valuable for evolutionary and ecological studies in chameleons as well as provide comparative genomic resources for squamate reptiles.
Unusually Divergent Ubiquitin Genes and Proteins in Plasmodium Species
Authors: Dalhuisen Thomas , Plenderleith Lindsey J , Ursani Ismail , Philip Nisha , Hahn Beatrice H , Sharp Paul M
Published: July 2023

Ubiquitin is an extraordinarily highly conserved 76 amino acid protein encoded by three different types of gene, where the primary translation products are fusions either of ubiquitin with one of two ribosomal proteins (RPs) or of multiple ubiquitin monomers from head to tail. Here, we investigate the evolution of ubiquitin genes in mammalian malaria parasites (Plasmodium species). The ubiquitin encoded by the RPS27a fusion gene is highly divergent, as previously found in a variety of protists. However, we also find that two other forms of divergent ubiquitin sequence, each previously thought to be extremely rare, have arisen recently during the divergence of Plasmodium subgenera. On two occasions, in two distinct lineages, the ubiquitin encoded by the RPL40 fusion gene has rapidly diverged. In addition, in one of these lineages, the polyubiquitin genes have undergone a single codon insertion, previously considered a unique feature of Rhizaria. There has been disagreement whether the multiple ubiquitin coding repeats within a genome exhibit concerted evolution or undergo a birth-and-death process; the Plasmodium ubiquitin genes show clear signs of concerted evolution, including the spread of this codon insertion to multiple repeats within the polyubiquitin gene.
Suture tie-down forces and cyclic contractile forces after undersized tricuspid annuloplasty using a Tri-Ad Adams tricuspid annuloplasty ring in an ovine model
Authors: Cho Sungkyu , Park Chan Hun , Shin Heean , Lim Jae Hong , Sohn Suk Ho , Kim Ji Seong , Choi Jae Woong , Lee Jung Chan , Kim Woong-Han , Hwang Ho Young
Published: July 2023

OBJECTIVES

This study evaluated suture tie-down forces and cyclic contractile forces (CCFs) after undersized tricuspid annuloplasty using a hybrid band.

METHODS

Downsized tricuspid annuloplasty was planned in adult male sheep using 8 force transducers attached from the septal to the anterior annular areas of the ring (segments 1 and 2, flexible septal; segments 3 and 4, semi-rigid posterior; segments 5 and 6, semi-rigid anterior; segments 7 and 8, flexible anterior). CCFs were analysed at 3 different levels of peak right ventricular pressure (RVP): 30, 50 and 70 mmHg.

RESULTS

Eight 5-year-old male Corriedale sheep (average body weight = 66.8 kg) were used. The average suture tie-down force was 4.42 [standard deviation (SD): 2.32] N. When the forces were compared, it was lowest in the flexible anterior area and highest in the flexible septal area (P < 0.001). With the RVP of 30 mmHg, the average CCFs was lowest at segment 3 [0.07 (SD: 0.07) N] and highest at segment 7 [0.15 (SD: 0.08) N]. The CCFs were 0.12 (SD: 0.1) N, 0.09 (SD: 0.12) N, 0.14 (SD: 0.1) N and 0.13 (SD: 0.09) N in the flexible septal, semi-rigid posterior, semi-rigid anterior and flexible anterior parts, respectively (P = 0.208). As the peak RVP increased to 50 and 70 mmHg, the CCFs of each area increased significantly (P < 0.001). Despite this increase, the CCFs remained low (0.1 and 0.3 N), and differences in CCFs between segments and between annular areas showed similar patterns.

CONCLUSIONS

The flexible end of the hybrid band reduces the CCFs and might prevent annular tears after ring tricuspid annuloplasty, and the risk of tear would be low even in the septal area.
Reasons and predictors of non-participation in a personalized digital prehabilitation care trial for patients undergoing elective cardiothoracic surgery
Authors: Scheenstra Bart , Bongers Bart C , Broeders Britney , Imkamp Maike , Van Susante Lieke , Kietselaer Bas , Maessen Jos , Van ’T Hof Arnoud , Sardari Nia Peyman
Published: July 2023

OBJECTIVES

Prehabilitation through a digital platform could preoperatively improve the physical and mental fitness of patients undergoing cardiothoracic surgery, thereby improving treatment outcomes. This study aimed to describe the reasons and predictors of non-participation in a personalized digital prehabilitation care trial (Digital Cardiac Counseling randomized controlled trial) for patients undergoing elective cardiothoracic surgery.

METHODS

Adult patients scheduled for elective cardiothoracic surgery at the Maastricht University Medical Center+ were approached to participate in a digital prehabilitation care trial, in which patients were informed about their care pathway, monitored for symptom progression and screened for preoperative modifiable risk factors. Baseline characteristics of all eligible patients and reasons of non-participation were registered prospectively. Predictors of non-participation were determined using logistic regression.

RESULTS

Between May 2020 and August 2022, 815 patients were eligible for participation; 421 (52%) did not participate in the personalized digital prehabilitation care trial. Reasons for non-participation were ‘lack of internet access or insufficient digital skills’ (32%), ‘wishing no participation’ (39%) and ‘other reasons’ (30%; e.g. vision or hearing impairments, analphabetism, language barriers). Independent predictors of non-participation were age [odds ratio (OR) 1.024 (1.003–1.046), P = 0.024], socioeconomic status [OR 0.267 (0.133–0.536), P < 0.001], current smoker [OR 1.823 (1.124–2.954), P = 0.015] and EuroSCORE II [OR 1.160 (1.042–1.292), P = 0.007].

CONCLUSIONS

Half of the eligible patients did not participate in a personalized digital prehabilitation care trial. Non-participants were vulnerable patients, with a more unfavourable risk profile and more modifiable risk factors, who could potentially benefit the most from prehabilitation.
Mortality-based indicators for measuring health system performance and population health in high-income countries: a systematic review
Authors: Liang Catherine Y , Kornas Kathy , Bornbaum Catherine , Shuldiner Jennifer , De Prophetis Eric , Buajitti Emmalin , Pach Beata , Rosella Laura C
Published: July 2023

Objectives

Mortality-based indicators are commonly used as measures of population health but less frequently applied to measuring health system performance. This systematic review aimed to identify and describe mortality indicators relevant to the measurement of population health and health system performance in high-income countries.

Methods

We searched peer-reviewed databases (MEDLINE, Embase, CINAHL, Health Business Elite, Health Policy Reference Center, and POPLINE) and grey literature (government agencies, professional associations, and international/non-governmental health organizations). The search was limited to indicators identified for use in high-income countries. We extracted information on indicator characteristics and alignment with dimensions of effectiveness, efficiency, and equity. We assessed the applicability of the indicator to the context of population health, health system, or both settings, alignment with SMART criteria (specific, measurable, actionable, relevant, and timely), and potential for analyses of population subgroups. Health system was defined as encompassing both medical care and public health services and activities.

Results

We extracted 385 mortality-based indicators from 240 sources. Indicators were organized into six major domains: all-cause mortality (n = 12), premature mortality (n = 92), life expectancy (n = 23), cause-specific mortality (n = 127), infant, child, and adolescent mortality (n = 50), and hospital-related mortality (n = 81). The majority of indicators (86%) could be applied to measuring health system performance. Premature mortality indicators showed the most potential to measuring both population health and health system performance.

Conclusions

This review compiled a wide range of mortality indicators relevant to measuring health system performance in high-income countries. Indicators of premature mortality were most relevant to measuring both population health and health system performance.
Integral p-Adic Cohomology Theories
Authors: Abe Tomoyuki , Crew Richard
Published: July 2023

In this paper, we show the non-existence of finitely generated integral $p$-adic cohomology that satisfies finite étale descent and the associated rational cohomology coincides with rigid cohomology.
A Generalization of the Murnaghan–Nakayama Rule for K-k-Schur and k-Schur Functions
Authors: Nguyen Duc-Khanh
Published: July 2023

The $K$-$k$-Schur functions and $k$-Schur functions appeared in the study of $K$-theoretic and affine Schubert Calculus as polynomial representatives of Schubert classes. In this paper, we introduce a new family of symmetric functions $\mathcal {F}_{\lambda }^{(k)}$, that generalizes the constructions via the Pieri rule of $K$-$k$-Schur functions and $ k$-Schur functions. Then we obtain the Murnaghan–Nakayama rule for the generalized functions. The rule is described explicitly in the cases of $K$-$k$-Schur functions and $k$-Schur functions, with concrete descriptions and algorithms for coefficients. Our work recovers the result of Bandlow, Schilling, and Zabrocki for $k$-Schur functions, and explains it as a degeneration of the rule for $K$-$k$-Schur functions. In particular, many other special cases and connections promise to be detailed in the future.
Lung group 2 innate lymphoid cells differentially depend on local IL-7 for their distribution, activation, and maintenance in innate and adaptive immunity-mediated airway inflammation
Authors: Takami Daichi , Abe Shinya , Shimba Akihiro , Asahi Takuma , Cui Guangwei , Tani-ichi Shizue , Hara Takahiro , Miyata Keishi , Ikutani Masashi , Takatsu Kiyoshi , Oike Yuichi , Ikuta Koichi
Published: July 2023

Interleukin-7 (IL-7) is a cytokine critical for the development and maintenance of group 2 innate lymphoid cells (ILC2s). ILC2s are resident in peripheral tissues such as the intestine and lung. However, whether IL-7 produced in the lung plays a role in the maintenance and function of lung ILC2s during airway inflammation remains unknown. IL-7 was expressed in bronchoalveolar epithelial cells and lymphatic endothelial cells (LECs). To investigate the role of local IL-7 in lung ILC2s, we generated two types of IL-7 conditional knockout (IL-7cKO) mice: Sftpc-Cre (SPC-Cre) IL-7cKO mice specific for bronchial epithelial cells and type 2 alveolar epithelial cells and Lyve1-Cre IL-7cKO mice specific for LECs. In steady state, ILC2s were located near airway epithelia, although lung ILC2s were unchanged in the two lines of IL-7cKO mice. In papain-induced airway inflammation dependent on innate immunity, lung ILC2s localized near bronchia via CCR4 expression, and eosinophil infiltration and type 2 cytokine production were reduced in SPC-Cre IL-7cKO mice. In contrast, in house dust mite (HDM)-induced airway inflammation dependent on adaptive immunity, lung ILC2s localized near lymphatic vessels via their CCR2 expression 2 weeks after the last challenge. Furthermore, lung ILC2s were decreased in Lyve1-Cre IL-7cKO mice in the HDM-induced inflammation because of decreased cell survival and proliferation. Finally, administration of anti-IL-7 antibody attenuated papain-induced inflammation by suppressing the activation of ILC2s. Thus, this study demonstrates that IL-7 produced by bronchoalveolar epithelial cells and LECs differentially controls the activation and maintenance of lung ILC2s, where they are localized in airway inflammation.
Advantages and disadvantages of using theory-based versus data-driven models with social and behavioral determinants of health data
Authors: Austin Robin R , McLane Tara M , Pieczkiewicz David S , Adam Terrence , Monsen Karen A
Published: July 2023

Objective

Theory-based research of social and behavioral determinants of health (SBDH) found SBDH-related patterns in interventions and outcomes for pregnant/birthing people. The objectives of this study were to replicate the theory-based SBDH study with a new sample, and to compare these findings to a data-driven SBDH study.

Materials and Methods

Using deidentified public health nurse-generated Omaha System data, 2 SBDH indices were computed separately to create groups based on SBDH (0–5+ signs/symptoms). The data-driven SBDH index used multiple linear regression with backward elimination to identify SBDH factors. Changes in Knowledge, Behavior, and Status (KBS) outcomes, numbers of interventions, and adjusted R-squared statistics were computed for both models.

Results

There were 4109 clients ages 13–40 years. Outcome patterns aligned with the original research: KBS increased from admission to discharge with Knowledge improving the most; discharge KBS decreased as SBDH increased; and interventions increased as SBDH increased. Slopes of the data-driven model were steeper, showing clearer KBS trends for data-driven SBDH groups. The theory-based model adjusted R-squared was 0.54 (SE = 0.38) versus 0.61 (SE = 0.35) for the data-driven model with an entirely different set of SBDH factors.

Conclusions

The theory-based approach provided a framework to identity patterns and relationships and may be applied consistently across studies and populations. In contrast, the data-driven approach can provide insights based on novel patterns for a given dataset and reveal insights and relationships not predicted by existing theories. Data-driven methods may be an advantage if there is sufficiently comprehensive SBDH data upon which to create the data-driven models.
Toward a high-resolution mechanism of intrinsically disordered protein self-assembly
Authors: Sekiyama Naotaka , Kobayashi Ryoga , Kodama Takashi S
Published: July 2023

Membraneless organelles formed via the self-assembly of intrinsically disordered proteins (IDPs) play a crucial role in regulating various physiological functions. Elucidating the mechanisms behind IDP self-assembly is of great interest not only from a biological perspective but also for understanding how amino acid mutations in IDPs contribute to the development of neurodegenerative diseases and other disorders. Currently, two proposed mechanisms explain IDP self-assembly: (1) the sticker-and-spacer framework, which considers amino acid residues as beads to simulate the intermolecular interactions, and (2) the cross-β hypothesis, which focuses on the β-sheet interactions between the molecular surfaces constructed by multiple residues. This review explores the advancement of new models that provide higher resolution insights into the IDP self-assembly mechanism based on new findings obtained from structural studies of IDPs.
Isolated Flat Epithelial Atypia: Upgrade Outcomes After Multidisciplinary Review–Based Management Using Excision or Imaging Surveillance
Authors: Xie Charlies L , Whitman Gary J , Middleton Lavinia P , Bevers Therese B , Bedrosian Isabelle , Chung Hannah L
Published: July 2023

Objective

To compare flat epithelial atypia (FEA) upgrade rates after excision versus surveillance and to identify variables associated with upgrade.

Methods

This single-institution retrospective study identified isolated FEA cases determined by percutaneous biopsy from April 2005 through July 2022 with excision or ≥2 years surveillance. All cases were recommended for excision or surveillance based on multidisciplinary discussion of clinical, imaging, and pathologic variables with emphasis on sampling adequacy and significant atypia. Truth was determined by pathology at excision or the absence of cancer on surveillance. Upgrade was defined as cancer occurring ≤2 cm from the biopsy site. Demographic, imaging, and biopsy variables were compared between those that did and did not upgrade.

Results

Among 112 cases of isolated FEA, imaging findings included calcifications in 81.3% (91/112), MRI lesions in 11.6% (13/112), and distortions or masses in 7.1% (8/112). Excision was recommended in 12.5% (14/112) and surveillance in 87.5% (98/112) of cases. Among those recommended for excision, 28.6% (4/14) of cases were upgraded, all to ductal carcinoma in situ. In those recommended for surveillance, 1.0% (1/98) were upgraded to invasive cancer. Overall, FEA had a 4.5% (5/112) upgrade rate, and 2.7% (3/112) also developed cancer >2 cm from the FEA. There were no significant differences in demographic, imaging, and biopsy variables between those that did and did not upgrade to cancer.

Conclusion

Multidisciplinary management of isolated FEA distinguishes those at higher risk of upgrade to cancer (28.6%) in whom surgery is warranted from those at low risk of upgrade (1.0%) who can be managed non-operatively.
Identification, biology, and management of conifer sawflies (Hymenoptera: Diprioninae) in eastern North America
Authors: Davis Jeremy S , Glover Ashleigh N , Everson Kathryn M , Coyle David R , Linnen Catherine R
Published: July 2023

Pine sawflies (Hymenoptera: Diprionidae) are eruptive herbivores found throughout eastern North America. The Diprionidae family, which contains at least 140 species, constitutes the most persistent threat to conifers as population outbreaks can cause widespread defoliation. Because some species are more prone to large, destructive outbreaks than others, species identification is critical to effective management. Although existing taxonomic keys are primarily based on internal adult morphology, substantial variation among species in larval color traits, geographic location, overwintering strategy, host plant, and egg patterns can be diagnostic at the species level. Here, we focus on the Pinaceae-feeding subfamily Diprioninae, of which there are 25 species in eastern North America. We describe the general biology, life cycle, and host-use ecology of Diprioninae, with an emphasis on the variation among these traits within this subfamily. In addition, we provide tools for species identification, including a taxonomic key that utilizes external diagnostic characteristics. Finally, we discuss available management strategies.
The longest reported survival of a child with McCune–Albright syndrome and a severe early presenting phenotype consisting of neonatal cushing syndrome, cardiac and liver diseases
Authors: Alhalabi Rawan , Elsayed Yasmine , Belsha Dalia , Muad Hussein , Zidan Hanaa , Alhubaishi Laila Y , Ramaiah Sridhar , Ba’ath Muhammad E
Published: July 2023

Neonatal cushing syndrome (NCS) is a rare disease that results from prolonged exposure to high cortisol levels. McCune–Albright syndrome (MAS) is an exceedingly rare genetic disorder characterized by cafe-au-lait skin spots, bone fibrous dysplasia and multiple endocrinopathies. We describe a case of a premature neonate with Intrauterine Growth Retardation who presented with hypercortisolemia, neonatal transaminitis and cardiac dysfunction. Further evaluation revealed significant bilateral adrenal hyperplasia leading to the diagnosis of NCS as part of MAS. Despite maximum medical therapy, including metyrapone, the baby’s refractory hypertension, hyperglycemia and persistent failure to thrive (weight of 1.4 kg at corrected age 38 weeks) necessitated bilateral adrenalectomy. This case did not initially demonstrate the classic MAS triad, notably, the absence of skeletal manifestations. There has been no previous description of a baby who has had all the early life-threatening features present and survived beyond 18 months. This case highlights the severity of the phenotype and the challenges involved in diagnosing and treating NCS and MAS in neonates.
Provincialism at Large: Reading Locality, Scale, and Circulation in Nineteenth-Century Britain
Authors: Livesey Ruth
Published: July 2023

This introduction situates the contributions to the New Agenda in the context of an apparent resurgence of the term ‘provincial’ and ‘provincialism’ in Britain since the Brexit debates and the 2016 United Kingdom European Union membership referendum. It takes the resurgence of provincial thinking as an invitation to explore the cultural history of provincialism in Victorian Britain and the unexpected part it played in the formation of Empire. By revaluing the cultural formation of provincialism through this historical lens the articles in this New Agenda help us see the roots of its power now and the alternative possibilities latent within it. Although provincialism emerged as a fraught and politically charged term during the nineteenth century it was also a means to expand access to print and material cultures to those previously excluded. At the same time as provincialism became a pejorative term in the hands of liberal critics such as Matthew Arnold, nineteenth-century Britain was powered by industry, intellectual enquiry, and newspapers emanating from non-metropolitan towns and cities. The provincial press and provincial fiction are crucial ways in which Victorian Britain represented itself as an entity composed of distinctive constituent regions and imagined itself as an imperial power.
Gut microbiota, immunity, and bile acid metabolism: decoding metabolic disease interactions
Authors: Zhao Qixiang , Wu Jiayu , Ding Yong , Pang Yanli , Jiang Changtao
Published: July 2023

In recent decades, the global prevalence of metabolic syndrome has surged, posing a significant public health challenge. Metabolic disorders, encompassing diabetes, obesity, nonalcoholic fatty liver disease, and polycystic ovarian syndrome, have been linked to alterations in the gut microbiota. Nonetheless, the connection between gut microbiota and host metabolic diseases warrants further investigation. In this review, we delve into the associations between various metabolic disorders and the gut microbiota, focusing on immune responses and bile acid (BA) metabolism. Notably, T helper cells, innate lymphoid cells, macrophages, and dendritic cells have been shown to modulate host metabolism through interactions with intestinal microorganisms and the release of cytokines. Furthermore, secondary BA metabolites, derived from the microbiota, are involved in the pathogenesis of metabolic diseases via the farnesoid X receptor and Takeda G protein-coupled receptor 5. By covering both aspects of this immune system-microorganism axis, we present a comprehensive overview of the roles played by the gut microbiota, microbiota-derived BA metabolites, and immune responses in metabolic diseases, as well as the interplay between these systems.
Spatiotemporal Trends in Vision Impairment, Hearing Loss, and Executive Dysfunction Among Active Duty Military Personnel, United States, 2015-2019
Authors: McDaniel Justin T , Collins Sandra , Collins Scott , McKinnies Rick , McKinney Stacey , Walker Jennifer , Albright David L
Published: July 2023

Introduction

Non-Department of Defense (DoD)-curated health surveillance data on military personnel is limited and that which is generated by sources other than the DoD is rarely analyzed for the purposes of disseminating intelligence about health trends in this population. The purpose of this study was to determine spatiotemporal variations in the prevalence of certain conditions (i.e., hearing loss, vision impairment, and executive dysfunction) among active duty and National Guard/Reserve (NGR) military personnel.

Materials and Methods

We obtained person-level data from the 2015–2019 United States Census Bureau’s American Community Survey on active duty military personnel (N = 44,503) and NGRs (N = 146,488). We estimated survey-weighted logistic regression models to determine spatiotemporal differences in hearing loss, vision impairment, and executive dysfunction.

Results

Results showed that when aggregated across time and stratified by military service status, hearing loss was most prevalent (1.71%, 95% CI = 1.55, 1.89), followed by executive dysfunction (1.48%, 95% CI = 1.34, 1.64) and vision impairment (0.65%, 95% CI = 0.55, 0.77), among active duty service members. Among the NGR sample, hearing loss was most prevalent (9.99%, 95% CI = 9.80, 10.18), followed by executive dysfunction (5.35%, 95% CI = 5.20, 5.50) and vision impairment (3.43%, 95% CI = 3.31, 3.55). Overall, disability rates were higher among individuals in the NGR than among those on active duty. Results showed that risk for the aforementioned disabilities varied between 2015 and 2019 and was dependent on the rural location of the respondent’s residence. Specifically, limiting condition prevalence increased from 2015 to 2019 for all types—except for hearing loss among NGRs—among active duty members and NGRs living in rural areas.

Conclusions

Proper surveillance, education, treatment/rehabilitation, and prevention are essential components of mitigating these impairments to help assure the health, wellness, and combat readiness of our military personnel. Recommendations for future military health surveillance activities and health care services are provided.
White dwarf–white dwarf collisions in AGN discs via close encounters
Authors: Luo Yan , Wu Xiao-Jun , Zhang Shu-Rui , Wang Jian-Min , Ho Luis C , Yuan Ye-Fei
Published: July 2023

White dwarfs (WDs) in active galactic nucleus (AGN) discs might migrate to the inner radii of the discs and form restricted three-body systems with two WDs moving around the central supermassive black hole (SMBH) in close orbits. These systems could be dynamically unstable, which can lead to very close encounters or direct collisions. In this work, we use N-body simulations to study the evolution of such systems with different initial orbital separation p, relative orbital inclination Δi, and SMBH mass M. It is found that close encounters of WDs occur mainly at $1.1R_{\rm H} \lesssim p \lesssim 2\sqrt{3}R_{\rm H}$, where RH is the mutual Hill radius. For p < 1.1RH, the majority of WDs move in horseshoe or tadpole orbits, and only few of them with small initial orbital phase difference undergo close encounters. For p = 3.0RH, WD–WD collisions occur in most of the samples within a time 105P1, and considerable collisions occur within a time t < 62P1 for small orbital radii, where P1 is the orbital period. The peak of the closest separation distribution increases and the WD–WD collision fraction decreases with an increase in relative inclination. The closest separation distribution is similar in cases with different SMBH mass, but the WD–WD collision fraction decreases as the mass of SMBHs increases. According to our estimation, the event rate of cosmic WD–WD collisions in AGN discs is about 300 Gpc−3 yr−1, roughly 1 per cent of that of observed Type Ia supernovae. The corresponding electromagnetic emission signals can be observed through large surveys of AGNs.