bluuebunny/crossref_metadata_2025 huggingface dataset:
DeOri 10.0: An Updated Database of Experimentally Identified Eukaryotic Replication Origins
Authors: Zeng Yu-Hao , Yin Zhen-Ning , Luo Hao , Gao Feng
Published: October 2024

DNA replication is a complex and crucial biological process in eukaryotes. To facilitate the study of eukaryotic replication events, we present a database of eukaryotic DNA replication origins (DeOri), which collects genome-wide data on eukaryotic DNA replication origins currently available. With the rapid development of high-throughput experimental technology in recent years, the number of datasets in the new release of DeOri 10.0 increased from 10 to 151 and the number of sequences increased from 16,145 to 9,742,396. Besides nucleotide sequences and browser extensible data (BED) files, corresponding annotation files, such as coding sequences (CDSs), mRNAs, and other biological elements within replication origins, are also provided. The experimental techniques used for each dataset, as well as related statistical data, are also presented on web page. Differences in experimental methods, cell lines, and sequencing technologies have resulted in distinct replication origins, making it challenging to differentiate between cell-specific and non-specific replication origins. Based on multiple replication origin datasets at the species level, we scored and screened replication origins in Homo sapiens, Gallus gallus, Mus musculus, Drosophila melanogaster, and Caenorhabditis elegans. The screened regions with high scores were considered as species-conservative origins, which are integrated and presented as reference replication origins (rORIs). Additionally, we analyzed the distribution of relevant genomic elements associated with replication origins at the genome level, such as CpG island (CGI), transcription start site (TSS), and G-quadruplex (G4). These analysis results can be browsed and downloaded as needed at http://tubic.tju.edu.cn/deori/.
The political economy of national health insurance schemes: evidence from Zambia
Authors: Osei Afriyie Doris , Titi-Ofei Regina , Masiye Felix , Chansa Collins , Fink Günther
Published: October 2024

Governments in low and middle-income countries (LMICs) are increasingly considering the introduction of national health insurance scheme (NHIS) as a strategy to achieve universal health coverage (UHC) targets. The literature has widely documented the technical challenges associated with implementing UHC policies in LMICs but much less is known about the political process necessary to pass UHC legislation. In this article, we document the political economy issues surrounding the establishment of the Zambia NHIS in 2018. We adapted a political economy framework incorporating, semi-structured interviews with diverse stakeholders and document analysis of policies, operational reports and legislatures from 1991 and 2018. Our findings show the 26-year journey towards the establishment of the NHIS in Zambia involved a long sequence of policy dialogue, technical review and stakeholder engagement. Our interviews with key stakeholders suggest that the act was eventually passed due to strong political will and dominant leadership of the Ministry of Health. Passing the law required trade-offs between choices influenced by stakeholder pressures and recommendations from research and actuarial studies. Another equally critical factor was the high public support and legacies of past policies, such as the removal of user fees that had created quality gaps and inequities in the health system. Furthermore, global ideas about UHC and initiatives implemented by other countries also generated support for Zambia’s NHIS. Overall, this study highlights the complex set of political economy factors that need to align in order for governments to be able to adopt health insurance in low-income settings. We show that political leadership and commitment to getting reforms passed is crucial. We also highlight how certain narratives about countries in the global health sphere can shape policies in other countries.
Understanding freshwater to marine transitional scale growth in Atlantic salmon (Salmo salar)
Authors: Ellingson Brandon , Haas-Castro Ruth E , Sigourney Douglas , Kocik John F , Sheehan Timothy F
Published: October 2024

The first marine circulus is the scale feature associated with marine entry and has been used to support research evaluating the relationships between size, growth, and survival for Atlantic salmon. Ambiguity in growth rates and circulus deposition during the transition from freshwater to the marine environment leads to difficulty in the correct identification of the first marine circulus. In this study, scale growth occurring after the last freshwater annulus (plus-growth) was characterized for Atlantic salmon smolts migrating out of the Narraguagus River in Maine. Plus-growth was present in over 95% of scales from smolts leaving the river and represented on average 12.2% of total freshwater growth. These findings suggest plus-growth presents a significant source of error in growth analyses, if ignored, and the characterization of this scale feature helps to inform accurate identification of marine entry for future studies. Run day was a driver of plus-growth, suggesting extended freshwater residency provides opportunity for growth prior to smolt emigration. The negative association between fork length and plus-growth suggests smaller smolts that delay migration are demonstrating compensatory growth. Cumulative air temperature was positively associated with plus-growth, suggesting warming spring temperatures driven by climate change may influence size at marine entry for smolts.
Staggered interventions with no control groups
Authors: Batomen Brice , Benmarhnia Tarik
Published: October 2024

The limitations of the two-way fixed effects for the impact evaluation of interventions that occur at different times for each group have meant that ‘staggered interventions’ have been highlighted in recent years in the econometric literature and, more recently, in epidemiology. Although many alternative strategies (such as staggered difference-in-differences) have been proposed, the focus has predominantly been on scenarios in which one or more control groups are available. However, control groups are often unavailable, due to limitations in the available data or because all units eventually receive the intervention. In this context, interrupted time series (ITS) designs can constitute an appropriate alternative. The extent to which common model specifications for ITS analyses are limited in the case of staggered interventions remains an underexplored area in the methodological literature. In this work, we aim to demonstrate that standard ITS model specifications typically yield biased results for staggered interventions and we propose alternative model specifications that were inspired by recent developments in the difference-in-differences literature to propose adapted analytical strategies.
Polynomial Analogs of Theta Functions and Rational Solutions of the KP Equation
Authors: Agostini Daniele , Çelik Türkü Özlüm , Little John B
Published: October 2024

In this paper we classify the singular curves whose theta divisors in their generalized Jacobians are algebraic, meaning that they are cut out by polynomial analogs of theta functions. We also determine the degree of an algebraic theta divisor in terms of the singularities of the curve. Furthermore, we show a precise relation between such algebraic theta functions and the corresponding tau functions for the KP hierarchy.
Polygenic risk scores stratify breast cancer risk among women with benign breast disease
Authors: Sherman Mark E , Winham Stacey J , Vierkant Robert A , McCauley Bryan M , Scott Christopher G , Schrup Sarah , Gaudet Mia M , Troester Melissa A , Pruthi Sandhya , Radisky Derek C , Degnim Amy C , Couch Fergus J , Bolla Manjeet K , Wang Qin , Dennis Joe , Michailidou Kyriaki , Guenel Pascal , Truong Therese , Chang-Claude Jenny , Obi Nadia , Aronson Kristan J , Murphy Rachel , Garcia-Closas Montserrat , Chanock Stephen , Ahearn Thomas , Yang Xiaohong , Dunning Alison M , Mavaddat Nasim , Pharoah Paul D P , Easton Douglas F , Vachon Celine M
Published: October 2024

Background

Most breast biopsies are diagnosed as benign breast disease, with 1.5- to 4-fold increased breast cancer risk. Apart from pathologic diagnoses of atypical hyperplasia, few factors aid in breast cancer risk assessment of these patients. We assessed whether a 313–single nucleotide variation (formerly single-nucleotide polymorphism) polygenic risk score stratifies risk of benign breast disease patients.

Methods

We pooled data from 5 Breast Cancer Association Consortium case-control studies (mean age = 59.9 years), including 6706 participants with breast cancer and 8488 participants without breast cancer. Using logistic regression, we estimated breast cancer risk associations by self-reported benign breast disease history and strata of polygenic risk score, with median polygenic risk score category among women without benign breast disease as the referent. We assessed interactions and mediation of benign breast disease and polygenic risk score with breast cancer risk.

Results

Benign breast disease history was associated with increased breast cancer risk (odds ratio [OR] = 1.48, 95% confidence interval [CI] = 1.37 to 1.60; P < .001). Polygenic risk score increased breast cancer risk, irrespective of benign breast disease history (Pinteraction = .48), with minimal evidence of mediation of either factor by the other. Women with benign breast disease and polygenic risk score in the highest tertile had more than twofold increased odds of breast cancer (OR = 2.73, 95% CI = 2.41 to 3.09), and those with benign breast disease and polygenic risk score in the lowest tertile experienced reduced breast cancer risk (OR = 0.79, 95% CI = 0.70 to 0.91) compared with the referent group. Women with benign breast disease and polygenic risk score in the highest decile had a 3.7-fold increase (95% CI = 3.00 to 4.61) compared with those with median polygenic risk score without benign breast disease.

Conclusion

Breast cancer risks are elevated among women with benign breast disease and increase progressively with polygenic risk score, suggesting that optimal combinations of these factors may improve risk stratification.
Pyrazolone-nicotinic acid derivative (4Z)-4-(2-hydroxybenzylidine)-5-methyl-2-(pyridine-3-ylcarbonyl)-2, 4-dihydro-3H-pyrazole-3-one (IIc) as multitarget inhibitor of neurodegeneration and behavioural impairment in Dementia
Authors: Kanwal Madiha , Sarwar Sadia , Nadeem Humaira , Alghamdi Suad A , Alamro Abir Abdullah , Malik Sumra , Maqsood Saima , Alghamdi Amani A , Tariq Muhammad Junaid , Malik Imran , Khan Arif Ullah , Muskan Aleena
Published: October 2024

Objective

The study was aimed at the synthesis and pharmacological investigation of (4Z)-4-(2-hydroxybenzylidine)-5-methyl-2-(pyridine-3-ylcarbonyl)-2, 4-dihydro-3H-pyrazole-3-one (IIc) in mice model of scopolamine-induced neurodegeneration and cognition impairment.

Methods

The behavioural studies included Y-Maze Test, Water Morris Test, and Novel Object Recognition Test in Albino mice (20–25 g). Scopalamine was used as an inducing agent. The acetylcholinesterase (AChE) inhibitory assay was used to assess the role of the test compounds in vitro. The Crystal Violet Staining (Nissl staining) was used to assess the neuroprotective and antiapoptotic effect through quantifying the number of neurons and viability. The expression of the anti-inflammatory enzyme cyclooxygenase-2 (COX-2), cytokine tumour necrotic factor (TNF-α), key transcription factor producing pro-inflammatory signals nuclear factor kappa B (P-NFkB), and apoptosis marker p-JNK was validated through enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) analysis. The tested compound reverted cognitive and behavioural impairment through inhibiting scopolamine-induced inflammation and oxidative stress.

Key findings

We found that the compound IIc improved the short-term memory and learning behaviour of the experimental animals. Further investigation into molecular mechanisms showed that this effect was the manifestation of immunomodulatory, antioxidant, and consequently, of downsizing of inflammatory cytokines. These results were further validated through docking analysis.

Conclusion

Finally, we conclude that the pyrazolone-nicotinic acid derivative IIc reversed the scopolamine-induced cognitive and behavioural deficits, attributed to acetylcholinesterase inhibition, neuronal recovery, antioxidant potential, and through downregulating the neuroinflammatory mediators p-NF-kB, cytokine TNF-α, and anti-inflammatory enzyme COX-2.
Successful surgical treatment of a right atrial myxoma with hypothermic circulatory arrest and venous cannulation in pulmonary artery
Authors: Miki Takao , Ohki Satoshi , Yamaguchi Ryo , Nagasawa Ayako , Okonogi Shuichi , Yasuhara Kiyomitsu , Obayashi Tamiyuki
Published: October 2024

Myxomas are the most common type of benign cardiac tumors, and the right atrium is the second most common location among them, with an incidence ranging from 8.6% to 20% of all cardiac myxomas. Herein, we described a rare case of right atrial myxoma originating from the inferior vena cava orifice. In this case, main pulmonary artery cannulation and moderate hypothermic circulatory arrest were helpful to obtain a clear and simple view of the operative field without blood, which led to complete resection of the tumor with safety and better outcomes with no future recurrence.
Cybersecurity risks of automated (and autonomous) offshore oil and gas units—the IMO cybersecurity rules framework
Authors: Jao Juei-Cheng , Chuah Jason C T
Published: October 2024

Automated and/or autonomous offshore platforms or units are becoming more important in the energy sector, whether they are being used for oil and gas extraction or for carbon storage purposes. Automation means that harsh working conditions and risks of personal injury to crew could be cut to virtually zero. Automation also provides significant cost savings and helps make less attractive oil and gas fields more economically viable to exploit. However, automation does come with its own set of challenges—the notable one being the cybersecurity threat. Any regulation or international standard dealing with the cybersecurity risk which is relevant to automated offshore units is usually framed within those rules that apply to ships. This article examines to what extent that regulatory approach, especially that of the International Maritime Organisation’s (IMO) regime, could and should apply to automated or autonomous offshore platforms. It argues that whilst, for now, the IMO cybersecurity guidelines are relevant, a more targeted regulatory approach is needed.
Intermittent Fasting Ameliorates Age-Induced Morphological Changes in Aged Albino Rat Kidney via Autophagy Activation and Reduction of Apoptosis and Inflammation
Authors: Rifaai Rehab Ahmed , El-Tahawy Nashwa Fathy Gamal , Abozaid Samah Mohammed Mahmoud , Abdelwahab Alzahraa
Published: October 2024

Aging is a biological process with gradual decrease of cell function. Kidneys are one of the organs with higher susceptibility to the development of age-dependent tissue damage. Intermittent fasting has several beneficial effects on age-related degenerative changes. The aim of this study was to investigate the possible beneficial effect of intermittent fasting in delaying age-related renal changes and the possible mechanisms of this effect. Thirty male albino rats were classified into three groups: control, adult rats aged 3 months; aged group, 15-month-old rats and maintained until the age of 18 months; and intermittent fasting-aged groups, 15-month-old rats maintained on intermittent fasting for 3 months. Kidneys were processed for histological and immunohistochemical study. Aging resulted in a significant reduction in renal function and significant several degenerative changes in renal corpuscles and tubules which showed abnormal histological structure with increased collagen deposition. Aging caused significant reduction in the expression of autophagic marker light chain 3 with increased expression of active caspase-3 and inducible nitric oxide synthase. Intermittent fasting significantly improved these age-related renal changes. Intermittent fasting effectively prevents age-related renal changes through the reduction of age-related oxidative stress, inflammation, apoptosis, and activation of autophagy.
Cytological Effects of Cadmium Poisoning and the Protective Effect of Quercetin: A Mechanism Exploration based on the Testicular Lamina Propria
Authors: Wang Dian , Xiang Yi , Zhu Zhaoxuan , Liu Jiyue , Wang Yisheng , Xu Zeyu , Chen Si , Dai Chunyuan , Feng Jiasen , Chen Jie , Ma Qianhui , Yang Ping
Published: October 2024

This comprehensive study delved into the detrimental effects of cadmium (Cd), a toxic heavy metal, on the testicular lamina propria (LP), a key player in spermatogenesis, and the maintenance of testicular stem cell niches. Utilizing transmission electron microscopy, immunohistochemistry, and double-labeling immunofluorescence, the research characterized the structural and cellular components of mouse testicular LP under Cd exposure and investigated the protective effects of quercetin. The findings illustrated that Cd exposure results in significant morphological and cellular modifications within the LP, including the apoptosis of peritubular myoid cells, an upsurge in CD34+ stromal cells displaying anti-apoptotic behaviors, and an excessive production of collagen Type I fibers and extracellular matrix. Remarkably, quercetin effectively counteracted these adverse changes by reversing apoptosis, reducing the proliferation of CD34+ stromal cells, and addressing fibrosis markers, thereby mitigating the cellular damage induced by Cd. This study not only highlighted the critical impact of apoptosis and fibrosis in Cd-related testicular damage but also elucidated the protective mechanism of quercetin, laying the groundwork for future clinical applications in addressing testicular damage from heavy metal poisoning through cellular therapeutics and pharmacological interventions.
Machine Learning Reveals the Diversity of Human 3D Chromatin Contact Patterns
Authors: Gilbertson Erin N , Brand Colin M , McArthur Evonne , Rinker David C , Kuang Shuzhen , Pollard Katherine S , Capra John A
Published: October 2024

Understanding variation in chromatin contact patterns across diverse humans is critical for interpreting noncoding variants and their effects on gene expression and phenotypes. However, experimental determination of chromatin contact patterns across large samples is prohibitively expensive. To overcome this challenge, we develop and validate a machine learning method to quantify the variation in 3D chromatin contacts at 2 kilobase resolution from genome sequence alone. We apply this approach to thousands of human genomes from the 1000 Genomes Project and the inferred hominin ancestral genome. While patterns of 3D contact divergence genome wide are qualitatively similar to patterns of sequence divergence, we find substantial differences in 3D divergence and sequence divergence in local 1 megabase genomic windows. In particular, we identify 392 windows with significantly greater 3D divergence than expected from sequence. Moreover, for 31% of genomic windows, a single individual has a rare divergent 3D contact map pattern. Using in silico mutagenesis, we find that most single nucleotide sequence changes do not result in changes to 3D chromatin contacts. However, in windows with substantial 3D divergence just one or a few variants can lead to divergent 3D chromatin contacts without the individuals carrying those variants having high sequence divergence. In summary, inferring 3D chromatin contact maps across human populations reveals variable contact patterns. We anticipate that these genetically diverse maps of 3D chromatin contact will provide a reference for future work on the function and evolution of 3D chromatin contact variation across human populations.
A Minimal Hybrid Sterility Genome Assembled by Chromosome Swapping Between Mouse Subspecies (Mus musculus)
Authors: Fotopulosova Vladana , Tanieli Giordano , Fusek Karel , Jansa Petr , Forejt Jiri
Published: October 2024

Hybrid sterility is a reproductive isolation barrier between diverging taxa securing the early steps of speciation. Hybrid sterility is ubiquitous in the animal and plant kingdoms, but its genetic control is poorly understood. In our previous studies, we have uncovered the sterility of hybrids between musculus and domesticus subspecies of the house mouse, which is controlled by the Prdm9 gene, the X-linked Hstx2 locus, and subspecific heterozygosity for genetic background. To further investigate this form of genic-driven chromosomal sterility, we constructed a simplified hybrid sterility model within the genome of the domesticus subspecies by swapping domesticus autosomes with their homologous partners from the musculus subspecies. We show that the “sterility” allelic combination of Prdm9 and Hstx2 can be activated by a musculus/domesticus heterozygosity of as few as two autosomes, Chromosome 17 (Chr 17) and Chr 18 and is further enhanced when another heterosubspecific autosomal pair is present, whereas it has no effect on meiotic progression in the pure domesticus genome. In addition, we identify a new X-linked hybrid sterility locus, Hstx3, at the centromeric end of Chr X, which modulates the incompatibility between Prdm9 and Hstx2. These results further support our concept of chromosomal hybrid sterility based on evolutionarily accumulated divergence between homologous sequences. Based on these and previous results, we believe that future studies should include more information on the mutual recognition of homologous chromosomes at or before the first meiotic prophase in interspecific hybrids, as this may serve as a general reproductive isolation checkpoint in mice and other species.
The genus Kelliella (Bivalvia) in the Atlantic Ocean
Authors: Utrilla Olga , Gofas Serge , Salas Carmen
Published: October 2024

Kelliella M. Sars, 1870 is a genus of small epibenthic bivalves inhabiting muddy bottoms of the outer shelf and slope worldwide, commonly in habitats that are oxygen-poor or enriched in organic carbon. Currently, there are five accepted species of Kelliella with an Atlantic type locality, and six more Atlantic species, including Vesicomya atlantica (Smith, 1885), the type species of Vesicomya Dall, 1886, were at some time placed in Kelliella. In this work, we revise the genus Kelliella from the North Atlantic waters, based on large amounts of new material from both sides, and describe a new species from Martinique (Kelliella madininae n. sp.). We here propose, after revision of the shell morphology, the synonymy of K.  biscayensis Allen, 2001 with K.  miliaris (Philippi, 1844), and consider a single West European and Mediterranean species of Kelliella. The fossil “Kelliella” barbara is also excluded from the genus Kelliella and reallocated as Coralliophaga barbara (Studencka, 1987) n. comb. In the Atlantic margin of America, we consider that Diplodonta pilula Dall, 1881 remains a nomen dubium. The type material of K.  concentrica Allen, 2001 is figured, and this species considered a member of the Vesicomyinae. The new Caribbean species, K.  madininae, resemble K. brasuca Passos, Machado & Fantinatti, 2017 from southeastern Brazil. We recorded new localities for Kelliella  goesi Odhner, 1960, so far known only from its original description. Diagnostic characters discriminating Vesicomya from Kelliella, stated by Krylova et al. (2018), Journal of Molluscan Studies, 84: 69–91, are discussed, and we consider the hinge architecture as the most robust.
Re-appraising the evidence for the source, regulation and function of p53-family isoforms
Authors: López Ignacio , Valdivia Irene Larghero , Vojtesek Borivoj , Fåhraeus Robin , Coates Philip J
Published: October 2024

The p53 family of proteins evolved from a common ancestor into three separate genes encoding proteins that act as transcription factors with distinct cellular roles. Isoforms of each member that lack specific regions or domains are suggested to result from alternative transcription start sites, alternative splicing or alternative translation initiation, and have the potential to exponentially increase the functional repertoire of each gene. However, evidence supporting the presence of individual protein variants at functional levels is often limited and is inferred by mRNA detection using highly sensitive amplification techniques. We provide a critical appraisal of the current evidence for the origins, expression, functions and regulation of p53-family isoforms. We conclude that despite the wealth of publications, several putative isoforms remain poorly established. Future research with improved technical approaches and the generation of isoform-specific protein detection reagents is required to establish the physiological relevance of p53-family isoforms in health and disease. In addition, our analyses suggest that p53-family variants evolved partly through convergent rather than divergent evolution from the ancestral gene.
Probing the mechanism of nick searching by LIG1 at the single-molecule level
Authors: Chatterjee Surajit , Chaubet Loïc , van den Berg Aafke , Mukhortava Ann , Almohdar Danah , Ratcliffe Jacob , Gulkis Mitchell , Çağlayan Melike
Published: October 2024

DNA ligase 1 (LIG1) joins Okazaki fragments during the nuclear replication and completes DNA repair pathways by joining 3′-OH and 5′-PO4 ends of nick at the final step. Yet, the mechanism of how LIG1 searches for a nick at single-molecule level is unknown. Here, we combine single-molecule fluorescence microscopy approaches, C-Trap and total internal reflection fluorescence (TIRF), to investigate the dynamics of LIG1-nick DNA binding. Our C-Trap data reveal that DNA binding by LIG1 full-length is enriched near the nick sites and the protein exhibits diffusive behavior to form a long-lived ligase/nick complex after binding to a non-nick region. However, LIG1 C-terminal mutant, containing the catalytic core and DNA-binding domain, predominantly binds throughout DNA non-specifically to the regions lacking nick site for shorter time. These results are further supported by TIRF data for LIG1 binding to DNA with a single nick site and demonstrate that a fraction of LIG1 full-length binds significantly longer period compared to the C-terminal mutant. Overall comparison of DNA binding modes provides a mechanistic model where the N-terminal domain promotes 1D diffusion and the enrichment of LIG1 binding at nick sites with longer binding lifetime, thereby facilitating an efficient nick search process.
RNALocate v3.0: Advancing the Repository of RNA Subcellular Localization with Dynamic Analysis and Prediction
Authors: Wu Le , Wang Luqi , Hu Shijie , Tang Guangjue , Chen Jia , Yi Ying , Xie Hailong , Lin Jiahao , Wang Mei , Wang Dong , Yang Bin , Huang Yan
Published: October 2024

Subcellular localization of RNA is a crucial mechanism for regulating diverse biological processes within cells. Dynamic RNA subcellular localizations are essential for maintaining cellular homeostasis; however, their distribution and changes during development and differentiation remain largely unexplored. To elucidate the dynamic patterns of RNA distribution within cells, we have upgraded RNALocate to version 3.0, a repository for RNA-subcellular localization (http://www.rnalocate.org/ or http://www.rna-society.org/rnalocate/). RNALocate v3.0 incorporates and analyzes RNA subcellular localization sequencing data from over 850 samples, with a specific focus on the dynamic changes in subcellular localizations under various conditions. The species coverage has also been expanded to encompass mammals, non-mammals, plants and microbes. Additionally, we provide an integrated prediction algorithm for the subcellular localization of seven RNA types across eleven subcellular compartments, utilizing convolutional neural networks (CNNs) and transformer models. Overall, RNALocate v3.0 contains a total of 1 844 013 RNA-localization entries covering 26 RNA types, 242 species and 177 subcellular localizations. It serves as a comprehensive and readily accessible data resource for RNA-subcellular localization, facilitating the elucidation of cellular function and disease pathogenesis.
Pipolins are bimodular platforms that maintain a reservoir of defense systems exchangeable with various bacterial genetic mobile elements
Authors: Mateo-Cáceres Víctor , Redrejo-Rodríguez Modesto
Published: October 2024

Defense genes gather in diverse types of genomic islands in bacteria and provide immunity against viruses and other genetic mobile elements. Here, we disclose pipolins, previously found in diverse bacterial phyla and encoding a primer-independent PolB, as a new category of widespread defense islands. The analysis of the occurrence and structure of pipolins revealed that they are commonly integrative elements flanked by direct repeats in Gammaproteobacteria genomes, mainly Escherichia, Vibrio or Aeromonas, often taking up known mobile elements integration hotspots. Remarkably, integrase dynamics correlates with alternative integration spots and enables diverse lifestyles, from integrative to mobilizable and plasmid pipolins, such as in members of the genera Limosilactobacillus, Pseudosulfitobacter or Staphylococcus. Pipolins harbor a minimal core and a large cargo module enriched for defense factors. In addition, analysis of the weighted gene repertoire relatedness revealed that many of these defense factors are actively exchanged with other mobile elements. These findings indicate pipolins and, potentially other defense islands, act as orthogonal reservoirs of defense genes, potentially transferable to immune autonomous MGEs, suggesting complementary exchange mechanisms for defense genes in bacterial populations.
Risk of Reinfection and Incidence of Chronic Symptoms After SARS-CoV-2 Infections
Authors: Golding Liam , Watts Allison W , Pitblado Mark , Clemens Felicity , Viñeta Paramo Marina , Shew Jacob , Irvine Michael A , Abu-Raya Bahaa , Goldfarb David M , Mâsse Louise C , Lavoie Pascal M
Published: October 2024

This study showed that a severe acute respiratory syndrome coronavirus 2 infection reduced the risk of reinfection among vaccinated individuals by 0.50 (95% CI, 0.39–0.64) over a 1-year period, after accounting for unreported infections using avidity-based serology. Reciprocally, chronic symptoms increased from a baseline of 21% (95% CI, 16%–28%) among infection-naïve individuals to 43% (95% CI, 30%–61%) in reinfected individuals.
Phytochrome B promotes blast disease resistance and enhances yield in rice
Authors: Li Xinrui , Chen Huan , Yang Shuo , Kumar Vikranth , Xuan Yuan Hu
Published: October 2024

Phytochromes are red/far-red light receptors that regulate various aspects of plant growth, development, and stress responses. The precise mechanism by which phytochrome B (PhyB)-mediated light signaling influences plant defense and development remains unclear. In this study, we showed that PhyB enhances rice (Oryza sativa) blast disease resistance, tillering, and grain size compared to wild-type plants. Notably, PhyB interacted with and degraded grassy tiller 1 (GT1), a negative regulator of tiller development. Knockdown of GT1 in a phyB background partially rescued the diminished tillering of phyB. However, GT1 negatively regulates rice resistance to blast, suggesting that PhyB degradation of GT1 promotes tillering but not blast resistance. Previously, PhyB was found to interact with and degrade phytochrome-interacting factor 15 (PIL15), a key regulator of seed development that reduces rice resistance to blast and seed size. pil15 mutation in phyB mutants rescued phyB seed size and blast resistance, suggesting that PhyB might interact with and degrade PIL15 to negatively regulate blast resistance and seed size. PIL15 directly activated sugar will be eventually exported transporter 2a (SWEET2a). sweet2a mutants were less susceptible to blast disease compared to wild type. Collectively, these data demonstrate that PhyB promotes rice yield and blast resistance by inhibiting the transcription factors GT1 and PIL15 and downstream signaling.
Anarchy, Evolution, and Ethics in International Relations
Authors: Davis James W
Published: October 2024

Challenging the Realist claim that international anarchy produces an amoral sphere of political action, Brian C. Rathbun argues that anarchy has selected for individuals with a particular moral sense. Flipping Realist arguments around, he claims that individuals would have never survived the hardships of anarchy if they were completely amoral. Rather, morality is a precondition for survival in anarchy. But unlike Constructivists, who maintain that socially constructed norms over time have civilized international politics, Rathbun claims that a morality is part of our human nature, and thus, a material feature of the world. To substantiate his claims, Rathbun adeptly applies insights from multiple disciplines, marshalling empirical evidence generated through a variety of natural and social scientific methods.
Current and future advances in practice: SAPHO syndrome and chronic non-bacterial osteitis (CNO)
Authors: Furer Victoria , Kishimoto Mitsumasa , Tomita Tetsuya , Elkayam Ori , Helliwell Philip S
Published: October 2024

Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is a rare, underdiagnosed disease with a wide clinical spectrum. Sterile bone inflammation, predominantly of the anterior chest, and skin manifestations (palmoplantar pustulosis, psoriasis vulgaris and acne) are the key features of SAPHO, which shares certain similarities with SpA. SAPHO is closely related to paediatric chronic non-bacterial osteitis (CNO), a spectrum of autoinflammatory bone diseases. The aetiology of SAPHO is considered multifactorial based on a complex interplay of genetic, immune and infectious factors. Despite the increasing awareness of SAPHO/CNO, diagnostic delay is common, as validated classification and diagnostic criteria are lacking. Treatment of SAPHO represents a challenge and includes anti-inflammatory drugs, antibiotics, bisphosphonates, synthetic conventional DMARDs and off-label use of anti-cytokine biologics and Janus kinase inhibitors. This review summarizes the current diagnostic and practical treatment approach to SAPHO/CNO and highlights the ongoing research endeavours concerning the definition and validation of diagnostic criteria, core domains and treatment.
Inflammation of the temporalis muscle and adjacent nerve tissue in giant cell arteritis: expanding the spectrum of inflammatory lesions
Authors: Ruffer Nikolas , Holzer Marie-Therese , Kawelke Leona , Goebel Hans-Hilmar , Poddubnyy Denis , Schänzer Anne , Preuße Corinna , Krusche Martin , Schneider Udo , Stenzel Werner
Published: October 2024

Objective

The objective of this study was to investigate the histopathological features of the temporalis muscle (TM) and adjacent nerve tissue in active cranial giant cell arteritis (C-GCA).

Methods

Temporal artery biopsy (TAB) specimens containing fragments of the TM from patients with active C-GCA fulfilling the 2022 ACR/EULAR classification criteria (n = 11) were assessed by conventional histology and immunohistochemistry in comparison with non-GCA controls (n = 3). Clinical, laboratory and imaging features based on patient charts at time of biopsy were retrospectively recorded.

Results

The majority of the studied TAB specimens showed inflammation of the TM (10/11) and adjacent nerve fascicles (7/11) that was characterized by prominent endomysial lymphomonocytic infiltrates, whereas controls showed no inflammatory lesions and no disruption of the local architecture. The association of active C-GCA with sarcolemmal MHC class I (8/8) and MHC class II (6/11) upregulation suggests primary inflammation of the TM in a subset of patients. αB-Crystallin positivity (10/11) highlights areas of pre-necrotic myofibres within the TM. The presence of endomysial fibrosis, signs of atrophy and variations in muscle fibre size suggest a rather longstanding and potentially subclinical process of myoinflammation.

Conclusion

Our results expand the spectrum of inflammatory lesions known to be associated with active C-GCA. Specifically, inflammatory infiltration of the TM and adjacent nerve structures could contribute to localized symptoms of the temporomandibular region and may be included in future concepts of pathophysiology.
Arthralgia with risk of progression to psoriatic arthritis: role of clinical assessments and ultrasound as prognostic factors
Authors: Garcia-Salinas Rodrigo , Magri Sebastian , Mareco Jonatan , Jaldin Rosario , Perez Ronald , Ruta Santiago , Baraliakos Xenofon
Published: October 2024

Objectives

Referral of patients from dermatology to rheumatology practices due to psoriasis is unnecessary delayed. Many times musculoskeletal symptoms are the first reason for consultation. We aimed to estimate the proportion of ARP-PsA (arthralgia with risk to progression) defined by patients with arthralgia and the presence of psoriasis and/or a family history. Also, identify clinical, laboratory and imaging prognostic factors of PsA progression within the ARP-PsA group over a one year follow-up period.

Methods

Patients were included in a comprehensive arthralgia evaluation program, with the ARP-PsA criteria defined as arthralgia with Pso and/or a family history of Pso, not referred from dermatology. Baseline characteristics were analysed, and the progression to PsA at one year was assessed. Multivariate analysis identified predictor features for progression.

Results

Of the 1419 patients, 8.4% met ARP-PsA criteria, and 29% of this subgroup developed PsA at one year. Baseline differences between those who developed PsA and those who did not included family history, Pso duration, pain severity, joint count and imaging findings (X-ray and ultrasound). Multivariate analysis revealed the predictive significance of a combination of Pso plus family history of psoriasis disease, synovitis by Power Doppler ultrasound, ultrasound enthesopathy findings and low tender joint count.

Conclusion

The frequency of patients ARP-PsA was 8.4%, of whom 29% developed PsA at one year. The main predictor variables for this progression were identified.
Associations Between Noise Exposure Level, Noise Kurtosis, and Distortion Product Otoacoustic Emissions in Young Workers With Normal Hearing
Authors: Wei Fang , Zhao Wulan , Gao Xiangjing , Xue Panqi , Xu Fei , Xie Hongwei , Yang Ning , Zou Hua , Qiu Wei
Published: October 2024

Objectives:

Growing evidence has suggested that, in addition to noise exposure level, noise temporal structure (i.e., kurtosis) plays an important role in the development of noise-induced hearing loss, while most of the relevant research has been on the results of pure-tone audiometry. This study focuses on the combined effect of noise exposure level and noise kurtosis on distortion product otoacoustic emissions (DPOAEs) in young workers with normal hearing.

Design:

A cross-sectional study among young workers in manufacturing industries was conducted in Zhejiang Province, China. Individual noise exposure measurements were performed on participants to obtain an A-weighted noise exposure level normalized to 8 hr (L
Aeq, 8hr), cumulative noise exposure (CNE), kurtosis, and kurtosis-adjusted CNE (CNE-K). The DPOAE test was performed on the participants and DPOAE levels were obtained. The relationships between noise exposure level, kurtosis, and DPOAE levels were explored by univariate analyses. Furthermore, multivariate regression models were conducted to estimate the combined effects of exposure level and kurtosis after adjusting for age, gender, and use of hearing protection devices.

Results:

The overall DPOAE curves across frequency bands presented a fluctuating downward trend with increasing frequency. Both exposure level and kurtosis were found to be associated with decreases in DPOAE levels. The multivariate regression model including CNE-K as a joint indicator of complex noise showed an increased R
2 compared with the model including CNE. After adjustment for age, gender, and the use of hearing protection devices, significant effects of CNE-K on DPOAE levels were observed at 3, 4, and 5 kHz frequencies, with maximum effect presented at 4 kHz.

Conclusions:

DPOAE is a sensitive test that can detect cochlear damage in limited areas that cannot be detected by conventional audiometry. The present study provided a more comprehensive understanding of the impact of complex noise on the DPOAE levels. It also suggested that CNE-K was an effective metric in assessing DPOAE levels associated with complex noise.
Erector Spinae Plane Block with Liposomal Bupivacaine for Adolescent Idiopathic Scoliosis Surgery
Authors: Young Ernest Y. , Gurd David , Kuivila Thomas , Seif John , Bess Leah , Goodwin Ryan
Published: October 2024

Study Design:

Retrospective Controlled Cohort

Objective:

To evaluate the effect of intraoperative liposomal bupivacaine (LB) via Erector Spinae Plane Block (ESPB) on postoperative adolescent idiopathic scoliosis (AIS) patients with and without patient-controlled analgesia (PCA).

Summary of Background Data:

Pain control after posterior spinal fusion (PSF) for AIS includes opioids and other modalities. The goal of these modalities is to reduce pain and opioid consumption. Two new modalities for pain control include LB and ESPB. There are scant studies on these modalities tested in concert on patients undergoing PSF for AIS

Methods:

72 consecutive patients with AIS who underwent PSF separated into patients who had a PCA (Group A) as part of their postoperative pain management and those who did not (Group B). Opioid consumption was measured via Morphine Milligram Equivalents (MME). Pain scores were measured via the Visual Acuity Score (VAS). Patient mobility was measured by steps taken. These were measured by function of postoperative day from surgery (POD).

Results:

Group B had significant lower MME at every point after surgery, most notably throughout the entire hospital stay (99.8 vs. 200.7). Postoperative pain scores in Group B were the same if not better than Group A. There was no difference in mobility between the cohorts. The Group B had lower LOS (3.7 s 4.1).

Conclusion:

In postoperative PSF for AIS patients receiving LB via ESPB, those who did not receive a PCA had lower opioid consumption without worse pain scores or mobility and had a lower LOS. Adding LB via ESPB to postoperative pain regimens effectively replaces a PCA by providing the same pain control and reducing overall opioid consumption and LOS.
ASSESSMENT OF RETINAL ARTERIOLAR TORTUOSITY IN PATIENTS WITH COL4A1 OR COL4A2 MUTATIONS
Authors: Krivosic Valérie , Goupillou Paul , Buffon-Porcher Frederic , Morel Hélène , Guey Stéphanie , Tadayoni Ramin , Lasserve Elisabeth Tournier , Chabriat Hugues , Gaudric Alain
Published: October 2024

Purpose:

Qualitative and quantitative analyses of retinal arteriolar tortuosity in patients with COL4A1 and COL4A2 mutations to identify a tortuosity index (TI) threshold for detecting increased retinal arteriolar tortuosity.

Methods:

Fifty-two eyes of 28 patients were included. Group 1 included eyes with a normal arteriolar pattern (n = 19, 37%), Group 2 included eyes with moderately increased arteriolar tortuosity (n = 13, 25%), and Group 3 included eyes with typical abnormal arteriolar tortuosity (n = 20, 38%). The TI was measured by calculating the arc-to-chord ratio of arterioles and venules in the posterior pole.

Results:

The mean arteriolar TI was significantly higher in all groups with a COL4A1/A2 mutation compared with controls: 1.19 ± 0.03, 1.24 ± 0.05, and 1.57 ± 0.23 in Groups 1, 2 and 3, respectively, versus 1.12 ± 0.01 (all P < 0.0001). The TI threshold was 1.13, with a sensitivity of 98.1% and a specificity of 100%. The area under the curve was 0.995.

Conclusion:

Measuring the arteriolar TI allowed diagnosing increased retinal arteriolar tortuosity in all eyes with a COL4A1/A2 mutation, whereas the subjective assessment suspected or detected it in only 62% of eyes. In adult patients with cerebral microangiopathy, detecting increased retinal arteriolar tortuosity, even when mild, directs the diagnosis toward COL4A1/A2-related cerebroretinal angiopathy.
The Utility and Limitations of Remotely Delivered Feedback Messages Regarding Physical Activity in a 12-Month Weight Loss Intervention: Insights From the SMARTER Trial Focus Groups
Authors: Kariuki Jacob Kigo , Burke Lora E. , Zickmund Susan , Beatrice Britney , Kimball Elisabeth R. , Galyean Patrick , Cheng Jessica , Sereika Susan M. , Bizhanova Zhadyra , Cedillo Maribel , Wells Jessica , Conroy Molly B.
Published: October 2024

Background

The increasing prevalence of obesity necessitates innovative interventions to address this grave public health concern. Standard behavioral therapy has been the mainstay for promoting weight loss, but its access and uptake are limited. The SMARTER randomized controlled trial aimed to explore the effects of self-monitoring with real-time, remotely delivered tailored feedback to recorded physical activity (PA) on weight loss.

Objective

This qualitative study examined the perceived utility and limitations of key intervention components in promoting PA and weight loss in the SMARTER trial.

Methods

Twenty-three participants who received feedback engaged in Zoom-based focus groups, providing insights into their interactions with the SMARTER app, Fitbit Charge 2 tracker, Aria II scale, and daily weighing. Participants' perspectives on feedback messages, personalized app experiences, and the impact of daily weighing on mental health emerged, providing nuanced insights into the multifaceted nature of success.

Results

Themes from the focus group emphasized the importance of tailoring feedback to individual preferences related to message timing, content, and engagement. The challenges that made the participants stop using the program as instructed included disappointment with not losing weight after several weeks of engagement, inability to open feedback messages within the 60-minute window, and environmental situations that prevented them from acting on the feedback received.

Conclusion

These findings contribute to ongoing efforts geared toward refining interventions targeting PA and weight loss among individuals with obesity and provide important insights for future studies seeking to optimize the design and delivery of remotely delivered feedback messages.
Functional and Social Recovery and Outcomes After Extracorporeal Membrane Oxygenation Support in COVID-19 Patients
Authors: Ozgur Mustafa Mert , Altinay Ece , Ogus Halide , Acar Rezzan Deniz , Atagun Guney Pinar , Kirali Kaan
Published: October 2024

With the COVID pandemic, veno-venous (VV) extracorporeal membrane oxygenation (ECMO) was implanted in many patients around the world. Data regarding follow-up and recovery of patients who are placed on ECMO support after COVID-related acute respiratory distress syndrome (ARDS) or ARDS for any other reason are limited. In our study, we share the 1 year follow-up results and cardiopulmonary exercise test results of the discharged patients. Between April 2020 and February 2022, a total of 29 patients who were supported with VV ECMO due to coronavirus disease 2019 (COVID-19)-related ARDS, weaned successfully and discharged to home, and who came for regular follow-up after discharge from the hospital and underwent examinations were included in the study. A total of 35 patients weaned successfully. Thirty patients were discharged to home. Mean age of the patients was 37.1 (±10.3) and 16 (55%) patients were male. Mean ECMO support time was 49.1 (±22.3) days. One year of survival after discharge was 100%. None of the patients had mobilization problems at the end of 12 month follow-up. Mean VO2 max was 18.9 at the end of 12 months. Return to work rate was 90%. We think that starting rehabilitation in the early period, and including patients in post-ECMO follow-up programs by ECMO centers will contribute significantly not only to the functional recovery of patients but also to their integration into social life.