bluuebunny/crossref_metadata_2025 huggingface dataset:
Atherosclerosis evaluation and cardiovascular risk estimation using coronary computed tomography angiography
Authors: Nurmohamed Nick S , van Rosendael Alexander R , Danad Ibrahim , Ngo-Metzger Quyen , Taub Pam R , Ray Kausik K , Figtree Gemma , Bonaca Marc P , Hsia Judith , Rodriguez Fatima , Sandhu Alexander T , Nieman Koen , Earls James P , Hoffmann Udo , Bax Jeroen J , Min James K , Maron David J , Bhatt Deepak L
Published: April 2024

Clinical risk scores based on traditional risk factors of atherosclerosis correlate imprecisely to an individual’s complex pathophysiological predisposition to atherosclerosis and provide limited accuracy for predicting major adverse cardiovascular events (MACE). Over the past two decades, computed tomography scanners and techniques for coronary computed tomography angiography (CCTA) analysis have substantially improved, enabling more precise atherosclerotic plaque quantification and characterization. The accuracy of CCTA for quantifying stenosis and atherosclerosis has been validated in numerous multicentre studies and has shown consistent incremental prognostic value for MACE over the clinical risk spectrum in different populations. Serial CCTA studies have advanced our understanding of vascular biology and atherosclerotic disease progression. The direct disease visualization of CCTA has the potential to be used synergistically with indirect markers of risk to significantly improve prevention of MACE, pending large-scale randomized evaluation.
Younger but sicker? Cohort trends in disease accumulation among middle-aged and older adults in Scotland using health-linked data from the Scottish Longitudinal Study
Authors: Ribe Eloi , Cezard Genevieve Isabelle , Marshall Alan , Keenan Katherine
Published: April 2024

Background

In the United Kingdom, rising prevalence of multimorbidity—the co-occurrence of two or more chronic conditions- is coinciding with stagnation in life expectancy. We investigate patterns of disease accumulation and how they vary by birth cohort, social and environmental inequalities in Scotland, a country which has long suffered from excess mortality and poorer health outcomes relative to its neighbours.

Methods

Using a dataset which links census data from 1991, 2001 and 2011 to disease registers and hospitalization data, we follow cohorts of adults aged 30–69 years for 18 years. We model physical and mental disease accumulation using linear mixed-effects models.

Results

Recent cohorts experience higher levels of chronic disease accumulation compared to their predecessors at the same ages. Moreover, in more recently born cohorts we observe socioeconomic status disparities emerging earlier in the life course, which widen over time and with every successive cohort. Patterns of chronic conditions are also changing, and the most common diseases suffered by later born cohorts are cancer, hypertension, asthma, drug and alcohol problems and depression.

Conclusion

We recommend policies which target prevention of chronic disease in working age adults, considering how and why certain conditions are becoming more prevalent across time and space.
Patterns of Change in Nucleotide Diversity Over Gene Length
Authors: Ali Farhan
Published: April 2024

Nucleotide diversity at a site is influenced by the relative strengths of neutral and selective population genetic processes. Therefore, attempts to estimate Effective population size based on the diversity of synonymous sites demand a better understanding of their selective constraints. The nucleotide diversity of a gene was previously found to correlate with its length. In this work, I measure nucleotide diversity at synonymous sites and uncover a pattern of low diversity towards the translation initiation site of a gene. The degree of reduction in diversity at the translation initiation site and the length of this region of reduced diversity can be quantified as “Effect Size” and “Effect Length” respectively, using parameters of an asymptotic regression model. Estimates of Effect Length across bacteria covaried with recombination rates as well as with a multitude of translation-associated traits such as the avoidance of mRNA secondary structure around translation initiation site, the number of rRNAs, and relative codon usage of ribosomal genes. Evolutionary simulations under purifying selection reproduce the observed patterns and diversity–length correlation and highlight that selective constraints on the 5′-region of a gene may be more extensive than previously believed. These results have implications for the estimation of effective population size, and relative mutation rates, and for genome scans of genes under positive selection based on “silent-site” diversity.
Evaluating the potential impacts of grey seal predation and fishery bycatch/discards on cod productivity on the Western Scotian Shelf and in the Bay of Fundy
Authors: Rossi Steven P , Wang Yanjun , den Heyer Cornelia E , Benoît Hugues P
Published: April 2024

The recovery of many groundfish stocks in the Northwest Atlantic has been impeded by elevated mortality among older/larger individuals. The sources of groundfish mortality are generally uncertain, though predation by growing grey seal herds and unreported fishing are thought to be drivers of mortality for Atlantic cod (Gadus morhua) on the Western Scotian Shelf and Bay of Fundy (4X5Y), as well as in nearby ecosystems. We developed a statistical catch-at-age model for 4X5Y cod that accounted for grey seal predation and bycatch/discards and tested the model across a broad range of consumption and discard scenarios. We found that most cod mortality was unexplained by seal predation and fishing when cod comprised a small to moderate portion of the grey seal diet. Predation and fishing accounted for slightly more than half of recent cod mortality when cod was highly prevalent in the seal diet (45% by weight) but explained little historical mortality. Bycatch was a minor source of mortality prior to 2019 and accounted for 0.%1–8.1% of recent mortality. Increased sampling of seal diets and monitoring of emerging seal colonies is necessary for reducing uncertainties around seal predation effects in the Northwest Atlantic.
Respiratory Syncytial Virus Prefusion F Vaccination: Antibody Persistence and Revaccination
Authors: Walsh Edward E , Falsey Ann R , Zareba Agnieszka M , Jiang Qin , Gurtman Alejandra , Radley David , Gomme Emily , Cooper David , Jansen Kathrin U , Gruber William C , Swanson Kena A , Schmoele-Thoma Beate
Published: April 2024

Background

Respiratory syncytial virus (RSV) causes substantial respiratory disease. Bivalent RSV prefusion F (RSVpreF) vaccine is licensed in ≥60-year-olds. RSVpreF was well tolerated and immunogenic in a phase 1/2 study. We evaluated antibody persistence after initial vaccination and safety and immunogenicity after revaccination from this study.

Methods

Healthy adults were randomized to receive initial vaccination and revaccination 12 months later with either placebo or RSVpreF (240 µg with or without aluminum hydroxide). RSV-A and RSV-B geometric mean neutralizing titers (GMTs) were measured through 12 months after both vaccinations. Tolerability and safety were assessed.

Results

There were 263 participants revaccinated (18–49 years old, n = 134; 65–85 years old, n = 129). Among 18- to 49-year-olds and 65- to 85-year-olds, geometric mean fold rises (GMFRs) for both RSV subgroups (RSV-A, RSV-B) 1 month after initial RSVpreF vaccination were 13.3 to 20.4 and 8.9 to 15.5, respectively, as compared with levels before initial vaccination; corresponding GMFRs 12 months after initial vaccination were 4.1 to 5.0 and 2.6 to 4.1. GMFRs 1 month after revaccination vs levels before revaccination were 1.4 to 2.3 and 1.4 to 2.2 for 18- to 49-year-olds and 65- to 85-year-olds. Peak GMTs after revaccination were lower than those after initial vaccination. GMTs 12 months after initial vaccination and revaccination were similar, with GMFRs ranging from 0.7 to 1.6. No safety signals occurred.

Conclusions

RSVpreF revaccination was immunogenic and well tolerated among adults.

Clinical Trials Registration. NCT03529773 (ClinicalTrials.gov).
Impact of deoxynivalenol in a calcium depletion and repletion nutritional strategy in piglets
Authors: Sauvé Béatrice , Guay Frédéric , Létourneau Montminy Marie-Pierre
Published: April 2024

This study evaluated the effect of dietary calcium (Ca) levels and deoxynivalenol (DON) contamination on Ca and phosphorus (P) utilization and bone mineralization in piglets. During an initial 13-d depletion phase, 64 piglets (15.7 ± 0.7 kg) received a control (DON−) or DON-contaminated treatment (DON+, 2.7 mg DON/kg) with either a low Ca (Ca−, 0.39%) or normal Ca level (Ca+, 0.65%) with a constant digestible P level (0.40%). A second group of 16 piglets received DON− or DON+ treatments for 9 d for gene expression analysis. During the subsequent 14-d repletion phase, all piglets were fed a Ca+ DON− diet containing 0.65% Ca and 0.35% digestible P without DON. After 5 d of the depletion phase, the absorption of P (DON × Ca; P < 0.05) and Ca was increased by the Ca− (P < 0.01) and DON+ (P < 0.01) diet. After 13 d, feed conversion ratio (P < 0.01) and average daily feed intake (P = 0.06) tended to decrease with the Ca− diet. The bone mineral content (BMC) gain was decreased by Ca, especially with Ca− DON + (DON × Ca, P < 0.05). The P absorption was increased by Ca− DON + (DON × Ca, P < 0.01), although the P retention efficiency was only increased by Ca+ DON + (DON × Ca, P < 0.001). The absorption of Ca was increased by DON+ (P < 0.001), and the Ca efficiency was increased by Ca− DON− (DON × Ca, P < 0.01). After 9 d, the gene expression of intestinal claudin 12 (P < 0.01) and CYP24A1 (P < 0.05), femur cortical RANKL (P < 0.05) and OPG (P = 0.06), and renal calbindin D9K (P < 0.05) and Klotho (P = 0.07) were decreased by DON+. The Ca (P = 0.06) and magnesium (P < 0.01) concentrations were decreased by DON+, and the Ca (P = 0.06) and P digestibility (P < 0.01) were increased. After the repletion phase, Ca− piglets recovered their BMC deficit, but not those receiving DON+ (DON × Ca; P = 0.06). The Ca (P < 0.05) and P (P = 0.06) retention efficiency tended to increase with Ca−. The absorption of Ca and P was increased by Ca− and DON+ (DON × Ca, P < 0.05). The results show that piglets increased their Ca and P utilization efficiency, allowing them to recover the BMC deficit caused by Ca−, but not when the piglets were exposed to DON. Pigs previously receiving Ca-deficient diet with DON still have lower body Ca and P, leading to elevated calcitriol concentrations and enhanced Ca and P intestinal absorption. The fact that DON decreased the expression of genes implicated in Ca intestinal and renal transport and P excretion after 9 d can potentially explain the reduced plasma Ca concentration.
Paratrypaea Komai & Tachikawa, 2008 (Decapoda: Axiidea: Callianassidae): more than two or three species
Authors: Poore Gary C B , Kou Qi
Published: April 2024

Paratrypaea Komai & Tachikawa, 2008 has for more than a decade been thought to contain only two species, both widespread throughout the Indo-West Pacific, or briefly three species. Molecular studies using mitochondrial 16S rRNA and 12S rRNA plus nuclear H3 and 18S rRNA genes, repeated here with samples from more individuals, have shown well separated clades within the genus. Morphological examination has found differences, especially in the form of the adult male cheliped, between the clades leading to the conclusion that Paratrypaea comprises at least eight species of which four are new and described herein. Not all closely related clades could be morphologically distinguished. Some species are narrowly and others widely distributed. The species are: P. baliensissp. nov. from Indonesia; P. bouvieri (Nobili, 1904) from the Red Sea and Indian Ocean; P. chichijimaensis (Sakai, 2015) comb. nov. from Japan; P. dworschakisp. nov. from the Hawaiian Islands; P. maldivensis (Borradaile, 1904) from the eastern Indian Ocean, Papua New Guinea, and possibly western Pacific; P. niuginiensissp. nov. from Papua New Guinea; P. rectangularis (Ngoc-Ho, 1991) from French Polynesia to the Red Sea; and P. rempiensissp. nov. from Papua New Guinea. A published partial 16S sequence from Japan has provided evidence of one more species than those proposed here. Paratrypaea cristata (Borradaile, 1910) comb. nov. remains a species inquirenda.
Natural genetic variation in dynamic photosynthesis is correlated with stomatal anatomical traits in diverse tomato species across geographical habitats
Authors: Yoshiyama Yugo , Wakabayashi Yu , Mercer Kristin L , Kawabata Saneyuki , Kobayashi Takayuki , Tabuchi Toshihito , Yamori Wataru
Published: April 2024

Plants grown under field conditions experience fluctuating light. Understanding the natural genetic variations for a similarly dynamic photosynthetic response among untapped germplasm resources, as well as the underlying mechanisms, may offer breeding strategies to improve production using molecular approaches. Here, we measured gas exchange under fluctuating light, along with stomatal density and size, in eight wild tomato species and two tomato cultivars. The photosynthetic induction response showed significant diversity, with some wild species having faster induction rates than the two cultivars. Species with faster photosynthetic induction rates had higher daily integrated photosynthesis, but lower average water use efficiency because of high stomatal conductance under natural fluctuating light. The variation in photosynthetic induction was closely associated with the speed of stomatal responses, highlighting its critical role in maximizing photosynthesis under fluctuating light conditions. Moreover, stomatal size was negatively correlated with stomatal density within a species, and plants with smaller stomata at a higher density had a quicker photosynthetic response than those with larger stomata at lower density. Our findings show that the response of stomatal conductance plays a pivotal role in photosynthetic induction, with smaller stomata at higher density proving advantageous for photosynthesis under fluctuating light in tomato species. The interspecific variation in the rate of stomatal responses could offer an untapped resource for optimizing dynamic photosynthetic responses under field conditions.
‘Border Country’: health law in a devolved UK
Authors: Harrington John , Hampton Abbie-Rose
Published: April 2024

How are we to understand and research health law under devolution in the UK? Building on work in law and geography, we argue that the figure of the border is key to the production and implementation of devolved health law and the variety of forms that this takes. The utility of border thinking in this context is shown through a review of thematic areas, including infectious disease control, access to health care, and abortion, each instantiating a distinct bordering process. In each, we consider recent developments in policy and legislation, framed with reference to constitutional change, and the politics of devolution in the UK. Taking Wales as an exemplary site, we argue that health law produces borders in traditional and non-traditional places. It creates and blurs territories. It is equally constituted by pluralistic bordering practices. On the basis of this theoretically informed review, we conclude by proposing a cross-disciplinary legal, ethical, and socio-legal research agenda for future research.
Predicting conditional probability distributions of redshifts of Active Galactic Nuclei using Hierarchical Correlation Reconstruction
Authors: Duda Jaroslaw , Bhatta Gopal
Published: April 2024

The Large Area Telescope (LAT) onboard the Fermi gamma-ray observatory continuously scans the sky in an energy range from 50 MeV to 1 TeV. The telescope has identified over 6000 gamma-ray emitting sources, approximately half of which are classified as active galactic nuclei (AGN). However, not all of these gamma-ray sources have known redshift values for the reason that redshift estimation following traditional methods can be an expensive, challenging task. Alternatively, as an effort to robustly predict the AGN redshift values, many researchers have recently turned to machine learning methods. However, while the focus has primarily been on predicting specific values, real-world data often allows us only to predict conditional probability distributions, constrained by conditional entropy [H(Y|X)]. In our study, we employ the Hierarchical Correlation Reconstruction approach to inexpensively predict complex conditional probability distributions, including multimodal ones. This is achieved through independent Mean Squared Error estimation of multiple moment-like parameters, combined into reconstruction of the conditional distribution. By employing linear regression for this purpose, we can develop interpretable models where coefficients describe the contributions of features to conditional moments. This article extends the original approach by incorporating Canonical Correlation Analysis for feature optimization and l1 ‘lasso’ regularization. Our primary focus is on the practical problem of predicting the redshift of AGN using data from the Fourth Fermi-LAT Data Release 3 (4LAC-DR3) data set.
Constraining the coronal properties of AB Dor in the radio regime
Authors: Brasseur C E , Jardine M M , Hussain G A J
Published: April 2024

We present a multiwavelength study of AB Doradus, combining modelling that incorporates a spectropolarimetric magnetic field map with 8.4 GHz radio interferometry to measure the coronal extent and density of this young star. We use the surface magnetic field map to produce a 3D extrapolation of AB Dor’s coronal magnetic field. From this model we create synthetic radio images throughout the stellar rotation period which we can compare with the interferometric radio observations. Our models reproduce the two-lobe structure seen in the radio observations. We successfully fit the observed flux magnitude and lobe separation with our model. We conclude that that the features seen in the radio images are a result of centrifugal containment of hot gas at the peak of closed magnetic loops, and that the corona of AB Dor extends to about 8–10 stellar radii, making it much more extended than the present-day solar corona.
Combating multidrug-resistance in S. pneumoniae: a G-quadruplex binding inhibitor of efflux pump and its bio-orthogonal assembly
Authors: Chaudhuri Ritapa , Prasanth Thumpati , Biswas Debasmita , Mandal Subhranshu , Dash Jyotirmayee
Published: April 2024

Antibiotic resistance poses a significant global health threat, necessitating innovative strategies to combat multidrug-resistant bacterial infections. Streptococcus pneumoniae, a pathogen responsible for various infections, harbors highly conserved DNA quadruplexes in genes linked to its pathogenesis. In this study, we introduce a novel approach to counter antibiotic resistance by stabilizing G-quadruplex structures within the open reading frames of key resistance-associated genes (pmrA, recD and hsdS). We synthesized An4, a bis-anthracene derivative, using Cu(I)-catalyzed azide-alkyne cycloaddition, which exhibited remarkable binding and stabilization of the G-quadruplex in the pmrA gene responsible for drug efflux. An4 effectively permeated multidrug-resistant S. pneumoniae strains, leading to a substantial 12.5-fold reduction in ciprofloxacin resistance. Furthermore, An4 downregulated pmrA gene expression, enhancing drug retention within bacterial cells. Remarkably, the pmrA G-quadruplex cloned into the pET28a(+) plasmid transformed into Escherichia coli BL21 cells can template Cu-free bio-orthogonal synthesis of An4 from its corresponding alkyne and azide fragments. This study presents a pioneering strategy to combat antibiotic resistance by genetically reducing drug efflux pump expression through G-quadruplex stabilization, offering promising avenues for addressing antibiotic resistance.
Choline in pregnant women: a systematic review and meta-analysis
Authors: Nguyen Hoan Thi , Oktayani Pande Putu Ida , Lee Shin-Da , Huang Li-Chi
Published: April 2024

Context: Choline is a critical nutrient. Inadequate choline intake during pregnancy increases the risk of adverse maternal and offspring health.

Objective

A systematic review and meta-analysis were conducted to examine the current recommendations for choline intake by pregnant women, estimate the overall prevalence of pregnant women with adequate choline intake, and explore associations between maternal choline level and adverse pregnancy outcomes (APOs).

Methods

Choline recommendations for pregnant women were assessed from eight nutrient guidelines of the United States, United Kingdom, Canada, Australia, Asia, International Federation of Gynecology and Obstetrics, and World Health Organization. Data on the prevalence of pregnant women with adequate choline intake and the association between maternal choline level and APOs were collected from 5 databases up to May 2023. Meta-analyses with random effects and subgroup analyses were performed for the pooled estimate of prevalence and association.

Results

Five recent nutrition guidelines from the United States (United States Department of Agriculture), United States (Food and Drug Administration), Canada, Australia, and the International Federation of Gynecology and Obstetrics have emphasized the importance of adequate choline intake for pregnant women. Of 27 publications, 19 articles explored the prevalence and 8 articles explored the association. Meta-analysis of 12 prevalence studies revealed a concerning 11.24% (95% confidence interval, 6.34–17.26) prevalence of pregnant women with adequate choline intake recommendations. A meta-analysis of 6 studies indicated a significant association between high maternal choline levels and a reduced risk of developing APOs, with an odds ratio of 0.51 (95% confidence interval, 0.40–0.65).

Conclusion

The existing guidelines highlight the importance of choline in supporting maternal health and fetal development during pregnancy. Furthermore, a high maternal choline level was likely to be associated with a lower risk of APOs. However, 88.76% of pregnant women do not achieve the optimal choline intake. Therefore, specific policies and actions may be necessary to improve choline intake in pregnant women’s care and support the well-being of pregnant women.

Systematic Review Registration

PROSPERO registration no. CDR42023410561.
BIG enhances Arg/N-degron pathway-mediated protein degradation to regulate Arabidopsis hypoxia responses and suberin deposition
Authors: Zhang Hongtao , Rundle Chelsea , Winter Nikola , Miricescu Alexandra , Mooney Brian C , Bachmair Andreas , Graciet Emmanuelle , Theodoulou Frederica L
Published: April 2024

BIG/DARK OVEREXPRESSION OF CAB1/TRANSPORT INHIBITOR RESPONSE3 is a 0.5 MDa protein associated with multiple functions in Arabidopsis (Arabidopsis thaliana) signaling and development. However, the biochemical functions of BIG are unknown. We investigated a role for BIG in the Arg/N-degron pathways, in which substrate protein fate is influenced by the N-terminal residue. We crossed a big loss-of-function allele to 2 N-degron pathway E3 ligase mutants, proteolysis6 (prt6) and prt1, and examined the stability of protein substrates. Stability of model substrates was enhanced in prt6-1 big-2 and prt1-1 big-2 relative to the respective single mutants, and the abundance of the PRT6 physiological substrates, HYPOXIA-RESPONSIVE ERF2 (HRE2) and VERNALIZATION2 (VRN2), was similarly increased in prt6 big double mutants. Hypoxia marker expression was enhanced in prt6 big double mutants; this constitutive response required arginyl transferase activity and RAP-type Group VII ethylene response factor (ERFVII) transcription factors. Transcriptomic analysis of roots not only demonstrated increased expression of multiple hypoxia-responsive genes in the double mutant relative to prt6, but also revealed other roles for PRT6 and BIG, including regulation of suberin deposition through both ERFVII-dependent and independent mechanisms, respectively. Our results show that BIG acts together with PRT6 to regulate the hypoxia-response and broader processes in Arabidopsis.
Effectiveness of intravenous methylprednisolone pulse in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis
Authors: Omura Satoshi , Kida Takashi , Noma Hisashi , Inoue Hironori , Sofue Hideaki , Sakashita Aki , Kadoya Masatoshi , Nakagomi Daiki , Abe Yoshiyuki , Takizawa Naoho , Nomura Atsushi , Kukida Yuji , Kondo Naoya , Yamano Yasuhiko , Yanagida Takuya , Endo Koji , Hirata Shintaro , Matsui Kiyoshi , Takeuchi Tohru , Ichinose Kunihiro , Kato Masaru , Yanai Ryo , Matsuo Yusuke , Shimojima Yasuhiro , Nishioka Ryo , Okazaki Ryota , Takata Tomoaki , Ito Takafumi , Moriyama Mayuko , Takatani Ayuko , Miyawaki Yoshia , Ito-Ihara Toshiko , Yajima Nobuyuki , Kawaguchi Takashi , Hirano Aiko , Fujioka Kazuki , Fujii Wataru , Seno Takahiro , Wada Makoto , Kohno Masataka , Kawahito Yutaka
Published: April 2024

Objectives

To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).

Methods

We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomized into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day and IVMP 1.0 g/day. The primary outcome was all-cause mortality, and the secondary outcomes were composite all-cause mortality and kidney failure, severe relapse and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine–Gray subdistribution hazard model were used.

Results

In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (3%) died, 4 (2.0%) had kidney failure, 11 (5.5%) had severe relapse, and 40 (19.9%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause mortality 0.46 (95% CI: 0.07, 2.81) and 0.07 (95% CI: 0.01, 0.41), respectively; all-cause mortality/kidney failure 1.18 (95% CI: 0.26, 5.31) and 0.59 (95% CI: 0.08, 4.52), respectively; subdistribution HRs for severe relapse were 1.26 (95% CI: 0.12, 13.70) and 3.36 (95% CI: 0.49, 23.29), respectively; and for serious infection 1.88 (95% CI: 0.76, 4.65) and 0.94 (95% CI: 0.28, 3.13), respectively.

Conclusion

IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.
Systemic cycles of accumulation and chaos in the world capitalist system: a missing link
Authors: Galanis Giorgos , Koutny Christian , Weber Isabella
Published: April 2024

We re-examine the systemic cycles of accumulation (SCA) of Arrighi (2010) and Arrighi and Silver (1999) which provide a framework for the analysis of the cyclical patterns of geographical expansion of trade and production and the related shifts of hegemonic power within the world capitalist system. Within the SCA framework, the last stage of a hegemonic cycle is characterized by what is called ‘systemic chaos’. However, the drivers of these dynamics have not been explicitly analyzed. This article fills this gap by providing a link between the accumulation process and systemic chaos. Introducing the logistic map into the SCA analysis, our approach provides the missing detailed understanding of how systemic chaos is an outcome of the contradictory socioeconomic dynamics of capital accumulation itself while being based on the key insights of the SCA framework of hegemonic cycles.
Pathogenesis of sleep-disordered breathing in the setting of opioid use: a multiple mediation analysis using physiology
Authors: Orr Jeremy E , Malhotra Atul , Gruenberg Eli , Marin Traci , Sands Scott A , Alex Raichel M , Owens Robert L , Schmickl Christopher N
Published: April 2024

Study Objectives

Opioid medications are commonly used and are known to impact both breathing and sleep and are linked with adverse health outcomes including death. Clinical data indicate that chronic opioid use causes central sleep apnea, and might also worsen obstructive sleep apnea. The mechanisms by which opioids influence sleep-disordered breathing (SDB) pathogenesis are not established.

Methods

Patients who underwent clinically indicated polysomnography confirming SDB (AHI ≥ 5/hour) were included. Each patient using opioids was matched by sex, age, and body mass index (BMI) to three control individuals not using opioids. Physiology known to influence SDB pathogenesis was determined from validated polysomnography-based signal analysis. PSG and physiology parameters of interest were compared between opioid and control individuals, adjusted for covariates. Mediation analysis was used to evaluate the link between opioids, physiology, and polysomnographic metrics.

Results

One hundred and seventy-eight individuals using opioids were matched to 534 controls (median [IQR] age 59 [50,65] years, BMI 33 [29,41] kg/m2, 57% female, and daily morphine equivalent 30 [20,80] mg). Compared with controls, opioids were associated with increased central apneas (2.8 vs. 1.7 events/hr; p = .001) and worsened hypoxemia (5 vs. 3% sleep with SpO2 < 88%; p = .013), with similar overall apnea–hypopnea index. The use of opioids was associated with higher loop gain, a lower respiratory rate (RR), and higher RR variability. Higher loop gain and increased RR variability mediated the effect of opioids on central apnea, but did not mediate the effect on hypoxemia.

Conclusions

Opioids have multi-level effects impacting SDB. Targeting these factors may help mitigate the deleterious respiratory consequences of chronic opioid use.
Co-culture of RhoA-overexpressed microtia chondrocytes and adipose-derived stem cells in the construction of tissue-engineered ear-shaped cartilage
Authors: Wu Yi , Wang Jian , Li Xiu , Wang Kang , Huang Zonglin , Wang Qian , Fu Xin , Jiang Haiyue , Pan Bo , Xiao Ran
Published: April 2024

Microtia is a congenital auricle dysplasia with a high incidence and tissue engineering technology provides a promising strategy to reconstruct auricles. We previously described that the engineered cartilage constructed from microtia chondrocytes exhibited inferior levels of biochemical and biomechanical properties, which was proposed to be resulted of the decreased migration ability of microtia chondrocytes. In the current study, we found that Rho GTPase members were deficient in microtia chondrocytes. By overexpressing RhoA, Rac1, and CDC42, respectively, we further demonstrated that RhoA took great responsibility for the decreased migration ability of microtia chondrocytes. Moreover, we constructed PGA/PLA scaffold-based cartilages to verify the chondrogenic ability of RhoA overexpressed microtia chondrocytes, and the results showed that overexpressing RhoA was of limited help in improving the quality of microtia chondrocyte engineered cartilage. However, coculture of adipose-derived stem cells (ADSCs) significantly improved the biochemical and biomechanical properties of engineered cartilage. Especially, coculture of RhoA overexpressed microtia chondrocytes and ADSCs produced an excellent effect on the wet weight, cartilage-specific extracellular matrix, and biomechanical property of engineered cartilage. Furthermore, we presented that coculture of RhoA overexpressed microtia chondrocytes and ADSCs combined with human ear-shaped PGA/PLA scaffold and titanium alloy stent fabricated by CAD/CAM and 3D printing technology effectively constructed and maintained auricle structure in vivo. Collectively, our results provide evidence for the essential role of RhoA in microtia chondrocytes and a developed strategy for the construction of patient-specific tissue-engineered auricular cartilage.
Brain Function and Pain Interference after Pediatric Intensive Interdisciplinary Pain Treatment
Authors: Epp Spencer , Walker Andrew , Boudes Elodie , Bray Signe , Noel Melanie , Rayner Laura , Rasic Nivez , Miller Jillian Vinall
Published: April 2024

Background and Objectives:

Intensive interdisciplinary pain treatments (IIPTs) are programs that aim to improve functioning in youth with severe chronic pain. Little is known about how the brain changes following IIPT, however, decreased brain responses to emotional stimuli have been identified previously in pediatric chronic pain relative to healthy controls. We examined whether IIPT increased brain responses to emotional stimuli, and whether this change was associated with a reduction in pain interference.

Methods:

Twenty youth with chronic pain aged 14-18 years were scanned using fMRI, pre- and post-IIPT. During the fMRI, patients were presented with emotional stimuli (i.e., faces expressing happiness/fear), neutral expressions, and control (i.e., scrambled) images. Patients completed a measure of pain interference pre- and post-IIPT. Paired t-tests were used to examine differences in brain activation in response to emotional versus neutral stimuli, pre- to post-IIPT. Data from significant brain clusters were entered into linear mixed models to examine the relationships between brain activation and impairment pre- and post-IIPT.

Results:

Patients demonstrated a decrease in middle frontal gyrus (MFG) activation in response to emotional stimuli (happy + fear) relative to scrambled images, between pre- and post-IIPT (P<0.05). Lower MFG activation was associated with lower pain interference, pre- and-post IIPT (P<0.05).

Conclusion:

Contrary to our hypothesis, IIPT was associated with a reduction in MFG activation to emotional stimuli, and this change was associated with reduced pain interference. The MFG is a highly interconnected brain area involved in both pain chronification and antinociception. With further validation of these results, the MFG may represent an important biomarker for evaluating patient treatment response and target for future pain interventions.
An Interpretable Machine Learning Approach to Predict Survival Outcomes in Spinal and Sacropelvic Chordomas
Authors: Karabacak Mert , Carr Matthew T. , Schupper Alexander J. , Bhimani Abhiraj D. , Steinberger Jeremy , Margetis Konstantinos
Published: April 2024

Study Design.

Retrospective, population-based cohort study.

Objective.

This study aimed to develop machine learning (ML) models to predict five-year and 10-year mortality in spinal and sacropelvic chordoma patients and integrate them into a web application for enhanced prognostication.

Summary of Background Data.

Past research has uncovered factors influencing survival in spinal chordoma patients. While identifying individual predictors is important, personalized survival predictions are equally vital. Though prior efforts have resulted in nomograms aiming to serve this purpose, they cannot capture complex interactions within data and rely on statistical assumptions that may not fit real-world data.

Methods.

Adult spinal and sacropelvic chordoma patients were identified from the National Cancer Database. Sociodemographic, clinicopathologic, diagnostic, and treatment-related variables were utilized as predictive features. Five supervised ML algorithms (TabPFN, CatBoost, XGBoost, LightGBM, and Random Forest) were implemented to predict mortality at five and 10 years postdiagnosis. Model performance was primarily evaluated using the area under the receiver operating characteristic (AUROC). SHapley Additive exPlanations (SHAP) values and partial dependence plots provided feature importance and interpretability. The top models were integrated into a web application.

Results.

From the NCDB, 1206 adult patients diagnosed with histologically confirmed spinal and sacropelvic chordomas were retrieved for the five-year mortality outcome [423 (35.1%) with five-year mortality] and 801 patients for the 10-year mortality outcome [588 (73.4%) with 10-year mortality]. Top-performing models for both of the outcomes were the models created with the CatBoost algorithm. The CatBoost model for five-year mortality predictions displayed a mean AUROC of 0.801, and the CatBoost model predicting 10-year mortality yielded a mean AUROC of 0.814.

Conclusions.

This study developed ML models that can accurately predict five-year to 10-year survival probabilities in spinal chordoma patients. Integrating these interpretable, personalized prognostic models into a web application provides quantitative survival estimates for a given patient. The local interpretability enables transparency into how predictions are influenced. Further external validation is warranted to support generalizability and clinical utility.
No-touch saphenous vein: current understanding of the conduit ‘less handled’
Authors: Deng Mimi X. , Lee Grace S. , Vervoort Dominique , Fremes Stephen E.
Published: April 2024

Purpose of review

The no-touch technique is an established method to harvest the saphenous vein (NT-SV), which is the most commonly used conduit in coronary artery bypass grafting. Herein, we summarize the foundational evidence, as well as highlight recent innovations and ongoing clinical trials involving NT-SV.

Recent findings

Through preservation of perivascular tissue for atraumatic handling and omission of manual distension, the NT-SV maintains endothelial nitrous oxide synthase levels and experiences less vascular smooth muscle cell activation, which translates to slower progression of atherosclerosis and less size mismatch of the graft and target vessel. These biomolecular advantages allow NT-SV to provide superior graft patency compared to conventional skeletonized saphenous vein and approximating that of the radial artery. Nonetheless, the clinical benefits of NT-SV for mortality and reduction in major adverse cardiac and cerebrovascular events are insufficiently studied in the long-term. The drawback of NT-SV is the short-term harvest site complications, which may potentially be addressed by the advent of endoscopic no-touch technique.

NT-SV is a promising conduit, and its role will be further clarified in upcoming clinical trials and as follow-up lengthens. However, conduit selection and harvest technique should ultimately be personalized to the individual patient.
Ustekinumab effectiveness in Crohn’s disease with lesions in the intestines
Authors: Tamura Satoshi , Asai Yusuke , Ishida Natsuki , Miyazu Takahiro , Tani Shinya , Yamade Mihoko , Hamaya Yasushi , Iwaizumi Moriya , Osawa Satoshi , Furuta Takahisa , Sugimoto Ken
Published: April 2024

Ustekinumab is prescribed for the treatment of patients with steroid-resistant moderate to severe Crohn’s disease. We investigated its clinical outcome in patients with small and large intestinal lesions. Patients who were newly administered ustekinumab between March 2014 and December 2020 at Hamamatsu University Hospital were included in the study. The primary endpoint was Crohn’s disease activity index score at baseline and weeks 8, 24, and 48 after the initiation of treatment, and secondary endpoints were albumin, hemoglobin, and C-reactive protein at these time points. Ustekinumab treatment retention was examined in both groups; the 2 groups were compared using the Friedman test, Mann–Whitney U test, or Fisher exact test. Overall, Crohn’s disease activity index scores improved between baseline and 48 weeks, but the difference was not significant. However, there was a significant improvement between baseline and 48 weeks in patients with lesions in the small intestine only. Overall, patients showed significant improvement in albumin levels between baseline and 48 weeks but not in C-reactive protein or hemoglobin levels. When limited to patients with lesions in the small intestine, albumin and hemoglobin levels showed significant improvement. Both types showed high rates of treatment retention, although there was no significant difference. Ustekinumab appears to be a safe and effective treatment option that may be particularly effective in patients with lesions in the small intestine only.
Psychological distress among unemployed migrants settling in southwestern Spain: A cross-sectional study
Authors: Gómez-Salgado Juan , Carrión-Rico David , García-Iglesias Juan Jesús , Climent-Rodríguez José Antonio , Miranda-Plata Rosario , Pichardo-Hexamer Rocío , Navarro-Abal Yolanda , Fagundo-Rivera Javier , Vaca-Acosta Rosa María , Ruiz-Frutos Carlos , Allande-Cussó Regina
Published: April 2024

Migrants living in the informal settlements of Southern Spain tend to have precarious employment and poor living conditions, making then vulnerable to mental health issues. This study aimed to assess psychological distress in a sample of unemployed migrants residing in informal settlements in the province of Huelva (southern Spain), during the fourth wave of the COVID-19 pandemic. A descriptive cross-sectional study was conducted during the months of April to June 2021, through a heteroadministered questionnaire, in informal settlements. The measurement instrument was the General Health Questionnaire (GHQ-12), used to analyze psychological distress, and other sociodemographic and health-related variables. Univariate and bivariate descriptive data analysis were performed, using the nonparametric statistics Mann–Whitney U test, Kruskal–Wallis H test, and Tau β correlation. A categorical regression analysis was performed to study the relationship between psychological distress and the rest of the variables. The sample consisted of 317 subjects, 83.9% of whom were males, and the mean age was 33.4 years (SD = 10.7 years). The mean score obtained in the GHQ-12 questionnaire was 13.69 points (SD = 3.86). Significant differences were found between levels of psychological distress and substance abuse (H = 14.085; P = .049), people who wished to stay in Spain (t = 6987; P = .049), people who experienced isolation due to COVID-19 contact (t = 1379.5; P = .001), people who needed medical assistance due to COVID-19 (t = 7.990; P = .018), and those who reported having chronic illnesses (t = 2686.5, P = .02). The mean score of psychological distress indicates general high levels of psychological distress. Participants who had experienced isolation due to COVID-19 contact, who consumed substances, and who had chronic illnesses reported the highest levels of psychological distress.
Combination of Fushengong decoction with Western medicine on patients with chronic renal failure: An observational study
Authors: Zou Bo , Yuan Qiaoqiao , Luo Hongyu , Wang Munan , Chen Xin , Gao Zuling , Wang Jianwei , Peng Yongbo , Yang Haijun , Dai Feng , Huang Xuekuan
Published: April 2024

Chronic renal failure (CRF) causes a reduction in glomerular filtration rate and damage to renal parenchyma. Fushengong decoction (FSGD) showed improvement in renal function in CRF rats. This study aims to analyze the differentially expressed proteins in CRF patients treated with Western medicine alone or in combination with FSGD. Sixty patients with CRF recruited from Yongchuan Traditional Chinese Medicine Hospital affiliated to Chongqing Medical University were randomly assigned into control (treated with Western medicine alone) and observation groups (received additional FSGD treatment thrice daily for 8 weeks). The clinical efficacy and changes in serum Bun, serum creatinine, Cystatin C, and transforming growth factor beta 1 (TGF-β1) before and after treatment were observed. We employed isotope relative labeling absolute quantification labeling and liquid chromatography–mass spectrometry to identify differentially expressed proteins and carried out bioinformatics Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Patients in the observation group showed greater clinical improvement and lower levels of serum Bun, serum creatinine, Cyc-c, and TGF-β1 than the control group. We identified 32 differentially up-regulated and 52 down-regulated proteins in the observation group. These proteins are involved in the blood coagulation system, protein serine/threonine kinase activity, and TGF-β, which are closely related to the pathogenesis of CRF. Protein–protein-interaction network analysis indicated that candidate proteins fibronectin 1, fibrinogen alpha chain, vitronectin, and Serpin Family C Member 1 were in the key nodes. This study provided an experimental basis suggesting that FSGD combined with Western medicine could significantly improve renal function and renal fibrosis of CRF patients, which may be through the regulation of fibronectin 1, fibrinogen alpha chain, vitronectin, Serpin Family C Member 1, TGF-β, and the complement coagulation pathway (see Graphical abstract S1, Supplemental Digital Content, http://links.lww.com/MD/L947).
Effectiveness and safety of remimazolam combined with alfentanil in hysteroscopic examination: A prospective, randomized, single-blind trial
Authors: Huang Bei , Li Nan-Ping , Tan Gang-Kai , Liang Na
Published: April 2024

Background:

Remimazolam is a novel, ultrashort-acting benzodiazepine. This study aimed to compare the efficacy and safety of remimazolam and propofol for hysteroscopic examination, to determine the optimal dose of remimazolam combined with alfentanil for painless hysteroscopy, and to calculate its median effective dose (ED50).

Methods:

Step 1: A total of 208 patients undergoing hysteroscopic examination were prospectively included in this study. Patients were randomized into 4 groups: 0.2 mg/kg remimazolam (group A), 0.25 mg/kg remimazolam besylate (group B), 0.3 mg/kg remimazolam (group C), and 2 mg/kg propofol (group D), with 52 patients in each group. One minute after losing consciousness, patients received an intravenous injection of alfentanil at 5 µg/kg, followed by a continuous infusion of alfentanil at 0.5 µg/kg/min. If patients showed frowning, movement, or MOAA/S > 1, sedatives were added: 0.05 mg/kg/dose of remimazolam for groups A, B, and C, and 0.5 mg/kg/dose of propofol for group D. Step 2: Dixon’s up-and-down method was used to calculate the ED50 of remimazolam combined with alfentanil during hysteroscopic examination.

Main results:

The sedation success rates of the remimazolam groups were 88.46%, 94.23%, and 98.08%, respectively, compared to 96.15% in the propofol group, with no significant difference (P = .175). MAP in groups A and B was higher than in group D (P < .05), and significantly higher in group C than in group D (P = .0016). SpO2 values in groups A, B, and C were higher than in group D at T2 to T3 (P < .001). HR in groups A, B, and C was significantly higher than in group D (P < .001). The ED50 of remimazolam combined with alfentanil in hysteroscopy was 0.244 mg/kg, 95%CI (0.195–0.22) and ED95 was 0.282 mg/kg, 95%CI (0.261–1.619).

Conclusion:

In hysteroscopy, the sedative effect of remimazolam is like that of propofol, with 0.25 mg/kg remimazolam showing better safety and efficacy, and less impact on the respiratory and circulatory systems. Additionally, under the influence of alfentanil, the ED50 of remimazolam in hysteroscopy is 0.244 mg/kg, with no severe adverse reactions observed.