bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuregulin-1, a member of the epidermal growth factor family, mitigates STING-mediated pyroptosis and necroptosis in ischaemic flaps
Authors: Zhu Xuwei , Yu Gaoxiang , Lv Ya , Yang Ningning , Zhao Yinuo , Li Feida , Zhao Jiayi , Chen Zhuliu , Lai Yingying , Chen Liang , Wang Xiangyang , Xiao Jian , Cai Yuepiao , Feng Yongzeng , Ding Jian , Gao Weiyang , Zhou Kailiang , Xu Hui 
Published: June 2024

Abstract

Background
Ensuring the survival of the distal end of a random flap during hypoperfusion (ischaemia) is difficult in clinical practice. Effective prevention of programmed cell death is a potential strategy for inhibiting ischaemic flap necrosis. The activation of stimulator of interferon genes (STING) pathway promotes inflammation and leads to cell death. The epidermal growth factor family member neuregulin-1 (NRG1) reduces cell death by activating the protein kinase B (AKT) signalling pathway. Moreover, AKT signalling negatively regulates STING activity. We aimed to verify the efficacy of NRG1 injection in protecting against flap necrosis. Additionally, we investigated whether NRG1 effectively enhances ischemic flap survival by inhibiting pyroptosis and necroptosis through STING suppression.

Methods
A random-pattern skin flap model was generated on the backs of C57BL/6 mice. The skin flap survival area was determined. The blood supply and vascular network of the flap was assessed by laser Doppler blood flow analysis. Cluster of differentiation 34 immunohistochemistry (IHC) and haematoxylin and eosin (H&E) staining of the flap sections revealed microvessels. Transcriptome sequencing analysis revealed the mechanism by which NRG1 promotes the survival of ischaemic flaps. The levels of angiogenesis, oxidative stress, necroptosis, pyroptosis and indicators associated with signalling pathways in flaps were examined by IHC, immunofluorescence and Western blotting. Packaging adeno-associated virus (AAV) was used to activate STING in flaps.

Results
NRG1 promoted the survival of ischaemic flaps. An increased subcutaneous vascular network and neovascularization were found in ischaemic flaps after the application of NRG1. Transcriptomic gene ontology enrichment analysis and protein level detection indicated that necroptosis, pyroptosis and STING activity were reduced in the NRG1 group. The phosphorylation of AKT and forkhead box O3a (FOXO3a) were increased after NRG1 treatment. The increased expression of STING in flaps induced by AAV reversed the therapeutic effect of NRG1. The ability of NRG1 to phosphorylate AKT-FOXO3a, inhibit STING and promote flap survival was abolished after the application of the AKT inhibitor MK2206.

Conclusions
NRG1 inhibits pyroptosis and necroptosis by activating the AKT-FOXO3a signalling pathway to suppress STING activation and promote ischaemic flap survival.
Consequences of partially recessive deleterious genetic variation for the evolution of inversions suppressing recombination between sex chromosomes
Authors: Olito Colin , Ponnikas Suvi , Hansson Bengt , Abbott Jessica K 
Published: June 2024

Abstract
The evolution of suppressed recombination between sex chromosomes is widely hypothesized to be driven by sexually antagonistic selection (SA), where tighter linkage between the sex-determining gene(s) and nearby SA loci is favored when it couples male-beneficial alleles to the proto-Y chromosome, and female-beneficial alleles to the proto-X. Although difficult to test empirically, the SA selection hypothesis overshadows several alternatives, including an incomplete but often-repeated “sheltering” hypothesis which suggests that expansion of the sex-linked region (SLR) reduces the homozygous expression of deleterious mutations at selected loci. Here, we use population genetic models to evaluate the consequences of partially recessive deleterious mutational variation for the evolution of otherwise neutral chromosomal inversions expanding the SLR on proto-Y chromosomes. Both autosomal and SLR-expanding inversions face a race against time: lightly-loaded inversions are initially beneficial, but eventually become deleterious as they accumulate new mutations, after which their chances of fixing become negligible. In contrast, initially unloaded inversions eventually become neutral as their deleterious load reaches the same equilibrium as non-inverted haplotypes. Despite the differences in inheritance and indirect selection, SLR-expanding inversions exhibit similar evolutionary dynamics to autosomal inversions over many biologically plausible parameter conditions. Differences emerge when the population average mutation load is quite high; in this case large autosomal inversions that are lucky enough to be mutation-free can rise to intermediate to high frequencies where selection in homozygotes becomes important (Y-linked inversions never appear as homozygous karyotypes); conditions requiring either high mutation rates, highly recessive deleterious mutations, weak selection, or a combination thereof.
The Physiologic Complexity of Prefrontal Oxygenation Dynamics Is Associated With Age and Executive Function: An Exploratory Study
Authors: Hong Yinglu , Zhou Junhong , Yu Wanting , Iloputaife Ikechukwu , Bao Dapeng , Zhou Yuncong , Manor Brad , Lipsitz Lewis A , Jor’dan Azizah J 
Published: June 2024

Abstract

Background
The hemodynamics of prefrontal cortex (PFC) oxygenation are regulated by numerous processes operating over multiple temporal scales, producing complex patterns in its output fluctuations. Age may alter this multiscale regulation of PFC oxygenation, leading to diminished physiologic complexity of this important regulatory process. We aimed to characterize the effects of age on such complexity and its relationship to performance of an executive n-back task.

Methods
Twenty-four younger (aged 28 ± 3 years) and 27 older (aged 78 ± 6 years) adults completed this study. Continuous oxygenation (HbO2) and deoxygenation (HHb) signals of PFC were recorded using functional near-infrared spectroscopy (fNIRS) while participants stood and watched a blank screen (blank), clicked a mouse when an X appeared (IdX), or when a letter was repeated from “2-back” in a sequence shown on a screen (2-back). We used multiscale entropy to quantify the HbO2 and HHb complexity of fNIRS signals.

Results
Older adults exhibited lower HbO2 and HHb complexity compared to younger adults, regardless of task (p = .0005–.002). Both groups exhibited greater complexity during the IdX and 2-back than blank task (p = .02–.04). Across all participants, those with greater HbO2 and/or HHb complexity during the blank task exhibited faster IdX and 2-back reaction time (β = −0.56 to −0.6, p = .009–.02). Those demonstrating greater increase in HbO2 and/or HHb complexity from IdX to 2-back task had lower percent increase in reaction time from IdX to 2-back task (β = −0.41 to −0.37, p = .005–.01).

Conclusions
The complexity of fNIRS-measured PFC oxygenation fluctuations may capture the influence of aging on the regulation of prefrontal hemodynamics involved in executive-function-based task performance.
Positive functional filters synthesis for positive linear systems
Authors: Ezzine Montassar , Darouach Mohamed , Souley Ali Harouna , Messaoud Hassani 
Published: June 2024

Abstract
This paper deals with the problem of positive functional $H_{\infty }$ filtering for positive linear systems subject to both bounded disturbances and unknown inputs. The order of the designed $H_{\infty }$ filter is equal to the dimension of the functional to be estimated, that can be useful for control purpose for example. We focus on the design of positive filters which guarantee that the functional (of the state) is always non-negative at any time and converges to the real functional state by minimizing the effect of the disturbances on the estimation error. In fact, we propose a new positive reduced order $H_{\infty }$ filter for positive linear systems for which the states remain in the non-negative orthant of the state space, subject to both disturbances and unknown inputs. This paper is a first attempt to design positive unknown inputs functional $H_{\infty }$ filter for such positive linear systems. The proposed approach is based on the positivity of an augmented system composed of dynamics of both considered system and proposed filter, on the unbiasedness of the estimation error by the resolution of Sylvester equation; then we derive conditions for the establishment of such filters in terms of an optimization problem. An algorithm that summarizes the different steps of the proposed positive functional $H_{\infty }$ filter design is given. Finally, numerical example and simulation results are given to showcase the effectiveness of the proposed design method.
Competitive inhibition and mutualistic growth in co-infections: deciphering Staphylococcus aureus–Acinetobacter baumannii interaction dynamics
Authors: Timme Sandra , Wendler Sindy , Klassert Tilman E , Saraiva Joao Pedro , da Rocha Ulisses Nunes , Wittchen Manuel , Schramm Sareda , Ehricht Ralf , Monecke Stefan , Edel Birgit , Rödel Jürgen , Löffler Bettina , Ramirez Maria Soledad , Slevogt Hortense , Figge Marc Thilo , Tuchscherr Lorena 
Published: June 2024

Abstract
Staphylococcus aureus (Sa) and Acinetobacter baumannii (Ab) are frequently co-isolated from polymicrobial infections that are severe and refractory to therapy. Here, we apply a combination of wet-lab experiments and in silico modeling to unveil the intricate nature of the Ab/Sa interaction using both, representative laboratory strains and strains co-isolated from clinical samples. This comprehensive methodology allowed uncovering Sa's capability to exert a partial interference on Ab by the expression of phenol-soluble modulins. In addition, we observed a cross-feeding mechanism by which Sa supports the growth of Ab by providing acetoin as an alternative carbon source. This study is the first to dissect the Ab/Sa interaction dynamics wherein competitive and cooperative strategies can intertwine. Through our findings, we illuminate the ecological mechanisms supporting their coexistence in the context of polymicrobial infections. Our research not only enriches our understanding but also opens doors to potential therapeutic avenues in managing these challenging infections.
Osteoporosis treatment prevents hip fracture similarly in both sexes: the FOCUS observational study
Authors: Keaveny Tony M , Adams Annette L , Orwoll Eric S , Khosla Sundeep , Siris Ethel S , McClung Michael R , Bouxsein Mary L , Fatemi Shireen , Lee David C , Kopperdahl David L 
Published: June 2024

Abstract
Randomized trials have not been performed, and may never be, to determine if osteoporosis treatment prevents hip fracture in men. Addressing that evidence gap, we analyzed data from an observational study of new hip fractures in a large integrated healthcare system to compare the reduction in hip fractures associated with standard-of-care osteoporosis treatment in men versus women. Sampling from 271,389 patients aged ≥ 65 who had a hip-containing CT scan during care between 2005 and 2018, we selected all who subsequently had a first hip fracture (cases) after the CT scan (start of observation) and a sex-matched equal number of randomly selected patients. From those, we analyzed all who tested positive for osteoporosis (DXA-equivalent hip BMD T-score ≤ −2.5, measured from the CT scan using VirtuOst). We defined “treated” as at least six months of any osteoporosis medication by prescription fill data during follow-up; “not-treated” was no prescription fill. Sex-specific odds ratios of hip fracture for treated vs not-treated patients were calculated by logistic regression; adjustments included age, BMD T-score, BMD-treatment interaction, BMD, race/ethnicity, and seven baseline clinical risk factors. At two-year follow-up, 33.9% of the women (750/2,211 patients) and 24.0% of the men (175/728 patients) were treated primarily with alendronate; 51.3% and 66.3%, respectively, were not-treated; and 721 and 269, respectively, had a first hip fracture since the CT scan. Odds ratio of hip fracture for treated vs not-treated was 0.26 (95% confidence interval: 0.21–0.33) for women and 0.21 (0.13–0.34) for men; the ratio of these odds ratios (men:women) was 0.81 (0.47–1.37), indicating no significant sex effect. Various sensitivity and stratified analyses confirmed these trends, including results at five-year follow-up. Given these results and considering the relevant literature, we conclude that osteoporosis treatment prevents hip fracture similarly in both sexes.
Bone mineral density is not associated with incident high-intensity back pain: a 10-year cohort study in men
Authors: Estee Mahnuma M , Wang YuanYuan , Heritier Stephane , Urquhart Donna M , Cicuttini Flavia M , Kotowicz Mark A , Anderson Kara B , Brennan-Olsen Sharon L , Pasco Julie A , Wluka Anita E 
Published: June 2024

Abstract
Although patients believe that osteoporosis is a painful condition, health professionals assume it is painless unless a fracture occurs. The association between BMD and back pain has not been examined longitudinally in community-based adults in an unbiased population using gold-standard measures. This study aimed to examine the association between BMD and incident high-intensity back pain and/or high disability over 10 years in Australian men without high-intensity symptoms at baseline. Men with no high-intensity back pain and/or high disability attending the Geelong Osteoporosis Study at the 5-year visit (occurring between 2006–2010) (considered the baseline for the current study) were followed for 10 years (reassessed between 2016–2021). Back pain and disability were assessed using the Graded Chronic Pain Scale at both time points. At baseline, DXA was used to measure lumbar spine and total hip BMD and spinal artefacts. The relationships between BMD and incident high-intensity pain and/or high disability at follow-up were examined using binary logistic regression, adjusted for age, body mass index, depression, education, smoking, mobility, and spinal artefacts. A total of 679 participants had no to low-intensity pain and/or no to low disability at baseline. A total of 441 attended follow-up, providing back pain and disability data. Thirty-seven men developed high-intensity pain and/or high disability. No association of BMD at any site was seen with incident high-intensity pain and/or high disability. BMD was not associated with incident high-intensity pain or disability in community-based men. These data provide evidence to dispel the erroneous community-held belief that low BMD is related to back pain and disability.
Post-settlement growth and sexual dimorphism in the size and proportion of the body of the varunid crab Gaetice depressus (De Haan, 1833) (Decapoda: Brachyura: Varunidae) based on laboratory-reared material
Authors: Hamasaki Katsuyuki , Takeda Yuji , Dan Shigeki 
Published: June 2024

Abstract
We investigated post-settlement growth patterns and sexual dimorphism in the carapace, pelon, and cheliped dimensions of the varunid crab Gaetice depressus (De Haan, 1833). We reared crabs in the laboratory from hatching through megalopae to the first to tenth instars, and measurements were made of exuviae or specimens of crabs that successively molted. The males were larger than the females in all instars. The molt increments of carapace width (CW) and carapace length (CL) did not differ between the sexes; the former decreased with growth, especially up to ~3–4 mm, whereas the latter did not change with growth. This may be due to the rapid growth in CW compared to CL during early ontogeny. The proportion of CW to CL was larger in the females than in the males, and the rate of increase in pleon width accelerated greatly after growth to ~4 mm CW. Cheliped dimensions were larger in males than in females, probably as a consequence of sexual selection. Cheliped propodus length and width increased with growth in both sexes, but the rates of increase tended to decelerate after ~7 mm CW in females. This indicates that females may allocate more energy to pleon growth while limiting cheliped growth.
Ukraine:
Authors: Anderson Robert D , Jones Alison , Kovacic William E 
Published: June 2024

Abstract
This chapter focuses on the ongoing challenges of deterring corruption and supplier collusion in public procurement in Ukraine, and their relation to Ukraine’s recent history and its ongoing struggle for independence, security, democratic governance, and a decent way of life. Ukraine’s challenges provide a compelling example of the problem of ‘systemic corruption’ as outlined in Chapter 4, offering insights as to both the persistence of related tendencies and their ability to frustrate the aims of a wide array of policy interventions and corrective measures. Notwithstanding the country’s historic institutional deficits, efforts to prevent and deter corruption and supplier collusion in public procurement in Ukraine are not starting from zero. The chapter highlights previous efforts to address corruption and supplier collusion, such as the enactment of relevant legislation, general measures to strengthen the rule of law and relevant institutions, implementation of a transparent e-procurement platform (the ‘ProZorro’ system), engagement of civil society, and bolstering the enforcement of competition law and policy. Overall, the chapter highlights the complexity and interdependence of the measures needed to combat corruption and supplier collusion in a context such as Ukraine’s and the compelling case for greater international support to strengthen related frameworks.
Persistent Corruption and Supplier Collusion in Public Procurement in a (Generally) Well-Governed Country: The Case of Canada
Authors: Anderson Robert D , Jones Alison , Kovacic William E 
Published: June 2024

Abstract
This chapter examines the issue of persistent corruption and supplier collusion in public procurement in Canada, notwithstanding the country’s reputation as a well-governed state having in place relatively sophisticated anti-corruption and competition law systems. It notes that Canada has faced, from its beginnings, problems with corruption and/or bid rigging in public procurement markets that have harmed the government’s finances and its citizens, and caused political embarrassment on various occasions. Multiple related cases are documented and discussed. The underlying causes of such conduct are considered, including generic structural and behavioural factors observed in many countries, and cultural and institutional considerations arguably unique to Canada. The evolution of Canada’s anti-corruption and anti-collusion systems is also reviewed, and multiple related insights are highlighted.
Conclusions
Authors: Anderson Robert D , Jones Alison , Kovacic William E 
Published: June 2024

Abstract
This chapter highlights the core findings of the book, which emphasize the central significance of public procurement to all nations and the pervasive need to shield it from corrupt and collusive practices. It recognizes the extensive challenges involved in developing, and ensuring the enduring effectiveness of, public procurement, anti-corruption and competition laws, and that corruption and collusion risks in the seven jurisdictions examined in the book, remain real. It identifies a number of common, and jurisdiction-specific, problems which create corruption and collusion risks and summarizes the range of solutions proposed for tackling them. It stresses the importance of preventative means, to avert infringements from arising in the first place; effective enforcement of anti-corruption and competition laws to deter infringements and to ensure that a sense of impunity does not develop amongst key players; the need for better policy coordination between relevant agencies; the necessity of political commitment for successful reforms; and the roles of domestic, regional, and international efforts in driving change.
The Deterrence-Based Rationale and the Specific Implications of the EU-Level Doctrine of Parental Antitrust Liability
Authors: Whelan Peter 
Published: June 2024

Abstract
This chapter continues this book’s consideration of the extent to which the EU-level doctrine of parental antitrust liability fulfils the second criterion in the legitimacy framework (‘effectiveness’). In examining the extent to which the specifics of the EU-level approach to parental antitrust liability line up with its identified enforcement justification, it critically evaluates the specific implications of the said approach from a deterrence perspective. In turn, it analyses from that perspective: the European Commission’s (the Commission’s) reliance upon (formal) strict liability when imposing parental liability; its increasing of the antitrust fine with parental liability; the attribution of joint and several liability without any consideration on a case-by-case basis of the specific underpinnings of the deterrence-based rationale, specifically the subsidiary’s inability to pay; and the imposition of joint and several liability for ‘novel’ antitrust violations by subsidiaries. Ultimately, this chapter also finds a specific, critical failing with respect to the alignment of current practice at EU level with the theoretical justification advanced on the basis of deterrence. It thus further emphasises that the second criterion in the legitimacy framework (‘effectiveness’) is not completely fulfilled.
Retribution and Its Relevance to the EU-Level Doctrine of Parental Liability
Authors: Whelan Peter 
Published: June 2024

Abstract
This chapter articulates the specifics of the punishment theory of retribution and establishes its status in EU competition law enforcement. It first sets out the basics of the theory of retribution, details its two most important principles (the principle of personal responsibility and the principle of proportionality), and highlights the EU Court’s acceptance of the applicability of (at least some form of) these principles to antitrust enforcement. Importantly, it establishes the inherent link between responsibility and proportionality, thereby allowing one to employ the principle of personal responsibility as the central analytical tool with which to evaluate the extent to which the EU-level doctrine of parental antitrust liability aligns with the objective of retribution. It then outlines how the theory of retribution is implemented within EU antitrust enforcement. It argues that one can reasonably take the stance that, in EU competition law, the principles of personal responsibility and proportionality seem to act as limiting principles (i.e. ones that serve to restrict in particular circumstances the application of punishment warranted under a deterrence-focused enforcement drive), rather than rationalising or normative principles (i.e. ones that serve to establish the reason for imposing antitrust sanctions per se).