bluuebunny/crossref_metadata_2025_split huggingface dataset:
The time-course augmentation of perivascular space enlargement in the basal ganglia among a community-dwelling elder population
Authors: Sugai Yasuhiro , Hiraka Toshitada , Shibata Akiko , Taketa Ayato , Tanae Taiyo , Moriya Yosuke , Komatsu Masanori , Iseki Chifumi , Ohta Yasuyuki , Kanoto Masafumi 
Published: June 2024

Abstract
Purpose
We examined whether time-course augmentation of perivascular space enlargement in the basal ganglia (BG-PVS) reflected cerebral small vessel disease (CSVD) severity by considering white matter hyperintensity lesion (WMHL) as an indicator for CSVD.

Materials and methods
This study population included 416 older participants from a community-based cohort. They participated in magnetic resonance imaging (MRI) studies more than once during the study period. The grades for BG-PVS and WMHL were evaluated by visual rating scales; BG-PVS time-course augmentation in 4–9 years was also evaluated. At baseline, the participants were asked about their smoking and drinking history, and medical history. They also underwent a blood examination and their office blood pressure (BP) examination. In addition, 24-h ambulatory BP monitoring was also performed within the study period.

Results
Of the 416 participants, 48 participants (11.5%) had BG-PVS time-course augmentation. The participants with BG-PVS augmentation had significantly lower LDL levels, hyper-nighttime BP, and lower nighttime BP fall in univariate analysis (p = 0.03, p = 0.03, p = 0.003, respectively). In multivariate analysis, lower nighttime BP fall and male sex showed significance (p = 0.02, 0.03, respectively). Additionally, BG-PVS time-course augmentation was significantly associated with subsequent WMHL severity in univariate analysis (p < 0.001), which remained significant in multivariate analysis adjusted by imaging and demographic factors (p = 0.03). In multivariate analysis, additionally adjusted by the clinical factors, the significance disappeared (p = 0.07).

Conclusion
This study revealed that the lower nighttime BP fall in ambulatory blood pressure monitoring was a factor significantly associated with BG-PVS augmentation. Moreover, the BG-PVS time-course augmentation would be a notable finding that was associated with the subsequent WMHL.
The newly-adopted Corporate Sustainability Due Diligence Directive: an overview of the lawmaking process and analysis of the final text
Authors: Ciacchi Silvia 
Published: June 2024

AbstractThis article provides an overview of the process leading up to the adoption of the Corporate Sustainability Due Diligence Directive (CSDDD) and delivers a comprehensive analysis of the Directive’s final text. The article contextualises the design process of the CSDDD within the international normative framework on sustainability due diligence and elaborates on key events surrounding the inter-institutional negotiations between the European Commission, the European Parliament and the Council of the European Union on the Directive. The article then delves into the content of the newly adopted text, highlighting key differences between the final version and the Commission’s original proposal.
Sex-Dimorphic Kidney-Brain Connectivity Map of Mice
Authors: Li Xulin , Zhou Yuan , Wang Feng , Wang Liping 
Published: June 2024

AbstractThe kidneys are essential organs that help maintain homeostasis, and their function is regulated by the neural system. Despite the anatomical multi-synaptic connection between the central autonomic nuclei and the kidneys, it remains unclear whether there are any variations in neural connections between the nervous systems and the renal cortex and medulla in male and female mice. Here, we used the pseudorabies virus to map the central innervation network of the renal cortex and medulla in both sexes. The data revealed that specific brain regions displayed either a contralateral-bias or ipsilateral-bias pattern while kidney-innervating neurons distributed symmetrically in the midbrain and hindbrain. Sex differences were observed in the distribution of neurons connected to the left kidney, as well as those connected to the renal cortex and medulla. Our findings provide a comprehensive understanding of the brain-kidney network in both males and females and may help shed light on gender differences in kidney function and disease susceptibility in humans.
Genomic and Phenotypic Safety Assessment of Probiotic Bacillus coagulans Strain JBI-YZ6.3
Authors: Zhang Yongmei , Overbeck Tom J. , Skebba Victoria L. Palmer , Gandhi Neil N. 
Published: June 2024

AbstractSpore-forming Bacillus coagulans has been widely recognized as an important probiotic, which is commonly used in products for human consumption and animal feeds. B. coagulans exhibits beneficial traits from both Bacillus and lactic acid-producing Lactobacillus. The present study evaluated the safety of the newly isolated B. coagulans strain JBI-YZ6.3, using combined genomic and phenotypic analysis approaches. The taxonomic classification based on genome sequence and biochemical tests identified strain JBI-YZ6.3 as B. coagulans. Comprehensive genome-based analyses established JBI-YZ6.3 as a novel strain of B. coagulans. Antibiotic susceptibility testing showed that the strain JBI-YZ6.3 was sensitive to a panel of fourteen antibiotics, and no genes related to antibiotic resistance were found in its genome. The spores of strain JBI-YZ6.3 exhibited tolerance to acid and bile salts, as well as stability at ambient and elevated conditions of temperature and relative humidity. There were no homologs of Bacillus toxin genes identified in the genome of JBI-YZ6.3, and the strain exhibited no cytotoxicity towards Vero cells and human peripheral blood mononuclear cells. In conclusion, findings from this study support the safety of B. coagulans strain JBI-YZ6.3, which can be developed into new probiotic products for preventive and therapeutic benefits in human and animal hosts.
Public Support for Business, Intermediary Organizations, and Knowledge Transfer: Critical Development and Innovation Policy Bottlenecks
Authors: Chatzinikolaou Dimos , Vlados Charis 
Published: June 2024

AbstractThis study explores the challenges of integrating macro, meso, and micro in the articulation of advanced innovation policy and examines, respectively, dimensions of public business support, intermediary organizations, and knowledge transfer. It conducts an integrative review of the pertinent literature and a bibliometric analysis of 440 articles. It reveals three major obstacles that seemingly impede the effective integration of macro, meso, and micro in contemporary policymaking and socioeconomic analyses: entrenched boundaries between different thematic areas, methodological discrepancies, and the relative lack of integrated theoretical models. These factors contribute to the absence of unified functional hubs focused on microlevel interventions. The proposed Institutes of Local Development and Innovation (ILDIs) could mitigate these challenges as they are presented as multilevel policy instruments intended to provide support to businesses—particularly to those facing chronic and structural problems.
Some Remarks on Linear-Quadratic Closed-Loop Games with Many Players
Authors: Cirant Marco , Redaelli Davide Francesco 
Published: June 2024

AbstractWe identify structural assumptions which provide solvability of the Nash system arising from a linear-quadratic closed-loop game, with stable properties with respect to the number of players. In a setting of interactions governed by a sparse graph, both short-time and long-time existence of a classical solution for the Nash system set in infinitely many dimensions are addressed, as well as convergence to the solution to the respective ergodic problem as the time horizon goes to infinity; in addition, equilibria for the infinite-dimensional game are shown to provide $$\epsilon $$
ϵ
-Nash closed-loop equilibria for the N-player game. In a setting of generalized mean-field type (where the number of interactions is large but not necessarily symmetric), directly from the N-player Nash system estimates on the value functions are deduced on an arbitrary large time horizon, which should pave the way for a convergence result as N goes to infinity.
Validation of a non-food or water motivated effort-based foraging task as a measure of motivational state in male mice
Authors: Xeni Foteini , Marangoni Caterina , Jackson Megan G. 
Published: June 2024

AbstractDisorders of motivation such as apathy syndrome are highly prevalent across neurological disorders but do not yet have an agreed treatment approach. The use of translational behavioural models can provide a route through which to meaningfully screen novel drug targets. Methods that utilise food deprivation in contrived environments may lack the sensitivity to detect deficits in self-initiated behaviour, and may have limited translation to normal behaviour. Animals monitored in more naturalistic environments may display more ethologically-relevant behaviours of greater translational value. Here, we aimed to validate a novel, non-food or water motivated effort-based foraging task as a measure of motivational state in mice. In this task, the mouse can freely choose to exert effort to forage nesting material and shuttle it back to a safe and enclosed environment. The amount of nesting material foraged is used as a readout of motivational state. Acute dopaminergic modulation with haloperidol, amphetamine and methylphenidate, and two phenotypic models known to induce motivational deficits (healthy ageing and chronic administration of corticosterone) were used to validate this task. Consistent with other effort-based decision-making tasks we find that foraging behaviour is sensitive to acute modulation of dopaminergic transmission. We find that both phenotypic models induce differing deficits in various aspects of foraging behaviour suggesting that the task may be used to parse different behavioural profiles from distinct disease phenotypes. Thus, without requiring extended training periods or physiological deprivation, this task may represent a refined and translational preclinical measure of motivation.
NIMH perspectives on future directions in neuroimaging for mental health
Authors: Wijtenburg S. Andrea , Rowland Laura M. , Vicentic Aleksandra , Rossi Andrew F. , Brady Linda S. , Gordon Joshua A. , Lisanby Sarah H. 
Published: June 2024

AbstractNIMH’s mission is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. New imaging techniques hold great promise for improving our understanding of the pathophysiology of mental illnesses, stratifying patients for treatment selection, and developing a personalized medicine approach. Here, we highlight emerging and promising new technologies that are likely to be vital in helping NIMH accomplish its mission, the potential for utilizing multimodal approaches to study mental illness, and considerations for data analytics and data sharing.
Gut microbiota-mediated activation of GSDMD ignites colorectal tumorigenesis
Authors: Chen Ju , Singh Neha , Ye Xiaoyang , Theune Eileen Victoria , Wang Kepeng 
Published: June 2024

AbstractActivation of Gasdermin D (GSDMD) results in its cleavage, oligomerization, and subsequent formation of plasma membrane pores, leading to a form of inflammatory cell death denoted as pyroptosis. The roles of GSDMD in inflammation and immune responses to infection are well documented. However, whether GSDMD also plays a role in sporadic cancer development, especially that in the gut epithelium, remains unknown. Here, we show that GSDMD is activated in colorectal tumors of both human and mouse origins. Ablation of GSDMD in a mouse model of sporadic colorectal cancer resulted in reduced tumor formation in the colon and rectum, suggesting a tumor-promoting role of the protein in the gut. Both antibiotic-mediated depletion of gut microbiota and pharmacological inhibition of NLRP3 inflammasome reduced the activation of GSDMD. Loss of GSDMD resulted in reduced infiltration of immature myeloid cells, and increased numbers of macrophages in colorectal tumors. Activation of GSDMD is also accompanied by the aggregation of the endosomal sorting complex required for transport (ESCRT) membrane repair proteins on the membrane of colorectal tumor cells, suggesting that active membrane repairment may prevent pyroptosis induced by the formation of GSDMD pore in tumor cells. Our results show that gut microbiota/NLRP3-mediated activation of GSDMD promotes the development of colorectal tumors, and supports the use of NLRP3 inhibitors to treat colon cancer.
The combination of immune checkpoint inhibitors and antibody-drug conjugates in the treatment of urogenital tumors: a review insights from phase 2 and 3 studies
Authors: Yu Puguang , Zhu Chunming , You Xiangyun , Gu Wen , Wang Xia , Wang Yuan , Bu Renge , Wang Kefeng 
Published: June 2024

AbstractWith the high incidence of urogenital tumors worldwide, urinary system tumors are among the top 10 most common tumors in men, with prostate cancer ranking first and bladder cancer fourth. Patients with resistant urogenital tumors often have poor prognosis. In recent years, researchers have discovered numerous specific cancer antigens, which has led to the development of several new anti-cancer drugs. Using protein analysis techniques, researchers developed immune checkpoint inhibitors (ICIs) and antibody-conjugated drugs (ADCs) for the treatment of advanced urogenital tumors. However, tumor resistance often leads to the failure of monotherapy. Therefore, clinical trials of the combination of ICIs and ADCs have been carried out in numerous centers around the world. This article reviewed phase 2 and 3 clinical studies of ICIs, ADCs, and their combination in the treatment of urogenital tumors to highlight safe and effective methods for selecting individualized therapeutic strategies for patients. ICIs activate the immune system, whereas ADCs link monoclonal antibodies to toxins, which can achieve a synergistic effect when the two drugs are combined. This synergistic effect provides multiple advantages for the treatment of urogenital tumors.
Hard-Flaccid syndrome: a survey of sexual medicine practitioners’ knowledge and experience
Authors: Gryzinski Gustavo , Hammad Muhammed Moukhtar , Alzweri Laith , Azad Babak , Barham David , Lumbiganon Supanut , Serefoglu Ege Can , Yafi Faysal 
Published: June 2024

AbstractHard-flaccid syndrome (HFS) is a poorly understood condition of male sexual dysfunction (MSD) that has more recently become a new topic of discussion in online forums and sexual medicine conferences. There has been limited research looking into HFS and consequently there are no evidence-based guidelines for its work-up and management. In order to identify the current level of understanding of HFS in the sexual medicine community, a survey was distributed at a national urologic conference focusing on pertinent management strategies employed by practitioners, and their own thoughts on HFS. This showed that nearly one-third of those surveyed had never seen HFS in their practice. Of those that had, diagnosis was mainly made via clinical history as well as patient self-diagnosis. Additionally, only about half of the respondents who had seen HFS were confident in its legitimacy as a real medical syndrome. This analysis is one of the first of its kind, and highlights the ongoing lack of familiarity of HFS among the sexual medicine community. There were limitations, most notably its survey format as well as low sample size, however, it importantly emphasizes the critical need for continued education and research into HFS to improve diagnostic accuracy, enhance patient care, and develop effective treatment strategies.
Interplay of two small RNAs fine-tunes hierarchical flagella gene expression in Campylobacter jejuni
Authors: König Fabian , Svensson Sarah L. , Sharma Cynthia M. 
Published: June 2024

AbstractLike for many bacteria, flagella are crucial for Campylobacter jejuni motility and virulence. Biogenesis of the flagellar machinery requires hierarchical transcription of early, middle (RpoN-dependent), and late (FliA-dependent) genes. However, little is known about post-transcriptional regulation of flagellar biogenesis by small RNAs (sRNAs). Here, we characterized two sRNAs with opposing effects on C. jejuni filament assembly and motility. We demonstrate that CJnc230 sRNA (FlmE), encoded downstream of the flagellar hook protein, is processed from the RpoN-dependent flgE mRNA by RNase III, RNase Y, and PNPase. We identify mRNAs encoding a flagella-interaction regulator and the anti-sigma factor FlgM as direct targets of CJnc230 repression. CJnc230 overexpression upregulates late genes, including the flagellin flaA, culminating in longer flagella and increased motility. In contrast, overexpression of the FliA-dependent sRNA CJnc170 (FlmR) reduces flagellar length and motility. Overall, our study demonstrates how the interplay of two sRNAs post-transcriptionally fine-tunes flagellar biogenesis through balancing of the hierarchically-expressed components.
The association of maternal factors with the neonatal microbiota and health
Authors: Zhu Bin , Edwards David J. , Spaine Katherine M. , Edupuganti Laahirie , Matveyev Andrey , Serrano Myrna G. , Buck Gregory A. 
Published: June 2024

AbstractThe human microbiome plays a crucial role in human health. However, the influence of maternal factors on the neonatal microbiota remains obscure. Herein, our observations suggest that the neonatal microbiotas, particularly the buccal microbiota, change rapidly within 24–48 h of birth but begin to stabilize by 48–72 h after parturition. Network analysis clustered over 200 maternal factors into thirteen distinct groups, and most associated factors were in the same group. Multiple maternal factor groups were associated with the neonatal buccal, rectal, and stool microbiotas. Particularly, a higher maternal inflammatory state and a lower maternal socioeconomic position were associated with a higher alpha diversity of the neonatal buccal microbiota and beta diversity of the neonatal stool microbiota was influenced by maternal diet and cesarean section by 24–72 h postpartum. The risk of admission of a neonate to the newborn intensive care unit was associated with preterm birth as well as higher cytokine levels and probably higher alpha diversity of the maternal buccal microbiota.
The hexosamine biosynthetic pathway rescues lysosomal dysfunction in Parkinson’s disease patient iPSC derived midbrain neurons
Authors: Wani Willayat Y. , Zunke Friederike , Belur Nandkishore R. , Mazzulli Joseph R. 
Published: June 2024

AbstractDisrupted glucose metabolism and protein misfolding are key characteristics of age-related neurodegenerative disorders including Parkinson’s disease, however their mechanistic linkage is largely unexplored. The hexosamine biosynthetic pathway utilizes glucose and uridine-5’-triphosphate to generate N-linked glycans required for protein folding in the endoplasmic reticulum. Here we find that Parkinson’s patient midbrain cultures accumulate glucose and uridine-5’-triphosphate, while N-glycan synthesis rates are reduced. Impaired glucose flux occurred by selective reduction of the rate-limiting enzyme, GFPT2, through disrupted signaling between the unfolded protein response and the hexosamine pathway. Failure of the unfolded protein response and reduced N-glycosylation caused immature lysosomal hydrolases to misfold and accumulate, while accelerating glucose flux through the hexosamine pathway rescued hydrolase function and reduced pathological α-synuclein. Our data indicate that the hexosamine pathway integrates glucose metabolism with lysosomal activity, and its failure in Parkinson’s disease occurs by uncoupling of the unfolded protein response-hexosamine pathway axis. These findings offer new methods to restore proteostasis by hexosamine pathway enhancement.
A spatial perturbation framework to validate implantation of the epileptogenic zone
Authors: Jaber Kassem , Avigdor Tamir , Mansilla Daniel , Ho Alyssa , Thomas John , Abdallah Chifaou , Chabardes Stephan , Hall Jeff , Minotti Lorella , Kahane Philippe , Grova Christophe , Gotman Jean , Frauscher Birgit 
Published: June 2024

AbstractStereo-electroencephalography (SEEG) is the gold standard to delineate surgical targets in focal drug-resistant epilepsy. SEEG uses electrodes placed directly into the brain to identify the seizure-onset zone (SOZ). However, its major constraint is limited brain coverage, potentially leading to misidentification of the ‘true’ SOZ. Here, we propose a framework to assess adequate SEEG sampling by coupling epileptic biomarkers with their spatial distribution and measuring the system’s response to a perturbation of this coupling. We demonstrate that the system’s response is strongest in well-sampled patients when virtually removing the measured SOZ. We then introduce the spatial perturbation map, a tool that enables qualitative assessment of the implantation coverage. Probability modelling reveals a higher likelihood of well-implanted SOZs in seizure-free patients or non-seizure free patients with incomplete SOZ resections, compared to non-seizure-free patients with complete resections. This highlights the framework’s value in sparing patients from unsuccessful surgeries resulting from poor SEEG coverage.
Identification of endothelial and mesenchymal FOXF1 enhancers involved in alveolar capillary dysplasia
Authors: Wang Guolun , Wen Bingqiang , Guo Minzhe , Li Enhong , Zhang Yufang , Whitsett Jeffrey A. , Kalin Tanya V. , Kalinichenko Vladimir V. 
Published: June 2024

AbstractMutations in the FOXF1 gene, a key transcriptional regulator of pulmonary vascular development, cause Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins, a lethal lung disease affecting newborns and infants. Identification of new FOXF1 upstream regulatory elements is critical to explain why frequent non-coding FOXF1 deletions are linked to the disease. Herein, we use multiome single-nuclei RNA and ATAC sequencing of mouse and human patient lungs to identify four conserved endothelial and mesenchymal FOXF1 enhancers. We demonstrate that endothelial FOXF1 enhancers are autoactivated, whereas mesenchymal FOXF1 enhancers are regulated by EBF1 and GLI1. The cell-specificity of FOXF1 enhancers is validated by disrupting these enhancers in mouse embryonic stem cells using CRISPR/Cpf1 genome editing followed by lineage-tracing of mutant embryonic stem cells in mouse embryos using blastocyst complementation. This study resolves an important clinical question why frequent non-coding FOXF1 deletions that interfere with endothelial and mesenchymal enhancers can lead to the disease.