bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cysteine protease cathepsin B promotes lysosome integrity to extend the lifespan of alternative day fasting worms
Authors: Yin Xue , Dai Fangzhou , Ran Dongyang , Zhang Yutong , Qu Zhi , Zheng Shanqing 
Published: July 2024

AbstractAlternative day fasting (ADF) has been shown to enhance the lifespan of animals. However, human trials evaluating the efficacy of ADF have only recently emerged, presenting challenges due to the extreme nature of this dietary regimen. To better understand the effects of ADF, we investigated its impact using Caenorhabditis elegans as a model organism. Our findings reveal that ADF extends the lifespan of worms nourished on animal‐based protein source, while those fed with plant‐based protein as the primary protein source do not experience such benefits. Remarkably, initiating ADF during midlife is sufficient to prolong lifespan, whereas implementation during youth results in developmental damage, and in older age, fails to provide additional extension effects. Furthermore, we discovered that midlife ADF up‐regulates the expression of two cysteine protease cathepsin B genes, cpr‐2 and cpr‐5, which preserve lysosomal integrity and enhance its function in digesting aggregated proteins, as well as enhancing lipid metabolism and ameliorating neurodegenerative disease markers and phenomena during aging. This suggests that midlife ADF has long lasting anti‐aging effects and may delay the onset of related diseases, specifically in animals consuming animal‐based protein source. These findings offer valuable insights into the effects of ADF and provide guidance for future research and potential applications in individuals.
Rent‐seeking or value‐creating? The impact of managerial autonomy from state‐built corporate pyramids on M&A performance
Authors: Jiachun Chen , Qingsong Hou , Shanmin Li 
Published: July 2024

AbstractHow to give managers autonomy to improve organisational performance has long been a focus of business practice. In this paper, we use a unique Chinese context to investigate the effect of managerial autonomy arising from state‐built corporate pyramids on mergers and acquisitions (M&A) performance. We find that the number of pyramidal layers between the government and the state‐owned enterprise (SOE) is positively associated with M&A performance. This relationship is stronger when the SOE managers possess professional M&A abilities but weaker when the SOE management team and the government are politically connected. We attribute the positive association to the career path incentives of SOE managers. Additionally, we address the role of managerial autonomy in the M&A process and integration. We also analyse this effect in contexts where managerial autonomy is crucial in some investment decisions. Taken together, our study fills a critical gap on managerial discretion within internal organisational contexts.
The relevance of integrating multiple sensory modalities into capturing devices: The case of the global pest Sirex noctilio
Authors: Masagué Santiago , Bruchhausen Axel , Rozas Guillermo , De La Vega Gerardo José , Villacide José , Corley Juan Carlos , Martínez Andrés S. 
Published: July 2024

Abstract
Sirex noctilio is an invasive forest wasp that affects pines in many parts of the globe and can result in severe economic losses.
Current trapping methods for monitoring the pest rely heavily on non‐specific semiochemicals. This lack of specificity can translate into low attraction/capture levels, something that is undesired, especially when the intent is to detect the pest when still at low population densities. In this context, an interesting opportunity arises to increase trap sensitivity by incorporating visual cues.
For this, we evaluated potential sources of visual information that, in accordance with the ecology of the species, could elicit an attractive response complementary to the olfactory cues.
We measured the reflectance spectra of pine bark, chlorotic needles and woodwasp male abdomens. The spectra were then compared with 120 commercial paint colours to be applied on panel traps.
During two flight seasons, field experiments were conducted with the deployment of 155 traps, combining the volatile bait (turpentine) and different coloured traps.
We observed a significantly higher number of captures towards traps with pine bark‐like colourations compared with the black control traps.
Our results are encouraging, as they suggest the potential of combining visual and chemical information for sustainable pest biomonitoring.
Cytotoxic T Lymphocytes, Tc17 Cells, Th1 Cells, and ThGM Cells are Increased in the Blood and Ectopic Endometrium of Patients With Adenomyosis
Authors: Zhang Li , Zhu Lei , Che Pengfei , Sun Xiaoyan , Guo Yupeng , Gao Mingjie , Wang Junjie 
Published: July 2024

ABSTRACTProblemAdenomyosis (AM) is associated with immune response and inflammation. However, the role of T cell subsets in AM development has not been thoroughly understood.Method of StudyPatients with focal or diffuse AM were recruited. Serum cytokines were quantified by enzyme‐linked immunosorbent assay (ELISA). Different T cell subsets in the blood and ectopic endometrium were determined by flow cytometry.ResultsSerum interleukin‐6 (IL‐6) and macrophage‐colony‐stimulating factor (GM‐CSF) were increased in patients with focal or diffuse AM before focused ultrasound ablation surgery (FUAS), but not after FUAS. Compared with the healthy control, the frequencies of CD8+ interferon‐gamma (IFN‐γ)‐expressing cytotoxic T lymphocytes (CTLs), interleukin‐17A (IL‐17A)‐expressing Tc17 cells, CD4+ T helper 1 (Th1) cells, and GM‐CSF‐expressing T helper (ThGM) cells were up‐regulated in the blood of patients with AM, especially those with diffuse AM. However, these changes were eradicated after FUAS. Meanwhile, the frequencies of these T cell subsets were positively correlated with the CA‐125 level. Furthermore, these T cell subsets were also increased in ectopic endometrium.ConclusionsOur study delineates for the first time the presence of CTLs, Tc17 cells, Th1, and ThGM cells in the blood and ectopic endometrium in AM. The results imply that T cell response might impact AM development.
Characterising the allergic fungal rhinosinusitis microenvironment using full‐length 16S rRNA gene amplicon sequencing and fungal ITS sequencing
Authors: Connell J. T. , Bouras G. , Yeo K. , Fenix K. , Cooksley C. , Bassiouni A. , Vreugde S. , Wormald P. J. , Psaltis A. J. 
Published: July 2024

AbstractIntroductionAllergic fungal rhinosinusitis (AFRS) is a severe phenotype of chronic rhinosinusitis with nasal polyposis (CRSwNP), characterised by localised and exaggerated type 2 inflammation. While fungal antigenic stimulation of unregulated Th2‐mediated inflammation is the core pathophysiological mechanism, the direct and synergistic role of bacteria in disease modification is a pervasive hypothesis. We set out to define the microenvironment of AFRS to elucidate virulent organisms that may be implicated in the pathophysiology of AFRS.MethodologyWe undertook a cross‐sectional study of AFRS patients and non‐fungal CRSwNP patients. Demographics, disease severity, culture and microbiome sequences were analysed. Multimodality microbiome sequencing included short‐read next‐generation sequencing (NGS) on the Illumina Miseq (16S rRNA and ITS) and full‐length 16S rRNA sequencing on the Oxford Nanopore Technologies GridION (ONT).ResultsThirty‐two AFRS and 29 non‐fungal CRSwNP patients (NF) were included in this study. Staphylococcus aureus was the dominant organism cultured and sequenced in both AFRS and NF groups (AFRS 27.54%; NF 18.04%; p = .07). Streptococcus pneumoniae (AFRS 12.31%; NF 0.98%; p = .03) and Haemophilus influenzae (AFRS 15.03%; NF 0.24%; p = .005) were significantly more abundant in AFRS. Bacterial diversity (Shannon's index) was considerably lower in AFRS relative to NF (AFRS 0.6; NF 1.0, p = .008). Aspergillus was the most cultured fungus in AFRS (10/32, 31.3%). The AFRS sequenced mycobiome was predominantly represented by Malassezia (43.6%), Curvularia (18.5%) and Aspergillus (16.8%), while the NF mycobiome was nearly exclusively Malassezia (84.2%) with an absence of Aspergillus or dematiaceous fungi.ConclusionA low diversity, dysbiotic microenvironment dominated by Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae characterised the bacterial microbiome of AFRS, with a mycobiome abundant in Malassezia, Aspergillus and Curvularia. While Staphylococcus aureus has been previously implicated in AFRS through enterotoxin superantigen potential, Streptococcus pneumoniae and Haemophilus influenzae are novel findings that may represent alternate cross‐kingdom pathophysiological mechanisms.
Disease modification in chronic spontaneous urticaria
Authors: Maurer Marcus , Kolkhir Pavel , Pereira Manuel P. , Siebenhaar Frank , Witte‐Händel Ellen , Bergmann Karl‐Christian , Bonnekoh Hanna , Buttgereit Thomas , Fluhr Joachim W. , Frischbutter Stefan , Grekowitz Eva Maria , Herzog Leonie , Kiefer Lea Alice , Krause Karoline , Magerl Markus , Muñoz Melba , Neisinger Sophia , Nojarov Nicole , Prins Samantha , Pyatilova Polina , Ramanauskaité Aisté , Scheffel Jörg , Terhorst‐Molawi Dorothea , Treudler Regina , Weller Karsten , Zuberbier Torsten , Metz Martin 
Published: July 2024

AbstractChronic spontaneous urticaria (CSU) is a debilitating, inflammatory skin condition characterized by infiltrating immune cells. Available treatments are limited to improving the signs and symptoms. There is an unmet need to develop therapies that target disease‐driving pathways upstream of mast cell activation to inhibit or delay the progression of CSU and associated comorbidities. Here, we aim to define disease modification due to a treatment intervention and criteria that disease‐modifying treatments (DMTs) must meet in CSU. We have defined disease modification in CSU as a favorable treatment‐induced change in the underlying pathophysiology and, therefore, the disease course, which is clinically beneficial and enduring. A DMT must fulfil the following criteria: (1) prevents or delays the progression of CSU, (2) induces long‐term, therapy‐free clinical remission, which is the sustained absence of CSU signs and symptoms without the need for treatment, and (3) affects the underlying mechanism of CSU, as demonstrated by an effect on disease‐driving signals and/or a biomarker. DMTs in CSU should slow disease progression, achieve long‐lasting disease remission, target disease‐driving mechanisms, reduce mast cell‐activating IgE autoantibodies, target cytokine profile polarization, and normalize the gut microbiome and barrier. Treating CSU at the immune system level could provide valuable alternatives to pharmacotherapy in CSU management. Specific DMTs in CSU are yet to be developed, but some show potential benefits, such as inhibitors of Bruton's Tyrosine Kinase, IL‐4 and IL‐13. Future therapies could prevent CSU signs and symptoms, achieve long‐term clinical benefits after discontinuing treatment, and prevent associated concomitant disorders.
Pterostilbene exerts anti‐lung squamous cell carcinoma function by suppressing the level of KANK3
Authors: He Hua , Li Tian 
Published: July 2024

AbstractEarly detection of lung squamous cell carcinoma (LUSC) has a significant impact on clinical outcomes, and pterostilbene (PT) is a natural compound with promising anti‐oncogenic activities. This study aimed to identify potential LUSC biomarkers through a series of bioinformatic analyses and clinical verification and explored the interaction between PT and selected biomarkers during the treatment of LUSC. The analysis of the expression profile of the clinical samples of LUSC was performed to identify dysexpressed genes (DEGs) and validated by IHC. The role of KANK3 in the anti‐LUSC effects of PT was assessed with a series of in vitro and in vivo assays. 4335 DEGs were identified, including 1851 upregulated genes and 2484 downregulated genes. Survival analysis showed that KANK3 was significantly higher in patients with LUSC with an advanced tumor stage. In in vitro assays, PT suppressed cell viability, induced apoptosis, and inhibited migration and invasion in LUSC cell lines, which was associated with downregulation of KANK3. After the reinduction of the KANK3 level in LUSC cells, the anti‐LUSC function of PT was impaired. In mice model, reinduction of KANK3 increased tumor growth and metastasis even under the treatment of PT. The findings outlined in the current study indicated that PT exerted anti‐LUSC function in a KANK3 inhibition‐dependent manner.
A cross‐sectional CBCT assessment of the relative position of one‐piece titanium‐zirconium mini‐implants placed for mandibular overdentures using non‐guided surgery
Authors: Leles Cláudio Rodrigues , de Oliveira Moura‐Neto Leuçon , Silva Jésio Rodrigues , Nascimento Lays Noleto , Curado Thalita Fernandes Fleury , Costa Nadia Lago , Schimmel Martin , McKenna Gerald 
Published: July 2024

AbstractObjectiveTo assess the relative position of mini‐implants to retain a mandibular overdenture, according to the surgical protocol, technical and anatomical factors.MethodsMandibular cone‐beam computed tomography (CBCT) scans were analyzed for 73 patients who received four one‐piece titanium‐zirconium mini‐implants. Drilling was performed using a 1.6 mm needle drill and a 2.2 mm Pilot Drill, according to the bone density with a surgical stent. Post‐insertion CBCT images in DICOM format were analyzed using the E‐Vol‐DX software with BAR filters. Divergence angle between implants and between implants and the overdenture path of insertion was measured using CliniView 10.2.6 software.ResultsDivergence between implants ranged from 0° to 22.3° (mean = 4.2; SD = 3.7) in the lateral and from 0° to 26.2° (mean = 5.3; SD = 4.1) in the frontal projections (p < .001). Only 1 (0.2%) and 3 (0.7%) of the measurements were higher than 20° in the lateral and frontal views, respectively. The mean angulations between the implant and the path of insertion for the overdenture were 9.3° (SD = 7.5) and 4.0° (SD = 2.9) for the lateral and frontal views, respectively (p < .001). Regression analyses showed a significant association between the divergence of implants and the frontal view projection (p < .001), greater distance between the paired implants (p = .017), the flapped surgical protocol (p = .002), higher final insertion torque (p = .011), and deeper preparation with the needle drill (p < .001).ConclusionsThe mini‐implants were placed with low divergence angles and satisfactory parallelism. Factors including shorter distances between the implants, higher density bone, and a flapless surgical approach all contributed positively to improved parallelism of the mini‐implants.
Examining the structure of plant–lemur interactions in the face of imperfect knowledge
Authors: Tonos Jadelys , Papinot Bastien , Park Daniel S. , Raelison Mihajatiana , Ramaroson Herilantonirina , Stubbs Jessica , Razafindratsima Onja H. 
Published: July 2024

AbstractBiotic interactions, such as plant–animal seed dispersal mutualisms, are essential for ecosystem function. Such interactions are threatened by the possible extinction of the animal partners. Using a data set that includes plant–lemur interactions across Madagascar, we studied the current state of knowledge of these interactions and their structure to determine which plant species are most at risk of losing dispersal services due to the loss of lemurs. We found substantial gaps in understanding of plant–lemur interactions; data were substantially skewed toward a few lemur species and locations. There was also a large gap in knowledge on the interactions of plants and small‐bodied or nocturnal lemurs and lemurs outside a few highly studied locations. Of the recorded interactions, a significant portion occurred between lemurs and endemic plants, rather than native or introduced plants. We also found that lemur species tended to primarily consume closely related plant species. Such interaction patterns may indicate the threats to Malagasy endemic plants and highlight how lemur population loss or reductions could affect plant phylogenetic diversity. When examining the impacts of lemur extinction, losing critically endangered species left 164 plant species with no known lemur frugivore partners. Despite phylogenetic patterns in lemur diet, plants for which the only known lemur frugivore is critically endangered were not closely related. These results emphasize the need for further studies to complete our knowledge on these essential interactions and to inform conservation priorities.
Designing cities for everyday nature
Authors: Visintin Casey , Garrard Georgia E. , Weisser Wolfgang W. , Baracco Mauro , Hobbs Richard J. , Bekessy Sarah A. 
Published: July 2024

AbstractThe motivations for incorporating nature into the design of cities have never been more compelling. Creating experiences with nature that occur every day (everyday nature) in cities could help reverse the fate of many threatened species and connect people with nature and living cultural traditions. However, this requires more than just urban greening; it involves ensuring daily doses of nature in a way that also supports nonhuman organisms. A major shift in the way nature is conceived of and is made part of the design of cities is required. Principles include reconsidering nature as a development opportunity rather than a constraint and eliminating offsetting of biodiversity site values. Processes include using biodiversity‐sensitive design frameworks and establishing meaningful professional engagement among ecologists, planners, and designers. Challenges include design obstacles, conflicts between nature and people (e.g., safety, disease, and noise) that require careful management, and socioeconomic and political considerations (e.g., Global North vs. Global South). Research to interrogate the multiple benefits of nature in cities can complement experimental interventions, ultimately supporting better urban design and creating much more resiliently built environments for people and nature.
Chronic kidney disease in type 2 diabetes: The size of the problem, addressing residual renal risk and what we have learned from the CREDENCE trial
Authors: Chaudhry Khuram , Karalliedde Janaka 
Published: July 2024

AbstractChronic kidney disease (CKD) associated with type 2 diabetes (T2DM) is a global challenge; progression to end‐stage kidney disease (ESKD) and increased risk of cardiovascular disease (CVD) associated with advancing nephropathy are a significant source of morbidity, mortality, and healthcare expenditure. Until recently, renin‐angiotensin system (RAS) blockade was the mainstay of pharmacotherapy in diabetic kidney disease (DKD), representing a therapeutic paradigm shift towards interventions that delay disease progression independently of antihypertensive effects. However, a significant residual risk of DKD progression persisted in patients established on RAS blockade, highlighting the need for additional treatment options. Sodium‐glucose cotransporter‐2 (SGLT2) inhibitors, originally licensed as glucose‐lowering agents in people with T2DM, serendipitously demonstrated beneficial renal and cardiovascular outcomes in clinical trials designed primarily to evaluate their cardiovascular safety. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial was the first to study the effect of SGLT2 inhibition on a primary composite renal endpoint of ESKD, doubling of serum creatinine, or renal or cardiovascular death in 4401 people with T2DM and CKD established on RAS blockade. The trial was stopped early due to efficacy, demonstrating a 30% relative risk reduction in the primary endpoint in the canagliflozin group (hazard ratio 0.70, 95% confidence interval 0.59–0.82; p = 0.00001). Through discussion of the primary analysis from CREDENCE, and selected post hoc analyses, we review the significant benefits highlighted by this landmark study, its role in shaping clinical guidelines, and in re‐establishing interest in interventions that reduce the residual risk of progression of DKD, alongside its interrelation with cardiovascular morbidity and heart failure. We also provide a brief narrative summary of key renal outcome trials since CREDENCE, which indicate emerging avenues for pharmacotherapy beyond SGLT2 inhibition.
WONOEP appraisal: Modeling early onset epilepsies
Authors: De Meulemeester Ann‐Sofie , Reid Christopher , Auvin Stéphane , Carlen Peter L. , Cole Andrew J. , Szlendak Roza , Di Sapia Rossella , Moshé Solomon L. , Sankar Raman , O'Brien Terence J. , Baulac Stéphanie , Henshall David C. , Akman Özlem , Galanopoulou Aristea S. 
Published: July 2024

AbstractEpilepsy has a peak incidence during the neonatal to early childhood period. These early onset epilepsies may be severe conditions frequently associated with comorbidities such as developmental deficits and intellectual disability and, in a significant percentage of patients, may be medication‐resistant. The use of adult rodent models in the exploration of mechanisms and treatments for early life epilepsies is challenging, as it ignores significant age‐specific developmental differences. More recently, models developed in immature animals, such as rodent pups, or in three‐dimensional organoids may more closely model aspects of the immature brain and could result in more translatable findings. Although models are not perfect, they may offer a more controlled screening platform in studies of mechanisms and treatments, which cannot be done in pediatric patient cohorts. On the other hand, more simplified models with higher throughput capacities are required to deal with the large number of epilepsy candidate genes and the need for new treatment options. Therefore, a combination of different modeling approaches will be beneficial in addressing the unmet needs of pediatric epilepsy patients. In this review, we summarize the discussions on this topic that occurred during the XVI Workshop on Neurobiology of Epilepsy, organized in 2022 by the Neurobiology Commission of the International League Against Epilepsy. We provide an overview of selected models of early onset epilepsies, discussing their advantages and disadvantages. Heterologous expression models provide initial functional insights, and zebrafish, rodent models, and brain organoids present increasingly complex platforms for modeling and validating epilepsy‐related phenomena. Together, these models offer valuable insights into early onset epilepsies and accelerate hypothesis generation and therapy discovery.