bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rutin is a potent senomorphic agent to target senescent cells and can improve chemotherapeutic efficacy
Authors: Liu Hanxin , Xu Qixia , Wufuer Halidan , Li Zi , Sun Rong , Jiang Zhirui , Dou Xuefeng , Fu Qiang , Campisi Judith , Sun Yu 
Published: July 2023

AbstractAging is a major risk factor for most chronic disorders, for which cellular senescence is one of the central hallmarks. Senescent cells develop the pro‐inflammatory senescence‐associated secretory phenotype (SASP), which significantly contributes to organismal aging and age‐related disorders. Development of senotherapeutics, an emerging class of therapeutic agents to target senescent cells, allows to effectively delay aging and alleviate chronic pathologies. Here we report preliminary outputs from screening of a natural medicinal agent (NMA) library for senotherapeutic candidates and validated several agents with prominent potential as senomorphics. Rutin, a phytochemical constituent found in a number of plants, showed remarkable capacity in targeting senescent cells by dampening expression of the full spectrum SASP. Further analysis indicated that rutin restrains the acute stress‐associated phenotype (ASAP) by specifically interfering with the interactions of ATM with HIF1α, a master regulator of cellular and systemic homeostasis activated during senescence, and of ATM with TRAF6, part of a key signaling axis supporting the ASAP development toward the SASP. Conditioned media produced by senescent stromal cells enhanced the malignant phenotypes of prostate cancer cells, including in vitro proliferation, migration, invasion, and more importantly, chemoresistance, while rutin remarkably downregulated these gain‐of‐functions. Although classic chemotherapy reduced tumor progression, the treatment outcome was substantially improved upon combination of a chemotherapeutic agent with rutin. Our study provides a proof of concept for rutin as an emerging natural senomorphic agent, and presents an effective therapeutic avenue for alleviating age‐related pathologies including cancer.
Forecasting Groundwater Remediation Timeframes: Site‐Specific Temporal Monitoring Results May Not Predict Future Performance
Authors: McHugh Thomas E. , Newell Charles J. , Beckley Lila M. , Adamson David T. , DeVaull George E. , Lahvis Matthew A. 
Published: July 2023

AbstractAt contaminated sites, groundwater monitoring results are commonly used (quantitatively or qualitatively) to predict remediation timeframes. If results are predictive, then there should be a strong positive correlation between attenuation rates for the first half of a temporal monitoring record and attenuation rates for the second half of the same record. We utilized the GeoTracker database to evaluate the power of historical groundwater monitoring results to predict future attenuation rates. For two data sets (petroleum and chlorinated solvent), we found a small negative correlation between the first‐order concentration vs. time attenuation rate observed during the earlier part of the monitoring record and the later part of the monitoring record: benzene—correlation coefficient (r) = −0.11, methyl tert‐butyl ether (MTBE)—r = −0.12, trichloroethene (TCE) = −0.12. For each data set, a small negative correlation between the first‐order attenuation rate observed during the earlier part of the monitoring record and the later part of the monitoring record was also observed for a subset of monitoring records exhibiting the best model fits (R2 > 0.8), a subset with a statistically significant (p < 0.05) positive attenuation rate for the first half of the monitoring record. For the TCE data set, this negative correlation was also observed for a subset of monitoring records with no change in site remedy during the monitoring period (r = −0.22). Our analysis suggests that the historical concentration vs. time attenuation rate for a contaminant at an individual site or monitoring well is a poor predictor of the future rate.
Real‐world effectiveness of abrocitinib treatment in patients with difficult‐to‐treat atopic dermatitis
Authors: Olydam J. I. , Schlösser A. R. , Custurone P. , Nijsten T. E. C. , Hijnen D. 
Published: July 2023

AbstractBackgroundAbrocitinib is a JAK‐1 selective inhibitor registered for the treatment of moderate‐to‐severe atopic dermatitis (AD). Although efficacy and safety have been shown in phase 3 clinical trials, data on real‐world patients with a treatment history of advanced systemics are scarce.ObjectivesThe objective of the study was to evaluate the effectiveness and safety of abrocitinib treatment in patients with difficult‐to‐treat AD in daily practice.MethodsIn this prospective observational single‐centre study, all AD patients who started abrocitinib treatment in the context of standard care between April 2021 and December 2022 were included. Effectiveness was assessed using clinician‐ and patient‐reported outcome measures. Adverse events were evaluated.ResultsForty‐one patients were included. The majority (n = 30; 73.2%) had failed (ineffectiveness) on other targeted therapies, including JAK inhibitors (n = 14, 34%) and biologics (n = 16, 39%). Abrocitinib treatment resulted in a significant decrease in disease severity during a median follow‐up period of 25 weeks (IQR 16–34). Median EASI score at baseline decreased from 14.7 (IQR 10.4–25.4) to 4.0 (IQR 1.6–11.4) at last review (p < 0.001). Median NRS itch decreased from 7.0 (IQR 5–8) to 3.0 (IQR 1–2) at last review (p < 0.001). The most frequently reported AEs included gastrointestinal symptoms (27.6%), acne (20.7%) and respiratory tract infections (17.2%). 16 (39%) patients discontinued abrocitinib treatment due to ineffectiveness, AEs or both (41.2%, 41.2% and 11.8%, respectively).ConclusionAbrocitinib can be an effective treatment for patients with moderate‐to‐severe AD in daily practice, including non‐responders to other targeted therapies.
Effect of botulinum toxin‐A injection applied to the mentalis muscle on free gingival graft operation: A retrospective study
Authors: Sökmen Kevser , Talo Yıldırım Tuba , Dündar Serkan 
Published: July 2023

AbstractObjectiveThe purpose of this retrospective study was to investigate the effects of Botulinum Toxin‐A (BTX‐A) injection into the mentalis muscle on the free gingival graft (FGG).Materials and MethodsForty patients with keratinized gingiva insufficiency and Cairo's RT 2 gingival recession (formerly classified as Miller class III) in their mandibular central incisors were randomly divided into two groups: FGG and FGG + BTX. Plaque index (PI), gingival index (GI), probing pocket depth (PPD), keratinized gingiva width (KGW), attached gingiva width (AGW), clinical attachment level (CAL), gingival thickness (GT), gingival recession amount (GRA), gingival recession width (GRW), and root closure percentage (RCP%) parameters were measured at baseline and at first, third, and sixth months after the operation.ResultsThere was no difference in PI, GI, and PPD levels in both groups (p > 0.05). While the change in GT and RCP% levels were found to be statistically significantly higher at FGG + BTX group than FGG group, the change in GRW and CAL levels were statistically significantly lower (p < 0.05).ConclusionThe findings of this study indicate that BTX‐A injection applied to the mentalis muscle after FGG operation may have positive effects in terms of KGW, AGW, GT, RCP%, GRW, and CAL parameters.Clinical SignificanceAs a result of the fact that BTX‐A injection into the mentalis muscle contributed to the nutrition and immobility of FGG, positive developments were obtained in terms of clinical periodontal parameters. BTX‐A injection into the mentalis muscle may be an alternative method that increases the success rate of Cairo's RT 2 gingival recession.
The use of chemical and biological settlement cues in enhancing the larval settlement of abalone (Haliotis midae): Implications for hatcheries and ocean ranching
Authors: Mzozo Ziyanda B. , Hugo Sanet , Vine Niall G. 
Published: July 2023

AbstractReducing the time to settlement and metamorphosis of abalone larvae is critical for ensuring that abalone larvae settle within the seeding site for ocean ranching or to increase production in hatcheries. This study investigated the effect of biological (planktonic Nitzschia sp.) and chemical (potassium chloride) cues in inducing settlement and metamorphosis of abalone larvae Haliotis midae on diatom‐coated plastic sheets. Larvae were exposed to different concentrations of KCl (10–20 mM), with settlement being highest at 10 mM in the first 20 h. Settlement of larvae exposed to a combined KCl and Nitzschia treatment for 24 h was highest, followed by larvae exposed to KCl for 12 h, while larvae exposed to KCl for 24 h, and both controls (12 and 24 h) had the lowest settlement. However, in both experiments, larval settlement in all treatments declined after 24 h of exposure, while that of the controls (no added settlement cues) increased and surpassed the other treatments after 24 h. Finally, the settlement was very low on uncoated sheets, compared to diatom‐coated sheets, regardless of exposure to different combinations of KCl and Nitzschia. The exposure period's results should be interpreted with caution when drawing biological conclusions for field studies. This is due to the dramatic decrease in mean settlement post‐exposure to the cue. Therefore, we hypothesize that exposure of H. midae larvae to 10 mM KCl and Nitzschia sp. will not enhance settlement in the ocean, as the inducers are primarily only effective at a KCl concentration level equal to 10 mM for 12 h. However, long‐term exposure to KCl and Nitzschia over 24 h could be used in hatcheries to improve the settlement of H. midae larvae.
Dogs with canine visceral leishmaniasis have a boost of extracellular vesicles and miR‐21‐5p up‐expression
Authors: da Cruz Allecineia Bispo , Carneiro Francieli Marinho , Maia Marta Marques , Pereira Ingrid de Siqueira , Taniwaki Noemi Nosomi , Namiyama Gislene Mitsue , Gava Ricardo , Hiramoto Roberto Mitsuyoshi , Pereira‐Chioccola Vera Lucia 
Published: July 2023

AbstractThis retrospective cohort study analysed extracellular vesicles (EVs) and microRNAs (miRNAs) excreted in canine sera from dogs with canine visceral leishmaniasis (CanVL). A total of 56 canine sera were divided into Group I (28, from healthy dogs) and Group II (28, from the same dogs, but already with CanVL). CanVL was determined by clinical and laboratory diagnoses. Canine sera were ultra‐centrifuged to recover EVs (Can‐EVs). Analyses by transmission electron microscopy, nanoparticle tracking analysis (NTA), sodium dodecyl sulfate‐poli‐acrylammide gel eletroforesis (SDS‐PAGE) and, Immunoblot confirmed the presence of (i) microvesicles/exosomes and (ii) the tetraspanins CD63 and CD9. EVs secreted by Leishmania (Leishmania) infantum‐EVs were reactive against sera from dogs with CanVL (performed by ELISA and Immunoblot). NTA analyses exhibited that concentrations of Can‐EVs from dogs with CanVL (7.78 × 1010 Can‐EVs/mL) were higher (p < .0001) than the non‐infected dogs (mean: 1.47 × 1010 Can‐EVs/mL). These results suggested that concentrations of Can‐EVs were able to distinguish dogs with CanVL from healthy dogs. The relative expressions of 11 miRNAs species (miR‐21‐5p, miR‐146a‐5p, miR‐125b‐5p, miR‐144‐3p, miR‐194‐5p, miR‐346, miR‐29c‐3p, miR‐155‐5p, miR‐24‐3p, miR‐181a‐5p, and miR‐9‐5p) were estimated in purified miRNAs of 30 canine sera. Dogs with CanVL up‐expressed miR‐21‐5p and miR‐146a‐5p when compared with healthy dogs. The other miRNA species were poorly or not expressed in canine sera. In conclusion, this study suggests that CanVL induces changes in size and concentration of Can‐EVs, as well as, the up‐expression of miR‐21‐5p and miR‐146a‐5p in infected dogs.
An Innovation in the Test for Material Jurisdiction under Certain Compromissory Clauses
Authors: de Vries-Zou Ivo Tarik 
Published: July 2023

Abstract
To decide on the question of material jurisdiction under a compromissory clause, the World Court has at times interpreted treaties provisionally, seeing whether these could reasonably, though not per se correctly, be read so as to apply to acts of which an applicant complains. Other times it has interpreted treaties definitively, to assess whether the respondent actually has the obligations it allegedly violated. The former method may be criticised for not basing jurisdiction in consent; the latter for prejudging the merits. This article shows that the Court has nevertheless made the latter its standard approach. But to avoid prejudging the merits, it will only use definitive interpretations to resolve those preliminary objections, or aspects of an objection, which it perceives as raising issues relevant to its material jurisdiction, as opposed to the merits. The article argues this innovation creates uncertainty for the parties and could be a misuse of the definitive approach.
Obligations Erga Omnes (Partes) and the Participation of Third States in Inter-State Litigation
Authors: McGarry Brian 
Published: July 2023

Abstract
This article addresses the role of third States in public interest litigation – i.e., ongoing proceedings concerning interests which they share with the international community. It scrutinizes third-State intervention in inter-State cases through the prism of rules and principles arising in public interest litigation, and aims to clarify the limits of such participation. Having synthesized the relevant law and doctrine of intervention practice before the ICJ and other institutional courts, it considers the extent to which third-State interests find expression through Articles 62 and 63 of the ICJ Statute. It examines the invocation of international legal responsibility on the basis of obligations erga omnes and erga omnes partes, as well as the prospect of intervention on this basis. It then identifies and addresses jurisdictional and procedural questions arising in these and other instances of “public interest” intervention. It concludes by envisaging the prospective institutional development of multilateral participation in public interest litigation.
Climatology and Changes in Extratropical Cyclone Activity in the Southern Hemisphere during Austral Winters from 1948 to 2017
Authors: Zhan Xinyue , Chen Lei 
Published: July 2023

Abstract
An objective detection and tracking algorithm based on relative vorticity at 850 hPa using National Centers for Environmental Prediction–National Center for Atmospheric Research (NCEP–NCAR) Reanalysis-1 data was applied to track cyclones in the Southern Hemisphere during austral winters from 1948 to 2017. The climatological characteristics of extratropical cyclones, including track density, frequency, intensity, lifetime, and their related variabilities, are discussed. The frequency and average lifetime of cyclones have substantially decreased. The average maximum intensity of cyclones has shown an increasing trend over the 70-yr study period. The cyclone track density shows a decreasing trend in lower latitudes, consistent with the region where the upper-troposphere zonal wind weakens. Baroclinicity can explain the increase in cyclone intensity: when a cyclone moves to higher latitudes and enters the region with greater baroclinicity, it strengthens. As there is no discernible increase in cyclogenesis in the medium latitudes (45°–70°S), but significantly less cyclogenesis in lower and higher latitudes, it is hypothesized that there is no clear poleward cyclogenesis shift over the Southern Hemisphere.

Significance Statement
While much is known about the Northern Hemisphere cyclones, few studies have examined how extratropical cyclones have changed in the Southern Hemisphere. We used an automatic tracking algorithm to study the climatological characteristics of extratropical cyclones over the past 70 years and found that the frequency of winter extratropical cyclones has decreased significantly in most parts of the Southern Hemisphere, with the number of intense cyclones increasing. Under global warming conditions, variability in regional low-level baroclinicity and a weakened upper-troposphere jet are likely to be responsible for this change. Future studies may focus on how the increasing autumn sea ice around Antarctica affects polar cyclone activities.
Causal effects of serum lipid biomarkers on early age-related macular degeneration using Mendelian randomization
Authors: Li Fen-Fen , Wang Yuqin , Chen Lishuang , Chen Chong , Chen Qi , Xiang Lue , Rao Feng-Qin , Shen Li-Jun , Zheng Qin-Xiang , Yi Quanyong , Huang Xiu-Feng 
Published: July 2023

Abstract

Background
Age-related macular degeneration (AMD) is one of the major causes of vision loss. Early AMD needs to be taken seriously, but the causal effects of lipid biomarkers on early AMD remain unclear.

Methods
In this study, two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between seven serum lipid biomarkers (apolipoprotein A (ApoA), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], and triglycerides (TG)) and risk of early AMD. In total, 14,034 cases and 91,214 controls of European ancestry were included in the analysis (number of SNPs = 11,304,110).

Results
MR estimates revealed that a higher HDL-C level is strongly associated with increased risk of early AMD (OR = 1.25, 95% CI: 1.15–1.35, P = 2.61 × 10−8). In addition, level of ApoA is also positively associated with risk of early AMD (OR = 2.04, 95% CI: 1.50–2.77, P = 6.27 × 10−6). Conversely, higher levels of TG significantly decrease the risk of early AMD (OR = 0.77, 95% CI: 0.71–0.84, P = 5.02 × 10−10). Sensitivity analyses further supported these associations. Moreover, multivariable MR analyses, adjusted for the effects of correlated lipid biomarkers, yielded similar results.

Conclusion
This study identifies causal relationships between elevated circulating HDL-C/ApoA levels and increased risk of early AMD, in addition to finding that TG specifically reduces the risk of early AMD. These findings contribute to a better understanding of the role of lipid metabolism in drusen formation, particularly in early AMD development.
Dietary flavonoids intake contributes to delay biological aging process: analysis from NHANES dataset
Authors: Xing Wenmin , Gao Wenyan , Zhao Zhenlei , Xu Xiaogang , Bu Hongyan , Su Huili , Mao Genxiang , Chen Jun 
Published: July 2023

Abstract

Background
Diet may influence biological aging and the discrepancy (∆age) between a subject’s biological age (BA) and chronological age (CA). We aimed to investigate the correlation of dietary flavonoids with the ∆age of organs (heart, kidney, liver) and the whole body.

Method
A total of 3193 United States adults were extracted from the National Health and Nutrition Examination Survey (NHANES) in 2007–2008 and 2017–2018. Dietary flavonoids intake was assessed using 24-h dietary recall method. Multiple linear regression analysis was performed to evaluate the association of dietary flavonoids intake with the ∆age of organs (heart, kidney, liver) and the whole body. BA was computed based on circulating biomarkers, and the resulting ∆age was tested as an outcome in linear regression analysis.

Results
The ∆age of the whole body, heart, and liver was inversely associated with higher flavonoids intake (the whole body ∆age β = − 0.58, cardiovascular ∆age β = − 0.96, liver ∆age β = − 3.19) after adjustment for variables. However, higher flavonoids intake positively related to renal ∆age (β = 0.40) in participants with chronic kidney disease (CKD). Associations were influenced by population characteristics, such as age, health behavior, or chronic diseases. Anthocyanidins, isoflavones and flavones had the strongest inverse associations between the whole body ∆age and cardiovascular ∆age among all the flavonoids subclasses.

Conclusion
Flavonoids intake positively contributes to delaying the biological aging process, especially in the heart, and liver organ, which may be beneficial for reducing the long-term risk of cardiovascular or liver disease.
Management of pain in Fabry disease in the UK clinical setting: consensus findings from an expert Delphi panel
Authors: Stepien Karolina M. , Broomfield Alexander , Cole Duncan , Deegan Patrick B. , Forshaw-Hulme Stuart , Hughes Derralynn , Jovanovic Ana , Morris Liz , Muir Alison , Ramaswami Uma 
Published: July 2023

Abstract
Background
Fabry disease is a rare, X-linked inherited lysosomal storage disorder, that manifests as a heterogeneous disease with renal, cardiac and nervous system involvement. The most common pain experienced by people with Fabry disease are episodes of neuropathic pain reported in up to 80% of classical hemizygous male patients and up to 65% of heterozygous female patients. No clear consensus exists within UK clinical practice for the assessment and management of pain in Fabry disease based on agreed clinical practice and clinical experience. Here we describe a modified Delphi initiative to establish expert consensus on management of pain in Fabry disease in the UK clinical setting.

Methods
Delphi panel members were identified based on their demonstrated expertise in managing adult or paediatric patients with Fabry disease in the UK and recruited by an independent third-party administrator. Ten expert panellists agreed to participate in two survey rounds, during which they remained anonymous to each other. Circulation of the questionnaires, and collection and processing of the panel’s responses were conducted between September 2021 and December 2021. All questions required an answer.

Results
The Delphi panel reached a consensus on 21 out of 41 aspects of pain assessment and management of pain in Fabry disease. These encompassed steps in the care pathway from the goals of therapy through to holistic support, including the use of gabapentin and carbamazepine as first-line analgesic medications for the treatment of neuropathic pain in Fabry disease, as well as the proactive management of symptoms of anxiety and/or depression associated with Fabry pain.

Conclusions
The consensus panel outcomes reported here have highlighted strengths in current UK clinical practice, along with unmet needs for further research and agreement. This consensus is intended to prompt the next steps towards developing clinical guidelines.