bluuebunny/crossref_metadata_2025_split huggingface dataset:
CircPCNXL2 promotes preeclampsia progression by suppressing trophoblast cell proliferation and invasion via miR-487a-3p/interferon regulatory factor 2 axis
Authors: Xu Hua , Qu Xin , Wang Xiaoli 
Published: October 2024

Background:
Preeclampsia (PE) has culminated in maternal and perinatal sickness and death across the world, affecting approximately 4.6% of pregnancies. Circular RNAs (circRNAs) have been linked to the biology of numerous pathologies, including PE. Here, we investigated the functional role of circPCNXL2 in the progression of PE.

Methods:
We employed the GEO database to get the expression profile of circPCNXL2 in patients with PE. This was followed by the detection of the expression of circPCNXL2 and miR-326 by qRT-PCR. The role of circPCNXL2 on trophoblast cell proliferation, migration, and invasion was confirmed with cell viability assays, the transwell assay, and the colony formation assay. Further, we employed dual luciferase, FISH, RNA pull-down assay and Western blot analysis to determine the interaction between the expression of circPCNXL2, miR-487a-3p, and IRF2.

Result:
Findings from this study revealed that proliferation and migration of trophoblast cells were significantly increased in the HTR-8/SVneo cells after silencing circPCNXL2. Additionally, knockdown of circPCNXL2 remarkably increased miR-487a-3p expression, while IRF2 expression was remarkably reduced (P < 0.05), indicating the presence of complementary binding sequence on miR-487a-3p with which they sequester circPCNXL2. Rescue experiments revealed that interaction occurs between circPCNXL2, miR-487a-3p, and the IRF2 protein, indicating that circPCNXL2 expression elicits suppression of migration and proliferation of trophoblast cells via the miR-487a-3p/IRF2 pathway.

Conclusions:
We demonstrated that circPCNXL2 upregulation promotes pre-eclampsia by inhibiting proliferation and migration of trophoblast cells via the miR-487a-3p/IRF2 pathway or axis.
Visual exposure to green light therapy reduces knee joint pain and alters the lipidome in osteoarthritic rats
Authors: O'Brien Melissa S. , Richter Emily , Woodward Taylor , Bradshaw Heather B. , McDougall Jason J. 
Published: October 2024

Abstract
Visual exposure to dim, green, light has been found to reduce pain levels in patients living with migraine, low back pain, and fibromyalgia. Preclinical studies discovered that the analgesic effect of green light was due to the central release of endogenous opioids and a reduction in inflammatory cytokines in the cerebrospinal fluid. The present study assessed the effect of green light therapy (GLT) on joint pain in a rat model of osteoarthritis (OA) and investigated the role of endolipids. Male and female Wistar rats (207-318 g) received an intra-articular injection of sodium monoiodoacetate (3 mg in 50 μL saline) into the knee to induce OA. On day 9, animals were placed in a room illuminated by either white (neutral-white 4000K; 20 lux) or green (wavelength: 525 nm; luminance: 20 lux) light for 5 days (8 hours per day). Joint nociception was assessed by von Frey hair algesiometry, dynamic weight bearing, and in vivo single unit extracellular recordings from knee joint mechanonociceptors. Compared to white light, GLT significantly reduced secondary mechanical hypersensitivity in both sexes and improved hindlimb weight bearing in females only. There was no effect of GLT on joint nociceptor activity in either sex. Serum lipidomics indicated an increase in circulating analgesic endolipids in response to GLT, particularly the N-acyl-glycines. Partial blockade of the endocannabinoid system with the G protein receptor-18/cannabinoid-1 receptor antagonist AM281 (500 μg/kg i.p.) attenuated GLT-induced analgesia. These data show for the first time that GLT acts to reduce OA pain by upregulating circulating analgesic endolipids, which then engage the endocannabinoid system.
Evaluating the diagnostic accuracy of microRNA-494 as a biomarker in cancers: A systematic review and meta-analysis
Authors: Liu Yuhan , Yu Libo , Mei Hongbing 
Published: October 2024

Abstract
MicroRNA-494 (miR-494) has emerged as a potential diagnostic biomarker for cancer detection, but conflicting reports have led to uncertainty regarding its clinical utility. This study aims to address these discrepancies by conducting a comprehensive meta-analysis of miR-494 diagnostic performance across various cancer types. A comprehensive literature search was performed across multiple databases, including PubMed, Web of Science, Wanfang databases, and CNKI (China National Knowledge Infrastructure), with a cutoff date of April 23, 2024. Eligible studies were identified using predefined inclusion criteria and various search strategies to ensure a thorough coverage of the available evidence. To evaluate the diagnostic performance of miR-494 in cancer detection, relevant measures such as sensitivity, specificity, and other diagnostic accuracy indicators were extracted from the included studies. These data were synthesized using bivariate meta-analysis models to generate pooled estimates of miR-494 diagnostic performance. All statistical analyses were conducted using the STATA 16.0 software. This meta-analysis pooled data from 8 studies, comprising a total of 647 cancer cases and 407 healthy controls. The aggregated diagnostic performance of miR-494 was as follows: a sensitivity of 0.67 (95% confidence interval [CI], 0.52–0.80), a specificity of 0.85 (95% CI, 0.77–0.91), and an area under the curve of 0.86 (95% CI, 0.82–0.88), indicating good overall diagnostic accuracy. The diagnostic odds ratio (DOR) was 12.11 (95% CI, 7–21), suggesting that miR-494 has strong discriminatory power in distinguishing cancer patients from healthy individuals. The positive likelihood ratio of 4.62 (95% CI, 3.1–6.8) and negative likelihood ratio of 0.38 (95% CI, 0.26–0.56) further support the diagnostic utility of miR-494. Deeks’ funnel plot asymmetry test was employed to assess potential publication bias, yielding a P value of 0.50, which suggests the absence of significant bias in the included studies. The meta-analysis results suggest that miR-494 exhibits promising diagnostic performance in detecting cancer, with moderate accuracy. The pooled sensitivity, specificity, and high area under the receiver operating characteristic curve highlight its potential as a cancer biomarker, indicating its utility in early detection and accurate diagnosis.
Advances in treatment strategies for non–clear cell renal cell carcinoma
Authors: Li Shangwei , Gu Liangyou , Ma Xin , Zhang Xu 
Published: October 2024

Abstract
Renal cell carcinoma is the sixth most commonly diagnosed cancer in men and the tenth in women, with clear cell renal cell carcinoma accounting for nearly 75% of cases. The remaining 25% consists of non–clear cell renal cell carcinoma, a diverse and less prevalent group. Although current treatments for clear cell types are well-defined, progress in treating non–clear cell renal cell carcinoma has been limited owing to its heterogeneity and rarity, relying primarily on findings from small-scale phase II clinical trials. This review examined recent advancements in the treatment of non–clear cell renal cell carcinoma, particularly in the areas of immunotherapy and targeted therapy.
Clinical Practice Patterns and Evidence-Based Medicine in Blepharoplasty: A 15-Year Review of Continuous Certification Tracer Data from the American Board of Plastic Surgery
Authors: Stein Michael J. , Stoehr Jenna R. , Harrast John , Zins James E. , Matarasso Alan , Gosain Arun K. 
Published: October 2024

Introduction:
The American Board of Plastic Surgery (ABPS) Continuous Certification tracer data on blepharoplasty offers valuable information on national trends in clinical practice. The present study was performed to analyze evolving trends in blepharoplasty and compare practice patterns to Evidence-Based Medicine (EBM) publications within the same timeframe.

Methods:
Tracer data for blepharoplasty procedures performed by ABPS-certified surgeons between 2005 and 2020 was analyzed. Data between two timeframes, 2005-2014 (early cohort, EC) and 2015-2020 (recent cohort, RC), were compared to identify evolving trends in blepharoplasty over time. Results were then compared to EBM-based publications.

Results:
Of 3,050 blepharoplasties (1,510 EC; 1,540 RC), 82% were performed in female patients and the average age was 56 years. Blepharoplasty was most frequently performed in an ambulatory setting (56%) compared to in hospital (25%); significantly more cases are being performed in the office (p< 0.001) in the RC compared to the EC. Mean surgical duration has decreased by 13 minutes (p< 0.001), and fewer surgeries are being performed with concomitant procedures (p< 0.001). Fewer surgeons use antibiotics (p< 0.001), and fewer surgeons use DVT prophylaxis in the form of sequential compression devices after anesthesia (p< 0.001). More skin resections were performed for upper blepharoplasties (p=0.016), while fewer cases of lower lid blepharoplasty involved either skin-muscle flaps (p=0.038) or transcutaneous fat removal (p=0.004). Most surgeons did not perform canthal tightening during their blepharoplasty (82%).

Conclusions:
A review of over 15-years of ABPS blepharoplasty tracer data allows surgeons to compare their practice with national trends and EBM. The tracer data illustrates a shift in technique towards shorter and simpler procedures in the office setting.
The Evolution of Unicoronal Synostosis Correction: Long-Term Aesthetic Outcomes of Fronto-Orbital Distraction Versus Traditional Advancement
Authors: Wu Meagan , Massenburg Benjamin B , Villavisanis Dillan F , Chang Ashley E , Romeo Dominic J , Ng Jinggang J , Napoli Joseph A , Bartlett Scott P , Swanson Jordan W , Taylor Jesse A 
Published: October 2024

Introduction:
This study compares the long-term aesthetic outcomes of patients with unicoronal synostosis (UCS) who underwent fronto-orbital distraction osteogenesis (FODO) versus traditional fronto-orbital advancement and remodeling (FOAR).

Methods:
Patients treated for nonsyndromic UCS from 2009 to 2023 were retrospectively reviewed. Perioperative and complication characteristics were compared between all patients who underwent FOAR, open FODO, and endoscopic-assisted FODO (“endo-FODO”). Aesthetic outcomes at greater than five years postoperatively were compared between patients who underwent FODO and a contemporaneous cohort of age-matched controls who underwent FOAR. Differences between pre- and postoperative periorbital symmetry ratios, canthal tilt symmetry, orbital dystopia angle (ODA), and frontal bossing angle were calculated, with positive differences representing postoperative improvement.

Results:
Forty-one patients were treated at a median age of 9.7, 5.4, and 5.4 months in the FOAR, open FODO, and endo-FODO groups, respectively. Among 28 patients photographed at a median of 6.3 years postoperatively, the FODO cohort demonstrated greater margin-to-reflex distance 1 symmetry (6.5 [-9.3, 0.0] vs. -13.9 [-22.9, -11.5], p=0.010) and canthal tilt symmetry (0.9° [0.2°, 2.9°] vs. 3.3° [2.3°, 5.3°], p=0.004) postoperatively as well as ODA correction (5.4° [4.0°, 7.5°] vs. 3.0° [2.5°, 4.4°], p=0.027) compared to the FOAR cohort. Fewer patients in the FODO cohort exhibited temporal hollowing postoperatively compared to the FOAR cohort (14% vs. 71%, p=0.002).

Conclusions:
Compared to FOAR, FODO was associated with greater periorbital symmetry, greater orbital dystopia correction, and reduced temporal hollowing in the long-term. Follow-up to cranial maturity is needed to adequately compare the two techniques.
Factors Associated With Acceptance of an Optional Diagnosis
Authors: Matthews Cortney , Ring David , Teunis Teun , Ramtin Sina 
Published: October 2024

Background:
A sensation becomes a symptom (a concern) when a person associates it with potential illness. In the absence of objective evidence of a pathophysiological process that has important health consequences without treatment, assigning a diagnosis to the sensation is optional. This is important because labeling of benign bodily sensations as pathophysiology has potential advantages and disadvantages.

Question:
We asked what patient and clinician factors are associated with willingness to accept an optional diagnosis.

Methods:
In a survey administered using Amazon M-Turk, 536 people anonymously completed validated measures for symptoms of anxiety and depression, intolerance of uncertainty, and skepticism regarding the healthcare system. They then viewed fictional personal medical scenarios in which they were asked to imagine they experienced certain symptoms, and were offered an optional diagnosis of a nerve problem, muscle pain syndrome, or fatigue syndrome, and were asked to rate their willingness to accept the diagnosis on an 12-point ordinal scale from 0 indicating “I do not accept it at all” to 11 indicating “I accept it with enthusiasm.” The language of the scenarios was varied to attempt to reflect critical thinking, denigration of other doctors, an alternative mental health focus, or a hopeful outlook. Multilevel linear regression was used to identify factors associated with likelihood of accepting an optional diagnosis.

Results:
Threshold likelihood of accepting an optional diagnosis greater than 5.5 on a 0 to 11 ordinal scale was independently associated with greater symptoms of anxiety (regression coefficient [RC] = 0.38, 95% confidence interval [95% CI] = 0.30-0.47, P < .001), greater skepticism regarding the healthcare system (RC = 0.11, 95% CI = 0.076-0.13, P < .001), and delivery tones characterized by either denigration of other doctors (RC = 0.39, 95% CI = 0.19-0.60, P < .001) or a hopeful outlook (RC = 0.50, 95% CI = 0.26-0.73, P < .001).

Conclusion:
Likelihood of accepting an optional diagnosis may be a sign of relative vulnerability from feelings of distress or distrust of medical evidence. Given this potential vulnerability, clinicians can take care to limit persuasive communication styles that can influence acceptance of optional diagnoses.

Level of Evidence:
III prognostic.
The concept of critical age group for density dependence: bridging the gap between demographers, evolutionary biologists and behavioural ecologists
Authors: Gamelon Marlène , Araya-Ajoy Yimen G. , Sæther Bernt-Erik 
Published: October 2024

Density dependence plays an important role in population regulation in the wild. It involves a decrease in population growth rate when the population size increases. Fifty years ago, Charlesworth introduced the concept of ‘critical age group’, denoting the age classes in which variation in the number of individuals most strongly contributes to density regulation. Since this pioneering work, this concept has rarely been used. In light of Charlesworth’s concept, we discuss the need to develop work between behavioural ecology, demography and evolutionary biology to better understand the mechanisms acting in density-regulated age-structured populations. We highlight demographic studies that explored age-specific contributions to density dependence and discuss the underlying evolutionary processes. Understanding competitive interactions among individuals is pivotal to identify the ages contributing most strongly to density regulation, highlighting the need to move towards behavioural ecology to decipher mechanisms acting in density-regulated age-structured populations. Because individual characteristics other than age can be linked to competitive abilities, expanding the concept of critical age to other structures (e.g. sex, dominance rank) offers interesting perspectives. Linking research fields based on the concept of the critical age group is key to move from a pattern-oriented view of density regulation to a process-oriented approach.
This article is part of the discussion meeting issue ‘Understanding age and society using natural populations’.
Wild capuchin monkeys as a model system for investigating the social and ecological determinants of ageing
Authors: Campos Fernando A. , Wikberg Eva C. , Orkin Joseph D. , Park Yeonjoo , Snyder-Mackler Noah , Cheves Hernandez Saul , Lopez Navarro Ronald , Fedigan Linda M. , Gurven Michael , Higham James P. , Jack Katharine M. , Melin Amanda D. 
Published: October 2024

Studying biological ageing in animal models can circumvent some of the confounds exhibited by studies of human ageing. Ageing research in non-human primates has provided invaluable insights into human lifespan and healthspan. Yet data on patterns of ageing from wild primates remain relatively scarce, centred around a few populations of catarrhine species. Here, we introduce the white-faced capuchin, a long-lived platyrrhine primate, as a promising new model system for ageing research. Like humans, capuchins are highly social, omnivorous generalists, whose healthspan and lifespan relative to body size exceed that of other non-human primate model species. We review recent insights from capuchin ageing biology and outline our expanding, integrative research programme that combines metrics of the social and physical environments with physical, physiological and molecular hallmarks of ageing across the natural life courses of multiple longitudinally tracked individuals. By increasing the taxonomic breadth of well-studied primate ageing models, we generate new insights, increase the comparative value of existing datasets to geroscience and work towards the collective goal of developing accurate, non-invasive and reliable biomarkers with high potential for standardization across field sites and species, enhancing the translatability of primate studies.
This article is part of the discussion meeting issue ‘Understanding age and society using natural populations’.
Receptor-based protein binding in the supramolecular network of velvet worm slime
Authors: Hu Zhaolong , Baer Alexander , Hering Lars , de Sena Oliveira Ivo , Browne Darren C. , Guo Xue , Perrin Quentin Moana , Sobota Radoslaw M. , Hoon Shawn , Mayer Georg , Harrington Matthew J. , Miserez Ali 
Published: October 2024

AbstractThe slime of velvet worms (Onychophora) is a protein-based bioadhesive that undergoes rapid, yet reversible transition from a fluid into stiff fibers used for prey capture and defense, but the mechanism by which this phase transition functions is largely unknown. Here, integrating transcriptomic and proteomic approaches with AI-guided structure predictions, we discover a group of evolutionarily conserved leucine-rich repeat (LRR) proteins in velvet worm slime that readily adopt a receptor-like, protein-binding “horseshoe” structure. Our structural predictions suggest dimerization of LRR proteins and support their interactions with conserved β-sheets-rich domains of high-molecular-weight proteins, the primary building blocks of velvet worm slime fibers. This previously unknown functional context of LRR proteins is presumably involved in reversible, receptor-based supramolecular network formation in these adhesive biofibers and provides possible new avenues for fabricating fully recyclable (bio)polymeric materials.Significance StatementAnalyzing structure-function-relationships underlying reversible fiber formation in velvet worm slime may inspire avenues for the sustainable fabrication of protein-based polymeric materials. Here, we present evidence for an evolutionarily conserved mechanism of reversible fiber formation in velvet worm slime based on the receptor-like binding of fiber forming proteins by a leucine-rich repeat (LRR) protein. The structures of both protein components are highly conserved evolutionarily in the two distantly related velvet worm subgroups, indicating pervasive presence of this mechanism across species that has been maintained through the last ∼380 MY. Our results suggest that the ubiquitously occurring LRR motif—better known for its innate immunity and developmental roles—has a novel identified function in processing a biological material, which might contribute to the development of sustainable bio-inspired materials.
Development of novel flavonoid senolytics through phenotypic drug screening and drug design
Authors: Zhang Lei Justan , Salekeen Rahagir , Soto-Palma Carolina , He Yuanjun , Elsallabi Osama , Hughes Brian , Nunes Allancer , Xu Wandi , Zhang Borui , Mohamed Abdalla , McGowan Sara J. , Angelini Luise , O’Kelly Ryan , Kamenecka Theodore M. , Niedernhofer Laura J. , Robbins Paul D. 
Published: October 2024

AbstractAccumulation of senescent cells drives aging and age-related diseases. Senolytics, which selectively kill senescent cells, offer a promising approach for treating many age-related diseases. Using a senescent cell-based phenotypic drug discovery approach that combines drug screening and drug design, we developed two novel flavonoid senolytics, SR29384 and SR31133, derived from the senolytic fisetin. These compounds demonstrated enhanced senolytic activities, effectively eliminating multiple senescent cell types, reducing tissue senescencein vivo, and extending healthspan in a mouse model of accelerated aging. Mechanistic studies utilizing RNA-Seq, machine learning, network pharmacology, and computational simulation suggest that these novel flavonoid senolytics target PARP1, BCL-xL, and CDK2 to induce selective senescent cell death. This phenotype-based discovery of novel flavonoid senolytics, coupled with mechanistic insights, represents a key advancement in developing next-generation senolyticss with potential clinical applications in treating aging and age-related diseases.
Cultivating inclusive leadership: a catalyst for enhanced organizational citizenship
Authors: Zaccone Maria Cristina , Pedrini Matteo 
Published: October 2024

Purpose
The present manuscript aims to develop and validate a theoretical model capable of explaining that organizational citizenship behavior is influenced by the extent to which employees feel valued, accepted and considered integral to the organizational fabric. To do this, the authors draw on social identity theory, according to which the level of identification of a person with a group or organization is not fixed but situational and context-dependent.

Design/methodology/approach
To validate the theoretical model, the authors surveyed the employees of eight large-scale distribution companies operating in Italy. Overall, the authors received completed data from 2,010 employees.

Findings
The authors theorize and demonstrate that the presence of an inclusive corporate climate positively influences employees’ perceptions of work inclusion and that this latter, in turn, positively affects organizational citizenship behavior. Furthermore, they show that the indirect effect of an inclusive corporate climate on organizational citizenship behavior becomes stronger when inclusive leadership is promoted within an organization.

Originality/value
Overall, this paper confirms social identity theory in a novel way. Social identity theory suggests that the context can impact an employee’s identification with the organization they work for, without specifying the characteristics that the context must possess. The authors’ contribution reaffirms this theory by proposing that it is specifically the inclusiveness of the context that positively influences the employee’s identification within the organization. By focusing on this aspect of inclusion, this research introduces a novel perspective that enriches the current discourse on OCB and underscores the importance of cultivating inclusive workplace environments. Also, the authors add theoretical nuance to previous literature by suggesting that the way top management exercises leadership over employees can amplify the strength of corporate climate influence on worker inclusion perception.