bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bulky glycocalyx drives cancer invasiveness by modulating substrate-specific adhesion
Authors: Barai Amlan , Piplani Niyati , Saha Sumon Kumar , Dutta Sarbajeet , Gomathi V , Ghogale Mayank M , Kumar Sushil , Kulkarni Madhura , Sen Shamik 
Published: August 2024

Abstract
The majority of the eukaryotic cell surface is decorated with a layer of membrane-attached polysaccharides and glycoproteins collectively referred to as the glycocalyx. While the formation of a bulky glycocalyx has been associated with the cancer progression, the mechanisms by which the glycocalyx regulates cancer invasiveness are incompletely understood. We address this question by first documenting subtype-specific expression of the major glycocalyx glycoprotein Mucin-1 (MUC1) in breast cancer patient samples and breast cancer cell lines. Strikingly, glycocalyx disruption led to inhibition of 2D motility, loss of 3D invasion, and reduction of clonal scattering in breast cancer cells at the population level. Tracking of 2D cell motility and 3D invasiveness of MUC1-based sorted subpopulations revealed the fastest motility and invasiveness in intermediate MUC1-expressing cells, with glycocalyx disruption abolishing these effects. While differential sensitivity in 2D motility is attributed to a nonmonotonic dependence of focal adhesion size on MUC1 levels, higher MUC1 levels enhance 3D invasiveness via increased traction generation. In contrast to inducing cell rounding on collagen-coated substrates, high MUC1 level promotes cell adhesion and confers resistance to shear flow on substrates coated with the endothelial surface protein E-selectin. Collectively, our findings illustrate how MUC1 drives cancer invasiveness by differentially regulating cell–substrate adhesion in a substrate-dependent manner.
Ubiquitin-driven protein condensation stabilizes clathrin-mediated endocytosis
Authors: Yuan Feng , Gollapudi Sadhana , Day Kasey J , Ashby Grant , Sangani Arjun , Malady Brandon T , Wang Liping , Lafer Eileen M , Huibregtse Jon M , Stachowiak Jeanne C 
Published: August 2024

Abstract
Clathrin-mediated endocytosis is an essential cellular pathway that enables signaling and recycling of transmembrane proteins and lipids. During endocytosis, dozens of cytosolic proteins come together at the plasma membrane, assembling into a highly interconnected network that drives endocytic vesicle biogenesis. Recently, multiple groups have reported that early endocytic proteins form flexible condensates, which provide a platform for efficient assembly of endocytic vesicles. Given the importance of this network in the dynamics of endocytosis, how might cells regulate its stability? Many receptors and endocytic proteins are ubiquitylated, while early endocytic proteins such as Eps15 contain ubiquitin-interacting motifs. Therefore, we examined the influence of ubiquitin on the stability of the early endocytic protein network. In vitro, we found that recruitment of small amounts of polyubiquitin dramatically increased the stability of Eps15 condensates, suggesting that ubiquitylation could nucleate endocytic assemblies. In live-cell imaging experiments, a version of Eps15 that lacked the ubiquitin-interacting motif failed to rescue defects in endocytic initiation created by Eps15 knockout. Furthermore, fusion of Eps15 to a deubiquitylase enzyme destabilized nascent endocytic sites within minutes. In both in vitro and live-cell settings, dynamic exchange of Eps15 proteins, a measure of protein network stability, was decreased by Eps15–ubiquitin interactions and increased by loss of ubiquitin. These results collectively suggest that ubiquitylation drives assembly of the flexible protein network responsible for catalyzing endocytic events. More broadly, this work illustrates a biophysical mechanism by which ubiquitylated transmembrane proteins at the plasma membrane could regulate the efficiency of endocytic internalization.
Smile variation leaks personality and increases the accuracy of interpersonal judgments
Authors: Witkower Zachary , Tian Laura , Tracy Jessica , Rule Nicholas O 
Published: August 2024

Abstract
People ubiquitously smile during brief interactions and first encounters, and when posing for photos used for virtual dating, social networking, and professional profiles. Yet not all smiles are the same: subtle individual differences emerge in how people display this nonverbal facial expression. We hypothesized that idiosyncrasies in people's smiles can reveal aspects of their personality and guide the personality judgments made by observers, thus enabling a smiling face to serve as a valuable tool in making more precise inferences about an individual's personality. Study 1 (N = 303) supported the hypothesis that smile variation reveals personality, and identified the facial-muscle activations responsible for this leakage. Study 2 (N = 987) found that observers use the subtle distinctions in smiles to guide their personality judgments, consequently forming slightly more accurate judgments of smiling faces than neutral ones. Smiles thus encode traces of personality traits, which perceivers utilize as valid cues of those traits.
Glucocorticoid sparing effect of Janus kinase inhibitors compared to biologic disease modifying anti-rheumatic drugs in rheumatoid arthritis, a single-centre retrospective analysis
Authors: Adami Giovanni , Bixio Riccardo , Virelli Giulia , Galvagni Isotta , Mastropaolo Francesca , Morciano Andrea , Ruzzon Francesca , Messina Valeria , Fracassi Elena , Gatti Davide , Viapiana Ombretta , Carletto Antonio , Rossini Maurizio 
Published: August 2024

Abstract

Background
Glucocorticoid sparing in rheumatoid arthritis (RA) treatment is crucial to minimizing adverse effects associated with long-term use. Janus kinase inhibitors (JAKi) could potentially offer a more potent glucocorticoid-sparing effect than biologic DMARDs (bDMARDs)

Material and methods
This is a single-centre retrospective analysis of RA patients treated with JAKi or bDMARDs. Glucocorticoid tapering, rescue therapy and discontinuation were analysed through mixed-effects models, Poisson regression and multivariable logistic regression, respectively, adjusting for baseline disease activity, demographic factors and treatment line.

Results
A total of 716 RA patients treated with JAKi (n = 156) or bDMARDs (n = 560) were evaluated. JAKi treatment was associated with a more rapid reduction in glucocorticoid dose within the first 6 months and 60% higher odds of discontinuation compared with bDMARDs (adjusted odds ratio 1.63; 95% CI: 1.02, 2.60, P = 0.039). Despite a higher baseline glucocorticoid dose, over 50% of JAKi-treated patients discontinued glucocorticoids after 12 months, vs ∼40% for bDMARDs. The need for glucocorticoid rescue therapy was significantly higher in the bDMARD group (rate ratio 2.66; 95% CI: 1.88, 3.74).

Conclusion
Our findings indicate that JAKi facilitate more rapid glucocorticoid tapering compared with bDMARDs in RA patients. These results underscore the potential of JAKi to reduce long-term glucocorticoid exposure, highlighting their value in RA management strategies, including minimizing glucocorticoid-related adverse effects.
Large vessel vasculitis is a risk factor for relapse only in giant cell arteritis patients without polymyalgia rheumatica
Authors: Moreel Lien , Betrains Albrecht , Boeckxstaens Lennert , Molenberghs Geert , Van Laere Koen , De Langhe Ellen , Vanderschueren Steven , Blockmans Daniel 
Published: August 2024

Abstract

Objectives
To evaluate differences in presentation and outcome of GCA patients with and without large vessel vasculitis (LVV) and according to the extent and severity of LVV.

Methods
Consecutive patients diagnosed with GCA between 2003 and 2020 who have had FDG PET imaging at diagnosis ≤3 days after initiation of glucocorticoids (GC) and followed for ≥12 months at the University Hospitals Leuven (Belgium) were included retrospectively. PET scans were visually scored (0–3) in seven vascular areas and a total vascular score (TVS) was calculated. LVV was defined as FDG uptake ≥2 in any large vessel.

Results
We included 238 GCA patients, of which 169 (71%) had LVV. LVV patients were younger (69 vs 74 years, P &lt; 0.001) and more frequently female (72% vs 49%, P = 0.001). In patients without PMR symptoms, the presence of LVV was associated with relapse (aOR 3.05 [95% CI 1.32–7.43], P = 0.011) and with a lower probability of stopping GC (aHR 0.59 [95% CI 0.37–0.94], P = 0.025). However, in those with PMR symptoms, there was no difference in relapse risk (aOR 1.20 [95% CI 0.53–2.66], P = 0.657) and in the probability of stopping GC (aHR 1.25 [95% CI 0.75–2.09], P = 0.394) between patients with and without LVV. A higher TVS was associated with an increased risk of relapse (aOR 1.09 [95% CI 1.04–1.15], P = 0.001) in patients without PMR symptoms, but not in those with PMR symptoms (aOR 1.01 [95% CI 0.96–1.07], P = 0.693).

Conclusion
LVV is a risk factor for relapse in GCA patients without PMR symptoms with a higher relapse risk in those with higher TVS.
Abstract 29: Utilizing Human Umbilical Cord Blood-Derived Exosomes for Inflammation Modulation and Tissue Regeneration: A Promising Therapeutic Strategy
Authors: Lee Wen-Jui 
Published: August 2024

Abstract

Introduction
Umbilical cord blood (UCB)-derived exosomes, with their cup-shaped morphology and rich cargo of proteins, lipids, and RNAs, are small extracellular vesicles isolated from the umbilical cord blood. Notably, they express specific markers such as CD9, CD63, and CD81. UCB-derived exosomes have shown remarkable potential in anti-inflammatory responses and tissue regeneration, making them a hope for therapeutic applications in various medical fields.

Objectives
This study aims to evaluate the effect of UCB-derived exosomes, a potential game-changer, on exploring potential future applications of these exosomes in regenerative medicine, immunotherapy, and other therapeutic areas.

Methods
The size distribution and concentration of exosomes were analyzed using nanoparticle tracking analysis (NTA). A scratch wound healing assay was used to measure wound coverage at 0 and 10 hours, both in the presence and absence of exosomes. The concentration of Tumor Necrosis Factor (TNF) was measured using an ELISA assay in control and exosome-treated samples under different conditions to assess the immunomodulatory properties of the exosomes. Cell proliferation was monitored over five days using the MTT assay to determine the proliferative effect of exosomes on cell growth.

Results
NTA was conducted to identify the purified nanoparticles derived from UCB. The isolated exosomes exhibited a spherical morphology with an average size of approximately 115.4 nm and expressed exosome-specific markers CD9, CD63, and CD81. The results demonstrated that all UCB-derived exosomes significantly reduced TNF expression in LPS-challenged macrophages. Subsequently, we incubated CCD966SK cells with UCB-derived exosomes. MTT and scratch wound assays showed that UCB-derived exosomes significantly promoted cell proliferation and migration.

Discussion
The study's findings, which highlight the significant therapeutic potential of exosomes in enhancing wound healing, modulating immune responses, and promoting cell proliferation, could potentially revolutionize regenerative medicine and immunotherapy. The wound healing assay results confirm that exosomes facilitate cellular repair processes. Immunomodulation assays showed that exosomes can effectively alter immune responses, which is potentially beneficial for treating inflammatory conditions. The increased cell growth observed in the MTT assay suggests that exosomes may support tissue regeneration and repair. These findings underscore the promising role of exosomes in therapeutic interventions, offering new avenues for treatment and healing.
Phylogenetic Biogeography Inference Using Dynamic Paleogeography Models and Explicit Geographic Ranges
Authors: Arias J Salvador 
Published: August 2024

Abstract
To model distribution ranges, the most popular methods of phylogenetic biogeography divide Earth into a handful of predefined areas. Other methods use explicit geographic ranges, but unfortunately, these methods assume a static Earth, ignoring the effects of plate tectonics and the changes in the landscape. To address this limitation, I propose a method that uses explicit geographic ranges and incorporates a plate motion model and a paleolandscape model directly derived from the models used by geologists in their tectonic and paleogeographic reconstructions. The underlying geographic model is a high-resolution pixelation of a spherical Earth. Biogeographic inference is based on diffusion, approximates the effects of the landscape, uses a time-stratified model to take into account the geographic changes, and directly integrates over all probable histories. By using a simplified stochastic mapping algorithm, it is possible to infer the ancestral locations as well as the distance traveled by the ancestral lineages. For illustration, I applied the method to an empirical phylogeny of the Sapindaceae plants. This example shows that methods based on explicit geographic data, coupled with high-resolution paleogeographic models, can provide detailed reconstructions of the ancestral areas but also include inferences about the probable dispersal paths and diffusion speed across the taxon history. The method is implemented in the program PhyGeo.
Research progress on the regulatory mechanism of cell senescence in arsenic toxicity: a systematic review
Authors: Gu Yun , Qiu Ying , Li Yujian , Wen Weihua 
Published: August 2024

Abstract
As an element with metalloid properties, arsenic is pervasively present in the environment and is recognized as a potent carcinogen. Consequently, the issue of human arsenic exposure has become a significant concern within the global public health sector. Numerous studies have indicated that arsenic induces cellular senescence through various mechanisms, including triggering epigenetic alterations, inducing the senescence-associated secretory phenotype (SASP), promoting telomere shortening, and causing mitochondrial dysfunction. This article collates and summarizes the latest research advancements on the involvement of cellular senescence in arsenic toxicity and explores the mechanisms of arsenic-induced toxicity. This study aims to provide new perspectives and directions for future research on arsenic toxicity and the development of prevention and treatment strategies.
Between Scylla and Charybdis: assessing the multidimensional aspects of pain behaviors in rats using a double avoidance place preference paradigm
Authors: Gieré Clémence , Thevenot Andréa , Menger Yannick , Gazzo Géraldine , Poisbeau Pierrick 
Published: August 2024

Abstract
Although the behavioral response to pain is complex and involves supraspinal processes, assessment of pain symptoms in animal models still mainly relies on reflex-based nociceptive tests, which do not account for the affective-motivational nor cognitive components of pain. We introduce a double avoidance place preference paradigm, an integrated testing procedure in freely moving rats that relies on the conflict between the avoidance of a dark compartment in which a thermal ramp is activated, and the escape towards an aversive brightly lit compartment. We were able to differentiate the first nociceptive threshold from the temperature of definitive escape from the dark compartment, conveying information on the adaptive behavior of animals. Measures were repeated after an hour to evaluate the adaptive learning response upon reexposure. In naive animals, there was a significant decrease in the time spent in the dark compartment at all stages of the testing paradigm upon reexposure, leading to a final escape before the flood had reached nociceptive values. This adaptive behavior was blunted by anxiolytic treatment. In animals exhibiting hyperalgesia following intraplantar complete Freund adjuvant injection, escape thresholds were significantly higher than that of control animals, hinting at a maladaptive affective-motivational response to noxious stimulation. However, in cuff animals, we failed to reveal any hot nociceptive hypersensitivity, but animals exhibited a strong adaptive response to cold simulation upon reexposure. Overall, the proposed paradigm allows for an integrated cortical response leading to a proactive avoidance behavior, while fully complying with ethical standards in animal experimentation.
Evaluation of the efficacy of chlorhexidine-alcohol vs. aqueous/alcoholic iodine solutions for the prevention of surgical site infections: a systematic review and meta-analysis
Authors: Yang Qiong , Sun Jingxian , Yang Zhao , Rastogi Sanjay , Liu Yan-feng , Zhao Bin-bin 
Published: August 2024

Background:
Surgical site infection (SSI) is the prevailing complication that occurs after surgery and significantly escalates healthcare expenses. Published meta-analyses and international standards vary in their recommendations for the most effective preoperative skin antiseptic solution and concentration.

Objective:
The aim of this systematic review and meta-analysis is to assess the effectiveness of chlorhexidine-alcohol compared to aqueous/alcoholic iodine solutions in preventing postoperative surgical site infections.

Methods:
A systematic search was conducted using four electronic databases (PubMed, Embase, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals. The risk ratio (RR) was calculated, along with their 95% confidence intervals. We assessed heterogeneity using Cochrane Q and I
2 statistics and the appropriate P value. The analysis used RevMan 5.4.

Results:
The current meta-analysis includes 14 randomized controlled trials (RCTs) comparing either 2–2.5% chlorhexidine-alcohol with aqueous/alcoholic iodine. It was demonstrated that the CAG-using group had an overall lower incidence of postoperative surgical site infections compared to the iodine-using group (RR=0.30, 95% CI=0.20–0.46, I
2=95%, P<0.00001). It exhibits comparable efficacy across various surgical procedures, as evidenced by its RR of 0.25 [95% CI 0.15–0.41], I
2=51%, and P<0.0001 for general surgery, RR=0.47 [95% CI 0.32–0.67], I
2=82%, P=0.0002 for cesarean section and RR of 0.47 [95% CI 0.34–0.65], I
2=76% and P<0.00001 for additional surgical procedures, including neurosurgery, orthopedic surgery, etc.

Conclusion:
This meta-analysis suggests using either 2.0–2.5% chlorhexidine in alcohol instead of aqueous, alcoholic iodine to prevent SSIs in adult patients undergoing surgery. Chlorhexidine in alcohol worked effectively for general surgery, cesarean sections, and other surgeries. Thus, preoperative skin cleansing with chlorhexidine-alcohol minimizes postoperative SSIs and bacterial colonization in diverse procedures.
Blood-brain barrier-associated biomarker correlated with cerebral small vessel disease and shunt outcome in normal pressure hydrocephalus: a prospective cohort study
Authors: Tseng Pao-Hui , Huang Li-Chuan , Huang Xiang-Ling , Huang Bor-Ren , Lin Shinn-Zong , Tsai Sheng-Tzung , Huang Hsin-Yi 
Published: August 2024

Background:
Blood-brain barrier (BBB) breakdown is associated with neurodegeneration and cognitive impairment. Cerebral small vessel disease (CSVD) is also common in idiopathic normal pressure hydrocephalus (iNPH). Biomarkers in the cerebrospinal fluid (CSF) may reflect the severity of neuropathological damage and indicate a relationship between BBB integrity and iNPH and its surgical outcome. The authors investigated the association of CSVD and comorbidity-related CSF biomarkers with shunt outcomes in iNPH.

Materials and Methods:
This prospective cohort study recruited 53 patients with iNPH, who were subgrouped by CSVD severity. CSF proteins were analyzed, including soluble platelet-derived growth factor receptor-β (sPDGFR-β), Alzheimer’s disease biomarkers, neurofilament light chain (NfL), and triggering receptor expressed on myeloid cells 2 (Trem2). We assessed symptom improvement, investigated its association with biomarkers levels, calculated protein cutoffs for surgical outcomes using receiver operating characteristic (ROC) curves, and compared model predictions using different proteins through hierarchical regression analysis.

Results:
Among patients with iNPH, 74% had comorbid CSVD. Patients with severe CSVD exhibited significantly higher sPDGFR-β levels (P=0.019) and better postoperative performance (β=0.332, t=2.174, P=0.039; r=0.573, P=0.001). Analysis of the predictive potential of the biomarkers showed that sPDGFR-β was predictive of surgical outcomes (area under curve=0.82, sensitivity=66.8%, specificity=94.7%). A Comparison of the models revealed a greater effect of sPDGFR-β (Adjusted R2=0.247, ∆R2=0.160, ∆F(1, 37)=8.238, P=0.007) on cognitive improvement.

Conclusion:
This study highlighted the relevance of CSF biomarkers in assessing CSVD severity and predicting iNPH surgical outcomes. CSF shunt surgery may provide an alternative treatment for neurodegenerative diseases with BBB breakdown and dysfunctional CSF clearance.
Pattern and extent of intrahepatic infiltration of perihilar cholangiocarcinoma – a case–control study based on liver panoramic digital pathology
Authors: Jin Shuo , Jiang Nan , Zhao Jing-Min , Xiao Ying , Wang Si-Yuan , Xiang Can-Hong , Lu Qian , Shan Si-Qiao , Ruan Hao-Tian , Yu Shao-Qing , Zeng Jian-Ping , Yang Shi-Zhong , Li Li , Dong Jia-Hong 
Published: August 2024

Background:
The extent of intrahepatic infiltration of perihilar cholangiocarcinoma (PHCC) remains unclear. This research aimed to explore the pattern and extent of intrahepatic infiltration of PHCC to guide surgical treatment and pathological research.

Materials and methods:
This study included 62 patients diagnosed with PHCC who underwent major hepatectomy. A whole-mount digital liver pathology system (WDLPS) for hepatectomy specimens greater than 10×10 cm was used to panoramically assess the intrahepatic infiltration extent of PHCC.

Results:
The distal intrahepatic infiltration (DIHI) and radial liver invasion (RLI) were important parts of intrahepatic infiltration for PHCC explored by WDLPS. The study confirmed that 75.8% of PHCCs had RLI and the infiltration distance in all patients were within 15 000 µm, 62.9% of PHCCs had DIHI greater than 1 cm away from the main tumor in the liver parenchyma. The recurrence-free survival rates and overall survival rates of patients with DIHI were poorer than the patients without DIHI (P<0.0001, P=0.0038). Arterial invasion on the resected side could be an excellent predictor. A total of 105 liver lobes were resected from 62 PHCC patients. The invasion rates of the left lateral, left medial, right anterior, and right posterior lobe of PHCC were 79%, 100%, 100%, and 69%, respectively.

Conclusion:
The presence of DIHI in most PHCCs was a significant factor for the poor survival. Based on the extent of intrahepatic infiltration, minor hepatectomy was not suitable as the curative surgery for PHCC. Major hepatectomy and liver transplantation were the ideal radical treatment.