bluuebunny/crossref_metadata_2025_split huggingface dataset:
VEGF, FGF1, FGF2 and EGF gene polymorphisms and psoriatic arthritis
Authors: Butt Christopher , Lim Sooyeol , Greenwood Celia , Rahman Proton 
Published: January 2007

Abstract

Background
Angiogenesis appears to be a first-order event in psoriatic arthritis (PsA). Among angiogenic factors, the cytokines vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and fibroblast growth factors 1 and 2 (FGF1 and FGF2) play a central role in the initiation of angiogenesis. Most of these cytokines have been shown to be upregulated in or associated with psoriasis, rheumatoid arthritis (RA) or ankylosing spondylitis (AS). As these diseases share common susceptibility associations with PsA, investigation of these angiogenic factors is warranted.

Methods
Two hundred and fifty-eight patients with PsA and 154 ethnically matched controls were genotyped using a Sequenom chip-based MALDI-TOF mass spectrometry platform. Four SNPs in the VEGF gene, three SNPs in the EGF gene and one SNP each in FGF1 and FGF2 genes were evaluated. Statistical analysis was performed using Fisher's exact test, and the Cochrane-Armitage trend test. Associations with haplotypes were estimated by using weighted logistic models, where the individual haplotype estimates were obtained using Phase v2.1.

Results
We have observed an increased frequency in the T allele of VEGF +936 (rs3025039) in control subjects when compared to our PsA patients [Fisher's exact p-value = 0.042; OR 0.653 (95% CI: 0.434, 0.982)]. Haplotyping of markers revealed no significant associations.

Conclusion
The T allele of VEGF in +936 may act as a protective allele in the development of PsA. Further studies regarding the role of pro-angiogenic markers in PsA are warranted.
Detection of weakly conserved ancestral mammalian regulatory sequences by primate comparisons
Authors: Wang Qian-fei , Prabhakar Shyam , Chanan Sumita , Cheng Jan-Fang , Rubin Edward M , Boffelli Dario 
Published: January 2007

Abstract
Background
Genomic comparisons between human and distant, non-primate mammals are commonly used to identify cis-regulatory elements based on constrained sequence evolution. However, these methods fail to detect functional elements that are too weakly conserved among mammals to distinguish them from non-functional DNA.

Results
To evaluate a strategy for large scale genome annotation that is complementary to the commonly used distal species comparisons, we explored the potential of deep intra-primate sequence comparisons. We sequenced the orthologs of 558 kb of human genomic sequence, covering multiple loci involved in cholesterol homeostasis, in 6 non-human primates. Our analysis identified six non-coding DNA elements displaying significant conservation among primates but undetectable in more distant comparisons. In vitro and in vivo tests revealed that at least three of these six elements have regulatory function. Notably, the mouse orthologs of these three functional human sequences had regulatory activity despite their lack of significant sequence conservation, indicating that they are ancestral mammalian cis-regulatory elements. These regulatory elements could be detected even in a smaller set of three primate species including human, rhesus and marmoset.

Conclusion
We have demonstrated that intra-primate sequence comparisons can be used to identify functional modules in large genomic regions, including cis-regulatory elements that are not detectable through comparison with non-mammalian genomes. With the available human and rhesus genomes and that of marmoset, which is being actively sequenced, this strategy can be extended to the whole genome in the near future.
Reciprocal Negative Regulation between Thyrotropin/3′,5′-Cyclic Adenosine Monophosphate-Mediated Proliferation and Caveolin-1 Expression in Human and Murine Thyrocytes
Authors: Costa Maria José , Senou Maximin , Van Rode Fabienne , Ruf Jean , Capello Matteo , Dequanter Didier , Lothaire Philippe , Dessy Chantal , Dumont Jacques Emile , Many Marie-Christine , Van Sande Jacqueline 
Published: January 2007

AbstractThe expression of caveolins is down-regulated in tissue samples of human thyroid autonomous adenomas and in the animal model of this disease. Because several cell types present in thyroid express caveolins, it remained unclear if this down-regulation occurs in thyrocytes and which are the mechanism and role of this down-regulation in the tumor context. Here we show that prolonged stimulation of isolated human thyrocytes by TSH/cAMP/cAMP-dependent protein kinase inhibits caveolins’ expression. The expression of caveolins is not down-regulated by activators of other signaling pathways relevant to thyroid growth/function. Therefore, the down-regulation of caveolins’ expression in autonomous adenomas is a direct consequence of the chronic activation of the TSH/cAMP pathway in thyrocytes. The down-regulation of caveolin-1 occurs at the mRNA level, with a consequent protein decrease. TSH/cAMP induces a transcription-dependent, translation-independent destabilization of the caveolin-1 mRNA. This effect is correlated to the known proliferative role of that cascade in thyrocytes. In vivo, thyrocytes of caveolin-1 knockout mice display enhanced proliferation. This demonstrates, for the first time, the in vivo significance of the specific caveolin-1 down-regulation by one mitogenic cascade and its relation to a human disease.
Matrix Metalloproteinases, Tissue Inhibitor of Matrix Metalloproteinase‐1, and Laminin‐5 γ2 Chain Immunolocalization in Gingival Tissue of Endotoxin‐Induced Periodontitis in Rats: Effects of Low‐Dose Doxycycline and Alendronate
Authors: Buduneli Eralp , Vardar‐Şengül Saynur , Buduneli Nurcan , Atilla Gül , Wahlgren Jaana , Sorsa Timo 
Published: January 2007

Background: Matrix metalloproteinases (MMPs) play important roles in tissue destruction mechanisms of periodontitis. MMP‐8 and ‐13 are the major collagenases that act in extracellular matrix degradation in periodontal tissues. MMP‐14 is a membrane‐type MMP, and laminin (Ln)‐‐ is a basal membrane component. The aim of the present study was to evaluate the effects of doxycycline and alendronate on gingival tissue expression of MMP‐8, ‐13, and ‐14; tissue inhibitors of MMP (TIMP)‐1; and Ln‐5 γ2 chain in experimental periodontitis induced by Escherichia coli endotoxin (LPS) in rats.Methods: Experimental periodontitis was induced by repeated injection of LPS. Forty‐four adult male Sprague‐Dawley rats were divided into five study groups: saline control, LPS, LPS + doxycycline, LPS + alendronate, and LPS + doxycycline + alendronate. Doxycycline and alendronate were given as a single agent or as combination therapy during the 7 days of the experimental study period. On day 7, the rats were sacrificed, and the gingival tissues were analyzed immunohistochemically for expression of MMP‐8, ‐13, and ‐14, Ln‐‐ γ2 chain, and TIMP‐1. Alveolar bone loss was evaluated morphometrically under a stereomicroscope. Data were tested statistically by Kruskal‐Wallis and Mann‐Whitney tests and Spearman correlation analysis.Results: Alveolar bone loss was significantly higher in the LPS, doxycycline, alendronate, and combination groups than in the saline control group (all P <0.01). MMP‐8 expression was significantly higher in the LPS group than in the saline control group (P = 0.001). Individual administration of doxycycline or alendronate significantly decreased the expression of MMP‐8 compared to LPS (P = 0.01). Combined drug administration reduced MMP‐14 significantly compared to doxycycline (P = 0.004). No significant differences in Ln‐5 γ2 chain expression were found between the study groups (P >0.05). MMP‐14 significantly correlated with the Ln‐5 γ2 chain in the LPS + alendronate group (P = 0.04) and with the amount of alveolar bone loss in the LPS + doxycycline + alendronate group (P = 0.03).Conclusions: Our findings suggest that alendronate and/or doxycycline may inhibit MMP‐8 expression significantly; particularly, their combined administration may provide beneficial effects in periodontal treatment. Moreover, individual administration of alendronate and doxycycline results in significant increases in TIMP‐1 expression in gingiva. However, these effects of combined low‐dose doxycycline and alendronate on MMPs and TIMP should be verified by clinical human trials before these agents are used in dental practice.
Ossification of a Novel Cross‐Linked Porcine Collagen Barrier in Guided Bone Regeneration in Dogs
Authors: Zubery Yuval , Goldlust Arie , Alves Antoine , Nir Eran 
Published: January 2007

Background: Collagen membranes for guided bone regeneration (GBR) and guided tissue regeneration (GTR) are used extensively as bioabsorbable barriers. Cross‐linking of collagen increases its biodurability and enables the control of its degradation kinetics and barrier function. A novel cross‐linking technology was used to produce a porcine type I collagen membrane (GLYM). The purpose of this study was to evaluate the safety, efficacy, and degradation kinetics of GLYM compared to a non–cross‐linked bilayer type I and III porcine collagen membrane (BCM) in surgically created defects in dogs.Methods: After tooth extraction, two mandibular bilateral critical size defects were created in 12 beagle dogs that were randomly assigned to one of five groups: GLYM + bovine bone mineral (BBM), BCM + BBM, BBM alone, sham‐operated, or GLYM alone. Dogs were euthanized after 8, 16, and 24 weeks, and sites were prepared for qualitative, semiquantitative, and quantitative light microscopy analyses.Results: Membrane‐protected sites displayed bone filling between the BBM particles with almost complete restoration of the original ridge morphology that increased with time up to 16 weeks and remained unchanged at 24 weeks. Both membranes showed marked degradation within 16 to 24 weeks, with BCM inconsistency that was undetectable in one of four sites at 8, 16, and 24 weeks. Membrane ossification was observed in all GLYM sites and in only one BCM site, which progressed with time to 24 weeks. Bone increased by ∼1 mm on the lingual side, where the GLYM membrane was in direct contact with bone.Conclusions: Both membranes were safe and effective in supporting bone regeneration in critical size alveolar ridge defects in dogs and completely degraded within 24 weeks with marked BCM inconsistency. In areas of direct contact with bone, all GLYM sites were progressively ossified with time and augmented the original alveolar ridge. To the best of our knowledge, this is the first report of complete ossification of a collagen barrier membrane in GBR procedures.
Treatment of Gingival Hyperpigmentation by Erbium‐Doped:Yttrium, Aluminum, and Garnet Laser for Esthetic Purposes
Authors: Azzeh Manal M. 
Published: January 2007

Background: The normal color of gingiva is pink. Gingival hyperpigmentation is mostly caused by the physiologic deposition of melanin by melanocytes. In “gummy smile” patients, melanin gingival hyperpigmentation causes an esthetic problem and may cause physiologic disturbances. Methods to remove gingival hyperpigmentation vary, but it seems that the most reliable and satisfactory procedure is laser ablation.Methods: Six white patients (five females and one male), who complain of having dark‐brown to black gingival hyperpigmentation were included in the study. Three of them were smokers. Laser ablation was performed by an erbium‐doped:yttrium, aluminum, and garnet (Er:YAG) laser (settings: 250 mJ, 15 Hz, with water and air and using the defocused mode) without using topical or local anesthesia. Each patient required about 20 to 25 minutes for completion of the procedure. After 4 days, another laser ablation (with the same previous settings) was performed to ensure good results. Patients were evaluated a month after completion of treatment and on a semiannual basis. The follow‐up period ranged between 6 and 18 months.Results: In all patients, no discomfort, pain, or bleeding complications were found intraoperatively or 4 days postoperatively. Ablated wounds healed almost completely within 4 days. No recurrence of gingival hyperpigmentation was found during the follow‐up periods. Achieved results were satisfactory for patients and the operator.Conclusions: Taking into account the advantages of using lasers, it seems to be that the depigmentation of melanin hyperpigmented gingiva by the Er:YAG laser is a reliable and satisfactory procedure. Esthetic results were satisfactory for patients and the operator, and no repigmentation was found during the follow‐up period.
Medical Home Implementation and Follow-Up of Cancer-Related Abnormal Test Results in the Veterans Health Administration
Authors: Rajan Suja S. , Sarvepalli Shashank , Wei Li , Meyer Ashley N. D. , Murphy Daniel R. , Choi Debra T. , Singh Hardeep 
Published: March 2024

ImportanceLack of timely follow-up of cancer-related abnormal test results can lead to delayed or missed diagnoses, adverse cancer outcomes, and substantial cost burden for patients. Care delivery models, such as the Veterans Affairs’ (VA) Patient-Aligned Care Team (PACT), which aim to improve patient-centered care coordination, could potentially also improve timely follow-up of abnormal test results. PACT was implemented nationally in the VA between 2010 and 2012.ObjectiveTo evaluate the long-term association between PACT implementation and timely follow-up of abnormal test results related to the diagnosis of 5 different cancers.Design, Setting, and ParticipantsThis multiyear retrospective cohort study used 14 years of VA data (2006-2019), which were analyzed using panel data-based random-effects linear regressions. The setting included all VA clinics and facilities. The participants were adult patients who underwent diagnostic testing related to 5 different cancers and had abnormal test results. Data extraction and statistical analyses were performed from September 2021 to December 2023.ExposureCalendar years denoting preperiods and postperiods of PACT implementation, and the PACT Implementation Progress Index Score denoting the extent of implementation in each VA clinic and facility.Main Outcome and MeasurePercentage of potentially missed timely follow-ups of abnormal test results.ResultsThis study analyzed 6 data sets representing 5 different types of cancers. During the initial years of PACT implementation (2010 to 2013), percentage of potentially missed timely follow-ups decreased between 3 to 7 percentage points for urinalysis suggestive of bladder cancer, 12 to 14 percentage points for mammograms suggestive of breast cancer, 19 to 22 percentage points for fecal tests suggestive of colorectal cancer, and 6 to 13 percentage points for iron deficiency anemia laboratory tests suggestive of colorectal cancer, with no statistically significant changes for α-fetoprotien tests and lung cancer imaging. However, these beneficial reductions were not sustained over time. Better PACT implementation scores were associated with a decrease in potentially missed timely follow-up percentages for urinalysis (0.3–percentage point reduction [95% CI, −0.6 to −0.1] with 1-point increase in the score), and laboratory tests suggestive of iron deficiency anemia (0.5–percentage point reduction [95% CI,−0.8 to −0.2] with 1-point increase in the score).Conclusions and RelevanceThis cohort study found that implementation of PACT in the VA was associated with a potential short-term improvement in the quality of follow-up for certain test results. Additional multifaceted sustained interventions to reduce missed test results are required to prevent care delays.
Preterm Birth Following Active Surveillance vs Loop Excision for Cervical Intraepithelial Neoplasia Grade 2
Authors: Lycke Kathrine Dyhr , Kahlert Johnny , Eriksen Dina Overgaard , Omann Camilla , Pedersen Lars Henning , Sundtoft Iben , Landy Rebecca , Petersen Lone Kjeld , Hammer Anne 
Published: March 2024

ImportanceActive surveillance for cervical intraepithelial neoplasia grade 2 (CIN2) is being implemented in many high-income countries due to the association of excisional treatment with preterm birth. However, it is unknown whether active surveillance results in lower risk of preterm birth given that cervical dysplasia itself is associated with higher risk of preterm birth.ObjectiveTo compare the preterm birth risk between women with CIN2 undergoing active surveillance or immediate loop electrosurgical excision procedure (LEEP).Design, Setting, and ParticipantsThis historical population-based cohort study included women with a first-time diagnosis of CIN2 and a subsequent singleton birth from 1998 to 2018 in Denmark. Women with prior CIN grade 3 or greater or LEEP were excluded. Data were collected from 4 Danish health care registries. Analyses were conducted from October 2022 to June 2023.ExposureWomen were categorized into active surveillance (cervical biopsy and/or cytology) or immediate LEEP based on their first cervical sample after CIN2 diagnosis. The active surveillance group was further subdivided based on whether a delayed LEEP was performed within 28 months from CIN2 diagnosis.Main Outcomes and MeasuresRisk of preterm birth (&amp;lt;37 + 0 weeks) was assessed and relative risks (RRs) were calculated using modified Poisson regression. Analyses used inverse probability treatment weighting of the propensity scores to adjust for age, parity, calendar year, index cytology, and smoking.ResultsA total of 10 537 women with CIN2 and a singleton birth were identified; 4430 (42%) underwent active surveillance and 6107 (58%) were treated with immediate LEEP. For both groups, most were aged 23 to 29 years at CIN2 diagnosis (3125 [70%] and 3907 [64%], respectively). Overall, 869 births (8.2%) were preterm. The risk of preterm birth was comparable between active surveillance and immediate LEEP (RR, 1.03; 95% CI, 0.90-1.18). However, for women undergoing delayed LEEP after active surveillance (1539 of the active surveillance group [35%]), the risk of preterm birth was higher than for women treated with immediate LEEP (RR, 1.29; 95% CI, 1.08-1.55).Conclusions and relevanceIn this cohort study of women with CIN2, the risk of preterm birth was comparable between active surveillance and immediate LEEP. However, delayed LEEP was associated with 30% higher risk of preterm birth than immediate LEEP. Thus, risk stratification at CIN2 diagnosis is important to identify women with increased risk of delayed LEEP.
Cucumber‐Derived Extracellular Vesicle‐Functionalized Metal‐Organic Frameworks for Enhanced Photodynamic Therapy of Hypertrophic Scars
Authors: Kong Tianyu , Zhang Kai , Wang Yanmin , Ye Yingmin , Hou Jun , Xu Chen , Zhao Nana , Xu Fu‐Jian 
Published: March 2024

AbstractPhotodynamic therapy (PDT) with noninvasiveness and high safety has emerged as a promising therapeutic approach for the management of hypertrophic scars (HS). However, the low transdermal delivery and overexpressed levels of intracellular glutathione (GSH) severely hinder its therapeutic effectiveness. Herein, a multifunctional biomimetic nanoplatform (NDs@EV‐RGD) composed of arginine‐glycine‐aspartic acid (RGD)‐modified cucumber‐derived extracellular vesicles (EVs) and copper‐based metal‐organic framework nanodots (Cu‐MOF NDs) is designed for PDT‐mediated HS treatment. The EVs with low Young's modulus exhibit excellent deformability which endow NDs@EV‐RGD with the capacity to overcome the compact stratum corneum barrier, thereby significantly improving their transdermal delivery efficiency. Notably, the RGD targeting peptide displays specific binding to α1β1 integrin on the fibroblast membranes within HS, leading to the high accumulation efficiency of NDs@EV‐RGD at the HS site. Under near‐infrared laser irradiation, NDs@EV‐RGD efficiently generates abundant reactive oxygen species, inducing the apoptosis of excessively proliferated fibroblasts. Moreover, Cu‐MOF NDs interact with the local GSH, leading to GSH depletion and a significant enhancement in PDT efficacy. Furthermore, NDs@EV‐RGD demonstrates a remarkable therapeutic effect in improving the appearance of HS in a rabbit ear HS model, promoting the apoptosis and remodeling of collagen fibers. Therefore, this work provides a promising biomimetic platform for HS treatment.
Controllable Dopamine Conjugation Boosts Fluorescence, Biocompatibility, and PET Imaging‐Guided Toxicity Assessment of Polycations
Authors: Zhao Mingming , Guo Xinhao , Su Chen , Li Meng , Wang Xinyu , Pan Donghui , Wang Lizhen , Xu Yuping , Chen Chongyang , Yang Min , Li Xiaotian , Yan Junjie 
Published: March 2024

AbstractAs well known in bioactives delivery and cancer/inflammation theranostics, polycations have recently extended their biomedical potentials in reducing visceral fat, embolizing body fluid, modulating blood coagulation, and ameliorating hyperammonemia. However, positive charges that dominate various action mechanisms, often raise risks in biosafety concerns. Also, the lack of intrinsic imaging properties of polycations makes it challenging to uncover their pharmacokinetic profiles in living objects. Herein, dopamine conjugation is demonstrated controllable and highly efficient in boosting the fluorescence or even white color emission of various polycations including hyperbranched poly(amido amine) (HPAA), polyethyleneimine and poly‐L‐lysine. By shielding partial surface positive charges, increasing hydrophobicity, and inducing aqueous self‐assembly, dopamine conjugation can significantly enhance the biocompatibility and decrease the toxicity and immunogenicity of polycations. Furthermore, the catechol‐metal binding interaction facilitates the accessibility of polycation‐based positron emission tomography (PET) probes. Different tissue uptake and biodistributions of gallium‐68‐radiolabeled HPAA before and after dopamine conjugation indicate that PET imaging can be a useful supplement to evaluate the dynamic toxicities of polycations.
Toward the Improvement of the Mechanical and Tribological Properties of Braided Ligament for ACL Reconstruction: A “Carrot and Stick” Strategy
Authors: Li Shenglin , Wang Shuhan , Shao Jiasheng , Wang Jiali , Liu Wenliang , Chen Linxin , Li Zeng , Zhang Chao , Song Jian 
Published: March 2024

AbstractBone tunnel enlargement has been troubling the clinical adoption of braided artificial ligaments for decades, to which mechanical and tribological performance promotion shall be an effective and promising approach. Herein, a “carrot and stick” strategy has been introduced with two types of polyethylene terephthalate (PET) fibers to fabricate hybrid textures, which is expected to advance fatigue and tribological performance without yielding essential mechanical strength and biocompatibility. Owing to advancements in such a “carrot and stick” strategy, the obtained grafts present three promising properties: i) enhancement of mechanical strength; ii) coefficient of friction (COF) reduction of 25% at the greatest extent, thus lowering the risk of bone tunnel enlargement; iii) final displacement shrinkage of graft length after cyclic loadings, favored in the clinic for isometric reconstruction. The results obtained in this study show that the “carrot and stick” strategy can be a creative and convenient method to optimize the service life, saving the complication rate of artificial ligaments for clinical applications.