bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medicare Reimbursement in Orthopaedic Foot and Ankle Surgery: A Continued Decline
Authors: Miskiel Sandra A. , Bye Matthew , Pagliaro Ava F. , Pagliaro Andre J. 
Published: December 2024

Category: Other Introduction/Purpose: The absence of an annual inflationary update for physician reimbursement from the Centers for Medicare & Medicaid Services threatens the financial stability of orthopaedic practices nationwide. Inflation-adjusted Medicare physician reimbursement for foot and ankle procedures has decreased by over 30% from 2000 to 2020. The effects of recent inflationary trends on orthopaedic foot and ankle reimbursement are unknown. Thus, our study sought to analyze trends in Medicare reimbursement rates from 2000 to 2024 for orthopaedic foot and ankle surgical procedures. Methods: The financial database of a single academic tertiary care center was queried to identify the Current Procedural Terminology (CPT) codes most frequently utilized in orthopaedic foot and ankle care. Next, the Physician Fee Schedule Look-Up Tool from the Centers for Medicare & Medicaid Services was queried for the top 30 CPT codes utilized, and physician reimbursement data extracted. Monetary data was subsequently adjusted for inflation utilizing the Consumer Price Index and reported in 2024 US dollars. The average annual and total percent change in reimbursement were calculated for included procedures. The compound annual growth rate (CAGR) was calculated using 2024 and 2000 inflation-adjusted monetary data. Results: Prior to adjusting for inflation, the average physician reimbursement decreased by 7.9% from 2000 to 2024 for all included foot and ankle CPT codes. After adjusting for inflation, the average physician reimbursement decreased by 48.0% for included CPT codes, with all 30 CPT codes decreasing by more than 40.8%. The greatest decrease in reimbursement observed from 2000 to 2024 was for open reduction internal fixation of calcaneal fracture at 58.9% ($2,697.69 to $1,109.05) followed by repair of flexor tendon at 58.5% ($886.82 to $368.05) and ankle arthroscopy at 55.4% ($1,031.07 to $459.40). The average CAGR was -2.83%. Conclusion: Our study demonstrates that Medicare physician reimbursement for common orthopaedic foot and ankle procedures continues to decrease at an unsustainable rate. It is imperative that policy-makers understand these untenable trends to ensure continued access to quality foot and ankle care, especially for Medicare beneficiaries.
Midterm Functional Outcomes of Synthetic Cartilage Implant (SCI) Arthroplasty for Hallux Rigidus
Authors: Rajeev Aysha , Koshy George , Devalia Kailash 
Published: December 2024

Category: Midfoot/Forefoot; Other Introduction/Purpose: Hallux rigidus is a degenerative condition of first metatarso-phalangeal joint, affecting people at all ages, but more commonly above 50 years of age. Multiple options are available to alleviate pain and improve movements of big toe. These include cheilectomy with Moberg osteotomy, silastic implants, ceramic and metal arthroplasties, hemiarthroplasties with Co-Cr and titanium implants with varying success. The aim of our study is to evaluate the midterm outcome of synthetic cartilage implant (SCI - Cartiva) arthroplasty for hallux rigidus. Methods: There were a total of 70 patients who underwent SCI interpositional arthroplasty. The five-year functional scores for all patients were collected and analysed. The functional evaluation was done using Manchester-Oxford Foot Questionnaire (MOxFQ). The general health was assessed by EQ-5D which included EQVAS. The data was obtained from hospital digital database Medway and Amplitude clinical outcomes. This was analysed by an independent assessor who was not involved in the patients’ care. The complications and revision rates were also documented. Results: Mean age at the time of operation was 63.4 years (range 42–84 years). The mean follow-up was 62.6 months. At five years follow up, 90% of the patients were satisfied with the outcome. The average preoperative MOxFQ score improved from 36.8 to 19.3 at one year after surgery. The EQ-5D scores improved from preoperative average of 9.4 to 4.4 at one year. The preoperative EQVAS was 75 and 85 at one year. At five years follow up the average MOxFQ score was 17.6, EQ-5D - 4.8 and EQVAS - 80. None of the patients had any infection. Three patients out of 70 had revision to first MTP fusion due to ongoing pain. Figure 1 shows the survival curve of the SCI implant at five years. Conclusion: Long term outcomes of Cartiva demonstrate clinical efficacy of this synthetic implant. The implant is durable, safe and is a viable treatment option to decrease pain, improve function and maintain motion for advanced hallux rigidus.
Identification of a suitable matching procedure in health services research: Insights into a study for stroke patients
Authors: Elkenkamp Svenja , Düvel Juliane , Gensorowsky Daniel , Greiner Wolfgang 
Published: December 2024

Background STROKE OWL is a quasi-experimental study using claims data from statutory health insurances in Germany to calculate the effect of case managers for stroke. Since there is no recruited control group, a suitable procedure needed to be identified to make the intervention effect measurable. Hence, the objective of this paper is to present an approach for comparing matching procedures before final data analyses take place. Methods We followed a four-step approach to identify an appropriate procedure on a partial dataset. First, we conducted a systematic review for identifying potential confounders of the study’s outcome. Afterwards we checked whether a matching procedure was able to balance the dataset with respect to the outcome, under the assumption that all relevant covariates including the intervention variable were balanced. Within the two last steps we checked covariate balances and remaining group sizes. Three matching procedures – coarsened exact matching, optimal full matching and propensity score matching – were tested. Results The coarsened exact matching was able to balance variables perfectly but on average lost >50% of the observations. Although optimal full and propensity score matching revealed some weaknesses concerning the variable balance, considerably more observations remained in the dataset. Based on the described approach and the external framework conditions of STROKE OWL the optimal full matching was chosen as matching procedure most suitable. Conclusion In summary, it was challenging to identify a suitable matching procedure for this study, since the detailed results of the different balance and group size checks varied.
ITGB3 is reduced in pregnancies with preeclampsia and its influence on biological behavior of trophoblast cells
Authors: Li Chunyan , Meng Yanan , Zhou Beibei , Zhang Yanrong , Xia Qing , Huang Yu , Meng Li , Shan Chunjian , Xia Jiaai , Zhang Xiangdi , Wang Qiuhong , Lv Mingming , Long Wei 
Published: December 2024

Abstract
Background
Preeclampsia (PE) is a serious pregnancy complication associated with impaired trophoblast function. Integrin β3 (ITGB3) is a cell adhesion molecule that plays a role in cell movement. The objective of this study was to identify the biological function and expression level of ITGB3 in PE.

Methods
Cell proliferation, migration, invasion, adhesion, and apoptosis were estimated by CCK8 assay, transwell, scratch assays, and flow cytometry, respectively. The expression levels of ITGB3 were determined by qRT-PCR, western blot, and immunohistochemistry (IHC). Co-immunoprecipitation and Alphafold-Multimer protein complex structure prediction software were employed to identify the molecules that interact with ITGB3.

Results
Cell functional experiments conducted on HTR8/SVneo cells demonstrated that ITGB3 significantly enhanced proliferation, migration, invasion, and adhesion, while simultaneously inhibiting apoptosis. Relative ITGB3 expression levels were observed to be lower in PE placental tissue than in normal tissue and similarly reduced in hypoxic HTR8/SVneo cells. RNA-sequencing data from PE placental samples in the GEO database were analyzed to identify differentially expressed genes associated with the disease. We identified a total of 1460 mRNAs that were significantly differentially expressed in PE patients. Specifically, 798 mRNAs were significantly upregulated, and 662 mRNAs were significantly downregulated. Notably, the ITGB3 exhibited a pronounced down-regulation among the differential expression mRNA.

Conclusions
This study suggested that ITGB3 plays an important role in promoting the proliferative, migratory, invasive, and adhesive capabilities of trophoblast cells. These findings may facilitate a more in-depth understanding of the molecular mechanisms that promote PE progression.
Crosstalk between cancer-associated fibroblasts and non-neuroendocrine tumor cells in small cell lung cancer involves in glycolysis and antigen-presenting features
Authors: Lu Yuanhua , Li Hui , Zhao Peiyan , Wang Xinyue , Shao Wenjun , Liu Yan , Tian Lin , Zhong Rui , Liu Haifeng , Cheng Ying 
Published: December 2024

Abstract
Background
Small cell lung cancer (SCLC) is a highly fatal malignancy, the complex tumor microenvironment (TME) is a critical factor affecting SCLC progression. Cancer-associated fibroblasts (CAFs) are crucial components of TME, yet their role in SCLC and the underlying mechanisms during their interaction with SCLC cells remain to be determined.

Methods
Microenvironmental cell components were estimated using transcriptome data from SCLC tissue available in public databases, analyzed with bioinformatic algorithms. A co-culture system comprising MRC5 fibroblasts and SCLC cell lines was constructed. RNA sequencing (RNA-seq) was performed on co-cultured and separately cultured MRC5 and H196 cells to identify differentially expressed genes (DEGs) and enriched signaling pathways. Glycolysis and STING signaling in SCLC cells were assessed using glucose uptake assays, qRT-PCR, and Western blot analysis. Immunohistochemical staining of SCLC tissue arrays quantified α-SMA, HLA-DRA and CD8 expression.

Results
Non-neuroendocrine (non-NE) SCLC-derived CAFs exhibited more abundance and DEGs than NE SCLC-derived CAFs did, which interact with non-NE SCLC cells can induce the enrichment of glycolysis-related genes, increasement of glucose uptake, upregulation of glycolytic signaling proteins in non-NE SCLC cells and accumulation of lactate in the extracellular environment, confirming CAF-mediated glycolysis promotion. Additionally, glycolysis-induced ATP production activated STING signaling in non-NE SCLC cells, which upregulated T cell chemo-attractants. However, CAF abundance did not correlate with CD8 + T cell numbers in SCLC tissues. Additionally, non-NE SCLC cell-educated CAFs exhibited features of antigen-presenting CAFs (apCAFs), as indicated by the expression of major histocompatibility complex (MHC) molecules. Co-localization of HLA-DRA and α-SMA signals in SCLC tissues confirmed apCAF presence. The apCAFs and CD8 + T cells were co-located in the SCLC stroma, and there was a positive correlation between CAFs and regulatory T cell (Treg) abundance.

Conclusion
Our findings suggest that crosstalk between CAFs and non-NE SCLC cells promotes glycolysis in non-NE SCLC cells, thereby increase T cell chemo-attractant expression via activating STING signaling. On the other hand, it promotes the presence of apCAFs, which probably contributes to CD8 + T cell trapping and Treg differentiation. This study emphasizes the pro-tumor function of CAFs in SCLC by promoting glycolysis and impairing T cell function, providing direction for the development of novel therapeutic approaches targeting CAF in SCLC.
A cross-sectional and longitudinal evaluation of serum creatinine as a biomarker in spinal muscular atrophy
Authors: Zhao Xin , Gong Zhenxiang , Luo Han , Li Zehui , Gao Rong , Yang Kangqin , Deng Wenhua , Peng Sirui , Ba Li , Liu Yang , Zhang Min 
Published: December 2024

Abstract
Objective
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by proximal muscle weakness and atrophy. The increasing availability of disease-modifying therapies has prompted the development of biomarkers to facilitate clinical assessments. We explored the association between disease severity and serum creatinine (Crn) levels in SMA patients undergoing up to two years of treatment with nusinersen.

Methods
We measured serum Crn levels and assessed function performance using the Hammersmith Functional Motor Scale-Expanded (HFMSE), Medical Research Council Scale (MRC), 6-Minute Walk Test (6MWT), ulnar Compound Muscle Action Potential (CMAP), and forced vital capacity (FVC) in a cohort comprising 28 adolescent and adult patients with SMA. The association between Crn and disease severity was investigated through partial rank correlation analysis and linear mixed models while accounting for age, gender, and BMI. Linear models were employed to predict functional performance.

Results
28 SMA patients and 28 gender- and age-matched healthy controls (HCs) were included, resulting in a dataset of 185 visits. Compared to HCs, SMA patients exhibited significantly lower Crn values ​​(67.4 ± 14 vs. 23.7 ± 14.8 umol/L, p<0.0001). After adjusting for age, sex, and BMI, Crn showed positive correlations with the HFMSE (p<0.0001, r = 0.884), MRC (p<0.0001, r = 0.827), FVC (p = 0.002, r = 0.730), and ulnar CMAP (p<0.0001, r = 0.807). Patients with SMN2 copy number ≥ 4 had nearly twice as high Crn levels as those with SMN2 copy number < 4 (34.1 ± 3.75 vs. 17.2 ± 2.52 umol/L, p = 0.00145). Ambulant SMA patients had more than double the Crn levels compared to non-ambulant ones (32 ± 2.33 vs. 12.9 ± 2.38 umol/L, p<0.0001). Furthermore, Crn explained that up to 83.5% of the variance in functional performance measured by HFMSE, MRC, and 6MWT was significantly higher than that of traditional biomarkers.

Conclusions
These findings suggest that Crn may be a potential biomarker for assessing disease severity in adolescents and adults with SMA, demonstrating its promise in clinical applications.
Evaluation of factors associated with immunoglobulin, protein, fat and lactose concentrations in colostrum of dairy cows from Austria
Authors: Lichtmannsperger Katharina , Hechenberger Nicole , Hartsleben Christina , Psenner Ariane , Marseiler Maren , Tichy Alexander , Albert Thiemo , Wittek Thomas 
Published: December 2024

Abstract
Background
Calves rely on the passive transfer with immunoglobulins derived from colostrum. Currently, there is a lack of knowledge on colostrum management practices and colostrum quality on small scale family-owned dairy farms in Austria. The objectives of this study were to describe factors that are associated with immunoglobulin, protein, fat and lactose concentrations in dairy cow colostrum from the federal state of Salzburg. Therefore, an online questionnaire was designed to gather information on general farm characteristics. Further, the farmers collected individual colostrum samples and completed a detailed accompanying questionnaire for each sample. Immunoglobulin levels were determined by using a Brix refractometer and protein, fat and lactose by standardized laboratory methods. Linear mixed effect models were built to test factors associated with colostrum immunoglobulin, fat, protein and lactose concentrations.

Results
In total, 1,050 colostrum samples from 72 dairy farms were collected. The number of calvings per year was distributed as follows: ≤10 calvings: 8.3% of the farms, 11 to 20: 31.9%, 21 to 30: 29.2%, 31 to 40: 15.3% and ≥ 41 calvings: 15.3%. Overall, the median Brix value was 22.0% (7.3–36.1%). The number of samples with good and poor-quality colostrum was 517 and 528, respectively. Cow-level factors significantly affecting colostrum Brix% were parity, calving season, ante partum colostrum leakage, time lag between parturition and colostrum collection. In total, a subset of 307 colostrum samples from 39 farms from pure-breed dual-purpose Simmental cows were further analysed for protein, fat and lactose concentration. The median concentration for fat was 5.1% (0.5–18.5%), protein 14.6% (4.2–27.5%) and lactose 2.3% (0.2–5.0%). The cow-level factors affecting protein concentration were similar to the factors influencing Brix%. Fat concentration was influenced by the time lag between calving and colostrum collection and by parity.

Conclusions
The present study confirmed the factors, which are currently known to have an impact on colostrum quality. This was the first large scale approach in the federal state of Salzburg to survey colostrum management including colostrum sample collection. The range of colostrum quality was wide (7.3% Brix to 36.1% Brix) therefore many calves will be at risk of receiving poor quality colostrum as defined by a Brix of ≤ 22%.
LINC01094 promotes gastric cancer through dual targeting of CDKN1A by directly binding RBMS2 and HDAC1
Authors: Zhou Xinyi , Gu Cheng , Xiao Linmei , Hu Li , Chen Guanhua , Zuo Fei , Shao Hongan , Fei Bojian 
Published: December 2024

Abstract
Background
Accumulating studies have focused on long noncoding RNAs (lncRNAs) because of their regulatory effects on multiple cancers. However, the biological functions and molecular mechanisms of lncRNAs in gastric cancer (GC) remain to be elucidated in depth.

Methods
Long intergenic nonprotein coding RNA 1094 (LINC01094), a differentially expressed lncRNA between GC tissues and adjacent normal tissues, was identified. Moreover, gain- and loss-of-function experiments in vitro and in vivo were carried out. To understand the mechanisms underlying the regulatory effects of LINC01094, we performed RNA pull-down assays, RNA immunoprecipitation assays, chromatin immunoprecipitation assays, luciferase reporter assays, etc.

Results
LINC01094 was markedly upregulated in GC tissues and cell lines, and LINC01094 upregulation was positively correlated with GC malignant behaviours in vitro and in vivo. Mechanistically, LINC01094 downregulated the expression of CDKN1A by interacting with RNA binding motif single stranded interacting protein 2 (RBMS2) and histone deacetylase 1 (HDAC1). Additionally, LINC01094 was confirmed to sponge miR-128-3p and participate in the LINC01094-miR-128-3p-RUNX family transcription factor 1 (RUNX1) feedback loop. Finally, Ro 5-3335, a validated RUNX1 inhibitor, was explored for anticancer drug development in GC.

Conclusions
The LINC01094-miR-128-3p-RUNX1 feedback loop downregulates CDKN1A and promotes GC cooperatively with RBMS2 and HDAC1. Furthermore, Ro 5-3335 may hold promising therapeutic potential in the treatment of GC. Hence, our study found an oncogenic lncRNA, LINC01094, which could be a promising target for cancer treatment and diagnosis.

Graphical Abstract
Improved efficacy of therapeutic HPV DNA vaccine using intramuscular injection with electroporation compared to conventional needle and needle-free jet injector methods
Authors: Peng Shiwen , Fan Darrell , Tu Hsin-Fang , Cheng Michelle , Arend Rebecca C. , Levinson Kimberly , Tao Julia , Roden Richard B. S. , Hung Chien-Fu , Wu T.-C. 
Published: December 2024

Abstract
Background
We have previously developed a candidate therapeutic HPV DNA vaccine (pBI-11) encoding mycobacteria heat shock protein 70 linked to HPV16/18 E6/E7 proteins for the control of advanced HPV-associated oropharyngeal cancer (NCT05799144). While naked DNA vaccines are readily produced, stable, and well tolerated, their potency is limited by the delivery efficiency. Here we compared three different IM delivery strategies, including intramuscular (IM) injection, either with a needle alone or with electroporation at the injection site, and a needle-free injection system (NFIS), for their ability to elicit gene expression and to improve the potency of pBI-11 DNA vaccine.

Results
We found that electroporation after IM injection significantly increases gene expression from a luciferase-encoding DNA construct compared to IM injection alone or NFIS. We also showed that single administration of pBI-11 DNA via electroporation-mediated delivery generates the greatest increase in HPV antigen-specific CD8 + T cell-mediated immune responses, resulting in the most potent antitumor effect compared to the other two methods. We further compared the response to three repeat immunizations via each of these different methods. We found that electroporation-mediated delivery of pBI-11 DNA generates the greatest HPV antigen-specific CD8 + T cell immune responses and therapeutic antitumor effects compared to the other two methods. Monitoring of mouse behaviors and body weight, and necropsy indicated that electroporation-mediated delivery of clinical grade pBI-11 DNA vaccine was well-tolerated and presented no evident local or systemic toxicity.

Conclusions
These findings provide rationale for clinical testing of pBI-11 DNA vaccine delivered by electroporation for the control of HPV16/18-associated infections and/or cancers.
Predictive role of [18F]FDG PET-CT radiomic parameters for KRAS/BRAF/EGFR mutations in metastatic colorectal cancer patients
Authors: Ali Magdi A. , Zahra Omar Shebl , Morsi Mohmed I. , El Safwany Mohamed M. , El Feky Shaymaa Essam 
Published: December 2024

Abstract
Objectives
The objective of this study was to evaluate the predictive value of 18F-fluorodeoxyglucose [18F]FDG positron emission tomography (PET-CT) radiomic parameters in relation to KRAS/BRAF/EGFR mutations in patients with metastatic colorectal cancer (mCRC).

Methods
Blood samples were collected from 90 mCRC patients to assess KRAS G13V, BRAF V600E, and EGFR exon 20 mutations. [18F]FDG PET-CT scans were performed, and radiomic parameters, including the SUV max, max TBR, total MTV, and total TLG, were calculated and correlated with different genotypes and haplotypes of the aforementioned mutations.

Results
The SUV max, TLG, and TBR were significantly greater in patients with the KRAS G13V and BRAF V600E mutations than in patients with the wild-type genotype. The SUVmax was also significantly greater in patients with EGFR exon 20 mutations. Haplotype analysis revealed that the SUVmax was significantly greater in patients with KRAS/BRAF/EGFR mutations than in other patients, with a specificity of 68.18% and sensitivity of 65.28%.

Conclusion
The results suggest that [18F] FDG PET-CT radiomic parameters, particularly the SUV max, have the potential to serve as noninvasive tools for predicting the KRAS/BRAF/EGFR mutation status in mCRC patients.