bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Outcomes Following Arthroscopic Treatment of Femoroacetabular Impingement Syndrome Across Different Surgeons, Surgical Techniques, and Postoperative Protocols: A Multi-institutional Study
Authors: Spencer Andrew D. , Newby Nathan L. , Nosrat Cameron , Wong Stephanie E. , Zhang Alan L. , Hagen Mia S. 
Published: January 2025

Background: Femoroacetabular impingement syndrome (FAIS) is frequently treated arthroscopically with osteoplasty and labral repair. Surgical preferences vary in terms of equipment, technique, and postoperative protocol. Patient-reported outcome measures (PROMs) are valuable tools to assess outcomes across different institutions. Purpose: To compare PROMs after FAIS arthroscopy and evaluate the impact on postoperative outcomes with independent surgeons utilizing different surgical techniques and postoperative protocols. Study Design: Cohort study; Level of evidence, 2. Methods: Prospective data were collected from patients with a 2-year follow-up after arthroscopic FAIS treatment by 2 orthopaedic surgeons from different states, each attending different sports medicine fellowships. Patients were matched according to age, sex, and body mass index. Data included patient characteristics, surgical findings, and the Hip disability and Osteoarthritis Outcome Score (HOOS) preoperatively and 2 years postoperatively. Patients with revision surgery, concomitant procedures, or incomplete pre- and postoperative data were excluded. Surgeon A utilized interportal capsulotomy, capsular repair, all-suture anchors, and a postoperative hip brace. Surgeon B employed periportal capsulotomy without repair, polyether ether ketone suture anchors, and no brace. The 2 high-volume arthroscopists (>100 hips/year) performed osteoplasty and labral repair and used a large perineal post. Cohorts were analyzed with appropriate t tests, with significance set at P < .05. The percentage of patients achieving minimal clinically important difference (MCID) was calculated using Pearson chi-square tests. Results: A total of 176 hips (100 women, 76 men) were included, with 88 matched patients from each institution. The mean age was 33.7 years and the body mass index was 26.3 kg/m2. Both cohorts significantly improved in all 5 HOOS subscales 2 years after surgery. When comparing the mean change in PROMs and the percentage of patients achieving the MCID, differences were only observed in the HOOS-Sports subscale (cohort A: 25.3 ± 29.7 vs cohort B: 34.3 ± 29.7; P = .048; MCID achieved in 57% of patients vs 76%; P = .01). Conclusion: This prospective cohort study on arthroscopic FAIS treatment indicates that matched patient cohorts from different institutions show similarly improved PROMs at 2 years. This study suggests consistent patient outcomes across sites despite geography, surgeon, training, surgical technique, implants, and postoperative protocol.
The mechanism of enterogenous toxin methylmalonic acid aggravating calcium-phosphorus metabolic disorder in uremic rats by regulating the Wnt/β-catenin pathway
Authors: Fan Xing , Li Jing , Gao Yan , Li Lin , Zhang Haisong , Bi Zhaoyu 
Published: January 2025

Abstract

Background
Uremia (UR) is caused by increased UR-related toxins in the bloodstream. We explored the mechanism of enterogenous toxin methylmalonic acid (MMA) in calcium-phosphorus metabolic disorder in UR rats via the Wnt/β-catenin pathway.

Methods
The UR rat model was established by 5/6 nephrectomy. The fecal bacteria of UR rats were transplanted into Sham rats. Sham rats were injected with exogenous MMA or Salinomycin (SAL). Pathological changes in renal/colon tissues were analyzed. MMA concentration, levels of renal function indicators, serum inflammatory factors, Ca2+/P3+, and parathyroid hormone, intestinal flora structure, fecal metabolic profile, intestinal permeability, and glomerular filtration rate (GFR) were assessed. Additionally, rat glomerular podocytes were cultured, with cell viability and apoptosis measured.

Results
Intestinal flora richness and diversity in UR rats were decreased, along with unbalanced flora structure. Among the screened 133 secondary differential metabolites, the MMA concentration rose, showing the most significant difference. UR rat fecal transplantation caused elevated MMA concentration in the serum and renal tissues of Sham rats. The intestinal flora metabolite MMA or exogenous MMA promoted intestinal barrier impairment, increased intestinal permeability, induced glomerular podocyte loss, and reduced GFR, causing calcium-phosphorus metabolic disorder. The intestinal flora metabolite MMA or exogenous MMA induced inflammatory responses and facilitated glomerular podocyte apoptosis by activating the Wnt/β-catenin pathway, which could be counteracted by repressing the Wnt/β-catenin pathway.

Conclusions
Enterogenous toxin MMA impelled intestinal barrier impairment in UR rats, enhanced intestinal permeability, and activated the Wnt/β-catenin pathway to induce glomerular podocyte loss and reduce GFR, thus aggravating calcium-phosphorus metabolic disorder.
Extracellular matrix turnover in severe COVID-19 is reduced by corticosteroids
Authors: Pillay Janesh , Flikweert Antine W. , van Meurs Matijs , Grootenboers Marco J. , van der Sar-van der Brugge Simone , van der Voort Peter H. J. , Karsdal Morten A. , Sand Jannie M. B. , Leeming Diana J. , Burgess Janette K. , Moser Jill 
Published: January 2025

Abstract

Background
Severe and critical COVID-19 is characterized by pulmonary viral infection with SARS-CoV-2 resulting in local and systemic inflammation. Dexamethasone (DEX) has been shown to improve outcomes in critically ill patients; however, its effect on tissue remodeling, particularly collagen turnover, remains unclear. This study investigated the association between circulating extracellular matrix (ECM) remodeling neo-epitopes and COVID-19 severity, their relationship with mortality, and the effect of DEX on these markers.

Methods
We conducted a multi-center prospective cohort study involving 226 COVID-19 patients: 157 with severe disease admitted to the ward and 69 with critical disease admitted to the ICU. Plasma samples were collected at ICU admission and at discharge or death. Circulating collagen degradation (C3M, C4Ma3, and C6M) and synthesis (PRO-C3, PRO-C4, and PRO-C6) neo-epitopes were measured. Longitudinal analysis of ECM neo-epitope changes during ICU stay and their association with mortality was performed, along with an evaluation of the impact of DEX treatment on these markers.

Results
Critically ill patients exhibited higher levels of collagen degradation (reflecting inflammatory driven ECM destruction) (C3M, C6M) and collagen synthesis (strongly related to fibroblast activity) (PRO-C3, PRO-C6) neo-epitopes than severe patients. Increased collagen turnover, measured during ICU stay, was associated with mortality. Non-survivors displayed rising levels of collagen degradation and synthesis markers over time, whereas survivors had stable or declining levels. In non-survivors without DEX treatment, C6M and PRO-C6 levels were significantly increased, whereas these elevations were less pronounced in patients treated with DEX.

Conclusion
Our findings suggest that elevated collagen turnover is associated with poor outcomes in critically ill COVID-19 patients. DEX treatment appeared to attenuate ECM remodeling, although this effect was not linked to improved survival. Further studies are needed to confirm these observations and better understand the role of ECM remodeling in COVID-19 and the potential therapeutic impact of corticosteroids.
The fibronectin-targeting PEG-FUD imaging probe shows enhanced uptake during fibrogenesis in experimental lung fibrosis
Authors: Harr Thomas J. , Gupta Nikesh , Rahar Babita , Stott Kristen , Medina-Guevara Yadira , Gari Metti K. , Oler Angie T. , McDermott Ivy Sohee , Lee Hye Jin , Rasoulianboroujeni Morteza , Weichmann Ashley M. , Forati Amir , Holbert Kelsey , Langel Trevor S. , Coulter Kade W. , Burkel Brian M. , Tomasini-Johansson Bianca R. , Ponik Suzanne M. , Engle Jonathan W. , Hernandez Reinier , Kwon Glen S. , Sandbo Nathan , Bernau Ksenija 
Published: January 2025

Abstract
Progressive forms of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), are deadly disorders lacking non-invasive biomarkers for assessment of early disease activity, which presents a major obstacle in disease management. Excessive extracellular matrix (ECM) deposition is a hallmark of these disorders, with fibronectin being an abundant ECM glycoprotein that is highly upregulated in early fibrosis and serves as a scaffold for the deposition of other matrix proteins. Due to its role in active fibrosis, we are targeting fibronectin as a biomarker of early lung fibrosis disease activity via the PEGylated fibronectin-binding polypeptide (PEG-FUD). In this work, we demonstrate the binding of PEG-FUD to the fibrotic lung throughout the course of bleomycin-induced murine model of pulmonary fibrosis. We first analyzed the binding of radiolabeled PEG-FUD following direct incubation to precision cut lung slices from mice at different stages of experimental lung fibrosis. Then, we administered fluorescently labeled PEG-FUD subcutaneously to mice over the course of bleomycin-induced pulmonary fibrosis and assessed peptide uptake 24 h later through ex vivo tissue imaging. Using both methods, we found that peptide targeting to the fibrotic lung is increased during the fibrogenic phase of the single dose bleomycin lung fibrosis model (days 7 and 14 post-bleomycin). At these timepoints we found a correlative relationship between peptide uptake and fibrotic burden. These data suggest that PEG-FUD targets fibronectin associated with active fibrogenesis in this model, making it a promising candidate for a clinically translatable molecular imaging probe to non-invasively determine pulmonary fibrosis disease activity, enabling accelerated therapeutic decision-making.
Provocation of brachial plexus and systemic symptoms during the elevated arm stress test in individuals with myalgic encephalomyelitis/chronic fatigue syndrome or idiopathic chronic fatigue
Authors: Edwards Charles C. , Byrnes Julia M. , Broussard Camille A. , Azola Alba M. , Swope Meghan E. , Marden Colleen L. , Swope Renee L. , Lum Ying Wei , Violand Richard L. , Rowe Peter C. 
Published: January 2025

Abstract

Background
We have noted that some adolescents and young adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) report difficulty with arms-overhead activities, suggestive of brachial plexus dysfunction or thoracic outlet syndrome (TOS). In the TOS literature, diagnostic maneuvers focus on the provocation of upper limb symptoms (arm fatigue and heaviness, paresthesias, neck and upper back pain), but not on elicitation of systemic symptoms.

Objectives
To estimate the proportion of patients with fatiguing illness who experience local and systemic symptoms during a common maneuver used in evaluating TOS—the elevated arm stress test (EAST).

Methods
Patients were eligible for this retrospective study if they had been referred to the Johns Hopkins Chronic Fatigue Clinic between January 2020 and July 2023 and (a) reported difficulty maintaining arms-overhead postures, (b) were evaluated with an abbreviated one-minute EAST, and (c) had not undergone surgery in the upper limb, neck, or skull base. Modified EAST procedure: patients sat with their arms in a “hands up” or “candlestick” position while opening and closing their hands every 2–3 s repeatedly for 1 min, rather than the customary 3 min. The test was considered abnormal for local symptoms if the participant experienced pain, fatigue, heaviness, paresthesias, warmth or tremulousness in the upper limb, shoulder, neck, head, or upper back. The test was considered abnormal for systemic symptoms if the participant experienced overall fatigue, cognitive fogginess, lightheadedness, racing heart, diaphoresis, dyspnea, overall warmth, or nausea.

Results
Of 154 patients evaluated during the study period, 64 (42%) met the eligibility criteria (61/64 female, median age 18 years [range, 13 to 50]). Of the 64, 50 (78%) had ME/CFS, 13 (20%) had idiopathic chronic fatigue with associated orthostatic intolerance (OI), and one had idiopathic chronic fatigue without OI. Of the 64, 58% had evidence of joint hypermobility. Local symptoms were provoked by EAST in 62/64 (97%) within a median of 20 s. During EAST, 26/64 (41%) reported systemic symptoms (1 had only systemic but no upper limb symptoms), most commonly lightheadedness (19%) and generalized fatigue (11%).

Conclusions
Even with an abbreviated test duration, the EAST maneuver provoked local and systemic symptoms in a substantial proportion of patients with chronic fatigue, OI, and ME/CFS who had reported difficulty with arms-overhead postures. Further studies are needed to explore the prevalence of brachial plexus or TOS symptoms in unselected individuals with ME/CFS or OI, and the proportion with systemic symptoms during and after EAST.
APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology
Authors: Tran Kristine M. , Kwang Nellie E. , Butler Claire A. , Gomez-Arboledas Angela , Kawauchi Shimako , Mar Cassandra , Chao Donna , Barahona Rocio A. , Da Cunha Celia , Tsourmas Kate I. , Shi Zechuan , Wang Shuling , Collins Sherilyn , Walker Amber , Shi Kai-Xuan , Alcantara Joshua A. , Neumann Jonathan , Duong Duc M. , Seyfried Nicholas T. , Tenner Andrea J. , LaFerla Frank M. , Hohsfield Lindsay A. , Swarup Vivek , MacGregor Grant R. , Green Kim N. 
Published: January 2025

Abstract

Background

Apolipoprotein E ε4 (APOE4) is the strongest genetic risk factor for late-onset Alzheimer’s disease (LOAD). A recent case report identified a rare variant in APOE, APOE3-R136S (Christchurch), proposed to confer resistance to autosomal dominant Alzheimer’s Disease (AD). However, it remains unclear whether and how this variant exerts its protective effects.

Methods
We introduced the R136S variant into mouse Apoe (ApoeCh) and investigated its effect on the development of AD-related pathology using the 5xFAD model of amyloidosis and the PS19 model of tauopathy. We used immunohistochemical and biochemical analysis along with single-cell spatial omics and bulk proteomics to explore the impact of the ApoeCh variant on AD pathological development and the brain’s response to plaques and tau.

Results
In 5xFAD mice, ApoeCh enhances a Disease-Associated Microglia (DAM) phenotype in microglia surrounding plaques, and reduces plaque load, dystrophic neurites, and plasma neurofilament light chain. By contrast, in PS19 mice, ApoeCh suppresses the microglial and astrocytic responses to tau-laden neurons and does not reduce tau accumulation or phosphorylation, but partially rescues tau-induced synaptic and myelin loss. We compared how microglia responses differ between the two mouse models to elucidate the distinct DAM signatures induced by ApoeCh. We identified upregulation of antigen presentation-related genes in the DAM response in a PS19 compared to a 5xFAD background, suggesting a differential response to amyloid versus tau pathology that is modulated by the presence of ApoeCh. Bulk proteomics show upregulated mitochondrial protein abundance with ApoeCh in 5xFAD mice, but reductions in mitochondrial and translation associated proteins in PS19 mice.

Conclusions
These findings highlight the ability of the ApoeCh variant to modulate microglial responses based on the type of pathology, enhancing DAM reactivity in amyloid models and dampening neuroinflammation to promote protection in tau models. This suggests that the Christchurch variant's protective effects likely involve multiple mechanisms, including changes in receptor binding and microglial programming.

Graphical Abstract
DNA methylation profiling at base-pair resolution reveals unique epigenetic features of early-onset colorectal cancer in underrepresented populations
Authors: Li Jason Sheng , Riggins Karen , Yang Li , Chen Chaorong , Castro Patricia , Alfarkh Wedad , Zarrin-Khameh Neda , Scheurer Michael E. , Creighton Chad J. , Musher Benjamin , Li Wei , Shen Lanlan 
Published: January 2025

Abstract

Background
The incidence of early-onset colorectal cancer (EOCRC) has been rising at an alarming rate in the USA, and EOCRC disproportionately affects racial/ethnic minorities. Here, we construct comprehensive profiles of EOCRC DNA methylomes at base-pair resolution for a cohort of Hispanic and African American patients.

Results
We show the epigenetic landscape of these EOCRC patients differs from that of late-onset colorectal cancer patients, and methylation canyons in EOCRC tumor tissue preferentially overlapped genes in cancer-related pathways. Furthermore, we identify epigenetic alterations in metabolic genes that are specific to our racial/ethnic minority EOCRC cohort but not Caucasian patients from TCGA. Top genes differentially methylated between these cohorts included the obesity-protective MFAP2 gene as well as cancer risk susceptibility genes APOL3 and RNASEL.

Conclusions
In this study, we provide to the scientific community high-resolution DNA methylomes for a cohort of EOCRC patients from underrepresented populations. Our exploratory findings in this cohort highlight epigenetic mechanisms underlying the pathogenesis of EOCRC and nominate novel biomarkers for EOCRC in underrepresented populations.
The algebraic extended atom-type graph-based model for precise ligand–receptor binding affinity prediction
Authors: Mukta Farjana Tasnim , Rana Md Masud , Meyer Avery , Ellingson Sally , Nguyen Duc D. 
Published: January 2025

Abstract
Accurate prediction of ligand-receptor binding affinity is crucial in structure-based drug design, significantly impacting the development of effective drugs. Recent advances in machine learning (ML)–based scoring functions have improved these predictions, yet challenges remain in modeling complex molecular interactions. This study introduces the AGL-EAT-Score, a scoring function that integrates extended atom-type multiscale weighted colored subgraphs with algebraic graph theory. This approach leverages the eigenvalues and eigenvectors of graph Laplacian and adjacency matrices to capture high-level details of specific atom pairwise interactions. Evaluated against benchmark datasets such as CASF-2016, CASF-2013, and the Cathepsin S dataset, the AGL-EAT-Score demonstrates notable accuracy, outperforming existing traditional and ML-based methods. The model’s strength lies in its comprehensive similarity analysis, examining protein sequence, ligand structure, and binding site similarities, thus ensuring minimal bias and over-representation in the training sets. The use of extended atom types in graph coloring enhances the model’s capability to capture the intricacies of protein-ligand interactions. The AGL-EAT-Score marks a significant advancement in drug design, offering a tool that could potentially refine and accelerate the drug discovery process.

Scientific Contribution

The AGL-EAT-Score presents an algebraic graph-based framework that predicts ligand-receptor binding affinity by constructing multiscale weighted colored subgraphs from the 3D structure of protein-ligand complexes. It improves prediction accuracy by modeling interactions between extended atom types, addressing challenges like dataset bias and over-representation. Benchmark evaluations demonstrate that AGL-EAT-Score outperforms existing methods, offering a robust and systematic tool for structure-based drug design.
Cell deconvolution-based integrated time-series network of whole blood transcriptome reveals systemic antiviral activities and cell-specific immunological changes against PRRSV infection
Authors: Lim Byeonghwi , Lim Chiwoong , Jang Min-Jae , Seo Young-Jun , Kim Do-Young , Tuggle Christopher K. , Lim Kyu-Sang , Kim Jun-Mo 
Published: January 2025

Abstract
Porcine reproductive and respiratory syndrome (PRRS) causes significant economic losses in the swine industry. However, the molecular mechanisms behind the common and cell type-specific systemic responses during PRRS virus (PRRSV) infection are not well understood. In this study, we collected viremia data, antibody levels, and whole-blood RNA-seq data obtained from eight PRRSV-infected piglets. We utilised a cell deconvolution approach to calculate cell type enrichment, constructed a time-serial gene co-expression network with differentially expressed genes, and conducted functional annotations. Three significant modules were identified within the network. The changes associated with viremia revealed an upregulated expression of genes related to antiviral activity. In the T-cell- and NK-cell-specific modules, infection led to an increased T-cell population and upregulation of genes related to T-cell defence responses. Conversely, in the monocyte- and neutrophil-specific module, genes involved in inflammatory responses were downregulated due to a decrease in monocyte proportion. This study highlights the time-series antiviral activities associated with viremia and the transcriptomic changes associated with immune responses in specific cell types. The findings provide comprehensive insights into host responses to PRRSV infection, including diagnostic biomarkers.
Coproantigen detection and molecular identification of Cryptosporidium species among newborn and adult farm animals
Authors: Aboelsoued Dina , Toaleb Nagwa I. , Abdel Megeed Kadria N. 
Published: January 2025

Abstract

Cryptosporidium sp. is an obligatory intracellular apicomplexan protozoan parasite that causes a disease called cryptosporidiosis with substantial veterinary and medical importance. Therefore, this study aimed to evaluate an early diagnosis of cryptosporidiosis using the anti-Cryptosporidium parvum oocyst immunoglobulin IgG polyclonal antibodies (anti-C. parvum IgG PAbs)-based sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of Cryptosporidium oocyst antigens in fecal samples of farm animals in Egypt. Further molecular identification and sequencing were performed for the detected isolates. Eight hundred and twenty fecal samples of farm animals; 102 buffalo calves, 120 cattle calves, 100 lambs and 98 goat kids, 80 buffaloes, 60 cattle, 160 sheep and 100 goats, collected from different small-scale farms and local holders were examined for cryptosporidiosis by Modified Ziehl-Neelsen (MZN) technique. The percentage of positivity was 45.1%, 50%, 20%, 18.4%, 31.25%, 38.3%, 18.8%, and 11% in buffalo calves, cattle calves, lambs, goat kids, adult buffaloes, adult cattle, sheep, and goats, respectively. Molecular identification of Cryptosporidium samples was performed based on COWP gene, revealing the isolates: GenBank: OQ121955.1, OR029973.1 and PP316107.1 which were identical to the C. parvum and GenBank: PP316108.1 and OR029972.1 which were identical to C. hominis and C. andersoni, respectively. Then, C. parvum oocysts were used for preparation of antigens and rabbit immunization. Anti-C. parvum IgG PAbs were purified and characterized by SDS-PAGE and then labeled with horseradish peroxidase (HRP). Anti-C. parvum IgG PAbs in-house sandwich ELISA was prepared, then tested this ELISA on 820 samples and compared results with MZN microscopical examination and a commercial sandwich ELISA kit. In this study, in-house sandwich ELISA scored higher sensitivity of 98%, 100% specificity, validity 99% and relative agreement 98.6% than (92%, 90%, 91% and 91.4%) of MZN and (96%, 95%, 95.5% and 95.7%) of coproantigen commercial sandwich ELISA kit, respectively. Moreover, we used PCR to evaluate the positivity of in-house sandwich ELISA results, and the total PCR positive samples were 263 out of 268 sandwich ELISA positive samples (98.13%). In conclusion, the prepared Anti-C. parvum IgG PAbs based sandwich ELISA offered a simple and accurate diagnostic method for cryptosporidiosis in the fecal samples of different species of farm animals in Egypt with high sensitivity (98%) and specificity (100%). Further studies on this Anti-C. parvum IgG PAbs may help also in the protection against cryptosporidiosis.