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Advances in Coccygectomy: A Comprehensive Review Evaluating Surgical Techniques for Coccygodynia
(MDPI, 2025-02-19) Obeng-Gyasi, Barnabas; Brown, Ethan D. L.; Chinthala, Anoop Sai; Mao, Gordon; Neurological Surgery, School of Medicine
Background: Coccygodynia presents significant challenges in diagnosis and treatment. While coccygectomy has emerged as a crucial intervention for refractory cases, significant heterogeneity exists in surgical techniques. Traditional approaches are increasingly complemented by novel methods, necessitating a comprehensive review of current surgical options.
Methods: A comprehensive literature review was conducted using Ovid MEDLINE, Cochrane Library and Embase databases from inception to present. Search terms included "coccygectomy", "coccydynia", "coccygodynia", "coccyx pain" and "tailbone pain". We analyzed peer-reviewed studies focusing on surgical techniques, outcomes and complications of coccygectomy. Studies were excluded if non-peer-reviewed, non-English without translation, or not directly addressing surgical management.
Results: Traditional midline approaches, while common, demonstrate increased wound complications compared to paramedian techniques. Minimally invasive methods, including coccygeoplasty and endoscopic coccygectomy, show promising early outcomes with reduced recovery times. Both partial and complete resections provide significant pain relief, with complete resection potentially offering superior results in severe cases. Wound closure technique significantly impacts surgical success.
Conclusions: Optimal outcomes in coccygectomy require individualized surgical approaches incorporating modern techniques like paramedian incision and advanced wound closure. Emerging minimally invasive procedures may further reduce complications and enhance recovery. Treatment success depends on careful patient selection and surgical technique optimization.
Prediction Model for Brain Metastasis in Patients With Metastatic Germ‐Cell Tumors
(Wiley, 2025) Salous, Tareq; Ashkar, Ryan; Althouse, Sandra K.; Cary, Clint; Masterson, Timothy; Hanna, Nasser H.; King, Jennifer; Einhorn, Lawrence H.; Adra, Nabil; Medicine, School of Medicine
Background: Brain metastasis (BM) is an independent adverse prognostic factor in metastatic germ cell tumors (mGCT). We aimed to establish an effective and practical BM prediction model.
Patients and methods: Between January 1990 and September 2017, 2291 patients with mGCT who were treated at Indiana University were identified. Patients were divided into two categories: BM present (N = 154) and BM absent (N = 2137). Kaplan-Meier methods were used to analyze progression free survival (PFS) and overall survival (OS). Logistic regression was used to determine a predictive model for whether BM was present. The data was separated into training and validation datasets with equal numbers of events in each.
Results: The 2-year PFS and OS for patients with versus without BM: 17% versus 65% (p < 0.001) and 62% versus 91% (p < 0.001) respectively. Among the 154 patients with BM, 64 (42%) had radiation only (whole-brain radiotherapy or gamma knife), 22 (14%) had BM-surgery only, 14 (9%) had both radiation and BM-surgery. 54 patients (35%) did not receive local therapy for BM. Stepwise selection was used to determine the best model with p < 0.15 as the entry and staying criteria. The model with the largest ROC AUC was used moving forward. The model was tested in the validation dataset. A model was generated including age at diagnosis ≥ 40, choriocarcinoma predominant histology, pre-chemotherapy hCG≥ 5000, presence of pulmonary metastases size < 3, or ≥ 3 cm, and presence of bone metastasis. Patients with score of 0, 1, 2, 3, 4, 5, 6, 7, 8 points had a 0.6%, 1.4%, 3.5%, 8.2%, 18.3%, 36%, 58%, 78%, 90% probability of having BM, respectively.
Conclusions: The prediction model developed in this study demonstrated discrimination capability of predicting BM occurrence in mGCT and can be used to identify high-risk patients.
Differential Regulation of Nav1.1 and SCN1A Disease Mutant Sodium Current Properties by Fibroblast Growth Factor Homologous Factors
(MDPI, 2025-02-15) Frazee, Ashley; Zybura, Agnes; Cummins, Theodore R.; Biology, School of Science
Fibroblast growth factor homologous factors (FHFs) regulate the activity of several different voltage-gated sodium channels (Navs). However, more work is needed to determine how specific FHF isoforms and variants affect the properties of different Nav isoforms. In addition, it is not known if FHFs can differentially modulate the properties of Nav variants associated with disease. Here, we investigated the effects of FHF2A and FHF2B on Nav1.1 properties as well as on a familial hemiplegic migraine 3 (FHM3) causing mutation in this channel, F1774S. We found that FHF2A, but not 2B, induced prominent long-term inactivation (LTI) in the wild-type (WT) Nav1.1. Interestingly, FHF2A induced LTI in the F1774S FHM3 mutant channel to a greater extent than in the WT. Furthermore, persistent currents caused by the F1774S mutation were attenuated by the co-expression of FHF2A, leading to a possible rescue of the mutant channel phenotype. By contrast, the P1894L mutation, which is associated with epilepsy and mild intellectual disability, greatly attenuated the LTI induced by FHF2A. Overall, our data show for the first time that FHF2A might be a significant modulator of Nav1.1 that can differentially modulate the impact of Nav1.1 disease-associated mutations.
In vivo pulse-chase in C. elegans reveals intestinal histone turnover changes upon starvation
(bioRxiv, 2025-02-16) Borchers, Christopher; Osburn, Kara; Roh, Hyun Cheol; Aoki, Scott T.; Biochemistry and Molecular Biology, School of Medicine
The ability to study protein dynamics and function in the authentic context of a multicellular organism is paramount to better understand biological phenomena in animal health and disease. Pulse-chase of self-labeling fusion protein tags provide the opportunity to label proteins of interest and track those proteins over time. There are currently several challenges associated with performing in vivo protein pulse-chase in animals, such as cost, reproducibility, and accurate detection methods. The C. elegans model organism has attributes that alleviate many of these challenges. This work tests the feasibility of applying the Halo modified enzyme (HaloTag) for in vivo protein pulse-chase in C. elegans. HaloTag intestinal histone reporters were created in the worm and used to demonstrate that reporter protein could be efficiently pulse-labeled by soaking animals in ligand. Labeled protein stability could be monitored over time by fluorescent confocal microscopy. Further investigation revealed reporter protein stability was dependent on the animal's nutritional state. Chromatin Immunoprecipitation and sequencing (ChIP-seq) of the reporters showed incorporation in chromatin with little change hours into starvation, implying a lack of chromatin regulation at the time point tested. Collectively, this work presents a straightforward method to label and track proteins of interest in C. elegans that can address a multitude of biological questions surrounding protein stability and dynamics in this animal model.
Ethical considerations for biobanks serving underrepresented populations
(Wiley, 2025) Lee, Yoon Seo; Garrido, Nelson Luis Badia; Lord, George; Maggio, Zane Allan; Khomtchouk, Bohdan B.; Biomedical Engineering and Informatics, Luddy School of Informatics, Computing, and Engineering
Biobanks are essential biological database resources for the scientific community, enabling research on the molecular, cellular, and genetic basis of human disease. They are crucial for computational, data-driven biomedical research, which advances precision medicine and the development of targeted therapies. However, biobanks often lack racial and ethnic diversity, with many data sets predominantly comprising individuals of white, primarily northern European, ancestry. Establishing or enhancing biobanks for the inclusion of historically underrepresented populations requires meticulous ethical and social planning beyond logistical, legal, and economic considerations. This guide provides a roadmap for building and sustaining diverse biobanks, emphasizing ethical guidelines and cultural sensitivity. We highlight the importance of obtaining informed consent from donors, respecting their bodily autonomy, and the economic and research benefits of diverse biobanks to enable precision medicine, drug discovery, and industry-academic partnerships. Prioritizing key ethical and social considerations allows biobanks to advance scientific knowledge while upholding the rights and autonomy of underrepresented populations. Diversity in biobank sample collection enhances research outcomes by ensuring findings are representative and applicable to various human population groups, fostering trust, promoting inclusivity, and addressing health disparities while informing health policy. This is vital to ensuring biobanking efforts contribute meaningfully to the advancement of health equity.