bluuebunny/crossref_metadata_2025_split huggingface dataset:
INBONE Total Ankle System: Clinical and Radiographic Outcomes
Authors: Padley Michelle A. , Albert Andrew J. , Anderson John G. , Bohay Donald R. , Maskill John D. , McKearney Daniel A. , Phillips Alexander , Potter Ramsey S. , Kothari Parin D. 
Published: November 2022

Category: Ankle Arthritis Introduction/Purpose: Ankle arthroplasties have undergone several generations of development since their initial introduction. Newer technologies in design have offered prosthetics which were more mobile and closer in articulation to human ankle joints. This includes increased motion of the coronal and sagittal planes, as well as less wear-and-tear of the prosthesis. Currently, second generation ankle arthroplasties have only shown promising results intermediately, and there has been very little research looking into the long term results of these devices. The INBONE total ankle system is a relatively new addition to the market that specifically has not been well researched. This project is aimed to outline their morbidly and mortality, as well as compare the long term results to other commonly used implants with data available. Methods: The study will be a retrospective, single-site cohort of past patients who have undergone INBONE total arthroplasty by Drs. Anderson, Bohay and Maskill at Orthopaedic Associates of Michigan (OAM). Pre-op indications will be evaluated, as well as lengthy post-op periods including 2 week, 6 week, 8 week, 1 year, and 2+ years follow up scores. Charts will be reviewed for inclusion and exclusion criteria. This includes demographic information, operative information, complications, reoperations, radiographic outcomes, and post-operative satisfaction scores. These scores include functional characteristics of ankle arthritis patients including pain level, walking distances, gait stability, varus/valgus stress, dorsi/plantarflexion ankle motion arc, hindfoot stability, and ankle alignment (AOFAS Score Criteria). Results: Study still in progress, results pending. Conclusion: Study still in progress, results pending.
Evaluation of the Clinical-Radiographic Results of Patients Undergoing Arthroscopic Metatarsal- Phalangeal Arthrodesis of the Hallux
Authors: Padua Bruno J. , Gomes Rogério d. , Gomes Anderson H. , Magalhães João Murilo B. , Fonseca Wagner V. 
Published: November 2022

Category: Arthroscopy; Midfoot/Forefoot Introduction/Purpose: Hallux rigidus is a common pathological condition of the foot, responsible for a great functional limitation. Metatarsophalangeal arthrodesis is an excellent therapeutic alternative for advanced stages of the disease, usually performed using an open technique. Forefoot arthroscopy has been developed in the last decade, with progressive expansion of indications, bringing encouraging results. Our objective is present the clinical-radiographic results of patients undergoing arthroscopic metatarsophalangeal arthrodesis of the hallux, showing the technique and reporting complications. Methods: This study involves a series of 9 patients (10 feet), all with advanced hallux rigidus (Coughlin-Shurnas grades 3 and 4). All patients underwent an arthroscopic procedure through two dorsal portals with small-joint instruments. Outcomes were assessed using the AOFAS functional score and a visual analogue scale of pain. The radiographic parameters of interest were metatarsal-phalangeal angulation in the anteroposterior (pre- and postoperative) and lateral (post-operative) views, as well as ray shortening. Results: All patients evolved with consolidation in radiographic control at 6 weeks postoperatively and showed a marked improvement in functional scores. We observed a reduction in the metatarsophalangeal angle, without shortening of the radius and of the finger. No patient had transfer metatarsalgia or complaints of cosmetic problems. Conclusion: Arthroscopic metatarsophalangeal arthrodesis is a very relevant therapeutic option for managing advanced stages of hallux rigidus, with minimal aggression and providing excellent results, in addition to a low incidence of complications.
Hindfoot Motion Analysis by Subtalar Compensation and Ankle Osteoarthritis Stage using a 3D Multi- Segment Foot Model
Authors: Park Gil Young , Lee Dong-Oh , Kwon So Hyeon , Lee Dong Yeon , Yoon Youngsik 
Published: November 2022

Category: Hindfoot Introduction/Purpose: Biomechanics of the hindfoot in ankle osteoarthritis (OA) have not yet fully understood. We aimed to identify hindfoot motions by gait analysis using multi-segment foot model (MFM) according to the stage of ankle OA or hindfoot alignment determined by the presence of subtalar compensation. Methods: We retrospectively reviewed the medical records, simple radiographs, and gait MFM data from 54 ankles which admitted to our hospital for the treatment of advanced ankle OA. Spatiotemporal gait parameters and 3-dimensional motions of hindfoot segment were analyzed according to sex, age, body mass index, the Takakura classification, and the presence of subtalar compensation. Results: As a result, all spatiotemporal gait parameters showed no significant difference according to the presence of subtalar compensation and the stage of ankle OA. With regard to the relationship between hindfoot segmental motion and the stage of ankle OA, only normalized step width was significantly different from each other (p value=0.028). Average motion of hindfoot (decompensation versus compensation) showed no significant difference in sagittal and transverse plane. In coronal movement of hindfoot, there were collapsed curves in both groups, which had constant significant difference. In comparison of 3a, 3b, and 4 stages of Takakura, more advanced 3b stages of ankle OA had the smaller sagittal range of motion compared to 3a (p value=0.028). Coronal movement of hindfoot in Takakura 3a/3b/4 all showed relatively flat pattern. Conclusion: In conclusion, spatiotemporal parameters were not affected by the alignment state of the heel resulted from subtalar compensation. Sagittal range of hindfoot motion decreased in the advanced ankle OA. Coronal movement of subtalar joint in ankle OA, once it was disrupted, showed no change regardless of the stage of ankle OA or compensation state of the hindfoot.
Clinical Profile of Physiotherapy Ambulatory Patients Adult Ankle and Foot Trauma Orthopedics Brazil
Authors: Santos Aquiles S. 
Published: November 2022

Category: Other; Ankle; Ankle Arthritis; Arthroscopy; Basic Sciences/Biologics; Bunion; Diabetes; Hindfoot; Lesser Toes; Midfoot/Forefoot; Sports; Trauma Introduction/Purpose: From a trauma point of view, the number of severely injured polytrauma patients decreased in the first few weeks of isolation. However, the number of cases observed with complex ankle and foot injuries. As ankle ligament injuries among the most prevalent traumatic conditions in an emergency care setting. Depending on the degree of energy, ankle and foot position, direction of the sprain, bone quality and soft tissue envelope, this trauma can have different outcomes and diagnoses. Methods: This is a retrospective study that will be carried out from the analysis of medical records of patients treated in an outpatient orthopedic trauma to the ankle and foot at UNIFESP, in which the care will be performed by a physical therapist provided to patients from the Unified Health System (SUS). Results: In this verification of medical records, it was analyzed that the profile of the outpatient patient with a predominance of atraumatic injuries. Conclusion: Most patients seen at the outpatient clinic have as their main source of treatment and the profile of these patients is chronic.
Tarsometatarsal Joint Preparation using a Modified Dorsal Approach vs Standard Approach: A Cadaver Study
Authors: Shah Ashish , Murali Sudarsan , Littlefield Zachary , Young Sean M. , Patch David A. , Jacob Roshan , Luque-Sanchez Kevin S. , Reed Logan , Elphingstone Joseph 
Published: November 2022

Category: Midfoot/Forefoot Introduction/Purpose: Lisfranc injuries are a relatively common midfoot injury involving the tarsometatarsal (TMT) joint. Surgical fixation typically involves open reduction with internal fixation or primary arthrodesis of the joint(s). The standard surgical approach to the TMT joint involves two dorsal incisions however, a recent study has suggested the use of a modified single dorsal incision approach. The goal of this paper is to compare the total surface area of the joint that can be prepared for primary arthrodesis of the TMT using the standard vs modified single dorsal approach. Methods: Ten fresh frozen below-the-knee cadaver specimens were randomly assigned to receive either the standard or modified dorsal single incision operative approach to the TMT joint. Prior to initiating the study, specimens were inspected with fluoroscopic radiographs for preexisting pathology or prior surgical intervention. The joint surface was visualized and then underwent articular preparation as for a joint fusion. After adequate joint preparation, the TMT joint was disarticulated and the surface was photographed for image analysis. Using ImageJ, articular joint surface preparation areas were measured by two blinded reviewers. to assess the joint surface preparation and this was compared by surgical approach. Results: After ImageJ and Mann-Whitney U statistical analysis, there was no significant difference in the amount of joint prepared when comparing the standard versus modified dorsal approach for the first three TMT joints (p= 0.548, p=0.310, p= 0.548). The percentage of joint preparation utilizing the standard dorsal approach versus the modified dorsal approach for TMT joints one through three are as follows (percentages utilized are listed as the median value with its correlating range): First TMT- 67.6% (range 26%) by the standard approach versus 71.7% (range 9%) by the modified dorsal approach, second TMT- 67.9% (range 24%) versus 65.7% (range 12%), and third TMT- 65.9% (range 42%) versus 59.6% (range 24%). Table 1 summarizes our results between each operative approach. Conclusion: With our findings, we demonstrate that a modified single dorsal approach to the Lisfranc joint provided comparable joint preparation for primary arthrodesis as the standard dual incision approach. However, the modified dorsal approach may be beneficial in that it avoids creating a skin bridge which has potential for necrosis with the standard two incision approach. The authors believe the comparable joint preparation combined with its potential to alleviate soft tissue complications make the modified dorsal approach a viable surgical approach for a TMT arthrodesis.
The Role of Diet and Nutrition on Fracture Healing: A Systematic Review
Authors: Singh Priya K. , Vankara Ashish , O'Sullivan Lucy , Aiyer Amiethab A. 
Published: November 2022

Category: Other Introduction/Purpose: Not only is poor nutritional status common amongst the elderly, but its incidence is also high amongst orthopedic trauma patients as injuries, and fractures more specifically, cause hypermetabolic states. The purpose of this review was to perform the most comprehensive analysis of literature published within the last decade to determine the effect of nutritional status on fracture healing, as well as outlining the effects of specific herbal supplements, vitamins and minerals. Methods: Following PRISMA guidelines, PubMed, Embase and Web of Science databases were searched using variations of the terms nutrition and malnutrition along with vitamins, minerals and proteins as well as fractures and fracture healing. Two independent reviewers screened articles, graded evidence quality, and extracted data. A total of 31 studies were related to nutritional status - 22 human studies and 9 animal studies - and 45 studies were related to specific herbs or food products - 2 human studies, 36 animal studies, and 7 review articles. Results: There is substantial variability in the definitions of nutritional status, with some quantitative measures including serum albumin and lymphocyte count being the most popular, and questionnaires like the Mini Nutritional Assessment (MNA) and the Malnutrition Universal Screening Tool (MUST). Published human studies predominately studied the effects of nutrition on traumatic fractures in the elderly or bone healing after spinal surgery. Consistently, hypoalbuminemia was found to be an independent risk factor of post-operative complications and longer hospital stays. Few studies reported on nutritional supplementation, but those that did found supplementation to be associated with lower rates of postoperative complications and wound infection, as well as shorter hospital stays. Although there is much evidence published on herbal supplements and food products in animals, there is a dearth of evidence of their benefits to humans with only two RCTs included in this analysis (demonstrating the benefits of Momiai and lactobacillus casei Shirota). Conclusion: Nutrition remains an easily targetable factor that can significantly improve fracture healing, especially amongst elderly populations. Although proper adherence to supplementation is rare, when attained its benefits are profound. To demonstrate that the beneficial effects of herbal supplements and food products on fracture healing seen in animal models persist in humans, future placebo-controlled trials are needed.
Host metabolome predicts the severity and onset of acute toxicities induced by CAR T-cell therapy
Authors: Jalota Akansha , Hershberger Courtney E. , Patel Manishkumar S. , Mian Agrima , Faruqi Aiman , Khademi Gholamreza , Rotroff Daniel M. , Hill Brian T. , Gupta Neetu 
Published: November 2022

Abstract
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a highly effective treatment option for patients with relapsed/refractory large B-cell lymphoma. However, widespread use is deterred by the development of clinically significant acute inflammatory toxicities, including cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), that induce significant morbidity and require close monitoring. Identification of host biochemical signatures that predict the severity and time-to-onset of CRS and ICANS may assist patient stratification to enable timely mitigation strategies. Here, we report pretreatment host metabolites that are associated with CRS and ICANS induced by axicabtagene ciloleucel or tisagenlecleucel therapy. Both untargeted metabolomics analysis and validation using targeted assays revealed a significant association between the abundance of specific pretreatment biochemical entities and an increased risk and/or onset of clinically significant CRS (q &lt; .1) and ICANS (q &lt; .25). Higher pretreatment levels of plasma glucose and lower levels of cholesterol and glutamate were associated with a faster onset of CRS. In contrast, low baseline levels of the amino acids proline and glycine and the secondary bile acid isoursodeoxycholate were significantly correlated with clinically significant CRS. Lower concentration of the amino acid hydroxyproline was associated with higher grade and faster onset of ICANS, whereas low glutamine was negatively correlated with faster development of ICANS. Overall, our data indicate that the pretreatment host metabolome has biomarker potential in determining the risk of clinically significant CRS and ICANS, and may be useful in risk stratification of patients before anti-CD19 CAR T-cell therapy.
Predictors of survival in patients with MALT lymphoma: a retrospective, case-control study
Authors: Qi Shunan , Liu Xin , Noy Ariela , Lee Jisun , Teckie Sewit , Hajj Carla , Joffe Erel , Imber Brandon S. , Yahalom Joachim 
Published: November 2022

Abstract
There is limited understanding of the extent to which mucosa-associated lymphoid tissue (MALT) lymphoma affects a patient’s risk of death and how classically considered prognostic factors affect lymphoma-specific vs other noncancer mortality. This study analyzed major long-term outcomes of patients with MALT lymphoma and the prognostic significance of baseline clinical features. We reviewed the clinical features, treatments, disease course, and survival of 593 patients with MALT lymphoma diagnosed at Memorial Sloan Kettering between 2000 to 2012. Outcomes were analyzed using crude overall survival (OS) and relative survival (RS) by standardized mortality ratio. The median age was 60 years, 72% were at stage I/II. With a median follow-up of 9.2 years, the 10-year OS, lymphoma-specific mortality, and competing nonlymphoma mortality was 75%, 4%, and 21%, respectively; the overall standardized mortality ratio was 1.41 (95% confidence interval, 1.19-1.67; P &lt; .001). Using multivariate analysis, older age, advanced stage, and poor performance status were independently associated with inferior OS. Several subgroups had similar RS to the normal matched population, including those with an age of ≥70 years, stage I, and skin or gastric origin. Increased lymphoma-specific death was associated with spread disease, whereas death from nonlymphoma causes was correlated with older age. Overall, a diagnosis of MALT lymphoma was associated with moderately compromised survival. Age and advanced-stage disease emerged as the most important prognostic factors. Younger patients had better OS but worse RS. Disease dissemination was the lymphoma-specific risk factor.
Antileukemic properties of the kinase inhibitor OTSSP167 in T-cell acute lymphoblastic leukemia
Authors: Bridges Cory Seth , Chen Taylor J. , Puppi Monica , Rabin Karen R. , Lacorazza H. Daniel 
Published: November 2022

AbstractNovel drugs are needed to increase treatment response in children with high-risk T-cell acute lymphoblastic leukemia (T-ALL). Following up on our previous report on the activation of the MAP2K7-JNK pathway in pediatric T-ALL, here we demonstrate that OTSSP167, recently shown to inhibit MAP2K7, has antileukemic capacity in T-ALL. OTSSP167 exhibited dose-dependent cytotoxicity against a panel of T-ALL cell lines with IC50 in the nanomolar range (10-50 nM). OTSSP167 induces apoptosis and cell cycle arrest in T-ALL cell lines, associated at least partially with the inhibition of MAP2K7 kinase activity and lower activation of its downstream substrate, JNK. Other leukemic T-cell survival pathways, such as mTOR and NOTCH1 were also inhibited. Daily intraperitoneal administration of 10 mg/kg OTSSP167 was well tolerated, with mice showing no hematological toxicity, and effective at reducing the expansion of human T-ALL cells in a cell-based xenograft model. The same dosage of OTSSP167 efficiently controlled the leukemia burden in the blood, bone marrow, and spleen of 3 patient-derived xenografts, which resulted in prolonged survival. OTSSP167 exhibited synergistic interactions when combined with dexamethasone, L-asparaginase, vincristine, and etoposide. Our findings reveal novel antileukemic properties of OTSSP167 in T-ALL and support the use of OTSSP167 as an adjuvant drug to increase treatment response and reduce relapses in pediatric T-ALL.
SIGIRR deficiency contributes to CD4 T cell abnormalities by facilitating the IL1/C/EBPβ/TNF-α signaling axis in rheumatoid arthritis
Authors: Teng Xiu , Mou Da-Chao , Li Hui-Fang , Jiao Ling , Wu Sha-Sha , Pi Jin-Kui , Wang Yan , Zhu Meng-Li , Tang Meng , Liu Yi 
Published: November 2022

Abstract
Background
Rheumatoid arthritis (RA) is a complex autoimmune disease with multiple etiological factors, among which aberrant memory CD4 T cells activation plays a key role in the initiation and perpetuation of the disease. SIGIRR (single immunoglobulin IL-1R-related receptor), a member of the IL-1 receptor (ILR) family, acts as a negative regulator of ILR and Toll-like receptor (TLR) downstream signaling pathways and inflammation. The aim of this study was to investigate the potential roles of SIGIRR on memory CD4 T cells in RA and the underlying cellular and molecular mechanisms.

Methods
Single-cell transcriptomics and bulk RNA sequencing data were integrated to predict SIGIRR gene distribution on different immune cell types of human PBMCs. Flow cytometry was employed to determine the differential expression of SIGIRR on memory CD4 T cells between the healthy and RA cohorts. A Spearman correlation study was used to determine the relationship between the percentage of SIGIRR+ memory CD4 T cells and RA disease activity. An AIA mouse model (antigen-induced arthritis) and CD4 T cells transfer experiments were performed to investigate the effect of SIGIRR deficiency on the development of arthritis in vivo. Overexpression of SIGIRR in memory CD4 T cells derived from human PBMCs or mouse spleens was utilized to confirm the roles of SIGIRR in the intracellular cytokine production of memory CD4 T cells. Immunoblots and RNA interference were employed to understand the molecular mechanism by which SIGIRR regulates TNF-α production in CD4 T cells.

Results
SIGIRR was preferentially distributed by human memory CD4 T cells, as revealed by single-cell RNA sequencing. SIGIRR expression was substantially reduced in RA patient-derived memory CD4 T cells, which was inversely associated with RA disease activity and related to enhanced TNF-α production. SIGIRR-deficient mice were more susceptible to antigen-induced arthritis (AIA), which was attributed to unleashed TNF-α production in memory CD4 T cells, confirmed by decreased TNF-α production resulting from ectopic expression of SIGIRR. Mechanistically, SIGIRR regulates the IL-1/C/EBPβ/TNF-α signaling axis, as established by experimental evidence and cis-acting factor bioinformatics analysis.

Conclusion
Taken together, SIGIRR deficiency in memory CD4 T cells in RA raises the possibility that receptor induction can target key abnormalities in T cells and represents a potentially novel strategy for immunomodulatory therapy.
Protein function annotation based on heterogeneous biological networks
Authors: Hu Sai , Luo Yingchun , Zhang Zhihong , Xiong Huijun , Yan Wei , Jiang Meiping , Zhao Bihai 
Published: November 2022

Abstract
Background
Accurate annotation of protein function is the key to understanding life at the molecular level and has great implications for biomedicine and pharmaceuticals. The rapid developments of high-throughput technologies have generated huge amounts of protein–protein interaction (PPI) data, which prompts the emergence of computational methods to determine protein function. Plagued by errors and noises hidden in PPI data, these computational methods have undertaken to focus on the prediction of functions by integrating the topology of protein interaction networks and multi-source biological data. Despite effective improvement of these computational methods, it is still challenging to build a suitable network model for integrating multiplex biological data.

Results
In this paper, we constructed a heterogeneous biological network by initially integrating original protein interaction networks, protein-domain association data and protein complexes. To prove the effectiveness of the heterogeneous biological network, we applied the propagation algorithm on this network, and proposed a novel iterative model, named Propagate on Heterogeneous Biological Networks (PHN) to score and rank functions in descending order from all functional partners, Finally, we picked out top L of these predicted functions as candidates to annotate the target protein. Our comprehensive experimental results demonstrated that PHN outperformed seven other competing approaches using cross-validation. Experimental results indicated that PHN performs significantly better than competing methods and improves the Area Under the Receiver-Operating Curve (AUROC) in Biological Process (BP), Molecular Function (MF) and Cellular Components (CC) by no less than 33%, 15% and 28%, respectively.

Conclusions
We demonstrated that integrating multi-source data into a heterogeneous biological network can preserve the complex relationship among multiplex biological data and improve the prediction accuracy of protein function by getting rid of the constraints of errors in PPI networks effectively. PHN, our proposed method, is effective for protein function prediction.