bluuebunny/crossref_metadata_2025_split huggingface dataset:
Charcot Ankle Deformity: Can the Limb be Salvaged?
Authors: Aminian Arash , Choi Daniel , Saghaeidehkordi Jalal , Black James , Lee David , Harris Thomas G. 
Published: November 2022

Category: Diabetes; Ankle Introduction/Purpose: Diabetes mellitus (DM) may result in Charcot arthropathy (CA) in 0.1% to 2.5% of diabetic patients. Complications may arise including joint dislocation, deformities, ulcerations, and limb amputation. Surgical intervention has been shown to improve patient's walking ability and health-related quality of life compared to use of orthotics in addition to reduction of ulcer, bone infection, use of orthoses, and amputation. A retrospective review of patients with ankle charcot arthropathy was performed with hindfoot nail fixation. The aim of the study was to determine radiographic healing, complication rates of surgical intervention, and patients' ability to ambulate with therapeutic inserts or boots. The results obtained from this study serve to provide evidence for intervention via operative fixation and limb salvage in this cohort of patients. Methods: A retrospective review of patients treated with hindfoot nail with CA of the ankle was performed between 2016 to 2022. The demographic data, BMI, cause of the charcot arthropathy, the pre-operative radiographic deformity, and prior wounds and infection data was recorded. We identified 18 consecutive patients that underwent surgical intervention. The surgical technique included bimalleolar exposure, correction of the deformity, hindfoot fusion nail with or without structural femoral head graft. The follow up data collected included post-operative complications, radiographic evaluation of union, and clinical data on type of shoe wear or boots used for ambulation. Results: We identified 17 consecutive patients undergoing hindfoot deformity correction with hindfoot nail. The average follow- up for the patients was 1.7 year. The cause of neuropathy was diabetes in 15 patient and idiopathic in 2 patients. The average BMI for the cohort was 29.5. The initial 90-day complications rate for surgical intervention was 17%; with one superficial infection, one deep infection, and one death related to a cardiac event. At latest follow up 12 patients were ambulating with a CROW boot, 3 in diabetic shoes with therapeutic inserts, 1 below knee prosthesis, and 1 patient is in the initial perioperative period of healing. Radiographic union was seen in 12 patient, 3 patients had stable pseudo-union of the ankle joint with neutral alignment. Conclusion: The development of an acquired ankle deformity is associated with a poor quality of life. Traditional treatment of CA has shown to be effective when resolving infection and avoiding amputation. Our study supports the use of hindfoot nail for deformity correction/fixation and limb salvage of ankle CA patients. This patient population is highly comorbid but can have meaningful improvement in ambulator status post-surgery in a CROW boot or shoes with therapeutic insoles.
Tarsal Coalition is Not Necessarily Associated with a Flatfoot Deformity: A Cohort of Clinically Misdiagnosed Cases and Alignment Features in 41 Feet
Authors: Ansah-Twum Jeremy , Zhu Mingjie , Carpenter Melissa L. , Sempson Sera , Hunt Kenneth J. , Myerson Mark S. , Li Shuyuan 
Published: November 2022

Category: Hindfoot; Ankle; Midfoot/Forefoot Introduction/Purpose: Tarsal coalition has been historically reported to be associated with a flatfoot deformity. There are however case reports demonstrating that it can be found in cavovarus and clubfoot deformities. The goal of this study was to retrospectively review all weightbearing CT (WBCT) scans that were taken in one medical center, to investigate the clinically diagnosed as well as missed cases of tarsal coalition, and to determine the hindfoot alignment and arch height features of each case. Methods: 800 WBCT scans were reviewed separately by two senior fellowship trained foot and ankle surgeons. The structure of the hindfoot and midfoot was carefully examined in all three views to screen for different types of tarsal coalition. For cases that were diagnosed with tarsal coalition on WBCT, the medical charts were then reviewed to determine the original clinical diagnoses. Hindfoot alignment and arch height features of the midfoot were subsequently evaluated on WBCT scans. Results: There were 41 feet that were diagnosed with tarsal coalition on WBCT (Figure 1). The clinical diagnosis of coalition was only made in 15 feet and 26 symptomatic feet were clinically missed. Among the 26 symptomatic feet diagnosed on WBCT but clinically missed, 16 had a clinical diagnosis of congenital or acquired flatfoot, 3 with subtalar arthritis, 1 with talonavicular arthritis, 1 with peroneal tendinopathy and a cavovarus foot deformity, 2 with cavovarus deformity and midfoot arthritis, 2 with posttraumatic ankle arthritis, and 1 with subtalar impingement. A valgus hindfoot was found in 19 feet, a neutral hindfoot in 18, and a varus hindfoot in 4 feet. In the midfoot, 38 feet had a positive (>=1) distal medial cuneiform/fifth metatarsal arch height index, and 3 feet had a negative index (<1); all 41 feet had a positive proximal cuneiform/cuboid height index (>=1). Conclusion: One should be aware that patients with tarsal coalition do not always present with a flatfoot and hindfoot valgus, since many can have a variety of hindfoot and midfoot alignment features. In cases presenting with history of trauma, degenerative arthritis, as well as a cavovarus or clubfoot deformity, tarsal coalition can easily be clinically overlooked. References: - Lemley F, Berlet G, Hill K, Philbin T, Isaac B, Lee T. Current concepts review: Tarsal coalition. Foot Ankle Int. 2006 Dec;27(12):1163-9. - Van Rysselberghe NL, Souder CD, Mubarak SJ. Unsuspected tarsal coalitions in equinus and varus foot deformities. J Pediatr Orthop B. 2020 Jul;29(4):370-374.
The Effects of Socioeconomic Status on Outcomes Following Total Ankle Arthroplasty
Authors: Athar Mohammad S. , Khan Ryan , Awoke Adam , Khoshbin Amir , Daniels Timothy R. , Halai Mansur 
Published: November 2022

Category: Ankle; Ankle Arthritis Introduction/Purpose: There is limited literature on the effects of socioeconomic factors on outcomes after total ankle arthroplasty (TAA). In the setting of hip or knee arthroplasty, patients of a lower socioeconomic status demonstrate poorer post- operative satisfaction, longer lengths of stay, and larger functional limitations. It is important to ascertain whether this phenomenon is present in ankle arthritis patients. This is the first study to address the weight of potential socioeconomic factors in affecting various socioeconomic classes, in terms of how they benefit from ankle arthroplasty. Methods: This is retrospective cohort study of 447 patients who underwent a TAA. Primary outcomes included pre-operative and final follow-up AAOS pain, AAOS disability, and SF-36 scores. We then used postal codes to determine median household income using Canadian 2015 census data. Incomes were divided into quintiles based on equal amounts over the range of incomes. These income groups were then compared for differences in outcome measures. Statistical analysis was done using unpaired t- test. Results: A total of 447 patients were divided into quintiles by income. From lowest income to highest income, the groups had 54, 207, 86, 64, and 36 patients, respectively. The average time from surgery to final follow up was 85.6 months. Interestingly, we found that patients within the middle household income groups had significantly lower AAOS disability scores compared to the lowest income groups at final follow-up (26.41 vs 35.70, p=0.035). Furthermore, there was a trend towards middle income households and lower post-operative AAOS pain scores compared to the lowest income group (19.57 vs 26.65, p=0.063). There was also a trend toward poorer AAOS disability scores when comparing middle income groups to high income groups post- operatively (26.41 vs 32.27, p=0.058). Pre-operatively, patients within the middle-income group had more pain, compared to the lowest and the highest income groups. Conclusion: Patients from middle income groups who have undergone TAA demonstrate poorer function and possibly more pain, compared to lower and higher income groups. This suggests that TAA is a viable option for lower socioeconomic groups and should not be a source of discouragement for surgeons. In this circumstance there is no real disparity between the rich and the poor. Further investigation is needed to explore reasons for diminished performance in middle class patients.
Treatment of Pediatric and Adolescent Talus Osteochondral Lesions
Authors: Ayvaz Elif Y. 
Published: November 2022

Category: Ankle Introduction/Purpose: Osteochondral lesions of the Talus are defined as any damage involving both articular cartilage and subchondral bone of the talar dome, and this condition is associated with persistent ankle pain and disability. The incidence of osteochondral lesions of the talus is increasing in the pediatric and adolescent population. There are a few studies regarding surgical treatment. The aim of this study is to report that need for surgical treatment is higher than expected in aforementioned lesions. Methods: Osteochondral lesions of the Talus are defined as any damage involving both articular cartilage and subchondral bone of the talar dome, and this condition is associated with persistent ankle pain and disability. The incidence of osteochondral lesions of the talus is increasing in the pediatric and adolescent population. There are a few studies regarding surgical treatment. The aim of this study is to report that need for surgical treatment is higher than expected in aforementioned lesions. Results: Average age was 14,5 (10-18) at beginning of the treatment. 69,2% of our patients were female. Foundation of conservative treatment was activity modification. 9 of our 13 patients were treated surgically. Arthroscopic debridement and microfracture surgery as well as various techniques were applied to all operated patients. In 7 of the operated patients (n=9), the lesion was on the right side and there was a history of trauma before the complaints started. While the mean AOFAS scores of the operated patients were 47 (24-75) before the operation, it was 83.8 in the last follow-up. While the mean AOFAS scores of our conservatively treated patients were 38.2 (21-74) before treatment, the mean AOFAS scores at the last follow-up after treatment (mean follow-up 2 years) were 70 (17-100). There were no minor and major postoperative complications and no need of reoperation. At the final follow up there was significant improvement in clinical results in all patients treated surgically and conservatively. Conclusion: Talus osteochondral lesions at younger ages is an increasing problem. Conservative management with close follow up is the mainstay of the treatment. However, need of surgical treatment may be higher than expected and the short-term results of surgical with various techniques are successful.
Opioid Use for Operative Foot and Ankle Fractures: A Systematic Review
Authors: Badin Daniel , Ortiz-Babilonia Carlos D. , Gupta Arjun , Leland Christopher R. , Musharbash Farah , Parrish James M. , Aiyer Amiethab A. 
Published: November 2022

Category: Ankle; Trauma Introduction/Purpose: Patients treated operatively for foot and ankle fractures may be at higher risk of undertreated pain as well as overuse of opioid medications. We sought to synthesize the recent literature investigating use of opioids for analgesia following foot and ankle fracture surgery. To accomplish this, we aimed to determine the patterns of opioid use and prescription (e.g., quantity, duration, incidence of persistent use), risk or protective factors for persistent opioid use, and clinical outcomes (e.g., relief of pain, adverse events) associated with opioid use in this population. Methods: We followed PRISMA guidelines for our review. We systematically searched PubMed, Embase, Scopus, Cochrane, and Web of Science. We included studies published from 2010 to present that assessed patterns of opioid use, risk factors for increased opioid use, and outcomes associated with opioid use following foot/ankle fracture surgery. Two reviewers performed title/abstract screening and full-text review. The quality of included studies was evaluated using MINORS criteria. Results: In our review, 1713 articles were assessed and 18 were included (Figure 1). MINORS scores ranged from 13 to 18, indicating moderate study quality. Overall, there was wide variability in opioid use between and within studies. Rates of postoperative persistent opioid use ranged from 7-39%. Risk factors for increased opioid use included preoperative opioid exposure, mental health disorders, tobacco consumption, and certain injury patterns. Protective factors were spinal anesthesia, peripheral nerve block, and postoperative ketorolac. Opioid use was not associated with decreased pain or improved satisfaction. Opioid use was associated with increased rates of pain-related emergency department visits and readmission. Preoperative opioid use was associated with the greatest odds of increased postoperative use. Conclusion: There is a high incidence of persistent opioid use after foot and ankle fracture surgery. Opioid use was associated with negative health outcomes without decreasing pain levels or increasing patient satisfaction after foot/ankle fracture surgery. The wide variability of reported opioid use emphasizes the need for standardized guidelines for postoperative opioid use in this patient population, and our findings suggest that lower opioid prescription may be advisable.
A novel RIPK1 inhibitor reduces GVHD in mice via a nonimmunosuppressive mechanism that restores intestinal homeostasis
Authors: Yu Xiaoliang , Ma Haikuo , Li Bohan , Ji Yuting , Du Yayun , Liu Siying , Li Zhanhui , Hao Yongjin , Tian Sheng , Zhao Cong , Du Qian , Jin Zhongqin , Zhu Xueming , Tian Yuanyuan , Chen Xin , Sun Xue , Yang Chengkui , Zhu Fang , Ju Jie , Zheng Yunjing , Zhang Wei , Wang Jingrui , Yang Tao , Wang Xinhui , Li Jingjing , Xu Xiangping , Du Shujing , Lu Haohao , Ma Feng , Zhang Haibing , Zhang Yi , Zhang Xiaohu , Hu Shaoyan , He Sudan 
Published: November 2022

AbstractIntestinal epithelial cells (IECs) are implicated in the propagation of T-cell–mediated inflammatory diseases, including graft-versus-host disease (GVHD), but the underlying mechanism remains poorly defined. Here, we report that IECs require receptor-interacting protein kinase-3 (RIPK3) to drive both gastrointestinal (GI) tract and systemic GVHD after allogeneic hematopoietic stem cell transplantation. Selectively inhibiting RIPK3 in IECs markedly reduces GVHD in murine intestine and liver. IEC RIPK3 cooperates with RIPK1 to trigger mixed lineage kinase domain-like protein-independent production of T-cell–recruiting chemokines and major histocompatibility complex (MHC) class II molecules, which amplify and sustain alloreactive T-cell responses. Alloreactive T-cell–produced interferon gamma enhances this RIPK1/RIPK3 action in IECs through a JAK/STAT1-dependent mechanism, creating a feed-forward inflammatory cascade. RIPK1/RIPK3 forms a complex with JAK1 to promote STAT1 activation in IECs. The RIPK1/RIPK3-mediated inflammatory cascade of alloreactive T-cell responses results in intestinal tissue damage, converting the local inflammation into a systemic syndrome. Human patients with severe GVHD showed highly activated RIPK1 in the colon epithelium. Finally, we discover a selective and potent RIPK1 inhibitor (Zharp1-211) that significantly reduces JAK/STAT1-mediated expression of chemokines and MHC class II molecules in IECs, restores intestinal homeostasis, and arrests GVHD without compromising the graft-versus-leukemia (GVL) effect. Thus, targeting RIPK1/RIPK3 in IECs represents an effective nonimmunosuppressive strategy for GVHD treatment and potentially for other diseases involving GI tract inflammation.
Pharmacokinetics, pharmacodynamics, safety, and efficacy of crizanlizumab in patients with sickle cell disease
Authors: Kanter Julie , Brown R. Clark , Norris Cynthia , Nair Santosh M. , Kutlar Abdullah , Manwani Deepa , Shah Nirmish , Tanaka Chiaki , Bodla Shankaranand , Sanchez-Olle Gessami , Albers Urs , Liles Darla 
Published: November 2022

Abstract
Crizanlizumab is an anti–P-selectin monoclonal antibody indicated to reduce the frequency/prevent recurrence of vaso-occlusive crises (VOCs) in patients with sickle cell disease (SCD) aged ≥16 years. This analysis of an ongoing phase 2, nonrandomized, open-label study reports the pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy of crizanlizumab 5.0 mg/kg (N = 45) and 7.5 mg/kg (N = 12) in patients with SCD with a history of VOCs. The median treatment duration was 104.7 and 85.7 weeks in the 5.0 and 7.5 mg/kg groups, respectively. For both doses, serum crizanlizumab concentrations rose to near maximum levels shortly after infusion, and near complete and sustained ex vivo P-selectin inhibition was observed. Grade ≥3 adverse events (AEs) occurred in 48.9% and 33.3% of patients in the 5.0 and 7.5 mg/kg groups, respectively; only 1 event was deemed treatment-related (7.5 mg/kg group). No treatment-related serious AEs occurred. One infusion-related reaction was recorded (5.0 mg/kg, grade 2 “pain during infusion”), which resolved without treatment withdrawal. Infections occurred in 57.8% and 41.7% of patients in the 5.0 and 7.5 mg/kg groups, respectively; none were drug-related. No treatment-related bleeding events were reported. No patients developed immunogenicity. The median (range) absolute reduction from baseline in the annualized rate of VOCs leading to a health care visit was −0.88 (−14.7 to 13.3) and −0.93 (−2.0 to 0.4) in the 5.0 and 7.5 mg/kg groups, respectively. Results here demonstrate the PK/PD properties of crizanlizumab in patients with SCD and the potential sustained efficacy and long-term safety of the drug after &gt;12 months’ treatment. This trial was registered at www.clinicaltrials.gov as #NCT03264989.
Lung dendritic cells and host immunity to infection
Authors: Lambrecht B.N. , Prins J-;B. , Hoogsteden H.C. 
Published: November 2022

The lung is a portal of entry for numerous microbial pathogens, against which evolution has created an adequate innate and adaptive immune response. Dendritic cells (DCs) are central to the integration of innate and specific immunity. These cells are located within the epithelium and interstitium of the lung where they are influenced by the innate immune system.Upon recognition and internalization of microbial antigens, DCs migrate to the draining lymph nodes of the lung to initiate the specific cellular and humoral immune response. By their capacity to integrate stimuli derived from the pathogen, the host and the environment, they are specialized to induce a protective immune response while at the same time avoiding damage to the host.It is becoming increasingly clear that dendritic cells are involved in the induction of immunity to viruses, bacteria, mycobacteria and fungi. Some pathogens subvert the function of dendritic cells to escape immune recognition. Not surprisingly, if dendritic cell function fails, the consequence for the host is immunodeficiency.
Dynamic analysis of gene signatures in the progression of COPD
Authors: Jiang Junchao , Chen Shengsong , Yu Tao , Chang Chenli , Liu Jixiang , Ren Xiaoxia , Niu Hongtao , Huang Ke , Li Baicun , Wang Chen , Yang Ting 
Published: November 2022

AimsOxidative stress is an important amplifying mechanism in COPD; however, it is unclear how oxidative stress changes and what its exact amplification mechanism is in the pathological process. We aimed to dynamically analyse the progression of COPD and further elucidate the characteristics of each developmental stage and unveil the underlying mechanisms.MethodsWe performed a holistic analysis by integrating Gene Expression Omnibus microarray datasets related to smoking, emphysema and Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification based on the concept of gene, environment and time (GET). Gene ontology (GO), protein–protein interaction (PPI) networks and gene set enrichment analysis (GSEA) were used to explore the changing characteristics and potential mechanisms. Lentivirus was used to promoteHIF3Aoverexpression.ResultsIn smokersversusnonsmokers, the GO term mainly enriched in “negative regulation of apoptotic process”. In later transitions between stages, the main enriched terms were continuous progression of “oxidation-reduction process” and “cellular response to hydrogen peroxide”. Logistic regression showed that these core differentially expressed genes (DEGs) had diagnostic accuracy in test (area under the curve (AUC)=0.828) and validation (AUC=0.750) sets. GSEA and PPI networks showed that one of the core DEGs,HIF3A, strongly interacted with the ubiquitin-mediated proteolysis pathway. Overexpression ofHIF3Arestored superoxide dismutase levels and alleviated the reactive oxygen species accumulation caused by cigarette smoke extract treatment.ConclusionOxidative stress was continuously intensified from mild emphysema to GOLD 4; thus, special attention should be paid to the identification of emphysema. Furthermore, the downregulatedHIF3Amay play an important role in the intensified oxidative stress in COPD.
Constructing metagenome-assembled genomes for almost all components in a real bacterial consortium for binning benchmarking
Authors: Wu Ziyao , Wang Yuxiao , Zeng Jiaqi , Zhou Yizhuang 
Published: November 2022

Abstract
Background
So far, a lot of binning approaches have been intensively developed for untangling metagenome-assembled genomes (MAGs) and evaluated by two main strategies. The strategy by comparison to known genomes prevails over the other strategy by using single-copy genes. However, there is still no dataset with all known genomes for a real (not simulated) bacterial consortium yet.

Results
Here, we continue investigating the real bacterial consortium F1RT enriched and sequenced by us previously, considering the high possibility to unearth all MAGs, due to its low complexity. The improved F1RT metagenome reassembled by metaSPAdes here utilizes about 98.62% of reads, and a series of analyses for the remaining reads suggests that the possibility of containing other low-abundance organisms in F1RT is greatly low, demonstrating that almost all MAGs are successfully assembled. Then, 4 isolates are obtained and individually sequenced. Based on the 4 isolate genomes and the entire metagenome, an elaborate pipeline is then in-house developed to construct all F1RT MAGs. A series of assessments extensively prove the high reliability of the herein reconstruction. Next, our findings further show that this dataset harbors several properties challenging for binning and thus is suitable to compare advanced binning tools available now or benchmark novel binners. Using this dataset, 8 advanced binning algorithms are assessed, giving useful insights for developing novel approaches. In addition, compared with our previous study, two novel MAGs termed FC8 and FC9 are discovered here, and 7 MAGs are solidly unearthed for species without any available genomes.

Conclusion
To our knowledge, it is the first time to construct a dataset with almost all known MAGs for a not simulated consortium. We hope that this dataset will be used as a routine toolkit to complement mock datasets for evaluating binning methods to further facilitate binning and metagenomic studies in the future.