bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of KIAA1199, a novel strong hyaluronidase, is a poor prognostic factor in patients with osteosarcoma
Authors: Ito Kan , Nishida Yoshihiro , Ikuta Kunihiro , Urakawa Hiroshi , Koike Hiroshi , Sakai Tomohisa , Zhang Jiarui , Shimoyama Yoshie , Imagama Shiro 
Published: July 2021

Abstract
Background
Hyaluronan (HA) has been shown to play important roles in the growth, invasion, and metastasis of malignant tumors. KIAA1199, which has potent HA-degrading activity, has been reported to be expressed in various malignancies and associated with patient prognosis. However, there are no reports on the expression of KIAA1199 in osteosarcoma. The aim of this study was to investigate the impact of KIAA1199 and HA expression in osteosarcoma tissues on the prognosis and other clinical characteristics of osteosarcoma patients.

Methods
From 2003 to 2013, we included 49 patients with osteosarcoma at our institution, whose FFPE (formalin fixed paraffin embedded) tissue was available at the time of biopsy. The expressions of KIAA1199 and HA in each sample were assessed by immunohistochemistry using the primary antibody for KIAA1199 and HA-binding protein (HABP), respectively. For evaluation of the positivity of KIAA1199 staining, we divided the samples into two groups: High group with more than 75% positive staining and Low group with less than 75% positive staining. In the HABP staining, those with more than and less than 60% were assigned to a High group, and Low group respectively. Various clinical features were correlated with staining positivity. Prognostic factors including positivity of the staining were analyzed. Levels of mRNA expression for enzymes related to HA metabolism were assessed in two osteosarcoma cell lines using real-time RT-PCR.

Results
In KIAA1199 staining, high positivity was significantly correlated with occurrence of distant metastases (P = 0.002). The necrosis rate after preoperative chemotherapy was significantly lower in the High positivity group (59%), compared to that in the Low group (84.8%) (P = 0.003). HABP positivity was not correlated with any demographic variables, although the Low positivity group had a significantly better overall survival than the High group with KIAA1199 and HABP staining (P = 0.026 and P = 0.029, respectively). In multivariable analysis, KIAA1199 (P = 0.036) and HABP staining (P = 0.002), location (P = 0.001), and distant metastasis at initial diagnosis (P < 0.001) were identified as significant prognostic factors. KIAA1199 and hyaluronan synthase mRNA were expressed at different levels in the two osteosarcoma cell lines.

Conclusions
Our results showed that high expression of KIAA1199 and HA are both poor prognostic factors in osteosarcoma. KIAA1199 may be a useful marker for distant metastasis and chemoresistance.
Surgical choice for patients with stage I non-small-cell lung cancer ≤2 cm: an analysis from surveillance, epidemiology, and end results database
Authors: Wu Liang , Zhao Weigang , Chen Tangbing , Yang Yi 
Published: July 2021

Abstract
Background
No consensus was reached on the surgical procedure for patients with stage I non-small-cell lung cancer (NSCLC) ≤ 2 cm. The aim of this study is to investigate the appropriate surgical procedure for stage I NSCLC ≤2 cm.

Methods
Patients with stage I NSCLC ≤2 cm received wedge resection, segmentectomy, lobectomy between January 2004 and December 2015 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Data were stratified by age, gender, race, side, location, grade, histology, extent of lymphadenectomy. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared among patients received wedge resection, segmentectomy, lobectomy. Univariate analysis and multivariable Cox regression were performed to identify the prognostic factors of OS and LCSS.

Results
A total of 16,511 patients with stage I NSCLC ≤2 cm were included in this study, of whom 2945 patients were classified as stage I NSCLC ≤1 cm. Lobectomy had better OS and LCSS when compared with wedge resection in patients with NSCLC ≤2 cm. Only OS favored lobectomy compared with segmentectomy in stage I NSCLC>1 to 2 cm. Multivariable analysis showed that segmentectomy had similar OS and LCSS compared with lobectomy in patients with stage I NSCLC ≤2 cm. Lymph node dissection (LND) was associated with better OS in patients with NSCLC ≤2 cm and better LCSS in patients with stage I NSCLC>1 to 2 cm.

Conclusions
Segmentectomy showed comparable survival compared with lobectomy in patients with stage I NSCLC ≤2 cm. LND can provide more accurate pathological stage, may affect survival, and should be recommended for above patients.
Retrospective analysis of factors associated with aortic remodeling in patients with Stanford type B aortic dissection after thoracic endovascular aortic repair
Authors: Yu Biao , Li Tangzhiming , Liu Huadong 
Published: July 2021

Abstract
Objective
Acute aortic dissection is a life-threatening condition. Thoracic endovascular aortic repair (TEVAR), together with optimized medical treatment, is currently the first line treatment for acute Stanford type B aortic dissection. TEVAR can close the entry tear and reduce mortality. Aortic remodeling after TEVAR can directly affect the patient’s long-term prognosis. The factors that influence aortic remodeling have, however, received insufficient clinical attention and remain unclear. It is very important to identify these factors.

Methods
A total of 100 patients were continuously enrolled from 2011 to 2018 in 2 centers. Relevant data, including time from hospital admission to surgery, medicine use and aortic computed tomography angiography images obtained before and 6 months after surgery were collected. Patients were divided into favorable and adverse aortic remodeling groups, according to the degree of aortic remodeling. Analysis of variance and the chi-square test were performed using SPSS software to compare differences between groups and to determine the factors that influence postoperative aortic remodeling.

Results
The proportion of single-stent implantations was higher in the favorable remodeling group than in the adverse remodeling group (79.5% vs. 53.8% in distal end of stent-graft level and 81.3% vs. 56.4% in diaphragm level, respectively, p < 0.05). The earlier the TEVAR procedure was performed, the better the aortic remodeling (3.4 days vs. 4.8 days in distal stent graft levels, and 3.6 days vs. 4.9 days in diaphragm level, respectively, p < 0.05), the presence of residual distal entry tears in the abdominal aorta also improved aortic remodeling after TEVAR (85.7% vs. 55.1% in the celiac trunk level, and 92.0% vs. 48.9% in the right renal artery level, respectively, p < 0.05).

Conclusion
Single stent-graft implantation and early surgery were associated with favorable aortic remodeling. Distal entry tears were also conducive to aortic remodeling after surgery for aortic dissection.
Weight changes in hypertensive patients with phlegm-dampness syndrome: an integrated proteomics and metabolomics approach
Authors: Zhang Chi , Li Li , Cheng Shiping , Chowdhury Debajyoti , Tan Yong , Liu Xinru , Zhao Ning , He Xiaojuan , Jiang Miao , Lu Cheng , Lyu Aiping 
Published: July 2021

AbstractBackgroundHypertension (HTN) patients who have phlegm-dampness syndrome (PDS) tend to be obese and have worse outcomes. However, the association of body weight (BW) changes and mechanisms underlying the pathophysiology of HTN-PDS are not well elucidated. This study aims to identify the longitudinal observations associated with the circulating markers discriminating BW changes of individuals with HTN-PDS.MethodsAn integrative approach relying on metabolomics and proteomics was applied to serum samples from HTN-PDS patients in a prospective cohort to identify the plausible mechanistic pathways underpinning HTN-PDS pathophysiology. Study participants were determined to have experienced a weight change if they showed a 5%–15% increase/reduction in BW at the end of the follow-up period. The joint pathway analysis and network analysis were performed using Ingenuity Pathway Analysis (IPA®) on the serum samples obtained from the participants over the period.ResultsThe study involved 22 HTN-PDS patients who were overweight initially and were able to lose enough weight and 24 HTN-PDS individuals who developed overweight from normal BMI during a one-year follow-up. Our analysis suggested three types of phosphatidylcholine (PC) were altered. PC (22:2(13Z,16Z)/24:1(15Z)) and LysoPC (16:1(9Z)) were decreased in Queryweight gain samples, whereas the levels of PC (14:0/16:0) were increased in weight loss samples. The metabolomic analysis suggested 24 metabolites associated with HTN-PDS. Of them, 13 were up-regulated and 11 were down-regulated. The two-dimensional difference gel electrophoresis (2D DIGE) identified 45 phosphorylated proteins got altered in the HTN-PDS patients, wherein 23 were up-regulated and 22 were down-regulated. Integrated proteomic and metabolomics analyse acknowledged biomarkers PC, Complement C3, C4a/C4b, A2M and SERPINF1 as strong predictors for BW changes in HTN-PDS patients.ConclusionThe combined serum proteomic and metabolomic profiling reveals a link between BW change and the complement system activity, altered phosphatidylcholine metabolism in HTN-PDS patients. Future studies with larger cohorts are required to strengthen and validate these findings.
Global trends and prospects about inflammasomes in stroke: a bibliometric analysis
Authors: Yin Junjun , Wan Jiayang , Zhu Jiaqi , Zhou Guoying , Pan Yuming , Zhou Huifen 
Published: July 2021

Abstract
Background
Sterile inflammation is a key pathological process in stroke. Inflammasome activation has been implicated in various inflammatory diseases, including ischemic stroke and hemorrhagic stroke. Hence, targeting inflammasomes is a promising approach for the treatment of stroke.

Methods
We applied bibliometric methods and techniques. The Web of Science Core Collection was searched for studies indexed from database inception to November 26, 2020. We generated various visual maps to display publications, authors, sources, countries, and keywords.

Results
Our literature search yielded 427 publications related to inflammasomes involved in stroke, most of which consisted of original research articles and reviews. In particular, we found that there was a substantial increase in the number of relevant publications in 2018. Furthermore, most of the publications with the highest citation rates were published in 2014. Relatively, the field about inflammasomes in stroke developed rapidly in 2014 and 2018. Many institutions contributed to these publications, including those from China, the United States, and worldwide. We found that NLR family pyrin domain containing 3 (NLRP3) was the most studied, followed by NLRP1, NLRP2, and NLRC4 among the inflammasomes associated with stroke. Analysis of keywords suggested that the most studied mechanisms involved dysregulation of extracellular pH, efflux of Ca2+ ions, dysfunction of K+/Na+ ATPases, mitochondrial dysfunction, and damage to mitochondrial DNA.

Conclusions
Given the potential diagnostic and therapeutic implications, the specific mechanisms of inflammasomes contributing to stroke warrant further investigation. We used bibliometric methods to objectively present the global trend of inflammasomes in stroke, and to provide important information for relevant researchers.
Cybernic treatment with wearable cyborg Hybrid Assistive Limb (HAL) improves ambulatory function in patients with slowly progressive rare neuromuscular diseases: a multicentre, randomised, controlled crossover trial for efficacy and safety (NCY-3001)
Authors: Nakajima Takashi , Sankai Yoshiyuki , Takata Shinjiro , Kobayashi Yoko , Ando Yoshihito , Nakagawa Masanori , Saito Toshio , Saito Kayoko , Ishida Chiho , Tamaoka Akira , Saotome Takako , Ikai Tetsuo , Endo Hisako , Ishii Kazuhiro , Morita Mitsuya , Maeno Takashi , Komai Kiyonobu , Ikeda Tetsuhiko , Ishikawa Yuka , Maeshima Shinichiro , Aoki Masashi , Ito Michiya , Mima Tatsuya , Miura Toshihiko , Matsuda Jun , Kawaguchi Yumiko , Hayashi Tomohiro , Shingu Masahiro , Kawamoto Hiroaki 
Published: July 2021

AbstractBackgroundRare neuromuscular diseases such as spinal muscular atrophy, spinal bulbar muscular atrophy, muscular dystrophy, Charcot-Marie-Tooth disease, distal myopathy, sporadic inclusion body myositis, congenital myopathy, and amyotrophic lateral sclerosis lead to incurable amyotrophy and consequent loss of ambulation. Thus far, no therapeutic approaches have been successful in recovering the ambulatory ability. Thus, the aim of this trial was to evaluate the efficacy and safety of cybernic treatment with a wearable cyborg Hybrid Assistive Limb (HAL, Lower Limb Type) in improving the ambulatory function in those patients.ResultsWe conducted an open-label, randomised, controlled crossover trial to test HAL at nine hospitals between March 6, 2013 and August 8, 2014. Eligible patients were older than 18 years and had a diagnosis of neuromuscular disease as specified above. They were unable to walk for 10 m independently and had neither respiratory failure nor rapid deterioration in gait. The primary endpoint was the distance passed during a two-minute walk test (2MWT). The secondary endpoints were walking speed, cadence, and step length during the 10-m walk test (10MWT), muscle strength by manual muscle testing (MMT), and a series of functional measures. Adverse events and failures/problems/errors with HAL were also evaluated. Thirty patients were randomly assigned to groups A or B, with each group of 15 receiving both treatments in a crossover design. The efficacy of a 40-min walking program performed nine times was compared between HAL plus a hoist and a hoist only. The final analysis included 13 and 11 patients in groups A and B, respectively. Cybernic treatment with HAL resulted in a 10.066% significantly improved distance in 2MWT (95% confidence interval, 0.667–19.464;p = 0.0369) compared with the hoist only treatment. Among the secondary endpoints, the total scores of MMT and cadence at 10MWT were the only ones that showed significant improvement. The only adverse effects were slight to mild myalgia, back pain, and contact skin troubles, which were easily remedied.ConclusionsHAL is a new treatment device for walking exercise, proven to be more effective than the conventional method in patients with incurable neuromuscular diseases.Trial registration: JMACTR, JMA-IIA00156
Ultrasound guided needle biopsy of axilla to evaluate nodal metastasis after preoperative systemic therapy in cohort of 106 breast cancers enriched with BRCA1/2 pathogenic variant carriers
Authors: Līcīte Baiba , Irmejs Arvīds , Maksimenko Jeļena , Loža Pēteris , Trofimovičs Genādijs , Miklaševičs Edvīns , Nazarovs Jurijs , Romanovska Māra , Deičmane Justīne , Irmejs Reinis , Purkalne Gunta , Gardovskis Jānis 
Published: July 2021

Abstract
Background
Aim of the study is to evaluate the role of ultrasound guided fine needle aspiration cytology (FNAC) in the restaging of node positive breast cancer after preoperative systemic therapy (PST).

Methods
From January 2016 – October 2020 106 node positive stage IIA-IIIC breast cancer cases undergoing PST were included in the study. 18 (17 %) were carriers of pathogenic variant in BRCA1/2. After PST restaging of axilla was performed with ultrasound and FNAC of the marked and/or the most suspicious axillary node. In 72/106 cases axilla conserving surgery and in 34/106 cases axillary lymph node dissection (ALND) was performed.

Results
False Positive Rate (FPR) of FNAC after PST in whole cohort and BRCA1/2 positive subgroup is 8 and 0 % and False Negative Rate (FNR) – 43 and 18 % respectively. Overall Sensitivity − 55 %, specificity- 93 %, accuracy 70 %.

Conclusion
FNAC after PST has low FPR and is useful to predict residual axillary disease and to streamline surgical decision making regarding ALND both in BRCA1/2 positive and negative subgroups. FNR is high in overall cohort and FNAC alone are not able to predict ypCR and omission of further axillary surgery. However, FNAC performance in BRCA1/2 positive subgroup is more promising and further research with larger number of cases is necessary to confirm the results.
Implementing an automated monitoring process in a digital, longitudinal observational cohort study
Authors: Lindner Lisa , Weiß Anja , Reich Andreas , Kindler Siegfried , Behrens Frank , Braun Jürgen , Listing Joachim , Schett Georg , Sieper Joachim , Strangfeld Anja , Regierer Anne C. 
Published: July 2021

Abstract
Background
Clinical data collection requires correct and complete data sets in order to perform correct statistical analysis and draw valid conclusions. While in randomized clinical trials much effort concentrates on data monitoring, this is rarely the case in observational studies- due to high numbers of cases and often-restricted resources. We have developed a valid and cost-effective monitoring tool, which can substantially contribute to an increased data quality in observational research.

Methods
An automated digital monitoring system for cohort studies developed by the German Rheumatism Research Centre (DRFZ) was tested within the disease register RABBIT-SpA, a longitudinal observational study including patients with axial spondyloarthritis and psoriatic arthritis. Physicians and patients complete electronic case report forms (eCRF) twice a year for up to 10 years. Automatic plausibility checks were implemented to verify all data after entry into the eCRF. To identify conflicts that cannot be found by this approach, all possible conflicts were compiled into a catalog. This “conflict catalog” was used to create queries, which are displayed as part of the eCRF. The proportion of queried eCRFs and responses were analyzed by descriptive methods. For the analysis of responses, the type of conflict was assigned to either a single conflict only (affecting individual items) or a conflict that required the entire eCRF to be queried.

Results
Data from 1883 patients was analyzed. A total of n = 3145 eCRFs submitted between baseline (T0) and T3 (12 months) had conflicts (40–64%). Fifty-six to 100% of the queries regarding eCRFs that were completely missing were answered. A mean of 1.4 to 2.4 single conflicts occurred per eCRF, of which 59–69% were answered. The most common missing values were CRP, ESR, Schober’s test, data on systemic glucocorticoid therapy, and presence of enthesitis.

Conclusion
Providing high data quality in large observational cohort studies is a major challenge, which requires careful monitoring. An automated monitoring process was successfully implemented and well accepted by the study centers. Two thirds of the queries were answered with new data. While conventional manual monitoring is resource-intensive and may itself create new sources of errors, automated processes are a convenient way to augment data quality.
Ganglionar tuberculosis infection evolving to hemophagocytic lymphohistiocytosis after anti-programmed cell death 1 treatment for high-risk melanoma: a case report
Authors: Costa Cesar M. , Gadotti Luiza L. , Seiwald Maria C. , Salgues Alessandra C. R. , Ganem Fernando , Nascimento Ellen C. T. , Uip David E. , Arrais-Rodrigues Celso , Munhoz Rodrigo R. 
Published: July 2021

AbstractBackgroundHemophagocytic lymphohistiocytosis is a rare, potentially fatal syndrome of immune hyperactivation. Here we describe a ganglionar tuberculosis evolving to hemophagocytic lymphohistiocytosis following adjuvant immunotherapy in a melanoma patient.Case presentationA 76-year-old Caucasian male with melanoma started with fever, diffuse petechiae, splenomegaly, anemia, thrombocytopenia, hypofibrinogenemia, and hyperferritinemia 2 months following completion of adjuvant treatment with nivolumab. Positron emission tomography scan showed significant hypermetabolism in cervical, supraclavicular, mediastinal, and abdominal lymph nodes. Bone marrow aspiration demonstrated no alterations, except for a hypercellular pattern. Dexamethasone and intravenous immunoglobulin were started owing to suspicion of hemophagocytic lymphohistiocytosis. Core biopsy of the infracarinal lymph node revealed a chronic granulomatous inflammation and caseous necrosis, with positivity forMycobacterium tuberculosisby polymerase chain reaction, and treatment for ganglionar tuberculosis was started.ConclusionThis case highlights the challenges involving programmed cell death 1 blockade in high-risk melanoma, in which infections, lymphoproliferative disorders, and sarcoidosis can mimic disease progression and trigger immune-related adverse events.
Reappraisal of metabolic dysfunction in neurodegeneration: Focus on mitochondrial function and calcium signaling
Authors: Jadiya Pooja , Garbincius Joanne F. , Elrod John W. 
Published: July 2021

AbstractThe cellular and molecular mechanisms that drive neurodegeneration remain poorly defined. Recent clinical trial failures, difficult diagnosis, uncertain etiology, and lack of curative therapies prompted us to re-examine other hypotheses of neurodegenerative pathogenesis. Recent reports establish that mitochondrial and calcium dysregulation occur early in many neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson’s disease, Huntington's disease, and others. However, causal molecular evidence of mitochondrial and metabolic contributions to pathogenesis remains insufficient. Here we summarize the data supporting the hypothesis that mitochondrial and metabolic dysfunction result from diverse etiologies of neuropathology. We provide a current and comprehensive review of the literature and interpret that defective mitochondrial metabolism is upstream and primary to protein aggregation and other dogmatic hypotheses of NDDs. Finally, we identify gaps in knowledge and propose therapeutic modulation of mCa2+ exchange and mitochondrial function to alleviate metabolic impairments and treat NDDs.
Implant-supported mandibular overdentures: a retrospective case series study in a daily dental practice
Authors: Abdoel Shebrina F. , Haagedoorn Stephanie S. , Raghoebar Gerry M. , Meijer Henny J. A. 
Published: July 2021

Abstract
Background
Evaluation of dental implant treatment is mostly based on studies with well-controlled study groups treated within a university-based setting. There are no long-term observational practice-based studies known on implant-supported overdentures. The present retrospective study deals with implant survival, peri-implant hard and soft tissue health, surgical and prosthetic aftercare, and satisfaction of patients treated with an implant-supported mandibular overdenture in a daily dental practice.

Materials and methods
Within the years 2006 till 2015, 295 patients were treated with two, three, or four implants for mandibular overdenture treatment in a daily dental practice in Zaandam, The Netherlands. Outcome parameters were scored at a routine yearly inspection including implant loss, plaque index, gingival index, bleeding index, presence of calculus, probing depth, and satisfaction with implant-supported overdenture. Radiographic analysis was performed to assess peri-implant bone changes. Surgical and prosthetic aftercare was obtained from the medical record.

Results
A total of 133 patients were seen for an evaluation visit (mean follow-up 51.2 months). Cumulative implant survival rate in the 2-implant group, 3-implant group, and 4-implant group was 100%, 99.1%, and 97.8% respectively, with a mean peri-implant bone loss of 0.53 mm, 0.61 mm, and 0.40 mm. Patients’ satisfaction was high in all groups.

Conclusion
It was demonstrated, within the limitations of this study, that patients, who were treated with an implant-supported mandibular overdenture in a daily dental practice, experienced a high cumulative implant survival rate and a good peri-implant health, and were very satisfied.

Trial registration
Netherlands Trial Register, NL8867. Registered 15 September 2020—retrospectively registered.