bluuebunny/crossref_metadata_2025_split huggingface dataset:
An incomplete form of anti-ganglioside antibody-positive Miller Fisher syndrome after an Epstein-Barr virus infection
Authors: Chang Le , Xiong Jing , Xue Yuying , Wang Jie , Zhu Xurong , Zheng Xuejiao , Gao Xiaoyu , Yan YuE , Hao Jiaduo , Zhao Hehuan , Di Zhengli 
Published: February 2021

Abstract

Rationale:
The Miller Fisher syndrome (MFS) is an acute polyradiculoneuritis regarded as an uncommon clinical variant of the Guillain-Barre syndrome (GBS). It is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia. The diagnosis of MFS is based on clinical presentation, presence of albuminocytologic dissociation in the cerebrospinal fluid (CSF), and normal brain imaging results. The presence of anti-ganglioside antibodies (GQlb) in the serum is helpful for the diagnosis. A history of upper respiratory tract infection or diarrhea 3 days to 6 weeks before the onset of MFS is common. However, there are some patients with atypical manifestations who are difficult to diagnose. Here, we present an incomplete form of MFS where antibodies against GQ1b were detected in the serum following an Epstein Barr virus (EBV) infection.

Patient concerns:
A 77-year-old Chinese woman was admitted to the hospital with acute diplopia and right blepharoptosis. She had a history of mild upper respiratory tract infection 2 weeks ago. In 1 week, the symptoms rapidly progressed into bilateral ophthalmoplegia and hyporeflexia of the limbs without ataxia. CSF analysis on the third day after onset was normal, without albuminocytologic dissociation. EBV immunoglobulin G (IgG) antibodies were detected in the CSF. GQ1b and GD1b IgG antibodies were positive in the serum and negative in the CSF. No responsible lesion was found on brain imaging examination.

Diagnoses:
In accordance with the progressive bilateral ophthalmoplegia and hyporeflexia, the history of upper respiratory tract infection, the detection of EBV and GQ1b antibodies, and the negative brain imaging examination, the diagnosis of MFS was confirmed.

Interventions:
The patient was administered intravenous immunoglobulin for 5 days.

Outcomes:
She had a favorable outcome after treatment. At the 6-week follow-up, bilateral ocular movement limitation and tendon reflexes had recovered.

Lessons:
The diagnosis of MFS can be challenging, especially when encountered with incomplete symptoms and normal CSF results. Attention should be paid to the presence of anti-GQ1b IgG antibodies when the clinical manifestations are incomplete. Furthermore, EBV primary infection could be associated with MFS and considered a potential causative agent.
Intraductal papillary neoplasm of intrahepatic bile ducts complicated by chronic disseminated intravascular coagulation and thrombosis
Authors: Xiao Ming , Sun Aijun , Yu Fan , Xiao Ying , Li Lihong , Shen Dongyan , Xiang Canhong , Dong Jiahong 
Published: February 2021

Abstract

Rationale:
Intraductal papillary neoplasm of the bile ducts (IPNB) is a relatively rare tumor that is clinically characterized by digestive symptoms. The concurrent occurrence of chronic disseminated intravascular coagulation (DIC) with thrombosis is an extremely rare combination, reported in patients with IPNB. The clinical features of chronic DIC include microangiopathic hemolytic anemia, thrombocytopenia, and hypofibrinogenemia. Here, we report the case of a mucin-producing IPNB patient with hematological abnormalities.

Patient concerns:
A 58-year-old male patient suffered from abdominal distension for more than 2 months with obstructive jaundice appearance. Abdominal contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography showed a neoplasm in the right hepatic lobe. Multiple intravascular fillings were found in the inferior vena cava, pulmonary artery, and right atrium. Anemia and hypofibrinogenemia were discovered through routine laboratory tests. The count of platelets began to decline 25 days after admission, while 1 month after hospitalization, the patient developed abdominal pain, fever, and shock.

Diagnosis:
Pathological examination demonstrated IPNB with a part of high-grade intraepithelial neoplasia. Cardiac and inferior vena cava emboli were diagnosed as thrombi without neoplastic cells. Immunohistochemically, tumor cells were positive for Vimentin (mesenchyme), CK7, CK19, MUC-1, MUC-5AC, MUC-6, S-100p (focal), Ki-67 (12%), and negative for Inhibin-α, ER, CK20, CEA, and MUC-2. Additionally, immunohistochemistry indicated that IPNB was a mucus-secretion gastric type. The laboratory tests confirmed the presence of chronic DIC.

Interventions:
The patient was given anticoagulant therapy before hepatectomy and right atrium thrombectomy was performed under cardiopulmonary bypass.

Outcomes:
After anticoagulant therapy, the levels of hemoglobin, platelet, and fibrinogen of the patient returned to normal. Hepatectomy and thrombus removal was successfully performed. Then, the patient was discharged 12 days after the operation. After 12 months of follow-up, the patient recovered well without any hematologic abnormalities and no signs of tumor recurrence were observed.

Lessons:
IPNB may cause hematological complications, which can be easily misdiagnosed. It is essential to pay particular attention to the hematological abnormalities of patients with IPNB. Early detection and differential diagnosis of chronic DIC and thrombosis are necessary. We note that anticoagulant therapy coupled with surgery is an effective strategy to treat these complications.
A strengthening the reporting of observational studies in epidemiology (STROBE)
Authors: Dellino Miriam , Gargano Giulio , Tinelli Raffele , Carriero Carmine , Minoia Carla , Tetania Skrypets , Silvestris Erica , Loizzi Vera , Paradiso Angelo , Casamassima Porzia , Tufaro Antonio , Cormio Gennaro , Garrisi Vito Michele 
Published: February 2021

Abstract
Paget disease is a complex disorder that can be identified in the breast (mammary Paget disease) or in other locations (extramammary Paget's disease) such as ano-genital skin (Paget disease of the vulva -PVD). This condition is associated with low mortality, but a late diagnosis and recurrence can negatively impact the prognosis. Therefore, the main objective of this study is to evaluate if the human epididymis protein 4 (HE4) and cancer antigen125 (CA125) can promote recognition of PVD in early stages and during the relapses.
we have conducted a prospective, observational and laboratory-based study, that included 50 patients, whose 25 healthy women represented the control group and 25 PVD patients, which have been operated in our Oncology Institute, from May 2017 to September 2019. Both in the control group and in PVD patients, the CA-125 and HE4 were evaluated before surgery and after 6 months. Finally, a comparison of markers serum level, both between before/after surgery and with control group, and a ROC (Receiver Operating Characteristic) curve were performed.
Dosing the markers in PVD patients, 3/25 (12%) showed a higher value of CA125 and 11/25 (44%) an increased HE4. In addition, after surgical treatment there were no statistically significant difference between levels of CA-125 (P = .3) and HE4 (P = .19). On the other hand, comparing HE4 in PVD patients with the control group, a statistically significant difference was found (P-value = .0036). Contrary, comparing CA-125 in PVD patients with the control group (P-value= .1969), no statistically significant difference was evidenced. Moreover, ROC (Receiver Operating Characteristic) curve showed low sensitivity and specificity for CA125 with area under curve (AUC) = 0.5608. Instead, the ROC curve of HE4 revealed a sensitivity and specificity of 76% and 88% respectively (AUC = 0.7408) using a cut-off at 90 pmol/L.
Despite the limited cases, our data showed that CA125 is not a sensitive marker for PVD. On the other hand, in 44% of PVD we’ve seen an increase in HE4. So, this could be a starting point for further research that could confirm the possibility to use this marker in order to support PVD early identification.
SS-A52 antigen expression in thymic carcinoma accompanied with Sjögren syndrome
Authors: Isono Tomomi , Wakasa Tomoko , Kusumoto Hidenori , Shimada Keiji , Ogawa Takafumi , Shiono Hiroyuki 
Published: February 2021

Abstract

Rationale:
The relationship between thymic tumors and Sjögren syndrome (SjS) is unknown, and surgical resection has not been optimized. Especially, thymic carcinoma with autoimmune disease is rare. Analysis of SS-A52, germinal centers, plasma cells, and Foxp3+ Treg in thymic carcinoma has never been reported, and their pathological roles in causing SjS have not been studied.

Patient concerns:
A 78-year-old man presented with sputum production and xerostomia while asleep. Chest computed tomography showed a homogeneous and hypodense mass in the anterosuperior mediastinum. Serum levels of the antinuclear antibody, antibody to SS-A, and antibody to SS-B were positive.

Diagnoses:
Thymic carcinoma (squamous cell carcinoma) and SjS.

Interventions:
Video-assisted thoracoscopic resection of the mediastinal tumor and postoperative radiation therapy was performed.

Outcomes:
The histological diagnosis was thymic squamous cell carcinoma. Histologically, the squamous carcinomatous cells were arranged in nests and cords in the fibrohyaline stroma with capsular invasion. In the stroma, dense lymphoid tissues containing large reactive germinal centers and many plasma cells were also noted. In the involuted thymus, CD20-positive mature lymphocytes infiltrated, and germinal centers were noted. Double immunohistochemical staining revealed that SS-A52 antigen was positive in both the carcinoma component and CD20-positive mature B cells. Postoperatively, the xerostomia persisted, and serum SS-A and SS-B remained positive. No evidence of carcinoma recurrence with chest computed tomography scan was observed at 18-months follow-up.

Lessons:
In the surgical treatment of thymic tumors with SjS, extended thymectomy might be worth considering to stop the progressive destruction of the targets of SjS-specific autoantibodies. However, the postoperative symptoms may not dramatically improve because the target organs might have changed irreversibly, and memory B cells might persist. This is the first report that demonstrated the SS-A52 antigen presentation in a thymic tumor to the best of our knowledge.
Is Qi Fu Yin effective in clinical treatment of dementia?
Authors: Wang Lei , Qiao Pengli , Yue Lulu , Sun Rong 
Published: February 2021

Abstract

Background:
Dementia, a kind of acquired and progressive intelligence-damaging syndrome, is induced by cerebral dysfunction. Ancient records show that Qi Fu Yin (QFY) has the advantages in age-related dementia treatment. This study aims to evaluate therapeutic efficacy of QFY on dementia through meta-analysis.

Methods:
We comprehensively reviewed articles from various databases, including China National Knowledge Infrastructure (CNKI), Wanfang, VIP, Chinese Biomedical Literature (CBM), PubMed, and Web of Science published before June 2020, for all randomized controlled trials (RCTs) on dementia treatment with QFY. Then, we selected eligible literatures, extracted related data, and assessed risk of bias. Forest plots of total clinical effective rate, MMSE score, HDS score and ADL score illustrated the difference between the experimental group (treatment with QFY alone or combined with routine western medicine) and the control group (treatment with routine western medicine only). Random effects model and fixed effects model were adopted. Finally, publication bias was further analyzed using funnel plot, sensitivity analysis, Begg and Egger test.

Results:
Finally, 9 RCTs, involving 697 patients, were included in this study. The results revealed that the total clinical effective rate of the experimental group was obviously higher than that of the control group (OR = 0.33, 95% CI [0.22, 0.50], P < .001). In comparison with the control group, the experimental group showed higher MMSE score (WMD = 2.60, 95% CI [2.16, 3.03], P < .001) and HDS score (WMD = 1.51, 95%CI [1.10, 1.92], P < .001). Due to few included studies, there were no statistically significance between experimental and control groups (WMD = -9.90, 95%CI [−26.09, 6.30], P = .231) regarding ADL score. In addition, there is no publication bias towards clinical effective rate and MMDE score.

Conclusions:
QFY only or combined with western medicine therapy can significantly improve cognitive ability compared with only western medicine therapy in dementia. However, multiple samples, RCTs of high quality are still needed to verify our conclusions.
Exercise intervention for the risk of falls in older adults
Authors: Zhang Qin , Liu Yi , Li Dongze , Jia Yu , Zhang Wei , Chen Bowen , Wan Zhi 
Published: February 2021

Abstract

Background:
Falls can easily lead to serious injury and even death in the older adults. Many exercise interventions, such as balance, flexibility, and endurance training have been shown to reduce the incidence of falls in this population. However, which mode of exercise is most beneficial for them remains unanswered.

Methods:
We will search the following databases as data sources: PUBMED, EMBASE, Cochrane Library, Wanfang, China knowledge Network (CNKI), Clinical Trials Database, and Science Network. Data extraction will be performed by two independent reviewers, who will discuss and resolve any differences, with the consensus of a third author. The RCTs will be selected according to prespecified inclusion criteria. The main outcome is the occurrence of a fall, and the secondary outcomes are the adverse consequences of a fall and a fall risk assessment index. If the heterogeneity test shows slight or no statistical heterogeneity, a fixed effect model will be used for data synthesis; otherwise, a random effect model will be used. We will develop a unified data extraction table including a number of parameters. The Cochrane cooperative bias risk tool will be used to evaluate the methodological quality of the selected RCTs. RevMan Manager v5.3 software and STATA v16.0 software will be used for data analysis. If enough randomized controlled trials (more than 10) are identified and selected.

Conclusion:
This protocol will be applied to synthesize the existing evidence so as to identify the most effective exercise program to prevent falls in the elderly.

INPLASY registration number:
INPLASY2020110008.
Quality assessment of traditional and conventional medicine clinical practice guidelines for osteoporosis
Authors: Kim Jung-Hyun , Seo Byung-Kwan , Baek Yong-Hyeon 
Published: February 2021

Abstract
Numerous studies have reported the variable quality of clinical practice guidelines (CPGs) across various domains. The aim of this study was to systematically assess the quality, methodology, and consistency of recently developed traditional and conventional medicine CPGs that focus on the management of osteoporosis and provide helpful recommendations for patients with osteoporosis.
From June 2020 to July 2020, CPGs with osteoporosis targeting any age were systematically retrieved. All CPGs of traditional and conventional medicine related to the assessment and diagnosis, management, and clinical therapeutic and pharmacological recommendations with osteoporosis were eligible for inclusion in this study. The excluded documents included guidelines without recommendations, secondary publications derived from CPGs, consensus statements, or consensus conferences based on the opinion of panelists, systematic reviews, editorials, clinical trials, and single-author documents. The quality of CPGs was independently examined by three assessors using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. AGREE II consists of 6 domains; scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence. Consequently, selected CPGs were graded as recommended (A), recommended with modifications (B), or not recommended (C), and the specific treatments and preventive recommendations in the CPGs were summarized.
The quality of the 15 CPGs assessed varied across the AGREE II domains. The overall quality ranged from 3.0 to 6.0 out of 7. The domain that had the highest scores were “clarity of presentation,” with a mean value of 69.0% (range 46%–83%); “editorial independence” had the lowest score of 30.2% (range 0%–75%). The conventional CPGs focused on pharmacological treatments, calcium and vitamin D intake, and prevention, while the traditional CPGs consistently emphasized on herbal medicine and non-pharmaceutical treatment and management.
Further development of CPGs will require improvement in domains where low item scores have been obtained in the quality assessment in this present study. Further research is needed on alternative modalities for osteoporosis, especially complementary approaches, and higher quality CPGs are needed to facilitate evidence-based clinical practice.
Advancing data science in drug development through an innovative computational framework for data sharing and statistical analysis
Authors: Mallon Ann-Marie , Häring Dieter A. , Dahlke Frank , Aarden Piet , Afyouni Soroosh , Delbarre Daniel , El Emam Khaled , Ganjgahi Habib , Gardiner Stephen , Kwok Chun Hei , West Dominique M. , Straiton Ewan , Haemmerle Sibylle , Huffman Adam , Hofmann Tom , Kelly Luke J. , Krusche Peter , Laramee Marie-Claude , Lheritier Karine , Ligozio Greg , Readie Aimee , Santos Luis , Nichols Thomas E. , Branson Janice , Holmes Chris 
Published: February 2021

AbstractBackgroundNovartis and the University of Oxford’s Big Data Institute (BDI) have established a research alliance with the aim to improve health care and drug development by making it more efficient and targeted. Using a combination of the latest statistical machine learning technology with an innovative IT platform developed to manage large volumes of anonymised data from numerous data sources and types we plan to identify novel patterns with clinical relevance which cannot be detected by humans alone to identify phenotypes and early predictors of patient disease activity and progression.MethodThe collaboration focuses on highly complex autoimmune diseases and develops a computational framework to assemble a research-ready dataset across numerous modalities. For the Multiple Sclerosis (MS) project, the collaboration has anonymised and integrated phase II to phase IV clinical and imaging trial data from ≈35,000 patients across all clinical phenotypes and collected in more than 2,200 centres worldwide. For the “IL-17” project, the collaboration has anonymised and integrated clinical and imaging data from over 30 phase II and IIICosentyxclinical trials including more than 15,000 patients, suffering from four autoimmune disorders (Psoriasis, Axial Spondyloarthritis, Psoriatic arthritis (PsA) and Rheumatoid arthritis (RA)).ResultsA fundamental component of successful data analysis and the collaborative development of novel machine learning methods on these rich data sets has been the construction of a research informatics framework that can capture the data at regular intervals where images could be anonymised and integrated with the de-identified clinical data, quality controlled and compiled into a research-ready relational database which would then be available to multi-disciplinary analysts. The collaborative development from a group of software developers, data wranglers, statisticians, clinicians, and domain scientists across both organisations has been key. This framework is innovative, as it facilitates collaborative data management and makes a complicated clinical trial data set from a pharmaceutical company available to academic researchers who become associated with the project.ConclusionsAn informatics framework has been developed to capture clinical trial data into a pipeline of anonymisation, quality control, data exploration, and subsequent integration into a database. Establishing this framework has been integral to the development of analytical tools.
Plasma Hydrogen Sulfide Production Capacity is Positively Associated with Post-Operative Survival in Patients Undergoing Surgical Revascularization
Authors: Longchamp Alban , MacArthur Michael R. , Trocha Kaspar , Ganahl Janine , Mann Charlotte G. , Kip Peter , King William W. , Sharma Gaurav , Tao Ming , Mitchell Sarah J. , Ditrói Tamás , Nagy Péter , Ozaki C. Keith , Hine Christopher , Mitchell James R. 
Published: February 2021

ABSTRACTObjectiveHydrogen sulfide (H2S) is a gaseous signaling molecule and redox factor important for cardiovascular function. Deficiencies in its production or bioavailability are implicated in atherosclerotic disease. However, it is unknown if circulating H2S levels differ between vasculopaths and healthy individuals, and if so, whether H2S measurements can be used to predict surgical outcomes. Here, we examine: 1) Plasma H2S levels in patients undergoing vascular surgery and compare these to healthy controls, and 2) Associations between H2S levels and mortality in surgical revascularization patients.Approach & ResultsPatients undergoing carotid endarterectomy, open lower extremity revascularization or leg amputation were enrolled. Peripheral blood was also collected from a matched cohort of 20 patients without peripheral or coronary artery disease. Plasma H2S production capacity and sulfide concentration were measured using the lead acetate and monobromobimane methods, respectively. Plasma H2S production capacity and plasma sulfide concentrations were reduced in patients with PAD (p<0.001, p=0.013 respectively). Patients that underwent surgical revascularization were divided into high versus low H2S production capacity groups by median split. Patients in the low H2S production group had increased probability of mortality (p=0.003). This association was robust to correction for potentially confounding variables using Cox proportional hazard models.ConclusionsCirculating H2S levels were lower in patients with atherosclerotic disease. Patients undergoing surgical revascularization with lower H2S production capacity, but not sulfide concentrations, had increased probability of mortality within 36 months post-surgery. This work provides insight on the role H2S plays as a diagnostic and potential therapeutic for cardiovascular disease.HIGHLIGHTSVascular disease patients have higher plasma hydrogen sulfide levels than controls without vascular disease as measured by two distinct methods, the lead acetate hydrogen sulfide release method and the HPLC-based monobromobimane method.Only the lead acetate hydrogen sulfide release method robustly predicts survival after vascular surgery intervention over 35 months of follow up.The lead acetate release method measures non-enzymatic hydrogen sulfide release from plasma which requires iron and is catalyzed by vitamin B6.