bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular bases for the association of FHR-1 with atypical hemolytic uremic syndrome and other diseases
Authors: Martin Merinero Héctor , Subías Marta , Pereda Amaia , Gómez-Rubio Elena , Juana Lopez Lucia , Fernandez Constantino , Goicoechea de Jorge Elena , Martin-Santamaria Sonsoles , Cañada Francisco Javier , Rodríguez de Córdoba Santiago 
Published: March 2021

Abstract
Factor H (FH)–related proteins are a group of partly characterized complement proteins thought to promote complement activation by competing with FH in binding to surface-bound C3b. Among them, FH-related protein 1 (FHR-1) is remarkable because of its association with atypical hemolytic uremic syndrome (aHUS) and other important diseases. Using a combination of biochemical, immunological, nuclear magnetic resonance, and computational approaches, we characterized a series of FHR-1 mutants (including 2 associated with aHUS) and unraveled the molecular bases of the so-called deregulation activity of FHR-1. In contrast with FH, FHR-1 lacks the capacity to bind sialic acids, which prevents C3b-binding competition between FH and FHR-1 in host-cell surfaces. aHUS-associated FHR-1 mutants are pathogenic because they have acquired the capacity to bind sialic acids, which increases FHR-1 avidity for surface-bound C3-activated fragments and results in C3b-binding competition with FH. FHR-1 binds to native C3, in addition to C3b, iC3b, and C3dg. This unexpected finding suggests that the mechanism by which surface-bound FHR-1 promotes complement activation is the attraction of native C3 to the cell surface. Although C3b-binding competition with FH is limited to aHUS-associated mutants, all surface-bound FHR-1 promotes complement activation, which is delimited by the FHR-1/FH activity ratio. Our data indicate that FHR-1 deregulation activity is important to sustain complement activation and C3 deposition at complement-activating surfaces. They also support that abnormally elevated FHR-1/FH activity ratios would perpetuate pathological complement dysregulation at complement-activating surfaces, which may explain the association of FHR-1 quantitative variations with diseases.
Proteomic and bioinformatic profiling of neutrophils in CLL reveals functional defects that predispose to bacterial infections
Authors: Subramaniam Nirojah , Bottek Jenny , Thiebes Stephanie , Zec Kristina , Kudla Matthias , Soun Camille , de Dios Panal Elena , Lill Julia K. , Pfennig Aaron , Herrmann Ralf , Bruderek Kirsten , Rahmann Sven , Brandau Sven , Johansson Patricia , Reinhardt Hans Christian , Dürig Jan , Seiffert Martina , Bracht Thilo , Sitek Barbara , Engel Daniel Robert 
Published: March 2021

AbstractPatients with chronic lymphocytic leukemia (CLL) typically suffer from frequent and severe bacterial infections. Although it is well known that neutrophils are critical innate immune cells facilitating the early defense, the underlying phenotypical and functional changes in neutrophils during CLL remain largely elusive. Using a murine adoptive transfer model of CLL, we demonstrate aggravated bacterial burden in CLL-bearing mice upon a urinary tract infection with uropathogenic Escherichia coli. Bioinformatic analyses of the neutrophil proteome revealed increased expression of proteins associated with interferon signaling and decreased protein expression associated with granule composition and neutrophil migration. Functional experiments validated these findings by showing reduced levels of myeloperoxidase and acidification of neutrophil granules after ex vivo phagocytosis of bacteria. Pathway enrichment analysis indicated decreased expression of molecules critical for neutrophil recruitment, and migration of neutrophils into the infected urinary bladder was significantly reduced. These altered migratory properties of neutrophils were also associated with reduced expression of CD62L and CXCR4 and correlated with an increased incidence of infections in patients with CLL. In conclusion, this study describes a molecular signature of neutrophils through proteomic, bioinformatic, and functional analyses that are linked to a reduced migratory ability, potentially leading to increased bacterial infections in patients with CLL.
Heart rate variability-derived features based on deep neural network for distinguishing different anaesthesia states
Authors: Zhan Jian , Wu Zhuo-xi , Duan Zhen-xin , Yang Gui-ying , Du Zhi-yong , Bao Xiao-hang , Li Hong 
Published: March 2021

Abstract
Background
Estimating the depth of anaesthesia (DoA) is critical in modern anaesthetic practice. Multiple DoA monitors based on electroencephalograms (EEGs) have been widely used for DoA monitoring; however, these monitors may be inaccurate under certain conditions. In this work, we hypothesize that heart rate variability (HRV)-derived features based on a deep neural network can distinguish different anaesthesia states, providing a secondary tool for DoA assessment.

Methods
A novel method of distinguishing different anaesthesia states was developed based on four HRV-derived features in the time and frequency domain combined with a deep neural network. Four features were extracted from an electrocardiogram, including the HRV high-frequency power, low-frequency power, high-to-low-frequency power ratio, and sample entropy. Next, these features were used as inputs for the deep neural network, which utilized the expert assessment of consciousness level as the reference output. Finally, the deep neural network was compared with the logistic regression, support vector machine, and decision tree models. The datasets of 23 anaesthesia patients were used to assess the proposed method.

Results
The accuracies of the four models, in distinguishing the anaesthesia states, were 86.2% (logistic regression), 87.5% (support vector machine), 87.2% (decision tree), and 90.1% (deep neural network). The accuracy of deep neural network was higher than those of the logistic regression (p < 0.05), support vector machine (p < 0.05), and decision tree (p < 0.05) approaches. Our method outperformed the logistic regression, support vector machine, and decision tree methods.

Conclusions
The incorporation of four HRV-derived features in the time and frequency domain and a deep neural network could accurately distinguish between different anaesthesia states; however, this study is a pilot feasibility study. The proposed method—with other evaluation methods, such as EEG—is expected to assist anaesthesiologists in the accurate evaluation of the DoA.
Prognostic dynamic nomogram integrated with metabolic acidosis for in-hospital mortality and organ malperfusion in acute type B aortic dissection patients undergoing thoracic endovascular aortic repair
Authors: Liu Jitao , Liu Weijie , Ma Wentao , Chen Lyufan , Liang Hong , Fan Ruixin , Zeng Hongke , Geng Qingshan , Yang Fan , Luo Jianfang 
Published: March 2021

Abstract
Background
Organ malperfusion is a lethal complication in acute type B aortic dissection (ATBAD). The aim of present study is to develop a nomogram integrated with metabolic acidosis to predict in-hospital mortality and organ malperfusion in patients with ATBAD undergoing thoracic endovascular aortic repair (TEVAR).

Methods
The nomogram was derived from a retrospectively study of 286 ATBAD patients who underwent TEVAR from 2010 to 2017 at a single medical center. Model performance was evaluated from discrimination and calibration capacities, as well as clinical effectiveness. The results were validated using a prospective study on 77 patients from 2018 to 2019 at the same center.

Results
In the multivariate analysis of the derivation cohort, the independent predictors of in-hospital mortality and organ malperfusion identified were base excess, maximum aortic diameter ≥ 5.5 cm, renal dysfunction, D-dimer level ≥ 5.44 μg/mL and albumin amount ≤ 30 g/L. The penalized model was internally validated by bootstrapping and showed excellent discriminatory (bias-corrected c-statistic, 0.85) and calibration capacities (Hosmer–Lemeshow P value, 0.471; Brier Score, 0.072; Calibration intercept, − 0.02; Slope, 0.98). After being applied to the external validation cohort, the model yielded a c-statistic of 0.86 and Brier Score of 0.097. The model had high negative predictive values (0.93–0.94) and moderate positive predictive values (0.60–0.71) for in-hospital mortality and organ malperfusion in both cohorts.

Conclusions
A predictive nomogram combined with base excess has been established that can be used to identify high risk ATBAD patients of developing in-hospital mortality or organ malperfusion when undergoing TEVAR.
Emergency department use by patients with end-stage renal disease in the United States
Authors: Wang Ningyuan , Pei Jiao , Fan Hui , Ali Yaseen , Prushinskaya Anna , Zhao Jian , Zhang Xingyu 
Published: March 2021

AbstractBackgroundWe sought to describe the national characteristics of ED visits by patients with end-stage renal disease (ESRD) in the United States in order to improve the emergency treatment and screening of ESRD patients.MethodsWe analyzed data from 2014 to 2016 ED visits provided by the National Hospital Ambulatory Medical Care Survey. We sampled adult (age ≥ 18 years) ED patients with ESRD. By proportion or means of weighted sample variables, we quantified annual ED visits by patients with ESRD. We investigated demographics, ED resource utilization, clinical characteristics, and disposition of patients with ESRD and compared these to those of patients without ESRD. Logistic regression models were used to estimate the association between these characteristics and ESRD ED visits.ResultsApproximately 722,692 (7.78%) out of 92,899,685 annual ED visits represented ESRD patients. Males were more likely to be ESRD patients than females (aOR: 1.34; 95% CI: 1.09–1.66). Compare to whites, non-Hispanic Blacks were 2.55 times more likely to have ESRD (aOR: 2.55; 95% CI: 1.97–3.30), and Hispanics were 2.68 times more likely to have ESRD (95% CI: 1.95–3.69). ED patients with ESRD were more likely to be admitted to the hospital (aOR: 2.70; 95% CI: 2.13–3.41) and intensive care unit (ICU) (aOR: 2.21; 95% CI: 1.45–3.38) than patients without ESRD. ED patients with ESRD were more likely to receive blood tests and get radiology tests.ConclusionWe described the unique demographic, socioeconomic, and clinical characteristics of ED patients with ESRD, using the most comprehensive, nationally representative study to date. These patients’ higher hospital and ICU admission rates indicate that patients with ESRD require a higher level of emergency care.
A community-based nurse-led medication self-management intervention in the improvement of medication adherence in older patients with multimorbidity: protocol for a randomised controlled trial
Authors: Yang Chen , Hui Zhaozhao , Zeng Dejian , Zhu Song , Wang Xiuhua , Lee Diana Tze Fan , Chair Sek Ying 
Published: March 2021

Abstract
Background
Older patients suffering from multimorbidity are at high risk of medication nonadherence. It has been well established that self-management support is an effective strategy to enhance medication adherence for patients with chronic conditions. However, little is known about the effect of the medication self-management intervention in older patients with multimorbidity. This paper presents the protocol for a study that aims to evaluate the effectiveness of a nurse-led medication self-management intervention in improving medication adherence and health outcomes for community-dwelling older patients with multimorbidity.

Methods
The study protocol follows the recommendations of the Standard Protocol Items: Recommendations for Interventional Trials 2013 statement. This study is a multicentre, single-blind, two-arm randomised controlled trial. Older patients with multimorbidity will be recruited from three community health centres in Changsha, China. A total of 136 participants will be randomly allocated to receive usual care or usual care plus the medication self-management intervention. The intervention will be delivered by community nurses. The 6-week intervention includes three face-to-face education sessions and two weekly follow-up phone calls. Participants in the control group continue to receive all respects of usual care offered by community healthcare providers, including chronic disease management, drug prescription, referral to hospital specialists, health education and consultations regarding patients’ diseases and treatments during centre visits. The primary outcome is medication adherence as measured by the 5-item Medication Adherence Report Scale. Secondary outcomes include medication self-management capacity (medication knowledge, medication beliefs, medication social support, medication skills, and medication self-efficacy), treatment experiences (medication treatment satisfaction and treatment burden), quality of life, and utilisation of healthcare services. All outcomes will be measured at baseline, immediately post-intervention, and at 3-month post-intervention.

Discussion
This study will provide evidence about the effectiveness of a medication self-management intervention, delivered by nurses, for older patients with multimorbidity and adherence problems. It is expected that the results of the study, if proven effective in improving patients’ adherence and health outcomes, will provide evidence-based self-management support strategies for healthcare providers in routine chronic disease management in community settings.

Trial registration
The trial is registered at ChiCTR.org.cn (ChiCTR2000030011; date February 19, 2020).
Case report: exome sequencing achieved a definite diagnosis in a Chinese family with muscle atrophy
Authors: Jiang Hui , Guo Chunmiao , Xie Jie , Pan Jingxin , Huang Ying , Li Miaoxin , Guo Yibin 
Published: March 2021

AbstractBackgroundDue to large genetic and phenotypic heterogeneity, the conventional workup for Charcot-Marie-Tooth (CMT) diagnosis is often underpowered, leading to diagnostic delay or even lack of diagnosis. In the present study, we explored how bioinformatics analysis on whole-exome sequencing (WES) data can be used to diagnose patients with CMT disease efficiently.Case presentationThe proband is a 29-year-old female presented with a severe amyotrophy and distal skeletal deformity that plagued her family for over 20 years since she was 5-year-old. No other aberrant symptoms were detected in her speaking, hearing, vision, and intelligence. Similar symptoms manifested in her younger brother, while her parents and her older brother showed normal. To uncover the genetic causes of this disease, we performed exome sequencing for the proband and her parents. Subsequent bioinformatics analysis on the KGGSeq platform and further Sanger sequencing identified a novel homozygousGDAP1nonsense mutation (c.218C > G, p.Ser73*) that responsible for the family. This genetic finding then led to a quick diagnosis of CMT type 4A (CMT4A), confirmed by nerve conduction velocity and electromyography examination of the patients.ConclusionsThe patients with severe muscle atrophy and distal skeletal deformity were caused by a novel homozygous nonsense mutation inGDAP1(c.218C > G, p.Ser73*), and were diagnosed as CMT4A finally. This study expanded the mutation spectrum of CMT disease and demonstrated how affordable WES could be effectively employed for the clinical diagnosis of unexplained phenotypes.
Pseudomembranous conjunctivitis with hand, foot and mouth disease in a pregnant woman : a case report
Authors: Kim Yoo Jin , Kim Tae Gi 
Published: March 2021

Abstract
Background
Hand, foot, and mouth disease (HFMD) is a common systemic infection that is caused by an enterovirus, normally Coxsackie A16. Generally, it affects children or immunocompromised adults. Only a few reports have described pseudomembranous conjunctivitis associated with HFMD. We aim to describe the clinical outcomes and ocular findings of a 37-year-old female with HFMD and concurrent severe pseudomembranous conjunctivitis, who was 28 weeks pregnant.

Case presentation
A female patient who was 28-weeks pregnant was referred for an ophthalmological review due to pain and injection in both eyes. The patient was hospitalized under obstetrics and gynecology and evaluated for Behcet’s disease with oral and perineal ulcers. In an ophthalmic examination, both eyes were observed to have a conjunctival injection. Behcet’s disease-associated conjunctivitis was diagnosed. Topical steroids and antibiotics were administered every 6 h. Two days after her presentation, a maculopapular eruption occurred on her palms. Enterovirus type 71 was detected in a serum virus antibody test, and the patient was diagnosed with HFMD. After 7 days, severe pseudomembranous conjunctivitis and corneal epithelial defects occurred in both eyes. Topical steroids were administered every 3 h, and the pseudomembrane was removed every 2 to 3 days. The pseudomembrane did not occur after 3 weeks, but corneal erosion persisted. After 3 months, the corneal erosion had completely resolved.

Conclusions
HFMD-associated conjunctivitis is a rare complication in adults, however it can appear as a severe pseudomembranous conjunctivitis. In this case, the removal of the pseudomembrane and topical steroids helped improve the symptoms.
Study protocol: a multicenter, uncontrolled, open-label study of palivizumab in neonates, infants, and preschool children at high risk of severe respiratory syncytial virus infection
Authors: Mori Masaaki , Watabe Shinichi , Taguchi Tomoaki , Hasegawa Hisaya , Ishige Mika , Tanuma Naoyuki , Hirakawa Akihiro , Koike Ryuji , Kusuda Satoshi 
Published: March 2021

Abstract
Background
The prophylactic use of anti-respiratory syncytial virus (RSV) antibody (palivizumab) for severe RSV infection is not approved in Japan in specified groups of infants with neuromuscular diseases or other rare diseases associated with reduced ventilation competence or difficulty in expectoration, which increase the risk of exacerbation of severe RSV infection. The objective of this study is to investigate the efficacy, safety, and pharmacokinetics of palivizumab in pediatric patients with those rare diseases for which palivizumab is not indicated at present.

Methods/design
This study is a multicenter, uncontrolled, open-label study planned to be carried out between July 1, 2019 and June 30, 2022 at 7 medical institutions in Japan. The study population will be recruited from among neonates, infants, or children aged 24 months or younger with a condition falling under any of the following 5 disease groups: pulmonary hypoplasia, airway stenosis, congenital esophageal atresia, inherited metabolic disease, or neuromuscular disease. The planned sample size is 18 subjects, including at least 3 subjects per disease group. Throughout the RSV season, at least 4 continuous doses of palivizumab will be administered intramuscularly at 15 mg/kg at intervals of 30 days. The efficacy and safety of palivizumab will be comprehensively evaluated based on the incidence of RSV-related hospitalization, and serum palivizumab concentration, serum anti-palivizumab antibody concentration, and the occurrence of adverse events/reactions after the start of palivizumab treatment.

Discussion
This study will evaluate the efficacy and safety of palivizumab in pediatric patients with rare diseases which place them at high risk of severe RSV infection, but which fall outside the current indications for palivizumab prophylaxis. The generated data will have implications for the regulatory approval of prophylactic palivizumab treatment in this patient group.

Trial registration
This study has been prospectively registered in Japic Clinical Trials Information, which is managed and administered by the Japan Pharmaceutical Information Center (registration number: JapicCTI-194946, registration date: September 10, 2019).
Validation of a three-item Fatigue Severity Scale for patients with substance use disorder: a cohort study from Norway for the period 2016–2020
Authors:   for the INTRO-HCV Study Group, Vold Jørn Henrik , Gjestad Rolf , Aas Christer F. , Meland Eivind , Johansson Kjell Arne , Fadnes Lars Thore 
Published: March 2021

Abstract
Background
Little attention has been paid to customising fatigue questionnaires for patients with Substance Use Disorders (SUDs). The present study aims to validate and shorten the nine-item Fatigue Severity Scale (FSS-9) and Visual Analogue Fatigue Scale (VAFS) for use with this population.

Methods
We used data from a nested cohort with annual health assessments with responses on the FSS-9 and VAFS. During the period 2016–2020, 917 health assessments were collected from 655 patients with SUD in Bergen and Stavanger, Norway. A total of 225 patients answered the health assessment at least twice. We defined baseline as the first annual health assessment when the health assessments were sorted chronologically per patient. We checked for internal consistency, and we used longitudinal confirmatory factor analysis (CFA) and linear mixed model (LMM) analysis to validate and shorten the FSS-9 and VAFS.

Results
The internal consistency of the FSS-9 was excellent with a Cronbach’s α of 0.94 at baseline and 0.93 at the second annual health assessment. When shortening the FSS-9 to a three-item FSS (FSS-3, items 5–7), the Cronbach’s α was 0.87 at baseline and 0.84 at the second health assessment. The internal consistency was not affected when the VAFS was added to the FSS-3 and the FSS-9. The longitudinal CFA model showed a well-fitting model for the FSS-3 (χ2 = 13.33, degree of freedom = 8, P = 0.101). The LMM analysis showed equal linear changes at the individual level for the FSS-3 (slope: 0.00, P > 0.05) and FSS-9 (slope: 0.01, P > 0.05) between the health assessments.

Conclusion
The FSS-9 could be shortened to the FSS-3 with high validity and reliability for patients with SUDs and the addition of VAFS did not provide much added variability.
Microendoscopy-assisted extraforaminal lumbar interbody fusion for treating single-level spondylodesis
Authors: Shibayama Motohide , Li Guang Hua , Zhu Li Guo , Ito Zenya , Ito Fujio 
Published: March 2021

AbstractBackgroundLumbar interbody fusion is a standard technique for treating degenerative lumbar disorders involving instability. Due to its invasiveness, a minimally invasive technique, extraforaminal lumbar interbody fusion (ELIF), was introduced. On surgically approaching posterolaterally, the posterior muscles and spinal canal are barely invaded. Despite its theoretical advantage, ELIF is technically demanding and has not been popularised. Therefore, we developed a microendoscopy-assisted ELIF (mELIF) technique which was designed to be safe and less invasive. Here, we aimed to report on the surgical technique and clinical results.MethodsUsing a posterolateral approach similar to that of lateral disc herniation surgery, a tubular retractor, 16 or 18 mm in diameter, was placed at the lateral aspect of the facet joint. The facet joint was partially excised, and the disc space was cleaned. A cage and local bone graft were inserted into the disc space. All disc-related procedures were performed under microendoscopy. The spinal canal was not invaded. Bilateral percutaneous screw-rod constructs were inserted and fixed.ResultsFifty-five patients underwent the procedure. The Oswestry Disability Index and visual analogue scale scores greatly improved. Over 90% of the patients obtained excellent or good results based on Macnab’s criteria. There were neither major adverse clinical effects nor the need for additional surgery.ConclusionsmELIF is minimally invasive because the spinal canal and posterior muscles are barely invaded. It produces good clinical results with fewer complications. This technique can be applied in most single-level spondylodesis cases, including those involving L5/S1 disorders.