Corrigendum to "Recognition motifs for importin 4 [(L)PPRS(G/P)P] and importin 5 [KP(K/Y)LV] binding, identified by bio-informatic simulation and experimental in vitro validation" [Comput Struct Biotechnol J 20 (2022) 5952-5961]

Nuclear translocation of large proteins is mediated through karyopherins, carrier proteins recognizing specific motifs of cargo proteins, known as nuclear localization signals (NLS). However, only few NLS signals have been reported until now. In the present work, NLS signals for Importins 4 and 5 were identified through an unsupervised in silico approach, followed by experimental in vitro validation. The sequences LPPRS(G/P)P and KP(K/Y)LV were identified and are proposed as recognition motifs for Importins 4 and 5 binding, respectively. They are involved in the trafficking of important proteins into the nucleus. These sequences were validated in the breast cancer cell line T47D, which expresses both Importins 4 and 5. Elucidating the complex relationships of the nuclear transporters and their cargo proteins is very important in better understanding the mechanism of nuclear transport of proteins and laying the foundation for the development of novel therapeutics, targeting specific importins

Multiple sclerosis registries in Europe – An updated mapping survey

Highlights Nineteen questionnaires from European MS registries were analysed. Aim and focus as well as number of patients and inclusion criteria vary considerably. Most of the MS registries collect data within common general categories. There are more pronounced differences regarding specific subcategories

Association of glucose variability at the last day of hospitalization with 30-day readmission in adults with diabetes

Objective To evaluate whether increased glucose variability (GV) during the last day of inpatient stay is associated with increased risk of 30-day readmission in patients with diabetes.Research design and methods A comprehensive list of clinical, pharmacy and utilization files were obtained from the Veterans Affairs (VA) Central Data Warehouse to create a nationwide cohort including 1 042 150 admissions of patients with diabetes over a 14-year study observation period. Point-of-care glucose values during the last 24 hours of hospitalization were extracted to calculate GV (measured as SD and coefficient of variation (CV)). Admissions were divided into 10 categories defined by progressively increasing SD and CV. The primary outcome was 30-day readmission rate, adjusted for multiple covariates including demographics, comorbidities and hypoglycemia.Results As GV increased, there was an overall increase in the 30-day readmission rate ratio. In the fully adjusted model, admissions with CV in the 5th–10th CV categories and admissions with SD in the 4th–10th categories had a statistically significant progressive increase in 30-day readmission rates, compared with admissions in the 1st (lowest) CV and SD categories. Admissions with the greatest CV and SD values (10th category) had the highest risk for readmission (rate ratio (RR): 1.08 (95% CI 1.05 to 1.10), p<0.0001 and RR: 1.11 (95% CI 1.09 to 1.14), p<0.0001 for CV and SD, respectively).Conclusions Patients with diabetes who exhibited higher degrees of GV on the final day of hospitalization had higher rates of 30-day readmission.Trial registration number NCT03508934, NCT03877068

Deciphering anti-MOG IgG antibodies: Clinical and radiological spectrum, and comparison of antibody detection assays

IgG antibodies to myelin oligodendrocyte glycoprotein (MOG) detected by cell based assays (CBA) have been identified in a constantly expanding spectrum of CNS demyelinating disorders. However, a universally accepted CBA has not been adopted yet. We aimed to analyze the clinical and radiological features of patients with anti-MOG IgG1-antibodies detected with a live-cell CBA and to compare the three most popular MOG-CBAs. We screened sera from 1300 Greek patients (including 426 patients referred by our 8 clinics) suspected for anti-MOG syndrome, and 120 controls with the live-cell MOG-CBA for IgG1-antibodies. 41 patients, versus 0 controls were seropositive. Clinical, serological and radiological data were available and analyzed for the 21 seropositive patients out of the 426 patients of our clinics. Their phenotypes were: 8 optic neuritis, 3 myelitis, 3 neuromyelitis optica, 2 encephalomyelitis, 2 autoimmune encephalitis and 3 atypical MS. We then retested all sera of our 426 patients with the other two most popular MOG-CBAs for total IgG (a live-cell and a commercial fixed-cell CBAs). Seven IgG1-seropositive patients were seronegative for one or both IgG-CBAs. Yet, all 21 patients had clinical and radiological findings previously described in MOG-antibody associated demyelination disease supporting the high specificity of the IgG1-CBA. In addition, all IgG1-CBA-negative sera were also negative by the IgG-CBAs. Also, all controls were negative by all three assays, except one serum found positive by the live IgG-CBA. Overall, our findings support the wide spectrum of anti-MOG associated demyelinating disorders and the superiority of the MOG-IgG1 CBA over other MOG-CBAs. © 2020 Elsevier B.V

Atrial High-Rate Episodes in Patients with Devices Without a History of Atrial Fibrillation: a Systematic Review and Meta-analysis

Purpose Atrial high-rate episodes (AHREs) recorded with cardiac implantable electronic devices (CIEDs) have been associated with the development of clinical atrial fibrillation (AF) and increase in stroke and death risk. We sought to perform a systematic review with a meta-analysis to evaluate the prevalence of AHREs detected by CIEDs, their association with stroke risk, development of clinical AF, and mortality among patients without a documented history of AF. Methods We searched several databases, ClinicalTrials.gov, references of reviews, and meeting abstract books without any language restrictions up to 9 September 2020. We studied patients with CIEDs in whom AHREs were detected. Exclusion criterion was AF history. Our primary outcome was the risk of ischemic stroke in patients with AHREs. Results We deemed eligible eight studies for the meta-analysis enrolling a total of 4322 patients with CIED and without a documented AF history. The overall AHRE incidence ratio was estimated to be 17.56 (95% CI, 8.61 to 35.79) cases per 100 person-years. Evidence of moderate certainty suggests that patients with documented AHREs were 4.45 times (95% CI 2.87-6.91) more likely to develop clinical AF. Evidence of low confidence suggests that AHREs were associated with a 1.90-fold increased stroke risk (95% CI 1.19-3.05). AHREs were not associated with a statistically significant increased mortality risk. Conclusion The present systematic review and meta-analysis demonstrated that among patients without a documented history of AF, the detection of AHREs by CIEDs was associated with significant increased risk of clinical AF and stroke

Multiple sclerosis registries in Europe – An updated mapping survey

There are significant geographical differences with the highest prevalence occurring in Northern Europe and North America (over 100/100,000) as compared to 2/100,000 in Japan . MS patients are typically diagnosed between the ages of 20 and 50 years and will in most cases be expected to live for a long time with MS. The value of MS registries for MS patients, health care providers and regulators is becoming increasingly recognised . The collection of patient data into a registry can benefit the patients by enabling the clinician to prospectively follow the individual patient concerning disease progression, treatment response and side effects, and other parameters including patient reported outcomes (PRO) measures . From a societal viewpoint there are also many advantages of using data from MS registries, especially within areas of epidemiology and treatment studies, such as post marketing effectiveness, comparative or post-authorisation safety studies . This was recognised by regulatory bodies in the EU resulting in the first EMA-Workshop on MS-Registries in July 2017 in London . Therefore it is important to improve and promote the collection of safety data by MS registries as this might provide an opportunity for the MS registries to replace the typical drug specific post-authorization safety studies