Pitfalls and perils of survival analysis under incorrect assumptions: the case of Covid-19 data

Non-parametric survival analysis has become a very popular statistical method in current medical research. Employing, however, survival methodology when its fundamental assumptions are not fulfilled can severely bias the results. Currently, hundreds of clinical studies are using survival methods to investigate factors potentially associated with the prognosis of Corona Virus Disease 2019 (Covid-19), and test new preventive and therapeutic strategies. In the pandemic era, it is more critical than ever that decision-making is evidence-based and relies on solid statistical methods. However, this is not always the case. Serious methodologic errors have been identified in recent seminal studies about Covid-19: one reporting outcomes of patients treated with remdesivir, and another one on the epidemiology, clinical course and outcomes of critically-ill patients. High-quality evidence is essential to inform clinicians about optimal Covid-19 therapies, and policymakers about the true effect of preventive measures aiming to tackle the pandemic. Though timely evidence is needed, we should encourage the appropriate application of survival analysis methods and careful peer-review to avoid publishing flawed results, which could affect decision-making. In this paper, we recapitulate the basic assumptions underlying non-parametric survival analysis and frequent errors in its application, and discuss how to handle data of Covid-19.

Internet of things-based energy-efficient optimized heuristic framework to monitor sportsperson’s health

BACKGROUND: Recently, wearable technologies have gained attention in diverse applications of the medical platform to guarantee the health and safety of the sportsperson with the assistance of the Internet of things (IoT) device. The IoT device’s topology varies due to the shift in users’ orientation and accessibility, making it impossible to assign resources, and routing strategies have been considered the prominent factor in the current medical research. Further, for sportspersons with sudden cardiac arrests, hospital survival rates are low in which wearable IoT devices play a significant role. OBJECTIVE: In this paper, the energy efficient optimized heuristic framework (EEOHF) has been proposed and implemented on a wearable device of the sportsperson’s health monitoring system. METHOD: The monitoring system has been designed with cloud assistance to locate the nearest health centers during an emergency. The wearable sensor technologies have been used with an optimized energy-efficient algorithm that helps athletes monitor their health during physical workouts. The monitoring system has fitness tracking devices, in which health information is gathered, and workout logs are tracked using EEOHF. The proposed method is applied to evaluate and track the sportsperson’s fitness based on case study analysis. RESULTS: The simulation results have been analyzed, and the proposed EEOHF achieves a high accuracy ratio of 97.8%, a performance ratio of 95.3%, and less energy consumption of 9.4%, delay of 13.1%, and an average runtime of 98.2% when compared to other existing methods.

Diabetes Mellitus and Renal Function: Current Medical Research and Opinion

Abstract:: Diabetes mellitus (DM) which is defined as high blood glucose level is a major public health worldwide. While discussing DM, the knowledge in this field is unlimited hence a syndrome that populations are living with for more than a decade is always an important matter to keep searching for updates on it. Challenges are always present in different means as comorbidities, poorly controlled DM especially type 2 Diabetes mellitus(T2DM) is considered as a risk factor for a lot of different diseases including but not limited to chronic kidney Disease (CKD). Complications might appear through time, as the aging process changes the body functions, while a significant number of antidiabetic medications are cleared eventually by the kidney; this increase the burden on kidney function placing the diabetic patients at risk. The significant high number of patients with uncontrolled diabetes resulting with kidney disease mirror the importance of this condition on patient’s quality of life. This review presents an overview, pathophysiology, etiology and prevalence of Chronic Kidney Disease (CKD) and abnormal renal parameters correlated with poorly controlled T2DM, with emphasis on and clinical studies involving the association between vitamin D Insufficiency/Deficiency and chronic kidney disease among patients with T2DM.

Prediction of Anti-COVID 19 Therapeutic Power of Medicinal Moroccan Plants Using Molecular Docking

The emerging pathogen SARS-CoV2 causing coronavirus disease 2019 (COVID-19) is a global public health challenge. To the present day, COVID-19 had affected more than 40 million people worldwide. The exploration and the development of new bioactive compounds with cost-effective and specific anti-COVID 19 therapeutic power is the prime focus of the current medical research. Thus, the exploitation of the molecular docking technique has become essential in the discovery and development of new drugs, to better understand drug-target interactions in their original environment. This work consists of studying the binding affinity and the type of interactions, through molecular docking, between 54 compounds from Moroccan medicinal plants, dextran sulfate and heparin (compounds not derived from medicinal plants), and 3CLpro-SARS-CoV-2, ACE2, and the post fusion core of 2019-nCoV S2 subunit. The PDB files of the target proteins and prepared herbal compounds (ligands) were subjected for docking to AutoDock Vina using UCSF Chimera, which provides a list of potential complexes based on the criteria of form complementarity of the natural compound with their binding affinities. The results of molecular docking revealed that Taxol, Rutin, Genkwanine, and Luteolin-glucoside have a high affinity with ACE2 and 3CLpro. Therefore, these natural compounds can have 2 effects at once, inhibiting 3CLpro and preventing recognition between the virus and ACE2. These compounds may have a potential therapeutic effect against SARS-CoV2, and therefore natural anti-COVID-19 compounds.

Medicine and Phlebolymphology: Time to Change?

Biomedical science is undergoing a reappraisal of its scientific advancement process and of the related healthcare management. Progress in medicine should combine improvements of knowledge, efficacy, and safety of diagnostic/therapeutic procedures, with adequate cost-effectiveness profiles. This narrative review is aimed at assessing in medicine, more specifically in phlebology and lymphology: (a) scientific literature possible biases, (b) the level of evidence, comprehensiveness, and cost-effectiveness of the main therapeutic options, and (c) the possible contribution of integrative and translational medicine. Current medical research may have cognitive biases, or industry-tied influences, which impacts clinical practice. Some reductionism, with an increasing use of drugs and technology, often neglecting the understanding and care of the root causative pathways of the diseases, is affecting biomedical science as well. Aging brings a relevant burden of chronic degenerative diseases and disabilities, with relevant socio-economic repercussions; thus, a major attention to cost-effectiveness and appropriateness of healthcare is warranted. In this scenario, costly and innovative but relatively validated therapies may tend to be adopted in venous and lymphatic diseases, such as varicose veins, leg venous ulcer, post-thrombotic syndrome, pelvic congestion syndrome, and lymphedema. Conversely, a more comprehensive approach to the basic pathophysiology of chronic venous and lymphatic insufficiency and the inclusion of pharmacoeconomics analyses would benefit overall patients’ management. Erroneous lifestyle and nutrition, together with chronic stress-induced syndromes, significantly influence chronic degenerative phlebo-lymphatic diseases. The main active epigenetic socio-biologic factors are obesity, dysfunctions of musculo-respiratory-vascular pumps, pro-inflammatory nutrition, hyperactivation of stress axis, and sedentarism. An overall critical view of the scientific evidence and innovations in phebolymphology could be of help to improve efficacy, safety, and sustainability of current practice. Translational and integrative medicine may contribute to a patient-centered approach. Conversely, reductionism, eminence/reimbursement-based decisional processes, patients’ lack of education, industry-influenced science, and physician’s improvable awareness, may compromise efficacy, safety, appropriateness, and cost-effectiveness of future diagnostic and therapeutic patterns of phlebology and lymphology.

The Characteristic of Virulence, Biofilm and Antibiotic Resistance of Klebsiella pneumoniae

Klebsiella pneumoniae is an important gram-negative opportunistic pathogen that causes a variety of infectious diseases, including urinary tract infections, bacteremia, pneumonia, and liver abscesses. With the emergence of multidrug-resistant (MDR) and hypervirulent K. pneumoniae (hvKP) strains, the rapid spread of these clinical strains in geography is particularly worrying. However, the detailed mechanisms of virulence and antibiotic resistance in K. pneumoniae are still not very clear. Therefore, studying and elucidating the pathogenic mechanisms and drug resistance mechanism of K. pneumoniae infection are important parts of current medical research. In this paper, we systematically summarized the virulence, biofilm, and antibiotic tolerance mechanisms of K. pneumoniae, and explored the application of whole genome sequencing and global proteomics, which will provide new clues for clinical treatment of K. pneumoniae.

PARE0019 DON’T DELAY - TIME2WORK

Background:Employment process of people with RMD is very sensitive and tough subject, especially in Republic of Serbia. For people with RMD it is very hard to get employed or to find a suitable job. Based on study 33% of the total health care costs was allocated to employers.Objectives:Raise awareness about employment of people with RMDs and identify barriers and bottlenecks of the process of employment. Connect with all relevant stakeholders and figure out a way to ease the whole process of employment.Methods:A round of surveys were conducted, one for employers and the other for people with RMDs.A round table was organized with participants from various relevant institutions.A series of articles were published online and in writing. A series of interviews were emitted on various TV stations.Results:Total of 136 persons with RMD took the survey and a total of 75 companies took the survey for employers.56.7% are employed. 31% of people with RMDs that took the survey said that they did not get the job because they have RMD. 37.1% are missing from work just when they are feeling really bad. 87.1% are open for prequalification and retraining. 90% is not familiar with process of qualifying for disability act. 42.60% are looking for a job via Internet. 45% does not get help at the workplace from their colleague when they are not feeling well. 42.3% met the difficulty of employer not understanding disease and it’s forecast. 39.7% does not get any feedback after interview. 40% of employers are not familiar with benefits from the state when employing person with disability act. 68% have not used any benefit provided by state. 2/3 of employers are giving advantage to work experience and probation impression over other when deciding about employment of person. Active communication between round table participants and our organization. Employment brochure, digital and hard copies.Conclusion:People with RMDs are more than interested and willing to take courses and prequalification in order to get employed. More than half that are not employed at the moment are actively seeking for a job opportunity. Employers are willing to employ people with RMDs and also send them for prequalification. They are not familiar with benefits that they can get when employing person with RMD. More than 2/3 of employers that took the survey stated number of benefits that they would see fit them when employing person with disability act, and 95% of those benefits are already on benefit list provided by Republic of Serbia. If more people with RMDs are employed causes less health care cost to the state, more funds for new medicines, more people on innovative drugs, which results in more people getting employed. The other thing that needs raise of awareness is the process of getting act of disability, since people with RMD in Serbia are not familiar with it.References:[1]H. Birnbaum, C. Pike, R. Kaufman, M. Marynchenko, Y. Kidolezi, & M. Cifaldi, (2010). Societal cost of rheumatoid arthritis patients in the US. Current Medical Research & Opinionhttps://www.ncbi.nlm.nih.gov/pubmed/19908947Disclosure of Interests:None declared

Consistent gene signature of schizophrenia identified by a novel feature selection strategy from comprehensive sets of transcriptomic data

The etiology of schizophrenia (SCZ) is regarded as one of the most fundamental puzzles in current medical research, and its diagnosis is limited by the lack of objective molecular criteria. Although plenty of studies were conducted, SCZ gene signatures identified by these independent studies are found highly inconsistent. As one of the most important factors contributing to this inconsistency, the feature selection methods used currently do not fully consider the reproducibility among the signatures discovered from different datasets. Therefore, it is crucial to develop new bioinformatics tools of novel strategy for ensuring a stable discovery of gene signature for SCZ. In this study, a novel feature selection strategy (1) integrating repeated random sampling with consensus scoring and (2) evaluating the consistency of gene rank among different datasets was constructed. By systematically assessing the identified SCZ signature comprising 135 differentially expressed genes, this newly constructed strategy demonstrated significantly enhanced stability and better differentiating ability compared with the feature selection methods popular in current SCZ research. Based on a first-ever assessment on methods’ reproducibility cross-validated by independent datasets from three representative studies, the new strategy stood out among the popular methods by showing superior stability and differentiating ability. Finally, 2 novel and 17 previously reported transcription factors were identified and showed great potential in revealing the etiology of SCZ. In sum, the SCZ signature identified in this study would provide valuable clues for discovering diagnostic molecules and potential targets for SCZ.

A Multifunctional Graphene Oxide Platform for Targeting Cancer

Diagnosis of oncological diseases remains at the forefront of current medical research. Carbonic Anhydrase IX (CA IX) is a cell surface hypoxia-inducible enzyme functionally involved in adaptation to acidosis that is expressed in aggressive tumors; hence, it can be used as a tumor biomarker. Herein, we propose a nanoscale graphene oxide (GO) platform functionalized with magnetic nanoparticles and a monoclonal antibody specific to the CA IX marker. The GO platforms were prepared by a modified Hummers and Offeman method from exfoliated graphite after several centrifugation and ultrasonication cycles. The magnetic nanoparticles were prepared by a chemical precipitation method and subsequently modified. Basic characterization of GO, such as the degree of oxidation, nanoparticle size and exfoliation, were determined by physical and chemical analysis, including X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), energy dispersive X-ray analysis (EDX), and atomic force microscopy (AFM). In addition, the size and properties of the poly-L-lysine-modified magnetic nanoparticles were characterized. The antibody specific to CA IX was linked via an amidic bond to the poly-L-lysine modified magnetic nanoparticles, which were conjugated to GO platform again via an amidic bond. The prepared GO-based platform with magnetic nanoparticles combined with a biosensing antibody element was used for a hypoxic cancer cell targeting study based on immunofluorescence.

Benchmarking of 4C-seq pipelines based on real and simulated data

Motivation With its capacity for high-resolution data output in one region of interest, chromosome conformation capture combined with high-throughput sequencing (4C-seq) is a state-of-the-art next-generation sequencing technique that provides epigenetic insights, and regularly advances current medical research. However, 4C-seq data are complex and prone to biases, and while specialized programs exist, an unbiased, extensive benchmarking is still lacking. Furthermore, neither substantial datasets with fully characterized ground truth, nor simulation programs for realistic 4C-seq data have been published. Results We conducted a benchmarking study on 66 4C-seq samples from 20 datasets, and developed a novel 4C-seq simulation software, Basic4CSim, to allow for detailed comparisons of 4C-seq algorithms on 50 simulated datasets with 10–120 samples each. Simulations and benchmarking were adapted to address different characteristics of 4C-seq data. Simulated data were compared with published samples to validate simulation settings. We identified differences between 4C-seq algorithms in terms of precision, recall, interaction structure, and run time, and observed general trends. Novel differential pipeline versions of single-sample based 4C-seq algorithms were included in the benchmarking. While no single tool was optimally suited for both near-cis and far-cis, and both single-sample and differential analyses, choosing a high-performing algorithm variant did improve results considerably. For near-cis scenarios, r3Cseq, peakC and FourCSeq offered high precision, while fourSig demonstrated high overall F1 scores in far-cis analyses. Finally, 4C-seq simulations may aid in the development of improved analysis algorithms. Availability and implementation Basic4CSim is available at https://github.com/walter–ca/Basic4CSim. Supplementary information Supplementary data are available at Bioinformatics online.