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Nevin Manimala Statistics

Quantum processor-inspired machine learning in the biomedical sciences

Patterns (N Y). 2021 Apr 28;2(6):100246. doi: 10.1016/j.patter.2021.100246. eCollection 2021 Jun 11.

ABSTRACT

Recent advances in high-throughput genomic technologies coupled with exponential increases in computer processing and memory have allowed us to interrogate the complex molecular underpinnings of human disease from a genome-wide perspective. While the deluge of genomic information is expected to increase, a bottleneck in conventional high-performance computing is rapidly approaching. Inspired by recent advances in physical quantum processors, we evaluated several unconventional machine-learning (ML) strategies on actual human tumor data, namely “Ising-type” methods, whose objective function is formulated identical to simulated annealing and quantum annealing. We show the efficacy of multiple Ising-type ML algorithms for classification of multi-omics human cancer data from The Cancer Genome Atlas, comparing these classifiers to a variety of standard ML methods. Our results indicate that Ising-type ML offers superior classification performance with smaller training datasets, thus providing compelling empirical evidence for the potential future application of unconventional computing approaches in the biomedical sciences.

PMID:34179840 | PMC:PMC8212142 | DOI:10.1016/j.patter.2021.100246

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Nevin Manimala Statistics

Repeats expansions in ATXN2, NOP56, NIPA1 and ATXN1 are not associated with ALS in Africans

IBRO Neurosci Rep. 2021 Feb 10;10:130-135. doi: 10.1016/j.ibneur.2021.02.002. eCollection 2021 Jun.

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized primarily by progressive loss of motor neurons. Although ALS occurs worldwide and the frequency and spectrum of identifiable genetic causes of disease varies across populations, very few studies have included African subjects. In addition to a hexanucleotide repeat expansion (RE) in C9orf72, the most common genetic cause of ALS in Europeans, REs in ATXN2, NIPA1 and ATXN1 have shown variable associations with ALS in Europeans. Intermediate range expansions in some of these genes (e.g. ATXN2) have been reported as potential risk factors, or phenotypic modifiers, of ALS. Pathogenic expansions in NOP56 cause spinocerebellar ataxia-36, which can present with prominent motor neuron degeneration. Here we compare REs in these genes in a cohort of Africans with ALS and population controls using whole genome sequencing data. Targeting genotyping of short tandem repeats at known loci within ATXN2, NIPA1, ATXN1 and NOP56 was performed using ExpansionHunter software in 105 Southern African (SA) patients with ALS. African population controls were from an in-house SA population control database (n = 25), the SA Human Genome Program (n = 24), the Simons Genome Diversity Project (n = 39) and the Illumina Polaris Diversity Cohort (IPDC) dataset (n = 50). We found intermediate RE alleles in ATXN2 (27-33 repeats) and ATXN1 (33-35 repeats), and NIPA1 long alleles (≥8 repeats) were rare in Africans, and not associated with ALS (p > 0.17). NOP56 showed no expanded alleles in either ALS or controls. We also compared the differences in allele distributions between the African and n = 50 European controls (from the IPDC). There was a statistical significant difference in the distribution of the REs in the ATXN1 between African and European controls (Chi-test p < 0.001), and NIPA1 showed proportionately more longer alleles (RE > 8) in Europeans vs. Africans (Fisher’s p = 0.016). The distribution of RE alleles in ATXN2 and NOP56 were similar amongst African and European controls. In conclusion, repeat expansions in ATXN2, NIPA1 and ATXN1, which showed associations with ALS in Europeans, were not replicated in Southern Africans with ALS.

PMID:34179866 | PMC:PMC8211917 | DOI:10.1016/j.ibneur.2021.02.002

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Nevin Manimala Statistics

Morphological and Fitness Attributes of Young Male Portuguese Basketball Players: Normative Values According to Chronological Age and Years From Peak Height Velocity

Front Sports Act Living. 2021 Jun 10;3:629453. doi: 10.3389/fspor.2021.629453. eCollection 2021.

ABSTRACT

The aims of the present study were: (i) to describe the structural and functional attributes of young male Portuguese basketball players aged 12-16 years and (ii) to generate normative data according to chronological age and years from peak height velocity. A total of 281 male Portuguese young basketball players between the ages of 12 and 16 years were assessed in this study. Chronological age, maturity parameters (maturity offset and predicted age at peak height velocity), morphological (body mass, height, and skinfolds and length), and fitness (sprint, change of direction ability, jump, and upper body strength) attributes were measured. Descriptive statistics were determined for the age and maturity status, and the 10th, 25th, 50th, 75th, and 90th percentiles were chosen as reference values. Descriptive and normative values of the players’ morphological and fitness attributes, stratified by age and maturity status, are provided. The normative values of age at peak height velocity (category YAPHV = 0) showed that regional basketball players presented average values (50th percentile) of 169.8 cm for height, 173.3 cm for arm span, 55.6 kg for body mass, 3.34 s for the 20-m speed test, 10.31 s for the T-test, 4.75 m for the 2-kg medicine ball throw, 66.9 kg for the combined right and left handgrip strength, and 30.1 and 35.9 cm for jump height in the countermovement jump (CMJ) and CMJ with arm swing, respectively. In conclusion, these results may be helpful to quantify and control an athlete’s performance over time and to adjust strength and conditioning programs to biological demands.

PMID:34179772 | PMC:PMC8222820 | DOI:10.3389/fspor.2021.629453

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Nevin Manimala Statistics

CoviChain: A Blockchain Based Framework for Nonrepudiable Contact Tracing in Healthcare Cyber-Physical Systems During Pandemic Outbreaks

SN Comput Sci. 2021;2(5):346. doi: 10.1007/s42979-021-00746-x. Epub 2021 Jun 20.

ABSTRACT

With the world facing the new virus SARS-CoV-2, many countries have introduced instant Internet applications to identify people carrying the infection. Internet-of-Medical-Things (IoMT) have proven useful in collecting medical data as well in tracing an individual carrying the virus. The data collected or traced belongs to an individual and should be revealed to themselves and hospital providers, but not to any third-party unauthorized agencies. In this paper we use an off-chain distributed storage solution for loading large medical data sets and a blockchain implementation to securely transfer the data from the infected person to the hospital system using the edge infrastructure, and call it CoviChain. The Coronavirus Disease (COVID-19) statistics are loaded on to the edge, and moved to InterPlanetary File Systems (IPFS) storage to retrieve the hash of the data file. Once the hash is obtained, it is moved to the blockchain by means of smart contracts. As the information is being hashed twice, CoviChain addresses the security and privacy issues and avoid exposing individuals’ data while achieving larger data storage on the blockchain with reduced cost and time.

PMID:34179827 | PMC:PMC8214843 | DOI:10.1007/s42979-021-00746-x

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Nevin Manimala Statistics

Phase IIB Randomized Trial on the Use of 4-Aminopyridine in Guillain-Barré Syndrome

Arch Rehabil Res Clin Transl. 2021 Apr 8;3(2):100123. doi: 10.1016/j.arrct.2021.100123. eCollection 2021 Jun.

ABSTRACT

OBJECTIVE: To determine the safety and efficacy of orally delivered 4-aminopyridine (4-AP) in persons with Guillain-Barré Syndrome (GBS) >6 months from initial diagnosis.

DESIGN: A randomized, double-blind, placebo-controlled, crossover study.

SETTING: Tertiary care clinical outpatient program.

PARTICIPANTS: Nineteen participants enrolled (14 male, 5 female; N=19), neurologic impairment secondary to GBS and functional loss on the FIM motor score (stable for ≥12mo) and >3.0 but <5.0 on the American Spinal Injury motor scale. Twelve participants (mean age, 59y; range, 23-77y) completed the study.

INTERVENTIONS: A 4-AP dose-escalation study with 8 weeks in each period with a 3-week washout period, followed by 3 months open-label follow-up.

MAIN OUTCOME MEASURES: FIM motor score was the primary outcome measure; also evaluated were the American Spinal Injury motor strength score (all limbs), handheld dynamometer, 6-minute walk test, Medical Outcomes Study 12-Item Short Form, Center for Epidemiological Studies Depression scale, Positive and Negative Affect Schedule, pain, GBS disability scale, Jepsen-Taylor Hand Function Test, Minnesota Manual Dexterity Test and Minnesota Rate of Manipulation Test, Get Up and Go Test, McGill Pain Inventory, Craig Handicap Assessment and Reporting Technique, and participant self-evaluation.

RESULTS: Seven participants discontinued the study prematurely: 3 because of adverse events, 3 because of travel difficulties or relocation, and 1 because of pretreatment laboratory abnormalities. After removing 3 participants with maximum FIM scores, 4-AP arm trended superior to placebo (P=.065). Patients subjectively could always tell when they were on the active agent usually by tingling sensations or a sense of wellness. No statistically significant differences were found for other outcome measures although there were strong trends.

CONCLUSIONS: This study demonstrates the safety of 4-AP in the patient population with GBS as the predominate goal of the study. A trend toward improved function after treatment was noted with most patients electing to stay on the medication after the trial.

PMID:34179759 | PMC:PMC8212006 | DOI:10.1016/j.arrct.2021.100123

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Nevin Manimala Statistics

Measuring Change in Health Status Over Time (Responsiveness): A Meta-analysis of the SF-36 in Cardiac and Pulmonary Rehabilitation

Arch Rehabil Res Clin Transl. 2021 Apr 10;3(2):100127. doi: 10.1016/j.arrct.2021.100127. eCollection 2021 Jun.

ABSTRACT

OBJECTIVE: The purpose of this meta-analysis is to gather and investigate pooled information on the responsiveness of the main patient outcome measure in cardiac rehabilitation (CR) and pulmonary rehabilitation (PR). The main outcome measure in CR and PR has been found to be the Medical Outcomes Study Short Form-36 health survey (SF-36).

DATA SOURCES: A previous systematic effectiveness review of this literature was used as the basis of this statistical analysis, with the bulk of articles being observational studies.

STUDY SELECTION: This meta-analysis assessed articles on CR that used SF-36 pre and post “within” (per interventional group) mean scores and in the PR literature that used the SF-36 and the Chronic Respiratory Questionnaire (CRQ) “within” change scores.

DATA EXTRACTION: Each group of patients in the chosen literature were taken to represent a single group, so that studies such as randomized controlled trials were listed twice. We undertook a correlation analysis between SF-36 pre and post “within” mean scores in the CR literature. In the PR literature, we undertook a correlation analysis between SF-36 and the CRQ “within” change scores; this involved Spearman correlation coefficients.

DATA SYNTHESIS: The SF-36 Mental Composite Score domain is the most responsive of the composite SF-36 domains, with the Physical Composite Score showing less ability to discriminate in the higher SF-36 scores. In the individual domains, Role Emotional scored r=0.52, P≤.001 with only 27% of the variance explained, and Role Physical with r=0.49, P≤.005 had only 24% of the variance explained. In the PR literature Spearman rank correlation coefficient shows that SF-36 Physical Composite Score has a weaker correlation to the CRQ at 0.39 than the SF-36 Mental Composite Score, which was 0.63.

CONCLUSIONS: This suggests that the SF-36 is not suited as a pre- to postprogram assessment tool for CR and PR. More studies, however, need to be conducted particularly in CR with regard to the responsiveness of the SF-36.

PMID:34179763 | PMC:PMC8211983 | DOI:10.1016/j.arrct.2021.100127

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Nevin Manimala Statistics

Preventing Failures by Dataset Shift Detection in Safety-Critical Graph Applications

Front Artif Intell. 2021 May 18;4:589632. doi: 10.3389/frai.2021.589632. eCollection 2021.

ABSTRACT

Dataset shift refers to the problem where the input data distribution may change over time (e.g., between training and test stages). Since this can be a critical bottleneck in several safety-critical applications such as healthcare, drug-discovery, etc., dataset shift detection has become an important research issue in machine learning. Though several existing efforts have focused on image/video data, applications with graph-structured data have not received sufficient attention. Therefore, in this paper, we investigate the problem of detecting shifts in graph structured data through the lens of statistical hypothesis testing. Specifically, we propose a practical two-sample test based approach for shift detection in large-scale graph structured data. Our approach is very flexible in that it is suitable for both undirected and directed graphs, and eliminates the need for equal sample sizes. Using empirical studies, we demonstrate the effectiveness of the proposed test in detecting dataset shifts. We also corroborate these findings using real-world datasets, characterized by directed graphs and a large number of nodes.

PMID:34179767 | PMC:PMC8223254 | DOI:10.3389/frai.2021.589632

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Nevin Manimala Statistics

Evaluating the Feasibility and Effects of a Short-Term Task Specific Power Training With and Without Cognitive Training Among Older Adults With Slow Gait Speed: A Pilot Study

Arch Rehabil Res Clin Transl. 2021 Mar 9;3(2):100118. doi: 10.1016/j.arrct.2021.100118. eCollection 2021 Jun.

ABSTRACT

OBJECTIVE: To investigate the feasibility and efficacy of short-term functional power training and further examine whether the addition of cognitive training targeting sustained attention and inhibitory control would augment the effect on the outcomes.

DESIGN: Randomized pilot study.

SETTING: Clinical research facility.

PARTICIPANTS: Community-dwelling primary care patients (N=25) aged >65 years with mobility limitation within the VA Boston Healthcare System.

INTERVENTIONS: Participants were randomly assigned to either functional power training (n=14) or functional power+cognitive training (n=11), offered 3 times a week for 6 weeks. Session durations were either 70 minutes (functional power+cognitive training) or 40 minutes (functional power training).

MAIN OUTCOME MEASURES: We evaluated feasibility (dropouts, attendance), mobility performance (Short Physical Performance Battery [SPPB]), leg power [stair climb test]), dynamic balance [figure-of-8], and gait characteristics [gait speed, stance time, step width, swing time, step length, variabilities under single-task and dual-task conditions]). Nonparametric analyses were used to compare overall pre-post changes and between-group differences.

RESULTS: Of the 39 veterans screened, 25 were randomized and enrolled. Twenty-one men with a mean age 76±7 years completed the study; 86% were white. Participants had a mean SPPB score of 8.3±1.6 out of 12. For those completing the study, overall attendance was 79%. Among all participants, clinically relevant and/or statistically significant median change in mobility performance (∆1 point), leg power (∆25.0W), dynamic balance (∆-1.1s), and gait characteristics (gait speed [∆0.08s, ∆0.09s], step length [∆1.9cm, ∆3.8cm], and stance time [∆-0.02s, ∆-0.05s] under single- and dual-task, respectively) were observed after 6 weeks of training. There were no statistically significant group differences in dropouts, attendance rate, or any of the outcomes based on cognitive training status.

CONCLUSIONS: Short-term functional power training with or without a cognitive training led to clinically meaningful improvements in mobility performance, leg power, dynamic balance, and gait characteristics. These findings add to the body of evidence supporting the benefits of functional power training on clinically relevant outcomes. Additional cognitive training did not have an added effect on the study outcomes from our study. Further research is needed.

PMID:34179754 | PMC:PMC8211979 | DOI:10.1016/j.arrct.2021.100118

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Nevin Manimala Statistics

Comparison of the Effects of Physiologic Saline Interfascial and Lidocaine Trigger Point Injections in Treatment of Myofascial Pain Syndrome: A Double-Blind Randomized Controlled Trial

Arch Rehabil Res Clin Transl. 2021 Mar 9;3(2):100119. doi: 10.1016/j.arrct.2021.100119. eCollection 2021 Jun.

ABSTRACT

OBJECTIVE: To compare the effects of physiological saline interfascial and lidocaine trigger point injections in the treatment of myofascial pain syndrome (MPS).

DESIGN: Double-blind randomized controlled study.

SETTING: Department of Rehabilitation Medicine.

PARTICIPANTS: Eighty patients (N=80; 15 men, 65 women; mean age, 40.4±10.9y) with MPS in the upper trapezius muscle.

INTERVENTIONS: Patients were randomly assigned to 1 of 2 groups: group 1 (n=40) received ultrasound-guided interfascial injection with physiological saline, and group 2 (n=40) underwent ultrasound-guided trigger point injection with lidocaine.

MAIN OUTCOME MEASURES: The primary outcome was pain scores measured by the visual analog scale (VAS). Secondary outcomes included cervical range of motion (ROM) and adverse effects of the procedure. The outcomes were assessed before treatment and 10 minutes, 2 weeks, and 4 weeks after treatment.

RESULTS: Lidocaine trigger point injection showed higher VAS score improvement at 10 minutes after the procedure (P=.037). However, there was no statistically significant difference at other follow-up points. Pain scores significantly decreased at 10 minutes, 2 weeks, and 4 weeks from baseline in both groups. Cervical ROM increased significantly over time in some directions without significant differences between the groups. There were no serious adverse effects in this study.

CONCLUSION: Physiologic saline interfascial and lidocaine trigger point injections effectively decreased MPS pain in the upper trapezius muscle at 2 and 4 weeks after treatment. However, lidocaine trigger point injection demonstrated better pain improvement at 10 minutes after treatment.

PMID:34179755 | PMC:PMC8211995 | DOI:10.1016/j.arrct.2021.100119

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Nevin Manimala Statistics

Influence of 25-hydroxy-cholecalciferol levels on SARS-CoV-2 infection and COVID-19 severity: A systematic review and meta-analysis

EClinicalMedicine. 2021 Jul;37:100967. doi: 10.1016/j.eclinm.2021.100967. Epub 2021 Jun 18.

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 19 (COVID-19), a respiratory infection that, starting from December 2019, has spread around the world in a few months, becoming a pandemic. The lack of initial knowledge on its management has led to a great effort in developing vaccines and in finding therapeutic weapons capable of improving the clinical outcome of the affected patients. In particular, the possible role of vitamin D status in the management of COVID-19 has been widely analysed, resulting in a great amount of data. This systematic review and meta-analysis aimed to assess whether hypovitaminosis D is a risk factor for developing SARS-CoV-2 infection and whether it affects the worsening of the clinical course of COVID-19.

METHODS: Data were extracted through extensive searches in the Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases from December 2019 to January 2021, using the keywords: “Vitamin D”, “25 hydroxy Vitamin D”, “25 hydroxycholecalciferol”, “cholecalciferol”, “COVID 19″, “SARS-CoV-2″. We included observational cohort, cross-sectional, and case-control studies that evaluated differences in serum levels of 25‑hydroxy-cholecalciferol [25(OH)D] in patients who were positive or negative for SARS-CoV-2, in patients with mild or severe forms of COVID-19, and in patients who died or were discharged from the hospital. Finally, studies that evaluated the risk of developing severe illness or death in patients with vitamin D deficiency (VDD), defined as levels of 25(OH)D <20 ng/ml, were also included. We calculated the mean difference (MD) and the 95% confidence intervals (CI) for quantitative variables such as 25(OH)D levels in patients with or without SARS-CoV-2 infection, in those with mild vs. severe COVID-19, or those who have died vs. those who have been discharged. Instead, we calculated odds ratios and 95% CI for qualitative ones, such as the number of patients with severe illness/death in the presence of VDD vs. those with normal serum 25(OH)D levels. A p-value lower than 0.05 was considered statistically significant. The study was registered on PROSPERO (CRD42021241473).

FINDINGS: Out of 662 records, 30 articles met inclusion criteria and, therefore, were included in the meta-analysis. We found that the serum levels of 25(OH)D were significantly lower in patients with SARS-CoV-2 infection than in negative ones [MD -3.99 (-5.34, -2.64); p <0.00001; I2= 95%]. Furthermore, its levels were significantly lower in patients with severe disease [MD -6.88 (-9.74, -4.03); p <0.00001; I2=98%] and in those who died of COVID-19 [MD -8.01 (-12.50, -3.51); p = 0.0005; I2=86%]. Finally, patients with VDD had an increased risk of developing severe disease [OR 4.58 (2.24, 9.35); p <0.0001; I2=84%] but not a fatal outcome [OR 4.92 (0.83, 29.31); p = 0.08; I2=94%].

INTERPRETATION: This meta-analysis revealed a large heterogeneity of the studies included due to the different enrolment criteria of patient samples (age, body mass index, ethnicity, comorbidities), the country where they live, all factors influencing serum 25(OH)D levels, and the different criteria used to define the severity of COVID-19. Furthermore, the observational nature of these studies does not allow to establish a cause-effect relationship, even taking into account that 25(OH)D represents a marker of acute inflammation. Treatment with vitamin D might be considered for the primary prevention of SARS-CoV-2 infection and the management of patients with COVID-19. However, further intervention studies are needed to prove this hypothesis.

PMID:34179737 | PMC:PMC8215557 | DOI:10.1016/j.eclinm.2021.100967