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Nevin Manimala Statistics

Along-tract analysis of the white matter is more informative about brain ageing, compared to whole-tract analysis

Clin Neurol Neurosurg. 2021 Nov 18;211:107048. doi: 10.1016/j.clineuro.2021.107048. Online ahead of print.

ABSTRACT

Diffusion Tensor Imaging (DTI) enabled the investigation of brain White Matter (WM), both qualitatively to study the macrostructure, and quantitatively to study the microstructure. The quantitative analyses are mostly performed at the whole-tract level, i.e., providing one measure of interest per tract; however, along-tract approaches may provide finer details of the quality of the WM tracts. In this study, using the DWI data collected from 40 young and 40 old individuals, we compared the DTI measures of FA, MD, AD, and RD, estimated by both whole-tract and along-tract approaches in 18 WM bundles, between the two groups. The results of the whole-tract quantitative analysis showed a statistically significant (p-FWER < 0.05) difference between the old and young groups in 6 tracts for FA, 8 tracts for MD, 1 tract for AD, and 7 tracts for RD. On the contrary, the along-tract approach showed differences between the two groups in 10 tracts for FA, 14 tracts for MD, 8 tracts for AD, and 11 tracts for RD. All the differences between the along-tract measures of the two groups had a large effect size (Cohen’d > 0.80). This study showed that the along-tract approach for the analysis of brain WM reveals changes in some WM tracts which had not shown any changes in the whole-tract approach, and therefore this finding emphasizes the utilization of the along-tract approach along with the whole-tract method for a more accurate study of the brain WM.

PMID:34826755 | DOI:10.1016/j.clineuro.2021.107048

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Nevin Manimala Statistics

Genomic history and forensic characteristics of Sherpa highlanders on the Tibetan Plateau inferred from high-resolution InDel panel and genome-wide SNPs

Forensic Sci Int Genet. 2021 Nov 18;56:102633. doi: 10.1016/j.fsigen.2021.102633. Online ahead of print.

ABSTRACT

Sherpa people, one of the high-altitude hypoxic adaptive populations, mainly reside in Nepal and the southern Tibet Autonomous Region. The genetic origin and detailed evolutionary profiles of Sherpas remain to be further explored and comprehensively characterized. Here we analyzed the newly-generated InDel genotype data from 628 Dingjie Sherpas by merging with 4222 worldwide InDel profiles and collected genome-wide SNP data (approximately 600K SNPs) from 1612 individuals in 191 modern and ancient populations to explore and reconstruct the fine-scale genetic structure of Sherpas and their relationships with nearby modern and ancient East Asians based on the shared alleles and haplotypes. The forensic parameters of 57 autosomal InDels (A-InDels) included in our used new-generation InDel amplification system showed that this focused InDel panel is informative and polymorphic in Dingjie Sherpas, suggesting that it can be used as the supplementary tool for forensic personal identification and parentage testing in Dingjie Sherpas. Descriptive findings from the PCA, ADMIXTURE, and TreeMix-based phylogenies suggested that studied Nepal Sherpas showed excess allele sharing with neighboring Tibeto-Burman Tibetans. Furthermore, patterns of allele sharing in f-statistics demonstrated that Nepal Sherpas had a different evolutionary history compared with their neighbors from Nepal (Newar and Gurung) but showed genetic similarity with 2700-year-old Chokhopani and modern Tibet Tibetans. QpAdm/qpGraph-based admixture sources and models further showed that Sherpas, core Tibetans, and Chokhopani formed one clade, which could be fitted as having the main ancestry from late Neolithic Qijia millet farmers and other deep ancestries from early Asians. Chromosome painting profiles and shared IBD fragments inferred from fineSTRUCTURE and ChromoPainter not only confirmed the abovementioned genomic affinity patterns but also revealed the fine-scale genetic microstructures among Sino-Tibetan speakers. Finally, natural-selection signals revealed via iHS, nSL and iHH12 showed natural selection signatures associated with disease susceptibility in Sherpas. Generally, we provided the comprehensive landscape of admixture and evolutionary history of Sherpa people based on the shared alleles and haplotypes from the InDel-based genotype data and high-density genome-wide SNP data. The more detailed genetic landscape of Sherpa people should be further confirmed and characterized via ancient genomes or single-molecule real-time sequencing technology.

PMID:34826721 | DOI:10.1016/j.fsigen.2021.102633

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Nevin Manimala Statistics

Calculating clinical mastitis frequency in dairy cows: Incidence risk at cow level, incidence rate at cow level, and incidence rate at quarter level

Prev Vet Med. 2021 Oct 28;198:105527. doi: 10.1016/j.prevetmed.2021.105527. Online ahead of print.

ABSTRACT

The lack of standardization in reporting clinical mastitis incidence limits the ability to compare results across multiple studies without additional calculations. There is both a biological and statistical rationale for evaluating the at-risk period at the quarter level. This study aimed to: (1) to outline an applied method for calculating clinical mastitis (CM) incidence rate at the quarter level using currently available software; and (2) to present the results of three different measurements: incidence risk at cow level, incidence rate at cow level, and incidence rate at quarter level. In an open population prospective cohort of eight commercial dairy farms monitored from May 15, 2016, to May 31, 2017, all CM cases (n = 7513) were identified by trained on-farm personnel, who collected all milk samples from all quarters with visibly abnormal milk. Microbiological identification was determined by culture and MALDI-TOF. All lactating quarters were at risk for CM. A quarter was at risk for a new CM case if there was at least 14 d between a previously diagnosed case and the current case in the same quarter, or if a different pathogen was isolated in the same quarter within 14 d. A total of 17,513,429 quarters days at risk (QDAR) were estimated. A statistical software macro and Structured Query Language (SQL) were used to bring all data together. The monthly incidence rate at the cow level was 16.6 cases per 10,000 cow-days, the monthly incidence rate at the quarter level was 4.4 cases per 10,000 QDAR and the monthly incidence risk at the cow level was 4.8 cases per 100 cows. Although the evaluation of QDAR requires additional computation when compared to other methods, it might allow for a more precise evaluation of the data and a more accurate evaluation of mastitis incidence. Clearly defining the methods used to report mastitis incidence will improve our ability to discuss and learn about the differences and similarities across studies, regions, and countries.

PMID:34826731 | DOI:10.1016/j.prevetmed.2021.105527

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Nevin Manimala Statistics

Geriatric All-Terrain Vehicle Trauma: An Unhelmeted and Severely Injured Population

J Surg Res. 2021 Nov 23;270:555-563. doi: 10.1016/j.jss.2021.09.009. Online ahead of print.

ABSTRACT

BACKGROUND: All-terrain vehicle (ATV) use is widespread, however, little is known about injury patterns and outcomes in geriatric patients. We hypothesized that geriatric patients would have distinct and more severe injuries than non-geriatric adults after ATV trauma.

METHODS: A retrospective cohort study was performed using the National Trauma Databank comparing non-geriatric (18-64) and geriatric adults (≥65) presenting after ATV trauma at Level 1 and 2 trauma centers from 2011 to 2015. Demographic, admission, and outcomes data were collected, including injury severity score (ISS), abbreviated injury scale (AIS) score, discharge disposition, and mortality. We performed univariate statistical tests between cohorts and multiple logistic regression models to assess for risk factors associated with severe injury (ISS>15) and mortality.

RESULTS: 23,568 ATV trauma patients were identified, of whom 1,954 (8.3%) were geriatric. Geriatric patients had higher rates of severe injury(29.2 v 22.5%,p<0.0001), and thoracic (55.2 v 37.8%,p<0.0001) and spine (31.5 v 26.0%,p<0.0001) injuries, but lower rates of abdominal injuries (14.6 v 17.9%,p<0.001) as compared to non-geriatric adults. Geriatric patients had overall lower head injury rates (39.2 v 42.1%,p=0.01), but more severe head injuries (AIS>3) (36.2 vs 30.2%,p<0.001). Helmet use was significantly lower in geriatric patients (12.0 v 22.8%,p<0.0001). On multivariate analysis age increased the odds for both severe injury (OR 1.50, 95% CI 1.31-1.72, p<0.0001) and mortality (OR 5.07, 95% CI 3.42-7.50, p<0.0001).

CONCLUSIONS: While severe injury and mortality after ATV trauma occurred in all adults, geriatric adults suffered distinct injury patterns and were at greater risk for severe injury and mortality.

LEVEL OF EVIDENCE: Level IV STUDY TYPE: Retrospective review of National Database.

PMID:34826691 | DOI:10.1016/j.jss.2021.09.009

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Gait characteristics under single-/dual-task walking conditions in elderly patients with cerebral small vessel disease: Analysis of gait variability, gait asymmetry and bilateral coordination of gait

Gait Posture. 2021 Nov 17;92:65-70. doi: 10.1016/j.gaitpost.2021.11.007. Online ahead of print.

ABSTRACT

BACKGROUND: Dual-task walking (DTW) is common in daily life and represents an ideal paradigm for elucidating gait irregularity. Under single-task walking (STW) and DTW conditions, the symmetric and bilaterally coordinated human gait pattern found in healthy individuals is absent in individuals with neurological ailments such as Parkinson’s disease, Alzheimer’s disease and post-stroke issues. Cerebral small vessel disease (CSVD) is a neuropathological and radiological issue that has been reported to be associated with cognitive and motor disorders. However, few gait analyses have focused on elderly individuals with CSVD under DTW conditions.

RESEARCH QUESTION: Are parameters of gait analysis helpful in elucidating gait abnormalities in elderly patients with CSVD under DTW conditions?

METHODS: A total of 46 elderly patients with CSVD (CSVD group) and 22 healthy, age-matched individuals (HE group) were recruited. Gait data were collected from both groups under STW and DTW conditions. Direct parameters and metrics reflecting gait variability, gait asymmetry, and bilateral coordination of gait in the two groups were compared.

RESULTS: Under STW conditions, elderly individuals with CSVD showed markedly shorter stride length, were slower, and had higher gait asymmetry (GA) and phase coordination index (PCI) than healthy controls after adjusting for age, sex and level of education. Under DTW conditions, there were statistically significant differences between the two groups in stride time, stride length, cadence, stride time variability, GA and PCI after adjusting for age, sex, and level of education.

SIGNIFICANCE: Reanalysis-generated parameters, such as gait variability, GA, and PCI, are biomarkers for gait dysfunction in elderly patients with CSVD. In this study, elderly individuals with CVSD showed abnormal gait features under both STW and DTW conditions.

PMID:34826695 | DOI:10.1016/j.gaitpost.2021.11.007

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Humoral immune responses against facultative pathogen Candida utilis in atopic patients with vulvovaginal candidiasis. Candida utilis glucomannan – New serologic biomarker

Immunobiology. 2021 Nov 19;227(1):152154. doi: 10.1016/j.imbio.2021.152154. Online ahead of print.

ABSTRACT

Vulvovaginal candidiasis is one of the most commonly reported female genital tract infections, affecting approximately 70-75% of childbearing age women at least once during their lifetime. Approximately 50% of patients have refractory episodes and in 5-10% of cases the disease has a chronic course. The fungal cell wall represents the important host-invader interface. Cell-wall polysaccharides represent biological response modifiers and the pathogen-associated molecular patterns and virulence factors. Glycans are sensed by germ-line encoded pattern recognition receptors and reactively participate in immune system cell signaling. The most dominant cell-wall antigenic structures of Candida species as ß-glucan, α- and ß-mannans, glucomannan and other immunogenic polysaccharides are of particular relevancy for specific in vitro diagnosis and long-term follow-up of the Candida infection. In this study we assessed the immunobiological activity of facultative pathogen Candida utilis cell glucomannan and its effectivity as in vitro serological marker for antibody testing. The novel serologic assay has been developed and optimized for C. utilis serodiagnosis. The comparison assays were performed to establish relationship between antibodies against C. utilis, C. albicans and S. cerevisiae main cell-wall antigens in patient sera. The study evaluates applicability of glucomannan as serodiagnostic antigen and as a trigger of antigenspecific IgG, IgM and IgA antibody isotypes in the cohort of 35 atopic female subjects with recurrent vulvovaginal candidiasis. Statistically significant sera values of specific anti-glycan IgM and IgA class antibodies were revealed. The results are suggestive for efficient serological application of C.utilis glucomannan as in vitro disease marker and prospectively for follow-up of the specific long-term antimycotic therapy.

PMID:34826687 | DOI:10.1016/j.imbio.2021.152154

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Long-term post-recurrence survival outcomes in young women receiving fertility-sparing surgery for epithelial ovarian cancer

Eur J Obstet Gynecol Reprod Biol. 2021 Nov 16;267:221-225. doi: 10.1016/j.ejogrb.2021.11.015. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to investigate long-term post-recurrence survival outcomes in young women receiving fertility-sparing surgery (FSS) to verify the feasibility of the limited surgery for epithelial ovarian cancer (OvCa).

STUDY DESIGN: We performed a regional multicenter retrospective study from January 1986 and March 2020, using clinical data corrected under the central pathological review system. Patients with recurrent tumor after surgery for stage I epithelial OvCa, aged equal or younger than 45 years were included for this study. We evaluated effect of FSS regarding long-term post-recurrence survival with statistical adjustment of propensity score-based method.

RESULTS: With the Kaplan-Meier method, original and adjusted survival curves were estimated for recurrence-after survival of patients with (n = 14) and without FSS (n = 26). Median time to disease-specific death was 18.6 months. In both original and adjusted cohorts, there were no significant difference between the two groups (log rank test; P > 0.05). Hazard ratio of disease-specific death was 1.264 (95% confidence interval, 0.563-2.836; P = 0.570) in original and 1.354 (95% confidence interval, 0.702-2.611; P = 0.366) in adjusted population. This result indicated that patients with FSS was not associated with poorer prognosis for recurrence-after survival than those without. When comparing patients not receiving FSS, patients receiving FSS with recurrence at spared ovary followed not significantly different survival outcome as well as those with extra-ovarian recurrence.

CONCLUSION: There was no significant difference of long-term post-recurrence survival outcomes between patients of epithelial OvCa with and without FSS in young women of reproductive age.

PMID:34826670 | DOI:10.1016/j.ejogrb.2021.11.015

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Nevin Manimala Statistics

A ferret model of immunosuppression induced with dexamethasone

Vet Immunol Immunopathol. 2021 Nov 18;243:110362. doi: 10.1016/j.vetimm.2021.110362. Online ahead of print.

ABSTRACT

Ferrets are nowadays frequently used as animal models for biomedical purposes; in many cases, immunosuppression of experimental animals is necessary. The aim of this study was to evaluate the effect of intramuscular dexamethasone administration (2 mg/kg as the initiation dose continued with 1 mg/kg q 12 h applied 5 times) on ferret’s immune system. In comparison with ferrets which received the saline (n = 5), significantly lower total counts of leukocytes (P < 0.01), lymphocytes (P < 0.01) and monocyte (P < 0.05), as well as absolute numbers of CD4+CD8- (P < 0.01) and CD4-CD8+ (P < 0.01) subsets were noted in dexamethasone treated ferrets (n = 5) the first day after the treatment (D1). Absolute number of CD79+ lymphocytes remained unchanged throughout the experiment. The proliferation activity of lymphocytes in dexamethasone treated ferrets was lower only in D1 using concanavalin A (conA), phytohemagglutinin (PHA) and pokeweed mitogen (PWM); statistical significance was noted using PHA 40 (P < 0.05) and PWM 10 (P < 0.01). Lower neutrophil activity (P < 0.01) was detected in D1 after the dexamethasone treatment in both production of reactive oxygen species (chemiluminescence test) and ingestion of particles (phagocytosis assay). The dexamethasone treatment proved to be useful for short-term immunosuppression in ferrets. The results closely resembled data previously reported in human studies and indicate classification of ferrets as steroid-resistant species.

PMID:34826685 | DOI:10.1016/j.vetimm.2021.110362

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Nevin Manimala Statistics

AutoScore-Survival: Developing interpretable machine learning-based time-to-event scores with right-censored survival data

J Biomed Inform. 2021 Nov 23:103959. doi: 10.1016/j.jbi.2021.103959. Online ahead of print.

ABSTRACT

BACKGROUND: Scoring systems are highly interpretable and widely used to evaluate time-to-event outcomes in healthcare research. However, existing time-to-event scores are predominantly created ad-hoc using a few manually selected variables based on clinician’s knowledge, suggesting an unmet need for a robust and efficient generic score-generating method.

METHODS: AutoScore was previously developed as an interpretable machine learning score generator, integrated both machine learning and point-based scores in the strong discriminability and accessibility. We have further extended it to the time-to-event outcomes and developed AutoScore-Survival, for generating time-to-event scores with right-censored survival data. Random survival forest provided an efficient solution for selecting variables, and Cox regression was used for score weighting. We implemented our proposed method as an R package. We illustrated our method in a study of 90-day survival prediction for patients in intensive care units and compared its performance with other survival models, the random survival forest, and two traditional clinical scores.

RESULTS: The AutoScore-Survival-derived scoring system was more parsimonious than survival models built using traditional variable selection methods (e.g., penalized likelihood approach and stepwise variable selection), and its performance was comparable to survival models using the same set of variables. Although AutoScore-Survival achieved a comparable integrated area under the curve of 0.782 (95% CI: 0.767-0.794), the integer-valued time-to-event scores generated are favorable in clinical applications because they are easier to compute and interpret.

CONCLUSIONS: Our proposed AutoScore-Survival provides a robust and easy-to-use machine learning-based clinical score generator to studies of time-to-event outcomes. It gives a systematic guideline to facilitate the future development of time-to-event scores for clinical applications.

PMID:34826628 | DOI:10.1016/j.jbi.2021.103959

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Rapid spatial learning in cooperative and non-cooperative cichlids

Behav Processes. 2021 Nov 23:104550. doi: 10.1016/j.beproc.2021.104550. Online ahead of print.

ABSTRACT

The number, duration and depth of social relationships that individuals maintain impact social cognition, but the connection between sociality and other aspects of cognition has hardly been explored. To date, the link between social living and intelligence has been mainly supported by studies on primates, and far fewer tests connecting sociality to cognitive abilities have used other taxa. Here, we present the first comparative study in fishes that examines whether complex social living is associated with better performance on a cognitively demanding spatial task. Using three cooperative, group-living cichlid fish species and three of their non-cooperative, more solitary close relatives, we studied maze learning and employed a new statistical extension for the ‘lme4’ and ‘glmmTMB’ packages in R that allows phylogeny to be included as a random effect term. Across trials, the three cooperative and the three non-cooperative species completed the maze faster, made fewer mistakes, and improved their inhibitory control. Although fish improved their performance, we did not detect any differences in the extent of improvement between cooperative and non-cooperative species. Both the cooperative species and the non-cooperative species took similar amounts of time to complete the maze, had comparable numbers of mistakes, and exhibited similar inhibitory control while in the maze. Our results suggest that living and breeding in complex social groups does not necessarily imply enhancement of other forms of cognition nor, more specifically, an enhanced spatial learning capacity.

PMID:34826584 | DOI:10.1016/j.beproc.2021.104550