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Nevin Manimala Statistics

Direct Measurement of Higher-Order Nonlinear Polarization Squeezing

Phys Rev Lett. 2022 Dec 23;129(26):263601. doi: 10.1103/PhysRevLett.129.263601.

ABSTRACT

We report on nonlinear squeezing effects of polarization states of light by harnessing the intrinsic correlations from a polarization-entangled light source and click-counting measurements. Nonlinear Stokes operators are obtained from harnessing the click-counting theory in combination with angular-momentum-type algebras. To quantify quantum effects, theoretical bounds are derived for second- and higher-order moments of nonlinear Stokes operators. The experimental validation of our concept is rendered possible by developing an efficient source, using a spectrally decorrelated type-II phase-matched waveguide inside a Sagnac interferometer. Correlated click statistics and moments are directly obtained from an eight-time-bin quasi-photon-number-resolving detection system. Macroscopic Bell states that are readily available with our source show the distinct nature of nonlinear polarization squeezing in up to eighth-order correlations, matching our theoretical predictions. Furthermore, our data certify nonclassical correlations with high statistical significance, without the need to correct for experimental imperfections and limitations. Also, our nonlinear squeezing can identify nonclassicality of noisy quantum states which is undetectable with the known linear polarization-squeezing criterion.

PMID:36608182 | DOI:10.1103/PhysRevLett.129.263601

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Nevin Manimala Statistics

Altered cortical gyrification, sulcal depth, and fractal dimension in the autism spectrum disorder comorbid attention-deficit/hyperactivity disorder than the autism spectrum disorder

Neuroreport. 2023 Feb 1;34(2):93-101. doi: 10.1097/WNR.0000000000001864. Epub 2022 Dec 17.

ABSTRACT

Autism spectrum disorder (ASD) frequently occurs accompanied by attention-deficit/hyperactivity disorder (ADHD), which catches increasing attention. The comorbid diagnosis of ASD with ADHD (ASD + ADHD) is permitted in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). However, compared to autism spectrum disorder without other symptoms (ASD-only), the special neural underpinnings in ASD+ADHD remain unclear. Therefore, this study aimed to uncover the differences in cortical complexity between ASD + ADHD and ASD-only patients. A total of 114 ASD participants (i.e. containing 40 ASD + ADHD and 74 ASD-only participants) with T1-weighted magnetic resonance images were collected from the Autism Brain Imaging Data Exchange II. Afterward, a surface-based morphometry method was carried out to compare the cortical complexity (i.e. gyrification index, fractal dimension, and sulcal depth) between the ASD + ADHD and ASD-only cohorts. Results showed the increased fractal dimension in the right fusiform gyrus of the ASD + ADHD cohort in comparison to the ASD-only cohort. Moreover, the ASD + ADHD cohort exhibited increased sulcal depth in the left middle temporal gyrus/inferior temporal gyrus and right middle temporal gyrus compared to the ASD-only cohort. Last but not least, the increased gyrification index in the insula/postcentral gyrus was observed in the ASD + ADHD cohort in comparison to the ASD-only cohort. Overall, the present study contributes to the delineation of particular structural abnormalities in ASD + ADHD than ASD-only, enriching the evidence of the combined phenotype of ASD + ADHD.

PMID:36608165 | DOI:10.1097/WNR.0000000000001864

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Nevin Manimala Statistics

A role for BCL2L13 and autophagy in germline purifying selection of mtDNA

PLoS Genet. 2023 Jan 6;19(1):e1010573. doi: 10.1371/journal.pgen.1010573. Online ahead of print.

ABSTRACT

Mammalian mitochondrial DNA (mtDNA) is inherited uniparentally through the female germline without undergoing recombination. This poses a major problem as deleterious mtDNA mutations must be eliminated to avoid a mutational meltdown over generations. At least two mechanisms that can decrease the mutation load during maternal transmission are operational: a stochastic bottleneck for mtDNA transmission from mother to child, and a directed purifying selection against transmission of deleterious mtDNA mutations. However, the molecular mechanisms controlling these processes remain unknown. In this study, we systematically tested whether decreased autophagy contributes to purifying selection by crossing the C5024T mouse model harbouring a single pathogenic heteroplasmic mutation in the tRNAAla gene of the mtDNA with different autophagy-deficient mouse models, including knockouts of Parkin, Bcl2l13, Ulk1, and Ulk2. Our study reveals a statistically robust effect of knockout of Bcl2l13 on the selection process, and weaker evidence for the effect of Ulk1 and potentially Ulk2, while no statistically significant impact is seen for knockout of Parkin. This points at distinctive roles of these players in germline purifying selection. Overall, our approach provides a framework for investigating the roles of other important factors involved in the enigmatic process of purifying selection and guides further investigations for the role of BCL2L13 in the elimination of non-synonymous mutations in protein-coding genes.

PMID:36608143 | DOI:10.1371/journal.pgen.1010573

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Nevin Manimala Statistics

Over-optimism in unsupervised microbiome analysis: Insights from network learning and clustering

PLoS Comput Biol. 2023 Jan 6;19(1):e1010820. doi: 10.1371/journal.pcbi.1010820. Online ahead of print.

ABSTRACT

In recent years, unsupervised analysis of microbiome data, such as microbial network analysis and clustering, has increased in popularity. Many new statistical and computational methods have been proposed for these tasks. This multiplicity of analysis strategies poses a challenge for researchers, who are often unsure which method(s) to use and might be tempted to try different methods on their dataset to look for the “best” ones. However, if only the best results are selectively reported, this may cause over-optimism: the “best” method is overly fitted to the specific dataset, and the results might be non-replicable on validation data. Such effects will ultimately hinder research progress. Yet so far, these topics have been given little attention in the context of unsupervised microbiome analysis. In our illustrative study, we aim to quantify over-optimism effects in this context. We model the approach of a hypothetical microbiome researcher who undertakes four unsupervised research tasks: clustering of bacterial genera, hub detection in microbial networks, differential microbial network analysis, and clustering of samples. While these tasks are unsupervised, the researcher might still have certain expectations as to what constitutes interesting results. We translate these expectations into concrete evaluation criteria that the hypothetical researcher might want to optimize. We then randomly split an exemplary dataset from the American Gut Project into discovery and validation sets multiple times. For each research task, multiple method combinations (e.g., methods for data normalization, network generation, and/or clustering) are tried on the discovery data, and the combination that yields the best result according to the evaluation criterion is chosen. While the hypothetical researcher might only report this result, we also apply the “best” method combination to the validation dataset. The results are then compared between discovery and validation data. In all four research tasks, there are notable over-optimism effects; the results on the validation data set are worse compared to the discovery data, averaged over multiple random splits into discovery/validation data. Our study thus highlights the importance of validation and replication in microbiome analysis to obtain reliable results and demonstrates that the issue of over-optimism goes beyond the context of statistical testing and fishing for significance.

PMID:36608142 | DOI:10.1371/journal.pcbi.1010820

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Nevin Manimala Statistics

Natural variation of codon repeats in COLD11 endows rice with chilling resilience

Sci Adv. 2023 Jan 6;9(1):eabq5506. doi: 10.1126/sciadv.abq5506. Epub 2023 Jan 6.

ABSTRACT

Abnormal temperature caused by global climate change threatens the rice production. Defense signaling network for chilling has been uncovered in plants. However, less is known about repairing DNA damage produced from overwhelmed defense and its evolution during domestication. Here, we genetically identified a major QTL, COLD11, using the data-merging genome-wide association study based on an algorithm combining polarized data from two subspecies, indica and japonica, into one system. Rice loss-of-function mutations of COLD11 caused reduced chilling tolerance. Genome evolution analysis of representative rice germplasms suggested that numbers of GCG sequence repeats in the first exon of COLD11 were subjected to strong domestication selection during the northern expansion of rice planting. The repeat numbers affected the biochemical activity of DNA repair protein COLD11/RAD51A1 in renovating DNA damage under chilling stress. Our findings highlight a potential way to finely manipulate key genes in rice genome and effectively improve chilling tolerance through molecular designing.

PMID:36608134 | DOI:10.1126/sciadv.abq5506

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Nevin Manimala Statistics

Exposure to isocyanates predicts atopic dermatitis prevalence and disrupts therapeutic pathways in commensal bacteria

Sci Adv. 2023 Jan 6;9(1):eade8898. doi: 10.1126/sciadv.ade8898. Epub 2023 Jan 6.

ABSTRACT

Atopic dermatitis (AD) is a chronic inflammatory skin condition increasing in industrial nations at a pace that suggests environmental drivers. We hypothesize that the dysbiosis associated with AD may signal microbial adaptations to modern pollutants. Having previously modeled the benefits of health-associated Roseomonas mucosa, we now show that R. mucosa fixes nitrogen in the production of protective glycerolipids and their ceramide by-products. Screening EPA databases against the clinical visit rates identified diisocyanates as the strongest predictor of AD. Diisocyanates disrupted the production of beneficial lipids and therapeutic modeling for isolates of R. mucosa as well as commensal Staphylococcus. Last, while topical R. mucosa failed to meet commercial end points in a placebo-controlled trial, the subgroup who completed the full protocol demonstrated sustained, clinically modest, but statistically significant clinical improvements that differed by study site diisocyanate levels. Therefore, diisocyanates show temporospatial and epidemiological association with AD while also inducing eczematous dysbiosis.

PMID:36608129 | DOI:10.1126/sciadv.ade8898

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Nevin Manimala Statistics

Diagnostic Accuracy of Microdialysis in Postoperative Flap Monitoring

J Craniofac Surg. 2023 Jan-Feb 01;34(1):288-290. doi: 10.1097/SCS.0000000000008878. Epub 2022 Aug 17.

ABSTRACT

Postoperative monitoring plays an important role in achieving success in microvascular free tissue transfer. A systematic review was designed to evaluate the clinical outcomes of microdialysis in flap monitoring and a meta-analysis was conducted for diagnostic accuracies. The search terms “microdialysis” and “flap” were used in a PubMed and Scopus search, resulting in 60 and 78 results, respectively. Among 78 titles, 15 articles were excluded. Among 63 abstracts, 43 abstracts were excluded. From 20 full texts, 7 articles were excluded because they did not have sufficient content (ie, the statistical values in question). A systematic review was conducted of the final 13 articles. The overall sensitivity was 97.24% [95% confidence interval (CI)=93.67%-99.10%]. Eleven of the 13 studies showed 100% sensitivity and 2 studies had 2 and 3 false negative results, resulting in sensitivity values of 85.8% and 95.3%. Specificity ranged from 91.89% to 100%, and the overall value was 98.15% (95% CI=96.80%-99.04%). The positive predictive value ranged from 84.62% to 100%, with an overall value of 93.62% (95% CI=89.33%-96.26%). The negative predictive value ranged from 94.44% to 100%, with an overall value of 99.22% (95% CI=98.17%-99.67%). The overall flap success rate (survival rate) was 93.7% (786/839). The lowest flap survival rate was 86.7% and the highest was 100%. Microdialysis provides excellent diagnostic accuracy and enables the early detection of ischemia in postoperative flap monitoring. Although microdialysis is not the most popular choice among surgeons, it should be considered adjacent to conventional clinical monitoring. Cost-effectiveness, availability, and ease of application remain hurdles.

PMID:36608107 | DOI:10.1097/SCS.0000000000008878

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Nevin Manimala Statistics

Nasal Anthropometric Analysis in Turkish Rhinoplasty Patients

J Craniofac Surg. 2023 Jan-Feb 01;34(1):267-271. doi: 10.1097/SCS.0000000000008864. Epub 2022 Aug 2.

ABSTRACT

This study aimed to determine the mean values of the nasal anthropometric measurements through 2-dimensional photogrammetry in for rhinoplasty patients. The study group included 72 healthy individuals, 36 men, and 36 women. The patients were aged 18 to 42 years. All patients had undergone primary rhinoplasty in our clinic between 2013 and 2020. Seven landmarks were identified from the preoperative photographs taken with the patient’s head in neutral position in the frontal and lateral planes. Five distances (total nasal length, nasal bridge length, morphological nose width, alar length, and nasal tip protrusion) and 2 angles (nasofrontal and nasolabial) measurements were calculated. We noted a statistically significant difference between the male and female sexes in terms of total nasal length and morphological nose width (P<0.05). The results were compared with the nasal anthropometric measurements reported in the literature for the Turkish population as well as other ethnic groups. We believe results of this study may facilitate preoperative planning in Turkish patients who request rhinoplasty and improve the success rate of the surgery.

PMID:36608106 | DOI:10.1097/SCS.0000000000008864

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Nevin Manimala Statistics

Residual Disease Threshold After Primary Surgical Treatment for Advanced Epithelial Ovarian Cancer, Part 1: A Systematic Review and Network Meta-Analysis

Am J Ther. 2023 Jan-Feb 01;30(1):e36-e55. doi: 10.1097/MJT.0000000000001584. Epub 2022 Dec 20.

ABSTRACT

BACKGROUND: We present a systematic review and network meta-analysis (NMA) that is the precursor underpinning the Bayesian analyses that adjust for publication bias, presented in the same edition in AJT. The review assesses optimal cytoreduction for women undergoing primary advanced epithelial ovarian cancer (EOC) surgery.

AREAS OF UNCERTAINTY: To assess the impact of residual disease (RD) after primary debulking surgery in women with advanced EOC. This review explores the impact of leaving varying levels of primary debulking surgery.

DATA SOURCES: We conducted a systematic review and random-effects NMA for overall survival (OS) to incorporate direct and indirect estimates of RD thresholds, including concurrent comparative, retrospective studies of ≥100 adult women (18+ years) with surgically staged advanced EOC (FIGO stage III/IV) who had confirmed histological diagnoses of ovarian cancer. Pairwise meta-analyses of all directly compared RD thresholds was previously performed before conducting this NMA, and the statistical heterogeneity of studies within each comparison was evaluated using recommended methods.

THERAPEUTIC ADVANCES: Twenty-five studies (n = 20,927) were included. Analyses demonstrated the prognostic importance of complete cytoreduction to no macroscopic residual disease (NMRD), with a hazard ratio for OS of 2.0 (95% confidence interval, 1.8-2.2) for <1 cm RD threshold versus NMRD. NMRD was associated with prolonged survival across all RD thresholds. Leaving NMRD was predicted to provide longest survival (probability of being best = 99%). The results were robust to sensitivity analysis including only those studies that adjusted for extent of disease at primary surgery (hazard ratio 2.3, 95% confidence interval, 1.9-2.6). The overall certainty of evidence was moderate and statistical adjustment of effect estimates in included studies minimized bias.

CONCLUSIONS: The results confirm a strong association between complete cytoreduction to NMRD and improved OS. The NMA approach forms part of the methods guidance underpinning policy making in many jurisdictions. Our analyses present an extension to the previous work in this area.

PMID:36608071 | DOI:10.1097/MJT.0000000000001584

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Nevin Manimala Statistics

Efficacy of Low-Dose Versus Traditional Buprenorphine Induction in the Hospital: A Quantitative and Qualitative Study

Am J Ther. 2023 Jan-Feb 01;30(1):e1-e9. doi: 10.1097/MJT.0000000000001573. Epub 2022 Nov 11.

ABSTRACT

BACKGROUND: Emerging evidence suggests low-dose buprenorphine (LDB) induction can expand opportunities for buprenorphine induction in patients who are taking taking methadone, short-acting opioid agonists, or who have anxiety about opioid withdrawal.

STUDY QUESTION: How is a rapid LDB protocol using transdermal buprenorphine tolerated in the hospital?

STUDY DESIGN: A prospective study of 20 patient encounters (n = 20 patients) with traditional buprenorphine induction before implementation of study protocol (control group) and 37 patient encounters (n = 34 patients) with LDB induction protocol (pilot group). Summary statistics were used to describe demographics, clinical opioid withdrawal scale and pain scores within 24 hours preprotocol and within 24 hours postprotocol initiation, hospital length of stay after protocol initiation, receipt of a buprenorphine prescription at discharge, and prescription activity at 30 days. T test and chi-square tests were used to analyze comparisons. A subset of pilot group patients completed a survey about their experience.

RESULTS: There were no statistically significant differences in pain and clinical opioid withdrawal scale scores between the pilot and control groups. There were 5 instances of precipitated withdrawal in the pilot group. There was no statistically significant difference in mean discharge time after protocol initiation between the pilot and control groups (P = 0.60). Most patients surveyed described a positive experience with LDB induction.

CONCLUSION: Hospitalization is a critical time to initiate buprenorphine for patients with opioid use disorder. Our data adds to the growing evidence that LDB induction is feasible for patients taking methadone and short-acting opioid agonists, and that a more rapid induction protocol is generally well-tolerated by patients although precipitated withdrawal is a risk. Finally, our rapid induction protocol did not seem to increase hospital length of stay compared with traditional induction.

PMID:36608069 | DOI:10.1097/MJT.0000000000001573