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Nevin Manimala Statistics

HAMdetector: A Bayesian regression model that integrates information to detect HLA-associated mutations

Bioinformatics. 2022 Mar 3:btac134. doi: 10.1093/bioinformatics/btac134. Online ahead of print.

ABSTRACT

MOTIVATION: A key process in anti-viral adaptive immunity is that the Human Leukocyte Antigen system (HLA) presents epitopes as Major Histocompatibility Complex I (MHC I) protein-peptide complexes on cell surfaces and in this way alerts CD8+ cytotoxic T-Lymphocytes (CTLs). This pathway exerts strong selection pressure on viruses, favoring viral mutants that escape recognition by the HLA/CTL system. Naturally, such immune escape mutations often emerge in highly variable viruses, e.g. HIV or HBV, as HLA-associated mutations (HAMs), specific to the hosts MHC I proteins. The reliable identification of HAMs is not only important for understanding viral genomes and their evolution, but it also impacts the development of broadly effective anti-viral treatments and vaccines against variable viruses. By their very nature, HAMs are amenable to detection by statistical methods in paired sequence/HLA data. However, HLA alleles are very polymorphic in the human host population which makes the available data relatively sparse and noisy. Under these circumstances, one way to optimize HAM detection is to integrate all relevant information in a coherent model. Bayesian inference offers a principled approach to achieve this.

RESULTS: We present a new Bayesian regression model for the detection of HAMs that integrates a sparsity-inducing prior, epitope predictions, and phylogenetic bias assessment, and that yields easily interpretable quantitative information on HAM candidates. The model predicts experimentally confirmed HAMs as having high posterior probabilities, and it performs well in comparison to state-of-the-art models for several data sets from individuals infected with HBV, HDV, and HIV.

AVAILABILITY: The source code of this software is available at https://github.com/HAMdetector/Escape.jl under a permissive MIT license.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:35238330 | DOI:10.1093/bioinformatics/btac134

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Nevin Manimala Statistics

Increased runs of homozygosity in the autosomal genome of Brazilian individuals with neurodevelopmental delay/intellectual disability and/or multiple congenital anomalies investigated by chromosomal microarray analysis

Genet Mol Biol. 2022 Feb 28;45(1):e20200480. doi: 10.1590/1678-4685-GMB-2020-0480. eCollection 2022.

ABSTRACT

Runs of homozygosity (ROH) in the human genome may be clinically relevant. The aim of this study was to report the frequency of increased ROH of the autosomal genome in individuals with neurodevelopmental delay/intellectual disability and/or multiple congenital anomalies, and to compare these data with a control group. Data consisted of calls of homozygosity from 265 patients and 289 controls. In total, 7.2% (19/265) of the patients showed multiple ROH exceeding 1% of autosomal genome, compared to 1.4% (4/289) in the control group (p=0.0006). Homozygosity ranged from 1.38% to 22.12% among patients, and from 1.53 to 2.40% in the control group. In turn, 1.9% (5/265) of patients presented ROH ≥10Mb in a single chromosome, compared to 0.3% (1/289) of individuals from the control group (p=0.0801). By excluding cases with reported consanguineous parents (15/24), the frequency of increased ROH was 3.4% (9/250) among patients and 1.7% (5/289) in the control group, considering multiple ROH exceeding 1% of the autosome genome and ROH ≥10Mb in a single chromosome together, although not statistically significant (p=0.1873). These results reinforce the importance of investigating ROH, which with complementary diagnostic tests can improve the diagnostic yield for patients with such conditions.

PMID:35238326 | DOI:10.1590/1678-4685-GMB-2020-0480

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In vivo evaluation of topical ascorbic acid application on skin aging by 50MHz ultrasound

J Cosmet Dermatol. 2022 Mar 2. doi: 10.1111/jocd.14892. Online ahead of print.

ABSTRACT

Ascorbic acid (AA) is a powerful antioxidant capable of acting significantly both in the prevention and treatment of the skin aging process. One way to assess the in vivo efficacy of anti-aging treatments is by using the high-frequency ultrasound (HFUS) skin image analysis technique, a non-invasive approach that allows for a new level of evaluating the effectiveness of dermatological and cosmetic products. The aim of the present study was to assess the performance of a topical emulsion of liquid crystalline structures containing AA using the 50 MHz HFUS skin image analysis method. Twenty-five healthy female participants between 35 and 60 years old were included, all of whom randomly applied a placebo formulation and an AA-containing formulation to each forearm, once a day, for 30 days. HFUS measurements were performed before using the products (T0), two hours later (T2h), and after 30 days of use (T30d). The analyzed parameters included total skin, dermal, and epidermal echogenicity; variation and mean thickness of total skin, the epidermis and dermis; and surface roughness. Statistical analyses were performed using the Friedman test, followed by Dunn’s test for comparisons of multiple means (α=0.05). A significant increase in total skin and dermal echogenicity was observed after topical AA application. Our findings suggest that collagen synthesis significantly increased after topical therapy with AA, which was responsible for the increment in dermal echogenicity. This study showed, through the HFUS technique, that the topical use of AA promoted dermal redensification after 30 days of application.

PMID:35238148 | DOI:10.1111/jocd.14892

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Nevin Manimala Statistics

Deconvolution of Light-Induced Ion Migration Phenomena by Statistical Analysis of Cathodoluminescence in Lead Halide-Based Perovskites

Adv Sci (Weinh). 2022 Mar 3:e2103729. doi: 10.1002/advs.202103729. Online ahead of print.

ABSTRACT

Studying the compositional instability of mixed ion perovskites under light illumination is important to understand the mechanisms underlying their efficiency and stability. However, current techniques are limited in resolution and are unable to deconvolute minor ion migration phenomena. Here, a method that enables ion migration to be studied allowing different segregation mechanisms to be elucidated is described. Statistical analysis is applied to cathodoluminescence data to generate compositional distribution histograms. Using these histograms, two different ion migration phenomena, horizontal ion migration (HIM) and vertical ion migration (VIM), are identified in different perovskite films. It is found that most passivating agents inhibit HIM, but not VIM. However, VIM can be reduced by deposition of imidazolium iodide on the perovskite surface. This method can be used to study perovskite-based devices efficiency and stability by providing molecular level mechanistic understanding of passivation approaches leading to performance improvement of perovskite solar cells via rational design.

PMID:35238172 | DOI:10.1002/advs.202103729

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Nevin Manimala Statistics

Preclinical dental training: Association between fine motor skills and compliance with ergonomic posture techniques

Eur J Dent Educ. 2022 Mar 2. doi: 10.1111/eje.12793. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the dental students’ fine motor skills and their compliance with ergonomic posture techniques over the course of a preclinical training year. The correlation between fine motor skills and compliance was also assessed.

METHODS: The ergonomic posture of students enrolled in the second year of a five-year undergraduate dental degree program (n=62) was assessed using the Compliance Assessment of Dental Ergonomic Posture Requirements (CADEP). This assessment relied on photos of the students performing preclinical laboratory procedures during the school year. The photos of each procedure received a score, and the final score obtained (0 to 10) corresponded to the extent of the student’s compliance with ergonomic posture techniques. Initial compliance was calculated during the first two months of the training program, while final compliance was calculated during the last two months. Fine motor skills were evaluated using the modified Dental Manual Dexterity Assessment (DMDA), which was also applied at the beginning and the end of the school year. Data was assessed statistically by Student’s paired t-test, and the correlation between fine motor skills and compliance with ergonomic posture techniques was estimated by Pearson correlation coefficient (r) and Student’s t-test (α=.05).

RESULTS: The compliance scores were higher at the end of academic year than at the beginning of year (p<0.001; t=-5.300). Fine motor skills improved significantly with time (p<0.001; t=-10.975). Non-significant correlations were found between students’ fine motor skills and their economic posture compliance both at the beginning (r=-0,197; p=0,126) and at the end of the training year (r=0.226; p=0,078).

CONCLUSION: The students’ manual dexterity and compliance with ergonomic posture techniques increased over the course of the preclinical training year, and the correlation between students’ fine motor skills and their ergonomic posture compliance was not significant.

PMID:35238116 | DOI:10.1111/eje.12793

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Nevin Manimala Statistics

COVID-19 pandemic lockdown – Is it affecting our skin hygiene and cosmetic practice?

J Cosmet Dermatol. 2022 Mar 3. doi: 10.1111/jocd.14894. Online ahead of print.

ABSTRACT

BACKGROUND: Orders like self-isolation, quarantine, social distancing, and lockdown implemented as a protective measure against COVID-19 has allowed people to devote their excess leisure time to their appearance, cosmetics, and hygiene.

OBJECTIVE: To assess the skin care routine regarding hygiene and cosmetic practices among female users of social media during the COVID-19 pandemic.

METHOD: A cross-sectional study was done among 300 female social media users using purposive sampling. A self-administered questionnaire that included questions related to hygiene practices such as hand washing, use of hand sanitizers, bathing, hair washing, and use of certain cosmetics before and during the pandemic was used to collect all relevant data.

RESULT: Handwashing after returning home and shaking hands with others increased during the pandemic as compared to prior practices. The frequency of using a hand sanitizer had also increased during the pandemic. There was a statistically significant decrease in the frequency of the hair removal and visits to beauty salons during the pandemic. Cosmetics were used less, although face creams and lip balm were used more. Even though most of our respondents thought pandemic practices were convenient to use, more than half of them said they wished to go back to their pre-pandemic routines once the pandemic was over.

CONCLUSION: The study revealed an increase in washing behavior, use of facial cream, and lip balms. Moreover, a decrease in using make-up cosmetics, hair removal, and beauty salon visits during the pandemic.

PMID:35238132 | DOI:10.1111/jocd.14894

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Nevin Manimala Statistics

Genomic analysis of familial pancreatic cancers and intraductal papillary mucinous neoplasms: A cross-sectional study

Cancer Sci. 2022 Mar 2. doi: 10.1111/cas.15316. Online ahead of print.

ABSTRACT

Environmental and genetic factors play a critical role in the pathogenesis of pancreatic cancer, which is likely to follows a multi-step process that includes intraductal papillary mucinous neoplasm. The pathogenesis of familial pancreatic cancer has been reported; however, epidemiological characteristics and causative genes remain unclear. This study aimed to determine the relationship between the family history of pancreatic cancer and tumor malignancy and identify novel susceptible germline variants of pancreatic cancer. We performed an epidemiologic study at our institute on a cohort of 668 patients with intraductal papillary mucinous neoplasm and 242 with pancreatic cancer but without associated intraductal papillary mucinous neoplasm stratified by family history of pancreatic cancer. Whole-exome sequencing was conducted for 10 patients from seven families with familial pancreatic cancer and intraductal papillary mucinous neoplasm. We found that patients who have intraductal papillary mucinous neoplasm with positive family history of pancreatic cancer within first-degree relatives, were more likely to develop malignancy in a shorter period than those without family history. Duplicate frameshift variants in TET2 c.3180dupG (p.Pro1061fs) and ASXL1 c.1934dupG (p.Gly646fs) in one family and POLN c.1194dupT (p.Glu399fs) in another were identified as pathogenic truncating germline variants which were previously recognised susceptibility genes. Moreover, PDIA2 c.1403C>T (p.Pro468Leu) and DPYSL4 c.926C>A (p.Pro309Gln) were shared in four and two patients, respectively. In particular PDIA2 was identified as a novel candidate for one of deleterious variants of familial pancreatic cancer.

PMID:35238112 | DOI:10.1111/cas.15316

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Non-surgical peri-implantitis treatment with or without systemic antibiotics; a randomized controlled clinical trial

Clin Oral Implants Res. 2022 Mar 2. doi: 10.1111/clr.13914. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the adjunctive effect of systemic amoxicillin (AMX) and metronidazole (MTZ) in patients receiving non-surgical treatment (NST) for peri-implantitis (PI).

MATERIALS AND METHODS: Thirty-seven patients were randomized into an experimental group treated with NST plus AMX + MTZ (N=18) and a control group treated with NST alone (N=19). Clinical parameters were evaluated at 12 weeks post-treatment. The primary outcome was the change in peri-implant pocket depth (PIPD) from baseline to 12 weeks, while secondary outcomes included bleeding on probing (BoP), suppuration on probing (SoP) and plaque. Data analysis was performed at patient level (one target site per patient).

RESULTS: All 37 patients completed the study. Both groups showed a significant PIPD reduction after NST. The antibiotics group showed a higher mean reduction of PIPD at 12 weeks, compared with the control group (2.28 ± 1.49 mm vs 1.47 ± 1.95 mm), however this difference did not reach statistical significance. There was no significant effect of various potential confounders on PIPD reduction. Neither treatment resulted in significant improvements in BoP at follow-up; thirty out of 37 (81%) target sites still had BoP after treatment. Only two implants, one in each group, exhibited a successful outcome defined as PIPD ≤5 mm, and absence of BoP and SoP.

CONCLUSIONS: NST was able to reduce PIPD at implants with PI. The adjunctive use of systemic AMX and MTZ did not show statistically significant better results compared to NST alone. NST with or without antibiotics was ineffective to completely resolve inflammation around dental implants.

PMID:35238084 | DOI:10.1111/clr.13914

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Opposite trends of glycosides and alkaloids in Dendrobium nobile of different age based on UPLC-Q/TOF-MS combined with multivariate statistical analyses

Phytochem Anal. 2022 Mar 2. doi: 10.1002/pca.3115. Online ahead of print.

ABSTRACT

INTRODUCTION: Alkaloids and glycosides are the active ingredients of the herb Dendrobium nobile, which is used in traditional Chinese medicine. The pharmacological effects of alkaloids include neuroprotective effects and regulatory effects on glucose and lipid metabolism, while glycosides improve the immune system. The pharmacological activities of the above chemical components are significantly different. In practice, the stems of 3-year-old D. nobile are usually used as the main source of Dendrobii Caulis. However, it has not been reported whether this harvesting time is appropriate.

OBJECTIVE: The aim of this study was to compare the chemical characteristics of D. nobile in different growth years (1-3 years).

METHODS: In this study, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) was employed to analyze the constituents of D. nobile. The relative abundance of each constituent was analyzed with multivariate statistical analyses to screen the characteristic constituents that contributed to the characterization and classification of D. nobile. Dendrobine, a component of D. nobile that is used for quality control according to the Chinese Pharmacopoeia, was assayed by gas chromatography.

RESULTS: As a result, 34 characteristic constituents (VIP > 2) were identified or tentatively identified as alkaloids and glycosides based on MS/MS data. Moreover, the content of alkaloids decreased over time, whereas the content of glycosides showed the opposite trend. The absolute quantification of dendrobine was consistent with the metabolomics results.

CONCLUSION: Our findings provide valuable information to optimize the harvest period and a reference for the clinical application of D. nobile.

PMID:35238089 | DOI:10.1002/pca.3115

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Comparing tissue oximetry to doppler monitoring in 1367 consecutive breast free flaps

Microsurgery. 2022 Mar 3. doi: 10.1002/micr.30873. Online ahead of print.

ABSTRACT

BACKGROUND: Retrospective studies evaluating tissue oximetry in a more recent cohort have shown superiority in flap outcomes. This study compares the use of tissue oximetry in a historical cohort to clinical observation and handheld doppler in a more recent cohort. We hypothesize that there is no benefit to using tissue oximetry.

METHODS: A retrospective review was performed on patients who underwent abdominal-based autologous breast reconstruction by five microsurgeons at an academic institution from 2009 to 2020. Method of postoperative flap monitoring was determined then operative details and complications were analyzed.

RESULTS: 1367 flaps were reviewed; 740 flaps in 460 patients were monitored with clinical observation and tissue oximetry, and 627 flaps in 391 patients were monitored with clinical observation and handheld doppler. There were no statistical differences in ischemic (p = .59) or congestive complications (p = .41), flap salvage rates when exploring for venous or arterial compromise (p = .52), or early flap loss (p = .56). Although not significant, acute flap-related return to the operating room was lower in the doppler group (4.6%) compared to the oximetry group (6.1%; p = .22). Flaps monitored with tissue oximetry had a statistical increase in length of stay (4.8 ± 1.4 days vs. 3.8 ± 1.6 days; p ≤ .001). The rates of late partial flap loss and fat necrosis were significantly higher in the oximetry group (2.6%, 19/740 vs. 0.3%, 2/740; p = .04) and (18.2%, 135/740 vs. 13.6%, 85/627; p = .02), respectively.

CONCLUSIONS: There is no statistical benefit to the use of tissue oximetry compared to handheld doppler in flap monitoring with regards to flap outcomes.

PMID:35238069 | DOI:10.1002/micr.30873