Nevin Manimala

Nat Commun. 2021 Aug 6;12(1):4763. doi: 10.1038/s41467-021-25089-2.

ABSTRACT

The comparison of gene regulatory networks between diseased versus healthy individuals or between two different treatments is an important scientific problem. Here, we propose sc-compReg as a method for the comparative analysis of gene expression regulatory networks between two conditions using single cell gene expression (scRNA-seq) and single cell chromatin accessibility data (scATAC-seq). Our software, sc-compReg, can be used as a stand-alone package that provides joint clustering and embedding of the cells from both scRNA-seq and scATAC-seq, and the construction of differential regulatory networks across two conditions. We apply the method to compare the gene regulatory networks of an individual with chronic lymphocytic leukemia (CLL) versus a healthy control. The analysis reveals a tumor-specific B cell subpopulation in the CLL patient and identifies TOX2 as a potential regulator of this subpopulation.

PMID:34362918 | DOI:10.1038/s41467-021-25089-2

J Neurol Neurosurg Psychiatry. 2021 Aug 6:jnnp-2021-326386. doi: 10.1136/jnnp-2021-326386. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate longitudinal brain atrophy in patients with neuromyelitis optica spectrum disorder (NMOSD).

METHODS: We investigated the longitudinal brain atrophy rate in patients with aquaporin-4 antibody-positive NMOSD (AQP4+NMOSD) and those with multiple sclerosis (MS) in a retrospective cohort study. Brain volume was calculated with statistical parametric mapping-12.

RESULTS: We enrolled 36 patients with AQP4+NMOSD and 60 with MS. Patients with NMOSD were older and had a higher Kurtzke’s expanded disability status scale score at baseline MRI compared with those with MS. Disease duration, annual relapse rate and intervals from the last attack and from disease-modifying drugs initiation were not significantly different between the two groups. Lower normalised lesion volume and higher normalised white matter volume were found in patients with NMOSD compared with those with MS at baseline MRI. However, the annualised atrophy rate of normalised brain volume was similar between the NMOSD (median 0.47; IQR 0.75; p=0.49) and MS (median 0.46; IQR 0.84) groups. After adjustment of age and the presence of clinical relapse, no differences of the annualised atrophy rate of normalised brain volume also were found for NMOSD and MS. Patients with AQP4+NMOSD with long cord lesion showed higher annualised atrophy rate of normalised grey matter volume compared with those without long cord lesion.

CONCLUSIONS: Silent progression of brain atrophy was present in patients with AQP4+NMOSD, as shown in patients with MS, even in the clinically inactive age-matched cases. Subclinical dying back degeneration may explain the brain atrophy in patients with AQP4 +NMOSD.

PMID:34362853 | DOI:10.1136/jnnp-2021-326386

Dent Med Probl. 2021 Aug 6. doi: 10.17219/dmp/131022. Online ahead of print.

ABSTRACT

BACKGROUND: There are studies that examined the effect of staining on the surface properties of composite resins, using different solutions and bleaching applications. However, the effect of both staining and bleaching on the same composite specimens is an issue that needs to be investigated.

OBJECTIVES: The aim of this study was to investigate the surface microhardness, roughness and color changes (ΔE) of 2 different composite resins after staining and bleaching.

MATERIAL AND METHODS: A microhybrid and a nanohybrid composite were used in the study. One hundred and fifty specimens were prepared from each composite. The specimens were divided into 5 groups and stained for 30 days with tea, coffee, cola, red wine, or distilled water (control). Subsequently, each group was divided into 3 subgroups. Each subgroup received a 14-day application of Opalescence™ Boost, Opalescence PF or VivaStyle® Paint On Plus bleaching materials. The color as well as surface microhardness and roughness of all specimens were determined at baseline, after staining and after bleaching. Data was analyzed using the repeated-measures analysis of variance (ANOVA) and the Bonferroni method.

RESULTS: A statistically significant decrease was observed in the surface microhardness of the microhybrid composite specimens after bleaching (p < 0.05).The highest ΔE values were observed in the red wine groups for both composite resins.

CONCLUSIONS: Staining and bleaching may affect surface properties and color, depending on the type, filler and matrix content of the composite resin.

PMID:34358420 | DOI:10.17219/dmp/131022

Clin Otolaryngol. 2021 Aug 6. doi: 10.1111/coa.13844. Online ahead of print.

ABSTRACT

OBJECTIVES: This study investigated the relationship between viral load and the incidence of olfactory and gustatory dysfunction (OD and GD), the incidence of respiratory and gastrointestinal symptoms, and the recovery of OD and GD in COVID-19 patients.

DESIGN: A Retrospective Cohort Study.

SETTING AND PARTICIPANTS: this cohort, conducted on 599 outpatients’ cases in Golestan province between February and Juan 2020.

MAIN OUTCOME MEASURES: The incidence, severity (complete or partial), and recovery time of OD and GD and their associations with cycle threshold (CT) values of SARS-CoV-2 polymerase chain reaction was assessed.

RESULTS: The mean age of patients was 38.27±13.62 years. The incidence of general symptoms included myalgia 70.1%, headache 51.8%, fever 47.7%, and dyspnea 21.4%. 41.9% of patients had gastrointestinal symptoms, including abdominal pain 26.5%, diarrhea 25.2%, nausea 20.5%, and vomiting 12.9%. 12.2% of patients had comorbidity. The trimester recovery rates of OD and GD were 93.94% and 94.74%, respectively. The mean recovery time of OD and GD was 14.56±13.37 and 13.8±3.77 days, respectively. The mean CT value in all patients was 27.45±4.55. There were significant associations between the mean of CT value with headache (P=0.04), GD (P=0.002) and OD (P=0.001).

CONCLUSIONS: The finding of this study indicates a possible association between viral load with incidence of OD and GD in COVID-19 patient’s cases and assures the recovery of OD/GD in these patients.

PMID:34358409 | DOI:10.1111/coa.13844

J Oral Pathol Med. 2021 Aug 6. doi: 10.1111/jop.13226. Online ahead of print.

ABSTRACT

BACKGROUND: Oral lichen planus is a relatively common oral disorder which shares clinical and histopathological features with other lichenoid lesions, leading to considerable inter-observer disagreement. This negatively impacts understanding of the pathogenesis and malignant transformation potential of this condition.

METHODS: Artificial intelligence was employed to create a machine-learning artificial neural network to identify and quantify mononuclear cells and granulocytes within the inflammatory infiltrates in digitized hematoxylin and eosin microscopic slides. Twenty-four regions of interest were extracted from oral lichen planus cases for learning purposes and validated on a retrospective cohort of 130 cases. All cases were related to patients with confirmed diagnoses of oral lichen planus, oral lichenoid lesions, or oral epithelial dysplasia with lichenoid host response.

RESULTS: The number of inflammatory cells was statistically significantly higher in oral lichen planus compared to oral lichenoid lesions or oral epithelial dysplasia with lichenoid host response (p <.0005). The proposed machine-learning method was reliably capable of detecting oral lichen planus cases based on the number of inflammatory cells and the number of mononuclear cells with an area under the curve of 0.982 and 0.988, respectively. Identifying a cut-off point between oral lichen planus and other lichenoid conditions based on the number of mononuclear cells showed a sensitivity of 100% and an accuracy of 94.62%.

CONCLUSION: Artificial intelligence has shown promising outcomes and provides a robust approach to enhance the accuracy of anatomical pathologists in accurately diagnosing oral lichen planus using features of disease pathogenesis.

PMID:34358361 | DOI:10.1111/jop.13226

Clin Oral Implants Res. 2021 Aug 6. doi: 10.1111/clr.13817. Online ahead of print.

ABSTRACT

OBJECTIVES: Resonance frequency analysis (RFA) is used to monitor implant stability. Its output, the Implant Stability Quotient (ISQ), supposedly correlates with insertion torque, a common measurement of primary stability. However, the reliability of RFA in condensed bone remains unclear.

MATERIAL AND METHODS: In this human cadaver study in edentulous jaws and fresh extraction sockets, implants were inserted using a split-mouth approach into condensed or untreated bone. Mean ISQ, peak insertion torque, as well as pre- and postoperative bone volume fractions (BV/TV) were assessed.

RESULTS: In edentulous jaws, insertion torque and ISQ correlated both in untreated (r = 0.63, p = 0.02) and in condensed (r = 0.82, p = < 0.01) bone. In extraction sockets, insertion torque and ISQ only correlated in untreated (r = 0.78, p < 0.01), but not in condensed bone (r = 0.15, p = 0.58). In all edentulous jaws, preoperative BV/TV correlated with insertion torque (r = 0.90, p < 0.0001), ISQ (r = 0.64, p < 0.001), and changes in BV/TV (r = -0.71, p < 0.01). In all extraction sockets, preoperative BV/TV did not correlate with either insertion torque (r = 0.33, p = 0.15), ISQ (r = 0.38, p = 0.09), or changes in BV/TV (r = -0.41, p = 0.09). Joint analysis identified preoperative BV/TV as a predictor of postoperative BV/TV (p < 0.001), insertion torque (p < 0.001), and ISQ (p < 0.001).

CONCLUSIONS: RFA is feasible for monitoring stability after late implant placement into condensed bone, but not after immediate placement into condensed fresh extraction sites.

PMID:34358360 | DOI:10.1111/clr.13817

Cancer. 2021 Aug 6. doi: 10.1002/cncr.33830. Online ahead of print.

ABSTRACT

BACKGROUND: Few evidence-based psychosocial programs have been tested among adolescents and young adults (AYAs) with advanced cancer (AC), and early advance care planning (ACP) in this population is rare. The authors aimed to determine the feasibility and acceptability of 1) delivering an established resilience-coaching program, and 2) integrating ACP into that program, among AYAs with AC.

METHODS: Eligible AYAs were 12 to 24 years old, diagnosed with advanced cancer (recurrent/refractory disease or a diagnosis associated with <50% survival) and fluent in English. The Promoting Resilience in Stress Management-Advanced Cancer (PRISM-AC) program included PRISM’s standard sessions targeting stress-management, goal-setting, cognitive-restructuring, and meaning-making, delivered 1:1, 1 to 2 weeks apart, plus a new session involving elements of the AYA-specific Voicing My Choices ACP guide. Participants completed surveys at baseline and 12 weeks, and exit interviews following study completion. Feasibility was defined as ≥70% completion of 1) standard 4-session PRISM and 2) the new ACP session among those completing standard PRISM. Acceptability was defined qualitatively. Trajectories of patient-reported anxiety, depression, and hope were examined descriptively.

RESULTS: Of 50 eligible, approached AYAs, 26 (52%) enrolled and completed baseline surveys. The AYAs had a mean age of 16 years (SD = 2.7 years), and the majority were male (73%) and White/Caucasian (62%). Twenty-two AYAs (85%) completed standard PRISM, and of those, 18 (82%) completed the ACP session. Feedback was highly positive; 100% and 91% described the overall and ACP programs as valuable, respectively. Anxiety, depression, and hope were unchanged after the program.

CONCLUSIONS: Resilience coaching followed by integrated ACP is feasible and acceptable for AYAs with AC. Participating did not cause distress or decrease hope.

LAY SUMMARY: Advance care planning (ACP) among adolescents and young adults (AYAs) with advanced cancer can be difficult to introduce. We investigated whether it is feasible and acceptable to integrate ACP into an existing resilience-coaching program for AYAs. In this cohort study of 26 AYAs with advanced cancer, we found the Promoting Resilience in Stress Management-Advanced Cancer program to be feasible (≥70% intervention-completion) and highly acceptable (positive post-participation feedback, no evidence of participant-distress). We conclude that an intervention integrating resilience coaching and ACP is feasible and acceptable among AYAs with advanced cancer.

PMID:34358332 | DOI:10.1002/cncr.33830

Sleep. 2021 Aug 6:zsab200. doi: 10.1093/sleep/zsab200. Online ahead of print.

ABSTRACT

STUDY OBJECTIVES: To assess the efficacy and safety of FT218, a novel once-nightly formulation of sodium oxybate (ON-SXB), in patients with narcolepsy in the phase 3 REST-ON trial.

METHODS: Narcolepsy patients aged ≥16 years were randomized 1:1 to uptitration of ON-SXB (4.5, 6, 7.5, and 9 g) or placebo. Three coprimary endpoints were change from baseline in mean sleep latency on the Maintenance of Wakefulness test, Clinical Global Impression-Improvement rating, and weekly cataplexy attacks at 9, 7.5, and 6 g. Secondary endpoints included change from baseline on the Epworth Sleepiness Scale. Safety included adverse drug reactions and clinical laboratory assessments.

RESULTS: In total, 222 patients were randomized; 212 received ≥1 dose of ON-SXB (n=107) or placebo (n=105). For the 3 coprimary endpoints and Epworth Sleepiness Scale, all 3 doses of ON-SXB demonstrated clinically meaningful, statistically significant improvement vs placebo (all P<0.001). For ON-SXB 9 g vs placebo, increase in mean sleep latency was 10.8 vs 4.7 min (LSMD [95% CI], 6.13 [3.52-8.75]), 72.0% vs 31.6% were rated much/very much improved on Clinical Global Impression-Improvement (OR [95% CI], 5.56 [2.76-11.23]), change in mean weekly number of cataplexy attacks was -11.5 vs -4.9 (LSMD [95% CI], -6.65 [-9.32 to -3.98]), and change in Epworth Sleepiness Scale was -6.5 and -2.7 (LSMD [95% CI], -6.52 [-5.47 to -2.26]). Common adverse reactions included nausea, vomiting, headache, dizziness, and enuresis.

CONCLUSIONS: ON-SXB significantly improved narcolepsy symptoms; its safety profile was consistent with SXB. ON-SXB conferred efficacy with a clearly beneficial single nighttime dose.

PMID:34358324 | DOI:10.1093/sleep/zsab200

Bioinformatics. 2021 Aug 6:btab574. doi: 10.1093/bioinformatics/btab574. Online ahead of print.

ABSTRACT

MOTIVATION: The investigation of quantitative trait loci (QTL) is an essential component in our understanding of how organisms vary phenotypically. However, many important crop species are polyploid (carrying more than two copies of each chromosome), requiring specialised tools for such analyses. Moreover, deciphering meiotic processes at higher ploidy levels is not straightforward, but is necessary to understand the reproductive dynamics of these species, or uncover potential barriers to their genetic improvement.

RESULTS: Here we present polyqtlR, a novel software tool to facilitate such analyses in (auto)polyploid crops. It performs QTL interval mapping in F1 populations of outcrossing polyploids of any ploidy level using identity-by-descent (IBD) probabilities. The allelic composition of discovered QTL can be explored, enabling favourable alleles to be identified and tracked in the population. Visualisation tools within the package facilitate this process, and options to include genetic co-factors and experimental factors are included. Detailed information on polyploid meiosis including prediction of multivalent pairing structures, detection of preferential chromosomal pairing and location of double reduction events can be performed.

AVAILABILITY: polyqtlR is freely available from the Comprehensive R Archive Network (CRAN) at http://cran.r-project.org/package=polyqtlR.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:34358315 | DOI:10.1093/bioinformatics/btab574

Clin Infect Dis. 2021 Aug 6:ciab679. doi: 10.1093/cid/ciab679. Online ahead of print.

ABSTRACT

BACKGROUND: 240-million people have schistosomiasis despite decades of interventions. Infections cannot be directly observed, and egg-based Kato-Katz thick smears lack sensitivity, impacting treatment efficacy and reinfection rate estimates. The Point-of-Care Circulating Cathodic Antigen test (POC-CCA) is advocated as an improvement upon the Kato-Katz, however improved estimates are limited by ambiguities in the interpretation of Trace results.

METHOD: We collected repeated Kato-Katz counts from 210 school-aged children and scored POC-CCAs according to manufacturer’s guidelines (POC-CCA+) and the externally developed G-Score. We used Hidden Markov Models parameterised with Kato-Katz; Kato-Katz and POC-CCA+; and Kato-Katz and G-Scores, inferring latent clearance and reinfection probabilities at four timepoints over six-months through a more formal statistical reconciliation of these diagnostics than previously conducted. Our approach required minimal but robust assumptions regarding Trace interpretations.

RESULTS: Antigen-based models estimated higher infection prevalence across all timepoints compared with the Kato-Katz model, corresponding to lower clearance and higher reinfection estimates. Specifically, pre-treatment prevalence estimates were 85% (Kato-Katz; 95% CI: 79-92%), 99% (POC-CCA+; 97-100%) and 98% (G-Score; 95-100%). Post-treatment, 93% (Kato-Katz; 88-96%), 72% (POC-CCA+; 64-79%) and 65% (G-Score; 57-73%) of those infected were estimated to clear infection. Of those who cleared infection, 35% (Kato-Katz; 27-42%), 51% (POC-CCA+; 41-62%) and 44% (G-Score; 33-55%) were estimated to have been reinfected by nine-weeks.

CONCLUSION: Treatment impact was shorter-lived than only Kato-Katz-based estimates suggested, with lower clearance and rapid reinfection. Three-weeks-post-treatment captured longer-term clearance dynamics. Nine-weeks-post-treatment captured reinfection, but alone could not discern between failed clearance and rapid reinfection. Therefore, frequent sampling is required to understand these important epidemiological dynamics.

PMID:34358299 | DOI:10.1093/cid/ciab679