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Nevin Manimala Statistics

Large-scale comparative genomics to refine the organization of the global Salmonella enterica population structure

Microb Genom. 2022 Dec;8(12). doi: 10.1099/mgen.0.000906.

ABSTRACT

The White-Kauffmann-Le Minor (WKL) scheme is the most widely used Salmonella typing scheme for reporting the disease prevalence of the enteric pathogen. With the advent of whole-genome sequencing (WGS), in silico methods have increasingly replaced traditional serotyping due to reproducibility, speed and coverage. However, despite integrating genomic-based typing by in silico serotyping tools such as SISTR, in silico serotyping in certain contexts remains ambiguous and insufficiently informative. Specifically, in silico serotyping does not attempt to resolve polyphyly. Furthermore, in spite of the widespread acknowledgement of polyphyly from genomic studies, the prevalence of polyphyletic serovars is not well characterized. Here, we applied a genomics approach to acquire the necessary resolution to classify genetically discordant serovars and propose an alternative typing scheme that consistently reflect natural Salmonella populations. By accessing the unprecedented volume of bacterial genomic data publicly available in GenomeTrakr and PubMLST databases (>180 000 genomes representing 723 serovars), we characterized the global Salmonella population structure and systematically identified putative non-monophyletic serovars. The proportion of putative non-monophyletic serovars was estimated higher than previous reports, reinforcing the inability of antigenic determinants to depict the complexity of Salmonella evolutionary history. We explored the extent of genetic diversity masked by serotyping labels and found significant intra-serovar molecular differences across many clinically important serovars. To avoid false discovery due to incorrect in silico serotyping calls, we cross-referenced reported serovar labels and concluded a low error rate in in silico serotyping. The combined application of clustering statistics and genome-wide association methods demonstrated effective characterization of stable bacterial populations and explained functional differences. The collective methods adopted in our study have practical values in establishing genomic-based typing nomenclatures for an entire microbial species or closely related subpopulations. Ultimately, we foresee an improved typing scheme to be a hybrid that integrates both genomic and antigenic information such that the resolution from WGS is leveraged to improve the precision of subpopulation classification while preserving the common names defined by the WKL scheme.

PMID:36748524 | DOI:10.1099/mgen.0.000906

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Tooth Fracture and Associated Risk Factors in Permanent Molars Treated with Vital Pulp Therapy and Restored with Direct Resin Composites: A Retrospective Survival Analysis in Young Patients

Eur Endod J. 2023 Jan;8(1):37-46. doi: 10.14744/eej.2022.18894.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the survival from fractures and risk factors of VPT-treated permanent molars restored with direct resin composites in young patients.

METHODS: The dental records of patients aged 6 to 18 years with VPT-treated permanent molars restored with resin composites were retrospectively evaluated for the presence of fractures on these teeth. Kaplan-Meier methods were used to estimate the survival probabilities. The potential risk factors were assessed using the multivariable Cox proportional hazard model.

RESULTS: A total of 234 treated molars from 189 patients were included. An overall average follow-up time was 33.34+-20.54 months (ranging from 6 to 83 months). At the end of the study, 21.8% of molars had fractures with the majority of them (92.2%) were restorable. Radiographically, only 3.9% of the fractured molars had periapical lesions and considered VPT failures. The percentages of the fracture types are as follows: 54.9% natural tooth structure fracture, 27.5% restoration fracture, and 17.6% combination fracture. The most common fracture location among the 37 molars with natural tooth fracture (either alone or in combination with restoration fracture) was at the marginal ridge (59.5%), followed by the marginal ridge extending to cusp (21.6%), and the cusp itself (18.9%). The cumulative survival probabilities of these teeth decreased over time, reaching 66.02% (95% CI: 55.89-74.36) after 5 years. VPT-treated molars in the mandible had a 2.1 times higher risk of fracture than those in the maxilla. Furthermore, the molars treated with partial and coronal pulpotomy had 2.4 times and 4.6 times higher risks of fracture when compared to those with indirect pulp capping, respectively.

CONCLUSION: In VPT-treated permanent molars in young patients, more fractures were seen in mandibular teeth and in teeth with pulp roof removal (partial and coronal pulpotomy). Clinicians should plan for proper restoration on these teeth. (EEJ-2022-08-097).

PMID:36748448 | DOI:10.14744/eej.2022.18894

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Fracture Resistance of Endodontically Treated Maxillary Premolars with Non-carious Cervical Lesions Restored with Different Post Systems

Eur Endod J. 2023 Jan;8(1):65-71. doi: 10.14744/eej.2022.96720.

ABSTRACT

OBJECTIVE: To test the hypothesis that the (i) presence of non-carious cervical lesions (NCCLs) and (ii) type of post system have no effect on the fracture resistance and pattern in endodontically treated maxillary premolars.

METHODS: Human maxillary first premolars (n=60) with two root canals were randomly allocated into four groups (n=15). Buccal wedge-shaped NCCLs were prepared in 45 teeth specimens. Following root canal treatment, the specimens were randomly divided into (i) composite resin core (CRC); (ii) NCCLs + composite resin core (NCCL+CRC); (iii) NCCLs+prefabricated fibre-reinforced composite post + composite resin core (NCCL+PFRC+CRC); (iv) NCCLs+custom fibre posts + composite resin core (NCCL+CFP+CRC). All specimens were subjected to thermocycling (5°C to 55°C/5000 cycles). The compressive load was applied non-axially to the palatal cusp with a universal testing machine at a crosshead speed of 0.5 mm/min at a 30° angle until fracture. Fracture patterns were examined using a loupe magnification (2.5×) under transillumination. Statistical analyses were performed using non-parametric tests and pairwise comparisons of the load-to-fracture among the groups. Chi-square test was used to analyse the fracture patterns (P=0.05).

RESULTS: Fracture resistance of NCCL+PFRC+CRC was significantly higher than NCCL+CRC (P=0.011), while NCCL+CFP+CRC did not show any significant difference when compared to NCCL+CRC (P=0.089). No statistical difference was found between CRC, NCCL+PFRC+CRC and NCCL+CFP+CRC (P=1.000). The frequencies of favourable fracture patterns in descending orders were as follows: CRC (80%), NCCL+CFP+CRC (73%), NCCL+PFRC+CRC (60%), and NCCL+CRC (40%). Chi-square test did not show significant differences in fracture patterns among all groups (P=0.110).

CONCLUSION: Restoration of the endodontically treated maxillary premolars with NCCLs, with or without post, resulted in similar fracture resistance as their counterparts without NCCLs. Placement of a prefabricated fibre-reinforced composite post exhibited greater fracture resistance to the maxillary premolars with restored NCCLs than those without a post. (EEJ-2022-06-077).

PMID:36748446 | DOI:10.14744/eej.2022.96720

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Advanced Electrochemical Reamer (EC-Reamer) for Root Canal Treatment

Eur Endod J. 2023 Jan;8(1):79-89. doi: 10.14744/eej.2022.86094.

ABSTRACT

OBJECTIVE: According to the American Association of Endodontists (AAE), 22 million endodontic procedures have been performed annually. Root canal treatment is needed to prevent infection and restore function when a tooth is severely infected or decayed. This procedure is the only way to preserve the natural tooth and avoid artificial replacement (implant, denture, etc.). The current study aims to develop an electrochemical reamer (EC-Reamer or EC-R) that can help to disinfect the canal system and thus improve the success rate of root canal treatment.

METHODS: The COMSOL Multiphysics software was utilized to simulate the experimental setup and confirm the current flow in the electrolyte. The benchtop experimental approach follows a specific electrochemical protocol, (i) open circuit potential to monitor the electrochemical stabilization and (ii) potentiostatic scan at -9.0 V as the treatment stage. Identification of feasible reference electrode (RE) and insulation material for the exploratory benchtop studies considered platinum (Pt) and gold (Au) wire as the REs and hot melt adhesive (HMA) and liquid tape as the insulation materials. The antimicrobial effects of EC-R were analysed using Enterococcus faecalis (E. faecalis). One-way ANOVA with the Tukey post hoc test and a significance level of P<0.05 is used to compare the groups with an experimental duration of 60 seconds.

RESULTS: The findings showed that magnitude and current fluctuations created by Pt wire are promising when compared to Au wire, while Pt-HMA pair is chosen considering Pt’s good electrochemical inertness and HMA’s easy handling, availability, and non-hazardous features. The use of potentiostatic duration of 1 s and 3 s resulted in >99.99% E. faecalis reduction. Duration at 5 s and above resulted in a total bacterial kill. Statistical analysis confirmed a significant difference among the groups tested with commercial and custom-built potentiostats.

CONCLUSION: The outcome provided preliminary data for developing an EC-R prototype to enhance the antimicrobial effect during root canal treatment potentially. (EEJ-2022-01-04).

PMID:36748441 | DOI:10.14744/eej.2022.86094

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Anti-Tumor Efficacy of Anti-PD-1/PD-L1 Antibodies in Combination With Other Anticancer Drugs in Solid Tumors: A Systematic Review and Meta-Analysis

Cancer Control. 2022 Jan-Dec;29:10732748221140694. doi: 10.1177/10732748221140694.

ABSTRACT

BACKGROUND: The clinical efficacy of immune checkpoint inhibitors (CPIs) has been proven; however, it is also known that their efficacy as monotherapy is limited, with a response rate of 20% or less in solid tumors. The combination of CPIs and anticancer agents has been actively attempted in solid tumors area. In this systematic review and meta-analysis, we aimed to find favorable combination therapies of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors in terms of anti-tumor efficacy in clinical settings.

METHODS: An electronic database search was performed using ClinicalTrials.gov, PubMed, and ASCO/ESMO annual meeting libraries. We included randomized or non-randomized trials designed to evaluate the efficacy and safety of combination therapies of PD-1/PD-L1 inhibitors and other anticancer drug-containing therapies. All clinical studies selected were solid tumors with objective response rate (ORR) data. The quality of the evidence was assessed with the Cochrane risk of bias tool or the Newcastle-Ottawa Scale. Meta-analysis used random effects models to pool results.

RESULTS: Sixteen studies involving 3793 patients were included in the primary analysis. These studies have a monotherapy group with PD-1/PD-L1 inhibitors as the control group or the in-study arm/cohort (1863 patients in the combination group with PD-1/PD-L1 inhibitors and 1930 patients in PD-1/PD-L1 inhibitor monotherapy). The pooled results showed that the combination of PD-1/PD-L1 inhibitors and other anticancer drugs significantly improved the ORR (relative risk [RR] = 1.79, 95% confidence interval [CI] 1.46, 2.20). In the subgroup analysis, PD-1/PD-L1 inhibitor plus DNA-synthesis or microtubule inhibitor led to a statistically significant improvement in the ORR compared to PD-1/PD-L1 inhibitor alone.

CONCLUSIONS: It was suggested that combinations of PD-1/PD-L1 inhibitors and potential immunogenic cell death (ICD) inducers improve the clinical anti-tumor efficacy, although updated meta-analyses based on the results of ongoing clinical trials are further needed.

PMID:36748438 | DOI:10.1177/10732748221140694

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Hantavirus infection as a risk factor for chronic kidney disease of unknown aetiology (CKDu) and its prevalence in endemic areas of Sri Lanka since 2010 according to a retrospective serological analysis

J Med Microbiol. 2022 Dec;71(12). doi: 10.1099/jmm.0.001630.

ABSTRACT

Background. Chronic kidney disease of unknown aetiology (CKDu) is a major public health problem in Sri Lanka, especially among agrarian communities. Although the cause of CKDu is still unknown, hantavirus infection has been proposed as a risk factor.Methods. This study was performed using serological samples collected from two CKDu-endemic areas, Anuradhapura (2010) and Badulla districts (2010 and 2016), and a non-endemic area, Matale (2016) district. The presence of anti-Thailand orthohantavirus IgG antibodies was investigated in serum samples. Hantavirus seroprevalence and demographic data were epidemiologically analysed.Results. Seroprevalence was higher in CKDu patients (40.6-60.0 %) and healthy individuals in CKDu-endemic areas (17.6-25.5 %) than in healthy individuals in non-endemic areas (3.0 %). Statistically significant odds ratios (ORs) for hantavirus infection in CKDu patients were detected in CKDu-endemic areas [ORs: 3.2 and 3.1; 95 % confidence interval (CI): 1.8-5.5 and 1.8-5.2 in Anuradhapura and Badulla districts in 2010; and OR: 4.4, 95 % CI: 2.3-8.5 in 2016 in Badulla district). Furthermore, the OR for hantavirus infection in Badulla district has increased in the last decade from 3.1 (95 % CI: 1.8-5.3) to 4.4 (95 % CI: 2.3-8.5).Conclusion. Hantavirus infection has been prevalent in two distant CKDu-endemic areas since 2010. The observed significant association of hantavirus seropositivity with CKDu indicates a possible role of hantavirus infection in CKDu pathogenesis.

PMID:36748416 | DOI:10.1099/jmm.0.001630

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Sintilimab plus chemotherapy for first-line treatment of advanced or metastatic nonsquamous non-small-cell lung cancer: network meta-analysis

Immunotherapy. 2023 Feb 7. doi: 10.2217/imt-2022-0252. Online ahead of print.

ABSTRACT

Aim: This systematic literature review and network meta-analysis evaluated the efficacy and safety of sintilimab + pemetrexed + platinum versus US FDA-approved/National Comprehensive Cancer Network-recommended immune checkpoint inhibitor (ICI) combination therapies for untreated advanced/metastatic non-squamous non-small-cell lung cancer without EGFR/ALK aberrations. Methods: Bayesian network meta-analysis was the base-case analysis and included assessment of fixed and random effects, and independent and simultaneous models, adjusting for baseline risk (placebo response). Chemotherapy was the common comparator. Results: Sintilimab + pemetrexed + platinum was associated with significantly longer progression-free survival than atezolizumab + platinum + nab-paclitaxel (hazard ratio [HR]: 0.57; 95% credible interval [CrI]: 0.40-0.82) and nivolumab + ipilimumab + pemetrexed + platinum (HR: 0.66; 95% CrI: 0.48-0.92). Sintilimab + pemetrexed + platinum and pembrolizumab + pemetrexed + platinum showed comparable progression-free survival (HR: 0.96; 95% CrI: 0.71-1.30). There was no significant difference in overall survival (HR range: 0.61-0.81) or overall response rates (odds ratio [OR] range: 0.29-0.75) between sintilimab + pemetrexed + platinum and the other ICI combinations. The incidence of high-grade adverse events was higher with sintilimab + pemetrexed + platinum than with nivolumab + ipilimumab (OR: 0.46; 95% CrI: 0.33-0.64) or without chemotherapy (OR: 0.25; 95% CrI: 0.19-0.34), with no significant difference between sintilimab + pemetrexed + platinum and the other ICI combinations. Conclusion: Sintilimab + pemetrexed + platinum showed comparable efficacy and safety versus US standard-of-care first-line ICI combinations for advanced/metastatic non-squamous non-small-cell lung cancer.

PMID:36748406 | DOI:10.2217/imt-2022-0252

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Trajectories of reproductive transition phase mood disorder from pregnancy to postpartum: A Swiss longitudinal study

Womens Health (Lond). 2023 Jan-Dec;19:17455057221147391. doi: 10.1177/17455057221147391.

ABSTRACT

BACKGROUND: Depressive symptoms are common in the peripartum period and pose a great risk to the well-being of the mother, the infant, and the entire family. Evidence from longitudinal studies suggests that affected women do not constitute one homogeneous group in terms of severity, chronicity, and onset of symptoms. To account for individual differences regarding the longitudinal course of depressive symptoms from pregnancy to the postpartum period, growth mixture models have proven to be useful.

METHODS: We conducted a group-based trajectory modeling analysis to identify perinatal depressive symptom trajectories in a Swiss sample (n = 151). Depressive symptoms were assessed six times, covering nearly 6 months from the third trimester of pregnancy to 3 months postpartum. In addition to determining perinatal depressive symptom trajectories, we aimed to examine whether these trajectories are linked to psychopathological risk factors such as a history of premenstrual syndrome (PMS), anxiety, prenatal stress, and somatic symptoms after delivery that are associated with hormonal fluctuations.

RESULTS: The findings revealed three trajectories of perinatal depressive symptoms that were relatively stable over time and differed in symptom load (low, medium, high), as well as one trajectory of decreasing symptoms, with a significant symptom reduction after giving birth. Women with a higher depressive symptom load experienced a greater degree of prior premenstrual symptoms, prenatal anxiety, and birth anxiety, as well as somatic symptoms after delivery.

CONCLUSION: Further research is needed to account for the distinct trajectories of perinatal depressive symptoms in order to provide appropriate care for affected women. A focus on somatic symptoms after delivery and their association with depressive mood is essential to better understand the potential shared etiopathology of reproductive transition phase mood disorders.

PMID:36748405 | DOI:10.1177/17455057221147391

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Variations in ERP data quality across paradigms, participants, and scoring procedures

Psychophysiology. 2023 Feb 7:e14264. doi: 10.1111/psyp.14264. Online ahead of print.

ABSTRACT

Although it is widely accepted that data quality for event-related potential (ERP) components varies considerably across studies and across participants within a study, ERP data quality has not received much systematic analysis. The present study used a recently developed metric of ERP data quality- the standardized measurement error (SME)-to examine how data quality varies across different ERP paradigms, across individual participants, and across different procedures for quantifying amplitude and latency values. The EEG recordings were taken from the ERP CORE, which includes data from 40 neurotypical college students for seven widely studied ERP components: P3b, N170, mismatch negativity, N400, error-related negativity, N2pc, and lateralized readiness potential. Large differences in data quality were observed across the different ERP components, and very large differences in data quality were observed across participants. Data quality also varied depending on the algorithm used to quantify the amplitude and especially the latency of a given ERP component. These results provide an initial set of benchmark values that can be used for comparison with previous and future ERP studies. They also provide useful information for predicting effect sizes and statistical power in future studies, even with different numbers of trials. More broadly, this study provides a general approach that could be used to determine which specific experimental designs, data collection procedures, and data processing algorithms lead to the best data quality.

PMID:36748399 | DOI:10.1111/psyp.14264

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A survey on the public’s discrimination rate of typical rumors during the coronavirus disease 2019 epidemic

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2022 Dec 28;47(12):1704-1710. doi: 10.11817/j.issn.1672-7347.2022.210799.

ABSTRACT

OBJECTIVES: During the epidemic of coronavirus disease-2019 (COVID-19), the wide spread of rumors caused significant public hazards. This study aims to understand the situation of discrimination for typical COVID-19 rumors by the public and related factors.

METHODS: An anonymous online survey was carried out using Questionnaire Star. The contents included participants’ gender, age, education level, the COVID-19 information sources, and the judgmental questions about 14 representative COVID-19 rumors. The discrimination rate and 95% confidence interval of 14 rumors were estimated, and the association of discrimination rate with gender, age, and education level was analyzed by binary logistic regression.

RESULTS: A total of 2 087 valid questionnaires were collected. The participants were mainly female (62.7%) and below 35 years old (63.4%); the education level was predominantly college/bachelor’s degree (47.3%) and master’s degree or above (39.1%); the participants, who accessed to COVID-19 information included internet media, accounted for 91%. The participants with different gender, age, and education level had significant differences in the distribution of COVID-19 information sources (all P<0.01). The participants’ discrimination rate for 14 rumors ranged from 67.4% to 98.6%, with 4 rumors less than 80%. Women’s discrimination rate of 9 rumors was significantly higher than men’s (all P<0.05). There was no significant difference in the discrimination rate of rumors among the different age groups (all P>0.05), but the differences in the discrimination rate of other rumors among the different age groups varied according to the rumor. Compared to those with high school or less education levels, the discrimination rates were also higher in the respondents with high education levels (P<0.05).

CONCLUSIONS: A few publics are still unable to identify typical rumors during the COVID-19 epidemic. There are associations among genders, age, and the education levels with the discrimination of some rumors. The government authorities should strengthen the true information regarding COVID-19, and therefore enhance the public’s ability to identify rumors.

PMID:36748381 | DOI:10.11817/j.issn.1672-7347.2022.210799