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Nevin Manimala Statistics

‘Invisible actors’-How poor methodology reporting compromises mouse models of oncology: A cross-sectional survey

PLoS One. 2022 Oct 20;17(10):e0274738. doi: 10.1371/journal.pone.0274738. eCollection 2022.

ABSTRACT

The laboratory mouse is a key player in preclinical oncology research. However, emphasis of techniques reporting at the expense of critical animal-related detail compromises research integrity, animal welfare, and, ultimately, the translation potential of mouse-based oncology models. To evaluate current reporting practices, we performed a cross-sectional survey of 400 preclinical oncology studies using mouse solid-tumour models. Articles published in 2020 were selected from 20 journals that specifically endorsed the ARRIVE (Animal Research: Reporting of In Vivo Experiments) preclinical reporting guidelines. We assessed reporting compliance for 22 items in five domains: ethical oversight assurance, animal signalment, husbandry, welfare, and euthanasia. Data were analysed using hierarchical generalised random-intercept models, clustered on journal. Overall, reporting of animal-related items was poor. Median compliance over all categories was 23%. There was little or no association between extent of reporting compliance and journal or journal impact factor. Age, sex, and source were reported most frequently, but verifiable strain information was reported for <10% of studies. Animal husbandry, housing environment, and welfare items were reported by <5% of studies. Fewer than one in four studies reported analgesia use, humane endpoints, or an identifiable method of euthanasia. Of concern was the poor documentation of ethical oversight information. Fewer than one in four provided verifiable approval information, and almost one in ten reported no information, or information that was demonstrably false. Mice are the “invisible actors” in preclinical oncology research. In spite of widespread endorsement of reporting guidelines, adherence to reporting guidelines on the part of authors is poor and journals fail to enforce guideline reporting standards. In particular, the inadequate reporting of key animal-related items severely restricts the utility and translation potential of mouse models, and results in research waste. Both investigators and journals have the ethical responsibility to ensure animals are not wasted in uninformative research.

PMID:36264974 | DOI:10.1371/journal.pone.0274738

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Nevin Manimala Statistics

Knowledge and awareness of mitochondrial diseases among physicians in the tertiary hospitals in Ghana

PLoS One. 2022 Oct 20;17(10):e0276549. doi: 10.1371/journal.pone.0276549. eCollection 2022.

ABSTRACT

BACKGROUND: Mitochondrial diseases/disorders (MDs), for decades, have been identified as a key underlying condition for many chronic diseases globally. However, data on the knowledge and prevalence of MDs in many countries in sub-Saharan Africa are lacking. This study assessed the knowledge, and awareness, of MDs among senior medical doctors in the five tertiary hospitals in Ghana.

METHOD: Data were collected from one hundred and twenty-eight (128) medical doctors in the five Tertiary Hospitals in Ghana using both closed and open-ended questionnaires and analysed using descriptive statistics.

RESULTS: Of the 128 respondents, 70.32% were senior medical officers and above, 87% of them indicated that they were aware of MDs and over 90% said physicians do not often diagnose MDs in Ghana. About 81% indicated that MDs are associated with chronic illnesses whilst 72% said the disease is diagnosed in both males and females. About 45% of the respondents alluded to the fact that MDs are difficult to diagnose, are associated with mutations in both the mitochondrial and the nuclear DNA, and are non-infectious diseases. Approximately 85% said nervous system dysfunction and muscle weakness are some of the symptoms associated with MDs whilst 77% said fatigue is also one of the symptoms. About 38% of the respondents specified that they encounter myopathies. A majority (70%) did not know about the availability of any consensus or standard diagnostic procedure and/or drugs for MDs.

CONCLUSION: There is a high level of knowledge and awareness of MDs among the respondents. However, there is a low disease encounter, which could be due to a lack of diagnostic protocols or a low disease prevalence. It is, therefore recommend that a patient perspective study, which looks at clinical records and laboratory data be conducted to fully ascertain the prevalence of MDs in Ghana and that appropriate educational strategies and interventions aimed at improving the diagnosis of mitochondrial diseases in Ghana be put in place.

PMID:36264964 | DOI:10.1371/journal.pone.0276549

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Nevin Manimala Statistics

Erectile dysfunction after COVID-19 recovery: A follow-up study

PLoS One. 2022 Oct 20;17(10):e0276429. doi: 10.1371/journal.pone.0276429. eCollection 2022.

ABSTRACT

OBJECTIVES: Several studies confirm multiple complications after COVID-19 infection, including men’s sexual health, which is caused by both physical and psychological factors. However, studies focusing on long-term effects among recovered patients are still lacking. Therefore, we aimed to investigate the erectile function at three months after COVID-19 recovery along with its predicting factors.

METHODS: We enrolled all COVID-19 male patients, who were hospitalized from May to July 2021, and declared to be sexually active within the previous two weeks. Demographic data, mental health status, and erectile function were collected at baseline and prospectively recollected three months after hospital discharge. To determine changes between baseline and the follow-up, a generalized linear mixed effect model (GLMM) was used. Also, logistic regression analysis was used to identify the associating factors of erectile dysfunction (ED) at three months.

RESULTS: One hundred fifty-three men with COVID-19 participated. Using GLMM, ED prevalence at three months after recovery was 50.3%, which was significantly lower compared with ED prevalence at baseline (64.7%, P = 0.002). Declination of prevalence of major depression and anxiety disorder was found, but only major depression reached statistical significance (major depression 13.7% vs. 1.4%, P < 0.001, anxiety disorder 5.2% vs. 2.8% P = 0.22). Logistic regression, adjusted for BMI, medical comorbidities, and self-reported normal morning erection, showed a significant association between ED at three months and age above 40 years and diagnosis of major depression with adjusted OR of 2.65, 95% CI 1.17-6.01, P = 0.02 and 8.93, 95% CI 2.28-34.9, P = 0.002, respectively.

CONCLUSION: Our study showed a high ED prevalence during the third month of recovery from COVID-19. The predicting factors of persistent ED were age over 40 years and diagnosis of major depression during acute infection.

PMID:36264947 | DOI:10.1371/journal.pone.0276429

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Nevin Manimala Statistics

Survival time to complications of congestive heart failure patients at Felege Hiwot comprehensive specialized referral hospital, Bahir Dar, Ethiopia

PLoS One. 2022 Oct 20;17(10):e0276440. doi: 10.1371/journal.pone.0276440. eCollection 2022.

ABSTRACT

BACKGROUNDS: Congestive heart failure is a serious chronic condition when the heart’s muscles become too damaged and a condition in which one or both ventricles cannot pump sufficient blood to meet the metabolic needs of the body. This study aimed to identify factors affecting the complications time of congestive heart failure patients treated from January 2016 to December 2019 at Felege Hiwot comprehensive specialized referral hospital in Bahir Dar, Ethiopia.

METHODS: A hospital-based retrospective data collection was collected from the medical charts of 218 randomly selected congestive heart failure patients. The Kaplan-Meier curve and the Cox proportional hazards model were used to compare and identify the factors associated with time to complication in patients with congestive heart failure.

RESULTS: The median complication time of congestive heart failure patients was 22 months [95% CI: 21.98-28.01]. About 194 (88.99%) of the patients were complicated. The Kaplan-Meier curve depicts the survival probability of complicated patients decreasing as the complication time increases. The hazard ratios for serum sodium concentration, left ventricular ejection fraction, patients from rural areas, age of patients, serum hemoglobin concentration, and New York heart association classes I, II, and III were given 0.94 [95% CI: 0.90-1.00], 0.74 [95% CI: 0.65-0.85], 0.75 [95% CI: 0.68-0.84], 1.28 [95% CI: 1.12-1.46], 0.89 [95% CI: 0.85-0.94], 0.44 [95% CI: 0.36-0.53], 0.54 [95% CI: 0.47-0.62] and 0.73 [95% CI: 0.65-0.81] respectively, and they are statistically associated with the complication time of congestive heart failure patients.

CONCLUSIONS: The median complication time of congestive heart failure patients was 22 months. This study strongly suggests that healthcare awareness should be strengthened earlier about the potential complications for patients with lower serum sodium concentrations below the threshold and aged congestive heart failure patients to reduce the risk of developing complications.

PMID:36264946 | DOI:10.1371/journal.pone.0276440

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Nevin Manimala Statistics

Skin microbiota of oxazolone-induced contact hypersensitivity mouse model

PLoS One. 2022 Oct 20;17(10):e0276071. doi: 10.1371/journal.pone.0276071. eCollection 2022.

ABSTRACT

Contact allergy is a common skin allergy, which can be studied utilising contact hypersensitivity (CHS) animal model. However, it is not clear, whether CHS is a suitable model to investigate skin microbiota interactions. We characterised the effect of contact dermatitis on the skin microbiota and studied the biological effects of oxazolone (OXA) -induced inflammation on skin thickness, immune cell numbers and changes of the microbiota in CHS mouse model (n = 72) for 28 days. Through 16S rRNA gene sequencing we defined the composition of bacterial communities and associations of bacteria with inflammation. We observed that the vehicle solution of acetone and olive oil induced bacterial community changes on day 1, and OXA-induced changes were observed mainly on day 7. Many of the notably enriched bacteria present in the OXA-challenged positive group represented the genus Faecalibaculum which were most likely derived from the cage environment. Additionally, skin inflammation correlated negatively with Streptococcus, which is considered a native skin bacterium, and positively with Muribacter muris, which is typical in oral environment. Skin inflammation favoured colonisation of cage-derived faecal bacteria, and additionally mouse grooming transferred oral bacteria on the skin. Due to the observed changes, we conclude that CHS model could be used for certain skin microbiome-related research set-ups. However, since vehicle exposure can alter the skin microbiome as such, future studies should include considerations such as careful control sampling and statistical tests to account for potential confounding factors.

PMID:36264944 | DOI:10.1371/journal.pone.0276071

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Nevin Manimala Statistics

Prevalence of premature loss of deciduous teeth and its relationship with gender among children from Acapulco, Guerrero: a cross-sectional study

Bol Med Hosp Infant Mex. 2022;79(5):293-299. doi: 10.24875/BMHIM.21000230.

ABSTRACT

BACKGROUND: Premature loss of deciduous teeth is the exfoliation or extraction before physiological replacement with < 50% or < 75% of the root of the substitute tooth formed or if there is > 1 mm of alveolar bone covering the permanent successor tooth organ. This study aimed to estimate the prevalence of premature tooth loss in children and identify associated factors in a health center in Acapulco, Guerrero.

METHODS: We conducted a cross-sectional study in which we collected information from 109 clinical records of children examined from January 2019 to August 2021. Sociodemographic data of the children and parents were collected: socioeconomic level, non-pathological personal history, and the history of premature deciduous tooth loss. Multivariate analysis to identify factors associated with premature deciduous tooth loss was performed with CIETmap statistical software. Odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the strength of the association.

RESULTS: The prevalence of premature loss of primary teeth was 40% (43/109). The leading cause was caries (84%, 36/43). The tooth organ with the highest loss occurrence was the lower right second molar (33%, 14/43). Gender was identified as an associated factor, with males having a higher risk of loss (ORa = 2.97; CI95% = 1.33-6.65).

CONCLUSIONS: Our results were similar to those reported in other studies. Strategies aimed at health promotion directed at parents and children should be reinforced.

PMID:36264924 | DOI:10.24875/BMHIM.21000230

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Nevin Manimala Statistics

Comprehensive analysis of the immune implication of FABP4 in colon adenocarcinoma

PLoS One. 2022 Oct 20;17(10):e0276430. doi: 10.1371/journal.pone.0276430. eCollection 2022.

ABSTRACT

BACKGROUND: Fatty acid-binding protein 4 (FABP4) has been reported to be associated with tumor progress and poor prognosis in various cancers. However, the relationship between FABP4 expression and tumor immunity in colon adenocarcinoma (COAD) is still poorly understood.

METHODS: FABP4 mRNA expression was analyzed using The Cancer Genome Atlas (TCGA)-COAD data. FABP4 protein staining was performed by immunohistochemistry (IHC) staining in our 10 paired COAD samples and corresponding adjacent noncancerous tissues. The association between FABP4 and immune cell infiltration was evaluated by Tumor Immune Estimation Resource (TIMER) database. FABP4 coexpressed genes were identified based on Cancer Cell Line Encyclopedia (CCLE) database, which were employed for further enrichment analysis. FABP4 related immunomodulators was identified by Tumor and Immune System Interaction Database (TISIDB) database, and a prognostic risk signature was constructed based on FABP4-related immunomodulators using stepwise Cox regression analysis. A nomogram consists of FABP4 related immunomodulators signature and clinical parameters was developed to predict the overall survival (OS).

RESULTS: In TCGA data, we found that the decreased FABP4 mRNA expression in COAD samples compared with normal samples, and low FABP4 mRNA expression was associated with B cells, CD4+ T cells, CD8+ T cells, myeloid dendritic cells, macrophages, and neutrophils. In our 10 paired samples, the protein levels of COAD were lower in all COAD tissues than in their adjacent noncancerous tissues. Functional enrichment analysis revealed that FABP4 coexpressed genes were mostly enriched in immune-related pathways. Based on 54 FABP4-related immunomodulators, a 2-gene FABP4-related prognostic risk signature was developed, and the signature stratified the patients into the high-risk and low-risk groups with statistically different survival outcomes. The Nomogram consists of the prognostic signature and clinical parameters had a certain predictability for prognosis of COAD patients.

CONCLUSION: These findings suggest that FABP4 is associated with 2-gene immune signature which also correlate with the prognosis of COAD patients.

PMID:36264920 | DOI:10.1371/journal.pone.0276430

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Nevin Manimala Statistics

CARD 2023: expanded curation, support for machine learning, and resistome prediction at the Comprehensive Antibiotic Resistance Database

Nucleic Acids Res. 2022 Oct 20:gkac920. doi: 10.1093/nar/gkac920. Online ahead of print.

ABSTRACT

The Comprehensive Antibiotic Resistance Database (CARD; card.mcmaster.ca) combines the Antibiotic Resistance Ontology (ARO) with curated AMR gene (ARG) sequences and resistance-conferring mutations to provide an informatics framework for annotation and interpretation of resistomes. As of version 3.2.4, CARD encompasses 6627 ontology terms, 5010 reference sequences, 1933 mutations, 3004 publications, and 5057 AMR detection models that can be used by the accompanying Resistance Gene Identifier (RGI) software to annotate genomic or metagenomic sequences. Focused curation enhancements since 2020 include expanded β-lactamase curation, incorporation of likelihood-based AMR mutations for Mycobacterium tuberculosis, addition of disinfectants and antiseptics plus their associated ARGs, and systematic curation of resistance-modifying agents. This expanded curation includes 180 new AMR gene families, 15 new drug classes, 1 new resistance mechanism, and two new ontological relationships: evolutionary_variant_of and is_small_molecule_inhibitor. In silico prediction of resistomes and prevalence statistics of ARGs has been expanded to 377 pathogens, 21,079 chromosomes, 2,662 genomic islands, 41,828 plasmids and 155,606 whole-genome shotgun assemblies, resulting in collation of 322,710 unique ARG allele sequences. New features include the CARD:Live collection of community submitted isolate resistome data and the introduction of standardized 15 character CARD Short Names for ARGs to support machine learning efforts.

PMID:36263822 | DOI:10.1093/nar/gkac920

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Nevin Manimala Statistics

Sudden cardiac death risk prediction in arrhythmogenic right ventricular cardiomyopathy: the challenge of complex statistical modelling and its impact in clinical practice

Eur Heart J. 2022 Oct 20:ehac538. doi: 10.1093/eurheartj/ehac538. Online ahead of print.

NO ABSTRACT

PMID:36263796 | DOI:10.1093/eurheartj/ehac538

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Nevin Manimala Statistics

Non-Invasive Vascular Elastography as a One-Step Imaging Technique to Evaluate Early Vascular Changes in Children Compared to B-Mode-Based Intima-Media Thickness Technique : A Validation Study Using Inter- and Intra-Rater Reliability

Can Assoc Radiol J. 2022 Oct 20:8465371221134055. doi: 10.1177/08465371221134055. Online ahead of print.

ABSTRACT

Background: Childhood obesity is linked to higher adult mortality and morbidity from atherosclerosis. It is primordial to detect at-risk children earlier-on to prevent disease progression. Carotid intima-media thickness (IMT) is a subclinical radiological marker for early atherosclerosis. B-mode ultrasound is a known technique to assess IMT, but no gold standard technique exists in children. Non-invasive vascular elastography (NIVE) using speckle statistics is an innovative alternative to evaluate IMT and adds by providing translation, strain and shear strain measurements. Validation studies for both techniques lack in children. Purpose: Validate the reproducibility of the 2 techniques in Canadian children. Methods: We conducted a prospective study where anthropometry, blood pressure, IMT and elastography were measured. Six operators obtained 2 measurements for both carotid arteries using both techniques, for a total of 720 measurements. Inter- and intra-class correlation coefficients (ICC) were calculated for each measurement technique and elastography parameters. Results: 30 participants (13.0 ± 1.26 years, 17 girls) were recruited. Twelve were overweight. No significant difference was found in mean IMT between weight groups for either technique (P = .15 and P = .60). We found excellent inter- (ICC = .98 [95% Confidence Interval (CI): .97; .99]) and intra- (ICC = .90-.93) operator reliability for the B-mode technique, and good inter (ICC = .70 [95% CI: .47; .85]) and intra- (ICC = .71-.91) operator reliability for the NIVE-based technique. Poor reliability was found between techniques (ICC = .30 [95% CI: -.31; .65). For elastography parameters, translation was the most reliable (ICC = .94-.95). Conclusion: IMT measurement is reproducible in children but not between techniques. NIVE gives the advantage of evaluating elastography.

PMID:36263774 | DOI:10.1177/08465371221134055