Tag: statistics

Nature. 2022 Apr 8. doi: 10.1038/s41586-022-04434-5. Online ahead of print.

ABSTRACT

Schizophrenia has a heritability of 60-80%¹, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.

PMID:35396580 | DOI:10.1038/s41586-022-04434-5

Acta Otorhinolaryngol Ital. 2022 Apr 8. doi: 10.14639/0392-100X-N1672. Online ahead of print.

ABSTRACT

OBJECTIVE: The PRO.M.E.THE.O. study (PredictiOn Models in Ent cancer for anti-EGFR based THErapy Optimization) aimed to develop a predictive model (PM) of overall survival (OS) for patients with locally advanced oropharyngeal cancer (LAOC) treated with radiotherapy (RT) and cetuximab (Cet) from an Italian dataset.

METHODS: We enrolled patients with LAOC from 6 centres treated with RT-Cet. Clinical and treatment variables were collected. Patients were randomly divided into training (TS) (80%) and validation (VS) (20%) sets. A binary logistic regression model was used on the TS with stepwise feature selection and then on VS. Timepoints of 2, 3 and 5 years were considered. The area under the curve (AUC) of receiver operating characteristic of 2, 3 and 5 year and confusion matrix statistics at 5-threshold were used as performance criteria.

RESULTS: Overall, 218 patients were enrolled and 174 (79.8%) were analysed. Age at diagnosis, gender, ECOG performance, clinical stage, dose to high-risk volume, overall treatment time and day of RT interruption were considered in the final PMs. The PMs were developed and represented by nomograms with AUC of 0.75, 0.73 and 0.73 for TS and 0.713, 0.713, 0.775 for VS at 2, 3 and 5 years, respectively.

CONCLUSIONS: PRO.M.E.THE.O. allows the creation of a PM for OS in patients with LAOC treated with RT-Cet.

PMID:35396587 | DOI:10.14639/0392-100X-N1672

Nature. 2022 Apr 8. doi: 10.1038/s41586-022-04556-w. Online ahead of print.

ABSTRACT

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P < 2.14 × 10^-6) and 32 genes at a false discovery rate of <5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure and function of the synapse. The associations of the NMDA (N-methyl-D-aspartate) receptor subunit GRIN2A and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GRIA3 provide support for dysfunction of the glutamatergic system as a mechanistic hypothesis in the pathogenesis of schizophrenia. We observe an overlap of rare variant risk among schizophrenia, autism spectrum disorders¹, epilepsy and severe neurodevelopmental disorders², although different mutation types are implicated in some shared genes. Most genes described here, however, are not implicated in neurodevelopment. We demonstrate that genes prioritized from common variant analyses of schizophrenia are enriched in rare variant risk³, suggesting that common and rare genetic risk factors converge at least partially on the same underlying pathogenic biological processes. Even after excluding significantly associated genes, schizophrenia cases still carry a substantial excess of URVs, which indicates that more risk genes await discovery using this approach.

PMID:35396579 | DOI:10.1038/s41586-022-04556-w

J Perinatol. 2022 Apr 8. doi: 10.1038/s41372-022-01376-8. Online ahead of print.

ABSTRACT

OBJECTIVE: Increase the proportion of ≤33 weeks newborns exposed to mother’s own milk (MOM) oral care by 12 h of age by 20% over 2 years to support a healthier microbiome.

STUDY DESIGN: We implemented interventions to support early expression of colostrum and reliable delivery of resultant MOM to premature newborns. Statistical process control charts were used to track progress and provide feedback to staff. Proportions of newborns exposed to MOM by 12 h were compared relative to baseline.

RESULTS: There were 46, 66, and 46 newborns in the baseline, implementation, and sustainability periods, respectively. The primary outcome improved from 48% to 61% in the implementation period (relative change 1.27, 95% CI 0.89, 1.81, p = 0.2), to 69% in sustainability period (relative to baseline 1.45, 95% CI 1.02, 2.08, p = 0.03).

CONCLUSION: An interdisciplinary team-based, multicycle, quality improvement intervention resulted in increased rates of early exposure to MOM.

PMID:35396577 | DOI:10.1038/s41372-022-01376-8

Sci Rep. 2022 Apr 8;12(1):5935. doi: 10.1038/s41598-022-10020-6.

ABSTRACT

mRNA- and vector-based vaccines are used at a large scale to prevent COVID-19. We compared Spike S1-specific (S1) IgG antibodies after vaccination with mRNA-based (Comirnaty, Spikevax) or vector-based (Janssen, Vaxzevria) vaccines, using samples from a Dutch nationwide cohort. In adults 18-64 years old (n = 2412), the median vaccination interval between the two doses was 77 days for Vaxzevria (interquartile range, IQR: 69-77), 35 days (28-35) for Comirnaty and 33 days (28-35) for Spikevax. mRNA vaccines induced faster inclines and higher S1 antibodies compared to vector-based vaccines. For all vaccines, one dose resulted in boosting of S1 antibodies in adults with a history of SARS-CoV-2 infection. For Comirnaty, two to four months following the second dose (n = 196), S1 antibodies in adults aged 18-64 years old (436 BAU/mL, IQR: 328-891) were less variable and median concentrations higher compared to those in persons ≥ 80 years old (366, 177-743), but differences were not statistically significant (p > 0.100). Nearly all participants seroconverted following COVID-19 vaccination, including the aging population. These data confirm results from controlled vaccine trials in a general population, including vulnerable groups.

PMID:35396570 | DOI:10.1038/s41598-022-10020-6

Sci Rep. 2022 Apr 8;12(1):5974. doi: 10.1038/s41598-022-10072-8.

ABSTRACT

Metal artefacts degrade clinical image quality which decreases the confidence of using computed tomography (CT) for the delineation of key structures for treatment planning and leads to dose errors in affected areas. In this work, we investigated accuracy of doses computed by the Eclipse treatment planning system near and inside metallic elements for two different computation algorithms. An impact of CT metal artefact reduction methods on the resulting calculated doses has also been assessed. A water phantom including Gafchromic film and metal inserts was irradiated (max dose 5 Gy) using a 6 MV photon beam. Three materials were tested: titanium, alloy 600, and tungsten. The phantom CT images were obtained with the pseudo-monoenergetic reconstruction (PMR) and the iterative metal artefact reduction (iMAR). Image sets were used for dose calculation using an Eclipse treatment planning station (TPS). Monte Carlo (MC) simulations were used to predict the true dose distribution in the phantom allowing for comparison with doses measured by film and calculated by TPS. Measured and simulated percentage depth doses (PDDs) were not statistically different (p > 0.618). Regional differences were observed at edges of metallic objects (max 8% difference). However, PDDs simulated with and without film were statistically different (p < 0.002). PDDs calculated by the Acuros XB algorithm based on the dose-to-medium approach best matched the MC reference regardless of the CT reconstruction methods and inserts used (p > 0.078). PDDs obtained using other algorithms significantly differ from the MC values (p < 0.011). The Acuros XB algorithm with a dose-to-medium approach provides reliable dose calculation in all metal regions when using the Varian system. The inability of the AAA algorithm to model backscatter dose significantly limits its clinical application in the presence of metal. No significant impact on the dose calculation was found for a range of metal artefact reduction strategies.

PMID:35396569 | DOI:10.1038/s41598-022-10072-8

Prim Care Companion CNS Disord. 2022 Apr 5;24(2):21m03197. doi: 10.4088/PCC.21m03197.

ABSTRACT

Objective: To compare the health anxiety and healthy lifestyle behavior experienced by psychiatric patients due to the coronavirus disease 2019 (COVID-19) pandemic with that of a control group.

Methods: The study included 120 outpatients (aged 18-65 years) diagnosed with a psychiatric illness (DSM-5 criteria) who presented to a psychiatry outpatient clinic between June and August 2020. The control group included 120 healthy individuals with a similar age and sex distribution as the patient group. Data were collected with a questionnaire developed by the authors to determine the participants’ adherence to COVID-19 hygiene rules and associated behavioral norms. The Health Anxiety Scale-Short Form, Health Perception Scale, and Health-Promoting Lifestyle Profile were completed by all participants.

Results: The mean Health Anxiety Scale score was significantly lower in the patient group compared to the control group (P < .01). Health anxiety was high in 8% of the patients and 32% of the controls. Also, the mean Health-Promoting Lifestyle Profile score was statistically significantly lower in the patient group compared to the control group (P < .01). There was no significant difference between the groups based on health perception scores and adherence to hygiene rules.

Conclusions: As expected, the healthy lifestyle behavior of individuals without psychiatric illness was higher compared to those with mental disorders. However, health anxiety about COVID-19 was higher among healthy individuals compared to those with a psychiatric disorder. Thus, it could be suggested that individuals without a psychiatric illness prior to the pandemic could need psychiatric assistance after the pandemic.

PMID:35395150 | DOI:10.4088/PCC.21m03197

Dermatol Ther. 2022 Apr 8:e15499. doi: 10.1111/dth.15499. Online ahead of print.

ABSTRACT

The pathogenesis of melasma is not fully understood yet and this often causes difficulties in treatment. In our study, we aimed to compare the clinical results of oral TA and PRP therapies in patients with melasma. The clinical results of 30 melasma patients treated with oral TA and 30 melasma patients treated with PRP over the age of 18 who applied to the İnönü University Turgut Özal Medical Center Dermatology and Venereal Diseases Outpatient Clinic between September 2017 and June 2019 were retrospectively evaluated. Both oral TA and PRP therapies provided statistically significant improvement in melasma patients. 75% improvement in the MASI score was statistically significantly higher in the oral TA group compared to the PRP group. Although oral TA and PRP are both successful in the treatment of melasma, it has been found in our study that oral TA gives better results. More studies are needed to support our study, which is the first study comparing oral TA and PRP therapies in the literature. This article is protected by copyright. All rights reserved.

PMID:35395121 | DOI:10.1111/dth.15499

Mol Ecol. 2022 Apr 8. doi: 10.1111/mec.16460. Online ahead of print.

ABSTRACT

The development of high-throughput sequencing (HTS) technologies has greatly improved our capacity to identify fungi and unveil their ecological roles across a variety of ecosystems. Here we provide an overview of current best practices in metabarcoding analysis of fungal communities, from experimental design through molecular and computational analyses. By re-analysing published datasets, we demonstrate that operational taxonomic units (OTUs) outperform amplified sequence variants (ASVs) in recovering fungal diversity, a finding that is particularly evident for long markers. Additionally, analysis of the full-length ITS region allows more accurate taxonomic placement of fungi and other eukaryotes compared to the ITS2 subregion. Finally, we show that specific methods for compositional data analyses provide more reliable estimates of shifts in community structure. We conclude that metabarcoding analyses of fungi are especially promising for integrating fungi into the full microbiome and broader ecosystem functioning context, recovery of novel fungal lineages and ancient organisms as well as barcoding of old specimens including type material.

PMID:35395127 | DOI:10.1111/mec.16460

Fam Pract. 2022 Apr 8:cmac024. doi: 10.1093/fampra/cmac024. Online ahead of print.

ABSTRACT

BACKGROUND: Before and throughout the COVID-19 pandemic, healthcare workers (HCWs) were victims of workplace violence (WPV). There are no reliable statistics on the occurrence and consequences of WPV against HCWs in Turkey throughout the pandemic period.

OBJECTIVE: We investigated the rates of WPV against HCWs in Turkey in the pre-pandemic and pandemic periods, variables associated with WPV, and the relationship between these variables and job satisfaction and burnout.

METHODS: A structured online questionnaire was disseminated through social media channels to HCWs in various healthcare settings. All the respondents also completed the Maslach Burnout Inventory (MBI) and Job Satisfaction Scale. Based on the data obtained, we determined the frequency, causes, and consequences of WPV against HCWs before and during the pandemic.

RESULTS: There were 701 completed questionnaires. 68.2% of participants were female, and 65.6% of them were doctors. The rate of WPV was 54.1% and 24.3% before and during the pandemic, respectively. Verbal abuse was the most common kind of WPV. Female HCWs were more likely to be physically assaulted than their male counterparts, especially those working in COVID-19 units. The majority of HCWs who were exposed to the violence at least once did not report WPV. HCWs exposed to WPV during the pandemic reported more emotional exhaustion and depersonalization and a lower perceived level of personal achievement.

CONCLUSION: HCWs were exposed to significant levels of violence both before and during the pandemic. Preventing WPV against HCWs and removing barriers to reporting abuse is crucial.

PMID:35395085 | DOI:10.1093/fampra/cmac024