Category: Statistics

Pediatr Res. 2023 Feb 11. doi: 10.1038/s41390-023-02513-5. Online ahead of print.

ABSTRACT

BACKGROUND: The risk of neurological complications is increased in children with sickle cell disease (SCD), such as silent cerebral infarction (SCI) and stroke. Brain-Derived Neurotrophic Factor (BDNF) is a nerve growth factor associated with elevated transcranial Doppler (TCD) velocities and increased risk of stroke in SCD patients. So, we assessed the BDNF level in children with SCD and its relation to neurological complication as silent stroke.

METHODS: A comparative cross-sectional study was conducted on 40 patients with SCD, recruited from the Hematology Unit, Pediatric Department, Menoufia University Hospital, and 40 healthy children as controls. Laboratory investigations including BDNF were done. TCD was done for all patients and Magnetic Resonance Imaging (MRI) was done on high-risk patients.

RESULTS: BDNF levels were significantly higher in children with SCD than in controls with a significant relation to TCD findings. There was a statistically significant diagnostic ability of BDNF in the prediction of SCD complications as its sensitivity was 89.5%, specificity (95% CI) was 80% with a cut-off point >0.69, AUC = 0.702, and p = 0.004).

CONCLUSION: Serum BDNF levels were higher in sickle disease patients who had abnormal transcranial Doppler. BDNF had a significant diagnostic ability in the detection of SCD complications.

IMPACT: Silent stroke is a very serious complication in children with sickle cell disease, so regular follow up should be every six months. BDNF is considered a potential biomarker for stroke risk prediction in patients unable to receive TCD.

PMID:36774398 | DOI:10.1038/s41390-023-02513-5

NPJ Parkinsons Dis. 2023 Feb 11;9(1):24. doi: 10.1038/s41531-023-00461-9.

ABSTRACT

The pathogenesis and clinical heterogeneity of Parkinson’s disease (PD) have been evaluated from molecular, pathophysiological, and clinical perspectives. High-throughput proteomic analysis of cerebrospinal fluid (CSF) opened new opportunities for scrutinizing this heterogeneity. To date, this is the most comprehensive CSF-based proteomics profiling study in PD with 569 patients (350 idiopathic patients, 65 GBA + mutation carriers and 154 LRRK2 + mutation carriers), 534 controls, and 4135 proteins analyzed. Combining CSF aptamer-based proteomics with genetics we determined protein quantitative trait loci (pQTLs). Analyses of pQTLs together with summary statistics from the largest PD genome wide association study (GWAS) identified 68 potential causal proteins by Mendelian randomization. The top causal protein, GPNMB, was previously reported to be upregulated in the substantia nigra of PD patients. We also compared the CSF proteomes of patients and controls. Proteome differences between GBA + patients and unaffected GBA + controls suggest degeneration of dopaminergic neurons, altered dopamine metabolism and increased brain inflammation. In the LRRK2 + subcohort we found dysregulated lysosomal degradation, altered alpha-synuclein processing, and neurotransmission. Proteome differences between idiopathic patients and controls suggest increased neuroinflammation, mitochondrial dysfunction/oxidative stress, altered iron metabolism and potential neuroprotection mediated by vasoactive substances. Finally, we used proteomic data to stratify idiopathic patients into “endotypes”. The identified endotypes show differences in cognitive and motor disease progression based on previously reported protein-based risk scores.Our findings not only contribute to the identification of new therapeutic targets but also to shape personalized medicine in CNS neurodegeneration.

PMID:36774388 | DOI:10.1038/s41531-023-00461-9

Nat Commun. 2023 Feb 11;14(1):780. doi: 10.1038/s41467-023-36492-2.

ABSTRACT

Dimension reduction is an indispensable part of modern data science, and many algorithms have been developed. However, different algorithms have their own strengths and weaknesses, making it important to evaluate their relative performance, and to leverage and combine their individual strengths. This paper proposes a spectral method for assessing and combining multiple visualizations of a given dataset produced by diverse algorithms. The proposed method provides a quantitative measure – the visualization eigenscore – of the relative performance of the visualizations for preserving the structure around each data point. It also generates a consensus visualization, having improved quality over individual visualizations in capturing the underlying structure. Our approach is flexible and works as a wrapper around any visualizations. We analyze multiple real-world datasets to demonstrate the effectiveness of the method. We also provide theoretical justifications based on a general statistical framework, yielding several fundamental principles along with practical guidance.

PMID:36774377 | DOI:10.1038/s41467-023-36492-2

Sci Rep. 2023 Feb 11;13(1):2480. doi: 10.1038/s41598-023-29376-4.

ABSTRACT

Gene expression, often determined by single nucleotide polymorphisms, short repeated sequences known as short tandem repeats (STRs), structural variants, and environmental factors, provides means for an organism to produce gene products necessary to live. Variation in expression levels, sometimes known as enrichment patterns, has been associated with disease progression. Thus, the STR enrichment patterns have recently gained interest as potential genetic markers for disease progression. However, to the best of our knowledge, we are unaware of any study that evaluates and explores STRs, particularly trinucleotide sequences, as machine learning features for classifying neurological disease genes for the purpose of discovering genetic features. Thus, in this paper, we proposed a new metric and a novel feature extraction and selection algorithm based on statistically significant STR-based features and their respective enrichment patterns to create a statistically significant feature set. The proposed new metric has shown that the neurological disease family genes have a non-random AA, AT, TA, TG, and TT enrichment pattern. This is an important result, as it supports prior research that has established that certain trinucleotides, such as AAT, ATA, ATT, TAT, and TTA, are favored during protein misfolding. In contrast, trinucleotides, such as TAA, TAG, and TGA, are favored during premature termination codon mutations as they are stop codons. This suggests that the metric has the potential to identify patterns that may be genetic features in a sample of neurological genes. Moreover, the practical performance and high prediction results of the statistically significant STR-based feature set indicate that variations in STR enrichment patterns can distinguish neurological disease genes. In conclusion, the proposed approach may have the potential to discover differential genetic features for other diseases.

PMID:36774368 | DOI:10.1038/s41598-023-29376-4

Neuromodulation. 2023 Feb 9:S1094-7159(23)00008-9. doi: 10.1016/j.neurom.2022.12.013. Online ahead of print.

ABSTRACT

BACKGROUND: Directional deep brain stimulation (DBS) leads allow a fine-tuning control of the stimulation field, however, this new technology could increase the DBS programming time because of the higher number of the possible combinations used in directional DBS than in standard nondirectional electrodes. Neuroimaging leads localization techniques and local field potentials (LFPs) recorded from DBS electrodes implanted in basal ganglia are among the most studied biomarkers for DBS programing.

OBJECTIVE: This study aimed to evaluate whether intraoperative LFPs beta power and neuroimaging reconstructions correlate with contact selection in clinical programming of DBS in patients with Parkinson disease (PD).

MATERIALS AND METHODS: In this retrospective study, routine intraoperative LFPs recorded from all contacts in the subthalamic nucleus (STN) of 14 patients with PD were analyzed to calculate the beta band power for each contact. Neuroimaging reconstruction obtained through Brainlab Elements Planning software detected contacts localized within the STN. Clinical DBS programming contact scheme data were collected after one year from the implant. Statistical analysis evaluated the diagnostic performance of LFPs beta band power and neuroimaging data for identification of the contacts selected with clinical programming. We evaluated whether the most effective contacts identified based on the clinical response after one year from implant were also those with the highest level of beta activity and localized within the STN in neuroimaging reconstruction.

RESULTS: LFPs beta power showed a sensitivity of 67%, a negative predictive value (NPV) of 84%, a diagnostic odds ratio (DOR) of 2.7 in predicting the most effective contacts as evaluated through the clinical response. Neuroimaging reconstructions showed a sensitivity of 62%, a NPV of 77%, a DOR of 1.20 for contact effectivity prediction. The combined use of the two methods showed a sensitivity of 87%, a NPV of 87%, a DOR of 2.7 for predicting the clinically more effective contacts.

CONCLUSIONS: The combined use of LFPs beta power and neuroimaging localization and segmentations predict which are the most effective contacts as selected on the basis of clinical programming after one year from implant of DBS. The use of predictors in contact selection could guide clinical programming and reduce time needed for it.

PMID:36774326 | DOI:10.1016/j.neurom.2022.12.013

J Microbiol Immunol Infect. 2023 Feb 2:S1684-1182(23)00013-0. doi: 10.1016/j.jmii.2023.01.013. Online ahead of print.

ABSTRACT

BACKGROUND/PURPOSE: Serotype 3 has persisted to be an important cause of invasive pneumococcal disease in adults in the post-vaccine era. We aimed to investigate clinical and microbiological characteristics of Streptococcus pneumoniae serotype 3 infection in Taiwan and identify the risk factors associated with severe clinical outcome.

METHODS: A multicenter observational study was conducted to analyze serotype 3 isolates collected between 2012 and 2021. Demographics, comorbidities, and risk categories were statistically compared with clinical outcome. Antimicrobial susceptibility testing and multilocus sequence typing were performed.

RESULTS: A total of 146 isolates were collected, including 12 isolates regarded as colonizers. Among 134 infected cases, 54 (40.3%) were aged 65 and older. Mortality was significantly associated with diabetes mellitus, immunosuppression, immunodeficiency, high-risk status, and older age. Susceptibility rates were high to levofloxacin (98.9%), moxifloxacin (100%), vancomycin (100%), and ceftriaxone (97.3%). 25.3% (37/146) of the isolates showed intermediate susceptibility and 0.7% (1/146) showed resistance to penicillin. ST180 was the dominant sequence type. ST13 and ST9625 isolates were less susceptible to penicillin and ceftriaxone.

CONCLUSIONS: Serotype 3 infection showed a high mortality rate, especially in patients with older ages and comorbidities. Although the incidence rates decreased during the COVID-19 pandemic, serotype 3 remained as an important cause of infection after the implementation of PCV13. Developing a more effective vaccine against serotype 3 and monitoring the antimicrobial-resistant sequence types are necessary.

PMID:36774315 | DOI:10.1016/j.jmii.2023.01.013

Int J Clin Pharm. 2023 Feb 11. doi: 10.1007/s11096-023-01542-8. Online ahead of print.

ABSTRACT

BACKGROUND: Community pharmacists contribute substantially to public health and person-centred care. Emotional intelligence (EI) may help health professionals better engage with patients, handle stress in challenging situations and, presumably, better introduce and implement new services.

AIM: The study’s aims were to compare the EI and perceived stress (PS) levels of community pharmacists who provided a new service to patients with diabetes with their controls who provided standard pharmaceutical services and to test the correlations between the two constructs.

METHOD: This study used a survey methodology. Well-validated instruments were distributed electronically to all participating pharmacists. To compare the continuous EI and PS data between the two study groups, the paired-samples t test was used. Pearson and Spearman’s correlations were used to test the associations between EI and PS and their respective subdomains.

RESULTS: A total of 86 pharmacists participated in the study (n = 43 in each group). The study groups did not differ by any characteristic except gender. Their mean EI and PS levels were 120.95 ± 11.53 and 17.45 ± 4.55, respectively, with no difference between the groups. In both study groups, inverse correlations were found between PS and EI levels, with statistical significance in the control group and in the overall study population (r = – 0.611 and r = – 0.370, respectively).

CONCLUSION: Our results suggest that the introduction of the EI agenda into certification programmes for new community pharmacy services should be considered. The results also suggest that higher EI may have protective effects against PS. Additional research would clarify the need to invest more in such programmes.

PMID:36773208 | DOI:10.1007/s11096-023-01542-8

Breast Cancer Res Treat. 2023 Feb 11. doi: 10.1007/s10549-023-06871-w. Online ahead of print.

ABSTRACT

PURPOSE: The safety of local estrogen therapy in patients on adjuvant endocrine treatment is questioned, but evidence on the issue is scarce. This nested case-control registry-based study aimed to investigate whether estrogen therapy affects breast cancer mortality risk in women on adjuvant endocrine treatment.

METHODS: In a cohort of 15,198 women diagnosed with early hormone receptor (HR)-positive breast cancer and adjuvant endocrine treatment, 1262 women died due to breast cancer and were identified as cases. Each case was matched with 10 controls. Exposure to estrogen therapy with concurrent use of aromatase inhibitors (AIs), tamoxifen, or both sequentially, was compared between cases and controls.

RESULTS: No statistically significant difference in breast cancer mortality risk was seen in patients with exposure to estrogen therapy concurrent to endocrine treatment, neither in short-term or in long-term estrogen therapy use.

CONCLUSIONS: The study strengthens current evidence on local estrogen therapy use in breast cancer survivors, showing no increased risk for breast cancer mortality in patients on adjuvant AIs or tamoxifen.

PMID:36773184 | DOI:10.1007/s10549-023-06871-w

Eur J Epidemiol. 2023 Feb 11. doi: 10.1007/s10654-023-00969-7. Online ahead of print.

ABSTRACT

The carcinogenicity of opium consumption was recently evaluated by a Working Group convened by the International Agency for Research on Cancer (IARC). We supplement the recent IARC evaluation by conducting an extended systematic review as well as a quantitative meta-analytic assessment of the role of opium consumption and risk for selected cancers, evaluating in detail various aspects of study quality on meta-analytic findings. We searched the published literature to identify all relevant studies on opium consumption and risk of selected cancers in humans through 31 October, 2022. Meta-relative risks (mRRs) and associated 95% confidence intervals (CIs) were estimated using random-effects models for studies of cancer of the urinary bladder, larynx, lung, oesophagus, pancreas, and stomach. Heterogeneity among studies was assessed using the I² statistic. We assessed study quality and conducted sensitivity analyses to evaluate the impact of potential reverse causation, protopathic bias, selection bias, information bias, and confounding. In total, 2 prospective cohort studies and 33 case-control studies were included. The overall pooled mRR estimated for ‘ever or regular’ versus ‘never’ use of opium ranged from 1.50 (95% CI 1.13-1.99, I² = 0%, 6 studies) for oesophageal cancer to 7.97 (95% CI 4.79-13.3, I² = 62%, 7 studies) for laryngeal cancer. Analyses of cumulative opium exposure suggested greater risk of cancer associated with higher opium consumption. Findings were robust in sensitivity analyses excluding studies prone to potential methodological sources of biases and confounding. Findings support an adverse association between opium consumption and cancers of the urinary bladder, larynx, lung, oesophagus, pancreas and stomach.

PMID:36773182 | DOI:10.1007/s10654-023-00969-7

Methods Mol Biol. 2023;2637:63-73. doi: 10.1007/978-1-0716-3016-7_5.

ABSTRACT

Genome sequencing technologies have rapidly evolved in the past decades, enabling us to interpret the human genome through multiple perspectives, ranging from cross-species comparisons, naturally occurring variation in health and disease state to regulatory mechanisms.Although such perspectives are all informative to narrow down the list of genes or variants for perturbation experiments based on specific biological aims, utilizing multiple sources of information is often challenging in practice.In this chapter, we provide an overview of major large-scale functional and population genomics resources, followed by a practical example of selecting target variants for genetic perturbation experiments involving genome engineering techniques such as CRISPR/Cas.

PMID:36773138 | DOI:10.1007/978-1-0716-3016-7_5