Category: Statistics

J Mol Neurosci. 2023 Feb 7. doi: 10.1007/s12031-023-02104-3. Online ahead of print.

ABSTRACT

Cytohesin-4 (CYTH4) is a member of the PSCD family. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. In previous studies, CYTH4 has been linked with multiple brain diseases, but not glioma, the most common type of brain tumor. We utilized multiple glioma single-cell RNA sequencing datasets and bulk data from the TCGA and CGGA and conducted GSEA and KEGG and GO analyses. Biomarker potential was tested via ROC curve analysis. Radar plots were used to study TMB and MSI correlations. Immune cell studies were conducted using CIBERSORT. All statistical analyses were performed in R software and GraphPad Prism 9. CYTH4 was overexpressed in the glioma macrophage population in several single-cell RNA sequencing datasets and was most correlated with M2 macrophages. CYTH4 expression was higher in tumor tissues and was correlated with survival and WHO grade. ROC curves suggested CYTH4 overexpression to be a potential glioma biomarker. GSEA results indicated a relationship between CYTH4 and apoptosis, and PPI analysis supported a pyroptosis correlation. KEGG and GO analysis results linked CYTH4 with antigen processing and presentation and neutrophil activities. In summary, the study identified a CYTH4/pyroptosis/M2 macrophage axis. CYTH4 was upregulated in M2 macrophages in glioma and affected pyroptosis. CYTH4 overexpression is a potential biomarker predicting a poor prognosis.

PMID:36749492 | DOI:10.1007/s12031-023-02104-3

Med Oncol. 2023 Feb 7;40(3):91. doi: 10.1007/s12032-023-01949-3.

ABSTRACT

A significant mortality rate is associated with oral cancer, particularly in cases of late-stage diagnosis. Since the last decades, oral cancer survival rates have only gradually improved despite advances in treatment. This poor success rate is mainly due to the development of secondary tumors, local recurrence, and regional failure. Invasive treatments frequently have a negative impact on the aesthetic and functional outcomes of survivors. Novel approaches are thus needed to manage this deadly disease in light of these statistics. In photodynamic therapy (PDT), a light-sensitive medication called a photosensitizer is given first, followed by exposure to light of the proper wavelength that matches the absorbance band of the photosensitizer. The tissue oxygen-induced cytotoxic free radicals kill tumor cells directly, harm the microvascular structure, and cause inflammatory reactions at the targeted sites. In the case of early lesions, PDT can be used as a stand-alone therapy, and in the case of advanced lesions, it can be used as adjuvant therapy. The current review article discussed the uses of PDT in oral cancer therapy based on recent advances in this field.

PMID:36749489 | DOI:10.1007/s12032-023-01949-3

Pharmacol Rep. 2023 Feb 7. doi: 10.1007/s43440-023-00455-7. Online ahead of print.

ABSTRACT

BACKGROUND: Perioperative anesthetic and/or analgesic demand present considerable variation, and part of that variation appears to be genetic in origin. Here we investigate the impact of common polymorphisms in OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 genes, on the intra-operative consumption of remifentanil and propofol, as well as the postoperative analgesic needs, in patients subjected to thyroidectomy surgery.

METHODS: We conducted a prospective cohort study with 90 patients scheduled to undergo elective thyroidectomy, under total intravenous anesthesia achieved by target control infusion (TCI) of propofol and remifentanil. Postoperative analgesics were administered by protocol and on-demand by the individual patient. Genotyping was established by PCR-RFLP methods. Genotyping data, intra-operative hemodynamics, and total consumption of remifentanil and propofol, as well as postoperative analgesic needs and pain perception, were recorded for each individual.

RESULTS: Patients with the ABCB1 3435TT genotype appeared to experience significantly less pain within one hour post-operatively, compared to C carriers [mean VAS (SD) = 0.86 (1.22) vs. 2.42 (1.75); p = 0.017], a finding limited to those seeking rescue analgesic treatment. Intra-operatively, homozygotes patients for the minor allele of OPRM1 A118G and CYP2B6 G516T appeared to consume less remifentanil [mean (SD) = 9.12 (1.01) vs. 13.53 (5.15), for OPRM1 118GG and A carriers] and propofol [median (range) = 14.95 (11.53, 1359.5) vs. 121.4 (1.43, 2349.4), for CYP2B6 516TT and G carriers, respectively] but the difference was not statistically significant in our sample.

CONCLUSIONS: The ABCB1 C3435T polymorphism appears to affect the postoperative perception of surgical pain among patients with low pain threshold. The small number of minor allele homozygotes for the OPRM1 A118G and CYP2B6 G516T polymorphisms precludes a definitive conclusion regarding the inclusion of the latter in a TCI-programming algorithm, based on the results of this study.

CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12616001598471.

PMID:36749481 | DOI:10.1007/s43440-023-00455-7

Rheumatol Ther. 2023 Feb 7. doi: 10.1007/s40744-022-00523-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Currently there is limited data to drive clinical decision making regarding the choice of biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARD); thus, head-to-head comparisons are needed to help guide prescribing. In recent years, significant advancements have helped clarify the mechanistic basis of the clinical associations of autoantibodies in rheumatoid arthritis (RA). This study evaluated the effectiveness of abatacept versus tofacitinib in anti-cyclic citrullinated peptide (CCP+) patients with rheumatoid arthritis (RA).

METHODS: CorEvitas (formerly known as CORRONA) Registry patients aged ≥ 18 years, who were CCP+ before initiating abatacept or tofacitinib (December 2012 onwards through October 2019), had 6-month follow-up data (baseline and 6-month Clinical Disease Activity Index [CDAI]), and were not in remission at index were included. Patients were frequency matched 1:1 by prior biologic use before propensity score matching (PSM). Primary (mean change [D] in CDAI) and secondary outcomes 6 months after index were compared using mixed-effects models adjusted for variables that remained unbalanced after PSM.

RESULTS: Following PSM, most baseline characteristics for 291 patient pairs were well balanced between treatments, although fewer patients initiating abatacept versus tofacitinib received prior non-TNFi biologic DMARDs, and patients initiating abatacept versus tofacitinib had a higher physician global assessment score, patient-reported fatigue, and modified Health Assessment Questionnaire (mHAQ). In adjusted analyses, there were no significant differences in mean [D] from baseline in CDAI at 6 months with abatacept versus tofacitinib (P = 0.936). Patients naïve for b/tsDMARDs initiating abatacept had a numerically greater mean [D] in CDAI at 6 months versus tofacitinib, although this difference was not statistically significant (P = 0.662). There were no significant differences for any secondary outcomes.

CONCLUSIONS: In adjusted analyses, CCP+ patients with RA initiating treatment with abatacept versus tofacitinib did not show a statistically significant difference in reducing disease activity or improving patient-reported outcomes.

PMID:36749478 | DOI:10.1007/s40744-022-00523-z

Int Urol Nephrol. 2023 Feb 7. doi: 10.1007/s11255-023-03506-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Chronic anemia, iron overload, and iron chelation therapy are the main contributing factors for renal complications in thalassemia, e.g., nephrolithiasis, glomerular disease, and renal tubular dysfunction. The prevalence and associated factors for developing renal dysfunctions in Thai patients with thalassemia, however, remained limited. This study aimed to determine the prevalence and risk factors of renal dysfunctions in patients with thalassemia.

METHODS: A cross-sectional study was conducted on adult patients with thalassemia disease at Srinagarind Hospital, Khon Kaen University, Thailand. All patients were evaluated for complete blood count, blood chemistry, urinalysis, and urine biochemistry. Renal tubular dysfunction was defined as existing in at least one of the following parameters including; proteinuria, hypercalciuria, hypouricemia with uricosuria, or hypophosphatemia with phosphaturia. Logistic regression analysis was used to identify associated factors for renal dysfunctions.

RESULTS: Of 105 patients, renal tubular dysfunction was found in 60 patients (57.1%). In multivariate analysis of the clinical risk factors for renal tubular dysfunction in thalassemia patients, age per 10 year increase (adjusted odds ratio [AOR] = 1.4, 95% CI: 1.0-2.0, p value 0.01) and Hb E/beta-thalassemia (AOR = 3.6, 95% CI: 1.3-10.3, p value 0.01) were statistically proven to be associated with renal tubular dysfunction. Hyperuricosuria was a significantly associated factor for microhematuria. (AOR = 2.9, 95% CI: 1.1-8.0, p value 0.03).

CONCLUSIONS: Renal dysfunctions are prevalent in thalassemia patients, with older age and Hb E/beta-thalassemia genotype as significant risk factors for renal tubular dysfunction. Hyperuricosuria is a risk factor for microhematuria. Renal dysfunctions should be recognized and monitored in aging patients with Hb E/beta-thalassemia.

PMID:36749473 | DOI:10.1007/s11255-023-03506-3

Forensic Sci Med Pathol. 2023 Feb 7. doi: 10.1007/s12024-023-00583-9. Online ahead of print.

ABSTRACT

The Abbreviated Injury Scale (AIS) and Injury Severity Score (ISS) are important evaluation tools used in clinical practice to determine the degree of injury in patients with trauma. However, they are not suitable for forensic practice and their use in forensic applications is limited. This study aimed to present a system that can objectively and quantitatively determine the severity of postmortem injuries and that can be applied to forensic medicine. Subsequently, we applied this system to individual postmortem cases and analyzed the injuries identified during autopsy. We performed a retrospective study of 119 autopsies performed between 2018 and 2021. Data were categorized and analyzed using the Forensic Injury Severity Score Template (FISST), a scoring system developed based on the AIS and ISS. The mean FISST scores were as follows: men, 53.6; women, 46.8; 20-65 years old, 55.6; older than 65 years, 41.4; natural death, 13.8; unnatural death, 66.3; and all deaths, 51.8. Statistically significant differences in the FISST scores were found between natural and unnatural deaths, suicidal and accidental deaths, and trauma-related death subtypes. Injuries identified during autopsy can be objectively and quantitatively evaluated using FISST. We suggest that FISST is a useful tool in forensic medicine because it is tailor-made for injury evaluation from a postmortem perspective.

PMID:36749470 | DOI:10.1007/s12024-023-00583-9

Health Justice. 2023 Feb 7;11(1):5. doi: 10.1186/s40352-023-00205-0.

ABSTRACT

BACKGROUND: Correctional settings are hotspots for SARS-CoV-2 transmission. Social and biological risk factors contribute to higher rates of COVID-19 morbidity and mortality among justice-involved individuals. Rapidly identifying new cases in congregate settings is essential to promote proper isolation and quarantine. We sought perspectives of individuals incarcerated during COVID-19 on how to improve carceral infection control and their perspectives on acceptability of wastewater-based surveillance (WBS) accompanying individual testing.

METHODS: We conducted semi-structured interviews with 20 adults who self-reported being incarcerated throughout the United States between March 2020 and May 2021. We asked participants about facility enforcement of the Centers for Disease Control and Prevention (CDC) COVID-19 guidelines, and acceptability of integrating WBS into SARS-CoV-2 monitoring strategies at their most recent facility. We used descriptive statistics to characterize the study sample and report on acceptability of WBS. We analyzed qualitative data thematically using an iterative process.

RESULTS: Participants were predominantly Black or multiple races (50%) and men (75%); 46 years old on average. Most received a mask during their most recent incarceration (90%), although only 40% received counseling on proper mask wearing. A quarter of participants were tested for SARS-CoV-2 at intake. Most (70%) believed they were exposed to the virus while incarcerated. Reoccurring themes included (1) Correctional facility environment leading to a sense of insecurity, (2) Perceptions that punitive conditions in correctional settings were exacerbated by the pandemic; (3) Importance of peers as a source of information about mitigation measures; (4) Perceptions that the safety of correctional environments differed from that of the community during the pandemic; and (5) WBS as a logical strategy, with most (68%) believing WBS would work in the last correctional facility they were in, and 79% preferred monitoring SARS-CoV-2 levels through WBS rather than relying on just individual testing.

CONCLUSION: Participants supported routine WBS to monitor for SARS-CoV-2. Integrating WBS into existing surveillance strategies at correctional facilities may minimize the impact of future COVID-19 outbreaks while conserving already constrained resources. To enhance the perception and reality that correctional systems are maximizing mitigation, future measures might include focusing on closer adherence to CDC recommendations and clarity about disease pathogenesis with residents.

PMID:36749465 | DOI:10.1186/s40352-023-00205-0

J Autism Dev Disord. 2023 Feb 7. doi: 10.1007/s10803-023-05902-1. Online ahead of print.

ABSTRACT

Statistical learning (SL), the ability to detect and extract regularities from inputs, is considered a domain-general building block for typical language development. We compared 55 verbal children with autism (ASD, 6-12 years) and 50 typically-developing children in four SL tasks. The ASD group exhibited reduced learning in the linguistic SL tasks (syllable and letter), but showed intact learning for the nonlinguistic SL tasks (tone and image). In the ASD group, better linguistic SL was associated with higher language skills measured by parental report and sentence recall. Therefore, the atypicality of SL in autism is not domain-general but tied to specific processing constraints related to verbal stimuli. Our findings provide a novel perspective for understanding language heterogeneity in autism.

PMID:36749457 | DOI:10.1007/s10803-023-05902-1

J Endocrinol Invest. 2023 Feb 7. doi: 10.1007/s40618-023-02026-2. Online ahead of print.

ABSTRACT

INTRODUCTION: Severe short stature is a feature of acrodysostosis, but data on growth are sparse. Treatment with recombinant human growth hormone (rhGH) is used in some centers to increase final height, but no studies have been published so far. Our objective was to conduct a multicenter, retrospective, cohort study to investigate growth in individuals with both types of acrodysostosis, treated with rhGH or not; we used the new nomenclature to describe acrodysostosis, as this disease belongs to the large group of inactivating PTH/PTHrP signaling disorders (iPPSD); acrodysostosis refers to iPPSD4 (acrodysostosis type 1 due to PRKAR1A mutations) and iPPSD5 (acrodysostosis type 2, due to PDE4D mutations).

METHODS: We present auxological data from individuals with genetically characterized iPPSD4, and participants with clinical features of iPPSD5.

RESULTS: We included 20 and 17 individuals with iPPSD4 and iPPSD5, respectively. The rhGH-treated iPPSD4 patients (n = 9) were smaller at birth than those who did not receive rhGH (median – 2.2 SDS vs. – 1.7 SDS); they showed a trend to catch-up growth during rhGH therapy (median 0.5 SDS in the first year). The rhGH-treated patients (n = 5) reached a better final height compared to those who did not receive rhGH (n = 4) (median – 2.8 SDS vs. – 3.9 SDS), suggesting that rhGH is efficient to increase height in those patients. The difference in target height to final height ranged between 1.6 and 3.0 SDS for iPPSD4 not treated with rhGH (n = 4), 2.1-2.8 SDS for rhGH-treated iPPSD4 (n = 5), 0.6-5.5 SDS for iPPSD5 not treated with rhGH (n = 5) and 2.5-3.1 for rhGH-treated iPPSD5 (n = 2).

CONCLUSION: Final height may be positively influenced by rhGH in patients with acrodysostosis/iPPSD. Our rhGH-treated cohort started therapy relatively late, which might explain, at least in part, the limited effect of rhGH on height.

PMID:36749450 | DOI:10.1007/s40618-023-02026-2

Health Care Manag Sci. 2023 Feb 7. doi: 10.1007/s10729-022-09625-0. Online ahead of print.

ABSTRACT

Cook et al. (Oper Res 61(3):666-676, 2013) propose a DEA-based model for the performance evaluation of non-homogeneous decision making units (DMUs) based on constant returns to scale (CRS), extended by Li et al. (Health Care Manag Sci 22(2):215-228, 2019) to variable returns to scale (VRS). This paper locates these models into more general DDF models to deal with nonhomogeneous DMUs and applies these to Hong Kong hospitals. The production process of each hospital is divided into subunits which have the same inputs and outputs and hospital performance is measured using the subunits. The paper provides CRS and VRS versions of DDF models and compares them with Cook et al. (Oper Res 61(3):666-676, 2013) and Li et al. (Health Care Manag Sci 22(2):215-228, 2019). A kernel-based method is used to estimate the distributions as well as a DEA-based efficiency analysis adapted by Simar and Zelenyuk to test the distributions. Both DDF CRS and VRS versions produce results similar to Cook et al. (Oper Res 61(3):666-676, 2013) and Li et al. (Health Care Manag Sci 22(2):215-228, 2019) respectively. However, the statistical tests find differences for the different technologies assumed as would be expected. For hospital managers, the more generalised DDF models expand their range of options in terms of directional improvements and priorities as well as dealing with non-homogeneity.

PMID:36749449 | DOI:10.1007/s10729-022-09625-0