Nevin Manimala

Clin Proteomics. 2024 Jun 16;21(1):42. doi: 10.1186/s12014-024-09494-5.

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) is a clinically and biologically heterogenous disease with currently unpredictable progression and relapse. After the development and success of neurofilament as a cerebrospinal fluid (CSF) biomarker, there is reinvigorated interest in identifying other markers of or contributors to disease. The objective of this study is to probe the predictive potential of a panel of brain-enriched proteins on MS disease progression and subtype.

METHODS: This study includes 40 individuals with MS and 14 headache controls. The MS cohort consists of 20 relapsing remitting (RR) and 20 primary progressive (PP) patients. The CSF of all individuals was analyzed for 63 brain enriched proteins using a method of liquid-chromatography tandem mass spectrometry. Wilcoxon rank sum test, Kruskal-Wallis one-way ANOVA, logistic regression, and Pearson correlation were used to refine the list of candidates by comparing relative protein concentrations as well as relation to known imaging and molecular biomarkers.

RESULTS: We report 30 proteins with some relevance to disease, clinical subtype, or severity. Strikingly, we observed widespread protein depletion in the disease CSF as compared to control. We identified numerous markers of relapsing disease, including KLK6 (kallikrein 6, OR = 0.367, p < 0.05), which may be driven by active disease as defined by MRI enhancing lesions. Other oligodendrocyte-enriched proteins also appeared at reduced levels in relapsing disease, namely CNDP1 (carnosine dipeptidase 1), LINGO1 (leucine rich repeat and Immunoglobin-like domain-containing protein 1), MAG (myelin associated glycoprotein), and MOG (myelin oligodendrocyte glycoprotein). Finally, we identified three proteins-CNDP1, APLP1 (amyloid beta precursor like protein 1), and OLFM1 (olfactomedin 1)-that were statistically different in relapsing vs. progressive disease raising the potential for use as an early biomarker to discriminate clinical subtype.

CONCLUSIONS: We illustrate the utility of targeted mass spectrometry in generating potential targets for future biomarker studies and highlight reductions in brain-enriched proteins as markers of the relapsing remitting disease stage.

PMID:38880880 | DOI:10.1186/s12014-024-09494-5

Eur J Med Res. 2024 Jun 16;29(1):334. doi: 10.1186/s40001-024-01924-2.

ABSTRACT

BACKGROUND: Cognitive impairment is a common non-motor symptom of Parkinson’s disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer’s disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD.

METHODS: A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson’s Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson’s Progression Marker Initiative (PPMI).

RESULTS: No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aβ42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance.

CONCLUSIONS: APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aβ42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.

PMID:38880878 | DOI:10.1186/s40001-024-01924-2

BMC Public Health. 2024 Jun 16;24(1):1603. doi: 10.1186/s12889-024-19120-6.

ABSTRACT

BACKGROUND: In the working population, there are risks of overload due to physical, mental, and emotional demands. No instrument is available in Spanish to measure these three types of work fatigue (WF) separately. This paper adapts the Three-Dimensional Work Fatigue Inventory (3D-WFI) (2015), which is of American origin and measures and differentiates these three different types of WF. It has adequate psychometric properties at its root, as do the subsequent German (2018), Lebanese (2022), and Chinese (2023) adaptations.

METHODS: A total of 1100 workers (average age = 40 years) from economic sectors such as security and transportation of valuables, secondary and university educational institutions, and healthcare centers participated. They responded to the 3D-WFI, the Health-Related Quality of Life Index, and the Individual Strength Checklist for concurrent validity effects, together with items with sociodemographic and lifestyle variables.

RESULTS: A confirmatory factor analysis with the total sample 3D-WFI supports its three-dimensionality; Cronbach’s alpha and Omega values are adequate by dimensions: for physical work fatigue (α = 0.92, Ω = 0.92), for mental work fatigue (α = 0.94. Ω = 0.94), and emotional work fatigue (α = 0.95, Ω = 0.95). The 3D-WFI correlates significantly with the Checklist Individual Strength (0.743), and a pattern of significant relationships is found between WF and antecedent variables (e.g., being exposed to heat and noise, emotional labor, concentration, and workwear), as well as some consequences of WF (for example, mental health, absenteeism, work satisfaction, and sleep quality).

CONCLUSIONS: We contribute here to the cross-cultural validity of the 3D-WFI, which can be used reliably and validly in the Chilean and probably Latin American working population. Some WF predictor variables are confirmed, as well as WF impacts on the absenteeism, health, and quality of life among workers.

PMID:38880877 | DOI:10.1186/s12889-024-19120-6

Eur Radiol Exp. 2024 Jun 17;8(1):71. doi: 10.1186/s41747-024-00468-8.

ABSTRACT

BACKGROUND: Radiomics is a quantitative approach that allows the extraction of mineable data from medical images. Despite the growing clinical interest, radiomics studies are affected by variability stemming from analysis choices. We aimed to investigate the agreement between two open-source radiomics software for both contrast-enhanced computed tomography (CT) and contrast-enhanced magnetic resonance imaging (MRI) of lung cancers and to preliminarily evaluate the existence of radiomic features stable for both techniques.

METHODS: Contrast-enhanced CT and MRI images of 35 patients affected with non-small cell lung cancer (NSCLC) were manually segmented and preprocessed using three different methods. Sixty-six Image Biomarker Standardisation Initiative-compliant features common to the considered platforms, PyRadiomics and LIFEx, were extracted. The correlation among features with the same mathematical definition was analyzed by comparing PyRadiomics and LIFEx (at fixed imaging technique), and MRI with CT results (for the same software).

RESULTS: When assessing the agreement between LIFEx and PyRadiomics across the considered resampling, the maximum statistically significant correlations were observed to be 94% for CT features and 95% for MRI ones. When examining the correlation between features extracted from contrast-enhanced CT and MRI using the same software, higher significant correspondences were identified in 11% of features for both software.

CONCLUSIONS: Considering NSCLC, (i) for both imaging techniques, LIFEx and PyRadiomics agreed on average for 90% of features, with MRI being more affected by resampling and (ii) CT and MRI contained mostly non-redundant information, but there are shape features and, more importantly, texture features that can be singled out by both techniques.

RELEVANCE STATEMENT: Identifying and selecting features that are stable cross-modalities may be one of the strategies to pave the way for radiomics clinical translation.

KEY POINTS: • More than 90% of LIFEx and PyRadiomics features contain the same information. • Ten percent of features (shape, texture) are stable among contrast-enhanced CT and MRI. • Software compliance and cross-modalities stability features are impacted by the resampling method.

PMID:38880866 | DOI:10.1186/s41747-024-00468-8

Environ Monit Assess. 2024 Jun 17;196(7):623. doi: 10.1007/s10661-024-12794-w.

ABSTRACT

Groundwater salinity is a critical factor affecting water quality and ecosystem health, with implications for various sectors including agriculture, industry, and public health. Hence, the reliability and accuracy of groundwater salinity predictive models are paramount for effective decision-making in managing groundwater resources. This pioneering study presents the validation of a predictive model aimed at forecasting groundwater salinity levels using three different validation methods and various data partitioning strategies. This study tests three different data validation methodologies with different data-partitioning strategies while developing a group method of data handling (GMDH)-based model for predicting groundwater salinity concentrations in a coastal aquifer system. The three different methods are the hold-out strategy (last and random selection), k-fold cross-validation, and the leave-one-out method. In addition, various combinations of data-partitioning strategies are also used while using these three validation methodologies. The prediction model’s validation results are assessed using various statistical indices such as root mean square error (RMSE), means squared error (MSE), and coefficient of determination (R²). The results indicate that for monitoring wells 1, 2, and 3, the hold-out (random) with 40% data partitioning strategy gave the most accurate predictive model in terms of RMSE statistical indices. Also, the results suggested that the GMDH-based models behave differently with different validation methodologies and data-partitioning strategies giving better salinity predictive capabilities. In general, the results justify that various model validation methodologies and data-partitioning strategies yield different results due to their inherent differences in how they partition the data, assess model performance, and handle sources of bias and variance. Therefore, it is important to use them in conjunction to obtain a comprehensive understanding of the groundwater salinity prediction model’s behavior and performance.

PMID:38880864 | DOI:10.1007/s10661-024-12794-w

Support Care Cancer. 2024 Jun 17;32(7):438. doi: 10.1007/s00520-024-08642-9.

ABSTRACT

PURPOSE: There are limited treatment options available for hematopoietic stem-cell transplant patients (HSCT) with oral graft-versus-host disease (GVHD). Intraoral phototherapy is a novel, yet promising therapeutic regimen.

RESEARCH QUESTION: To assess the safety and effectiveness of intraoral narrowband UVB (nbUVB) phototherapy in the treatment of oral GVHD.

METHODS: This case series evaluated 10 patients with refractory oral GVHD, who were treated at Northwestern Memorial Hospital with nbUVB between July 2019 and October 2023. Primary outcomes were to evaluate the safety and efficacy of phototherapy. Efficacy was measured by objective improvement in symptom scores and subjective improvement in patient reported symptoms. Safety was determined by the withdrawal due to adverse events. Total nbUVB exposure, number of treatments, and change in systemic immunosuppressive medications were also examined.

RESULTS: The study cohort comprised 10 patients who developed oral GVHD at a median of 9.5 months after HSCT. The total median dose of nbUVB was 36 J/cm², and the median number of sessions was 55. All 10 patients demonstrated some degree of improvement in symptoms. Notably, there was a reduction in the number of patients who reported symptoms of oral pain (83%), bleeding (67%), xerostomia (50%), and oral sensitivity (78%) after initiating phototherapy. There was also a statistically significant decrease in the levels of pain, erythema, and edema (p ≤ 0.001, < 0.001, 0.01, respectively). Most patients tolerated phototherapy well, but 1 patient withdrew from treatment due to adverse effects. Seventy-five percent of patients who were on immunosuppressive medications were able to decrease or stop these medications.

CONCLUSION: This case series suggests that nbUVB phototherapy is well tolerated and efficacious in patients with oral GVHD.

PMID:38880860 | DOI:10.1007/s00520-024-08642-9

Prog Orthod. 2024 Jun 17;25(1):24. doi: 10.1186/s40510-024-00520-8.

ABSTRACT

INTRODUCTION: Metallic and elastomeric ligatures are widely used in orthodontics to secure the archwire within the bracket slots, but elastomeric ligatures have traditionally been associated with increased microbial colonization, which could adversely affect periodontal health.

AIM: This systematic review compares the periodontal effects of elastomeric and steel ligatures used for orthodontic fixed appliances.

METHODS: Unrestricted literature search of 7 databases (MEDLINE, Scopus, Web of Science, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Virtual Health Library) up to July 2023 were performed for randomized / non-randomized clinical studies on humans comparing the two ligation methods during fixed-appliance therapy. After duplicate study selection, data extraction, and risk-of-bias assessment with the Risk of Bias (RoB) 2 or the Risk Of Bias In Non-randomized Studies – of Interventions (ROBINS-I) tool, random-effects meta-analyses of Mean Differences (MD) or Standardized Mean Differences (SMD) and their 95% confidence intervals (CIs) were carried out, followed by assessment of certainty of existing evidence with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach.

RESULTS: A total of 11 studies (3 randomized / 8 non-randomized) with 354 patients (mean age 14.7 years and 42% male) were included. No statistically significant differences were seen for plaque index (5 studies; SMD = 0.48; 95% CI = -0.03 to 1.00; P = 0.07), gingival index (2 studies; MD = 0.01; 95% CI = -0.14 to 0.16; P = 0.89), probing pocket depth (2 studies; MD = 0; 95% CI = -0.17 to 0.16; P = 0.97), or Streptococcus mutans counts (4 studies; SMD = 0.40; 95% CI=-0.41 to 1.20; P = 0.21). Elastomeric ligatures were associated with moderately increased total bacterial load (3 studies; SMD = 0.43; 95% CI = 0.10 to 0.76; P = 0.03). Confidence in these estimates was low in all instances due to the inclusion of non-randomized studies with high risk of bias.

CONCLUSIONS: Existing low quality evidence indicates that ligature method does not seem to influence the periodontal health during fixed treatment, even if elastomeric ligatures are associated with a moderate increase of bacterial load.

REGISTRATION: PROSPERO (CRD42023444383).

PMID:38880839 | DOI:10.1186/s40510-024-00520-8

Sci Rep. 2024 Jun 16;14(1):13875. doi: 10.1038/s41598-024-62645-4.

ABSTRACT

After obtaining an exact regular-AdS black hole resulting from the coupling of general relativity with nonlinear electrodynamics (NED), we explore the thermodynamics of the extended phase space, treating the cosmological constant ( $\Lambda$ ) as the pressure (P) of the black holes and its conjugate as thermodynamic volume (V). Considering the NED parameter (g), we investigate the Hawking temperature, entropy, Gibb’s free energy and specific heat at the horizon radius. Due to the presence of NED charge, the black hole exhibits van der Waals-like phase transition instead of Hawking-Page phase transition, which could be observed through the $G–T$ plots, which display a swallowtail pattern below the critical pressure, and it gives rise to second-order phase transitions when pressure attains its critical value. The first-order phase transition shares similarities with the liquid-gas phase transition. We determine the exact critical points and explore the influence of NED on $P–V$ criticality, revealing that the isotherms undergo a liquid-gas-like phase transition for temperatures below its critical value $T_C$ , especially at lower $T_C$ . The identical critical exponent to that of the van der Waals fluid suggests that the NED does not alter the critical exponents, as observed in other arbitrary AdS black holes.

PMID:38880829 | DOI:10.1038/s41598-024-62645-4

Neuroradiology. 2024 Jun 17. doi: 10.1007/s00234-024-03400-4. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Quantitative T1 mapping can be an essential tool for assessing tissue injury in multiple sclerosis (MS). We introduce T1-REQUIRE, a method that converts a single high-resolution anatomical 3D T1-weighted Turbo Field Echo (3DT1TFE) scan into a parametric T1 map that could be used for quantitative assessment of tissue damage. We present the accuracy and feasibility of this method in MS.

METHODS: 14 subjects with relapsing-remitting MS and 10 healthy subjects were examined. T1 maps were generated from 3DT1TFE images using T1-REQUIRE, which estimates T1 values using MR signal equations and internal tissue reference T1 values. Estimated T1 of lesions, white, and gray matter regions were compared with reference Inversion-Recovery Fast Field Echo T1 values and analyzed via correlation and Bland-Altman (BA) statistics.

RESULTS: 159 T1-weighted (T1W) hypointense MS lesions and 288 gray matter regions were examined. T1 values for MS lesions showed a Pearson’s correlation of r = 0.81 (p < 0.000), R² = 0.65, and Bias = 4.18%. BA statistics showed a mean difference of -53.95 ms and limits of agreement (LOA) of -344.20 and 236.30 ms. Non-lesional normal-appearing white matter had a correlation coefficient of r = 0.82 (p < 0.000), R² = 0.67, Bias = 8.78%, mean difference of 73.87 ms, and LOA of -55.67 and 203.41 ms.

CONCLUSIONS: We demonstrate the feasibility of retroactively derived high-resolution T1 maps from routinely acquired anatomical images, which could be used to quantify tissue pathology in MS. The results of this study will set the stage for testing this method in larger clinical studies for examining MS disease activity and progression.

PMID:38880824 | DOI:10.1007/s00234-024-03400-4

J Hum Genet. 2024 Jun 17. doi: 10.1038/s10038-024-01257-2. Online ahead of print.

ABSTRACT

Variants in voltage-gated sodium channel (VGSC) genes are implicated in seizures, epilepsy, and neurodevelopmental disorders, constituting a significant aspect of hereditary epilepsy in the Chinese population. Through retrospective analysis utilizing next-generation sequencing (NGS), we examined the genotypes and phenotypes of VGSC-related epilepsy cases from a cohort of 691 epilepsy subjects. Our findings revealed that 5.1% of subjects harbored VGSC variants, specifically 22 with SCN1A, 9 with SCN2A, 1 with SCN8A, and 3 with SCN1B variants; no SCN3A variants were detected. Among these, 14 variants were previously reported, while 21 were newly identified. SCN1A variant carriers predominantly presented with Dravet Syndrome (DS) and Genetic Epilepsy with Febrile Seizures Plus (GEFS + ), featuring a heightened sensitivity to fever-induced seizures. Statistically significant disparities emerged between the SCN1A-DS and SCN1A-GEFS+ groups concerning seizure onset and genetic diagnosis age, incidence of status epilepticus, mental retardation, anti-seizure medication (ASM) responsiveness, and familial history. Notably, subjects with SCN1A variants affecting the protein’s pore region experienced more frequent cluster seizures. All SCN2A variants were of de novo origin, and 88.9% of individuals with SCN2A variations exhibited cluster seizures. This research reveals a significant association between variations in VGSC-related genes and the clinical phenotype diversity of epilepsy subjects in China, emphasizing the pivotal role of NGS screening in establishing accurate disease diagnoses and guiding the selection of ASM.

PMID:38880818 | DOI:10.1038/s10038-024-01257-2