Tag: nevin manimala

J Dev Orig Health Dis. 2023 Sep 21:1-11. doi: 10.1017/S2040174423000247. Online ahead of print.

ABSTRACT

The deleterious effects of adversity are likely intergenerational, such that one generation’s adverse experiences can affect the next. Epidemiological studies link maternal adversity to offspring depression and anxiety, possibly via transmission mechanisms that influence offspring fronto-limbic connectivity. However, studies have not thoroughly disassociated postnatal exposure effects nor considered the role of offspring sex. We utilized infant neuroimaging to test the hypothesis that maternal childhood maltreatment (CM) would be associated with increased fronto-limbic connectivity in infancy and tested brain-behavior associations in childhood. Ninety-two dyads participated (32 mothers with CM, 60 without; 52 infant females, 40 infant males). Women reported on their experiences of CM and non-sedated sleeping infants underwent MRIs at 2.44 ± 2.74 weeks. Brain volumes were estimated via structural MRI and white matter structural connectivity (fiber counts) via diffusion MRI with probabilistic tractography. A subset of parents (n = 36) reported on children’s behaviors at age 5.17 ± 1.73 years. Males in the maltreatment group demonstrated greater intra-hemispheric fronto-limbic connectivity (b = 0.96, p= 0.008, [95%CI 0.25, 1.66]), no differences emerged for females. Fronto-limbic connectivity was related to somatic complaints in childhood only for males (r = 0.673, p = 0.006). Our findings suggest that CM could have intergenerational associations to offspring brain development, yet mechanistic studies are needed.

PMID:37732425 | DOI:10.1017/S2040174423000247

Stat Med. 2023 Sep 21. doi: 10.1002/sim.9900. Online ahead of print.

ABSTRACT

When multiple candidate subgroups are considered in clinical trials, we often need to make statistical inference on the subgroups simultaneously. Classical multiple testing procedures might not lead to an interpretable and efficient inference on the subgroups as they often fail to take subgroup size and subgroup effect relationship into account. In this paper, built on the selective traversed accumulation rules (STAR), we propose a data-adaptive and interactive multiple testing procedure for subgroups which can take subgroup size and subgroup effect relationship into account under prespecified tree structure. The proposed method is easy-to-implement and can lead to a more interpretable and efficient inference on prespecified tree-structured subgroups. Possible accommodations to post hoc identified tree-structure subgroups are also discussed in the paper. We demonstrate the merit of our proposed method by re-analyzing the panitumumab trial with the proposed method.

PMID:37732390 | DOI:10.1002/sim.9900

Sci Rep. 2023 Sep 20;13(1):15562. doi: 10.1038/s41598-023-42657-2.

ABSTRACT

Unsupervised clustering of intensive care unit (ICU) medications may identify unique medication clusters (i.e., pharmacophenotypes) in critically ill adults. We performed an unsupervised analysis with Restricted Boltzmann Machine of 991 medications profiles of patients managed in the ICU to explore pharmacophenotypes that correlated with ICU complications (e.g., mechanical ventilation) and patient-centered outcomes (e.g., length of stay, mortality). Six unique pharmacophenotypes were observed, with unique medication profiles and clinically relevant differences in ICU complications and patient-centered outcomes. While pharmacophenotypes 2 and 4 had no statistically significant difference in ICU length of stay, duration of mechanical ventilation, or duration of vasopressor use, their mortality differed significantly (9.0% vs. 21.9%, p < 0.0001). Pharmacophenotype 4 had a mortality rate of 21.9%, compared with the rest of the pharmacophenotypes ranging from 2.5 to 9%. Phenotyping approaches have shown promise in classifying the heterogenous syndromes of critical illness to predict treatment response and guide clinical decision support systems but have never included comprehensive medication information. This first-ever machine learning approach revealed differences among empirically-derived subgroups of ICU patients that are not typically revealed by traditional classifiers. Identification of pharmacophenotypes may enable enhanced decision making to optimize treatment decisions.

PMID:37730817 | DOI:10.1038/s41598-023-42657-2

Bull Math Biol. 2023 Sep 21;85(11):105. doi: 10.1007/s11538-023-01204-w.

ABSTRACT

Current research in Human Immunodeficiency Virus (HIV) focuses on eradicating virus reservoirs that prevent or dampen the effectiveness of antiretroviral treatment (ART). One such reservoir, the brain, reduces treatment efficacy via the blood-brain barrier (BBB), causing an obstacle to drug penetration into the brain. In this study, we develop a mathematical model to examine the impact of the BBB on ART effectiveness for mitigating brain HIV. A thorough analysis of the model allowed us to fully characterize the global threshold dynamics with the viral clearance and persistence in the brain for the basic reproduction number less than unity and greater than unity, respectively. Our model showed that the BBB has a significant role in inhibiting the effect of ART within the brain despite the effective viral load suppression in the plasma. The level of impact, however, depends on factors such as the CNS Penetration Effectiveness (CPE) score, the slope of the drug dose-response curves, the ART initiation timing, and the number of drugs in the ART protocol. These results suggest that reducing the plasma viral load to undetectable levels due to some drug regimen may not necessarily indicate undetectable levels of HIV in the brain. Thus, the effect of the BBB on viral suppression in the brain must be considered for developing proper treatment protocols against HIV infection.

PMID:37730794 | DOI:10.1007/s11538-023-01204-w

Sci Rep. 2023 Sep 20;13(1):15612. doi: 10.1038/s41598-023-42809-4.

ABSTRACT

Total hip arthroplasty (THA) is a successful orthopaedic surgical procedure, and its longevity depends on bearing components and implant fixation. Optimizing polyethylene and ceramics has led to improved wear parameters and contributed to improved long-term outcomes. The present systematic review investigated whether time span from implantation, patient characteristics and performance status exert an influence on liner wear and head migration in THA. This study was conducted in conformity to the 2020 PRISMA guidelines. All the clinical investigations which reported quantitative data on the amount of liner wear and head migration in THA were considered. Only studies which reported quantitative data at least on one of the following patient characteristics were suitable: mean age, mean BMI (kg/m²), sex, side, time span between the index THA and the last follow-up (months) were eligible. A multiple linear model regression analysis was employed to verify the association between patient characteristics and the amount of liner wear and/or head migration. The Pearson Product-Moment Correlation Coefficient was used to assess the association between variables. Data from 12,629 patients were considered. The mean length of the follow-up was 90.5 ± 50.9 months. The mean age of patients at surgery was 58.4 ± 9.4 years, and the mean BMI was 27.2 ± 2.5 kg/m². 57% (7199 of 12,629 patients) were women, and in 44% (5557 of 12,629 patients) THAs were performed on the left. The mean pre-operative Harris hip score was 46.5 ± 6.0 points. There was evidence of a moderate positive association between the amount of liner wear and the time elapsed between the index surgery to the follow-up (P = 0.02). There was evidence of a moderate positive association between the amount of head migration and the time elapsed between the index surgery to the follow-up (P = 0.01). No further statistically significant association was found. The time elapsed between the index surgery to the follow-up was the most important factor which influence the head migration and liner wear in THA. Patients’ characteristics and preoperative physical activity did not influence the amount of head migration and liner wear.

PMID:37730762 | DOI:10.1038/s41598-023-42809-4

Sci Rep. 2023 Sep 20;13(1):15590. doi: 10.1038/s41598-023-42433-2.

ABSTRACT

The spatial analysis of horizontal stress orientation is important to study stress sources and understand tectonics and the deformation of the lithosphere. Additional to the stress sources, the geometry of stress fields depends on the underlying coordinate reference system, which causes spatial distortions that bias the analysis and interpretation of stresses. The bias can be avoided when the stress field is decomposed and transformed into the reference frame of its first-order stress source. We present a modified and extended theory based on the empirical link between the orientation of first-order stresses and the trajectories of lateral plate boundary forces. This link is applied to analyze the orientation of horizontal stresses, their patterns, and tectonic structures from the perspective of their first-order source or cause. By using only parameters for the relative motion between two neighboring plates, we model the first-order orientation of the maximum horizontal stress that statistically fits the orientation of [Formula: see text]80% of the global stress data adjacent to plate boundaries. Considerable deviations of the observed stress from the predicted first-order stress direction can reveal the geometry of second-order stresses and confine areas where other stress sources dominate. The model’s simple assumptions, independence from the sample size, potential application to regional to global scale analysis, and compatibility with other spatial interpolation algorithms make it a powerful method for analyzing stress fields. For immediate use, the presented method is implemented in the free and open-source software package tectonicr, which is written in the computer language R.

PMID:37730752 | DOI:10.1038/s41598-023-42433-2

Sci Rep. 2023 Sep 20;13(1):15591. doi: 10.1038/s41598-023-42414-5.

ABSTRACT

Brain development is regularly studied using structural MRI. Recently, studies have used a combination of statistical learning and large-scale imaging databases of healthy children to predict an individual’s age from structural MRI. This data-driven, predicted ‘Brainage’ typically differs from the subjects chronological age, with this difference a potential measure of individual difference. Few studies have leveraged higher-order or connectomic representations of structural MRI data for this Brainage approach. We leveraged morphometric similarity as a network-level approach to structural MRI to generate predictive models of age. We benchmarked these novel Brainage approaches using morphometric similarity against more typical, single feature (i.e., cortical thickness) approaches. We showed that these novel methods did not outperform cortical thickness or cortical volume measures. All models were significantly biased by age, but robust to motion confounds. The main results show that, whilst morphometric similarity mapping may be a novel way to leverage additional information from a T1-weighted structural MRI beyond individual features, in the context of a Brainage framework, morphometric similarity does not provide more accurate predictions of age. Morphometric similarity as a network-level approach to structural MRI may be poorly positioned to study individual differences in brain development in healthy participants in this way.

PMID:37730747 | DOI:10.1038/s41598-023-42414-5

Sci Rep. 2023 Sep 20;13(1):15582. doi: 10.1038/s41598-023-42096-z.

ABSTRACT

The evolution of the hominin hand has been widely linked to the use and production of flaked stone tool technologies. After the earliest handheld flake tools emerged, shifts in hominin hand anatomy allowing for greater force during precision gripping and ease when manipulating objects in-hand are observed in the fossil record. Previous research has demonstrated how biometric traits, such as hand and digit lengths and precision grip strength, impact functional performance and ergonomic relationships when using flake and core technologies. These studies are consistent with the idea that evolutionary selective pressures would have favoured individuals better able to efficiently and effectively produce and use flaked stone tools. After the advent of composite technologies during the Middle Stone Age and Middle Palaeolithic, fossil evidence reveals differences in hand anatomy between populations, but there is minimal evidence for an increase in precision gripping capabilities. Furthermore, there is little research investigating the selective pressures, if any, impacting manual anatomy after the introduction of hafted composite stone technologies (‘handles’). Here we investigated the possible influence of tool-user biometric variation on the functional performance of 420 hafted Clovis knife replicas. Our results suggest there to be no statistical relationships between biometric variables and cutting performance. Therefore, we argue that the advent of hafted stone technologies may have acted as a ‘performance equaliser’ within populations and removed (or reduced) selective pressures favouring forceful precision gripping capabilities, which in turn could have increased the relative importance of cultural evolutionary selective pressures in the determination of a stone tool’s performance.

PMID:37730739 | DOI:10.1038/s41598-023-42096-z

Nat Commun. 2023 Sep 20;14(1):5825. doi: 10.1038/s41467-023-41562-6.

ABSTRACT

Tumor recognition by T cells is essential for antitumor immunity. A comprehensive characterization of T cell diversity may be key to understanding the success of immunomodulatory drugs and failure of PD-1 blockade in tumors such as multiple myeloma (MM). Here, we use single-cell RNA and T cell receptor sequencing to characterize bone marrow T cells from healthy adults (n = 4) and patients with precursor (n = 8) and full-blown MM (n = 10). Large T cell clones from patients with MM expressed multiple immune checkpoints, suggesting a potentially dysfunctional phenotype. Dual targeting of PD-1 + LAG3 or PD-1 + TIGIT partially restored their function in mice with MM. We identify phenotypic hallmarks of large intratumoral T cell clones, and demonstrate that the CD27^– and CD27⁺ T cell ratio, measured by flow cytometry, may serve as a surrogate of clonal T cell expansions and an independent prognostic factor in 543 patients with MM treated with lenalidomide-based treatment combinations.

PMID:37730678 | DOI:10.1038/s41467-023-41562-6

BMC Sports Sci Med Rehabil. 2023 Sep 20;15(1):114. doi: 10.1186/s13102-023-00732-1.

ABSTRACT

BACKGROUND: Lumbar spine injuries in fast bowlers account for the greatest missed playing time in cricket. A range of extrinsic and intrinsic variables are hypothesised to be associated with low back pain and lumbar spine injury in fast bowlers, and an improved understanding of intrinsic variables is necessary as these may alter load tolerance and injury risk associated with fast bowling. This review critically evaluated studies reporting intrinsic variables associated with low back pain and lumbar spine injury in fast bowlers and identified areas for future investigation.

METHODS: OVID Medline, EMBASE, SPORTDiscus, CINAHL, Web of Science and SCOPUS databases were last searched on 3 June 2022 to identify studies investigating intrinsic variables associated with low back pain and lumbar spine injury in cricket fast bowlers. Terms relevant to cricket fast bowling, and intrinsic variables associated with lumbar spine injury and low back pain in fast bowlers were searched. 1,503 abstracts were screened, and 118 full-text articles were appraised to determine whether they met inclusion criteria. Two authors independently screened search results and assessed risk of bias using a modified version of the Quality in Prognostic Studies tool.

RESULTS: Twenty-five studies met the inclusion criteria. Overall, no included studies demonstrated a low risk of bias, two studies were identified as moderate risk, and twenty-three studies were identified as high risk. Conflicting results were reported amongst studies investigating associations of fast bowling kinematics and kinetics, trunk and lumbar anatomical features, anthropometric traits, age, and neuromuscular characteristics with low back pain and lumbar spine injury.

CONCLUSION: Inconsistencies in results may be related to differences in study design, injury definitions, participant characteristics, measurement parameters, and statistical analyses. Low back pain and lumbar spine injury occurrence in fast bowlers remain high, and this may be due to an absence of low bias studies that have informed recommendations for their prevention. Future research should employ clearly defined injury outcomes, analyse continuous datasets, utilise models that better represent lumbar kinematics and kinetics during fast bowling, and better quantify previous injury, lumbar anatomical features and lumbar maturation.

TRIAL REGISTRATION: Open Science Framework https://doi.org/10.17605/OSF.IO/ERKZ2 .

PMID:37730648 | DOI:10.1186/s13102-023-00732-1