Category: Statistics

Plant Cell. 2023 Oct 5:koad247. doi: 10.1093/plcell/koad247. Online ahead of print.

ABSTRACT

NAKED ENDOSPERM1 (NKD1), NKD2 and OPAQUE2 are transcription factors important for cell patterning and nutrient storage in maize (Zea mays) endosperm. To study the complex regulatory interrelationships among these three factors in co-regulating gene networks, we developed a set of nkd1, nkd2 and o2 homozygous lines, including all combinations of mutant and wild-type genes. Among the eight genotypes tested, we observed diverse phenotypes and gene interactions affecting cell patterning, starch content, and storage proteins. From ∼8 to ∼16 days after pollination, maize endosperm undergoes a transition from cellular development to nutrient accumulation for grain filling. Gene network analysis showed that NKD1, NKD2 and O2 dynamically regulate a hierarchical gene network during this period, directing cellular development early, then transitioning to constrain cellular development while promoting the biosynthesis and storage of starch, proteins and lipids. Genetic interactions regulating this network are also dynamic. The assay for transposase-accessible chromatin using sequencing (ATAC-seq) showed that O2 influences the global regulatory landscape, decreasing NKD1 and NKD2 target site accessibility, while NKD1 and NKD2 increase O2 target site accessibility. In summary, interactions of NKD1, NKD2 and O2 dynamically affect the hierarchical gene network and regulatory landscape during the transition from cellular development to grain filling in maize endosperm.

PMID:37795691 | DOI:10.1093/plcell/koad247

Psychol Med. 2023 Sep;53(12):5405-5414. doi: 10.1017/S003329172200246X. Epub 2022 Aug 24.

ABSTRACT

BACKGROUND: Preschool psychiatric symptoms significantly increase the risk for long-term negative outcomes. Transdiagnostic hierarchical approaches that capture general (‘p’) and specific psychopathology dimensions are promising for understanding risk and predicting outcomes, but their predictive utility in young children is not well established. We delineated a hierarchical structure of preschool psychopathology dimensions and tested their ability to predict psychiatric disorders and functional impairment in preadolescence.

METHODS: Data for 1253 preschool children (mean age = 4.17, s.d. = 0.81) were drawn from three longitudinal studies using a similar methodology (one community sample, two psychopathology-enriched samples) and followed up into preadolescence, yielding a large and diverse sample. Exploratory factor models derived a hierarchical structure of general and specific factors using symptoms from the Preschool Age Psychiatric Assessment interview. Longitudinal analyses examined the prospective associations of preschool p and specific factors with preadolescent psychiatric disorders and functional impairment.

RESULTS: A hierarchical dimensional structure with a p factor at the top and up to six specific factors (distress, fear, separation anxiety, social anxiety, inattention-hyperactivity, oppositionality) emerged at preschool age. The p factor predicted all preadolescent disorders (ΔR² = 0.04-0.15) and functional impairment (ΔR² = 0.01-0.07) to a significantly greater extent than preschool psychiatric diagnoses and functioning. Specific dimensions provided additional predictive power for the majority of preadolescent outcomes (disorders: ΔR² = 0.06-0.15; functional impairment: ΔR² = 0.05-0.12).

CONCLUSIONS: Both general and specific dimensions of preschool psychopathology are useful for predicting clinical and functional outcomes almost a decade later. These findings highlight the value of transdiagnostic dimensions for predicting prognosis and as potential targets for early intervention and prevention.

PMID:37795688 | DOI:10.1017/S003329172200246X

J Infect Dis. 2023 Oct 5:jiad420. doi: 10.1093/infdis/jiad420. Online ahead of print.

ABSTRACT

BACKGROUND: Varicella is a highly infectious disease, particularly affecting children, that can lead to complications requiring antibiotics or hospitalization. Antibiotic use for varicella management is poorly documented. This study assessed antibiotic use for varicella and its complications in a pediatric population in England.

METHODS: Data were drawn from medical records in the Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Patients <18 years old diagnosed with varicella during 2014-2018 with 3-month follow-up available were included. We described varicella-related complications, medication use, healthcare resource utilization, and costs from diagnosis until 3-month post-diagnosis.

RESULTS: We identified 114,578 children with a primary varicella diagnosis. 7.7% (n = 8,814) had a varicella-related complication, the most common being ear, nose, and throat related (37.1%, n = 3,271). In all, 25.9% (n = 29,706/114,578) were prescribed antibiotics. A higher proportion of patients with complications than those without complications were prescribed antibiotics (64.3%, n = 5,668/8,814 vs. 22.7%, n = 24,038/105,764). Mean annualized varicella-related costs were £2,231,481 for the study cohort. Overall, antibiotic prescriptions cost ∼£262,007.

CONCLUSIONS: This study highlights high antibiotic use and healthcare resource utilization associated with varicella management, particularly in patients with complications. A national varicella vaccination program in England may reduce varicella burden and related complications, medication use, and costs.

PMID:37795662 | DOI:10.1093/infdis/jiad420

Pediatr Obes. 2023 Oct 5:e13079. doi: 10.1111/ijpo.13079. Online ahead of print.

ABSTRACT

BACKGROUND: Energy balance-related behaviours (EBRBs), that is, dietary intake, screen, outdoor play and sleep, tend to combine into ‘lifestyle patterns’, with potential synergistic influences on health. To date, studies addressing this theme mainly focused on school children and rarely accounted for sleep, with a cross-country perspective.

OBJECTIVES: We aimed at comparing lifestyle patterns among preschool-aged children across Europe, their associations with socio-demographic factors and their links with body mass index (BMI).

METHODS: Harmonized data on 2-5-year-olds participating in nine European birth cohorts from the EU Child Cohort Network were used (EBRBs, socio-demographics and anthropometrics). Principal component analysis and multivariable linear and logistic regressions were performed.

RESULTS: The most consistent pattern identified across cohorts was defined by at least three of the following EBRBs: discretionary consumption, high screen time, low outdoor play time and low sleep duration. Consistently, children from low-income households and born to mothers with low education level had higher scores on this pattern compared to their socioeconomically advantaged counterparts. Furthermore, it was associated with higher BMI z-scores in the Spanish and Italian cohorts (β = 0.06, 95% CI = [0.02; 0.10], both studies).

CONCLUSION: These findings may be valuable in informing early multi-behavioural interventions aimed at reducing social inequalities in health at a European scale.

PMID:37795656 | DOI:10.1111/ijpo.13079

Clin Physiol Funct Imaging. 2023 Oct 5. doi: 10.1111/cpf.12857. Online ahead of print.

ABSTRACT

BACKGROUND: SGLT2 inhibitors have been shown to reduce hospitalization in patients with chronic heart failure (CHF). The cardioprotective mechanisms of gliflozins however have not been fully elucidated. Aim of this study was therefore to evaluate the effect of SGLT2 inhibitors on right and left ventricular function in patients with diabetes and HF.

METHODS: Seventy-eight patients with diabetes and CHF were enrolled in the study and followed up; 38 started treatment with SGLT2i, while the remaining 40 continued their previous antidiabetic therapy. All patients underwent conventional, TDI and strain echocardiography in an ambulatory setting, at the beginning and after 3 months of therapy with SGLT2i.

RESULTS: After 3 months of therapy with SGLT2i, echocardiographic parameters assessing both left and right ventricular dimensions and function were found as significantly improved in patients switching to SGLT2i than control group: LVEF (45±9% vs 40±8%, p<0.001), LVEDD (54±6.5 vs 56±6.5 mm, p<0.01), GLS (-13±4% vs -10±3%, p<0.001), TAPSE (21±3 vs 19±3 mm, p<0.001), RV S’ (13±2.5 vs 11±2, p<0.001), and PAsP (24±8 vs 31±9 mmHg, p<0.001). Also mitral (1.0±0.5 vs 1.3±0.5, p<0.01) and tricuspid regurgitation (1.0±0.5 vs 1.3±0.5, p<0.01) improved after SGLT2i therapy. Changes were not statistically significant in patients not treated with SGLT2i (p n.s. in all cases).

CONCLUSIONS: In a real-world scenario, treatment with SGLT2i in patients with CHF and diabetes is associated with an improvement in both left and right ventricular function assessed at echocardiography. These data may explain potential anti-remodelling effects of gliflozins. This article is protected by copyright. All rights reserved.

PMID:37795627 | DOI:10.1111/cpf.12857

Adv Mater. 2023 Oct 5:e2303253. doi: 10.1002/adma.202303253. Online ahead of print.

ABSTRACT

Functional biomaterial has already become an important aspect in modern therapeutics, yet the design of novel multi-functional biomaterial is still a challenging task nowadays. When several biofunctional components are present, the complexity that arises from their combinations and interactions would lead to tedious trial-and-error screening. In this work, we present a novel strategy of biomaterial rational design through the marriage of gradient surface generation with statistical learning. Not only parameter combinations can be screened in a high-throughput fashion, the optimal conditions beyond the experimentally tested range can also be extrapolated from the models. We have demonstrated the power of our strategy in rationally designing an unprecedented ternary functionalized surface for orthopedic implant, with optimal osteogenic, angiogenic and neurogenic activities, and have confirmed its optimality in vitro and the best osteointegration promotion in vivo. The presented strategy is expected to open up new possibilities in the rational design of biomaterials. This article is protected by copyright. All rights reserved.

PMID:37795620 | DOI:10.1002/adma.202303253

J Cereb Blood Flow Metab. 2023 Oct 5:271678X231204426. doi: 10.1177/0271678X231204426. Online ahead of print.

ABSTRACT

Type 2 diabetes (T2D) is associated with dyslipidemia and mild cognitive impairment. This study investigated the relationships between serum lipids metabolism, cognition, and functional connectivity (FC) within and between brain networks in T2D patients. The study included 102 T2D patients and 45 healthy controls who underwent functional magnetic resonance imaging, lipid profile tests, and cognitive assessments. Thirteen functional networks were identified using independent component analysis. The statistical analyses included multivariate analysis of covariance, partial correlation, canonical correlation, and mediation analyses. We found widely reduced between-network FCs in T2D, especially between the ventral sensorimotor network (SMN) and dorsal attention network (DAN) (p = 0.001) and between the ventral SMN and lateral visual network (VN) (p < 0.001). Moreover, lower between-network FCs were correlated with worse serum lipids metabolism and poorer cognitive performance (all p < 0.05). Importantly, between-network FCs mediated the relationship between lipid metabolism and cognition (β = -0.3136, 95% CI: -0.7660, -0.0186). Within-network analyses revealed altered FCs within the anterior default mode network, DAN, and lateral VN, each positively correlated with global cognition (all p < 0.01). Our results suggest the potential of improving cognitive function by regulating serum lipids in individuals with T2D.

PMID:37795619 | DOI:10.1177/0271678X231204426

Pediatr Pulmonol. 2023 Oct 5. doi: 10.1002/ppul.26695. Online ahead of print.

ABSTRACT

INTRODUCTION: We determined if the heart rate (HR) monitoring performance of a wireless and nonadhesive belt is non-inferior compared to standard electrocardiography (ECG). Secondary objective was to explore the belt’s respiratory rate (RR) monitoring performance compared to chest impedance (CI).

METHOD: In this multicenter non-inferiority trial, preterm and term infants were simultaneously monitored with the belt and conventional ECG/CI for 24 h. HR monitoring performance was estimated with the HR difference and ability to detect cardiac events compared to the ECG, and the incidence of HR-data loss per second. These estimations were statistically compared to prespecified margins to confirm equivalence/non-inferiority. Exploratory RR analyses estimated the RR trend difference and ability to detect apnea/tachypnea compared to CI, and the incidence of RR-data loss per second.

RESULTS: Thirty-nine infants were included. HR monitoring with the belt was non-inferior to the ECG with a mean HR difference of 0.03 beats per minute (bpm) (standard error [SE] = 0.02) (95% limits of agreement [LoA]: [-5 to 5] bpm) (p < 0.001). Second, sensitivity and positive predictive value (PPV) for cardiac event detection were 94.0% (SE = 0.5%) and 92.6% (SE = 0.6%), respectively (p ≤ 0.001). Third, the incidence of HR-data loss was 2.1% (SE = 0.4%) per second (p < 0.05). The exploratory analyses of RR showed moderate trend agreement with a mean RR-difference of 3.7 breaths/min (SE = 0.8) (LoA: [-12 to 19] breaths/min), but low sensitivities and PPV’s for apnea/tachypnea detection. The incidence of RR-data loss was 2.2% (SE = 0.4%) per second.

CONCLUSION: The nonadhesive, wireless belt showed non-inferior HR monitoring and a moderate agreement in RR trend compared to ECG/CI. Future research on apnea/tachypnea detection is required.

PMID:37795597 | DOI:10.1002/ppul.26695

J Neurotrauma. 2023 Oct 5. doi: 10.1089/neu.2023.0377. Online ahead of print.

ABSTRACT

Intracranial pressure (ICP) data from traumatic brain injury (TBI) patients in the intensive care unit (ICU) cannot be interpreted appropriately without accounting for the effect of administered therapy intensity level (TIL) on ICP. A 15-point scale was originally proposed in 1987 to quantify the hourly intensity of ICP-targeted treatment. This scale was subsequently modified &ndash; through expert consensus &ndash; during the development of TBI Common Data Elements to address statistical limitations and improve usability. The latest, 38-point scale (hereafter referred to as TIL) permits integrated scoring for a 24-hour period and has a five-category, condensed version (TIL^(Basic)) based on qualitative assessment. Here, we perform a total- and component-score analysis of TIL and TIL^(Basic) to: (1) validate the scales across the wide variation in contemporary ICP management, (2) compare their performance against that of predecessors, and (3) derive guidelines for proper scale use. From the observational Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study, we extract clinical data from a prospective cohort of ICP-monitored TBI patients (<em>n</em>=873) from 52 ICUs across 19 countries. We calculate daily TIL and TIL^(Basic) scores (TIL₂₄ and TIL^(Basic)₂₄, respectively) from each patient&rsquo;s first week of ICU stay. We also calculate summary TIL and TIL^(Basic) scores by taking the first-week maximum (TIL_max and TIL^(Basic)_max) and first-week median (TIL_median and TIL^(Basic)_median) of TIL₂₄ and TIL^(Basic)₂₄ scores for each patient. We find that, across all measures of construct and criterion validity, the latest TIL scale performs significantly greater than or similarly to all alternative scales (including TIL^(Basic)) and integrates the widest range of modern ICP treatments. TIL_median outperforms both TIL_max and summarised ICP values in detecting refractory intracranial hypertension (RICH) during ICU stay. The RICH detection thresholds which maximise the sum of sensitivity and specificity are TIL_median&ge;7.5 and TIL_max&ge;14. The TIL₂₄ threshold which maximises the sum of sensitivity and specificity in the detection of surgical ICP control is TIL₂₄&ge;9. The median scores of each TIL component therapy over increasing TIL₂₄ reflect a credible staircase approach to treatment intensity escalation, from head positioning to surgical ICP control, as well as considerable variability in the use of cerebrospinal fluid drainage and decompressive craniectomy. Since TIL^(Basic)_max suffers from a strong statistical ceiling effect and only covers 17% (95% CI: 16&ndash;18%) of the information in TIL_max, TIL^(Basic) should not be used instead of TIL for rating maximum treatment intensity. TIL^(Basic)₂₄ and TIL^(Basic)_median can be suitable replacements for TIL₂₄ and TIL_median, respectively (with up to 33% [95% CI: 31&ndash;35%] information coverage) when TIL assessment is infeasible. Accordingly, we derive numerical ranges for categorising TIL₂₄ scores into TIL^(Basic)₂₄ scores. In conclusion, our results validate TIL across a spectrum of ICP management and monitoring approaches. TIL is a more sensitive surrogate for pathophysiology than ICP…

PMID:37795563 | DOI:10.1089/neu.2023.0377

Angew Chem Int Ed Engl. 2023 Oct 5:e202308675. doi: 10.1002/anie.202308675. Online ahead of print.

ABSTRACT

The mechanism for interaction and bonding of single guest molecules with active sites fundamentally determines the sorption and subsequent catalytic processes occurring in host zeolitic frameworks. However, no real-space studies on these significant issues have been reported thus far, since atomically visualizing guest molecules and recognizing single Al T-sites in zeolites remain challenging. Here, we atomically resolved single thiophene probes interacting with acid T-sites in the ZSM-5 framework to study the bonding behaviors between them. The synergy of bifurcated three-centered hydrogen bonds and van der Waals interactions can “freeze” the near-horizontal thiophene and make it stable enough to be imaged. By combining the imaging results with simulations, direct atomic observations enabled us to precisely locate the single Al T-sites in individual straight channels. Then, we statistically found that the thiophene bonding probability of the T11 site is 15 times higher than that of the T6 site. For different acid T-sites, the variation in the interaction synergy changes the inner angle of the host-guest O-H···S hydrogen bond, thereby affecting the stability of the near-horizontal thiophene and leading to considerable bonding inhomogeneities.

PMID:37795545 | DOI:10.1002/anie.202308675