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Our research investigates the magnon bands and their topological characteristics in a ferromagnetic pyrochlore lattice, with the Dzyaloshinskii–Moriya (DM) interaction playing a significant role. Given its kagome AB bilayer structure, the ferromagnetic exchange couplings, which may differ among the AB triangles, are further considered for their implications on the system's magnetic properties. By employing the non-equilibrium Green's function method, we explicitly demonstrate that the one-way chiral edge magnon transport is indeed regulated by the DM interaction direction (D → − D) and the exchange interaction of J 1 and J 2 (J 1 ↔ J 2). Moreover, we demonstrate that the topological edge state predominantly resides along the edges and exhibits an oscillatory decay as it penetrates into the bulk in a non-equilibrium state. Although the chiral edge magnons and the corresponding energy current tend to travel along one edge from the hot region to the cold one, in the bulk, however, the energy current flows reversely from the cold to the hot region. The valley magnon Hall effects and chiral edge transport proposed here may be realized in the thin films of the insulating ferromagnet, such as Lu 2 V 2 O 7. Thus, it will pave the way for a more extensive use of magnonics in future technologies. [ABSTRACT FROM AUTHOR]

Owing to charge free property, magnon is highly promising to achieve dissipationless transport without Joule heating and, thus, potentially applicable to energy efficient devices. In this paper, using the non-equilibrium Green's function, we present the bulk-boundary correspondence for magnonic Kagome lattices by studying the edge magnons transport. With staggered exchange interaction and Dzyaloshinskii–Moriya interaction in the Kagome lattices, one can observe valley contrasting magnon Hall effect, which endows magnon transport with the valley degree of freedom and adds a new dimension to regulate magnon excitation. In particular, we demonstrate that the valley splitting in the Kagome lattice enables a tunable single edge chiral transport. Thermal rectification is a direction-dependent asymmetric heat transfer phenomenon; here, we report the tunable thermal rectification by asymmetric nonlinear effect, and it is, indeed, regulated by the Dzyaloshinskii–Moriya interaction direction (D → − D) and the exchange of J 1 and J 2 (J 1 ↔ J 2). Moreover, we show that the topological edge state mainly localizes around edges and leaks into the bulk with oscillatory decay. These give full play to spin and valley degrees of freedom and provide various avenues for information encoding and manipulation based on valley related magnonic flux. [ABSTRACT FROM AUTHOR]

Objective: Children born small for gestational age (SGA) are at increased risk of health issues. This study evaluated the efficacy, safety and optimal dose of PEGylated‐recombinant human growth hormone (PEG‐rhGH) in these children. Design: In this multicentre, randomised, open‐label, Phase 2 trial conducted at nine clinical sites in China, patients were randomised 1:1 to receive subcutaneous injections of PEG‐rhGH at 0.1 mg/kg/week (low dose) or 0.2 mg/kg/week (high dose) for 52 weeks. Patients: Ninety‐six children were born SGA. Measurements: The primary endpoint was the change in height standard deviation score (HT‐SDS) at Week 52. Results: At Week 52, the change in HT‐SDS in the high‐ and low‐dose groups was 0.923 ± 0.352 (p < 0.0001) and 0.511 ± 0.336 (p < 0.0001), respectively (least‐squares means difference, 0.410; 95% confidence interval 0.270–0.551; p < 0.0001). Height velocity (9.94 ± 1.55 vs. 8.37 ± 1.50 cm/year) was also significantly higher in the high‐dose than in the low‐dose group (p < 0.0001). Change in insulin‐like growth factor (IGF)‐1 SDS was 1.867 ± 1.747 and 1.168 ± 1.193 in the high‐ and low‐dose groups, respectively (p = 0.0189). IGF‐1/IGF binding protein‐3 and bone maturity were improved in both groups at Week 52. Most treatment‐emergent adverse events were mild to moderate; the safety profile was similar in both groups. Conclusions: PEG‐rhGH at either dose for 52 weeks was effective and well tolerated in children born SGA. Patients in the high‐dose group achieved greater improvement in HT‐SDS than in the low‐dose group. Trial Registration: ClinicalTrials. gov identifier: NCT02375620 [ABSTRACT FROM AUTHOR]

Context Genetic testing for 21-hydroxylase deficiency (21-OHD) is always challenging. The current approaches of short-read sequencing and multiplex ligation-dependent probe amplification (MLPA) are insufficient for the detection of chimeric genes or complicated variants from multiple copies. Recently developed long-read sequencing (LRS) can solve this problem. Objective To investigate the clinical utility of LRS in precision diagnosis of 21-OHD. Methods In the cohort of 832 patients with 21-OHD, the current approaches provided the precise molecular diagnosis for 81.7% (680/832) of cases. LRS was performed to solve the remaining 144 cases with complex chimeric variants and 8 cases with variants from multiple copies. Clinical manifestations in patients with continuous deletions of CYP21A 2 extending to TNXB (namely CAH-X) were further evaluated. Results Using LRS in combination with previous genetic test results, a total of 16.9% (281/1664) CYP21A1P/CYP21A2 or TNXA/TNXB chimeric alleles were identified in 832 patients, with CYP21A1P / CYP21A2 accounting for 10.4% and TNXA / TNXB for 6.5%. The top 3 common chimeras were CYP21 CH-1, TNX CH-1, and TNX CH-2, accounting for 77.2% (217/281) of all chimeric alleles. The 8 patients with variants on multiple copies of CYP21A2 were accurately identified with LRS. The prevalence of CAH-X in our cohort was 12.1%, and a high frequency of connective tissue-related symptoms was observed in CAH-X patients. Conclusion LRS can detect all types of CYP21A2 variants, including complex chimeras and pathogenic variants on multiple copies in patients with 21-OHD, which could be utilized as a first-tier routine test for the precision diagnosis and categorization of congenital adrenal hyperplasia. [ABSTRACT FROM AUTHOR]

Regions of homozygosity (ROH) could implicate uniparental disomy (UPD) on specific chromosomes associated with imprinting disorders. Though the algorithms for ROH detection in exome sequencing (ES) have been developed, optimal reporting thresholds and when to pursue confirmatory UPD testing for imprinting disorders remain in ambiguity. This study used a data-driven approach to assess optimal reporting thresholds of ROH in clinical practice. ROH analysis was performed using Automap in a retrospective cohort of 8,219 patients and a prospective cohort of 1,964 patients with ES data. Cases with ROH on imprinting-disorders related chromosomes were selected for additional methylation-specific confirmatory testing. The diagnostic yield, the ROH pattern of eventually diagnosed cases and optimal thresholds for confirmatory testing were analyzed. In the retrospective analysis, 15 true UPD cases of imprinting disorders were confirmed among 51 suspected cases by ROH detection. Pattern of ROH differed between confirmed UPD and non-UPD cases. Maximized yield and minimized false discovery rate of confirmatory UPD testing was achieved at the thresholds of >20 Mb or >25 % chromosomal coverage for interstitial ROH, and >5 Mb for terminal ROH. Current recommendation by ACMG was nearly optimal, though refined thresholds as proposed in this study could reduce the workload by 31 % without losing any true UPD diagnosis. Our refined thresholds remained optimal after independent evaluation in a prospective cohort. ROH identified in ES could implicate the presence of clinically relevant UPD. This study recommended size and coverage thresholds for confirmatory UPD testing after ROH detection in ES, contributing to the development of evidence-based reporting guidelines. [ABSTRACT FROM AUTHOR]

Introduction: Growth hormone (GH) is crucial for immune system development and regulation, potentially benefiting COVID-19 outcomes. However, there are limited studies on the role of GH treatment in COVID-19 in children with short stature. Methods: We conducted a survey study to evaluate the association between GH treatment and COVID-19 risk in short stature children aged 7 to 18 years. Two groups were defined: GH Treated and GH Untreated. The primary endpoint was the proportion of children with COVID-19 histories. Secondary endpoints included the presence, severity, and duration of COVID-19 symptoms. Exploratory endpoints included the frequency of common colds after GH treatment. We further performed two-sample Mendelian randomization (MR) analyses to explore the causal relationship between GH levels and COVID-19 susceptibility, hospitalization, and severity using genome-wide association study summary-level data. Results: Of the 201 children, 113 (56.2%) reported COVID-19 history, and 149 (74.1%) used GH. The mean age was 11.02 ± 2.10 years. GH treatment was associated with a somewhat lower proportion of COVID-19 history (− 9.77%, 95% confidence interval [CI] − 26.41% to 6.87%; P = 0.289), and the odds ratio (OR) is 0.58 (95% CI 0.29 to 1.14, P = 0.120) after adjusting for confounders. Among the 113 children with COVID-19 histories, the highest body temperature was significantly lower in the GH Treated group (P = 0.040). In the MR analyses, for one unit increase in GH level, the OR was 0.95 (95% CI 0.92 to 0.99, P = 0.022) for COVID-19 susceptibility, 0.86 (95% CI 0.77 to 0.96, P = 0.007) for COVID-19 hospitalization, and 0.95 (95% CI 0.84 to 1.07, P = 0.392) for COVID-19 severity. Conclusion: GH treatment was associated with somewhat decreased COVID-19 susceptibility but was not statistically significant. Higher GH levels were causally associated with a significantly lower rate of COVID-19 susceptibility and hospitalization. [ABSTRACT FROM AUTHOR]

• We described the genetic composition of familial chylomicronemia syndrome (FCS) of Chinese patients. • Seven novel variants were identified in non-LPL-FCS, including five in GPIHBP1 and two in LMF1. • Fat-restricted diet markedly lowered TG levels in non-LPL-FCS patients. • GPIHBP1-FCS patients experienced greater challenges in managing TG levels in non-LPL-FCS. Familial chylomicronemia syndrome (FCS) comprises a group of ultrarare disorders caused by biallelic variants in LPL or, less frequently, by GPIHBP1, APOC2, APOA5 , or LMF1. To evaluate the phenotypes and management of eight non-lipoprotein lipase (LPL)-FCS patients. Seven pediatric and one adult patients with non-LPL-FCS were enrolled. Clinical features, treatment outcomes, and genetic profiles were assessed. Among the 33 patients with FCS, 25 (76%) had LPL-FCS and eight (24%) had non-LPL-FCS; five had variants in GPIHBP1 , one each in the LMF1, APOC2, and one with composite heterozygous variants in APOA5 and LPL. Twelve non-LPL variants were identified, five of which were novel variants in GPIHBP1 and two in LMF1. In silico predictions indicated that all novel variants might impact protein function. Elevated baseline triglyceride (TG) levels [22.9 (17.4-30.8) mmol/L, 2026.7 (1540.0-2728.5) mg/dL] were observed in all patients. Among the pediatric patients (7/7), chylomicronemia was the most common onset symptom. Acute pancreatitis was observed in only one patient with LMF1-FCS during pregnancy. The frequency of symptoms and lipid levels in the non-LPL-FCS group were slightly lower than those in the LPL-FCS group (P > 0.05). Dietary fat restriction reduced TG levels by 84.0% to 4.21 mmol/L (372.6 mg/dL, P < 0.01). Compared with other non-LPL-FCS patients, GPIHBP1-FCS patients experienced greater challenges in managing TG levels (P < 0.05). This study unveiled the genetic profile of the Chinese FCS cohort and enriched the mutation spectrum of non-LPL-FCS. The clinical characteristics and treatment outcomes of patients with non-LPL-FCS were delineated. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does fetal genetically determined birth weight associate with the timing of puberty? SUMMARY ANSWER Lower fetal genetically determined birth weight was causally associated with an earlier onset of puberty, independent of the indirect effects of the maternal intrauterine environment. WHAT IS KNOWN ALREADY Previous Mendelian randomization (MR) studies have indicated a potential causal link between birth weight, childhood BMI, and the onset of puberty. However, they did not distinguish between genetic variants that have a direct impact on birth weight through the fetal genome (referred to as fetal genetic effects) and those that influence birth weight indirectly by affecting the intrauterine environment (known as maternal genetic effects). It is crucial to emphasize that previous studies were limited because they did not account for the potential bias caused by unaddressed correlations between maternal and fetal genetic effects. Additionally, the proportion of birth weight variation explained by the fetal genome is considerably larger than that of the maternal genome. STUDY DESIGN, SIZE, DURATION We performed two-sample MR analyses to investigate the causal effect of fetal genetically determined birth weight on puberty timing using summary data from large-scale genome-wide association studies (GWASs) in individuals of European ancestry. PARTICIPANTS/MATERIALS, SETTING, METHODS From the two most recent GWASs specifically centered on birth weight, which included 406 063 individuals and 423 683 individuals (63 365 trios) respectively, we identified genetic variants associated with fetal genetically determined birth weight, while adjusting for maternal genetic effects. We identified genetic variants associated with childhood BMI from an independent GWAS involving 21 309 European participants. On this basis, we employed two-sample MR techniques to examine the possible causal effects of fetal genetically determined birth weight on puberty timing using a large-scale GWAS of puberty timing (including 179 117 females of European ancestry). Furthermore, we employed advanced analytical methods, specifically MR mediation and MR-Cluster, to enhance our comprehension of the causal relationship between birth weight determined by fetal genetics and the timing of puberty. We also explored the pathways through which childhood BMI might act as a mediator in this relationship. MAIN RESULTS AND THE ROLE OF CHANCE In the univariable MR analysis, a one SD decrease in fetal genetically determined birth weight (∼ 418 g) was associated with a 0.16 (95% CI [0.07–0.26]) years earlier onset of puberty. The multivariable MR analysis including fetal genetically determined birth weight and childhood BMI in relation to puberty timing provided compelling evidence that birth weight had a direct influence on the timing of puberty. Lower birth weight (one SD) was associated with an earlier onset of puberty, with a difference of 0.23 (95% CI [0.05–0.42]) years. We found little evidence to support a mediating role of childhood BMI between birth weight and puberty timing (−0.07 years, 95% CI [−0.20 to 0.06]). LIMITATIONS, REASONS FOR CAUTION Our data came from European ancestry populations, which may restrict the generalizability of our results to other populations. Moreover, our analysis could not investigate potential non-linear relationships between birth weight and puberty timing due to limitations in genetic summary data. WIDER IMPLICATIONS OF THE FINDINGS Findings from this study suggested that low birth weight, determined by the fetal genome, contributes to early puberty, and offered supporting evidence to enhance comprehension of the fetal origins of disease hypothesis. STUDY FUNDING/COMPETING INTEREST(S) C.Z. was funded by the Sichuan Province Science and Technology Program [grant number 2021JDR0189]. J.Z. was supported by grants from the National Natural Science Foundation of China [grant number 82373588]. No other authors declare any sources of funding. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]