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Truncating variants in titin (TTNtv) are the most prevalent genetic etiology of dilated cardiomyopathy (DCM). Although TTNtv has been associated with atrial fibrillation, it remains unknown whether and how left atrial (LA) function differs between patients with DCM with and without TTNtv. We aimed to determine and compare LA function in patients with DCM with and without TTNtv and to evaluate whether and how left ventricular (LV) function affects the LA using computational modeling. Patients with DCM from the Maastricht DCM registry that underwent genetic testing and cardiovascular magnetic resonance (CMR) were included in the current study. Subsequent computational modeling (CircAdapt model) was performed to identify potential LV and LA myocardial hemodynamic substrates. In total, 377 patients with DCM (n = 42 with TTNtv, n = 335 without a genetic variant) were included (median age 55 years, interquartile range [IQR] 46–62 years, 62% men). Patients with TTNtv had a larger LA volume and decreased LA strain compared with patients without a genetic variant (LA volume index 60 mLm−2 [IQR 49–83] vs 51 mLm−2 [IQR 42–64]; LA reservoir strain 24% [IQR 10–29] vs 28% [IQR 20–34]; LA booster strain 9% [IQR 4–14] vs 14% [IQR 10–17], respectively; all P <.01). Computational modeling suggests that while the observed LV dysfunction partially explains the observed LA dysfunction in the patients with TTNtv, both intrinsic LV and LA dysfunction are present in patients with and without a TTNtv. Patients with DCM with TTNtv have more severe LA dysfunction compared with patients without a genetic variant. Insights from computational modeling suggest that both intrinsic LV and LA dysfunction are present in patients with DCM with and without TTNtv. Higher LV and LA volumes on CMR are observed in patients with TTNtv with DCM compared with those without a TTNtv, accompanied by lower LA strain values. Simulating the observed LV values using computational modeling does not provide the observed LA values, indicating that intrinsic LA dysfunction contributes to the observed LA myopathy in addition to the well-known LV myopathy. CMR = cardiac magnetic resonance; LA = left atrial; LV = left ventricular; TTNtv = truncating variants in titin. [Display omitted] [ABSTRACT FROM AUTHOR]

This QI study compared the completeness of HRCT radiology reports before and after the implementation of a disease-specific structured reporting template for suspected cases of interstitial lung disease (ILD). A pre-post study of radiology reports for HRCT of the thorax at a multicenter health system was performed. Data was collected in 6-month period intervals before (June 2019–November 2019) and after (January 2021–June 2021) the implementation of a disease-specific template. The use of the template was voluntary. The primary outcome measure was the completeness of HRCT reports graded based on the documentation of ten descriptors. The secondary outcome measure assessed which descriptor(s) improved after the intervention. 521 HRCT reports before and 557 HRCT reports after the intervention were reviewed. Of the 557 reports, 118 reports (21%) were created using the structured reporting template. The mean completeness score of the pre-intervention group was 9.20 (SD = 1.08) and the post-intervention group was 9.36 (SD = 1.03) with a difference of −0.155, 95% CI [−0.2822, −0.0285, p < 0.0001]. Within the post-intervention group, the mean completeness score of the unstructured reports was 9.25 (SD = 1.07) and the template reports was 9.93 (SD = 0.25) with a difference of −0.677, 95% CI [−0.7871, −0.5671, p < 0.0001]. After the intervention, the use of two descriptors improved significantly: presence of honeycombing from 78.3% to 85.1% (p < 0.0039) and technique from 90% to 96.6% (p < 0.0001). Shifting to disease-specific structured reporting for HRCT exams of suspected ILD is beneficial, as it improves the completeness of radiology reports. Further research on how to improve the voluntary uptake of a disease-specific template is needed to help increase the acceptance of structured reporting among radiologists. • Disease-specific template can improve the completeness of HRCT radiology reports in evaluating interstitial lung disease. • Multiple factors contribute to radiologists' reluctance to adopting structured reporting. • More research on how to improve the voluntary uptake of a disease-specific template is needed. [ABSTRACT FROM AUTHOR]

The exomes of two unrelated cranioectodermal dysplasia (CED) patients were sequenced to identify compound heterozygous mutations in WDR35 as the cause of the disease in each of two patients independently. The results provided insight into the potential use of sequencing the exome of a single sporadic patient to find the causative gene and characterized WDR35 as homologous to TULP4 as an intraflagellar transport component, confirming that sensenbrenner syndrome is a ciliary disorder.

Several analyses are conducted to determine the different aspects of the human phenotype databases, which are shown to demonstrate the biology of different diseases. The results prove that the genetic disease analysis of humans can be easily enhanced by the curation and a more systematic annotation of these databases.

Research has been conducted on the low peak mass that presents significant risk factor for osteoporosis. The effect of the LRP5 encoding the low-density lipoprotein receptor-related protein 5 on the bone mass accrual during growth has been investigated and the results are reported.

Heterozygous germline mutations in the p53 homolog p63 are discussed and shown to be cause of EEC syndrome, which takes in ecrodactyly, ectrodermal dysplasia and cleft lip with/without cleft palate and may affect the hair, skin, nails and teeth. The region was implicated in the EEC-like disorder limb mammary syndrome (LMS). Analysis of the p63 gene showed heterozygous mutations in nine unrelated EEC families. A molecular explanation for the dominant nature of p63 mutations in EEC syndrome is seen.

Medium manganese (Mn) steel has excellent strength and ductility and is widely used in the automobile industry and elsewhere; however, hydrogen embrittlement (HE) is considered as one of the most serious issues of its application. In this paper, in situ transmission electron microscopy was used to study the microstructural evolution and fracture micromechanisms of medium Mn steel under the influence of hydrogen and annealing. The results indicated that two specimens with different annealing processes showed transformation-induced plasticity and twinning-induced plasticity, albeit to a varying degree due to different microstructures with distinct mechanical properties. It was shown that hydrogen affected the fracture micromechanisms, which promoted the initiation of microcracks at the boundaries of martensite transformed from austenite. Moreover, the main cracks propagate in a zigzag fashion, following hydrogen charging, due to the hardness of the martensite. These findings provide directions for improving HE resistance through microstructural regulation of medium Mn steel. • In situ TEM tensile tests verify fracture mechanism of medium Mn steel. • Hydrogen promotes crack initiation at specific interface, e.g. martensite boundary. • Annealing greatly alters deformation mode, work hardening rate and the L u ¨ ders band. • The detailed fracture process of pre-hydrogen charged steel is in situ tracked. [ABSTRACT FROM AUTHOR]

Background: Metabolomic profiling may have diagnostic and prognostic value in heart failure. This study investigated whether targeted blood and urine metabolomics reflects disease severity in patients with nonischemic dilated cardiomyopathy (DCM) and compared its incremental value on top of N-terminal prohormone of brain natriuretic peptide (NT-proBNP).Methods and Results: A total of 149 metabolites were measured in plasma and urine samples of 273 patients with DCM and with varying stages of disease (patients with DCM and normal left ventricular reverse remodeling, n = 70; asymptomatic DCM, n = 72; and symptomatic DCM, n = 131). Acylcarnitines, sialic acid and glutamic acid are the most distinctive metabolites associated with disease severity, as repeatedly revealed by unibiomarker linear regression, sparse partial least squares discriminant analysis, random forest, and conditional random forest analyses. However, the absolute difference in the metabolic profile among groups was marginal. A decision-tree model based on the top metabolites did not surpass NT-proBNP in classifying stages. However, a combination of NT-proBNP and the top metabolites improved the decision tree to distinguish patients with DCM and left ventricular reverse remodeling from symptomatic DCM (area under the curve 0.813 ± 0.138 vs 0.739 ± 0.114; P = 0.02).Conclusion: Functional cardiac recovery is reflected in metabolomics. These alterations reveal potential alternative treatment targets in advanced symptomatic DCM. The metabolic profile can complement NT-proBNP in determining disease severity in nonischemic DCM. [ABSTRACT FROM AUTHOR]

This study sought to investigate the prevalence of systolic dysfunction using global longitudinal strain (GLS) and its prognostic value in relatives of dilated cardiomyopathy (DCM) patients that had normal left ventricular ejection fraction (LVEF). DCM relatives are advised to undergo cardiac assessment including echocardiography, irrespective of the genetic status of the index patient. Even though LVEF is normal, the question remains whether this indicates absence of disease or simply normal cardiac volumes. GLS may provide additional information regarding (sub)clinical cardiac abnormalities and thus allow earlier disease detection. A total of 251 DCM relatives and 251 control subjects with a normal LVEF (≥55%) were screened. Automated software measured the GLS on echocardiographic 2-, 3-, and 4-chamber views. The cutoff value for abnormal strain was >−21.5. Median follow-up was 40 months (interquartile range: 5 to 80 months). Primary outcome was the combination of death and cardiac hospitalization. A total of 120 relatives and 83 control subjects showed abnormal GLS (48% vs. 33%, respectively; p < 0.001). Abnormal GLS was independently associated with DCM relatives and cardiovascular risk factors, rather than genetic mutations. Subjects with abnormal GLS had more frequent cardiac hospitalizations and a higher mortality as compared with subjects with normal GLS (hazard ratio: 3.29; 95% confidence interval: 1.58 to 6.87; p = 0.001). Additionally, follow-up LVEF was measured in a subset of relatives, and it decreased significantly in those with abnormal as compared with normal GLS (p = 0.006). Relatives of DCM patients had a significantly higher prevalence of systolic dysfunction detected by GLS despite normal LVEF compared with control subjects, independent of age, sex, comorbidities, and genotype. Abnormal GLS was associated with LVEF deterioration, cardiac hospitalization, and death. [ABSTRACT FROM AUTHOR]

The impact of intercritical annealing (IA) temperature and time on retained austenite and mechanical properties are elucidated in a low carbon steel containing 2.85 wt% Mn. Experimental studies indicated that the multi-phase microstructure consisted of intercritical ferrite, martensite/bainite, retained austenite and fine dispersion of precipitations. The volume fraction of retained austenite attained a maximum value of 14% on IA at 680 °C for 30 min. The partition behavior of alloying elements during intercritical annealing was studied by scanning transmission electron microscopy (STEM) and analyzed kinetically by DICTRA simulation. Appropriate fraction of retained austenite obtained at 680 °C for 30 min was attributed to the extent of partitioning of carbon and manganese into the reverted austenite that contributed to best balance of mechanical properties. • ~13% volume fraction of retained austenite was obtained in a low carbon steel. • Microstructural development during annealing was characterized. • Stabilization of retained austenite was studied by characterization and simulations. • 700 MPa yield strength with high ductility and low Y/T ratio was obtained. [ABSTRACT FROM AUTHOR]

Recently, we found that in ovo feeding of L-leucine (L-Leu) stimulated the metabolism of lipids and afforded thermotolerance in male Chunky broiler chicks. In this study, we investigated the effects of feeding L-Leu in ovo on the metabolism of amino acids and on the cellular stress response mainly in the central and peripheral tissues in neonatal male broiler chicks and partly in embryonic tissues. Chicks (9 d old) were exposed to high ambient temperature (HT : 35 ± 1°C) or control thermoneutral temperature (CT : 28 ± 1°C) for 180 min. The ambient temperatures were based on our recent reports and the recommendation of the Chunky broiler manual in which 28°C has been suggested as a normal ambient temperature for 5 to 9-d-old broiler chicks. In ovo feeding of L-Leu caused a significant (P < 0.05) decline in diencephalic arginine concentrations but it increased the diencephalic and plasma lysine concentrations when compared with the control chicks under HT. Notably, in ovo feeding of L-Leu significantly (P < 0.05) attenuated the increment of hepatic arginine compared with the control chicks under HT. Interestingly, in ovo feeding of L-Leu significantly (P < 0.05) attenuated the diencephalic gene expression of heat-shock protein (HSP) −70 and −90 in heat-exposed chicks. The gene expressions of mammalian target of rapamycin (mTOR) and its downstream genes (ribosomal protein S6 kinase (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1)) in the central and peripheral tissues were not influenced in the chicks under heat stress. We found that the gene expressions of mTOR, S6K1, and 4E-BP1 were significantly (P < 0.05) stimulated only in the embryonic breast muscle, and not in the other embryonic tissues, by in ovo feeding of L-Leu. In conclusion, in ovo feeding of L-Leu caused a change in the metabolism of amino acids in response to heat stress in broiler chicks. Attenuated gene expressions of HSP-70 and −90 under heat stress further suggests that in ovo feeding of L-Leu may afford thermotolerance in broilers. [ABSTRACT FROM AUTHOR]

A significant volume fraction of 26% retained austenite was obtained via a two-step intercritical treatment in a low carbon low alloy steel with ultra-high tensile strength of ~1200 MPa, ultra-low yield ratio of 0.32, excellent uniform elongation of ~16.4% and total elongation of ~23%. The ultra-low yield ratio and excellent uniform elongation implied high work hardening and excellent formability. The high work hardening and ultra-high tensile strength are attributed to deformation-induced twin-martensite. [ABSTRACT FROM AUTHOR]

Intercritical tempering at 680 °C for different times was carried out in a low carbon copper-bearing steel to study the evolution of the crystal structure of Cu precipitates by high resolution transmission electron microscopy. With increased tempering time, four different types of crystal structure of copper precipitates with different sizes were observed, namely, (a) nano-ordered clusters comprised of B2 FeCu nano-ordered clusters (2–3 nm) and weak ordered BCC Cu nanoclusters (2–3 nm), (b) 9R Cu (5–12 nm) - multiple twinned structure consisted of two, six or seven 9R twins with an orientation relationship of (1 1–4) 9R ∥(0 1 1) α , [− 1 1 0] 9R ∥[1 − 1 1] α , (c) detwinned 9R Cu (24–26 nm) consisted of two 9R parts and a removable interface (1 1–4) 9R , and (d) FCC Cu (~ 37 nm) precipitates consisted of two parts of FCC Cu and a micro-twinned region. The evolution sequence of crystal structure of Cu precipitates was: nano-ordered clusters → 9R Cu → detwinned 9R Cu → FCC Cu. The maximum contribution to precipitation hardening is attributed to nano-ordered clusters. [ABSTRACT FROM AUTHOR]