Cryptic exon activation caused by a novel deep-intronic splice-altering variant in Becker muscular dystrophy.

BACKGROUND: An accurate genetic diagnosis of Becker muscular dystrophy (BMD) can be sometimes challenging due to deep intronic DMD variants. Here, we report on the genetic diagnosis of a BMD patient with a novel deep-intronic splice-altering variant in DMD. METHODS: The index case was a 3.8-year-old boy who was suspected of having a diagnosis of BMD based on his clinical, muscle imaging, and pathological features. Routine genomic detection approaches did not detect any disease-causing variants in him. Muscle-derived DMD mRNA studies, followed by genomic Sanger sequencing and in silico bioinformatic analyses, were performed in the patient. RESULTS: DMD mRNA studies detected a cryptic exon-containing transcript and normally spliced DMD transcript in the patient. The cryptic exon-containing transcript encoded a frameshift and premature termination codon (NP_003997.1:p.[=,Asp2740Valfs*52]). Further genomic Sanger sequencing and bioinformatic analysis identified a novel deep-intronic splice-altering variant in DMD (c.8217 + 23338A > G). The novel variant strengthened a cryptic donor splice site and activated a cryptic acceptor splice site in the deep-intronic region of DMD intron 55, resulting in the activation of a new dystrophin cryptic exon found in the patient. CONCLUSION: Our case report expands the genetic spectrum of BMD and highlights the essential role of deep-intronic cryptic exon-activating variants in genetically unsolved BMD patients.

Different antioxidant regulation mechanisms in response to aluminum-induced oxidative stress in Eucalyptus species.

Forest ecosystems play an important role in environmental protection and maintaining ecological balance. Understanding the physiological mechanisms of tree species response to aluminum (Al) toxic is crucial to reveal the main causes of plantation decline in acid rain area. As an important afforestation tree species in tropical and subtropical areas, Eucalyptus has high economic value and plays crucial ecological roles. However, continuous fertilization and acid precipitation can exacerbate soil acidification and increase soil active Al, which has a significant negative impact on Eucalyptus growth. Hence, species and genotypes with high Al resistance are required to solve the problem of Al toxicity of acidic soils for sustainable forest production. In this study, E. urophylla was better adapted to Al stress than E. grandis or E. tereticornis; its high Al resistance was attributed to greater antioxidant enzyme activity and non-enzymatic antioxidant content, and a lower degree of membrane lipid peroxidation than E. grandis or E. tereticornis. The differences in adaptability among the three pure species were attributed to their distinct habitats. Eucalyptus urophylla × E. grandis inherited the outstanding adaptability to Al stress from its maternal species (E. urophylla), indicating that Al tolerance is highly heritable and can be selected in Eucalyptus breeding. Our results indicated that the response of Eucalyptus to Al stress may fluctuate according to the time under stress, and might be related to dynamic changes in ROS elimination and accumulation.

Structure and reactivity of a water-covered anatase TiO2(001) surface.

We systematically studied water adsorption and oxidation on the unreconstructed TiO2(001) surface using first-principles calculations. Water first adsorbs on the surface in a dissociative state and then in a molecular state, as water coverage increases. The geometric properties of all adsorption structures suggest that the dissociative water molecules can induce stress release of the (001) surface at low coverage, reducing reactivity of the surface and thus leading to molecular adsorption of water on the surface at high coverage. The adsorption energy (or the surface energy) monotonously increases (or decreases) with the increase of the coverage, which further confirms that water, irrespective of its dissociative or molecular state, can improve the stability of the (001) surface and reduce its activity. We deeply investigated the mechanism of the oxygen evolution reaction (OER) on the water-covered (001) surface. A new water-assisted OER pathway is identified on the (001) surface, which includes the sequential transfer of protons from molecular water and surface hydroxyls, and O-O coupling processes. During the OER pathway, the O-O coupling step exhibits the largest thermodynamic energy and highest energy barrier, clarifying that it is the rate-determining step in the whole pathway. Our findings provide new insights into the strong dependence of water adsorption modes on coverage for the anatase TiO2(001) surface and may explain the high oxidation activity of the TiO2(001) surface in aqueous environments typical of TiO2 photocatalysis.

Clinical study of chlamydia pneumoniae infection in patients with coronary heart disease.

BACKGROUND: This study aims to investigate the chlamydia pneumoniae infection (PC) in patients with coronary heart disease. METHODS: A total of 92 patients with coronary heart disease, who were treated with percutaneous coronary intervention (PCI), were selected as the case group. In addition, 50 healthy people were enrolled as the control group. The incidences of CP infection and serum Chlamydia pneumoniae IgA antibody (CP-IgA), high sensitive C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were compared in these two groups. The classification of coronary artery lesion, the incidence of perioperative cardiovascular events, and adverse prognosis events within six months after procedure were compared. RESULTS: The incidence of CP infection in the case group was higher (42.4% vs. 0%, P < 0.05). Furthermore, 17 patients were at grade I, 39 patients were at grade II, and 36 patients were at grade III. The incidences for these three kinds of patients were 17.6, 30.8, and 66.7%. The incidence of CP infection at grade III was higher than that of grade I or II (P < 0.05). Serum CP-IgA, hs-CRP and IL-6 levels increased with the severity of the coronary artery disease (P < 0.05), and the serum hs-CRP and IL-6 levels of patients with perioperative cardiovascular events were higher (P < 0.05). Moreover, the serum CP-IgA levels of the patients with adverse prognosis events were also higher (P < 0.05). CONCLUSIONS: Patients with coronary heart disease have a high CP infection rate. The degree of infection is relevant to the severity of the coronary artery lesions and postoperative prognosis of patients, suggesting that CP infection may be an important factor affecting the incidence and prognosis of coronary heart disease.

Hyperoxia-mediated transcriptional activation of cytochrome P4501A1 (CYP1A1) and decreased susceptibility to oxygen-mediated lung injury in newborn mice.

Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. In this study, we tested the hypothesis that newborn transgenic mice carrying the human CYP1A1-Luc promoter will display transcriptional activation of the human CYP1A1 promoter in vivo upon exposure to hyperoxia, and that these mice will be less susceptible to hyperoxic lung injury and alveolar simplification than similarly exposed wild type (WT) mice. Newborn WT (CD-1) or transgenic mice carrying a 13.2 kb human CYP1A1 promoter and the luciferase (Luc) reporter gene (CYP1A1-luc) were maintained in room air or exposed to hyperoxia (85% O2) for 7-14 days. Hyperoxia exposure of CYP1A1-Luc mice for 7 and 14 days resulted in 4- and 30-fold increases, respectively, in hepatic Luc (CYP1A1) expression, compared to room air controls. In lung, hyperoxia caused a 2-fold induction of reporter Luc at 7 days, but the induction declined after 14 days. The newborn CYP1A1-Luc mice were less susceptible to lung injury and alveolar simplification than similarly exposed wild type (WT) CD-1 mice. Also, the CYP1A1-Luc mice showed increased levels of hepatic and pulmonary CYP1A1 expression and hepatic CYP1A2 activity after hyperoxia exposure. Hyperoxia also increased NADP(H) quinone reductase (NQO1) pulmonary gene expression in both CD-1 and CYP1A1-Luc mice at both time points, but this was more pronounced in the latter at 14 days. Our results support the hypothesis that hyperoxia activates the human CYP1A1 promoter in newborn mice, and that increased endogenous expression of CYP1A1 and NADP(H) quinone reductase (NQO1) contributes to the decreased susceptibilities to hyperoxic lung injury in the transgenic animals. This is the first report providing evidence of hyperoxia-mediated transcriptional activation of the human CYP1A1 promoter in newborn mice, and this in conjunction with decreased lung injury, suggests that these phenomena have important implications for BPD.

ß-Naphthoflavone treatment attenuates neonatal hyperoxic lung injury in wild type and Cyp1a2-knockout mice.

Exposure to supraphysiological concentrations of oxygen (hyperoxia) leads to bronchopulmonary dysplasia (BPD), one of the most common pulmonary morbidities in preterm neonates, which is more prevalent in males than females. Beta-naphthoflavone (BNF) is protective against hyperoxic lung injury in adult and neonatal wild type (WT) mice and in and mice lacking Cyp1a1gene. In this investigation, we tested the hypothesis that BNF treatment will attenuate neonatal hyperoxic lung injury in WT and Cyp1a2-/- mice, and elucidated the effect of sex-specific differences. Newborn WT or Cyp1a2-/- mice were treated with BNF (10mg/kg) or the vehicle corn oil (CO) i.p., from postnatal day (PND) 2 to 8 once every other day, while being maintained in room air or hyperoxia (85% O2) for 14days. Hyperoxia exposure lead to alveolar simplification and arrest in angiogenesis in WT as well as Cyp1a2-/- mice No significant differences were seen between WT and Cyp1a2-/- mice. Cyp1a2-/- female mice had better preservation of pulmonary angiogenesis at PND15 compared to similarly exposed males. BNF treatment attenuated lung injury and inflammation in both genotypes, and this was accompanied by a significant induction of hepatic and pulmonary CYP1A1 in WT but not in Cyp1a2-/- mice. BNF treatment increased NADPH quinone oxidoreductase (NQO1) mRNA levels in Cyp1a2-/- mouse livers compared to WT mice. These results suggest that BNF is protective in neonatal mice exposed to hyperoxia independent of CYP1A2 and this may entail the protective effect of phase II enzymes like NQO1.

Novel Knob-integrated fiber Bragg grating sensor with polyvinyl alcohol coating for simultaneous relative humidity and temperature measurement.

A novel high performance optical fiber sensor for simultaneous measurement of relative humidity (RH) and temperature based on our newly designed knob-integrated fiber Bragg grating (FBG) is proposed and experimentally demonstrated. The knob-shaped taper followed by an FBG works as a multifunctional joint that not only excites the cladding modes but also recouples the cladding modes reflected by the FBG back into the leading single mode fiber. Polyvinyl alcohol (PVA) film is plated on the fiber surface by dip-coating technique as a humidity-to-refractive index (RI) transducer, and affects the intensity of reflected cladding modes by way of evanescent fields. By monitoring the intensity and wavelength of the reflected cladding modes, the RH and temperature variance can be determined simultaneously. Experimental results show an RH sensitivity of up to 1.2 dB/%RH within an RH range of 30-95%, which is significantly better than previously reported values. And the temperature sensitivity of 8.2 pm/°Ccould be achieved in the temperature range of 25-60°C. A fast and reversible time response has also been demonstrated, enabling to pick up a humidity change as fast as 630 ms. The capability of simultaneous measurement of RH and temperature, the fast response, the reusability and the simple fabrication process make this structure a highly promising sensor for real-time practical RH monitoring applications.

Chain or ring: which one is favorable in nitrogen-rich molecules N6XHm, N8XHm, and N10XHm (X = B, Al, Ga, m = 1 and X = C, Si, Ge, m = 2)?

A series of nitrogen-rich molecules N6XHm, N8XHm, and N10XHm (X = B, Al, Ga, m = 1 and X = C, Si, Ge, m = 2) consisting of N3 and N5 radicals, are systematically investigated by using B3LYP and B3PW91 DFT methods. It is found that for the nitrogen-rich molecules, the structures with N3-chains (N5-ring) are more stable than those containing a N3-ring (N5-chain). This result could be well-explained by the intrinsic stability of the N3 and N5 radicals and their charge distribution in nitrogen-rich molecules. The dissociation energies further indicate that the B-doped and C-doped structures are the most stable among the molecules with three elements of group 13 and 14, respectively. Energy decomposition analysis shows the bond of boron-nitrogen is stronger than that of carbon-nitrogen. Detailed bonding analysis demonstrates that the B-N bond is determined by σ and π interactions between the B and N atoms, whereas C-N bonds by only σ interactions. These results imply that the boron atom is more suitable than the carbon atom for building the nitrogen-rich molecules studied in this article.

An efficient grasping shared control architecture for unpredictable and unspecified tasks.

Robot control in complex and unpredictable scenarios presents challenges such as adaptability, robustness, and human-robot interaction. These scenarios often require robots to perform tasks that involve unknown objects in unstructured environments with high levels of uncertainty. Traditional control methods, such as automatic control, may not be suitable due to their limited adaptability and reliance on prior knowledge. Human-in-the-loop method faces issues such as insufficient feedback, increased failure rates due to noise and delays, and lack of operator immersion, preventing the achievement of human-level performance. This study proposed a shared control framework to achieve a trade-off between efficiency and adaptability by combing the advantages of both teleoperation and automatic control method. The proposed approach combines the advantages of both human and automatic control methods to achieve a balance between performance and adaptability. We developed a linear model to compare three control methods and analyzed the impact of position noise and communication delays on performance. The real-world implementation of the shared control system demonstrates its effectiveness in object grasping and manipulation tasks. The results suggest that shared control can significantly improve grasping efficiency while maintaining adaptability in task execution for practical robotics applications.

Modeling three-dimensional bait ball collective motion.

Collective motion of animal groups such as fish schools and bird flocks in three-dimensional (3D) space are modeled by considering a topological (Voronoi) neighborhood. The tridimensionality of the group is quantified. Apart from the patterns of swarming, schooling, and milling, we identify a 3D bait ball around the phase transition boundary. More significantly, we find that by considering a blind angle in this topology based model, an individual interacts statistically with six to seven neighbors, consistent precisely with the previous field observations of the starling flocks. This model could be expected to enable more insightful investigation on realistic collective motion of shoals or flocks.

Utilization of an individualized nursing plan based on the comprehensive geriatric assessment to improve quality of life in older patients with osteoporosis.

PURPOSE: This study aimed to observe the effect of individualized nursing based on a comprehensive geriatric assessment (CGA) on improving the quality of life of elderly osteoporosis patients. METHODS: Ninety-two elderly osteoporosis patients were divided into two groups using the random number table method, with 46 patients in each group. The control group received routine nursing, while the observation group was the recipients of personalized care intervention based on a CGA. The abbreviated generic Quality of Life Scale developed through the World Health Organization and an inpatient nursing satisfaction scale were used to evaluate the quality of life and patient satisfaction scores of the two groups before and 6 months after the nursing intervention. RESULTS: There were no significant differences in the WHOQOL-BREF scores between the two groups before intervention (p > 0.05). After 6 months of intervention, the index of each domain was significantly higher than that before the intervention (p < 0.05), and the index of each domain in the observation group was significantly higher than that in the control group after 6 months of intervention (p < 0.05). There was no significant difference in patient satisfaction scores between the two groups before the intervention (p > 0.05). However, after 6 months of intervention, the patient satisfaction scores in the observation group were significantly higher than those in the control group after 6 months of intervention (p < 0.05). CONCLUSION: Individualized nursing intervention based on a CGA can effectively improve the quality of life of elderly osteoporosis patients and improve patient satisfaction.

Bacterial diversity in surface sediments of collapsed lakes in Huaibei, China.

The collapse lake area due to coal mining in Huaibei shows high biodiversity, but the bacterial community composition and diversity in the lake sediments are still rarely studied. Therefore, based on 16S rRNA high-throughput sequencing and combined with analysis of environmental factors, we comparatively analyzed the bacterial community composition and diversity of surface sediments from East Lake (DH) and South Lake (NH) and Middle Lake (ZH) in the collapse lake area of Huaibei. The bacterial community compositions are significantly different in the sediments among Huaibei collapsed lakes, with DH having the largest number of species, and NH having a higher species diversity. Pseudomonadota is the most abundant phylum in the sediments of DH and NH, while the most abundant phyla in ZH are Bacteroidales, Chloroflexales, Acidobacteriales, and Firmicutes. Anaerolineae (24.05% ± 0.20%) is the most abundant class in the DH sediments, and Gammaproteobacteria (25.94% ± 0.40%) dominates the NH sediments, Bacteroidia (32.12% ± 1.32%) and Clostridia (21.98% ± 0.90%) contribute more than 50% to the bacteria in the sediments of ZH. Redundancy analysis (RDA) shows that pH, TN, and TP are the main environmental factors affecting the bacterial community composition in the sediments of the collapsed lake area. The results reveal the bacterial community composition and biodiversity in the sediments of the Huaibei coal mining collapsed lakes, and provide new insights for the subsequent ecological conservation and restoration of the coal mining collapsed lakes.

Prenatal administration of the cytochrome P4501A inducer, Β-naphthoflavone (BNF), attenuates hyperoxic lung injury in newborn mice: implications for bronchopulmonary dysplasia (BPD) in premature infants.

Supplemental oxygen contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. In this investigation, we tested the hypothesis that prenatal treatment of pregnant mice (C57BL/6J) with the cytochrome P450 (CYP)1A1 inducer, ß-napthoflavone (BNF), will lead to attenuation of lung injury in newborns (delivered from these dams) exposed to hyperoxia by mechanisms entailing transplacental induction of hepatic and pulmonary CYP1A enzymes. Pregnant mice were administered the vehicle corn oil (CO) or BNF (40 mg/kg), i.p., once daily for 3 days on gestational days (17-19), and newborns delivered from the mothers were either maintained in room air or exposed to hyperoxia (>95% O(2)) for 1-5 days. After 3-5 days of hyperoxia, the lungs of CO-treated mice showed neutrophil infiltration, pulmonary edema, and perivascular inflammation. On the other hand, BNF-pretreated neonatal mice showed decreased susceptibility to hyperoxic lung injury. These mice displayed marked induction of ethoxyresorufin O-deethylase (EROD) (CYP1A1) and methoxyresorufin O-demethylase (MROD) (CYP1A2) activities, and levels of the corresponding apoproteins and mRNA levels until PND 3 in liver, while CYP1A1 expression alone was augmented in the lung. Prenatal BNF did not significantly alter gene expression of pulmonary NAD(P)H quinone reductase (NQO1). Hyperoxia for 24-72 h resulted in increased pulmonary levels of the F(2)-isoprostane 8-iso-PGF(2α), whose levels were decreased in mice prenatally exposed to BNF. In conclusion, our results suggest that prenatal BNF protects newborns against hyperoxic lung injury, presumably by detoxification of lipid hydroperoxides by CYP1A enzymes, a phenomenon that has implications for prevention of BPD in infants.

Bio-Inspired Isoalloxazine Redox Moieties for Rechargeable Aqueous Zinc-Ion Batteries.

Organic electrode materials hold great potential for fabricating sustainable energy storage systems, however, the development of organic redox-active moieties for rechargeable aqueous zinc-ion batteries is still at an early stage. Here, we report a bio-inspired riboflavin-based aqueous zinc-ion battery utilizing an isoalloxazine ring as the redox center for the first time. This battery exhibits a high capacity of 145.5 mAh g-1 at 0.01 A g-1 and a long-life stability of 3000 cycles at 5 A g-1 . We demonstrate that isoalloxazine moieties are active centers for reversible zinc-ion storage by using optical and photoelectron spectroscopies as well as theoretical calculations. Through molecule-structure tailoring of riboflavin, the obtained alloxazine and lumazine molecules exhibit much higher theoretical capacities of 250.3 and 326.6 mAh g-1 , respectively. Our work offers an effective redox-active moiety for aqueous zinc batteries and will enrich the valuable material pool for electrode design.

Effects of whey protein nutritional supplement on muscle function among community-dwelling frail older people: A multicenter study in China.

BACKGROUND: Frailty, featured by the presence of fatigue, weight loss, decrease in grip strength, decline gait speed and reduced activities substantially increase the risk of falls, disability, hospitalizations, and mortality of older people. Nutritional supplementation and resistance exercise may improve muscle function and reverse frailty status. OBJECTIVE: To evaluate whether whey protein supplements can improve muscle function of frail older people in addition to resistance exercise. METHODS: 115 community-dwelling older adults who met the Fried's criteria for frailty from four hospitals' out-patients clinic in Beijing, China completed the study. It's a case-control study which whey protein was used as daily supplementation for 12 weeks for active group and regular resistance exercise for active group and control group. Handgrip strength, gait speed, chair-stand test, balance score, and SPPB score were compared in both groups during the 12-week follow-up. RESULTS: Overall, 115 subjects were enrolled for study with 66 in active group and 49 in control group. Handgrip strength, gait speed, and chair-stand time were all significantly improved in both groups with significant between-group differences. The active group improved significantly in handgrip strength compared with the control group, which between-group effect (95% confidence interval) for female was 0.107 kg (0.066-0.149), p = 0.008 and for male was 0.89 kg (0.579-1.201), p = 0.007. For chair-stand time, between-group effect (95% confidence interval) was -2.875 s (-3.62 to -2.124), p = 0.004 and for gait speed, between-group effect (95% confidence interval) was 0.109 m/s (0.090 to 0.130), p = 0.003. CONCLUSIONS: The 12-week intervention of whey protein oral nutritional supplement revealed significant improvements in muscle function among the frailty elderly besides aiding with resistance exercise. These results warrant further investigations into the role of a multi-modal supplementation approach which could prevent adverse outcomes among frailty elderly at risk for various disabilities.

Self-Assembled Biomolecular 1D Nanostructures for Aqueous Sodium-Ion Battery.

Aqueous sodium-ion battery of low cost, inherent safety, and environmental benignity holds substantial promise for new-generation energy storage applications. However, the narrow potential window of water and the enlarged ionic radius because of hydration restrict the selection of electrode materials used in the aqueous electrolyte. Here, inspired by the efficient redox reaction of biomolecules during cellular energy metabolism, a proof of concept is proposed that the redox-active biomolecule alizarin can act as a novel electrode material for the aqueous sodium-ion battery. It is demonstrated that the specific capacity of the self-assembled alizarin nanowires can reach as high as 233.1 mA h g-1, surpassing the majority of anodes ever utilized in the aqueous sodium-ion batteries. Paired with biocompatible and biodegradable polypyrrole, this full battery system shows excellent sodium storage ability and flexibility, indicating its potential applications in wearable electronics and biointegrated devices. It is also shown that the electrochemical properties of electrodes can be tailored by manipulating naturally occurring 9,10-anthroquinones with various substituent groups, which broadens application prospect of biomolecules in aqueous sodium-ion batteries.

Quercetin attenuates the hyperoxic lung injury in neonatal mice: Implications for Bronchopulmonary dysplasia (BPD).

Quercetin (QU) is one of the most common flavonoids that are present in a wide variety of fruits, vegetables, and beverages. This compound possesses potent anti-inflammatory and anti-oxidant properties. Supplemental oxygen is routinely administered to premature infants with pulmonary insufficiency. However, hyperoxia is one of the major risk factors for the development of bronchopulmonary dysplasia (BPD), which is also termed chronic lung disease in premature infants. Currently, no preventive approaches have been reported against BPD. The treatment of BPD is notably limited to oxygen administration, ventilatory support, and steroids. Since QU has been shown to be effective in reducing inflammation and oxidative stress in various disease models, we hypothesized that the postnatal QU treatment of newborn mice will protect against hyperoxic lung injury by the upregulation of the phase I (CYP1A/B) and/or phase II, NADPH quinone reductase enzymes. Newborn C57BL/6J mice within 24 h of birth with the nursing dams were exposed to either 21% O2 (air) and/or 85% O2 (hyperoxia) for 7 days. The mice were treated, intraperitoneally (i.p.) once every other day with quercetin, at a concentration of 20 mg/kg, or saline alone from postnatal day (PND) 2-6. The mice were sacrificed on day 7, and lung and liver tissues were collected. The expression levels of CYP1A1, CYP1B1, NQO1 proteins and mRNA as well as the levels of MDA-protein adducts were analyzed in lung and liver tissues. The findings indicated that QU attenuated hyperoxia-mediated lung injury by reducing inflammation and improving alveolarization with decreased number of neutrophil and macrophage infiltration. The attenuation of this lung injury correlated with the upregulation of CYP1A1/CYP1B1/NQO1 mRNA, proteins and the down regulation of NF-kB levels and MDA-protein adducts in lung and liver tissues. The present study demonstrated the potential therapeutic value of quercetin in the prevention and/or treatment of BPD.

A severity index study of long-term prognosis in patients with chronic heart failure.

AIMS: The present study describes the derivation and validation of the Chronic Heart Failure Severity Index (CHFSI). MAIN METHODS: The CHFSI was derived using data obtained from a single-center prospective cohort study (2000-2014) that enrolled 756 patients. Logistic regression was used to identify independent predictors of mortality and quality of life over a 15-year follow-up period. KEY FINDINGS: The score was validated at the first 5-year (n = 644), second 5-year (n = 364), and third 5-year (n = 262). Independent predictors of mortality were older age (OR = 2.04, P < 0.001), etiology score (OR = 2.61, P < 0.001), faster heart rate (OR = 1.46, P = 0.027), higher systolic blood pressure (OR = 2.35, P < 0.001), and left ventricular ejection fraction ≤45% (OR = 1.97, P = 0.018). The derived CHFSI predicted the mortality, and the AUC for the logistic model was 0.78 (95% confidence interval = 0.74-0.81, P < 0.001). Based on the logistic model, an integer scoring system was derived. Patients were classified into three groups: low risk (0-7 points), intermediate risk (8-11 points) and high risk (≥12 points) groups. The cumulative mortality for 15 years was 45.5% (125/275), 84.0% (204/243), and 100% (99/99), respectively (P < 0.001). The 6-min walk test revealed a significant difference in quality of life among patients in the low, medium and high risk groups (all, P < 0.0001). SIGNIFICANCE: The CHFSI is a very useful clinical predictive tool that identifies patients at risk of future mortality and their quality of life across healthcare systems.

Whole exome sequencing identifies a KCNJ12 mutation as a cause of familial dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation, and is associated with systolic dysfunction and increased action potential duration. Approximately 50% of DCM cases are caused by inherited gene mutations with genetic and phenotypic heterogeneity. Next generation sequencing may be useful in screening unknown mutations in such cases.A family was identified with DCM, in which the affected family members developed heart failure, arrhythmia, and sudden death. Probands and 4 affected family members underwent whole exome sequencing (WES), bioinformatics methods, and gene annotation to identify potentially causative variants. The Sanger sequencing method was used to verify the candidate mutation.WES yielded 2,238,831 variations. KCNJ12 (p.Glu334del) was identified as a candidate mutation, and the heterozygous mutation was verified by Sanger sequencing.Our study emphasizes the application of WES in identifying causative mutations in DCM. This report is the first to describe the KCNJ12 gene as a cause of DCM in patients.