Optimized Cytogenetic Risk-Group Stratification of KMT2A-Rearranged Pediatric Acute Myeloid Leukemia.

Comprehensive international consensus on cytogenetic risk-group stratification of KMT2A-rearranged (KMT2A-r) pediatric acute myeloid leukemia (AML) is lacking. This retrospective (2005-2016) International Berlin-Frankfurt-Münster Study Group study on 1,256 children with KMT2A-r AML aimed to validate the prognostic value of established recurring KMT2A fusions and additional cytogenetic aberrations (ACAs), and secondly, to define additional, recurring KMT2A fusions and ACAs, evaluating their prognostic relevance. Compared to our previous study, three additional, recurring KMT2A-r groups were defined: Xq24/KMT2A::SEPT6, 1p32/KMT2A::EPS15, 17q12/t(11;17)(q23;q12). Across 13 KMT2A-r groups, 5-year event-free survival probabilities varied significantly (21.8% to 76.2%; P<0.01). ACAs occurred in 46.8% of 1,200 patients with complete karyotypes, correlating with inferior overall survival (56.8% vs 67.9%; P<0.01). Multivariable analyses confirmed independent associations of 4q21/KMT2A::AFF1, 6q27/KMT2A::AFDN, 10p12/KMT2A::MLLT10, 10p11.2/KMT2A::ABI1, and 19p13.3/KMT2A::MLLT1 with adverse outcomes, but not those of 1q21/KMT2A::MLLT11 and trisomy 19 with favorable and adverse outcomes, respectively. Newly identified ACAs with independent adverse prognoses were monosomy 10, trisomies 1, 6, 16, and X, add(12p), and del(9q). Among patients with 9p22/KMT2A::MLLT3, the independent association of French-American-British-type M5 with favorable outcome was confirmed, and those of trisomy 6 and measurable residual disease at end of induction with adverse outcomes were identified. We provide evidence to incorporate the five adverse-risk KMT2A fusions into the cytogenetic risk-group stratification of KMT2A-r pediatric AML, to revise the favorable-risk classification of 1q21/KMT2A::MLLT11 to intermediate risk, and to refine risk-stratification of 9p22/KMT2A::MLLT3 AML. Future studies should validate the associations between the newly identified ACAs and outcome, and unravel the underlying biological pathogenesis of KMT2A fusions and ACAs.

Highly stabilized and efficient thermoelectric copper selenide.

The liquid-like feature of thermoelectric superionic conductors is a double-edged sword: the long-range migration of ions hinders the phonon transport, but their directional segregation greatly impairs the service stability. We report the synergetic enhancement in figure of merit (ZT) and stability in Cu1.99Se-based superionic conductors enabled by ion confinement effects. Guided by density functional theory and nudged elastic band simulations, we elevated the activation energy to restrict ion migrations through a cation-anion co-doping strategy. We reduced the carrier concentration without sacrificing the low thermal conductivity, obtaining a ZT of ∼3.0 at 1,050 K. Notably, the fabricated device module maintained a high conversion efficiency of up to ∼13.4% for a temperature difference of 518 K without obvious degradation after 120 cycles. Our work could be generalized to develop electrically and thermally robust functional materials with ionic migration characteristics.

Synergistic Combination of Sb2Si2Te6 Additives for Enhanced Average ZT and Single-Leg Device Efficiency of Bi0.4Sb1.6Te3-based Composites.

Thermoelectric materials are highly promising for waste heat harvesting. Although thermoelectric materials research has expanded over the years, bismuth telluride-based alloys are still the best for near-room-temperature applications. In this work, a ≈38% enhancement of the average ZT (300-473 K) to 1.21 is achieved by mixing Bi0.4Sb1.6Te3 with an emerging thermoelectric material Sb2Si2Te6, which is significantly higher than that of most BiySb2-yTe3-based composites. This enhancement is facilitated by the unique interface region between the Bi0.4Sb1.6Te3 matrix and Sb2Si2Te6-based precipitates with an orderly atomic arrangement, which promotes the transport of charge carriers with minimal scattering, overcoming a common factor that is limiting ZT enhancement in such composites. At the same time, high-density dislocations in the same region can effectively scatter the phonons, decoupling the electron-phonon transport. This results in a ≈56% enhancement of the thermoelectric quality factor at 373 K, from 0.41 for the pristine sample to 0.64 for the composite sample. A single-leg device is fabricated with a high efficiency of 5.4% at ΔT = 164 K further demonstrating the efficacy of the Sb2Si2Te6 compositing strategy and the importance of the precipitate-matrix interface microstructure in improving the performance of materials for relatively low-temperature applications.

Development and validation of a prediction model for unexpected poor ovarian response during IVF/ICSI.

Background: Identifying poor ovarian response (POR) among patients with good ovarian reserve poses a significant challenge within reproductive medicine. Currently, there is a lack of published data on the potential risk factors that could predict the occurrence of unexpected POR. The objective of this study was to develop a predictive model to assess the individual probability of unexpected POR during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments. Methods: The development of the nomogram involved a cohort of 10,404 patients with normal ovarian reserve [age, ≤40 years; antral follicle count (AFC), ≥5; and anti-Müllerian hormone (AMH), ≥1.2 ng/ml] from January 2019 to December 2022. Univariate regression analyses and least absolute shrinkage and selection operator regression analysis were employed to ascertain the characteristics associated with POR. Subsequently, the selected variables were utilized to construct the nomogram. Results: The predictors included in our model were body mass index, basal follicle-stimulating hormone, AMH, AFC, homeostasis model assessment of insulin resistance (HOMA-IR), protocol, and initial dose of gonadotropin. The area under the receiver operating characteristic curve (AUC) was 0.753 [95% confidence interval (CI) = 0.7257-0.7735]. The AUC, along with the Hosmer-Lemeshow test (p = 0.167), demonstrated a satisfactory level of congruence and discrimination ability of the developed model. Conclusion: The nomogram can anticipate the probability of unexpected POR in IVF/ICSI treatment, thereby assisting professionals in making appropriate clinical judgments and in helping patients to effectively manage expectations.

Modulating Inorganic Dimensionality of Ultrastable Lead Halide Coordination Polymers for Photocatalytic CO2 Reduction to Ethanol.

Lead halide hybrids have shown great potentials in CO2 photoreduction, but challenging to afford C2+ reduced products, especially using H2O as the reductant. This is largely due to the trade-off problem between instability of the benchmark 3D structures and low carrier mobility of quasi-2D analogues. Herein, the lead halide dimensionality of robust coordination polymers (CP) was modulated by organic ligands differing in a single-atom change (NH vs. CH2), in which the NH groups coordinate with interlamellar [PbI2] clusters to achieve the important 2D→3D transition. This first CP based on 3D cationic lead iodide sublattice possesses both high aqueous stability and a low exciton binding energy of 25 meV that is on the level of ambient thermal energy, achieving artificial photosynthesis of C2H5OH. Photophysical studies combined with theoretical calculations suggest the bridging [PbI2] clusters in the 3D structure not only results in enhanced carrier transport, but also promotes the intrinsic charge polarization to facilitate the C-C coupling. With trace loading of Rh cocatalyst, the apparent quantum efficiency of the 3D CP reaches 1.4 % at 400 nm with a high C2H5OH selectivity of 89.4 % (product basis), which presents one of the best photocatalysts for C2 products to date.

Promoting the formation of metal-carboxylate coordination to modulate the dimensionality of ultrastable lead halide hybrids.

Crystal engineering of metal halide hybrids is critical to investigate their structure-property relationship and advance their photophysical applications, but there have been limited efforts to employ coordination chemistry to precisely control the dimensionality of metal halide sublattices. Herein, we present a coordination-assembly synthetic strategy developed for the rational modulation of lead halide dimensionality, realizing the transition from 2D to 3D architectures. This manipulation is achieved by utilizing three organocarboxylates featuring the identical cyclohexane backbone unit. Specifically, the 1,4-cyclohexanedicarboxylate and 1,2,4,5-cyclohexanetetracarboxylate ligands facilitate the formation of quasi-2D layered structures, characterized by weakly corrugated and strongly corrugated lead halide layers, respectively. Importantly, the introduction of the 1,2,3,4,5,6-cyclohexanehexacarboxylate ligand results in coordination architectures featuring 3D lead chloride/bromide sublattices. The formation of the 3D coordination architectures templated by the 1,2,3,4,5,6-cyclohexanehexacarboxylate ligand affords extended wavelength coverage and superior carrier transport properties compared to their quasi-2D layered analogues. Importantly, both the 2D and 3D lead halide-based coordination polymers exhibit high aqueous stability over a wide pH range, outperforming the conventional ionic-bound lead halides. Notably, the chemically stable 3D lead bromide exhibits efficient photocatalytic ethylbenzene oxidation with the conversion rate of 498 µmol g-1 h-1, substantially higher than its 2D lead bromide counterparts. This work highlights the important role of coordination chemistry in the rational design of metal halide hybrids, which is crucial for advancing their photophysical properties and applications.

Inotuzumab ozogamicin combined with chemotherapy in pediatric B-cell precursor CD22+ acute lymphoblastic leukemia: results of the phase IB ITCC-059 trial.

Inotuzumab Ozogamicin (InO) is a CD22-directed antibody conjugated with calicheamicin. The Phase 1B of the ITCC-059 trial tested InO combined with chemotherapy in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Relapsed /refractory CD22+ BCP-ALL pediatric patients were enrolled. The primary objective was to establish the Recommended Phase 2 Dose (RP2D). Secondary objectives included preliminary efficacy and tolerability. InO was combined with 1.5 mg/m2 of vincristine (days 3, 10, 17, 24), 20 mg/m2 of dexamethasone (two 5-day blocks, then amended), and intrathecal therapy. A rolling-6 design was used testing InO from 0.8 to 1.8 mg/m2/cycle. Between May-2020 and Apr-2022, 30 patients were treated, and 29 were evaluable for dose limiting toxicities (DLTs). At 1.1 mg/m2/cycle, two out of four patients had DLTs (liver toxicity). InO was de-escalated to 0.8 mg/m2/cycle (n=6) without DLTs while awaiting a protocol amendment to reduce dexamethasone dose to 10 mg/m2. Post amendment, InO was re-escalated to 1.1 mg/m2/cycle (n=6, 1 DLT), then to 1.4 mg/m2/cycle (n=3, no DLTs), and finally to 1.8 mg/m2/cycle (n=7, 1 DLT). Three additional patients were treated in an expansion cohort. The pooled response rate was 80% (24/30; 95%CI: 61.4% to 92.3%) and, among responders, 66.7% achieved minimal residual disease negativity. The RP2D of InO combined with vincristine, dexamethasone and IT therapy was declared at 1.8 mg/m2/cycle (1.5 mg/m2/cycle after remission) in a fractionated schedule. This combination showed an response rate similar to the single agent cohorts of this trial, with liver toxicity issues at the initial higher dexamethasone dose. #NTR5736.

Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921.

PURPOSE: Bosutinib is approved for adults with chronic myeloid leukemia (CML): 400 mg once daily in newly diagnosed (ND); 500 mg once daily in resistant/intolerant (R/I) patients. Bosutinib has a different tolerability profile than other tyrosine kinase inhibitors (TKIs) and potentially less impact on growth (preclinical data). The primary objective of this first-in-child trial was to determine the recommended phase II dose (RP2D) for pediatric R/I and ND patients. PATIENTS AND METHODS: In the phase I part of this international, open-label trial (ClinicalTrials.gov identifier: NCT04258943), children age 1-18 years with R/I (per European LeukemiaNet 2013) Ph+ CML were enrolled using a 6 + 4 design, testing 300, 350, and 400 mg/m2 once daily with food. The RP2D was the dose resulting in 0/6 or 1/10 dose-limiting toxicities (DLTs) during the first cycle and achieving adult target AUC levels for the respective indication. As ND participants were only enrolled in phase II, the ND RP2D was selected based on data from R/I patients. RESULTS: Thirty patients were enrolled; 27 were evaluable for DLT: six at 300 mg/m2, 11 at 350 mg/m2 (one DLT), and 10 at 400 mg/m2 (one DLT). The mean AUCs at 300 mg/m2, 350 mg/m2, and 400 mg/m2 were 2.20 µg h/mL, 2.52 µg h/mL, and 2.66 µg h/mL, respectively. The most common adverse event was diarrhea (93%; ≥grade 3: 11%). Seven patients stopped because of intolerance and eight because of insufficient response. Complete cytogenetic and major molecular response to bosutinib appeared comparable with other published phase I/II trials with second-generation TKIs in children. CONCLUSION: Bosutinib was safe and effective. The pediatric RP2D was 400 mg/m2 once daily (max 600 mg/d) with food in R/I patients and 300 mg/m2 once daily (max 500 mg/d) with food in ND patients, which achieved targeted exposures as per adult experience.

CRISPR/Cas9-based genome editing of 14 lipid metabolic genes reveals a sporopollenin metabolon ZmPKSB-ZmTKPR1-1/-2 required for pollen exine formation in maize.

Lipid biosynthesis and transport are essential for plant male reproduction. Compared with Arabidopsis and rice, relatively fewer maize lipid metabolic genic male-sterility (GMS) genes have been identified, and the sporopollenin metabolon in maize anther remains unknown. Here, we identified two maize GMS genes, ZmTKPR1-1 and ZmTKPR1-2, by CRISPR/Cas9 mutagenesis of 14 lipid metabolic genes with anther stage-specific expression patterns. Among them, tkpr1-1/-2 double mutants displayed complete male sterility with delayed tapetum degradation and abortive pollen. ZmTKPR1-1 and ZmTKPR1-2 encode tetraketide α-pyrone reductases and have catalytic activities in reducing tetraketide α-pyrone produced by ZmPKSB (polyketide synthase B). Several conserved catalytic sites (S128/130, Y164/166 and K168/170 in ZmTKPR1-1/-2) are essential for their enzymatic activities. Both ZmTKPR1-1 and ZmTKPR1-2 are directly activated by ZmMYB84, and their encoded proteins are localized in both the endoplasmic reticulum and nuclei. Based on protein structure prediction, molecular docking, site-directed mutagenesis and biochemical assays, the sporopollenin biosynthetic metabolon ZmPKSB-ZmTKPR1-1/-2 was identified to control pollen exine formation in maize anther. Although ZmTKPR1-1/-2 and ZmPKSB formed a protein complex, their mutants showed different, even opposite, defective phenotypes of anther cuticle and pollen exine. Our findings discover new maize GMS genes that can contribute to male-sterility line-assisted maize breeding and also provide new insights into the metabolon-regulated sporopollenin biosynthesis in maize anther.

A prediction model for high ovarian response in the GnRH antagonist protocol.

Backgrounds: The present study was designed to establish and validate a prediction model for high ovarian response (HOR) in the GnRH antagonist protocol. Methods: In this retrospective study, the data of 4160 cycles were analyzed following the in vitro fertilization (IVF) at our reproductive medical center from June 2018 to May 2022. The cycles were divided into a training cohort (n=3121) and a validation cohort (n=1039) using a random sampling method. Univariate and multivariate logistic regression analyses were used to screen out the risk factors for HOR, and the nomogram was established based on the regression coefficient of the relevant variables. The area under the receiver operating characteristic curve (AUC), the calibration curve, and the decision curve analysis were used to evaluate the performance of the prediction model. Results: Multivariate logistic regression analysis revealed that age, body mass index (BMI), follicle-stimulating hormone (FSH), antral follicle count (AFC), and anti-mullerian hormone (AMH) were independent risk factors for HOR (all P< 0.05). The prediction model for HOR was constructed based on these factors. The AUC of the training cohort was 0.884 (95% CI: 0.869-0.899), and the AUC of the validation cohort was 0.884 (95% CI:0.863-0.905). Conclusion: The prediction model can predict the probability of high ovarian response prior to IVF treatment, enabling clinicians to better predict the risk of HOR and guide treatment strategies.

Wide-temperature-range thermoelectric n-type Mg3(Sb,Bi)2 with high average and peak zT values.

Mg3(Sb,Bi)2 is a promising thermoelectric material suited for electronic cooling, but there is still room to optimize its low-temperature performance. This work realizes >200% enhancement in room-temperature zT by incorporating metallic inclusions (Nb or Ta) into the Mg3(Sb,Bi)2-based matrix. The electrical conductivity is boosted in the range of 300-450 K, whereas the corresponding Seebeck coefficients remain unchanged, leading to an exceptionally high room-temperature power factor >30 µW cm-1 K-2; such an unusual effect originates mainly from the modified interfacial barriers. The reduced interfacial barriers are conducive to carrier transport at low and high temperatures. Furthermore, benefiting from the reduced lattice thermal conductivity, a record-high average zT > 1.5 and a maximum zT of 2.04 at 798 K are achieved, resulting in a high thermoelectric conversion efficiency of 15%. This work demonstrates an efficient nanocomposite strategy to enhance the wide-temperature-range thermoelectric performance of n-type Mg3(Sb,Bi)2, broadening their potential for practical applications.

Non-invasive mid-term electrocardiogram patch monitoring is effective in detecting atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a cause of serious morbidity such as stroke. Early detection and treatment of AF is important. Current guidelines recommend screening via opportunistic pulse taking or 12­lead electrocardiogram. Mid-term ECG patch monitors increases the sensitivity of AF detection. METHODS: The Singapore Atrial Fibrillation Study is a prospective multi-centre study aiming to study the incidence of AF in patients with no prior AF and a CHA2DS2-VASc score of at least 1, with the use of a mid-term continuous ECG monitoring device (Spyder ECG). Consecutive patients from both inpatient and outpatient settings were recruited from 3 major hospitals from May 2016 to December 2019. RESULTS: Three hundred and fifty-five patients were monitored. 6 patients (1.7%) were diagnosed with AF. There were no significant differences in total duration of monitoring between the AF and non-AF group (6.39 ± 3.19 vs 5.42 ± 2.46 days, p = 0.340). Patients with newly detected AF were more likely to have palpitations (50.0% vs 11.8%, p = 0.027). Half of the patients (n = 3, 50.0%) were diagnosed on the first day of monitoring and the rest were diagnosed after 24 h. On univariate analysis, only hyperlipidemia was associated with reduced odds of being diagnosed with AF (OR HR 0.08 CI 0.01-0.74, p = 0.025). In a group of 128 patients who underwent coronary artery bypass grafting and had post-operative ECG monitoring, 9 patients (7.0%) were diagnosed with post-operative AF. CONCLUSIONS: The use of non-invasive mid-term patch-based ECG monitoring is an effective modality for AF screening.

N-Type Thermoelectric AgBiPbS3 with Nanoprecipitates and Low Thermal Conductivity.

Thermoelectric sulfide materials are of particular interest due to the earth-abundant and cost-effective nature of sulfur. Here, we report a new n-type degenerate semiconductor sulfide, AgBiPbS3, which adopts a Fm3̅m structure with a narrow band gap of ∼0.32 eV. Despite the homogeneous distribution of elements at the scale of micrometer, Ag2S nanoprecipitates with dimensions of several nanometers were detected throughout the matrix. AgBiPbS3 exhibits a low room-temperature lattice thermal conductivity of 0.88 W m-1 K-1, owing to the intrinsic low lattice thermal conductivity of Ag2S and the effective scattering of phonons at nanoprecipitate boundaries. Moreover, compared to AgBiS2, AgBiPbS3 demonstrates a significantly improved weighted mobility of >16 cm2 V-1 s-1 at 300 K, leading to an enhanced PF of 1.6 µW cm-1 K-2 at 300 K. The superior electrical transport in AgBiPbS3 can be attributed to the high valley degeneracy of the L point (the conduction band minimum), which is contributed by the Pb s and Pb p orbitals. Further, Ga doping is found to be effective in modulating the Fermi levels of AgBiPbS3, leading to further enhancement of PF with a PFave of 2.7 µW cm-1 K-2 in the temperature range of 300-823 K. Consequently, a relatively high ZTave of 0.22 and a peak ZT of ∼0.4 at 823 K have been achieved in 3% Ga-doped AgBiPbS3, highlighting the potential of AgBiPbS3 as an n-type thermoelectric sulfide.

Enhanced therapeutic effect of PEDF-loaded mesenchymal stem cell-derived small extracellular vesicles against oxygen-induced retinopathy through increased stability and penetrability of PEDF.

BACKGROUND: Several common retinal diseases that cause blindness are characterised by pathological neovascularisation accompanied by inflammation and neurodegeneration, including retinopathy of prematurity (ROP), diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). The current treatment strategies for these diseases have limited benefits. Thus, safer and more effective alternative approaches are required. In this study, we loaded small extracellular vesicles (sEVs) derived from mesenchymal stem cell (MSC) with pigment epithelium-derived factor (PEDF), and tested the therapeutic effect of PEDF-loaded sEVs (PEDF-sEVs) using an oxygen induced retinopathy (OIR) mouse model, aiming to establish a new therapy strategy for the treatment of retinal pathological angiogenesis. RESULTS: We formulated PEDF-loaded sEVs (PEDF-sEVs) containing high concentrations of PEDF and evaluated their effects through in vivo and in vitro experiments. In OIR mice, PEDF-sEVs showed significantly better effects on retinal avascular areas, inflammation, and neuronal degeneration compared with the anti-vascular endothelial growth factor (VEGF) drug, which may indicate a possible advantage of PEDF-sEVs over anti-VEGF drugs in the treatment of pathological neovascularisation. In vitro, PEDF-sEVs greatly inhibited endothelial cell (EC) proliferation, migration, and tube formation by suppressing the VEGF-induced phosphorylation of extracellular signal-regulated kinase (ERK) and AKT (also known as Protein Kinase B). All experiments and analyses were performed in triplicate. PEDF-sEVs were more effective than PEDF or sEVs alone, both in vitro and in vivo. Furthermore, to determine the distribution of PEDF-sEVs, we used DiD-labelled sEVs and FITC-labelled PEDF to track the sEVs and PEDF, respectively. We found that PEDF-sEVs effectively reduced the degradation of PEDF. CONCLUSIONS: Loading PEDF on sEVs effectively enhanced the anti-angiogenic, anti-inflammatory, and neuroprotective effects of PEDF by increasing the stability and penetrability. These results suggest a potential role for PEDF-sEVs in retinal pathological neovascularisation.

Effects of body mass index and insulin resistance on first-time assisted conception and perinatal outcomes in young polycystic ovary syndrome patients.

Objective: The objective of the study was to explore the effect of body mass index (BMI) and insulin resistance (IR) levels on first-time assisted conception results and perinatal outcomes in young polycystic ovary syndrome (PCOS) patients. Design: This was a single-center, retrospective, observational cohort study. Patients: Young women with PCOS undergoing their first embryo transfer were included in the study. Main outcome measure: Early pregnancy loss rate was the main outcome measure. Results: The early pregnancy loss rate in the overweight + insulin resistance group (OW+IR group) was significantly higher than that in the non-overweight + non-insulin resistance group (NOW+NIR group) (18.16% vs. 9.02%, Bonferroni correction, P = 0.012). The early pregnancy loss rate in the non-overweight + insulin resistance group (NOW+IR group) and overweight + non-insulin resistance group (OW+NIR group) (18.18% and 17.14%, respectively) were also higher than that in the NOW+NIR group (6.07%), but the difference was not statistically significant (Bonferroni correction, all P > 0.05). No significant difference was found in clinical pregnancy rate, live birth rate, and macrosomia rate (all P > 0.05). After adjusting for confounding factors, BMI and IR levels were identified as independent risk factors for early pregnancy loss rate. Conclusion: BMI and IR levels are independent risk factors for early pregnancy loss in young PCOS patients during the first embryo transfer cycle. Multiple indicators should be considered when assessing pregnancy outcomes, which will promote individualized pregnancy guidance and treatment procedures for PCOS patients.

Orthodontic treatment of traumatically avulsed maxillary central incisors with bimaxillary dentoalveolar protrusion in an adult female: a case report.

BACKGROUND: Clinicians agree that obtaining and retaining good treatment results for missing maxillary central incisors owing to trauma is not easy. Management of adult patients with permanent maxillary central incisor loss who visit the clinic with high expectations for aesthetics and function pose a significant diagnostic dilemma. Therefore, esthetic and functional outcomes should be taken into consideration when deciding the proper treatment method. The treatment described in this study aimed to reestablish smile esthetics by proposing an effective multidisciplinary clinical approach that includes orthodontic-prosthetic-periodontal procedures, optimally reduced lip protrusion, center dental midlines, and establishment of stable occlusion. CASE PRESENTATION: The patient was a 19-year-old adult female with bimaxillary arch protrusion who had been wearing removable dentures for several years since the loss of her maxillary central permanent incisors. A multidisciplinary treatment including the extraction of two mandibular primary premolars was adopted. The treatment plan consisted of orthodontic space closure by shifting the adjacent teeth towards the central incisor spaces combined with appropriate morphologic remodeling and gingival reshaping to obtain good aesthetic and functional results. The duration to complete the orthodontic treatment was 35 months. Clinical and radiographic results after treatment suggested smile harmony with an improvement in the facial profile, good function of the occlusion, and a positive effect on bone remodeling in the area of the missing incisors during orthodontic tooth movement. CONCLUSIONS: This clinical case illustrated the necessity for using multidisciplinary methods involving orthodontic, prosthodontic, and periodontic procedures to treat an adult female patient with bimaxillary arch protrusion and long-term absence of anterior teeth due to severe trauma.

Impact of COVID-19 pandemic early response measures on myocardial infarctions and acute cardiac care in Singapore.

The COVID -19 pandemic impacted acute myocardial infarction (AMI) attendances, ST-elevation myocardial infarction (STEMI) treatments, and outcomes. We collated data from majority of primary percutaneous coronary intervention (PPCI)-capable public healthcare centres in Singapore to understand the initial impact COVID-19 had on essential time-critical emergency services. We present data comparisons from 'Before Disease Outbreak Response System Condition (DORSCON) Orange', 'DORSCON Orange to start of circuit breaker (CB)', and during the first month of 'CB'. We collected aggregate numbers of weekly elective PCI from four centres and AMI admissions, PPCI, and in-hospital mortality from five centres. Exact door-to-balloon (DTB) times were recorded for one centre; another two reported proportions of DTB times exceeding targets. Median weekly elective PCI cases significantly decreased from 'Before DORSCON Orange' to 'DORSCON Orange to start of CB' (34 vs 22.5, P = 0.013). Median weekly STEMI admissions and PPCI did not change significantly. In contrast, the median weekly non-STEMI (NSTEMI) admissions decreased significantly from 'Before DORSCON Orange' to 'DORSCON Orange to start of CB' (59 vs 48, P = 0.005) and were sustained during CB (39 cases). Exact DTB times reported by one centre showed no significant change in the median. Out of three centres, two reported significant increases in the proportion that exceeded DTB targets. In-hospital mortality rates remained static. In Singapore, STEMI and PPCI rates remained stable, while NSTEMI rates decreased during DORSCON Orange and CB. The severe acute respiratory syndrome (SARS) experience may have helped prepare us to maintain essential services such as PPCI during periods of acute healthcare resource strain. However, data must be monitored and increased pandemic preparedness measures must be explored to ensure that AMI care is not adversely affected by continued COVID fluctuations and future pandemics.

Bi-Deficiency Leading to High-Performance in Mg3 (Sb,Bi)2 -Based Thermoelectric Materials.

Mg3 (Sb,Bi)2 is a potential nearly-room temperature thermoelectric compound composed of earth-abundant elements. However, complex defect tuning and exceptional microstructural control are required. Prior studies have confirmed the detrimental effect of Mg vacancies (VMg ) in Mg3 (Sb,Bi)2 . This study proposes an approach to mitigating the negative scattering effect of VMg by Bi deficiency, synergistically modulating the electrical and thermal transport properties to enhance the thermoelectric performance. Positron annihilation spectrometry and Cs -corrected scanning transmission electron microscopy analyses indicated that the VMg tends to coalesce due to the introduced Bi vacancies (VBi ). The defects created by Bi deficiency effectively weaken the scattering of electrons from the intrinsic VMg and enhance phonon scattering. A peak zT of 1.82 at 773 K and high conversion efficiency of 11.3% at ∆T = 473 K are achieved in the optimized composition of Mg3 (Sb,Bi)2 by tuning the defect combination. This work demonstrates a feasible and effective approach to improving the performance of Mg3 (Sb,Bi)2 as an emerging thermoelectric material.

Measurable Residual Disease and Fusion Partner Independently Predict Survival and Relapse Risk in Childhood KMT2A-Rearranged Acute Myeloid Leukemia: A Study by the International Berlin-Frankfurt-Münster Study Group.

PURPOSE: A previous study by the International Berlin-Frankfurt-Münster Study Group (I-BFM-SG) on childhood KMT2A-rearranged (KMT2A-r) AML demonstrated the prognostic value of the fusion partner. This I-BFM-SG study investigated the value of flow cytometry-based measurable residual disease (flow-MRD) and evaluated the benefit of allogeneic stem-cell transplantation (allo-SCT) in first complete remission (CR1) in this disease. METHODS: A total of 1,130 children with KMT2A-r AML, diagnosed between January 2005 and December 2016, were assigned to high-risk (n = 402; 35.6%) or non-high-risk (n = 728; 64.4%) fusion partner-based groups. Flow-MRD levels at both end of induction 1 (EOI1) and 2 (EOI2) were available for 456 patients and were considered negative (<0.1%) or positive (≥0.1%). End points were 5-year event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS). RESULTS: The high-risk group had inferior EFS (30.3% high risk v 54.0% non-high risk; P < .0001), CIR (59.7% v 35.2%; P < .0001), and OS (49.2% v 70.5%; P < .0001). EOI2 MRD negativity was associated with superior EFS (n = 413; 47.6% MRD negativity v n = 43; 16.3% MRD positivity; P < .0001) and OS (n = 413; 66.0% v n = 43; 27.9%; P < .0001), and showed a trend toward lower CIR (n = 392; 46.1% v n = 26; 65.4%; P = .016). Similar results were obtained for patients with EOI2 MRD negativity within both risk groups, except that within the non-high-risk group, CIR was comparable with that of patients with EOI2 MRD positivity. Allo-SCT in CR1 only reduced CIR (hazard ratio, 0.5 [95% CI, 0.4 to 0.8]; P = .00096) within the high-risk group but did not improve OS. In multivariable analyses, EOI2 MRD positivity and high-risk group were independently associated with inferior EFS, CIR, and OS. CONCLUSION: EOI2 flow-MRD is an independent prognostic factor and should be included as risk stratification factor in childhood KMT2A-r AML. Treatment approaches other than allo-SCT in CR1 are needed to improve prognosis.

Clinical outcomes in end stage renal disease on dialysis and severe coronary artery disease: A real-world study.

BACKGROUND: The optimal management of patients with end-stage renal disease (ESRD) on dialysis with severe coronary artery disease (CAD) has not been determined. METHODS: Between 2013 and 2017, all patients with ESRD on dialysis who had left main (LM) disease, triple vessel disease (TVD) and/or severe CAD for consideration of coronary artery bypass graft (CABG) were included. Patients were divided into 3 groups based on final treatment modality: CABG, percutaneous coronary intervention (PCI), optimal medical therapy (OMT). Outcome measures include in-hospital, 180-day, 1-year and overall mortality and major adverse cardiac events (MACE). RESULTS: In total, 418 patients were included (CABG 11.0%, PCI 65.6%, OMT 23.4%). Overall, 1-year mortality and MACE rates were 27.5% and 55.0% respectively. Patients who underwent CABG were significantly younger, more likely to have LM disease and have no prior heart failure. In this non-randomized setting, treatment modality did not impact on 1-year mortality, although the CABG group had significantly lower 1-year MACE rates (CABG 32.6%, PCI 57.3%, OMT 59.2%; CABG vs. OMT p < 0.01, CABG vs. PCI p < 0.001). Independent predictors of overall mortality include STEMI presentation (HR 2.31, 95% CI 1.38-3.86), prior heart failure (HR 1.84, 95% CI 1.22-2.75), LM disease (HR 1.71, 95% CI 1.26-2.31), NSTE-ACS presentation (HR 1.40, 95% CI 1.03-1.91) and increased age (HR 1.02, 95% CI 1.01-1.04). CONCLUSION: Treatment decisions for patients with severe CAD with ESRD on dialysis are complex. Understanding independent predictors of mortality and MACE in specific treatment subgroups may provide valuable insights into the selection of optimal treatment options.