Application of machine learning algorithms for accurate determination of bilirubin level on in vitro engineered tissue phantom images.

Neonatal Jaundice is a common occurrence in neonates. High excess bilirubin would lead to hyperbilirubinemia, leading to irreversible adverse damage such as kernicterus. Therefore, it is necessary and important to monitor neonates' bilirubin levels in real-time for immediate intervention. However, current screening protocols have their inherent limitations, necessitating more convenient measurements. In this proof-of-concept study, we evaluated the feasibility of using machine learning for the screening of hyperbilirubinemia in neonates from smartphone-acquired photographs. Different machine learning models were compared and evaluated to gain a better understanding of feature selection and model performance in bilirubin determination. An in vitro study was conducted with a bilirubin-containing tissue phantom to identify potential biological and environmental confounding factors. The findings of this study present a systematic characterization of the confounding effect of various factors through separate parametric tests. These tests uncover potential techniques in image pre-processing, highlighting important biological features (light scattering property and skin thickness) and external features (ISO, lighting conditions and white balance), which together contribute to robust model approaches for accurately determining bilirubin concentrations. By obtaining an accuracy of 0.848 in classification and 0.812 in regression, these findings indicate strong potential in aiding in the design of clinical studies using patient-derived images.

Semi-Transparent, Pixel-Free Upconversion Goggles with Dual Audio-Visual Communication.

The intractable brittleness and opacity of the crystalline semiconductor restrict the prospect of developing low-cost imaging systems. Here, infrared visualization technologies are established with large-area, semi-transparent organic upconversion devices that bring high-resolution invisible images into sight without photolithography. To exploit all photoinduced charge carriers, a monolithic device structure is proposed built on the infrared-selective, single-component charge generation layer of chloroaluminum phthalocyanine (ClAlPc) coupled to two visible light-emitting layers manipulated with unipolar charges. Transient pump-probe spectroscopy reveals that the ClAlPc-based device exhibits an efficient charge dissociation process under forward bias. This process is indicated by the prompt and strong features of electroabsorption screening. Furthermore, by imposing the electric field, the ultrafast excited state dynamic suggests a prolonged charge carrier lifetime from the ClAlPc, which facilitates the charge utilization for upconversion luminance. For the first time, >30% of the infrared photons are utilized without photomultiplication strategies owing to the trivial spectrum overlap between ClAlPc and the emitter. In addition, the device can broadcast the acoustic signal by synchronizing the device frequency with the light source, which enables to operate it in dual audio-visual mode. The work demonstrates the potential of upconversion devices for affordable infrared imaging in wearable electronics.

Engineering the Macrocyclic Donor Structures towards Deep-Blue Thermally Activated Delayed Fluorescence Emitters.

Deep-blue thermally activated delayed fluorescence (TADF) molecules present promising potential in organic light-emitting diodes (OLEDs), especially for display applications. Here, an efficient molecular engineering approach to modifying the donor or acceptor features of the D-π-A-configured TADF molecules for deep-blue emission is reported. By introducing oxygen and sulfone as a bridge unit onto the macrocyclic donor, two emitters, c-ON-MeTRZ and c-NS-MeTRZ, are synthesized and characterized, respectively. The reduced donor strength of c-ON-MeTRZ and c-NS-MeTRZ as compared to that of the model molecule c-NN-MeTRZ leads to blue-shifted emissions with high photoluminescence quantum yields (PLQYs) and retains TADF characters, while the new emitter c-NN-MePym with the most blue-shifted emission only exhibits a pure fluorescent nature because of the electron-accepting feature of pyrimidine that is insufficient for inducing the TADF property. In the presence of macrocyclic donors, these new emitters show high horizontal dipole ratios (Θ// = 85-89%), which are beneficial for improving the light out-coupling efficiency. Deep-blue TADF OLEDs incorporating c-ON-MeTRZ as an emitter doped in the mCPCN host achieves a high maximum external quantum efficiency (EQEmax) of 30.2% together with 1931 Commission Internationale de I'Eclairage (CIE) coordinates of (0.14, 0.13), while the counter device employing c-NS-MeTRZ as a dopant gives EQEmax of 15.4% and CIE coordinates of (0.14, 0.09). The EQEmax of c-ON-MeTRZ- and c-NS-MeTRZ-based devices can be significantly improved to 34.4 and 29.3%, respectively, with a polar host DPEPO, which stabilizes the charge transfer (CT) S1 state to give lower ΔEST for improving the reverse intersystem crossing process. The efficient TADF character, high PLQYs, and high anisotropic emission dipole ratios work together to render the superior electroluminescence (EL) efficiencies. Based on the detailed characterizations of physical properties, theoretical analyses, and comprehensive study on the corresponding devices, a clear structure-property-performance relationship has been successfully established to verify the effective molecular design strategy of modulating the macrocyclic donor characters for efficient deep-blue TADF emitters.

The one-step fabrication of porous hASC-laden GelMa constructs using a handheld printing system.

The fabrication of highly porous cell-loaded structures in tissue engineering applications has been a challenging issue because non-porous cell-laden struts can cause severe cell necrosis in the middle region owing to poor transport of nutrients and oxygen. In this study, we propose a versatile handheld 3D printer for the effective fabrication of porous cell-laden methacrylated gelatin (GelMa) with high porosity (≈97%) by air injection and a bubble-making system using mesh filters through which a mixture of air/GelMa bioink is passed. In particular, the pore size and foamability of the cell constructs could be manipulated using various processing parameters (rheological properties of GelMa, filter size and number, and air-bioink volume ratio). To demonstrate the feasibility of the cell construct as a tissue engineering substitute for muscle regeneration, in vitro cellular activities and in vivo regeneration ability of human adipose stem cells were assessed. The in vitro results demonstrated that the human adipose stem cells (hASCs) fabricated using the handheld 3D printer were alive and well-proliferated. Furthermore, the in vivo results showed that the hASCs-constructs directly printed from the handheld 3D printer showed significant restoration of functionality and efficient muscle regeneration in the volumetric muscle loss model of mice. Based on these results, the fabrication method of the porous cell-laden construct could be a promising tool for regenerating muscle tissues.

Transparent organic upconversion devices displaying high-resolution, single-pixel, low-power infrared images perceived by human vision.

Crystalline photodiodes remain the most viable infrared sensing technology of choice, yet the opacity and the limitation in pixel size reduction per se restrict their development for supporting high-resolution in situ infrared images. In this work, we propose an all-organic non-fullerene-based upconversion device that brings invisible infrared signal into human vision via exciplex cohost light-emissive system. The device reaches an infrared-to-visible upconversion efficiency of 12.56% by resolving the 940-nm infrared signal (power density of 103.8 µW cm-2). We tailor a semitransparent (AVT, ~60%), large-area (10.35 cm2), lightweight (22.91 g), single-pixel upconversion panel to visualize the infrared power density down to 0.75 µW cm2, inferring a bias-switching linear dynamic range approaching 80 dB. We also demonstrate the possibility of visualizing low-intensity infrared signals from the Face ID and LiDAR, which should fill the gap in the existing technology based on pixelated complementary metal-oxide semiconductors with optical lenses.

Power Efficiency Enhancement of Organic Light-Emitting Diodes Due to the Favorable Horizontal Orientation of a Naphthyridine-Based Thermally Activated Delayed Fluorescence Luminophore.

Four emitters based on the naphthyridine acceptor moiety and various donor units exhibiting thermally activated delayed fluorescence (TADF) were designed and synthesized. The emitters exhibited excellent TADF properties with a small ΔE ST and a high photoluminescence quantum yield. A green TADF organic light-emitting diode based on 10-(4-(1,8-naphthyridin-2-yl)phenyl)-10H-phenothiazine exhibited a maximum external quantum efficiency of 16.4% with Commission Internationale de L'éclairage coordinates of (0.368, 0.569) as well as a high current and power efficiency of 58.6 cd/A and 57.1 lm/W, respectively. The supreme power efficiency is a record-high value among the reported values of devices with naphthyridine-based emitters. This results from its high photoluminescence quantum yield, efficient TADF, and horizontal molecular orientation. The molecular orientations of the films of the host and the host doped with the naphthyridine emitter were explored by angle-dependent photoluminescence and grazing-incidence small-angle X-ray scattering (GIWAXS). The orientation order parameters (ΘADPL) were found to be 0.37, 0.45, 0.62, and 0.74 for the naphthyridine dopants with dimethylacridan, carbazole, phenoxazine, and phenothiazine donor moieties, respectively. These results were also proven by GIWAXS measurement. The derivative of naphthyridine and phenothiazine was shown to be more flexible to align with the host and to show the favorable horizontal molecular orientation and crystalline domain size, benefiting the outcoupling efficiency and contributing to the device efficiency.

Shape-memory collagen scaffold combined with hyaluronic acid for repairing intervertebral disc.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a common cause of chronic low back pain (LBP) and a socioeconomic burden worldwide. Conservative therapies and surgical treatments provide only symptomatic pain relief without promoting intervertebral disc (IVD) regeneration. Therefore, the clinical demand for disc regenerative therapies for disc repair is high. METHODS: In this study, we used a rat tail nucleotomy model to develop mechanically stable collagen-cryogel and fibrillated collagen with shape-memory for use in minimally invasive surgery for effective treatment of IVDD. The collagen was loaded with hyaluronic acid (HA) into a rat tail nucleotomy model. RESULTS: The shape-memory collagen structures exhibited outstanding chondrogenic activities, having completely similar physical properties to those of a typical shape-memory alginate construct in terms of water absorption, compressive properties, and shape-memorability behavior. The treatment of rat tail nucleotomy model with shape-memory collagen-cryogel/HA alleviated mechanical allodynia, maintained a higher concentration of water content, and preserved the disc structure by restoring the matrix proteins. CONCLUSION: According to these results, the collagen-based structure could effectively repair and maintain the IVD matrix better than the controls, including HA only and shape-memory alginate with HA.

Trends in neonatal mortality and morbidity in very-low-birth-weight (VLBW) infants over a decade: Singapore national cohort study.

BACKGROUND: Very preterm infants are at risk for neurodevelopmental impairment because of postnatal morbidities. This study aims to (1) compare the outcomes of very-low-birth-weight (VLBW) infants in Singapore during two time periods over a decade; 2) compare performances among Singaporean neonatal intensive care units (NICUs); and 3) compare a Singapore national cohort with one from the Australian and New Zealand Neonatal Network (ANZNN). METHODS: Singapore national data on VLBW infants born during two periods, 2007-2008 (SG2007, n = 286) and 2015-2017 (SG2017, n = 905) were extracted from patient medical records. The care practices and clinical outcomes among three Singapore NICUs were compared using SG2017 data. Third, using data from the ANZNN2017 annual report, infants with gestational age (GA) ≤29 weeks in SG2017 were compared with their Oceania counterparts. RESULTS: SG2017 had 9.9% higher usage of antenatal steroids (p < 0.001), 8% better survival for infants ≤26 weeks (p = 0.174), and used 12.7% lesser nonsteroidal anti-inflammatory drugs for patent ductus arteriosus closure (p < 0.001) than those of SG2007 cohort. Rate of late-onset sepsis (LOS) was almost halved (7.4% vs. 14.0%, p < 0.001), and exclusive human milk feeding after discharge increased threefold (p < 0.001). SG2017, in contrast, had a higher rate of chronic lung disease (CLD) (20.0% vs. 15.1%, p = 0.098). Within SG2017, the rates of LOS, CLD, and human milk feeding varied significantly between the three NICUs. When compared with ANZNN2017, SG2017 had significantly lower rates of LOS for infants ≤25 weeks (p = 0.001), less necrotizing enterocolitis for infants ≤27 weeks (p = 0.002), and less CLD across all GA groups. CONCLUSION: Postnatal morbidities and survival rates for VLBW infants in Singapore have improved over a decade. Outcomes for VLBW infants varied among three Singapore NICUs, which provide a rationale for collaboration to improve clinical quality. The outcomes of Singaporean VLBW infants were comparable to those of their ANZNN counterparts.

Birth anthropometry among three Asian racial groups in Singapore: proposed new growth charts.

OBJECTIVE: We analysed birth anthropometry of babies of Chinese, Malay and Indian ancestry living in Singapore with an aim to develop gestational age (GA) and gender-specific birth anthropometry charts and compare these with the widely used Fenton charts. DESIGN: Retrospective observational study. SETTING: Department of Neonatology, National University Hospital, Singapore. POPULATION: We report data from 52 220 infants, born between 1991-1997 and 2010-2017 in Singapore. METHODS: Anthropometry charts were built using smoothened centile curves and compared with Fenton's using binomial test. Birth weight (BW), crown-heel length and head circumference (HC) were each modelled with maternal exposures using general additive model. MAIN OUTCOME MEASURES: BW, crown-heel length and HC. RESULTS: There were 22 248 Chinese (43%), 16 006 Malay (31%) and 8543 Indian (16%) babies. Mean BW was 3103 g (95% CI 3096 to 3109), 3075 g (95% CI 3067 to 3083) and 3052 g (95% CI 3041 to 3062) for Chinese, Malays and Indians, respectively. When exposed to a uniform socioeconomic environment, intrauterine growth and birth anthropometry of studied races were almost identical. From our GA-specific anthropometric charts until about late prematurity, Asian growth curves mirrored that of Fenton's; thereafter, Asian babies showed a reduction in growth velocity. CONCLUSIONS: These findings suggest that Asian babies living in relatively uniform socioeconomic strata exhibit similar growth patterns. There is a slowing of growth among Asian babies towards term, prompting review of existing birth anthropometry charts. The proposed charts will increase accuracy of identification of true fetal growth restriction as well as true postnatal growth failure in preterm infants when applied to the appropriate population.

Multicenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer.

Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival (OS), prognosis in Stage I, Stage II, Stage II-high-risk, and microsatellite-stable (MSS) patients. RESULTS: High-Immunoscore presented with the lowest risk of recurrence in both cohorts. In Stage I/II, recurrence-free rates at 5 years were 78.4% (95%-CI, 74.4−82.6), 88.1% (95%-CI, 85.7−90.4), 93.4% (95%-CI, 91.1−95.8) in low, intermediate and high Immunoscore, respectively (HR (Hi vs. Lo) = 0.27 (95%-CI, 0.18−0.41); p < 0.0001). In Cox multivariable analysis, the association of Immunoscore to outcome was independent (TTR: HR (Hi vs. Lo) = 0.29, (95%-CI, 0.17−0.50); p < 0.0001) of the patient's gender, T-stage, sidedness, and microsatellite instability-status (MSI). A significant association of Immunoscore with survival was found for Stage II, high-risk Stage II, T4N0 and MSS patients. The Immunoscore also showed significant association with TTR in Stage-I (HR (Hi vs. Lo) = 0.07 (95%-CI, 0.01−0.61); P = 0.016). The Immunoscore had the strongest (69.5%) contribution χ2 for influencing survival. Patients with a high Immunoscore had prolonged TTR in T4N0 tumors even for patients not receiving chemotherapy, and the Immunoscore remained the only significant parameter in multivariable analysis. CONCLUSION: In early CC, low Immunoscore reliably identifies patients at risk of relapse for whom a more intensive surveillance program or adjuvant treatment should be considered.

Direct detection of virus-like particles using color images of plasmonic nanostructures.

We propose a measurement method for sensitive and label-free detections of virus-like particles (VLPs) using color images of nanoplasmonic sensing chips. The nanoplasmonic chip consists of 5×5 gold nanoslit arrays and the gold surface is modified with specific antibodies for spike protein. The resonant wavelength of the 430-nm-period gold nanoslit arrays underwater environment is about 570 nm which falls between the green and red bands of the color CCD. The captured VLPs by the specific antibodies shift the plasmonic resonance of the gold nanoslits. It results in an increased brightness of green pixels and decreased brightness of red pixels. The image contrast signals of (green - red) / (red + green) show good linearity with the surface particle density. The experimental tests show the image contrast method can detect 100-nm polystyrene particles with a surface density smaller than 2 particles/µm2. We demonstrate the application for direct detection of SARS-CoV-2 VLPs using a simple scanner platform. A detection limit smaller than 1 pg/mL with a detection time less than 30 minutes can be achieved.

Effects of electron transport layer thickness on light extraction in corrugated OLEDs.

This study reported the effects of electron transport layer (ETL) thickness on light extraction in corrugated organic light-emitting diodes (OLEDs) and each layer in OLEDs exhibited a periodical corrugated structure, which was determined by depositing thin films on a glass substrate with a nanoimprinted blazed grating structure. The insight is that light extraction in corrugated OLEDs significantly depends on the ETL thickness. Varying the ETL thickness changed the distribution of carrier recombination and led to exciton formation and optical interference, thereby resulting in different attribution of optical loss modes in OLEDs, which increased or even decreased light extraction and device efficiency. Trapped light extraction from the surface plasmon polariton (SPP) and waveguide (WG) modes was identified by splitting the light into transverse electric and transverse magnetic emissions. Thus, the contributions from the individual SPP and WG modes to the external quantum efficiency (EQE) were distinctly clarified by comparing the experimental results with the theoretical calculations. At the ETL thickness of 115 nm, the corrugated OLED exhibited a significantly enhanced (1.83-fold) EQE compared to the planar one due to the effective extraction of trapped light from the SPP and WG modes. The EQE was enhanced by 0.5%, wherein 0.39% came from the WG mode and 0.11% came from the SPP mode.

Clinical Performance of the Consensus Immunoscore in Colon Cancer in the Asian Population from the Multicenter International SITC Study.

BACKGROUND: In this study, we evaluated the prognostic value of Immunoscore in patients with stage I−III colon cancer (CC) in the Asian population. These patients were originally included in an international study led by the Society for Immunotherapy of Cancer (SITC) on 2681 patients with AJCC/UICC-TNM stages I−III CC. METHODS: CD3+ and cytotoxic CD8+ T-lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The association of Immunoscore with prognosis was evaluated for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS). RESULTS: Immunoscore stratified Asian patients (n = 423) into different risk categories and was not impacted by age. Recurrence-free rates at 3 years were 78.5%, 85.2%, and 98.3% for a Low, Intermediate, and High Immunoscore, respectively (HR[Low-vs-High] = 7.26 (95% CI 1.75−30.19); p = 0.0064). A High Immunoscore showed a significant association with prolonged TTR, OS, and DFS (p < 0.05). In Cox multivariable analysis stratified by center, Immunoscore association with TTR was independent (HR[Low-vs-Int+High] = 2.22 (95% CI 1.10−4.55) p = 0.0269) of the patient's gender, T-stage, N-stage, sidedness, and MSI status. A significant association of a High Immunoscore with prolonged TTR was also found among MSS (HR[Low-vs-Int+High] = 4.58 (95% CI 2.27−9.23); p ≤ 0.0001), stage II (HR[Low-vs-Int+High] = 2.72 (95% CI 1.35−5.51); p = 0.0052), low-risk stage-II (HR[Low-vs-Int+High] = 2.62 (95% CI 1.21−5.68); p = 0.0146), and high-risk stage II patients (HR[Low-vs-Int+High] = 3.11 (95% CI 1.39−6.91); p = 0.0055). CONCLUSION: A High Immunoscore is significantly associated with the prolonged survival of CC patients within the Asian population.

Mechanically and biologically enhanced 3D-printed HA/PLLA/dECM biocomposites for bone tissue engineering.

Poly (L-lactic acid) (PLLA)-based biocomposites have been used in tissue engineering applications because of their reasonable biocompatibility and mechanical properties. However, the imperfect bioactive and mechanical properties of the composite make it difficult to be used in the region of bone defects that require high load-bearing. Therefore, this study introduced two fabricating strategies to induce mechanically and biologically enhanced hydroxyapatite (HA)/PLLA biocomposites. By introducing an in situ plasma treatment, which was simultaneously applied during the 3D-printing process, followed by the thermal annealing process, the flexural modulus of the composite was increased by 2.1-fold compared to the normal HA/PLLA composite. Furthermore, using the combinational process, efficient coating of bioactive material [decellularized extracellular matrix (dECM) derived from porcine bones] was possible. The fabricated biocomposite scaffold was assessed for various in vitro cellular activities such as cell proliferation and osteogenic activity. Based on the mechanical and biological studies, the HA/PLLA/dECM biocomposite scaffold is one of the promising scaffolds that can be applied in bone tissue regeneration.

Highly elastic 3D-printed gelatin/HA/placental-extract scaffolds for bone tissue engineering.

Bioengineering scaffolds have been improved to achieve efficient regeneration of various damaged tissues. In this study, we attempted to fabricate mechanically and biologically activated 3D printed scaffold in which porous gelatin/hydroxyapatite (G/H) as a matrix material provided outstanding mechanical properties with recoverable behavior, and human placental extracts (hPE) embedded in the scaffold were used as bioactive components. Methods: Various cell types (human adipose-derived stem cells; hASCs, pre-osteoblast; MC3T3-E1, human endothelial cell line; EA.hy926, and human dermal fibroblast; hDFs) were used to assess the effect of the hPE on cellular responses. High weight fraction (~ 70 wt%) of hydroxyapatite (HA) in a gelatin solution supplemented with glycerol was used for the G/H scaffold fabrication, and the scaffolds were immersed in hPE for the embedding (G/H/hPE scaffold). The osteogenic abilities of the scaffolds were investigated in cultured cells (hASCs) assaying for ALP activity and expression of osteogenic genes. For the in vivo test, the G/H and G/H/hPE scaffolds were implanted in the rat mastoid obliteration model. Results: The G/H/hPE scaffold presented unique elastic recoverable properties, which are important for efficient usage of implantable scaffolds. The effects of G/H and G/H/hPE scaffold on various in vitro cell-activities including non-toxicity, biocompatibility, and cell proliferation were investigated. The in vitro results indicated that proliferation (G/H = 351.1 ± 13.3%, G/H/hPE = 430.9 ± 8.7% at day 14) and expression of osteogenic markers (ALP: 3.4-fold, Runx2: 3.9-fold, BMP2: 1.7-fold, OPN: 2.4-fold, and OCN: 4.8-fold at day 21) of hASCs grown in the G/H/hPE scaffold were significantly enhanced compared with that in cells grown in the G/H scaffold. In addition, bone formation was also observed in an in vivo model using rat mastoid obliteration. Conclusion:In vitro and in vivo results suggested that the G/H/hPE scaffold is a potential candidate for use in bone tissue engineering.

Wound healing ability of acellular fish skin and bovine collagen grafts for split-thickness donor sites in burn patients: Characterization of acellular grafts and clinical application.

Due to its high polyunsaturated fatty acid content, acellular fish skin has emerged as a dermal substitute for the promotion of wound healing as it decreases scar formation while providing pain relief. However, various systematic studies on acellular fish skin, such as its biophysical analysis, in vitro activities, and clinical application, have not been sufficiently investigated. In this study, we conducted a comparative study to evaluate the wound-healing ability of acellular fish skin graft (Kerecis®) with that of the widely used bovine collagen skin graft (ProHeal®). The skin grafts were evaluated not only in terms of their biophysical properties, but also their in vitro cellular activities, using fibroblasts, keratinocytes, and human endothelial cells. The clinical study evaluated wound healing in 52 patients with acute burns who underwent skin grafting on donor sites from January 2019 to December 2020. The study was conducted with two groups; while only Kerecis® was tested in one group, Kerecis® and ProHeal® were compared in the other. In both groups, the application time of the dressing material was one to two days after split-thickness skin grafting to the donor sites. The Kerecis®-treatment group experienced faster healing than the other treatment group. In particular, the average wound healing time using the Kerecis® treatment and the ProHeal® treatment was 10.7 ± 1.5 days and 13.1 ± 1.4 days, respectively. We believe that the faster healing of the Kerecis® treatment, compared to that of the ProHeal® treatment, maybe due to the synergistic effect of the unique biophysical structure and the bioactive components of acellular fish skin.

An extended π-backbone for highly efficient near-infrared thermally activated delayed fluorescence with enhanced horizontal molecular orientation.

Near-infrared thermally activated delayed fluorescence (NIR-TADF) materials with emission over 700 nm have been insufficiently investigated mainly due to the limited choice of strong donor/acceptor units for molecular construction and the limited electronic coupling between the donors and acceptors. Herein, a novel D-A1-A2-A3 configuration was developed for the design of a NIR-TADF material (TPA-CN-N4-2PY), in which three types of sub-acceptor units (CN: cyano; N4: dipyrido[3,2-a:2',3'-c]phenazine; PY: pyridine) were incorporated into a molecular skeleton to reinforce the electron-accepting strength. The attachment of two pyridine units on TPA-CN-N4 produced TPA-CN-N4-2PY with an extended π-backbone, which shifted the electroluminescence (EL) emission into the NIR region and enhanced the horizontal ratio of emitting dipole orientation (Θ//) simultaneously. TPA-CN-N4-2PY-based OLEDs demonstrated a record-high external quantum efficiency (EQE) of 21.9% with an emission peak at 712 nm and Θ// = 85% at the doping ratio of 9.0 wt%. On the contrary, the parent compound TPA-CN-N4-based OLEDs at the same doping ratio achieved an EQE of 23.4% at 678 nm with Θ// = 75%. This multiple sub-acceptors approach could enrich the design strategy of the NIR-TADF materials, and the large conjugated system could improve the Θ// for achieving efficient emitters.

Deep Blue Fluorescent Material with an Extremely High Ratio of Horizontal Orientation to Enhance Light Outcoupling Efficiency (44%) and External Quantum Efficiency in Doped and Non-Doped Organic Light-Emitting Diodes.

A novel bis-4Ph-substituted 9,10-dipehnylanthracene deep blue [1931 CIE (0.15, 0.08)] fluorescent compound, AnB4Ph, has been synthesized and characterized for organic light-emitting diode (OLED) applications. Our experimental study of AnB4Ph excludes the possibility of triplet-triplet annihilation, hybridized local and charge transfer, or thermally activated delayed fluorescent characteristics of the material. Since the solid-state photoluminescence quantum yield of AnB4Ph was determined to be 48%, assuming a 100% for the charge recombination efficiency, the light outcoupling efficiency (ηout) of an AnB4Ph non-doped OLED achieving an external quantum efficiency (EQE) of 5.3% is at least 44%, which is more than twofold higher than 20% for conventional OLEDs. Both grazing incidence wide-angle X-ray scattering (GIWAXS) and angle-dependent photoluminescence (ADPL) measurements reveal AnB4Ph having a high value of order parameter (SGIWAXS) of 0.61 for a ππ stacking along the normal direction and an orientation order parameter (SADPL) for a horizontal emitting dipole moment of -0.50 or Θ (horizontal-dipole ratios) of 100%, respectively. Otherwise, a refractive index (n) measurement provides a n = 1.80 for AnB4Ph thin films. Based on ηout = 1.2 × n-2, the calculated ηout is 37%, which is also in accordance with the results of GIWAXS and ADPL. We have also fabricated the classical fluorescent DPAVBi-doped AnB4Ph OLEDs, which display a true blue [1931 CIE (0.15 and 0.16)] electroluminescence with a high efficiency (EQE = 6.9%), surpassing the conventional ∼5% EQE. Based on an ηout of 42% for DPAVBi-doped AnB4Ph OLEDs, our studies suggest that the extremely horizontally aligned AnB4Ph host material exerts the same horizontal alignment on the DPAVBi dopant molecules.

Self-aligned myofibers in 3D bioprinted extracellular matrix-based construct accelerate skeletal muscle function restoration.

To achieve rapid skeletal muscle function restoration, many attempts have been made to bioengineer functional muscle constructs by employing physical, biochemical, or biological cues. Here, we develop a self-aligned skeletal muscle construct by printing a photo-crosslinkable skeletal muscle extracellular matrix-derived bioink together with poly(vinyl alcohol) that contains human muscle progenitor cells. To induce the self-alignment of human muscle progenitor cells, in situ uniaxially aligned micro-topographical structure in the printed constructs is created by a fibrillation/leaching of poly(vinyl alcohol) after the printing process. The in vitro results demonstrate that the synergistic effect of tissue-specific biochemical signals (obtained from the skeletal muscle extracellular matrix-derived bioink) and topographical cues [obtained from the poly(vinyl alcohol) fibrillation] improves the myogenic differentiation of the printed human muscle progenitor cells with cellular alignment. Moreover, this self-aligned muscle construct shows the accelerated integration with neural networks and vascular ingrowth in vivo, resulting in rapid restoration of muscle function. We demonstrate that combined biochemical and topographic cues on the 3D bioprinted skeletal muscle constructs can effectively reconstruct the extensive muscle defect injuries.

The tumor immune contexture of salivary duct carcinoma.

BACKGROUND: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy. Recently, biomarker studies found promising targetable alterations. In this study, we provide a descriptive analysis of tumor and immune biomarkers and survival associations. METHODS: We extracted clinical data and performed immunohistochemistry for AR, AR-V7, HER-2, PD-L1, LAG-3, and tumor-infiltrating immune cells. RESULTS: We included 17 patients. Age ranged from 42 to 85 years old; HER-2 was overexpressed or amplified in 65%. AR was positive in 88% of patients, while AR-V7 was positive in 13% by IHC. We found low scores of immune infiltration and a PD-L1 expression in 53%. We found no clinically significant association between biomarkers and survival outcomes. CONCLUSION: In this small series of SDC, biomarkers do not seem to correlate with disease biology, although they provide additional treatment options. SDC may harbor a different immune profile compared to other subtypes, with an indication of T-cell dysfunction.