Growth of diamond in liquid metal at 1 atm pressure.

Natural diamonds were (and are) formed (thousands of million years ago) in the upper mantle of Earth in metallic melts at temperatures of 900-1,400 °C and at pressures of 5-6 GPa (refs. 1,2). Diamond is thermodynamically stable under high-pressure and high-temperature conditions as per the phase diagram of carbon3. Scientists at General Electric invented and used a high-pressure and high-temperature apparatus in 1955 to synthesize diamonds by using molten iron sulfide at about 7 GPa and 1,600 °C (refs. 4-6). There is an existing model that diamond can be grown using liquid metals only at both high pressure and high temperature7. Here we describe the growth of diamond crystals and polycrystalline diamond films with no seed particles using liquid metal but at 1 atm pressure and at 1,025 °C, breaking this pattern. Diamond grew in the subsurface of liquid metal composed of gallium, iron, nickel and silicon, by catalytic activation of methane and diffusion of carbon atoms into and within the subsurface regions. We found that the supersaturation of carbon in the liquid metal subsurface leads to the nucleation and growth of diamonds, with Si playing an important part in stabilizing tetravalently bonded carbon clusters that play a part in nucleation. Growth of (metastable) diamond in liquid metal at moderate temperature and 1 atm pressure opens many possibilities for further basic science studies and for the scaling of this type of growth.

Single-crystal, large-area, fold-free monolayer graphene.

Chemical vapour deposition of carbon-containing precursors on metal substrates is currently the most promising route for the scalable synthesis of large-area, high-quality graphene films1. However, there are usually some imperfections present in the resulting films: grain boundaries, regions with additional layers (adlayers), and wrinkles or folds, all of which can degrade the performance of graphene in various applications2-7. There have been numerous studies on ways to eliminate grain boundaries8,9 and adlayers10-12, but graphene folds have been less investigated. Here we explore the wrinkling/folding process for graphene films grown from an ethylene precursor on single-crystal Cu-Ni(111) foils. We identify a critical growth temperature (1,030 kelvin) above which folds will naturally form during the subsequent cooling process. Specifically, the compressive stress that builds up owing to thermal contraction during cooling is released by the abrupt onset of step bunching in the foil at about 1,030 kelvin, triggering the formation of graphene folds perpendicular to the step edge direction. By restricting the initial growth temperature to between 1,000 kelvin and 1,030 kelvin, we can produce large areas of single-crystal monolayer graphene films that are high-quality and fold-free. The resulting films show highly uniform transport properties: field-effect transistors prepared from these films exhibit average room-temperature carrier mobilities of around (7.0 ± 1.0) × 103 centimetres squared per volt per second for both holes and electrons. The process is also scalable, permitting simultaneous growth of graphene of the same quality on multiple foils stacked in parallel. After electrochemical transfer of the graphene films from the foils, the foils themselves can be reused essentially indefinitely for further graphene growth.

L-type Ca2+ channels mediate regulation of glutamate release by subthreshold potential changes.

Subthreshold depolarization enhances neurotransmitter release evoked by action potentials and plays a key role in modulating synaptic transmission by combining analog and digital signals. This process is known to be Ca2+ dependent. However, the underlying mechanism of how small changes in basal Ca2+ caused by subthreshold depolarization can regulate transmitter release triggered by a large increase in local Ca2+ is not well understood. This study aimed to investigate the source and signaling mechanisms of Ca2+ that couple subthreshold depolarization with the enhancement of glutamate release in hippocampal cultures and CA3 pyramidal neurons. Subthreshold depolarization increased presynaptic Ca2+ levels, the frequency of spontaneous release, and the amplitude of evoked release, all of which were abolished by blocking L-type Ca2+ channels. A high concentration of intracellular Ca2+ buffer or blockade of calmodulin abolished depolarization-induced increases in transmitter release. Estimation of the readily releasable pool size using hypertonic sucrose showed depolarization-induced increases in readily releasable pool size, and this increase was abolished by the blockade of calmodulin. Our results provide mechanistic insights into the modulation of transmitter release by subthreshold potential change and highlight the role of L-type Ca2+ channels in coupling subthreshold depolarization to the activation of Ca2+-dependent signaling molecules that regulate transmitter release.

Androgen action in cell fate and communication during prostate development at single-cell resolution.

Androgens/androgen receptor (AR)-mediated signaling pathways are essential for prostate development, morphogenesis and regeneration. Specifically, stromal AR signaling has been shown to be essential for prostatic initiation. However, the molecular mechanisms underlying AR-initiated mesenchymal-epithelial interactions in prostate development remain unclear. Here, using a newly generated mouse model, we have directly addressed the fate and role of genetically marked AR-expressing cells during embryonic prostate development. Androgen signaling-initiated signaling pathways were identified in mesenchymal niche populations at single-cell transcriptomic resolution. The dynamic cell-signaling networks regulated by stromal AR were additionally characterized in relation to prostatic epithelial bud formation. Pseudotime analyses further revealed the differentiation trajectory and fate of AR-expressing cells in both prostatic mesenchymal and epithelial cell populations. Specifically, the cellular properties of Zeb1-expressing progenitors were assessed. Selective deletion of AR signaling in a subpopulation of mesenchymal rather than epithelial cells dysregulated the expression of the master regulators and significantly impaired prostatic bud formation. These data provide novel, high-resolution evidence demonstrating the important role of mesenchymal androgen signaling in the cellular niche controlling prostate early development by initiating dynamic mesenchyme-epithelia cell interactions.

Stromal androgen and hedgehog signaling regulates stem cell niches in pubertal prostate development.

Stromal androgen-receptor (AR) action is essential for prostate development, morphogenesis and regeneration. However, mechanisms underlying how stromal AR maintains the cell niche in support of pubertal prostatic epithelial growth are unknown. Here, using advanced mouse genetic tools, we demonstrate that selective deletion of stromal AR expression in prepubescent Shh-responsive Gli1-expressing cells significantly impedes pubertal prostate epithelial growth and development. Single-cell transcriptomic analyses showed that AR loss in these prepubescent Gli1-expressing cells dysregulates androgen signaling-initiated stromal-epithelial paracrine interactions, leading to growth retardation of pubertal prostate epithelia and significant development defects. Specifically, AR loss elevates Shh-signaling activation in both prostatic stromal and adjacent epithelial cells, directly inhibiting prostatic epithelial growth. Single-cell trajectory analyses further identified aberrant differentiation fates of prostatic epithelial cells directly altered by stromal AR deletion. In vivo recombination of AR-deficient stromal Gli1-lineage cells with wild-type prostatic epithelial cells failed to develop normal prostatic epithelia. These data demonstrate previously unidentified mechanisms underlying how stromal AR-signaling facilitates Shh-mediated cell niches in pubertal prostatic epithelial growth and development.

Olaparib enhances sensitization of BRCA-proficient breast cancer cells to x-rays and protons.

PURPOSE: This study aimed to compare the radiosensitizing effect of the PARP inhibitor, Olaparib, between proton and X-rays irradiations in BRCA-proficient breast cancer (BC) cells. METHODS: Two BRCA-proficient BC cell lines, MDA-MB-231 and T47D BC, were used. Cell proliferation was assessed using the CCK-8 assay, and radiosensitivity was determined through the clonogenic survival assay. Flow cytometry was employed to analyze cell cycle distribution and apoptosis. The kinetics of DNA damage repair were evaluated using γH2AX immunofluorescence imaging and the comet assay. Tumor spheroid assays were conducted to test radiosensitivity in a three-dimensional culture condition. RESULTS: Olaparib sensitized both MDA-MB-231 and T47D cells to proton and X-ray irradiation in the clonogenic assay. MDA-MB-231 cells exhibited a higher dose enhancement factor for Olaparib than T47D cells. Olaparib increased radiation-induced G2/M cell cycle arrest and apoptosis specifically in MDA-MB-231 cells. γH2AX immunostaining and the comet assay showed Olaparib augmented radiation-induced DNA damage and apoptosis. The enhancement effect of Olaparib was more pronounced in proton irradiation than in X-ray irradiation, particularly in MDA-MB-231 cells than T47D cells. Both radiation and Olaparib dose-dependently inhibited spheroid growth in both cell lines. The synergy scores demonstrated that Olaparib interacted more strongly with protons than X-rays. The addition of an ATR inhibitor further enhanced Olaparib-induced proton radiosensitization in MDA-MB-231 cells. CONCLUSION: This study found that Olaparib enhanced radiation efficacy in BRCA-proficient breast cancer cells, with a more pronounced effect observed with proton irradiation compared to X-ray irradiation. Combining Olaparib with an ATR inhibitor increased the radiosensitizing effect of protons.

Quantitative assessment of breast volume changes after whole-breast irradiation for breast cancer using breast auto-segmentation.

PURPOSE: This study aimed to quantitatively estimate the changes in breast volume associated with radiotherapy in patients undergoing breast-conserving surgery and whole-breast irradiation (WBI). METHODS: Pre-WBI simulation computed tomography (CT) scans and post-WBI follow-up chest CT scans from a total of 1,151 breast cancer patients were analyzed using a deep-learning-driven auto-segmentation approach. The CT-based asymmetry index (CTAI) was calculated by dividing the volume of the irradiated breast by the volume of the contralateral breast. Significant breast shrinkage was defined as a CTAI < 0.85. To quantify changes in CTAI over the follow-up period, the CTAI ratio was determined as the post-WBI CTAI divided by the pre-WBI CTAI. A multivariate logistic regression analysis was conducted to identify potential variables associated with post-WBI significant breast shrinkage. RESULTS: The median CTAI values for pre- and post-WBI CT scans were 0.973 (interquartile range: 0.887-1.069) and 0.866 (interquartile range: 0.773-0.967), respectively. The difference between them was statistically significant (p < 0.001). Following WBI, there was an increase in the rate of significant breast shrinkage from 16.3 to 44.8%. The CTAI ratio showed a negative association with the time interval (p < 0.001, Pearson r = - 0.310). In the multivariate logistic regression analysis, lower pre-WBI CTAI, younger age, and longer interval between CT scans were found to be significantly associated with a higher occurrence of post-WBI significant breast shrinkage. CONCLUSION: Breast volume decreases following WBI, and this decrease is correlated with an increased duration after WBI. These findings highlight the long-term consequences of WBI on breast asymmetry.

Effect of Sample Geometry on Graphitization of Polyacrylonitrile.

In this study, it is analyzed how sample geometry (spheres, nanofibers, or films) influences the graphitization behavior of polyacrylonitrile (PAN) molecules. The chemical bonding and changes in the composition of these three geometries are studied at the oxidation, carbonization, and graphitization stages via scanning electron microscopy (SEM), in situ thermogravimetric-infrared (TGA-IR) analysis, elemental analysis, Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). The influence of molecular alignment on the graphitization of the three sample geometries is investigated using synchrotron wide-angle X-ray diffraction (WAXD) and transmission electron microscopy (TEM). The effects of molecular alignment at different draw rates during spinning are explored in detail.

Risk Factors Affecting Clinical Outcomes of Low-risk Early-stage Human Papillomavirus-Associated Endocervical Adenocarcinoma Treated by Surgery Alone: Application of Silva Pattern.

This study aimed to report the clinical outcomes and risk factors for survival of patients with low-risk early-stage human papillomavirus-associated (HPVA) endocervical adenocarcinoma (EAC) treated with surgery alone. This retrospective study obtained the clinicopathological data of patients with early-stage HPVA EAC who underwent surgery between 2012 and 2018. The Silva pattern of invasion was determined by reviewing pathology slides. Locoregional recurrence-free survival (RFS), RFS, and overall survival were calculated, and the risk factors for survival were analyzed. One hundred seventeen patients with a median follow-up of 5.2 years (0.5-9.7 yr) were included. The most common histologic type was usual (94/117, 80.3%). The Silva pattern was A in 79 patients (67.5%), B in 30 (25.6%), and C in 8 (6.8%). The 5-year locoregional RFS, RFS, and overall survival rates were 92.4%, 87.8%, and 97.2%, respectively. The presence of intermediate-risk factors and Silva pattern C were significantly associated with worse survival. Based on these findings, patients were categorized into 2 groups: Group 1 (Silva pattern A or Silva pattern B without intermediate-risk factors) and Group 2 (Silva pattern B with intermediate-risk factors or Silva pattern C ). Group 2 showed significantly worse outcomes than Group 1, including the 5-year locoregional RFS (98.6% vs 68.0%), RFS (96.4% vs 54.6%), and overall survival (100.0% vs 86.5%). In conclusion, surgery alone for early-stage HPVA EAC resulted in favorable outcomes. Consideration of the Silva pattern, in addition to well-known risk factors, could help in precise risk group stratification of low-risk, early-stage HPVA EAC.

Chalazion-mimicked eyelid angiosarcoma in a young Asian with good prognosis: a case report.

BACKGROUND: Angiosarcoma is an extremely rare malignant tumor. So far, only about 42 cases of angiosarcoma involving the eyelids have been reported. Eyelid angiosarcoma occurs more frequently in elderly Caucasian males and is prone to misdiagnosis. We present a case report in a young Asian male patient with eyelid angiosarcoma that was misdiagnosed as a chalazion. CASE PRESENTATION: A 46-year-old South Korean male with no underlying disease had a right lower lid mass. The lesion was initially misdiagnosed as a chalazion at a local clinic, but a diagnosis of eyelid angiosarcoma was made after the first biopsy trial. PET-CT was performed to ensure that there was no metastasis in the whole body. Surgical excision with enough surgical margin was used alone for treatment and reconstruction was performed with a tarsoconjunctival advancement flap (modified Hughes procedure), which helped ensure good cosmesis. No recurrence was observed 4 years and 5 months after the surgery. CONCLUSIONS: The current study presents the first case of chalazion-mimicked eyelid angiosarcoma in a young Asian male aged under 50 years. This case shows that even if a benign eyelid disease is suspected in a young patient, an incisional biopsy must be performed to confirm whether the lesion is malignant. Since the prognosis is good for the case of eyelid angiosarcoma, if there is no clear evidence of distal metastasis, surgical resection should be performed with an enough safety margin.

Protective effect of the mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt extract on respiratory disorders.

Air pollutants, such as particulate matter (PM) and diesel exhaust particles (DEP), are associated with respiratory diseases. Therefore, preventive and therapeutic strategies against PM-and DEP (PM10D)-induced respiratory diseases are needed. Herein, we evaluate the protective effects of a mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt (LJH) extract against airway inflammation associated with exposure to PM10D. To determine the anti-inflammatory effects of the LJH extract, reactive oxygen species (ROS) production and the expression of inflammatory pathways were determined in PM10-induced MH-S cells. For the respiratory protective effects, BALB/c mice were exposed to PM10D via intranasal injection, and a mixture of L. plantarum KC3 and LJH extract was administered orally for 12 days. LJH extract inhibited ROS production and the phosphorylation of downstream factors of NF-κB in PM10-stimulated MH-S cells. The mixture of L. plantarum KC3 and LJH repressed the infiltration of neutrophils, reduced the immune cells number, and suppressed the proinflammatory mediators and cyclooxygenase (COX)-2 expressions in PM10D-induced airway inflammation with reduced phosphorylation of downstream factors of NF-κB. In addition, these effects were not observed in an alveolar macrophage depleted PM10D-induced mouse model using clodronate liposomes. The extract mixture also regulated gut microbiota in feces and upregulated the mRNA expression of Foxp3, transforming growth factor (TGF)-ß1, and interleukin (IL)-10 in the colon. The L. plantarum KC3 and LJH extract mixture may inhibit alveolar macrophage- and neutrophil-mediated inflammatory responses and regulate gut microbiota and immune response in PM10D-induced airway inflammation, suggesting it is a potential remedy to prevent and cure airway inflammation and respiratory disorders.

Mitigating Trunk Compensatory Movements in Post-Stroke Survivors through Visual Feedback during Robotic-Assisted Arm Reaching Exercises.

Trunk compensatory movements frequently manifest during robotic-assisted arm reaching exercises for upper limb rehabilitation following a stroke, potentially impeding functional recovery. These aberrant movements are prevalent among stroke survivors and can hinder their progress in rehabilitation, making it crucial to address this issue. This study evaluated the efficacy of visual feedback, facilitated by an RGB-D camera, in reducing trunk compensation. In total, 17 able-bodied individuals and 18 stroke survivors performed reaching tasks under unrestricted trunk conditions and visual feedback conditions. In the visual feedback modalities, the target position was synchronized with trunk movement at ratios where the target moved at the same speed, double, and triple the trunk's motion speed, providing real-time feedback to the participants. Notably, trunk compensatory movements were significantly diminished when the target moved at the same speed and double the trunk's motion speed. Furthermore, these conditions exhibited an increase in the task completion time and perceived exertion among stroke survivors. This outcome suggests that visual feedback effectively heightened the task difficulty, thereby discouraging unnecessary trunk motion. The findings underscore the pivotal role of customized visual feedback in correcting aberrant upper limb movements among stroke survivors, potentially contributing to the advancement of robotic-assisted rehabilitation strategies. These insights advocate for the integration of visual feedback into rehabilitation exercises, highlighting its potential to foster more effective recovery pathways for post-stroke individuals by minimizing undesired compensatory motions.

Gossypetin Prevents the Progression of Nonalcoholic Steatohepatitis by Regulating Oxidative Stress and AMP-Activated Protein Kinase.

Nonalcoholic steatohepatitis (NASH) is a severe liver metabolic disorder, however, there are still no effective and safe drugs for its treatment. Previous clinical trials used various therapeutic approaches to target individual pathologic mechanisms, but these approaches were unsuccessful because of the complex pathologic causes of NASH. Combinatory therapy in which two or more drugs are administered simultaneously to patients with NASH, however, carries the risk of side effects associated with each individual drug. To solve this problem, we identified gossypetin as an effective dual-targeting agent that activates AMP-activated protein kinase (AMPK) and decreases oxidative stress. Administration of gossypetin decreased hepatic steatosis, lobular inflammation and liver fibrosis in the liver tissue of mice with choline-deficient high-fat diet and methionine-choline deficient diet (MCD) diet-induced NASH. Gossypetin functioned directly as an antioxidant agent, decreasing hydrogen peroxide and palmitate-induced oxidative stress in the AML12 cells and liver tissue of MCD diet-fed mice without regulating the antioxidant response factors. In addition, gossypetin acted as a novel AMPK activator by binding to the allosteric drug and metabolite site, which stabilizes the activated structure of AMPK. Our findings demonstrate that gossypetin has the potential to serve as a novel therapeutic agent for nonalcoholic fatty liver disease /NASH. SIGNIFICANCE STATEMENT: This study demonstrates that gossypetin has preventive effect to progression of nonalcoholic steatohepatitis (NASH) as a novel AMP-activated protein kinase (AMPK) activator and antioxidants. Our findings indicate that simultaneous activation of AMPK and oxidative stress using gossypetin has the potential to serve as a novel therapeutic approach for nonalcoholic fatty liver disease /NASH patients.

Ultrathin Crystalline Silicon Nano and Micro Membranes with High Areal Density for Low-Cost Flexible Electronics.

Ultrathin crystalline silicon is widely used as an active material for high-performance, flexible, and stretchable electronics, from simple passive and active components to complex integrated circuits, due to its excellent electrical and mechanical properties. However, in contrast to conventional silicon wafer-based devices, ultrathin crystalline silicon-based electronics require an expensive and rather complicated fabrication process. Although silicon-on-insulator (SOI) wafers are commonly used to obtain a single layer of crystalline silicon, they are costly and difficult to process. Therefore, as an alternative to SOI wafers-based thin layers, here, a simple transfer method is proposed for printing ultrathin multiple crystalline silicon sheets with thicknesses between 300 nm to 13 µm and high areal density (>90%) from a single mother wafer. Theoretically, the silicon nano/micro membrane can be generated until the mother wafer is completely consumed. In addition, the electronic applications of silicon membranes are successfully demonstrated through the fabrication of a flexible solar cell and flexible NMOS transistor arrays.

Inhibition of the H3K27 demethylase UTX enhances the epigenetic silencing of HIV proviruses and induces HIV-1 DNA hypermethylation but fails to permanently block HIV reactivation.

One strategy for a functional cure of HIV-1 is "block and lock", which seeks to permanently suppress the rebound of quiescent HIV-1 by epigenetic silencing. For the bivalent promoter in the HIV LTR, both histone 3 lysine 27 tri-methylation (H3K27me3) and DNA methylation are associated with viral suppression, while H3K4 tri-methylation (H3K4me3) is correlated with viral expression. However, H3K27me3 is readily reversed upon activation of T-cells through the T-cell receptor. In an attempt to suppress latent HIV-1 in a stable fashion, we knocked down the expression or inhibited the activity of UTX/KDM6A, the major H3K27 demethylase, and investigated its impact on latent HIV-1 reactivation in T cells. Inhibition of UTX dramatically enhanced H3K27me3 levels at the HIV LTR and was associated with increased DNA methylation. In latently infected cells from patients, GSK-J4, which is a potent dual inhibitor of the H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A, effectively suppressed the reactivation of latent HIV-1 and also induced DNA methylation at specific sites in the 5'LTR of latent HIV-1 by the enhanced recruitment of DNMT3A to HIV-1. Nonetheless, suppression of HIV-1 through epigenetic silencing required the continued treatment with GSK-J4 and was rapidly reversed after removal of the drug. DNA methylation was also rapidly lost after removal of drug, suggesting active and rapid DNA-demethylation of the HIV LTR. Thus, induction of epigenetic silencing by histone and DNA methylation appears to be insufficient to permanently silence HIV-1 proviral transcription.

Involvement of Ca2+ in Signaling Mechanisms Mediating Muscarinic Inhibition of M Currents in Sympathetic Neurons.

Acetylcholine can excite neurons by suppressing M-type (KCNQ) potassium channels. This effect is mediated by M1 muscarinic receptors coupled to the Gq protein. Although PIP2 depletion and PKC activation have been strongly suggested to contribute to muscarinic inhibition of M currents (IM), direct evidence is lacking. We investigated the mechanism involved in muscarinic inhibition of IM with Ca2+ measurement and electrophysiological studies in both neuronal (rat sympathetic neurons) and heterologous (HEK cells expressing KCNQ2/KCNQ3) preparations. We found that muscarinic inhibition of IM was not blocked either by PIP2 or by calphostin C, a PKC inhibitor. We then examined whether muscarinic inhibition of IM uses multiple signaling pathways by blocking both PIP2 depletion and PKC activation. This maneuver, however, did not block muscarinic inhibition of IM. Additionally, muscarinic inhibition of IM was not prevented either by sequestering of G-protein ßγ subunits from Gα-transducin or anti-Gßγ antibody or by preventing intracellular trafficking of channel proteins with blebbistatin, a class-II myosin inhibitor. Finally, we re-examined the role of Ca2+ signals in muscarinic inhibition of IM. Ca2+ measurements showed that muscarinic stimulation increased intracellular Ca2+ and was comparable to the Ca2+ mobilizing effect of bradykinin. Accordingly, 20-mM of BAPTA significantly suppressed muscarinic inhibition of IM. In contrast, muscarinic inhibition of IM was completely insensitive to 20-mM EGTA. Taken together, these data suggest a role of Ca2+ signaling in muscarinic modulation of IM. The differential effects of EGTA and BAPTA imply that Ca2+ microdomains or spatially local Ca2+ signals contribute to inhibition of IM.

Non-immune and immune functions of interleukin-36γ suppress epithelial repair at the ocular surface.

Regulation of innate inflammation is critical for maintaining tissue homeostasis and barrier function, especially in those interfacing the external environments such as the skin and cornea. Expression of pro-inflammatory cytokines by injured tissues has been shown to exacerbate the inflammatory cascade, causing tissue damage. Interleukin 36, a subfamily of the IL-1 superfamily, consists of three pro-inflammatory agonists-IL36α, IL36ß, and IL36γ and an IL36 receptor antagonist (IL36Ra). The current investigation, for the first time, reports that IL36γ is the primary agonist expressed by the corneal epithelium, which is significantly upregulated following corneal injury. The function of IL36γ on non-immune cells, in addition to innate inflammatory cells, in regulating tissue homeostasis has not been well investigated. Using a loss-of-function approach via neutralizing antibody treatment, our data demonstrate that blocking endogenously expressed IL36γ in epithelial cells promotes rapid re-epithelialization in in vitro wound closure assay. Finally, by utilizing a naturally occurring antagonist IL36Ra in a well-established murine model of ocular injury, our study demonstrates that inhibition of IL36γ accelerates epithelial regeneration and suppresses tissue inflammation. Given rapid wound healing is critical for re-establishing normal tissue structure and function, our investigation on the function of IL36γ provides evidence for the development of novel IL36γ-targeting strategies to promote tissue repair.

Electrocardiogram-based deep learning algorithm for the screening of obstructive coronary artery disease.

BACKGROUND: Information on electrocardiogram (ECG) has not been quantified in obstructive coronary artery disease (ObCAD), despite the deep learning (DL) algorithm being proposed as an effective diagnostic tool for acute myocardial infarction (AMI). Therefore, this study adopted a DL algorithm to suggest the screening of ObCAD from ECG. METHODS: ECG voltage-time traces within a week from coronary angiography (CAG) were extracted for the patients who received CAG for suspected CAD in a single tertiary hospital from 2008 to 2020. After separating the AMI group, those were classified into ObCAD and non-ObCAD groups based on the CAG results. A DL-based model adopting ResNet was built to extract information from ECG data in the patients with ObCAD relative to those with non-ObCAD, and compared the performance with AMI. Moreover, subgroup analysis was conducted using ECG patterns of computer-assisted ECG interpretation. RESULTS: The DL model demonstrated modest performance in suggesting the probability of ObCAD but excellent performance in detecting AMI. The AUC of the ObCAD model adopting 1D ResNet was 0.693 and 0.923 in detecting AMI. The accuracy, sensitivity, specificity, and F1 score of the DL model for screening ObCAD were 0.638, 0.639, 0.636, and 0.634, respectively, while the figures were up to 0.885, 0.769, 0.921, and 0.758 for detecting AMI, respectively. Subgroup analysis showed that the difference between normal and abnormal/borderline ECG groups was not notable. CONCLUSIONS: ECG-based DL model showed fair performance for assessing ObCAD and it may serve as an adjunct to the pre-test probability in patients with suspected ObCAD during the initial evaluation. With further refinement and evaluation, ECG coupled with the DL algorithm may provide potential front-line screening support in the resource-intensive diagnostic pathways.

Patterns of regional recurrence according to molecular subtype in patients with pN2 breast cancer treated with limited field regional irradiation.

OBJECTIVE: There is little evidence regarding the radiotherapy modification based on molecular subtypes in breast cancer. This study aimed to identify the risk and patterns of regional recurrence according to molecular subtype in patients with pN2 breast cancer. METHODS: We identified 454 patients who underwent radical surgery for breast cancer with 4-9 axillary lymph node metastases. All patients underwent axillary lymph node dissection, adjuvant chemotherapy and limited-field regional nodal irradiation. The rates and patterns of regional recurrence were compared between the following three subgroups: luminal type (estrogen receptor- and/or progesterone receptor-positive), HER2-type (estrogen receptor- and progesterone receptor-negative and HER2-positive) and triple-negative type (estrogen receptor-, progesterone receptor- and HER2-negative). RESULTS: Regional recurrence occurred in 18/454 patients (4%). The risk of regional recurrence was higher in the triple-negative (hazard ratio 7.641) and HER2-type (hazard ratio 4.032) subtypes than in the luminal subtype. The predominant pattern of regional recurrence was inside the radiotherapy field in triple-negative breast cancer and outside the radiotherapy field in HER2-type and luminal-type cancers. CONCLUSIONS: In patients with pN2 breast cancer, the risk of regional recurrence was higher in the triple-negative and HER2-type than in the luminal type. In-field recurrence was predominant in triple-negative cancer, while out-field recurrence was frequent in luminal and HER2-type breast cancers.

Role of salvage radiotherapy for recurrent ovarian cancer.

OBJECTIVE: This study aimed to report clinical outcomes of salvage radiotherapy for recurrent ovarian cancer and identify predictors of clinical outcomes. METHODS: We retrospectively reviewed data of patients who received salvage radiotherapy for recurrent ovarian cancer between January 2011 and June 2021. Stereotactic body radiotherapy, involved-field radiotherapy with conventional fractionation, and non-involved-field radiotherapy with conventional fractionation were included in this study. Local failure-free survival, progression-free survival, chemotherapy-free survival, and overall survival were assessed. Additionally, potential prognostic factors for survival were analyzed. RESULTS: A total of 79 patients were included with 114 recurrent lesions. The median follow-up was 18.3 months (range 1.7-83). The 2-year local failure-free survival, progression-free survival, chemotherapy-free survival, and overall survival rates were 80.7%, 10.6%, 21.2%, and 74.7%, respectively. Pre-radiotherapy platinum resistance (hazard ratio (HR) 3.326, p<0.001) and short pre-radiotherapy CA-125 doubling time (HR 3.664, p<0.001) were associated with poor chemotherapy-free survival. The 1-year chemotherapy-free survival rates of patients with both risk factors, a single risk factor, and no risk factor were 0%, 20.4%, and 53.5%, respectively. The difference between risk groups was statistically significant: low risk versus intermediate risk (p<0.001) and intermediate risk versus high risk (p<0.001). CONCLUSIONS: Salvage radiotherapy for recurrent ovarian cancer resulted in local control with improved chemotherapy-free survival in carefully selected patients. Our results suggest that the consideration of pre-radiotherapy platinum resistance and pre-radiotherapy CA-125 doubling time could help with patient selection.