Search

The trend toward broadband communications in space is foreseeable, and its features predestine ATM as the basic mode of operation. Some of the low and medium earth orbit satellite concepts make use of intersatellite links (ISLs) to provide global connectivity with minimal usage of terrestrial fixed network resources. Interconnecting neighbouring satellites with ISLs results in a partially meshed switching subnetwork in space. The ISLs have a time-varying distance or may even lose sight of each other. This feature of the ISL topology dynamics significantly increases the complexity of connection-oriented network operation and routing. We deal with the routing problem to minimize the virtual path connection handover rate and path delay in the time-varying ISL subnetwork topology with ISL capacity constraints. A heuristic algorithm is proposed to deal with this problem, which is based on Lagrangean relaxation and dynamic programming. When there is sufficient capacity at every ISL, the algorithm produces an optimal solution easily using only dynamic programming. For evaluation of our algorithm, some computational results have been presented. These results show that our optimization algorithm can produce a solution close to an optimal solution when there exist ISL capacity constraints. Keywords: telecommunication; optimization; Lagrangean relaxation; dynamic programming; satellite; capacity constraints

Presents a model that delivers closed-form solutions for bond prices and a concave relationship between the interest rate and the yields. Alternative stochastic process of the interest; Analyses of the characteristics of the implied interest rate distribution; Empirical evidence of a nonlinear relationship between the short rate and the yields to maturity.

Purpose: This phase II study evaluated the efficacy and tolerability of onvansertib, a polo-like kinase 1 (PLK1) inhibitor, in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) + bevacizumab for the second-line treatment of KRAS -mutant metastatic colorectal cancer (mCRC)., Patients and Methods: This multicenter, open-label, single-arm study enrolled patients with KRAS -mutated mCRC previously treated with oxaliplatin and fluorouracil with or without bevacizumab. Patients received onvansertib (15 mg/m 2 once daily on days 1-5 and 15-19 of a 28-day cycle) and FOLFIRI + bevacizumab (days 1 and 15). The primary end point was the objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), duration of response (DOR), and tolerability. Translational and preclinical studies were conducted in KRAS -mutant CRC., Results: Among the 53 patients treated, the confirmed ORR was 26.4% (95% CI, 15.3 to 40.3). The median DOR was 11.7 months (95% CI, 9.4 to not reached). Grade 3/4 adverse events were reported in 62% of patients. A post hoc analysis revealed that patients with no prior bevacizumab treatment had a significantly higher ORR and longer PFS compared with patients with prior bevacizumab treatment: ORR of 76.9% versus 10.0% (odds ratio of 30.0, P < .001) and median PFS of 14.9 months versus 6.6 months (hazard ratio of 0.16, P < .001). Our translational findings support that prior bevacizumab exposure contributes to onvansertib resistance. Preclinically, we showed that onvansertib inhibited the hypoxia pathway and exhibited robust antitumor activity in combination with bevacizumab through the inhibition of angiogenesis., Conclusion: Onvansertib in combination with FOLFIRI + bevacizumab showed significant activity in the second-line treatment of patients with KRAS -mutant mCRC, particularly in patients with no prior bevacizumab treatment. These findings led to the evaluation of the combination in the first-line setting (ClinicalTrails.gov identifier: NCT06106308).

Diagnosing cancer in its early stages can play an important role in prolonging the lifespan of patients, which demands the use of powerful tools to detect biomarkers accurately. However, since most fluorescent probes described for cancer diagnosis are limited to recognizing a single molecule, achieving the high accuracy criteria remains difficult. Here, sensor 1 is constructed for the sequential detection of D , ONOO - , and viscosity. Initially, sensor 1 detected D and underwent an intramolecular charge transfer mechanism, resulting in the formation of 2 and fluorescence quenching at 587 nm. Subsequently, the intermediate ( 2 ) monitored ONOO - and reproduced sensor 1 reversibly with fluorescence enhancement at 496 nm, showing concentration-related quantitative analysis. Similar sensing processes were observed in monitoring ONOO - and viscosity by synthetically developed sensor 2 . The proposed mechanisms of sensors 1 and 2 are verified through various characterizations ( 1 H NMR, HR-MS, and HPLC) and DFT calculations. Investigations on endogenous ONOO - and mitochondrial viscosity in cancer (HeLa) and normal (NCM460) cells were conducted to distinguish cancerous cells from normal cells. We anticipated that sensor 2 could effectively serve as a reliable bioanalytical reagent for cancer diagnosis at an earlier stage through sequential detection of two cancer markers, ONOO - and mitochondrial viscosity, in living cells. Importantly, sensor 2 has been employed for imaging ONOO - in normal and liver injury mouse models and tissues, achieving outstanding results.

We performed intra- and intermolecular charge transfer (CT) excitation energy calculations of (a) conjugated carbon chain [H 2 N-(CH=CH) n -X] and (b) its equidistant H 2 NH∙∙∙H X ( n = 2~8) with various electron acceptors ( X = NH 2 , OH, Cl, CHO, CN, and NO 2 ) using EOM-CCSD, time-dependent (TD) Hartree-Fock (HF) and various density functional theory (DFT) functionals, such as BLYP, B3LYP, long-range corrected (LC) DFT, and LC-DFT with an optimally tuned (OT) range separation parameter ( µ ) using Koopman's theorem to investigate the effect of the electron-withdrawing (or -donating) strength of end-capped functional group ( X ) and CT distance ( R ) on intra- and intermolecular CT excitation energies. As the electron-withdrawing strength of X increases, both intra- and intermolecular CT excitation energies tend to decrease, since energy gaps between orbitals corresponding to CT excitations (e.g., HOMO and LUMO) decrease. However, the effect of the electron-withdrawing group on intramolecular CT excitation energy is negligible (at most 0.5 eV). OT-LC-DFT shows accurate intermolecular CT excitation energy, but worse results in intramolecular CT excitation energy than LC-DFT with the default µ value (0.47). Therefore, we conclude that the optimal tuning method is not effective in predicting intramolecular CT excitation energy. While intermolecular CT excitation energy has excitonic binding energy with asymptotic behavior to CT distance that is not affected by the choice of range separation parameter, intramolecular CT excitation energy is affected by orbital relaxation energy, which strongly depends on the choice of range separation parameter, which makes the OT method of range separation parameter ineffective in predicting intramolecular CT excitation energy as well as local excitation with high accuracy.

Conventional DRAM, consisting of one transistor and one capacitor (1T1C), requires periodic data refresh processes due to its limited retention time and data-destructive read operation. Here, we propose and demonstrate a novel 3D-DRAM memory scheme available with a single transistor and a single ferroelectric field-effect transistor (FeFET) DRAM (2T0C-FeDRAM), which offers extended retention time and non-destructive read operation. This architecture uses a back-end-of-line (BEOL)-compatible amorphous oxide semiconductor (AOS) that is suitable for increasing DRAM cell density. Notably, the device structures of a double gate a-ITZO/a-IGZO FeFET, used for data storage and reading, are engineered to achieve an enlarged memory window (MW) of 1.5 V and a prolonged retention time of 10 4 s. This is accomplished by a double gate and an a-ITZO/a-IGZO heterostructure channel to enable efficient polarization control in hafnium-zirconium oxide (HZO) layers. We present successful program/erase operations of the double gate a-ITZO/a-IGZO FeFET through incremental step pulse programming (ISPP), demonstrating multi-level states with remarkable retention characteristics. Most importantly, we perform 2T0C-FeDRAM operations by electrically connecting the double gate a-ITZO/a-IGZO FeFET and the a-ITZO FET. Leveraging the impressive performance of the double gate a-ITZO/a-IGZO FeFET technology, we have effectively showcased an exceptionally record-long retention time exceeding 2000 s and 4-bit multi-level states, positioning it as a robust contender among emerging memory solutions in the era of artificial intelligence.

In the previous work, LCgau-core-BOP, which includes the short-range interelectronic Gaussian attenuating Hartree-Fock (HF) exchange to the long-range HF exchange, showed high accuracy core-excitation energies from 1s orbitals of the second-row atoms (1s → π*, 1s → σ*, 1s → n *, and 1s → Rydberg), but underestimates the core-excitation energies from 1s orbitals of the third-row atoms. To improve this, we added one more Gaussian attenuating HF exchange to LCgau-core-BOP. We named it LC2gau-core-BOP, which achieves a mean absolute error (MAE) of 0.6 and 0.3 eV for core excitation energies of the second- and third-row atoms of the tested small molecules, respectively. We found that the inclusion of the short-range interelectronic HF exchange at a distance ranging from 0.2 to 0.6 a.u. contributes to the increase of performances on 1s orbital energy calculations of the second-row atoms, while the inclusion of more short-range interelectronic HF exchange at a distance ranging from 0 to 0.2 a.u. does to the increase of performance on 1s orbital energy calculations of the third-row atoms. It is notable that all of these improvements were accomplished using flexible Gaussian attenuating HF exchange inclusion. LC2gau-core-BOP shows deviations of less than 0.8 eV from experimental values for all of the core-excitation energies of the tested medium-size molecules consisting of thymine, oxazole, glycine, and dibenzothiophene sulfone. Moreover, by optimizing one parameter of the OP correlation functional, LC2gau-core-BOP provides atomization energies over the G3 test set with an accuracy comparable to that of B3LYP.

Background: The investigation of circulating tumor DNA (ctDNA) as a substitute for minimal residual disease (MRD) has been a central focus in various clinical trials, with findings highlighting its effectiveness as a sensitive marker for detecting recurrence. In 2018, a joint review by the American Society of Clinical Oncology and the College of American Pathologists acknowledged a lack of current evidence guiding clinical decisions regarding ctDNA. Nevertheless, there are a multitude of ongoing studies exploring the future applications of ctDNA and its role in clinical decision making for select patient populations., Case Description: The case presented involves a patient with Lynch syndrome who developed synchronous left-sided colorectal cancers (CRC). Each primary malignancy exhibited a distinct mutational profile, introducing complexity to the personalized tumor-informed assays used for quantifying ctDNA levels. Initial ctDNA levels were negative until the assay was calibrated to the transverse colon primary tumor. Unfortunately, surveillance imaging showed radiographic recurrence coinciding with positive ctDNA findings. Treatment with the anti-PD-1 inhibitor pembrolizumab was initiated, resulting in the clearance of ctDNA after just four cycles. As of now, there is no radiographic or biologic evidence indicating disease recurrence., Conclusions: This case study sheds light on the evolving landscape and current limitations of ctDNA as a surrogate for MRD. We describe a patient with synchronous CRC who had radiographic recurrence and a negative MRD assay. Current tumor-informed assays are limited in their capacity to detect a single tumor, and by nature can miss both synchronous and metachronous malignancies. Assays tailored to multiple tumors or utilizing tumor agnostic methods should be a part of clinical decision making in this patient population., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-81/coif). D.H.A. reports that he receives consulting fees from Exelixis, Genentech, Eisai, Advanced Accelerator Applications, Daiichi Sankyo, and holds stock or stock options in Natera. The other authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)

Microbial lysates, rich in protein and essential nutrients, demonstrate remarkable capabilities in forming gels and stable foams when heated and whisked, similar to liquid eggs. These characteristics make them an excellent alternative to animal-derived liquid eggs, contributing to sustainable food production and consumption while maintaining high nutritional value. Their versatility positions microbial lysates as promising ingredients in culinary applications, offering a sustainable and nutritious substitute., (© 2024. The Author(s).)

Monolithic integration of III-V quantum dot (QD) lasers onto a Si substrate is a scalable and reliable approach for obtaining highly efficient light sources for Si photonics. Recently, a combination of optimized GaAs buffers and QD gain materials resulted in monolithically integrated butt-coupled lasers on Si. However, the use of thick GaAs buffers up to 3 μm not only hinders accurate vertical alignment to the Si optical waveguide but also imposes considerable growth costs and time constraints. Here, for the first time, we demonstrate InAs QD lasers epitaxially grown on a 700 nm thick GaAs/Si template, which is approximately four times thinner than the conventional III-V buffers on Si. The optimized 700 nm GaAs buffer yields a remarkably smooth surface and low threading dislocation density of 4 × 10 8 cm -2 , which is sufficient for QD laser growth. The InAs QD lasers fabricated on these ultrathin templates still lase at room temperature with a threshold current density of 661 A/cm 2 and a characteristic temperature of 50 K. We believe that these results are important for the monolithically integrated III-V QD lasers for Si photonics applications.

Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform., (© 2024. The Author(s).)

Purpose: Onvansertib is a highly specific inhibitor of polo-like kinase 1 (PLK1), with demonstrated safety in solid tumors. We evaluated, preclinically and clinically, the potential of onvansertib in combination with chemotherapy as a therapeutic option for KRAS-mutant colorectal cancer., Patients and Methods: Preclinical activity of onvansertib was assessed (i) in vitro in KRAS wild-type and -mutant isogenic colorectal cancer cells and (ii) in vivo, in combination with irinotecan, in a KRAS-mutant xenograft model. Clinically, a phase Ib trial was conducted to investigate onvansertib at doses 12, 15, and 18 mg/m2 (days 1-5 and 14-19 of a 28-day cycle) in combination with FOLFIRI/bevacizumab (days 1 and 15) in patients with KRAS-mutant metastatic colorectal cancer who had prior oxaliplatin exposure. Safety, efficacy, and changes in circulating tumor DNA (ctDNA) were assessed., Results: In preclinical models, onvansertib displayed superior activity in KRAS-mutant than wild-type isogenic colorectal cancer cells and demonstrated potent antitumor activity in combination with irinotecan in vivo. Eighteen patients enrolled in the phase Ib study. Onvansertib recommended phase II dose was established at 15 mg/m2. Grade 3 and 4 adverse events (AE) represented 15% of all treatment-related AEs, with neutropenia being the most common. Partial responses were observed in 44% of patients, with a median duration of response of 9.5 months. Early ctDNA dynamics were predictive of treatment efficacy., Conclusions: Onvansertib combined with FOLIFRI/bevacizumab exhibited manageable safety and promising efficacy in second-line treatment of patients with KRAS-mutant metastatic colorectal cancer. Further exploration of this combination therapy is ongoing. See related commentary by Stebbing and Bullock, p. 2005., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. Methods: A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints. Patient advocates were central to discussions, which evaluated endpoints according to regulatory standards and the FDA's 'feels, functions, survives' criteria. Results: Three themes emerged: 1 ) consensus on endpoints mirroring the lived experiences of patients with IPF; 2 ) consideration of replacing forced vital capacity (FVC) as the primary endpoint, potentially by composite endpoints that include 'feels, functions, survives' measures or FVC as components; 3 ) support for simplified, user-friendly patient-reported outcomes (PROs) as either components of primary composite endpoints or key secondary endpoints, supplemented by functional tests as secondary endpoints and novel biomarkers as supportive measures (FDA Guidance for Industry (Multiple Endpoints in Clinical Trials) available at: https://www.fda.gov/media/162416/download). Conclusions: This report, detailing the proceedings of this pivotal symposium, suggests a potential turning point in designing future IPF clinical trials more attuned to outcomes meaningful to patients, and documents the collective agreement across multidisciplinary stakeholders on the importance of anchoring IPF trial endpoints on real patient experiences-namely, how they feel, function, and survive. There is considerable optimism that clinical care in IPF will progress through trials focused on patient-centric insights, ultimately guiding transformative treatment strategies to enhance patients' quality of life and survival.

2 µm photonics and optoelectronics is promising for potential applications such as optical communications, LiDAR, and chemical sensing. While the research on 2 µm detectors is on the rise, the development of InP-based 2 µm gain materials with 0D nanostructures is rather stalled. Here, we demonstrate low-threshold, continuous wave lasing at 2 µm wavelength from InAs quantum dash/InP lasers enabled by punctuated growth of the quantum structure. We demonstrate low threshold current densities from the 7.1 µm width ridge-waveguide lasers, with values of 657, 1183, and 1944 A/cm 2 under short pulse wave (SPW), quasi-continuous wave (QCW), and continuous wave operation. The lasers also exhibited good thermal stability, with a characteristic temperature T0 of 43 K under SPW mode. The lasing spectra is centered at 1.97 µm, coinciding with the ground-state emission observed from photoluminescence studies. We believe that the InAs quantum dash/InP lasers emitting near 2 µm will be a key enabling technology for 2 µm communication and sensing.

What Is This Summary About?: This summary describes the results from a phase 2 study called FOENIXCCA2. The study evaluated treatment with futibatinib in people with a rare form of advanced bile duct cancer called intrahepatic cholangiocarcinoma (or iCCA), where the tumors have changes in the structure of a gene called FGFR2. These changes include FGFR2 gene fusions. Bile duct cancer often returns after surgery or cannot be treated by surgery because the tumor has spread, so it requires treatment with chemotherapy. People live for a median of 1 year after their first chemotherapy treatment and 6 months after their second treatment. This study included people whose cancer had grown/spread after one or more chemotherapy treatments. The aims of the study were to see if futibatinib could shrink the size of tumors and stop the cancer from growing/spreading and to see how long people lived when treated with futibatinib. Clinicians also looked at side effects from taking futibatinib and at how it affected people's quality of life., What Were the Results?: Futibatinib treatment shrank tumors in over 80% of people who received treatment. Tumors shrank by at least 30% in 42% of people. Futibatinib stopped tumors from growing/spreading for a median of 9.7 months. People who took the medicine lived for a median of 21.7 months, and 72% of people were still alive after 1 year. Side effects from taking futibatinib were like those reported for similar medicines, and clinicians considered the side effects to be manageable by adjusting the dose of futibatinib or treating the side effects. Most people reported that their quality of life stayed the same or improved during the first 9 months of taking futibatinib., What Do the Results Mean?: The results support the use of futibatinib for treating people with advanced bile duct cancer. Based on the results of this study, futibatinib is now approved in the US, Europe, and Japan. Futibatinib is approved for treating adults with advanced bile duct cancer who have received previous treatment for their cancer, and whose tumors have a gene fusion or other change in the FGFR2 gene. Clinical Trial Registration: NCT02052778 (FOENIX-CCA2).

Background: Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC 50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient's groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test., Methods: On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides., Results: The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response., Conclusions: Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform., (© 2023. The Author(s).)

This study was to investigate the anti-inflammatory activity of ethanolic extract of Sargassum confusum (SCEE). LPS is recognized by TLR4 on the macrophage surface, which activates the NF-κB and MAPK signaling pathways, increasing the expression of inflammatory cytokine like interleukin-6 (IL-6), IL-1β, and tumor necrosis factor (TNF)-α and inflammatory mediators such as nitric oxide (NO) and cyclooxygenase-2 (COX-2). The anti-inflammatory effect of SCEE (0, 1, 10, 50 μg/mL) was identified using LPS stimulated RAW 264.7 macrophages. As a result, it was confirmed that inflammatory factors were suppressed by inhibiting expression of COX-2 and iNOS without any cytotoxicity. In addition, phosphorylation of ERK, JNK and NF-κB p65, transcription factors, were inhibited by SCEE does-dependent manner. These results suggest that SCEE has an anti-inflammatory effect and can be used as a material for health functional foods to prevent inflammatory diseases., Competing Interests: Conflict of interestThe authors declare they have no conflict of interest., (© The Korean Society of Food Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Organic light-emitting diode (OLED) microdisplays have received great attention owing to their excellent performance for augmented reality/virtual reality devices applications. However, high pixel density of OLED microdisplay causes electrical crosstalk, resulting in color distortion. This study investigated the current crosstalk ratio and changes in the color gamut caused by electrical crosstalk between sub-pixels in high-resolution full-color OLED microdisplays. A pixel structure of 3147 pixels per inch (PPI) with four sub-pixels and a single-stack white OLED with red, green, and blue color filters were used for the electrical crosstalk simulation. The results showed that the sheet resistance of the top and bottom electrodes of OLEDs rarely affected the electrical crosstalk. However, the current crosstalk ratio increased dramatically and the color gamut decreased as the sheet resistance of the common organic layer decreased. Furthermore, the color gamut of the OLED microdisplay decreased as the pixel density of the panel increased from 200 to 5000 PPI. Additionally, we fabricated a sub-pixel circuit to measure the electrical crosstalk current using a 3147 PPI scale multi-finger-type pixel structure and compared it with the simulation result., (© 2023. Springer Nature Limited.)

Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement response criteria to evaluate their prognostic effect on overall survival (OS)., Patients and Methods: Patients enrolled in 17 first-line clinical trials, who had mCRC with ≥ 2 lesions at baseline, and a restaging scan by 12 weeks were included. For each patient, lesions were categorized as a progressing lesion (PL: > 20% increase in the longest diameter (LD)), responding lesion (RL: > 30% decrease in LD), or stable lesion (SL: neither PL nor RL) based on the 12-week scan. Lesion-based response criteria were defined for each patient as follows: PL only, SL only, RL only, and varied responses (mixture of RL, SL, and PL). Lesion-based response criteria and OS were correlated using stratified multivariable Cox models. The concordance between OS and classifications was measured using the C statistic., Results: Among 10,551 patients with mCRC from 17 first-line studies, varied responses were noted in 51.6% of patients, among whom, 3.3% had RL/PL at 12 weeks. Among patients with RL/SL, 52% had stable disease (SD) by RECIST 1.1, and they had a longer OS (median OS (mOS) = 19.9 months) than those with SL only (mOS = 16.8 months, HR (95% CI) = 0.81 (0.76, 0.85), p < 0.001), although a shorter OS than those with RL only (mOS = 25.8 months, HR (95% CI) = 1.42 (1.32, 1.53), p < 0.001). Among patients with SL/PL, 74% had SD by RECIST 1.1, and they had a longer OS (mOS = 9.0 months) than those with PL only (mOS = 8.0 months, HR (95% CI) = 0.75 (0.57, 0.98), p = 0.040), yet a shorter OS than those with SL only (mOS = 16.8 months, HR (95% CI) = 1.98 (1.80, 2.18), p < 0.001). These associations were consistent across treatment regimen subgroups. The lesion-based response criteria showed slightly higher concordance than RECIST 1.1, although it was not statistically significant., Conclusion: Varied responses at first restaging are common among patients receiving first-line therapy for mCRC. Our lesion-based measurement criteria allowed for better mortality discrimination, which could potentially be informative for treatment decision-making and influence patient outcomes.

Background: For patients with resected stage III colon cancer, 6 months of adjuvant fluoropyrimidine-based chemotherapy has been the standard of care. The IDEA collaboration aimed to evaluate whether 3 months of adjuvant chemotherapy was noninferior to 6 months. Despite failing to meet its primary endpoint, the subgroup analyses demonstrated noninferiority based on regimen and treatment duration when a risk-stratified approach was used., Patients and Methods: To evaluate the impact of the results of the IDEA collaboration, we evaluated adjuvant chemotherapy prescribing practice patterns, including planned adjuvant treatment regimen and duration from January 1, 2016, to January 31, 2021. The time period was selected to evaluate chemotherapy prescribing patterns prior to the abstract presentation of the IDEA collaboration in June 2017 and after full manuscript publication in March 2018., Results: A total of 399 patients with stage III colon cancer who received adjuvant chemotherapy were included in the analysis. A significant increasing trend for use of 3 months of adjuvant chemotherapy was observed after presentation of the IDEA abstract (P<.001). A significant change in CAPOX (capecitabine/oxaliplatin) prescribing was also observed, increasing from 14% of patients prior to presentation of the IDEA abstract to 48% after presentation (P<.001). Comparing 3 months of CAPOX with 6 months of FOLFOX (fluorouracil/leucovorin/oxaliplatin), 3 months of CAPOX use also steadily increased over time (adjusted odds ratio [aOR], 1.28; 95% CI, 1.20-1.37; P<.001). Among subgroups of interest, no differences in adoption of CAPOX were observed. The adoption of 3 months of CAPOX was similar in patients with low-risk cancer (aOR, 1.27; 95% CI, 1.17-1.37) and those with high-risk cancer (aOR, 1.31; 95% CI, 1.16-1.47)., Conclusions: Despite the IDEA collaboration failing to demonstrate noninferiority of 3 months' duration of adjuvant therapy compared with 6 months, the findings have influenced practice prescribing patterns, favoring CAPOX and a shorter duration of planned adjuvant treatment.

Background and Objective: Immune checkpoint inhibitors (ICI) were a major clinical advancement that provided an opportunity to improve the prognosis of patients with non-small cell lung cancer (NSCLC). However, programmed death-ligand-1 (PD-L1) expression does not sufficiently predict ICI efficacy in NSCLC patients. In recent studies, the tumor immune microenvironment (TIME) was shown to have a central role in lung cancer progression and to affect clinical outcome of patients diagnosed with lung cancer. As development of new therapeutic targets to overcome ICI resistance is a priority, understanding the TIME is important. Recently, a series of studies was conducted to target each component of TIME to improve efficacy of cancer treatment. In this review, important features related to TIME, its heterogeneity and current trends in treatment targeting the component of TIME are discussed., Methods: PubMed and PMC were searched from January 1st, 2012 to August 16th, 2022 using the following key words: "NSCLC", "Tumor microenvironment", "Immune", "Metastasis" and "Heterogeneity"., Key Content and Findings: Heterogeneity in the TIME can be either spatial or temporal. Subsequent to heterogeneous changes in the TIME, treatment of lung cancer can be more challenging because drug resistance is more likely to occur. In terms of the TIME, the main concept for increasing the chance of successful NSCLC treatment is to activate immune responses against tumor cells and inhibit immunosuppressive activities. In addition, relevant research is focused on normalizing an otherwise aberrant TIME in NSCLC patients. Potential therapeutic targets include immune cells, cytokine interactions, and non-immune cells such as fibroblasts or vessels., Conclusions: In management of lung cancer, understanding TIME and its heterogeneity is significant to treatment outcomes. Ongoing trials including various treatment modalities such as radiotherapy, cytotoxic chemotherapy, and anti-angiogenic treatment and regimens inhibiting other immunoinhibitory molecules are promising., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-633/coif). SJK reports that this research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. 2019M3A9H2032425). The other authors have no conflicts of interest to declare., (2023 Translational Lung Cancer Research. All rights reserved.)

Atopic dermatitis (AD) is a chronic inflammation associated with skin hypersensitivity caused by environmental factors. The objent of this study was to assess the hot water extracts of Sargassum horneri (SHHWE) on AD. AD was induced by spreading 2,4-dinitrochlorobenzene (DNCB) on the BALB/c mice. The efficacy of SHHWE was tested by observing the immunoglobulin E (IgE), cytokine, skin clinical severity score and cytokine secretions in concanavalin A (Con A)-stimulated splenocytes. The levels of interleukine (IL)-4, IL-5 and IgE, the pro-inflammatory cytokines that are closely related, were notably suppressed in a does-dependent manner by SHHWE, whereas the level of interferon γ (IFN-γ), the atopy-related Th1 cytokine inhibiting the production of Th2 cytokines, was increased. Therefore, these results show that SHHWE has a potent anti-inhibitory effect on AD and is highly valuable for cosmetic development.

Bio-based production of chemicals and materials has attracted much attention due to the urgent need to establish sustainability and enhance human health. Metabolic engineering (ME) allows purposeful modification of cellular metabolic, regulatory, and signaling networks to achieve enhanced production of desired chemicals and degradation of environmentally harmful chemicals. ME has significantly progressed over the past 30 years through further integration of the strategies of synthetic biology, systems biology, evolutionary engineering, and data science aided by artificial intelligence. Here we review the field of ME from its emergence to the current state-of-the-art, highlighting its contribution to sustainable production of chemicals, health, and the environment through representative examples. Future challenges of ME and perspectives are also discussed., Competing Interests: Declaration of interests The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: The objective of this study was to analyze the microbial profile of individuals with peri-implantitis (PI) compared to those of periodontally healthy (PH) subjects and periodontitis (PT) subjects using Illumina sequencing., Methods: Buccal, supragingival, and subgingival plaque samples were collected from 109 subjects (PH: 30, PT: 49, and PI: 30). The V3-V4 region of 16S rRNA was sequenced and analyzed to profile the plaque microbiota., Results: Microbial community diversity in the PI group was higher than in the other groups, and the 3 groups showed significantly separated clusters in the buccal samples. The PI group showed different patterns of relative abundance from those in the PH and PT groups depending on the sampling site at both genus and phylum levels. In all samples, some bacterial species presented considerably higher relative abundances in the PI group than in the PH and PT groups, including Anaerotignum lactatifermentans , Bacteroides vulgatus , Faecalibacterium prausnitzii , Olsenella uli , Parasutterella excrementihominis , Prevotella buccae , Pseudoramibacter alactolyticus , Treponema parvum , and Slackia exigua . Network analysis identified that several well-known periodontal pathogens and newly recognized bacteria were closely correlated with each other., Conclusions: The composition of the microbiota was considerably different in PI subjects compared to PH and PT subjects, and these results could shed light on the mechanisms involved in the development of PI., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2023. Korean Academy of Periodontology.)

Scrub typhus is an acute febrile, mite-borne disease endemic to the Asia-Pacific region. In South Korea, it is a seasonal disease that occurs frequently in the autumn, and its incidence has increased steadily. In this study, we used a liquid chromatography and flow injection analysis-tandem mass spectrometry-based targeted urine metabolomics approach to evaluate the host response to Orientia tsutsugamushi infection. Balb/c mice were infected with O. tsutsugamushi Boryong, and their urine metabolite profile was examined. Metabolites that differed significantly between the experimental groups were identified using the Kruskal-Wallis test. Sixty-five differential metabolites were identified. The principal metabolite classes were acylcarnitines, glycerophospholipids, biogenic amines, and amino acids. An ingenuity pathway analysis revealed that several toxic (cardiotoxic, hepatotoxic, and nephrotoxic) metabolites are induced by scrub typhus infection. This is the first report of urinary metabolite biomarkers of scrub typhus infection and it enhances our understanding of the metabolic pathways involved.

Although attention deficit hyperactivity disorder (ADHD) in children is rising worldwide, fewer studies have focused on screening than on the treatment of ADHD. Most previous similar ADHD classification studies classified only ADHD and normal classes. However, medical professionals believe that better distinguishing the ADHD-RISK class will assist them socially and medically. We created a projection-based game in which we can see stimuli and responses to better understand children's abnormal behavior. The developed screening game is divided into 11 stages. Children play five games. Each game is divided into waiting and game stages; thus, 10 stages are created, and the additional waiting stage includes an explanation stage where the robot waits while explaining the first game. Herein, we classified normal, ADHD-RISK, and ADHD using skeleton data obtained through games for ADHD screening of children and a bidirectional long short-term memory-based deep learning model. We verified the importance of each stage by passing the feature for each stage through the channel attention layer. Consequently, the final classification accuracy of the three classes was 98.15% using bi-directional LSTM with channel attention model. Additionally, the attention scores obtained through the channel attention layer indicated that the data in the latter part of the game are heavily involved in learning the ADHD-RISK case. These results imply that for ADHD-RISK, the game is repeated, and children's attention decreases as they progress to the second half.

We demonstrate the programmable light intensity of a micro-LED by compensating threshold voltage variability of thin-film transistors (TFTs) by introducing a non-volatile programmable ferroelectric material, HfZrO 2 (HZO) into the gate stack of the TFT. We fabricated an amorphous ITZO TFT, ferroelectric TFTs (FeTFTs), and micro-LEDs and verified the feasibility of our proposed current-driving active matrix circuit. Importantly, we successfully present the programmed multi-level lighting of the micro-LED, utilizing partial polarization switching in the a-ITZO FeTFT. We expect that this approach will be highly promising for the next-generation display technology, replacing complicated threshold voltage compensation circuits with a simple a-ITZO FeTFT., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Despite multiple randomized trials, the role of perioperative chemotherapy in colorectal cancer liver metastasis (CRLM) is still under debate. In this systematic review and network meta-analysis (NMA), we aim to evaluate the efficacy of perioperative systemic therapies for patients with CRLM., Methods: We searched various databases for abstracts and full-text articles published from database inception through May 2021.We included randomized controlled trials (RCTs) comparing the addition of perioperative (post, pre, or both) systemic therapies to surgery alone in patients with CRLM. The outcomes were compared according to the chemotherapy regimen using a random effects model. Outcomes of interest included disease-free survival (DFS) and overall survival (OS)., Results: Seven RCTs with a total of 1504 patients with CRLM were included. Six studies included post-operative treatment and one evaluated perioperative (pre- and postoperative) therapy. Fluoropyrimidine-based chemotherapy was the most used systemic therapy. NMA showed benefit of adding perioperative therapy to surgery in terms of DFS (HR 0.73, 95% CI 0.63 to 0.84). However, these findings did not translate into a statistically significant OS benefit (HR 0.88, 95% CI 0.74 to 1.05). NMA did not show any advantage of one regimen over another including oxaliplatin or irinotecan., Conclusions: This systematic review and NMA of 7 RCTs found that the addition of perioperative systemic treatment for resectable CRLM could improve disease-free survival but not overall survival. Based on the findings, addition of perioperative treatment in resectable CRLM should be individualized weighing the risks and benefits., (© The Author(s) 2022. Published by Oxford University Press.)

Using ozonesonde measurements from 2015 to 2018 at the Jang Bogo station located in the southeastern Antarctic region, we evaluate ozone profiles retrieved from the three satellite measurements that are widely used: Ozone Monitoring Instrument (OMI), Microwave Limb Sounder (MLS), and Ozone Mapping Profiler Suite (OMPS) data. For the fair validation, ozonesonde profiles are smoothed using the weighting function of each satellite retrieval algorithm (i.e., convolution process). Compared with limb-viewing MLS and OMPS ozone profiles, the OMI ozone profiles are relatively less qualified: coarser vertical resolution and larger inter-annual variation. Nevertheless, our validation reveals that the quality of all three satellite ozone profiles looks comparable; In general, difference from ozonesonde profile is ∼1 ppm absolutely, and -20 to 30% relatively at maximum. This quantitative range well corresponds to previous work, meaning that our new validation confirms the reliability of satellite ozone profiles in the southeastern Antarctic region where the measurement data for the validation were not enough. Another interesting feature is the role of a priori ozone profile; Nadir-viewing OMI satellite can have qualified ozone profiles by a proper assumption of a priori ozone profile. Since the performance of limb-viewing ozone profiles is better, however, the careful usage of nadir-viewing ozone profile is still required. We think that the simultaneous usage of multiple satellite ozone profiles can contribute to better understanding of Antarctic ozone characteristics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

(1) Background: Cabozantinib, a multikinase inhibitor, is approved by the Food and Drug Administration (FDA) for the treatment of advanced hepatocellular carcinoma (HCC) following progression on sorafenib. Recently, atezolizumab plus bevacizumab has been approved in the first line setting for advanced HCC and has become the new standard of care. Whether cabozantinib improves outcomes following progression on immunotherapy remains unknown. We describe the clinical outcomes following treatment with immunotherapy in patients with advanced HCC who received cabozantinib. (2) Methods: We conducted a multicentric, retrospective analysis of patients with advanced HCC diagnosed between 2010-2021 at Mayo Clinic in Minnesota, Arizona, and Florida who received cabozantinib. Median overall survival and progression free survival analyses were performed using the Kaplan-Meier method. Adverse events were determined using Common Terminology Criteria for Adverse Events (CTCAE). (3). Results: We identified 26 patients with advanced HCC who received cabozantinib following progression on immunotherapy. Median progression free survival on cabozantinib therapy was 2.1 months (95% CI: 1.3-3.9) and median overall survival from time of cabozantinib initiation was 7.7 months (95% CI: 5.3-14.9). (4) Conclusion: The optimal sequencing of therapy for patients with advanced HCC following progression on immunotherapy remains unknown. Our study demonstrates that patients may benefit from treatment with cabozantinib following progression on immunotherapy.

We report on the photoluminescence enhancement of 1.3 μm InAs quantum dots (QDs) epitaxially grown on an ultrathin 250 nm GaAs buffer on a Si substrate. Decreasing the GaAs buffer thickness from 1000 to 250 nm was found to not only increase the coalesced QD density from 6.5 × 10 8 to 1.9 × 10 9 cm -2 but also decrease the QD photoluminescence emission intensity dramatically. Inserting an Al 0.4 Ga 0.6 As potential barrier layer maintained strong photoluminescence from the QDs by effectively suppressing carrier leakage to the GaAs/Si interfacial region even when the GaAs buffer was thinned to 250 nm. We then fabricated a light-emitting diode using the ultrathin 250 nm GaAs buffer on Si and confirmed strong electroluminescence peaking at 1.28 μm without interfacial defect emission at room temperature. We believe that this work is promising for monolithically integrated evanescent Si lasers using InAs/GaAs QDs.

This study was conducted to investigate the general properties of an enzymatic extract of Sargassum muticum (SM) produced using a crude enzyme from Shewanella oneidensis PKA 1008 and their anti-inflammatory activities. The SM was mixed with crude enzymes from S. oneidensis PKA 1008 (1:1 (v/v)) and incubated at 30 °C for 0, 3, 6, 12, 24, 48, and 60 h. S. oneidensis PKA 1008 crude enzyme showed the highest SM enzymatic extracts degradation ability when reacted with SM for 48 h. These evaluations demonstrated a 134.25% increase in reducing sugar content and a 14.90% reduction in viscosity at 48 h. The pH, lightness (L*) and yellowness (b*) of the SM enzymatic extracts decreased significantly with increasing reaction time. Moreover, the SM enzymatic extracts demonstrated significant anti-inflammatory activity. These results indicate that the crude enzyme from S. oneidensis PKA 1008 can be used to enhance the polysaccharide degradation of SM, and the resultant oligosaccharides may have an anti-inflammatory effect., Competing Interests: Conflict of interestThe authors declare that there are no conflicts of interest., (© The Korean Society of Food Science and Technology 2022.)

Background: FGFR2 genomic alterations are observed in 10-20% of cholangiocarcinoma (CCA). Although FGFR2 fusions are an important actionable target, FGFR2 protein expression has not been thoroughly characterized., Aims: To evaluate FGFR2 protein expression in cholangiocarcinoma harboring FGFR2 genomic alterations., Methods: FGFR2 protein expression was evaluated in 99 CCA cases with two different antibodies. FGFR2 genomic alterations were confirmed via next-generating sequencing (NGS) or FISH. Primary objective was to determine the specificity and sensitivity of FGFR2 immunohistochemistry staining for detecting FGFR2 genomic alterations. Secondary objectives included overall FGFR2 immunohistochemistry staining in CCA patients, and evaluation of whether FGFR2 expression correlates with clinical outcomes including overall survival (OS), progression-free survival (PFS), and time-to-tumor recurrence (TTR)., Results: Immunohistochemistry staining with two antibodies against FGFR2, FPR2-D, and clone 98706 showed high accuracy (78.7% and 91.9%) and specificity (82.9% and 97.7%), and moderate sensitivity (53.9% and 57.1%), respectively, when compared with the standard methods for detecting FGFR2 genomic alterations. In a median follow-up of 72 months, there were no statistically significant differences in OS, PFS, and TTR, for patients with positive or negative FGFR2 staining., Conclusion: FGFR2 protein expression by immunohistochemistry has high specificity and therefore could be used to imply the presence of FGFR2 genomic alterations in the context of a positive test. In the case of a negative test, NGS or FISH would be necessary to ascertain cases with FGFR2 genomic alterations., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Checkpoint inhibitor (CPI) therapies provide limited benefit to patients with tumors of low immune reactivity. T cell-inducing vaccines hold promise to exert long-lasting disease control in combination with CPI therapy. Safety, tolerability and recommended phase 2 dose (RP2D) of an individualized, heterologous chimpanzee adenovirus (ChAd68) and self-amplifying mRNA (samRNA)-based neoantigen vaccine in combination with nivolumab and ipilimumab were assessed as primary endpoints in an ongoing phase 1/2 study in patients with advanced metastatic solid tumors (NCT03639714). The individualized vaccine regimen was safe and well tolerated, with no dose-limiting toxicities. Treatment-related adverse events (TRAEs) >10% included pyrexia, fatigue, musculoskeletal and injection site pain and diarrhea. Serious TRAEs included one count each of pyrexia, duodenitis, increased transaminases and hyperthyroidism. The RP2D was 10 12 viral particles (VP) ChAd68 and 30 µg samRNA. Secondary endpoints included immunogenicity, feasibility of manufacturing and overall survival (OS). Vaccine manufacturing was feasible, with vaccination inducing long-lasting neoantigen-specific CD8 T cell responses. Several patients with microsatellite-stable colorectal cancer (MSS-CRC) had improved OS. Exploratory biomarker analyses showed decreased circulating tumor DNA (ctDNA) in patients with prolonged OS. Although small study size limits statistical and translational analyses, the increased OS observed in MSS-CRC warrants further exploration in larger randomized studies., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: This phase Ib/2 trial investigated pembrolizumab-containing trimodality therapy in patients with gastroesophageal junction (GEJ) adenocarcinoma., Patients and Methods: Patients with GEJ adenocarcinoma (cT1-3NanyM0) received neoadjuvant pembrolizumab-containing chemoradiation (CROSS regimen) followed by surgical resection and adjuvant pembrolizumab. The primary endpoints were tolerability in the first 16 patients and pathologic complete response [pCR (ypT0N0)]. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). An independent propensity-score-matched cohort (treated with CROSS without immunotherapy) was used for comparison. Exploratory analyses included immune biomarkers in the tumor microenvironment (TME) and plasma., Results: We enrolled 31 eligible patients, of whom 29 received all expected doses of neoadjuvant pembrolizumab and 28 underwent R0 resection. Safety endpoints were met. The primary efficacy endpoint was not met [7/31 (22.6%) achieved pCR]. Patients with high [i.e., combined positive score (CPS) ≥ 10] baseline expression of programmed death (PD)-L1 in the TME had a significantly higher pCR rate than those with low expression [50.0% (4/8) vs. 13.6% (3/22); P = 0.046]. Patients with high PD-L1 expression also experienced longer PFS and OS than propensity-score-matched patients. Among trial patients with PD-L1 CPS < 10, unprespecified analysis explored whether extracellular vesicles (EV) could identify further responders: an elevated plasma level of PD-L1-expressing EVs was significantly associated with higher pCR., Conclusions: Adding pembrolizumab to trimodality therapy showed acceptable tolerability but did not meet the pre-specified pCR endpoint. Exploratory analyses suggested that high PD-L1 expression in the TME and/or on EVs may identify patients most likely to achieve tumor response., (©2022 American Association for Cancer Research.)

In this study, gamma-irradiated mackerel ( Scomber japonicus ) meat was stored in a refrigerator for 20 days to examine the physicochemical changes related to fishy smell. The effect of gamma irradiation on the inhibition of the activity of crude urease extracted from Vibrio parahaemolyticus was also evaluated. Increased levels of trimethylamine (TMA) and volatile basic nitrogen (VBN) content, which are the main components causing fishy smell, were significantly reduced by day 20 of storage after gamma irradiation, indicating that freshness was maintained during storage. The ammonia nitrogen contents of 3, 7, 10, and 20 kGy gamma-irradiated groups were significantly decreased by 6.5, 15.2, 17.4, and 23.9%, respectively, compared to non-irradiated groups on day 20 of storage. In addition, urease activity decreased in a gamma irradiation intensity-dependent manner. Volatile organic compounds (VOCs) were measured during the storage of gamma-irradiated mackerel meat. The contents of ethanol, 2-butanone, 3-methylbutanal, and trans-2-pentenal, which are known to cause off-flavors due to spoilage of fish, were significantly reduced by day 20 of storage. Therefore, gamma irradiation can be considered useful for inhibiting urease activity and reducing fishy smell during fish storage.

Herein, the color gamut change by optical crosstalk between sub-pixels in high-resolution full-color organic light-emitting diode (OLED) microdisplays was numerically investigated. The color gamut of the OLED microdisplay decreased dramatically as the pixel density of the panel increased from 100 pixels per inch (PPI) to 3000 PPI. In addition, the increase in thickness of the passivation layer between the bottom electrode and the top color filter results in a decrease in the color gamut. We also calculated the color gamut change depending on the pixel structures in the practical OLED microdisplay panel, which had an aspect ratio of 32:9 and a pixel density of 2,490 PPI. The fence angle and height, refractive index of the passivation layer, black matrix width, and white OLED device structure affect the color gamut of the OLED microdisplay panel because of the optical crosstalk effect.

A charge trap device based on field-effect transistors (FET) is a promising candidate for artificial synapses because of its high reliability and mature fabrication technology. However, conventional MOSFET-based charge trap synapses require a strong stimulus for synaptic update because of their inefficient hot-carrier injection into the charge trapping layer, consequently causing a slow speed operation and large power consumption. Here, we propose a highly efficient charge trap synapse using III-V materials-based tunnel field-effect transistor (TFET). Our synaptic TFETs present superior subthreshold swing and improved charge trapping ability utilizing both carriers as charge trapping sources: hot holes created by impact ionization in the narrow bandgap InGaAs after being provided from the p + -source, and band-to-band tunneling hot electrons (BBHEs) generated at the abrupt p + n junctions in the TFETs. Thanks to these advances, our devices achieved outstanding efficiency in synaptic characteristics with a 5750 times faster synaptic update speed and 51 times lower sub-fJ/um 2 energy consumption per single synaptic update in comparison to the MOSFET-based synapse. An artificial neural network (ANN) simulation also confirmed a high recognition accuracy of handwritten digits up to ∼90% in a multilayer perceptron neural network based on our synaptic devices.

Purpose: This investigation sought to evaluate the prognostic value of pretreatment of circulating tumor DNA (ctDNA) in metastatic biliary tract cancers (BTCs) treated with platinum-based first-line chemotherapy treatment., Materials and Methods: We performed a retrospective analysis of 67 patients who underwent ctDNA testing before platinum-based chemotherapy for first-line treatment for metastatic BTC. For analysis, we considered the detected gene with highest variant allele frequency as the dominant clone allele frequency (DCAF). Results of ctDNA analysis were correlated with patients' demographics, progression-free survival (PFS), and overall survival (OS)., Results: The median age of patients was 67 (27-90) years. Fifty-four (80.6%) of 67 patients evaluated had intrahepatic cholangiocarcinoma; seven had extrahepatic cholangiocarcinoma, and six gallbladder cancers. Forty-six (68.6%) of the patients were treated with cisplatin plus gemcitabine, and 16.4% of patients received gemcitabine and other platinum (carboplatin or oxaliplatin) combinations, whereas 15% of patients were treated on a clinical trial with gemcitabine and cisplatin plus additional agents (CX4945, PEGPH20, or nab-paclitaxel). TP53, KRAS, FGFR2, ARID1A, STK11, and IDH1 were the genes with highest frequency as DCAF. The median DCAF was 3% (0%-97%). DCAF > 3% was associated with worse OS (median OS: 10.8 v 18.8 months, P = .032). Stratifying DCAF in quartiles, DCAF > 10% was significantly related to worse PFS (median PFS: 3 months, P = .014) and worse OS (median OS: 7.0 months, P = .001). Each 1% increase in ctDNA was associated with a hazard ratio of 13.1 in OS when adjusting for subtypes, metastatic sites, size of largest tumor, age, sex, and CA19-9., Conclusion: DCAF at diagnosis of advanced BTC can stratify patients who have worse outcomes when treated with upfront platinum-based chemotherapy. Each increase in %ctDNA decreases survival probabilities., Competing Interests: Jun YinEmployment: Mayo Clinic Mohamad Bassam SonbolResearch Funding: Lilly (Inst), Taiho Oncology (Inst) Daniel H. AhnStock and Other Ownership Interests: NateraConsulting or Advisory Role: Eisai, Exelixis, Genentech/Roche, Advanced Accelerator Applications, Novartis, Daiichi Sankyo/Astra ZenecaResearch Funding: Bayer, AstraZeneca Jason S. StarrConsulting or Advisory Role: Natera, Ipsen, Pfizer, Taiho Oncology, TerSera, Advanced Accelerator ApplicationsResearch Funding: Incyte (Inst), Merus (Inst), Rafael Pharmaceuticals (Inst), Molecular Templates (Inst), MacroGenics (Inst), Vedanta Biosciences (Inst), Leap Therapeutics Hani BabikerConsulting or Advisory Role: Endocyte, Celgene, Idera, Myovant Sciences, NovocureSpeakers' Bureau: Guardant Health Tanios S. Bekaii-SaabConsulting or Advisory Role: Amgen (Inst), Ipsen (Inst), Lilly (Inst), Bayer (Inst), Roche/Genentech (Inst), AbbVie, Incyte (Inst), Immuneering, Seattle Genetics (Inst), Pfizer (Inst), Boehringer Ingelheim, Janssen, Eisai, Eisai, Daiichi Sankyo/UCB Japan, AstraZeneca, Exact Sciences, Natera, Treos Bio, Celularity, SOBI, BeiGene, Foundation Medicine, Arcus Biosciences (Inst), Stemline Therapeutics, Kanaph Therapeutics, Deciphera, Illumina, Foundation MedicinePatents, Royalties, Other Intellectual Property: Patent WO/2018/183488, Patent WO/2019/055687Other Relationship: Exelixis, Merck (Inst), AstraZeneca, Lilly, Pancreatic Cancer Action Network, FibroGen, Suzhou Kintor Pharmaceuticals, 1-Globe, Imugene, Xilis, Replimune, Sun Biopharma, UpToDateOpen Payments Link: https://openpaymentsdata.cms.gov/physician/636276 Gregory J. GoresHonoraria: Sagimet Biosciences Rory SmootConsulting or Advisory Role: AstraZeneca Bolni NagaloPatents, Royalties, Other Intellectual Property: Patent “Chimeric Vesiculoviruses and Methods of Use” Mitesh J. Borad, and Bolni M. Nagalo James BogenbergerStock and Other Ownership Interests: Xpecting Diagnostics IncResearch Funding: Agios, RedHill Biopharma, Tolero Pharmaceuticals, Lexicon Aaron MansfieldHonoraria: RocheConsulting or Advisory Role: Genentech (Inst), Bristol Myers Squibb (Inst), AbbVie (Inst), AstraZeneca (Inst)Research Funding: Novartis (Inst)Travel, Accommodations, Expenses: AbbVie, Roche Kabir ModyStock and Other Ownership Interests: CytoDyn, ONCOtherapeuticsConsulting or Advisory Role: Celgene, Genentech/Roche, Merrimack, Eisai, AstraZeneca, Vicus Therapeutics, Ipsen, Boston Scientific, BTG, BTG, Exelixis, Exelixis, Incyte (Inst), QED TherapeuticsResearch Funding: FibroGen (Inst), Senhwa Biosciences (Inst), ARIAD (Inst), TRACON Pharma (Inst), MedImmune (Inst), Agios (Inst), ArQule (Inst), Taiho Pharmaceutical (Inst), Gritstone Bio (Inst), Incyte (Inst), Merck (Inst), Vyriad (Inst), Turnstone Bio (Inst), AstraZeneca (Inst), Basilea (Inst) Mitesh J. BoradStock and Other Ownership Interests: Gilead Sciences, AVEO, Intercept Pharmaceuticals, Spectrum PharmaceuticalsConsulting or Advisory Role: G1 Therapeutics, Fujifilm (Inst), Agios (Inst), Insys Therapeutics (Inst), Novartis (Inst), ArQule (Inst), Celgene (Inst), Inspyr Therapeutics, Halozyme (Inst), Pieris Pharmaceuticals (Inst), Taiho Pharmaceutical (Inst), Immunovative Therapies, Exelixis, Lynx Group, Genentech, Western Oncolytics, Klus Pharma, De Novo Pharmaceuticals, Merck, ImvaxResearch Funding: Boston Biomedical (Inst), miRNA Therapeutics (Inst), Senhwa Biosciences (Inst), MedImmune (Inst), BioLineRx (Inst), Agios (Inst), Halozyme (Inst), Celgene (Inst), Threshold Pharmaceuticals (Inst), Toray Industries (Inst), Dicerna (Inst), SillaJen (Inst), Eisai (Inst), Taiho Pharmaceutical (Inst), EMD Serono (Inst), Isis Pharmaceuticals (Inst), Incyte (Inst), Sun Biopharma (Inst), ARIAD (Inst), ImClone Systems (Inst), QED Therapeutics (Inst), Incyte (Inst), Puma Biotechnology (Inst), Adaptimmune (Inst), Merck Serono (Inst), RedHill Biopharma (Inst), Basilea (Inst), AstraZeneca (Inst)Travel, Accommodations, Expenses: ArQule, Celgene, AstraZenecaNo other potential conflicts of interest were reported.

Automated crop monitoring using image analysis is commonly used in horticulture. Image-processing technologies have been used in several studies to monitor growth, determine harvest time, and estimate yield. However, accurate monitoring of flowers and fruits in addition to tracking their movements is difficult because of their location on an individual plant among a cluster of plants. In this study, an automated clip-type Internet of Things (IoT) camera-based growth monitoring and harvest date prediction system was proposed and designed for tomato cultivation. Multiple clip-type IoT cameras were installed on trusses inside a greenhouse, and the growth of tomato flowers and fruits was monitored using deep learning-based blooming flower and immature fruit detection. In addition, the harvest date was calculated using these data and temperatures inside the greenhouse. Our system was tested over three months. Harvest dates measured using our system were comparable with the data manually recorded. These results suggest that the system could accurately detect anthesis, number of immature fruits, and predict the harvest date within an error range of ±2.03 days in tomato plants. This system can be used to support crop growth management in greenhouses.

Background: We report our experience with 3 strategies for treating hilar and extrahepatic cholangiocarcinoma (CCA) including chemoradiotherapy: neoadjuvant chemoradiotherapy (nCRT) and orthotopic liver transplant, surgical resection and adjuvant chemoradiotherapy (aCRT), and definitive chemoradiotherapy (dCRT)., Methods: We included patients treated from 1998 through 2019. Kaplan-Meier estimates, log-rank testing, and univariate/multivariate Cox models were used to assess outcomes (local progression-free survival, disease-free survival, and overall survival)., Results: Sixty-five patients (nCRT, n=20; aCRT, n=16; dCRT, n=29) met inclusion criteria [median (range) age 65 years (27-84 years)]. Median posttreatment follow-up was 19.1 months (0.8-164.8 months) for all patients and 38.6, 24.3, and 9.0 months for the nCRT, aCRT, and dCRT groups, respectively. At 3 and 5 years, overall survival was 78% and 59% for the nCRT group; 47% and 35%, aCRT group; and 11% and 0%, dCRT group. Compared with the dCRT group, the nCRT group (hazard ratio =0.13, 95% CI: 0.05-0.33) and the aCRT group (hazard ratio =0.29, 95% CI: 0.14-0.64) had significantly improved overall survival (P<0.001). The 5-year local progression-free survival (50% nCRT vs. 30% aCRT vs. 0% dCRT, P<0.001) and 5-year disease-free survival (61% nCRT vs. 30% aCRT vs. 0% dCRT, P=0.01) were significantly better for strategies combined with surgery., Conclusions: Outcomes for patients with extrahepatic CCA were superior for those who underwent nCRT/orthotopic liver transplant or postsurgical aCRT than for patients treated with dCRT. The excellent outcomes after nCRT/orthotopic liver transplant provide additional independent data supporting the validity of this strategy. The poor survival of patients treated with dCRT highlights a need for better therapies when surgery is not possible., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-21-615/coif). DHA is an advisor for Genentech, Eisai, Advanced Accelerator Applications, Exelixis, and Daiichi Sankyo. TTS provides strategic and scientific recommendations as a member of the Advisory Board and speaker for Novocure, Inc., which is not in any way associated with the content presented in this manuscript. TSBS receives research funding from Agios, Arys, Arcus, Atreca, Boston Biomedical, Bayer, Amgen, Merck, Celgene, Lilly, Ipsen, Clovis, Seattle Genetics, Genentech, Novartis, Mirati, Merus, Abgenomics, Incyte, Pfizer, and BMS; has consulting relationships with Ipsen, Arcus, Array Biopharma, Pfizer, Seattle Genetics, Bayer, Genentech, Incyte, Merck, Stemline, AbbVie, Boehringer Ingelheim, Janssen, Eisai, Daichii Sankyo, Natera, TreosBio, Celularity, Exact Science, Sobi, Beigene, Kanaph, Xilis, Astra Zeneca, and Foundation Medicine; participates on the Data Safety Monitoring Boards of Fibrogen, Suzhou Kintor, Astra Zeneca, Exelixis, Lilly, PanCan, and 1Globe; is a member of the Scientific Advisory Boards of Imugene, Immuneering, and Panbela Therapeutics; and has the following patents pending: WO/2018/183488 and WO/2019/055687. The other authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Background Biliary tract cancers (BTC) are rare, chemo resistant and are associated with a poor prognosis. Preclinical and early clinical work had demonstrated interesting anti-tumor activity from targeting fibroblast growth factor receptor (FGFR) pathway. We hypothesized that ponatinib, a multi-targeted tyrosine kinase inhibitor with activity against FGFR, would be active in BTC patients with FGFR alterations. Methods This was a multi-center, single institution pilot study of ponatinib in patients with advanced, refractory BTC with FGFR alterations. The primary end point was overall response rate, with secondary points of overall survival (OS), progression-free survival (PFS) and Health Related Quality of Life (HRQoL) assessment. Results Twelve patients were enrolled prior to early termination of the trial. Partial responses were observed in 1 from 12 patients. Median PFS was 2.4 months and median OS was 15.7 months. All observed toxicities were manageable and reversible. Toxicities were mild, with lymphopenia (75%), rash (63%) and fatigue (50%) being the most frequent. No significant detriment in global QoL was observed. Conclusions Ponatinib as a single agent in FGFR altered BTC is tolerable with limited clinical activity. This is the first report of prospective assessment of FGFR inhibition in BTC using ponatinib, and the first study to report its effect on HRQoL. Further development of ponatinib will involve correlative studies to better refine patient selection, focus on combinations with other molecular targeted agents, conventional cytotoxic chemotherapy, and studies to better understand mechanisms of treatment resistance., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)