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Abstract The route of oncolytic virotherapy is pivotal for immunotherapeutic efficacy in advanced cancers. In this preclinical study, an oncolytic reovirus (RC402) is orally administered to induce antitumor immunity. Oral reovirus treatment shows no gross toxicities and effectively suppresses multifocal tumor lesions. Orally administered reovirus interacts with the host immune system in the Peyer’s patch of the terminal ileum, increases IgA+ antibody-secreting cells in the lamina propria through MAdCAM-1+ blood vessels, and reshapes the gut microbiome. Oral reovirus promotes antigen presentation, type I/II interferons, and T cell activation within distant tumors, but does not reach or directly infect tumor cells beyond the gastrointestinal tract. In contrast to intratumoral reovirus injection, the presence of the gut microbiome, Batf3+ dendritic cells, type I interferons, and CD8+ T cells are indispensable for orally administered reovirus-induced antitumor immunity. Oral reovirus treatment is most effective when combined with αPD-1(L1) and/or αCTLA-4, leading to complete colon tumor regression and protective immune memory. Collectively, oral reovirus virotherapy is a feasible and effective immunotherapeutic strategy in preclinical studies.

Estimating canopy volumes of strawberry plants can be useful for predicting yields and establishing advanced management plans. Therefore, this study evaluated the spatial variability of strawberry canopy volumes using a ResNet50V2-based convolutional neural network (CNN) model trained with RGB images acquired through manual unmanned aerial vehicle (UAV) flights equipped with a digital color camera. A preprocessing method based on the You Only Look Once v8 Nano (YOLOv8n) object detection model was applied to correct image distortions influenced by fluctuating flight altitude under a manual maneuver. The CNN model was trained using actual canopy volumes measured using a cylindrical case and small expanded polystyrene (EPS) balls to account for internal plant spaces. Estimated canopy volumes using the CNN with flight altitude compensation closely matched the canopy volumes measured with EPS balls (nearly 1:1 relationship). The model achieved a slope, coefficient of determination (R2), and root mean squared error (RMSE) of 0.98, 0.98, and 74.3 cm3, respectively, corresponding to an 84% improvement over the conventional paraboloid shape approximation. In the application tests, the canopy volume map of the entire strawberry field was generated, highlighting the spatial variability of the plant’s canopy volumes, which is crucial for implementing site-specific management of strawberry crops.

In strawberry cultivation, precise disease management is crucial for maximizing yields and reducing unnecessary fungicide use. Traditional methods for measuring leaf wetness duration (LWD), a critical factor in assessing the risk of fungal diseases such as botrytis fruit rot and anthracnose, have been reliant on sensors with known limitations in accuracy and reliability and difficulties with calibrating. To overcome these limitations, this study introduced an innovative algorithm for leaf wetness detection systems employing high-resolution imaging and deep learning technologies, including convolutional neural networks (CNNs). Implemented at the University of Florida’s Plant Science Research and Education Unit (PSREU) in Citra, FL, USA, and expanded to three additional locations across Florida, USA, the system captured and analyzed images of a reference plate to accurately determine the wetness and, consequently, the LWD. The comparison of system outputs with manual observations across diverse environmental conditions demonstrated the enhanced accuracy and reliability of the artificial intelligence-driven approach. By integrating this system into the Strawberry Advisory System (SAS), this study provided an efficient solution to improve disease risk assessment and fungicide application strategies, promising significant economic benefits and sustainability advances in strawberry production.

ABSTRACTAntiangiogenic therapy is a recognized method for countering the immunosuppressive tumor microenvironment (TME) and improving anti-tumor immunity. PB101 is a glycosylated decoy receptor that binds to VEGF-A and PlGF with high affinity, based on the VEGFR1 backbone. Here, we elucidated PB101-induced remodeling of tumor angiogenesis and immunity, which enhances anti-PD-L1 immune checkpoint blockade. PB101 inhibited tumor growth by suppressing angiogenesis and enhancing CD8+ T cell infiltration into the tumors. PB101 induced robust reprogramming of antitumor immunity and activates intratumoral CD8+ T cells. Anti-tumor efficacy of PB101 is mostly dependent on CD8+ T cells and IFN-γ. PB101 reprograms tumor immunity in a manner distinct from that of the conventional VEGF decoy receptor, VEGF-trap. With its potent immune-modulating capability, PB101 synergizes with an anti-PD-L1, triggering strengthened antitumor immunity. Combining PB101 and anti-PD-L1 could establish durable protective immunity against tumor recurrence and metastasis. The findings of this study offer scientific rationales for further clinical development of PB101, particularly when used in combination with immune checkpoint inhibitors, as a potential treatment for advanced cancers.

The pedicled transverse rectus abdominis myocutaneous (TRAM) flap is often used during breast reconstruction. After completely elevating the flap, a medial tunnel is created to connect the dissection area to the mastectomy defect. This tunnel should typically accommodate four of the surgeon’s fingers, although this may vary depending on flap volume. Wider tunneling facilitates flap delivery, but can damage the breast and inframammary fold. Therefore, we introduce a technique to move the flap easily and safely through a small tunnel. During breast reconstruction using a pedicled TRAM flap, a tunnel was made in the mastectomy defect along the meridian of the breast. This tunnel accommodated a width of three of the surgeon’s fingers (6 cm). After completely elevating the flap, it was inserted into a funnel with an inner surface made of polymeric vinyl and a hydrophilic coating. The flap was propelled into the mastectomy defect via the funnel. Our novel technique for pedicled TRAM flap delivery using a funnel was easy and safe, and it is deemed to be suitable for delivering a pedicled TRAM flap.

Strawberries are an important and high-value crop in the United States. The total value of strawberry production in the United States was $3.42 billion in 2021. However, a major pest of strawberries, two-spotted spider mites (TSSM) (Tetranychus urticae Koch), can cause severe economic losses due to mites feeding on chlorophyll which interferes with photosynthesis. Predatory mites (Neoseiulus californicus and Phytoseiulus persimilis) can control TSSM populations and provide an alternative to conventional pesticides. Predatory mites are more friendly to the environment than pesticides. To monitor TSSM and predatory mite populations in the field, frequent sampling is required. However, manual counting of mites using a hand lens is challenging for a large field. Therefore, this study applied deep learning models to detect TSSM and predatory mites in strawberries from smartphone images. Three different smartphones (Motorola Moto E5 Play, OnePlus A5000, and iPhone XR) and a 25x macro lens were used to collect a total of 3,013 images, including 1,779 TSSM images and 1,234 predatory mite images. TSSM images were collected by the three smartphones, and only the OnePlus A5000 and iPhone XR were used to collect predatory mite images that only contained predatory mites or contained both predatory mites and TSSM in the same image. TSSM images were used to compare two deep learning models (YOLOv4 and Faster R-CNN Resnet50) and three different smartphone cameras. This study found that the average detection accuracy of YOLOv4 and Faster R-CNN was 0.935 and 0.863, respectively. Deep learning models achieved the best detection accuracy on the image collected by iPhone XR. The YOLOv4 model was trained to compare the detection performance of three different input image sizes (160 × 160, 320 × 320, 640 × 640 pixels) for TSSM and predatory mite detection. This study found that the mean average precision of the YOLOv4 increased as the image size increased, and the model trained with an image size of 640 × 640 pixels achieved the detection accuracy of 0.933 for TSSM and predatory mites. This study also found that the YOLOv4 could detect pests under different field illumination conditions. The smartphone image-based method can detect the TSSM and predatory mites quickly from images and with high detection accuracy, which can help growers use less time to monitor mite populations in the field.

Background & Aims: We elucidated the clinical and immunologic implications of serum IL-6 levels in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Ate/Bev). Methods: We prospectively enrolled 165 patients with unresectable HCC (discovery cohort: 84 patients from three centres; validation cohort: 81 patients from one centre). Baseline blood samples were analysed using a flow cytometric bead array. The tumour immune microenvironment was analysed using RNA sequencing. Results: In the discovery cohort, clinical benefit 6 months (CB6m) was defined as complete or partial response, or stable disease for ≥6 months. Among various blood-based biomarkers, serum IL-6 levels were significantly higher in participants without CB6m than in those with CB6m (mean 11.56 vs. 5.05 pg/ml, p = 0.02). Using maximally selected rank statistics, the optimal cut-off value for high IL-6 was determined as 18.49 pg/ml, and 15.2% of participants were found to have high IL-6 levels at baseline. In both the discovery and validation cohorts, participants with high baseline IL-6 levels had a reduced response rate and worse progression-free and overall survival after Ate/Bev treatment compared with those with low baseline IL-6 levels. In multivariable Cox regression analysis, the clinical implications of high IL-6 levels persisted, even after adjusting for various confounding factors. Participants with high IL-6 levels showed reduced interferon-γ and tumour necrosis factor-α secretion from CD8+ T cells. Moreover, excess IL-6 suppressed cytokine production and proliferation of CD8+ T cells. Finally, participants with high IL-6 levels exhibited a non-T-cell-inflamed immunosuppressive tumour microenvironment. Conclusions: High baseline IL-6 levels can be associated with poor clinical outcomes and impaired T-cell function in patients with unresectable HCC after Ate/Bev treatment. Impact and implications: Although patients with hepatocellular carcinoma who respond to treatment with atezolizumab and bevacizumab exhibit favourable clinical outcomes, a fraction of these still experience primary resistance. We found that high baseline serum levels of IL-6 correlate with poor clinical outcomes and impaired T-cell response in patients with hepatocellular carcinoma treated with atezolizumab and bevacizumab.

Abstract In living-donor liver transplantation, the safety of the donor is critical. In addition, accurately measuring the liver volume is significant as the amount that can be resected from living donors is limited. In this paper, we propose an automated segmentation and volume estimation method for the liver in computed tomography imaging based on a deep learning-based segmentation network. Our framework was trained using the data of 191 donors, achieved a dice similarity coefficient of 0.789, 0.869, 0.955, and 0.899, respectively, in the segmentation task for the left lobe, right lobe, caudate lobe, and whole liver. Moreover, the R^2 score reached 0.980, 0.996, 0.953, and 0.996 in the volume estimation task. We demonstrate that our approach provides accurate and quantitative liver segmentation results, reducing the error in liver volume estimation. Therefore, we expected to be used as an aid in estimating liver volume from CT volume data for living-donor liver transplantation.

Introduction: Atezolizumab and bevacizumab (Ate/Bev) combination has become the new first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). Although several studies reported thyroid dysfunction after treatment with immune checkpoint inhibitors, the clinical and immunological significance of thyroid dysfunction in patients treated with Ate/Bev has not been comprehensively addressed. We aimed to comprehensively evaluate the clinical and immunological implications of thyroid dysfunction in unresectable HCC patients treated with Ate/Bev. Methods: We enrolled 208 patients with unresectable HCC treated with Ate/Bev from three Korean cancer centers. Thyroid adverse events (AEs) were reviewed, and cytokines and T cells in the blood samples were analyzed at baseline. For external validation, we analyzed clinical outcomes according to thyroid AEs in patients treated with Ate/Bev in the IMbrave150 study. Results: Forty-one (19.7%) out of 208 patients experienced thyroid dysfunction (hypothyroidism [17.3%] and thyrotoxicosis [5.8%]) after Ate/Bev treatment. Median time to onset of hypothyroidism and thyrotoxicosis after Ate/Bev treatment was 3.5 and 1.3 months, respectively. Patients with thyroid AEs demonstrated significantly better progression-free survival, overall survival, and objective response rate than those without thyroid AEs. These findings were still consistent even after adjusting for confounding factors. Furthermore, favorable survival outcomes in patients with thyroid AEs were also validated in a cohort of IMbrave150 patients. While patients with thyrotoxicosis showed a significantly lower level of baseline IL-6, those with hypothyroidism did not show significant differences in circulating cytokine levels and CD8+ T-cell fractions. Conclusions: A fraction of patients with HCC treated with Ate/Bev experienced thyroid dysfunction, and the development of thyroid AEs was associated with favorable clinical outcomes.

Cancer: Combination treatment targeting tumor blood vessels and immunity Combining anti-angiogenesis drugs that reduce the growth of blood vessels and immune checkpoint inhibitors that promote the activation of cancer-killing immune cells offers a promising new therapeutic regimen for patients with cancer. In a review article, a team led by Chan Kim and Hong Jae Chon from the CHA University School of Medicine in Seongnam, South Korea, discuss the molecular crosstalk between blood vessels and immune cells in the tumor microenvironment, a biological interconnectedness that provides a compelling rationale for the dual treatment strategy. The researchers summarize preclinical and clinical data demonstrating the potential of combining immunotherapy with treatment targeting blood vessel growth across a range of tumor types. These data have so far led to regulatory approvals for patients with cancers of the lung, kidney, liver and endometrium.

Strawberry is ranked third in the value of production of the crops in Florida, USA. Classifying strawberry maturity and monitoring strawberry growth status in the field is very critical for accurate strawberry yield prediction, efficient strawberry field management, and achieving the highest crop production. The traditional method of distinguishing strawberry maturity is based on either physical appearance or internal chemical substance content. However, the traditional method is time-consuming and costly. In this research, an automatic strawberry maturity classification system was developed for the rapid and accurate classification of different strawberry maturity stages. A state-of-the-art deep learning method, You Only Look Once (YOLOv3), which is good at small object detection, was trained and applied to detect strawberry flowers and strawberry fruit at different maturity stages. Two strawberry image acquisition methods, aerial imaging and near-ground imaging, were compared by using the same deep learning image processing method. As a result, three and seven strawberry maturity stages were classified for unmanned aerial vehicle (UAV) images and near-ground digital camera images, respectively. For UAV images, the highest mean average precision (mAP) of strawberry maturity classification was 0.88 for a test data set at 2 m, and the highest classification average precision (AP) was 0.93 for fully matured fruit. For near-ground digital camera images, the mAP of strawberry maturity classification was 0.89, and the highest classification AP was 0.94 for fully matured fruit as well. The result shows that YOLOv3 is an excellent approach for strawberry maturity classification on both image types.

Botrytis fruit rot and anthracnose are fungal diseases of strawberry. These diseases are a significant contributor to yield losses, requiring farmers to use fungicides frequently to prevent them. The proliferation of botrytis and anthracnose is directly linked to the duration of the presence of free water on the plant canopy, which is generally defined as leaf wetness duration (LWD). LWD is an important measure in determining the risk for these diseases to develop in the strawberry crop. By accurately measuring LWD, the risk of disease can be calculated more accurately, and specific fungicide application recommendations can be given to the farmers. This reduces the frequency with which fungicide is applied and ultimately reduces costs for farmers. There is no standard method to detect leaf wetness, but leaf wetness sensors are widely used for that purpose. These wetness sensors are difficult to calibrate and not very accurate, which reduces their reliability. The objective of this study was to find a better alternative to the commonly used leaf wetness sensors. This study implemented color and thermal imaging-based approaches as a solution to the problem of leaf wetness detection in strawberry plants. The proposed method used deep learning and computer vision techniques to detect leaf wetness from color and thermal images. The deep learning model was highly accurate in detecting wetness when compared with the visual observation of the images. It was also found that leaf wetness could be detected with a high degree of accuracy using deep learning with color images. In the future, using the findings of this study, a portable device can be developed to replace the commonly used wetness sensor with a more reliable imaging-based device.

The decline of natural pollinators necessitates the development of novel pollination technologies. In this work, we propose a drone-enabled autonomous pollination system (APS) that consists of five primary modules: environment sensing, flower perception, path planning, flight control, and pollination mechanisms. These modules are highly dependent upon each other, with each module relying on inputs from the other modules. In this paper, we focus on approaches to the flower perception, path planning, and flight control modules. First, we briefly introduce a flower perception method from our previous work to create a map of flower locations. With a map of flowers, APS path planning is defined as a variant of the Travelling Salesman Problem (TSP). Two path planning approaches are compared based on mixed-integer programming (MIP) and genetic algorithms (GA), respectively. The GA approach is chosen as the superior approach due to the vast computational savings with negligible loss of optimality. To accurately follow the generated path for pollination, we develop a convex optimization approach to the quadrotor flight control problem (QFCP). This approach solves two convex problems. The first problem is a convexified three degree-of-freedom QFCP. The solution to this problem is used as an initial guess to the second convex problem, which is a linearized six degree-of-freedom QFCP. It is found that changing the objective of the second convex problem to minimize the deviation from the initial guess provides improved physical feasibility and solutions similar to a general-purpose optimizer. The path planning and flight control approaches are then tested within a model predictive control (MPC) framework where significant computational savings and embedded adjustments to uncertainty are observed. Coupling the two modules together provides a simple demonstration of how the entire APS will operate in practice.

The Strawberry Advisory System (SAS) is a tool developed to help Florida strawberry growers determine the risk of common fungal diseases and the need for fungicide applications. Leaf wetness duration (LWD) is one of the important parameters in SAS disease risk modeling. By accurately measuring the LWD, disease risk can be better assessed, leading to less fungicide use and more economic benefits to the farmers. This research aimed to develop and test a more accurate leaf wetness detection system than traditional leaf wetness sensors. In this research, a leaf wetness detection system was developed and tested using color imaging of a reference surface and a convolutional neural network (CNN), which is one of the artificial-intelligence-based learning methods. The system was placed at two separate field locations during the 2021–2022 strawberry-growing season. The results from the developed system were compared against manual observation to determine the accuracy of the system. It was found that the AI- and imaging-based system had high accuracy in detecting wetness on a reference surface. The developed system can be used in SAS for determining accurate disease risks and fungicide recommendations for strawberry production and allows the expansion of the system to multiple locations.

Background Peritoneal carcinomatosis is a fatal clinical presentation of colon cancer, characterized by unresponsiveness to conventional anticancer therapies, including immune checkpoint inhibitors. Here, we elucidated the immune-evasion mechanisms during the peritoneal carcinomatosis of colon cancer and developed a novel immunotherapy by activating the stimulator of interferon genes (STING) pathway.Methods We generated a syngeneic peritoneal carcinomatosis model of colon cancer. Mice were intraperitoneally treated with either STING agonist (MIW815, also known as ADU-S100) or PD-1 blockade or both. The tumor microenvironment was comprehensively analyzed using multiplexed immunofluorescence imaging, flow cytometry, and NanoString immune profiling.Results Intraperitoneal colon cancer cells induce a massive influx of immunosuppressive M2-like macrophages, upregulate immune checkpoints, and impair effector T cell functions during peritoneal dissemination; these collectively create a highly angiogenic and immunosuppressive milieu that is resistant to anti-PD-1 monotherapy. Intraperitoneal administration of a STING agonist suppressed aberrant angiogenesis, increased pericyte coverage, and normalized tumor vessels, thereby facilitating the infiltration of activated CD8+ T cells into peritoneal tumor nodules. Moreover, STING activation reprogramed tumor-associated macrophages toward the M1 phenotype. STING activation converted immunologically cold peritoneal tumors into T-cell-inflamed tumors in a type-I interferon-dependent manner. Lastly, the STING agonist synergistically cooperated with PD-1 and/or COX2 blockade to further suppress the peritoneal dissemination of colon cancer, resulting in complete eradication of tumor and ascites, and inducing durable antitumor immunity.Conclusions STING activation can normalize the peritoneal vascular and immune microenvironment, providing a rationale for a novel combination therapeutic strategy for peritoneal carcinomatosis in colon cancer.

Summary: Objective: We performed a prospective randomized study to assess whether the use of sodium hyaluronate-based bioresorbable membrane (Seprafilm®) and liquid-based hyaluronic acid and carboxymethyl cellulose solution (Guardix) to reduce postoperative small bowel small bowel obstruction in patients undergoing colorectal surgery. This study aimed to compare the incidence of postoperative bowel obstruction. Methods: One hundred seven patients were assigned to the Seprafilm® group and 155 were assigned to the Guardix® group during the study period. The control group of 166 patients received no anti-adhesive. Patients were randomly assigned. Results: The overall small bowel obstruction rate was 7.6% (N = 37/488 patients). Small bowel obstruction developed in 9 patients (5.8%) in the Guardix® group and 9 patients (7.1%) in the Seprafilm® group and 19 patients (11.4%) in the control group. Seprafilm® group had significantly lower obstruction rate as compared to control group (P = 0.036). Guardix® solution and Seprafilm® did not alter the liver and renal function, as assessed by the blood chemistry. Conclusions: The use of Seprafilm significantly reduces the incidence of postoperative small bowel obstruction in patients undergoing colorectal surgery. We observed no difference in the incidence of postoperative small bowel obstruction after the application of Seprafilm® and Guardix® in patients undergoing colorectal surgery. Keywords: Small bowel obstruction, Antiadhesive, Surgery

During laparoscopic surgery for colorectal or gastric cancers, locating the tumor for excision is difficult owing to it being obscured by mucous membranes. Therefore, a clip can be installed around the tumor, which can be located using a sensor. Most of the clip–detectors developed thus far can only detect tumors in either the colon or stomach and require a wire to connect the clip and detector. This study designs a clip and detector that can locate a tumor in the stomach and colon. The clip contains a neodymium magnet that generates a magnetic field, and the detector includes a Colpitts oscillator that allows magnetic coupling of the clip and detector. After installing the prepared clip at the tumor location, the detector is used to locate the clip. To test the clip and detector, we conducted animal experiments, during which four clips were installed in the colon and stomach of a mini pig. We succeeded in locating the clips within 2.17 and 3.14 s in the stomach and colon, respectively, which were shorter than the detection times reported in previous studies. The demand for laparoscopic surgery and endoscopes is predicted to increase owing to this method.

Purpose Double primary colorectal cancer (CRC) and gastric cancer (GC) represent the most common multiple primary malignant tumors (MPMT) in Korea. The recognition and screening of hidden malignancies other than the primary cancer are critical. This study aimed to investigate the clinicopathologic characteristics and survival rates in patients with synchronous or metachronous double primary CRC and GC. Methods Between January 1994 and May 2018, 11,050 patients were diagnosed with CRC (n=5,454) or GC (n=5,596) at Gil Medical Center. MPMT and metastatic malignant tumors were excluded from this study. A total of 103 patients with double primary CRC and GC were divided into two groups: the synchronous group (n=40) and the metachronous group (n=63). The incidence, clinicopathologic characteristics, and survival rate of the two groups were analyzed. Results The incidence of synchronous and metachronous double primary CRC and GC was 0.93%. Double primary CRC and GC commonly occurred in male patients aged over 60 years with low comorbidities and minimal previous cancer history. There were significant differences between the synchronous and metachronous groups in terms of age, morbidity, and overall survival. Metachronous group patients were 6 years younger on average (P=0.009), had low comorbidities (P=0.008), and showed a higher 5-year overall survival rate (94.8% and 61.3%, P

Purpose: This study aimed to compare surgical revisions and balloon angioplasty after surgical thrombectomy on thrombosed dialysis access as a first event. Materials and Methods: Records of patients undergoing creation of arteriovenous grafts (AVGs) at the Gachon University Gil Medical Center between March 2008 and February 2016 were reviewed. Among them, patients who underwent treatment on first-time thrombotic occlusion after AVG creation were identified. Outcomes were primary, primary-assisted, and secondary patency. The patency was generated using the Kaplan-Meier method, and patency rates were compared by log-rank test. Results: A total of 59 de novo interventions (n=26, hybrid interventions; n=33, surgical revisions) for occlusive AVGs were identified. The estimated 1-year primary patency rates were 47% and 30% in the surgery and hybrid groups, respectively. The estimated primary patency rates were not different between the two groups (log-rank test, P=0.73). The Kaplan-Meier estimates of 6 and 12 months for primary-assisted patency rates were 68% and 57% in the surgery group and 56% and 56% in the hybrid group. The Kaplan-Meier estimates of 12 and 24 months secondary patency rates were 90% and 71% in the surgery group and 79% and 62% in the hybrid group. There were no differences in the estimated primary-assisted and secondary patency rates between the two groups. Conclusion: Our results showed no significant difference between the two groups in terms of primary patency (P=0.73), primary-assisted patency (P=0.85), and secondary patency (P=0.78). However, percutaneous transluminal angioplasty can give more therapeutic options for both surgeons and patients.

Kynurenine (Kyn) is a key inducer of an immunosuppressive tumor microenvironment (TME). Although indoleamine 2,3-dioxygenase (IDO)-selective inhibitors have been developed to suppress the Kyn pathway, the results were not satisfactory due to the presence of various opposing mechanisms. Here, we employed an orally administered novel Kyn pathway regulator to overcome the limitation of anti-tumor immune response. We identified a novel core structure that inhibited both IDO and TDO. An orally available lead compound, STB-C017 (designated hereafter as STB), effectively inhibited the enzymatic and cellular activity of IDO and TDO in vitro. Moreover, it potently suppressed Kyn levels in both the plasma and tumor in vivo. STB monotherapy increased the infiltration of CD8+ T cells into TME. In addition, STB reprogrammed the TME with widespread changes in immune-mediated gene signatures. Notably, STB-based combination immunotherapy elicited the most potent anti-tumor efficacy through concurrent treatment with immune checkpoint inhibitors, leading to complete tumor regression and long-term overall survival. Our study demonstrated that a novel Kyn pathway regulator derived using deep learning technology can activate T cell immunity and potentiate immune checkpoint blockade by overcoming an immunosuppressive TME.

Background Peritoneal carcinomatosis (PC) is a common and devastating manifestation of colon cancer and refractory to conventional anticancer therapeutics. During the peritoneal dissemination of colon cancer, peritoneal immunity is nullified by various mechanisms of immune evasion. Here, we employed the armed oncolytic vaccinia virus mJX-594 (JX) to rejuvenate the peritoneal antitumor immune responses in the treatment of PC.Methods PC model of MC38 colon cancer was generated and intraperitoneally treated with JX and/or anti-programmed cell death protein 1 (PD-1) antibody. The peritoneal tumor burden, vascular leakage, and malignant ascites formation were then assessed. Tumors and peritoneal lavage cells were analyzed by flow cytometry, multiplex tissue imaging, and a NanoString assay.Results JX treatment effectively suppressed peritoneal cancer progression and malignant ascites formation. It also restored the peritoneal anticancer immunity by activating peritoneal dendritic cells (DCs) and CD8+ T cells. Moreover, JX selectively infected and killed peritoneal colon cancer cells and promoted the intratumoral infiltration of DCs and CD8+ T cells into peritoneal tumor nodules. JX reinvigorates anticancer immunity by reprogramming immune-related transcriptional signatures within the tumor microenvironment. Notably, JX cooperates with immune checkpoint inhibitors (ICIs), anti-programmed death-1, anti-programmed death-ligand 1, and anti-lymphocyte-activation gene-3 to elicit a stronger anticancer immunity that eliminates peritoneal metastases and malignant ascites of colon cancer compared with JX or ICI alone.Conclusions Intraperitoneal immunotherapy with JX restores peritoneal anticancer immunity and potentiates immune checkpoint blockade to suppress PC and malignant ascites in colon cancer.

At an early immature growth stage of citrus, a hyperspectral camera of 369–1042 nm was employed to acquire 30 hyperspectral images in order to detect immature green fruit within citrus trees under natural illumination conditions. First, successive projections algorithm (SPA) were implemented to select 677, 804, 563, 962, and 405 nm wavebands and to construct multispectral images from the original hyperspectral images for further processing. Then, histogram threshold segmentation using NDVI of 804 and 677 nm was implemented to remove image backgrounds. Three slope parameters, calculated from the pairs 405 and 563 nm, 563 and 677 nm, and 804 and 962 nm were used to construct a classifier to identify the potential citrus fruit. Then, a marker-controlled watershed segmentation based on wavelet transform was applied to obtain potential fruit areas. Finally, a green fruit detection model was constructed according to Grey Level Co-occurrence Matrix (GLCM) texture features of the independent areas. Three supervised classifiers, logistic regression, random forest and support vector machine (SVM) were developed using texture features. The detection accuracies were 79%, 75%, and 86% for the logistic regression, random forest, and SVM models, respectively. The developed algorithm showed a great potential for identifying immature green citrus for an early yield estimation.

Purpose The status of tumor regression in rectal cancer after neoadjuvant concurrent chemoradiotherapy (CCRT) has significant effect on tumor recurrence and patient survival. The aim of this study was to evaluate the long-term oncologic outcomes of rectal cancer patients presenting complete response or down-staging of rectal cancer compared to patients with non-response after neoadjuvant therapy in advanced mid-to-lower rectal cancer. Methods We retrospectively reviewed 79 patients with stage II/III mid-to-lower rectal cancer following neoadjuvant CCRT between March 2003 and April 2012. Patients were classified into three groups according to down-staging tumor response after neoadjuvant CCRT: complete response group (CRG), partial response group (PRG), and non-response group (NRG). Results Of the 79 patients in the study, eight (10.1%), 31 (39.2%), and 40 (50.7%) were classified as CRG, PRG, and NRG, respectively. Median follow-up period was 57 months. There was significant difference in local recurrence (P=0.012) between the three groups, yet there was no significant difference in overall survival (CRG, 100%; PRG, 82.5%; NRG, 74.0%; P=0.244). There was a significant difference in disease-free survival (CRG, 100%; PRG, 90.1%; NRG, 57.7%; P=0.006). Conclusion Tumor response with complete response or down-staging provided better oncologic outcomes in terms of disease-free survival and local recurrence in locally advanced rectal cancer patients.

Objective Especially in emergency departments (EDs), a lack of internal medicine (IM) residents in charge causes difficulties in medical care and ED overcrowding. Thus, protocols without IM residents in EDs is needed. This study aimed to investigate changes in medical care when emergency medicine residents replaced the roles of IM residents. Methods This study was conducted at a single-site ED of a university medical center. The study group contained patients admitted to the IM department between September and December 2015, during which IM residents were absent in the ED. The control group contained patients admitted to the IM department between September and December 2014, during which IM residents were present in the ED. Changes in medical care between the presence and absence of IM residents in the ED were studied by comparing admission rates from the ED, length of ED stay, duration of hospitalization, and concordance of diagnoses between admission and discharge by the IM department. Results The study group contained 2,341 patients; the control group contained 2,215 patients. Admission rates from the ED increased by 53.4% (95% confidence interval [CI], P

Premise When plants are exposed to stress conditions, irreversible damage can occur, negatively impacting yields. It is therefore important to detect stress symptoms in plants, such as the accumulation of anthocyanin, as early as possible. Methods and Results Twenty‐two regression models in five color spaces were trained to develop a prediction model for plant anthocyanin levels from digital color imaging data. Of these, a quantile random forest regression model trained with standard red, green, blue (sRGB) color space data most accurately predicted the actual anthocyanin levels. This model was then used to noninvasively monitor the spatial and temporal accumulation of anthocyanin in Arabidopsis thaliana leaves. Conclusions The digital imaging–based nature of this protocol makes it a low‐cost and noninvasive method for the detection of plant stress. Applying a similar protocol to more economically viable crops could lead to the development of large‐scale, cost‐effective systems for monitoring plant health.

FAM19A5 is a secretory protein that is predominantly expressed in the brain. Although the FAM19A5 gene has been found to be associated with neurological and/or psychiatric diseases, only limited information is available on its function in the brain. Using FAM19A5-LacZ knock-in mice, we determined the expression pattern of FAM19A5 in developing and adult brains and identified cell types that express FAM19A5 in naïve and traumatic brain injury (TBI)–induced brains. According to X-gal staining results, FAM19A5 is expressed in the ventricular zone and ganglionic eminence at a very early stage of brain development, suggesting its functions are related to the generation of neural stem cells and oligodendrocyte precursor cells (OPCs). In the later stages of developing embryos and in adult mice, FAM19A5 expression expanded broadly to particular regions of the brain, including layers 2/3 and 5 of the cortex, cornu amonis (CA) region of the hippocampus, and the corpus callosum. X-gal staining combined with immunostaining for a variety of cell-type markers revealed that FAM19A5 is expressed in many different cell types, including neurons, OPCs, astrocytes, and microglia; however, only some populations of these cell types produce FAM19A5. In a subpopulation of neuronal cells, TBI led to increased X-gal staining that extended to the nucleus, marked by slightly condensed content and increased heterochromatin formation along the nuclear border. Similarly, nuclear extension of X-gal staining occurred in a subpopulation of OPCs in the corpus callosum of the TBI-induced brain. Together, these results suggest that FAM19A5 plays a role in nervous system development from an early stage and increases its expression in response to pathological conditions in subsets of neurons and OPCs of the adult brain.

BACKGROUND:Watson for oncology (WFO) is a cognitive computing system providing decision support. We evaluated the concordance rates between the treatment options determined by WFO and those determined by a multidisciplinary team (MDT). METHODS:We reviewed the medical charts of patients diagnosed with colorectal cancer who visited the MDT at a single tertiary medical center from November 2016 to April 2017. WFO classified the treatment options for specific patients into three categories: 'Recommended', 'For consideration', and 'Not recommended'. Concordance rates between the WFO- and MDT-determined chemotherapy options, and the factors that potentially influence the concordance rate, were analyzed. RESULTS:Sixty-nine patients with colorectal cancer met with the MDT from Nov. 2016 to Feb. 2017. The mean age of the patients was 62 years (range: 34-86 years), and more patients were male (47/69) than female. Of the 69 patients, 51 (73.9%) were diagnosed with colon cancer, of whom 46.4% received the same regimen recommendation from WFO ('Recommended') as they did from the MDT. After inclusion of the 'For consideration' category from WFO, the concordance rate increased to 87.0%. The concordance rate between MDT and NCCN guidelines was 97.1%, and that between the WFO and NCCN guidelines was 88.4%. The concordance rates between WFO and MDT were significantly lower in patients with stage II, IIIC, or IV disease (P