Surgical management for hepatocellular carcinoma with concurrent portal vein tumour thrombus and bile duct tumour thrombus: a case report.

Introduction: Hepatocellular carcinoma (HCC) associated with concurrent portal vein tumour thrombus (PVTT) and bile duct tumour thrombus (BDTT) is sporadic and presents a puzzle to management with miserable prognostic. Case presentation: The authors reported a case of HCC in the right liver with PVTT involving the right portal vein and BDTT developing in the common bile duct, detected in a 43-year-old man. The patient was admitted to our hospital with abdominal pain in the right hypochondrium and obstructive jaundice. Imaging studies showed a large mass in the right liver with invasion of the first branch of the portal vein and dilated intrahepatic bilateral bile ducts. A liver biopsy confirmed the diagnosis of hepatocellular carcinoma. Right hepatectomy plus thrombectomy en bloc with extrahepatic bile duct resection was performed. Subsequently, the patient received a postoperative adjuvant transarterial chemoembolization (PA-TACE) 1 month after surgery. Discussion: In the present case, the authors were not aiming for curative treatment by aggressive management but for palliative treatment. At the time of diagnosis, the tumour had already invaded the portal bifurcation. Hepatectomy plus thrombectomy en bloc with resection of common bile duct can remove biliary obstruction caused by BDTT, optimize portal flow by eliminating PVTT, and reduce the tumour burden, consequently improving the quality of life and liver function. Then, PA-TACE takes care of microfoci left behind by the surgery, which may prolong survival time. Conclusion: An aggressive therapeutic strategy should be considered in exceptional cases for resectable HCC with PVTT and obstructive BDTT. However, the follow-up period remains limited. A longer duration of observation is necessary to definitively assess the surgery's impact on patient's recurrence and survival time.

Artificial Intelligence in Colorectal Cancer: From Patient Screening over Tailoring Treatment Decisions to Identification of Novel Biomarkers.

BACKGROUND: Artificial intelligence (AI) is increasingly entering and transforming not only medical research but also clinical practice. In the last 10 years, new AI methods have enabled computers to perform visual tasks, reaching high performance and thereby potentially supporting and even outperforming human experts. This is in particular relevant for colorectal cancer (CRC), which is the 3rd most common cancer type in general, as along the CRC patient journey many complex visual tasks need to be performed: from endoscopy over imaging to histopathology; the screening, diagnosis, and treatment of CRC involve visual image analysis tasks. SUMMARY: In all these clinical areas, AI models have shown promising results by supporting physicians, improving accuracy, and providing new biological insights and biomarkers. By predicting prognostic and predictive biomarkers from routine images/slides, AI models could lead to an improved patient stratification for precision oncology approaches in the near future. Moreover, it is conceivable that AI models, in particular together with innovative techniques such as single-cell or spatial profiling, could help identify novel clinically as well as biologically meaningful biomarkers that could pave the way to new therapeutic approaches. KEY MESSAGES: Here, we give a comprehensive overview of AI in colorectal cancer, describing and discussing these developments as well as the next steps which need to be taken to incorporate AI methods more broadly into the clinical care of CRC.

Redox-Responsive Gold Nanoparticles Coated with Hyaluronic Acid and Folic Acid for Application in Targeting Anticancer Therapy.

Methotrexate (MTX) has poor water solubility and low bioavailability, and cancer cells can become resistant to it, which limits its safe delivery to tumor sites and reduces its clinical efficacy. Herein, we developed novel redox-responsive hybrid nanoparticles (NPs) from hyaluronic acid (HA) and 3-mercaptopropionic acid (MPA)-coated gold NPs (gold@MPA NPs), which were further conjugated with folic acid (FA). The design of FA-HA-ss-gold NPs aimed at enhancing cellular uptake specifically in cancer cells using an active FA/HA dual targeting strategy for enhanced tumor eradication. MTX was successfully encapsulated into FA-HA-ss-gold NPs, with drug encapsulation efficiency (EE) as high as >98.7%. The physicochemical properties of the NPs were investigated in terms of size, surface charges, wavelength reflectance, and chemical bonds. MTX was released in a sustained manner in glutathione (GSH). The cellular uptake experiments showed effective uptake of FA-HA-ss-gold over HA-ss-gold NPs in the deep tumor. Moreover, the release studies provided strong evidence that FA-HA-ss-gold NPs serve as GSH-responsive carriers. In vitro, anti-tumor activity tests showed that FA-HA-ss-gold/MTX NPs exhibited significantly higher cytotoxic activity against both human cervical cancer (HeLa) cells and breast cancer (BT-20) cells compared to gold only and HA-ss-gold/MTX NPs while being safe for human embryonic kidney (HEK-293) cells. Therefore, this present study suggests that FA-HA-ss-gold NPs are promising active targeting hybrid nanocarriers that are stable, controllable, biocompatible, biodegradable, and with enhanced cancer cell targetability for the safe delivery of hydrophobic anticancer drugs.

Injectable and Multifunctional Hydrogels Based on Poly(N-acryloyl glycinamide) and Alginate Derivatives for Antitumor Drug Delivery.

Chemotherapy is a conventional treatment that uses drugs to kill cancer cells; however, it may induce side effects and may be incompletely effective, leading to the risk of tumor recurrence. To address this issue, we developed novel injectable thermal/near-infrared (NIR)-responsive hydrogels to control drug release. The injectable hydrogel formulation was composed of biocompatible alginates, poly(N-acryloyl glycinamide) (PNAGA) copolymers with an upper critical solution temperature, and NIR-responsive cross-linkers containing coumarin groups, which were gelated through bioorthogonal inverse electron demand Diels-Alder reactions. The hydrogels exhibited quick gelation times (120-800 s) and high drug loading efficiencies (>90%). The hydrogels demonstrated a higher percentage of drug release at 37 °C than that at 25 °C due to the enhanced swelling behavior of temperature-responsive PNAGA moieties. Upon NIR irradiation, the hydrogels released most of the entrapped doxorubicin (DOX) (97%) owing to the cleavage of NIR-sensitive coumarin ester groups. The hydrogels displayed biocompatibility with normal cells, while induced antitumor activity toward cancer cells. DOX/hydrogels treated with NIR light inhibited tumor growth in nude mice bearing tumors. In addition, the injected hydrogels emitted red fluorescence upon excitation at a green wavelength, so that the drug delivery and hydrogel degradation in vivo could be tracked in the xenograft model.

WITHDRAWN: TRIM44 promotes autophagy through SQSTM1 oligomerization in the response to oxidative stress induced by Arsenic Trioxide in cancer cells.

The authors have requested that this preprint be removed from Research Square.

NIR-responsive carboxymethyl-cellulose hydrogels containing thioketal-linkages for on-demand drug delivery system.

Near-infrared (NIR) light-responsive hydrogels have emerged as a highly promising strategy for effective anticancer therapy owing to the remotely controlled release of chemotherapeutic molecules with minimal invasive manner. In this study, novel NIR-responsive hydrogels were developed from reactive oxygen species (ROS)-cleavable thioketal cross-linkers which possessed terminal tetrazine groups to undergo a bio-orthogonal inverse electron demand Diels Alder click reaction with norbornene modified carboxymethyl cellulose. The hydrogels were rapidly formed under physiological conditions and generated N2 gas as a by-product, which led to the formation of porous structures within the hydrogel networks. A NIR dye, indocyanine green (ICG) and chemotherapeutic doxorubicin (DOX) were co-encapsulated in the porous network of the hydrogels. Upon NIR-irradiation, the hydrogels showed spatiotemporal release of encapsulated DOX (>96 %) owing to the cleavage of thioketal bonds by interacting with ROS generated from ICG, whereas minimal release of encapsulated DOX (<25 %) was observed in the absence of NIR-light. The in vitro cytotoxicity results revealed that the hydrogels were highly cytocompatible and did not induce any toxic effect on the HEK-293 cells. In contrast, the DOX + ICG-encapsulated hydrogels enhanced the chemotherapeutic effect and effectively inhibited the proliferation of Hela cancer cells when irradiated with NIR-light.

Endoscopic papillectomy for ampullary lesions of minor papilla.

BACKGROUND AND AIMS: Ampullary lesions (ALs) of the minor duodenal papilla are extremely rare. Endoscopic papillectomy (EP) is a routinely used treatment for AL of the major duodenal papilla, but the role of EP for minor AL has not been accurately studied. METHODS: We identified 20 patients with ALs of minor duodenal papilla in the multicentric database from the Endoscopic Papillectomy vs Surgical Ampullectomy vs Pancreatitcoduodenectomy for Ampullary Neoplasm study, which included 1422 EPs. We used propensity score matching (nearest-neighbor method) to match these cases with ALs of the major duodenal papilla based on age, sex, histologic subtype, and size of the lesion in a 1:2 ratio. Cohorts were compared by means of chi-square or Fisher exact test as well as Mann-Whitney U test. RESULTS: Propensity score-based matching identified a cohort of 60 (minor papilla 20, major papilla 40) patients with similar baseline characteristics. The most common histologic subtype of lesions of minor papilla was an ampullary adenoma in 12 patients (3 low-grade dysplasia and 9 high-grade dysplasia). Five patients revealed nonneoplastic lesions. Invasive cancer (T1a), adenomyoma, and neuroendocrine neoplasia were each found in 1 case. The rate of complete resection, en-bloc resection, and recurrences were similar between the groups. There were no severe adverse events after EP of lesions of minor papilla. One patient had delayed bleeding that could be treated by endoscopic hemostasis, and 2 patients showed a recurrence in surveillance endoscopy after a median follow-up of 21 months (interquartile range, 12-50 months). CONCLUSIONS: EP is safe and effective in ALs of the minor duodenal papilla. Such lesions could be managed according to guidelines for EP of major duodenal papilla.

Flexible Iron-On Sensor Embedded in Smart Sock for Gait Event Detection.

Portable and wearable electronics for biomechanical data collection have become a growing part of everyday life. As smart technology improves and integrates into our lives, some devices remain ineffective, expensive, or difficult to access. We propose a washable iron-on textile pressure sensor for biometric data acquisition. Biometric data, such as human gait, are a powerful tool for the monitoring and diagnosis of ambulance and physical activity. To demonstrate this, our washable iron-on device is embedded into a sock and compared to gold standard force plate data. Biomechanical testing showed that our embedded sensor displayed a high aptitude for gait event detection, successfully identifying over 96% of heel strike and toe-off gait events. Our device demonstrates excellent attributes for further investigations into low-cost, washable, and highly versatile iron-on textiles for specialized biometric analysis.

Facile Fabrication of NIR-Responsive Alginate/CMC Hydrogels Derived through IEDDA Click Chemistry for Photothermal-Photodynamic Anti-Tumor Therapy.

Novel chemically cross-linked hydrogels derived from carboxymethyl cellulose (CMC) and alginate (Alg) were prepared through the utilization of the norbornene (Nb)-methyl tetrazine (mTz) click reaction. The hydrogels were designed to generate reactive oxygen species (ROS) from an NIR dye, indocyanine green (ICG), for combined photothermal and photodynamic therapy (PTT/PDT). The cross-linking reaction between Nb and mTz moieties occurred via an inverse electron-demand Diels-Alder chemistry under physiological conditions avoiding the need for a catalyst. The resulting hydrogels exhibited viscoelastic properties (G' ~ 492-270 Pa) and high porosity. The hydrogels were found to be injectable with tunable mechanical characteristics. The ROS production from the ICG-encapsulated hydrogels was confirmed by DPBF assays, indicating a photodynamic effect (with NIR irradiation at 1-2 W for 5-15 min). The temperature of the ICG-loaded hydrogels also increased upon the NIR irradiation to eradicate tumor cells photothermally. In vitro cytocompatibility assessments revealed the non-toxic nature of CMC-Nb and Alg-mTz towards HEK-293 cells. Furthermore, the ICG-loaded hydrogels effectively inhibited the metabolic activity of Hela cells after NIR exposure.

Comprehensive Analysis of the Prognostic Significance of the TRIM Family in the Context of TP53 Mutations in Cancers.

The p53 protein is an important tumor suppressor, and TP53 mutations are frequently associated with poor prognosis in various cancers. Mutations in TP53 result in a loss of p53 function and enhanced expression of cell cycle genes, contributing to the development and progression of cancer. Meanwhile, several tripartite motif (TRIM) proteins are known to regulate cell growth and cell cycle transition. However, the prognostic values between TP53 and TRIM family genes in cancer are unknown. In this study, we analyzed the relationship between the TP53 mutations and TRIM family proteins and evaluated the prognostic significance of TRIM family proteins in cancer patients with P53 mutations. Our findings identified specific TRIM family members that are upregulated in TP53 mutant tumors and are associated with the activation of genes related to a cell-cycle progression in the context of TP53 mutations.

Spinal cysticercosis: A case report.

Spinal cysticercosis is a rare and severe cysticercosis complication. The pathology is from the inflammatory reaction and granuloma formation around the eggs, which cause focal neurological deficits. Because of the rarity of this condition, diagnosis may be delayed and confused with other myelopathies such as neoplasms or myelitis. We report a 42-year-old woman with low back pain and paraplegia. Magnetic resonance imaging showed a lesion in the spinal canal at the level of L4/L5 that was toward the diagnosis of myelitis. The patient underwent an open biopsy, and the result was granulomatosis caused by cysticercosis. The patient was then given an anticysticercosis medication and gradually recovered.

[Interventional endoscopy in gastroenterology]. / Interventionelle Endoskopie in der Gastroenterologie.

Essential innovations in interventional endoscopy have significantly broadened the treatment armamentarium in gastroenterology. The treatment and complication management of intraepithelial neoplasms and early forms of cancer are increasingly being primarily addressed endoscopically. In cases of endoluminal lesions with no risk of lymph node or distant metastases, endoscopic mucosal resection and endoscopic submucosal dissection have become established as standards. For broad-based adenomas, coagulation of the resection margins should be performed in the case of a piecemeal resection. Submucosal lesions can be reached and resected by tunneling techniques. Peroral endoscopic myotomy in cases of achalasia is a new treatment option for hypertensive and hypercontractile motility disorders. In addition, endoscopic myotomy for gastroparesis has shown very promising results. In this article, new resection techniques and so-called third space endoscopy are presented and critically discussed.

Charge-Reduced Particles via Self-Propelled Electrohydrodynamic Atomization for Drug Delivery Applications.

Electrohydrodynamic atomization (EHDA) provides unparalleled control over the size and production rate of particles from solution. However, conventional methods produce highly charged particles that are not appropriate for inhalation drug delivery. We present a self-propelled EHDA system to address this challenge, a promising one-step platform for generating and delivering charge-reduced particles. Our approach uses a sharp electrode to produce ion wind, which reduces the cumulative charge in the particles and transports them to a target in front of the nozzle. We effectively controlled the morphologies of polymer products created from poly(vinylidene fluoride) (PVDF) at various concentrations. Our technique has also been proven safe for bioapplications, as evidenced by the delivery of PVDF particles onto breast cancer cells. The combination of simultaneous particle production and charge reduction, along with its direct delivery capability, makes the self-propelled EHDA a versatile technique for drug delivery applications.

Reduction-Responsive Chitosan-Based Injectable Hydrogels for Enhanced Anticancer Therapy.

Selective delivery of anticancer drug molecules to the tumor site enhances local drug dosages, which leads to the death of cancer cells while simultaneously minimizing the negative effects of chemotherapy on other tissues, thereby improving the patient's quality of life. To address this need, we developed reduction-responsive chitosan-based injectable hydrogels via the inverse electron demand Diels-Alder reaction between tetrazine groups of disulfide-based cross-linkers and norbornene groups of chitosan derivatives, which were applied to the controlled delivery of doxorubicin (DOX). The swelling ratio, gelation time (90-500 s), mechanical strength (G'~350-850 Pa), network morphology, and drug-loading efficiency (≥92%) of developed hydrogels were investigated. The in vitro release studies of the DOX-loaded hydrogels were performed at pH 7.4 and 5.0 with and without DTT (10 mM). The biocompatibility of pure hydrogel and the in vitro anticancer activity of DOX-loaded hydrogels were demonstrated via MTT assay on HEK-293 and HT-29 cancer cell lines, respectively.

Modified gracilis muscle flap in facial reanimation: U-shaped design.

BACKGROUND: Surgical treatment of long-term facial palsy has been reported using various techniques, including functioning muscle-free flaps. The free gracilis muscle flap is the most common because of its many advantages. Our study presents a modified way of shaping the gracilis muscle for transfer to the face to improve the restoration of natural smiles. METHODS: This retrospective study assessed 5 patients who received the classical technique and 43 patients who received modified, U-shaped, free gracilis muscle flap for smile reanimation from 2013 to 2018. The surgery is single-staged. Preoperative and postoperative photos were taken. Functional outcomes were evaluated using the Terzis and Noah score and the Chuang smile excursion score. RESULTS: The mean patient age at the time of operation was 31 years. The length of gracilis muscle harvested was 12-13 cm. Of the 43 patients who received U-shaped design-free gracilis muscle, results were excellent for 15 (34.9%), good for 20 (46.5%), and fair for 8 (18.6%) followed the Terzis and Noah score. The Chuang smile excursion score was 2 for 16.3%, 3 for 46.5%, and 4 for 37.2% of 43 patients. Of the 5 patients who underwent classical technique, there are no excellent results based on the Terzis and Noah score. The Chuang smile excursion score was only 1 and 2. CONCLUSIONS: The U-shaped modification to the gracilis muscle-free flap is a simple and effective technique to help restore a symmetrical and natural smile in patients with facial palsy.

Comprehensive transcriptomic analysis to identify biological and clinical differences in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CC) is a rare and aggressive disease with limited therapeutic options and a poor prognosis. All available public records of cohorts reporting transcriptomic data on intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) were collected with the aim to provide a comprehensive gene expression-based classification with clinical relevance. METHODS: A total of 543 patients with primary tumor tissues profiled by RNAseq and microarray platforms from seven public datasets were used as a discovery set to identify distinct biological subgroups. Group predictors developed on the discovery sets were applied to a single cohort of 131 patients profiled with RNAseq for validation and assessment of clinical relevance leveraging machine learning techniques. RESULTS: By unsupervised clustering analysis of gene expression data we identified both in the ICC and ECC discovery datasets four subgroups characterized by a distinct type of immune infiltrate and signaling pathways. We next developed class predictors using short gene list signatures and identified in an independent dataset subgroups of ICC tumors at different prognosis. CONCLUSIONS: The developed class-predictor allows identification of CC subgroups with specific biological features and clinical behavior at single-sample level. Such results represent the starting point for a complete molecular characterization of CC, including integration of genomics data to develop in clinical practice.

Prediction model for drug response of acute myeloid leukemia patients.

Despite some encouraging successes, predicting the therapy response of acute myeloid leukemia (AML) patients remains highly challenging due to tumor heterogeneity. Here we aim to develop and validate MDREAM, a robust ensemble-based prediction model for drug response in AML based on an integration of omics data, including mutations and gene expression, and large-scale drug testing. Briefly, MDREAM is first trained in the BeatAML cohort (n = 278), and then validated in the BeatAML (n = 183) and two external cohorts, including a Swedish AML cohort (n = 45) and a relapsed/refractory acute leukemia cohort (n = 12). The final prediction is based on 122 ensemble models, each corresponding to a drug. A confidence score metric is used to convey the uncertainty of predictions; among predictions with a confidence score >0.75, the validated proportion of good responders is 77%. The Spearman correlations between the predicted and the observed drug response are 0.68 (95% CI: [0.64, 0.68]) in the BeatAML validation set, -0.49 (95% CI: [-0.53, -0.44]) in the Swedish cohort and 0.59 (95% CI: [0.51, 0.67]) in the relapsed/refractory cohort. A web-based implementation of MDREAM is publicly available at https://www.meb.ki.se/shiny/truvu/MDREAM/ .

Endoscopic papillectomy for ampullary lesions in patients with familial adenomatous polyposis compared with sporadic lesions: a propensity score-matched cohort.

BACKGROUND: Familial adenomatous polyposis (FAP) is a rare inherited syndrome that predisposes the patient to cancer. Treatment of FAP-related ampullary lesions is challenging and the role of endoscopic papillectomy has not been elucidated. We retrospectively analyzed the outcomes of endoscopic papillectomy in matched cohorts of FAP-related and sporadic ampullary lesions (SALs). METHODS: This retrospective multicenter study included 1422 endoscopic papillectomy procedures. Propensity score matching including age, sex, comorbidity, histologic subtype, and size was performed. Main outcomes were complete resection (R0), technical success, complications, and recurrence. RESULTS: Propensity score matching identified 202 patients (101 FAP, 101 SAL) with comparable baseline characteristics. FAP patients were mainly asymptomatic (79.2 % [95 %CI 71.2-87.3] vs. 46.5 % [95 %CI 36.6-56.4]); P < 0.001). The initial R0 rate was significantly lower in FAP patients (63.4 % [95 %CI 53.8-72.9] vs. 83.2 % [95 %CI 75.8-90.6]; P = 0.001). After repeated interventions (mean 1.30 per patient), R0 was comparable (FAP 93.1 % [95 %CI 88.0-98.1] vs. SAL 97.0 % [95 %CI 93.7-100]; P = 0.19). Adverse events occurred in 28.7 %. Pancreatitis and bleeding were the most common adverse events in both groups. Severe adverse events were rare (3.5 %). Overall, 21 FAP patients (20.8 % [95 %CI 12.7-28.8]) and 16 SAL patients (15.8 % [95 %CI 8.6-23.1]; P = 0.36) had recurrence. Recurrences occurred later in FAP patients (25 [95 %CI 18.3-31.7] vs. 2 [95 %CI CI 0.06-3.9] months). CONCLUSIONS: Endoscopic papillectomy was safe and effective in FAP-related ampullary lesions. Criteria for endoscopic resection of ampullary lesions can be extended to FAP patients. FAP patients have a lifetime risk of relapse even after complete resection, and require long-time surveillance.

Comparison between traumatic and atraumatic over-the-scope clips in patients with duodenal ulcer bleeding: a retrospective analysis with propensity score-based matching.

BACKGROUND AND AIMS: Over-the-scope clips (OTSCs) substantially improved the endoscopic armamentarium for the treatment of severe GI bleeding and can potentially overcome limitations of standard clips. Data indicate a superiority of OTSCs in hemostasis as first- and second-line therapy. However, the impact of the OTSC designs, in particular the traumatic (-t) or atraumatic (-a) type, in duodenal ulcer bleeding has not been analyzed so far. METHODS: This was a retrospective analysis of a prospective collected database from 2009 to 2020 of 6 German endoscopic centers. All patients who underwent emergency endoscopy and were treated using an OTSC for duodenal ulcer bleeding were included. OTSC-t and OTSC-a patients were compared by the Fisher exact test, χ2 test, or Mann-Whitney U test as appropriate. A propensity score-based 1:1 matching was performed to obtain equal distribution of baseline characteristics in both groups. RESULTS: The entire cohort comprised 173 patients (93 OTSC-a, 80 OTSC-t). Age, gender, anticoagulant therapy, Rockall score, and treatment regimen had similar distributions in the 2 groups. However, the OTSC-t group showed significantly more active bleeding ulcers (Forrest Ia/b). Matching identified 132 patients (66 in both groups) with comparable baseline characteristics. Initial bleeding hemostasis (OTSC-a, 90.9%; OTSC-t, 87.9%; P = .82) and 72-hour mortality (OTSC-a, 4.5%; OTSC-t, 6.0%; P > .99) were not significantly different, but the OTSC-t group revealed a clearly higher rate of recurrent bleeding (34.9% vs 7.6%, P < .001) and necessity of red blood cell transfusions (5.1 ± 3.4 vs 2.5 ± 2.4 concentrates, P < .001). CONCLUSIONS: For OTSC use, the OTSC-a should be the preferred option for duodenal ulcer bleeding.

A Comprehensive Landscape of Imaging Feature-Associated RNA Expression Profiles in Human Breast Tissue.

The expression abundance of transcripts in nondiseased breast tissue varies among individuals. The association study of genotypes and imaging phenotypes may help us to understand this individual variation. Since existing reports mainly focus on tumors or lesion areas, the heterogeneity of pathological image features and their correlations with RNA expression profiles for nondiseased tissue are not clear. The aim of this study is to discover the association between the nucleus features and the transcriptome-wide RNAs. We analyzed both microscopic histology images and RNA-sequencing data of 456 breast tissues from the Genotype-Tissue Expression (GTEx) project and constructed an automatic computational framework. We classified all samples into four clusters based on their nucleus morphological features and discovered feature-specific gene sets. The biological pathway analysis was performed on each gene set. The proposed framework evaluates the morphological characteristics of the cell nucleus quantitatively and identifies the associated genes. We found image features that capture population variation in breast tissue associated with RNA expressions, suggesting that the variation in expression pattern affects population variation in the morphological traits of breast tissue. This study provides a comprehensive transcriptome-wide view of imaging-feature-specific RNA expression for healthy breast tissue. Such a framework could also be used for understanding the connection between RNA expression and morphology in other tissues and organs. Pathway analysis indicated that the gene sets we identified were involved in specific biological processes, such as immune processes.