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Subepithelial lesions (SEL) of the GI tract represent a mix of benign and potentially malignant entities including tumors, cysts, or extraluminal structures causing extrinsic compression of the gastrointestinal wall. SEL can occur anywhere along the GI tract and are frequently incidental findings encountered during endoscopy or cross-sectional imaging. This clinical guideline of the American College of Gastroenterology was developed using the Grading of Recommendations Assessment, Development, and Evaluation process and is intended to suggest preferable approaches to a typical patient with a SEL based on the currently available published literature. Among the recommendations, we suggest endoscopic ultrasound (EUS) with tissue acquisition to improve diagnostic accuracy in the identification of solid nonlipomatous SEL and EUS fine-needle biopsy alone or EUS fine-needle aspiration with rapid on-site evaluation sampling of solid SEL. There is insufficient evidence to recommend surveillance vs resection of gastric gastrointestinal stromal tumors (GIST) <2 cm in size. Owing to their malignant potential, we suggest resection of gastric GIST >2 cm and all nongastric GIST. When exercising clinical judgment, particularly when statements are conditional suggestions and/or treatments pose significant risks, health-care providers should incorporate this guideline with patient-specific preferences, medical comorbidities, and overall health status to arrive at a patient-centered approach.

This article examines how patent protection in developing countries affects the technology licensing strategy of US multinational firms and the associated technology transfer flows. Strengthening patent rights lowers appropriability hazards and so reduces the firms' reliance on affiliated licensing as the more secure means of transfer (the internalization effect). However lower appropriability hazards also encourage the firms to increase of teachnology transfer via licensing both within and outside the firm (the appropriability effect). Which effect prevails depends on the underlying technological complexity of the firms' product. We find that a strengthening of patent protection in the host country increases the incentive to license innovations to unaffiliated parties. While unaffiliated licensing rises among all firms, the volume of affiliated licensing falls among complex-technology firms but rises among simple-technology firms. The positive appropriability effect on affiliated licensing is strong enough among simple-technology firms that the entire composition of their licensing further shifts towards affiliated parties. The results are significant for recent work on the internalization theories of multinational firms and the interaction between firm strategy and the institutional environment, as well as for patent policy in the developing world, where access to knowledge is critical.

Global standards of patent protection have been strengthened and harmonized in recent years. Despite the heated policy debates and theoretical controversies, empirical studies of the consequences for innovative activity are scant. This paper contributes to the debate by providing an empirical analysis of the effects of patent strength on different aspects of innovative activity, namely firm-level research and development (R&D), domestic patenting, and foreign patenting. The analysis employs an updated index of patent rights. The results show the complexity of evaluating the effects of patent reform on innovative activity, since the effects vary nonlinearly (depending on the initial level of patent strength) and vary by a country's level of economic development. Overall, for developing economies, patent strength negatively affects domestic patent filings and insignificantly affects R&D and foreign patent filings. For developed economies, patent strength positively affects R&D and domestic patent filings, and negatively affects foreign patent filings, after some critical level of patent protection is reached.

Molecular imaging using positron emission tomography (PET) provides sensitive detection and mapping of molecular targets. While cancer-associated fibroblasts and integrins have been proposed as targets for imaging of pancreatic ductal adenocarcinoma (PDAC), herein, spatial transcriptomics and proteomics of human surgical samples are applied to select PDAC targets. We find that selected cancer cell surface markers are spatially correlated and provide specific cancer localization, whereas the spatial correlation between cancer markers and immune-related or fibroblast markers is low. Claudin-4 expression increases ~16 fold in cancer as compared with normal pancreas, and tight junction localization confers low background for imaging in normal tissue. We develop a peptide-based molecular imaging agent targeted to claudin-4 with accumulation to ~25% injected activity per cubic centimeter (IA/cc) in metastases and ~18% IA/cc in tumors. Our work motivates a data-driven approach to selection of molecular targets. Improved imaging methods are crucial to map pancreatic ductal adenocarcinoma (PDAC). Here, the authors analyse PDAC samples using spatial transcriptomics and proteomics, identify claudin-4 as a potential theranostic target, and develop an imaging agent to track claudin-4 in primary and metastatic PDAC tumours.

PurposeTo determine if quantitative MRI techniques can be helpful to evaluate chronic pancreatitis (CP) in a setting of multi-institutional study.MethodsThis study included a subgroup of participants (n = 101) enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study (NCT03099850) from February 2019 to May 2021. MRI was performed on 1.5 T using Siemens and GE scanners at seven clinical centers across the USA. Quantitative MRI parameters of the pancreas included T1 relaxation time, extracellular volume (ECV) fraction, apparent diffusion coefficient (ADC), and fat signal fraction. We report the diagnostic performance and mean values within the control (n = 50) and CP (n = 51) groups. The T1, ECV and fat signal fraction were combined to generate the quantitative MRI score (Q-MRI).ResultsThere was significantly higher T1 relaxation time; mean 669 ms (± 171) vs. 593 ms (± 82) (p = 0.006), ECV fraction; 40.2% (± 14.7) vs. 30.3% (± 11.9) (p < 0.001), and pancreatic fat signal fraction; 12.2% (± 5.5) vs. 8.2% (± 4.4) (p < 0.001) in the CP group compared to controls. The ADC was similar between groups (p = 0.45). The AUCs for the T1, ECV, and pancreatic fat signal fraction were 0.62, 0.72, and 0.73, respectively. The composite Q-MRI score improved the diagnostic performance (cross-validated AUC: 0.76).ConclusionQuantitative MR parameters evaluating the pancreatic parenchyma (T1, ECV fraction, and fat signal fraction) are helpful in the diagnosis of CP. A Q-MRI score that combines these three MR parameters improves diagnostic performance. Further studies are warranted with larger study populations including patients with acute and recurrent acute pancreatitis and longitudinal follow-ups.

Defecation, a fundamental physiological process, remains underexplored despite its importance in human health. To address this gap, a smart toilet system is developed that enables real‐time monitoring of defecation behaviors. Analyzing 45 defecation events from 11 participants, key defecation parameters are identified, including stool dropping duration, stool thickness, and eu‐tenesmus interval. Stool dropping duration follows a log‐normal distribution, with longer durations (>5 s) linked to lower Bristol Stool Form Scale (BSFS) scores, suggesting constipation (p = 0.008 for BSFS1/2/3 vs BSFS5/6/7). Stool thickness decreases with increasing BSFS scores (p = 5 × 10⁻⁶ for BSFS1/2/3 vs BSFS5/6/7), validating its role as an objective marker for bowel function. Eu‐tenesmus is introduced, defined as the interval between the last stool drop and cleansing, averaging 74.8 s. It shows significant gender differences (p = 0.014) but no correlation with stool consistency, suggesting its potential as an independent biomarker for gut health. Defecation behaviors between humans and animals is also compared in detail. Longitudinal monitoring demonstrates the potential for personalized health tracking and dietary recommendations. Furthermore, the feasibility of biometric identification is established using 11 defecation‐related parameters, including stool properties and cleansing behavior. These features enable high participant differentiation, supporting non‐invasive identity verification. A healthcare toilet system is introduced to passively measure defecation behavior. Real‐time data on stool dropping duration, thickness, and a newly defined “eu‐tenesmus” interval show correlations with stool form and gender differences. Results from 45 defecation events reveal a promising method for comprehensive defecation analysis. Defecation‐time and behavior metrics offer potential for biometric identification, illuminating personalized gut health monitoring.

Do Southern intellectual property rights (IPRs) affect Northern innovation? There is much theoretical debate on the impact of IPRs in the South on the incentives of Northern firms to innovate and transfer technologies to the South. While empirical research exists on the effects of Southern IPRs on Northern technology transfers, empirical evidence on the effects of Southern IPRs on Northern innovation is absent. This paper seeks to fill that gap. Using a comprehensive micro-database of US multinational firms and their foreign affiliates in developed countries, this study finds that patent protection in the South has statistically insignificant effects on the research and development of these firms. Rather, the patent regimes of developed countries matter significantly to the R&D of these firms. Developing countries constitute a relatively small share of the world market so that variations in the patent rights of developing economies have contributed marginally to Northern incentives for R&D.

Abstract Purpose Pancreatogenic diabetes refers to diabetes mellitus (DM) that develops in the setting of a disease of the exocrine pancreas, including pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). We sought to evaluate whether a blunted nutrient response of pancreatic polypeptide (PP) can differentiate these DM subtypes from type 2 DM (T2DM). Methods Subjects with new-onset DM (<3 years’ duration) in the setting of PDAC (PDAC-DM, n = 28), CP (CP-DM, n = 38), or T2DM (n = 99) completed a standardized mixed meal tolerance test, then serum PP concentrations were subsequently measured at a central laboratory. Two-way comparisons of PP concentrations between groups were performed using Wilcoxon rank-sum test and analysis of covariance while adjusting for age, sex, and body mass index. Results The fasting PP concentration was lower in both the PDAC-DM and CP-DM groups than in the T2DM group (P = 0.03 and <0.01, respectively). The fold change in PP at 15 minutes following meal stimulation was significantly lower in the PDAC-DM (median, 1.869) and CP-DM (1.813) groups compared with T2DM (3.283; P < 0.01 for both comparisons). The area under the curve of PP concentration was significantly lower in both the PDAC-DM and CP-DM groups than in T2DM regardless of the interval used for calculation and remained significant after adjustments. Conclusions Fasting PP concentrations and the response to meal stimulation are reduced in new-onset DM associated with PDAC or CP compared with T2DM. These findings support further investigations into the use of PP concentrations to characterize pancreatogenic DM and to understand the pathophysiological role in exocrine pancreatic diseases (NCT03460769).