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* Context.--Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood. Objective.--To characterize the potential morphologic and clinical outcome differences in PDACs harboring distinct mutant KRAS alleles. Design.--Cohort 1 consisted of 127 primary conventional PDACs with no neoadjuvant therapy, excluding colloid/ mucinous, adenosquamous, undifferentiated, and intraductal papillary mucinous neoplasm-associated carcinomas, for which an in-house 42-gene mutational panel had been performed. A morphologic classification system was devised wherein each tumor was assigned as conventional, papillary/ large duct (P+LD, defined as neoplastic glands with papillary structure and/or with length [greater than or equal to]0.5 mm), or poorly differentiated (when the aforementioned component was 60% or more of the tumor). Cohort 2 was a cohort of 88 PDACs in The Cancer Genome Atlas, which were similarly analyzed. Results.--In both cohorts, there was significant enrichment of P+LD morphology in PDACs with KRAS G12V and G12R compared with G12D. In the entire combined cohort, Kaplan-Meier analyses showed longer overall survival (OS) with KRAS G12R as compared with G12D (median OS of 1255 versus 682 days, P = .03) and in patients whose PDACs displayed P+LD morphology as compared with conventional morphology (median OS of 1175 versus 684 days, P = .04). In the adjuvant-only subset, KRAS G12R had the longest OS compared with G12D, G12V, and other alleles (median OS unreached/undefined versus 1009,1129, and 1222 days, respectively). Conclusions.--PDACs with different mutant KRAS alleles are associated with distinct morphologies and clinical outcomes, with KRAS G12R allele associated with P+LD morphology and longer OS when compared with G12D using Kaplan-Meier studies. (Arch Pathol Lab Med. 2024;148:1299-1309; doi: 10.5858/arpa.2023-0005-OA), Pancreatic cancer, the majority of which consists of pancreatic ductal adenocarcinomas (PDACs), is projected to become the second leading cause of cancer-related deaths by 2030. (1) Surgical resectability is the [...]

Fluorinated small molecules are prevalent across the functional small-molecule spectrum, but the scarcity of naturally occurring sources creates an opportunity for creative endeavour in developing routes to access these important materials. Iodine(I)/iodine(III) catalysis has proven to be particularly well-suited to this task, enabling abundant alkene substrates to be readily intercepted by in situ-generated λ3-iodanes and processed to high-value (di)fluorinated products. These organocatalysis paradigms often emulate metal-based processes by engaging the π bond and, in the case of styrenes, facilitating fluorinative phenonium-ion rearrangements to generate difluoromethylene units. Here we demonstrate that enynes are competent proxies for styrenes, thereby mitigating the recurrent need for aryl substituents, and enabling highly versatile homopropargylic difluorides to be generated in an operationally simple manner. The scope of the method is disclosed, together with application in target synthesis (>30 examples, up to >90% yield).

Functional movement disorder (FMD) is a common subtype of functional neurological disorder (FND), mainly manifested as gait abnormality, tremor, dystonia, postural abnormality, and so on. In recent years, researchers have adopted multi⁃ disciplinary team (MDT) to improve the treatment effect of FMD, among which cognitive behavioral therapy (CBT) has been widely used as an effective psychotherapy program. This article reviews the research progress of CBT for FMD in order to provide guidance for clinical treatment.

Highly accurate testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the point of care (POC) is an unmet diagnostic need in emergency care and time-sensitive outpatient care settings. Reverse transcription-PCR (RT-PCR) technology is the gold standard for SARS-CoV-2 diagnostics. We performed a multisite U.S. study comparing the clinical performance of the first U.S. Food and Drug Administration (FDA)-authorized POC RT-PCR for detection of SARS-CoV-2 in 20 min, the cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test, to the most widely used RT-PCR laboratory test, the cobas 68/8800 SARS-CoV-2 test. Clinical nasopharyngeal swab specimens from 444 patients with 357 evaluable specimens at five U.S. clinical laboratories were enrolled from 21 September 2020 to 23 October 2020. The overall agreement between the Liat and 68/8800 systems for SARS-CoV-2 diagnostics was 98.6% (352/357). Using Liat, positive percent agreement for SARS-CoV-2 was 100% (162/162) and the negative percent agreement was 97.4% (190/195). The Liat is an RT-PCR POC test that provides highly accurate SARS-CoV-2 results in 20 min with performance equivalent to that of high-throughput laboratory molecular testing. Rapid RT-PCR testing at the POC can enable more timely infection control and individual care decisions for coronavirus disease 2019.

Formation control of high-order linear discrete-time multiple unmanned aerial vehicles (multi-UAVs) systems with multiplicative noises is studied in this article. Because of the existence of multiplicative noises, classical methods for discrete-time system control problems should be improved. Here, we develop a new discrete-time formation protocol for multi-UAVs systems. The stochastic Lyapunov stability theory and the positive definiteness theory of a generalized algebraic Riccati equation are then used to derive sufficient conditions for formation feasibility. [ABSTRACT FROM AUTHOR]

The applications of resveratrol (RES) and puerarin (PUE) with notable physiological functions are greatly limited in functional food and pharmaceutical industries due to their poor water solubility and chemical instability. Accordingly, co‐loading of RES and PUE into chitosan‐based nanoparticles (NPs) is performed here by an anti‐solvent method to improve their bioavailability. The fabricated NPs at 8:1 mass ratio of carboxymethyl chitosan (CMC) to chitosan hydrochloride (CHC) with the particle size of 375.1 nm and zeta potential of +36.5 mV showed encouraging encapsulation efficiency and loading capacity at 85.2% (RES), 89.5% (PUE), and 15.5%. The microstructure of core–shell CMC–CHC was confirmed through dynamic light scattering and transmission electron microscopy. Molecular docking and storage stability indicating the more beneficial encapsulation of chitosan derivatives to PUE in comparison to RES. Cellular antioxidant activity experiments showed that the bioactivities of PUE/RES after loading with 20 and 40 mg·mL−1 were improved by 13.2% and 18.5%, respectively, with respect to free ones. Therefore, RES/PUE‐loaded CHC–CMC NPs were successfully prepared in this study, thus significantly improving the RES and PUE bioavailability and promoting their applications in functional food and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

The abnormal overexpression of FLT3 kinase is intimately associated with pathogenesis of acute myeloid leukemia (AML), positioning FLT3 inhibitors as pivotal therapeutic agents. Despite the availability of three FDA‐approved FLT3 inhibitors, their clinical utility is hampered by resistance stemming from tyrosine kinase domain (TKD) mutations. Through an integrative analysis of case studies, we identified a potential advantage of type I FLT3 inhibitors in overcoming TKD mutation‐induced resistance. Structure–activity relationships (SAR) analysis indicated that FW‐1 exhibited over 50% inhibition against FLT3 at a concentration of 1 μM and demonstrated potent activity against AML cell lines MV4‐11 (IC50 = 2.68 μM) and MOLM‐13 (IC50 = 1.03 μM). In our cellular mechanistic studies, FW‐1 also effectively induced apoptosis by arresting cell cycle progression in the G0/G1 phase. This study introduces FW‐1 as a promising lead for type I FLT3 inhibitor, warranting further optimization. [ABSTRACT FROM AUTHOR]