Comparison of MRI artificial intelligence-guided cognitive fusion-targeted biopsy versus routine cognitive fusion-targeted prostate biopsy in prostate cancer diagnosis: a randomized controlled trial.

Background: Cognitive fusion MRI-guided targeted biopsy (cTB) has been widely used in the diagnosis of prostate cancer (PCa). However, cTB relies heavily on the operator's experience and confidence in MRI readings. Our objective was to compare the cancer detection rates of MRI artificial intelligence-guided cTB (AI-cTB) and routine cTB and explore the added value of using AI for the guidance of cTB.

Discovery and Optimization of N-Heteroaryl Indazole LRRK2 Inhibitors.

Inhibition of leucine-rich repeat kinase 2 is a genetically supported mechanism for the treatment of Parkinson's disease. We previously disclosed the discovery of an indazole series lead that demonstrated both safety and translational risks. The safety risks were hypothesized to be of unknown origin, so structural diversity in subsequent chemical matter was prioritized.

[Diagnostic efficacy of targeted biopsy combined with regional systematic biopsy in prostate cancer in patients with PI-RADS 4-5].

Objective: To investigate the diagnostic efficacy of targeted biopsy combined with regional systematic biopsy in prostate cancer (PCa) in patients with prostate imaging reporting and data system v2.1 (PI-RADS v2.1) 4-5.

[Predictive effect of the dual-parametric MRI modified maximum diameter of the lesions with PI-RADS 4 and 5 on the clinically significant prostate cancer].

Objective: To assess the rationality of the maximum lesion diameter of 15 mm in prostate imaging reporting and data system (PI-RADS) as a criterion for upgrading a lesion from category 4 to 5 and improve it to enhance the prediction of clinically significant prostate cancer (csPCa).

Methods: In this study, the patients who underwent prostate magnetic resonance imaging (MRI) and prostate biopsy at Peking University First Hospital from 2019 to 2022 as a development cohort, and the patients in 2023 as a validation cohort were reviewed. The localization and maximum diameter of the lesion were fully evaluated.

A novel biopsy scheme for prostate cancer: targeted and regional systematic biopsy.

Purpose: To explore a novel biopsy scheme for prostate cancer (PCa), and test the detection rate and pathological agreement of standard systematic (SB) + targeted (TB) biopsy and novel biopsy scheme.

Methods: Positive needles were collected from 194 patients who underwent SB + TB (STB) followed by radical prostatectomy (RP). Our novel biopsy scheme, targeted and regional systematic biopsy (TrSB) was defined as TB + regional SB (4 SB-needles closest to the TB-needles).

Recent Progress in the Application of Ion Beam Technology in the Modification and Fabrication of Nanostructured Energy Materials.

The development of green, renewable energy conversion and storage systems is an urgent task to address the energy crisis and environmental issues in the future. To achieve high performance, stable, and safe operation of energy conversion and storage systems, energy materials need to be modified and fabricated through rationalization. Among various modification and fabrication strategies, ion beam technology has been widely used to introduce various defects/dopants into energy materials and fabricate various nanostructures, where the structure, composition, and property of prefabricated materials can be further accurately tailored to achieve better performance.

Minimally invasive ureteroplasty with lingual mucosal graft for complex ureteral stricture: analysis of surgical and patient-reported outcomes.

Objective: To evaluate objective treatment efficacy and safety, and subjective patient-reported outcomes in patients with complex ureteral strictures (US) undergoing minimally invasive lingual mucosal graft ureteroplasty (LMGU).

Materials And Methods: We prospectively enrolled patients underwent robotic or laparoscopic LMGU between May 2020 and July 2022. Clinical success was defined as symptom-free and no radiographic evidence of re-obstruction.

Broadband spectral combining of three pulse-shaped fiber amplifiers with 42fs compressed pulse duration.

We demonstrate ultra-broadband spectral combining of ultrashort pulses from Yb-doped fiber amplifiers, with coherently spectrally synthesized pulse shaping, to achieve tens-of-fs pulses. This method can fully compensate for gain narrowing and high order dispersion over broad bandwidth. We produce 42fs pulses by spectrally synthesizing three chirped-pulse fiber amplifiers and two programmable pulse shapers across an 80nm overall bandwidth.

Facile method to activate substrate for oxygen evolution by a galvanic-cell reaction.

NiFe layered double hydroxide (NiFe LDH) is a promising material with multiple functions. In this communication, a novel method is used to prepare NiFe LDH. This synthesis method is achieved galvanic-cell corrosion between nickel and iron substrates in aqueous solutions containing a halogen group anion (, Cl) at ambient temperature.

Fully automated detection and localization of clinically significant prostate cancer on MR images using a cascaded convolutional neural network.

Purpose: To develop a cascaded deep learning model trained with apparent diffusion coefficient (ADC) and T2-weighted imaging (T2WI) for fully automated detection and localization of clinically significant prostate cancer (csPCa).

Methods: This retrospective study included 347 consecutive patients (235 csPCa, 112 non-csPCa) with high-quality prostate MRI data, which were randomly selected for training, validation, and testing. The ground truth was obtained using manual csPCa lesion segmentation, according to pathological results.

Experimental beam combining stabilization using machine learning trained while phases drift.

An 8-beam, diffractive coherent beam combiner is phase controlled by a learning algorithm trained while optical phases drift, using a differential mapping technique. Combined output power is stable to 0.4% with 95% of theoretical maximum efficiency, limited by the diffractive element.

Magnetic resonance imaging features of prostatic stromal tumour of uncertain malignant potential.

Introduction: Prostatic stromal tumours of uncertain malignant potential (STUMPs) are rare prostate tumours. The purpose of this study was to investigate the magnetic resonance imaging features of STUMPs.

Methods: A total of 12 patients with STUMP confirmed with pathology who underwent MRI from 2012 to 2020 were retrospectively reviewed.

Oxetane Promise Delivered: Discovery of Long-Acting IDO1 Inhibitors Suitable for Q3W Oral or Parenteral Dosing.

3,3-Disubstituted oxetanes have been utilized as bioisosteres for gem-dimethyl and cyclobutane functionalities. We report the discovery of a novel class of oxetane indole-amine 2,3-dioxygenase (IDO1) inhibitors suitable for Q3W (once every 3 weeks) oral and parenteral dosing. A diamide class of IDO inhibitors was discovered through an automated ligand identification system (ALIS).

Comprehensive Strategies to Bicyclic Prolines: Applications in the Synthesis of Potent Arginase Inhibitors.

Comprehensive synthetic strategies afforded a diverse set of structurally unique bicyclic proline-containing arginase inhibitors with a high degree of three-dimensionality. The analogs that favored the Cγ-exo conformation of the proline improved the arginase potency over the initial lead. The novel synthetic strategies reported here not only enable access to previously unknown stereochemically complex proline derivatives but also provide a foundation for the future synthesis of bicyclic proline analogs, which incorporate inherent three-dimensional character into building blocks, medicine, and catalysts and could have a profound impact on the conformation of proline-containing peptides and macrocycles.

Utilization of Metabolite Identification and Structural Data to Guide Design of Low-Dose IDO1 Inhibitors.

Herein the discovery of potent IDO1 inhibitors with low predicted human dose is discussed. Metabolite identification (MetID) and structural data were used to strategically incorporate cyclopropane rings into this tetrahydronaphthyridine series of IDO1 inhibitors to improve their metabolic stability and potency. Enabling synthetic chemistry was developed to construct these unique fused cyclopropyl compounds, leading to inhibitors with improved pharmacokinetics and human whole blood potency and a predicted human oral dose as low as 9 mg once daily (QD).

Structure-Based Discovery of Proline-Derived Arginase Inhibitors with Improved Oral Bioavailability for Immuno-Oncology.

Recent data suggest that the inhibition of arginase (ARG) has therapeutic potential for the treatment of a number of indications ranging from pulmonary and vascular disease to cancer. Thus, high demand exists for selective small molecule ARG inhibitors with favorable druglike properties and good oral bioavailability. In light of the significant challenges associated with the unique physicochemical properties of previously disclosed ARG inhibitors, we use structure-based drug design combined with a focused optimization strategy to discover a class of boronic acids featuring a privileged proline scaffold with superior potency and oral bioavailability.

Discovery of IDO1 inhibitors containing a decahydroquinoline, decahydro-1,6-naphthyridine, or octahydro-1H-pyrrolo[3,2-c]pyridine scaffold.

A series of IDO1 inhibitors containing a decahydroquinoline, decahydro-1,6-naphthyridine, or octahydro-1H-pyrrolo[3,2-c]pyridine scaffold were identified with good cellular and human whole blood activity against IDO1. These inhibitors contain multiple chiral centers and all diastereomers were separated. The absolute stereochemistry of each isomers were not determined.

SAR towards indoline and 3-azaindoline classes of IDO1 inhibitors.

A novel series of IDO1 inhibitors have been identified with good IDO1 Hela cell and human whole blood activity. These inhibitors contain an indoline or a 3-azaindoline scaffold. Their structure-activity-relationship studies have been explored.

Carbamate and -Pyrimidine Mitigate Amide Hydrolysis: Structure-Based Drug Design of Tetrahydroquinoline IDO1 Inhibitors.

Indoleamine-2,3-dioxygenase-1 (IDO1) has emerged as an attractive target for cancer immunotherapy. An automated ligand identification system screen afforded the tetrahydroquinoline class of novel IDO1 inhibitors. Potency and pharmacokinetic (PK) were key issues with this class of compounds.

Stabilization of the 81-channel coherent beam combination using machine learning.

We develop a rapidly converging algorithm for stabilizing a large channel-count diffractive optical coherent beam combination. An 81-beam combiner is controlled by a novel, machine-learning based, iterative method to correct the optical phases, operating on an experimentally calibrated numerical model. A neural-network is trained to detect phase errors based on interference pattern recognition of uncombined beams adjacent to the combined one.

81-beam coherent combination using a programmable array generator.

We have generated 81 independently controllable beams using a spatial light modulator and combined them on a diffractive combiner, to characterize the combiner and develop a fast phase error detection scheme. A key parameter of the diffractive combiner is measured in a new way, enabling an efficient combination when programming calibrated phases of each beam. This testbed provides a platform for development of advanced feedback phase control of high channel-count beam combination.

Self-derivation-behaviour of substrates realizing enhanced oxygen evolution reaction.

Self-derivation-behaviour of substrates is utilized to fabricate monolithic electrodes for oxygen evolution, in which the selected substrate functions as both the precursor of the active catalyst and a conductive support. In particular, NiFe layered double hydroxide (LDH) can be directly derived from the surface metal of commercial NiFe foam (NFF). Moreover, the as-prepared monolithic electrode exhibits enhanced activity and durability, originating from the resultant defective nanosheet structure and autologous catalyst-support features.

[Magnetic resonance imaging-transrectal ultrasound cognitive fusion targeted biopsy on the diagnosis of prostate cancer: a research of 614 cases in single center].

This study aims to compare the prostate cancer detection rate between magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) cognitive fusion targeted biopsy and systematic biopsy. A total of 614 patients who underwent transrectal prostate biopsy during 2016-2018 with multiparametric magnetic resonance imaging (mpMRI) were included. All patients with a PI-RADS V2 score ≥ 3 accepted both targeted biopsy and systematic biopsy, and those with a PI-RADS V2 score ≤ 2 only accepted systematic biopsy.

Discovery and Optimization of Rationally Designed Bicyclic Inhibitors of Human Arginase to Enhance Cancer Immunotherapy.

The action of arginase, a metalloenzyme responsible for the hydrolysis of arginine to urea and ornithine, is hypothesized to suppress immune-cell activity within the tumor microenvironment, and thus its inhibition may constitute a means by which to potentiate the efficacy of immunotherapeutics such as anti-PD-1 checkpoint inhibitors. Taking inspiration from reported enzyme-inhibitor cocrystal structures, we designed and synthesized novel inhibitors of human arginase possessing a fused 5,5-bicyclic ring system. The prototypical member of this class, , when dosed orally, successfully demonstrated serum arginase inhibition and concomitant arginine elevation in a syngeneic mouse carcinoma model, despite modest oral bioavailability.