All-Optical Reconfigurable Excitonic Charge States in Monolayer MoS2.

Excitons are quasi-particles composed of electron-hole pairs through Coulomb interaction. Due to the atomic-thin thickness, they are tightly bound in monolayer transition metal dichalcogenides (TMDs) and dominate their optical properties. The capability to manipulate the excitonic behavior can significantly influence the photon emission or carrier transport performance of TMD-based devices. However, on-demand and region-selective manipulation of the excitonic states in a reversible manner remains challenging so far. Herein, harnessing the coordinated effect of femtosecond-laser-driven atomic defect generation, interfacial electron transfer, and surface molecular desorption/adsorption, we develop an all-optical approach to manipulate the charge states of excitons in monolayer molybdenum disulfide (MoS2). Through steering the laser beam, we demonstrate reconfigurable optical encoding of the excitonic charge states (between neutral and negative states) on a single MoS2 flake. Our technique can be extended to other TMDs materials, which will guide the design of all-optical and reconfigurable TMD-based optoelectronic and nanophotonic devices.

Preclinical validation of a novel deep learning-based metal artifact correction algorithm for orthopedic CT imaging.

PURPOSE: To validate a novel deep learning-based metal artifact correction (MAC) algorithm for CT, namely, AI-MAC, in preclinical setting with comparison to conventional MAC and virtual monochromatic imaging (VMI) technique. MATERIALS AND METHODS: An experimental phantom was designed by consecutively inserting two sets of pedicle screws (size Φ 6.5 × 30-mm and Φ 7.5 × 40-mm) into a vertebral specimen to simulate the clinical scenario of metal implantation. The resulting MAC, VMI, and AI-MAC images were compared with respect to the metal-free reference image by subjective scoring, as well as by CT attenuation, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and correction accuracy via adaptive segmentation of the paraspinal muscle and vertebral body. RESULTS: The AI-MAC and VMI images showed significantly higher subjective scores than the MAC image (all p < 0.05). The SNRs and CNRs on the AI-MAC image were comparable to the reference (all p > 0.05), whereas those on the VMI were significantly lower (all p < 0.05). The paraspinal muscle segmented on the AI-MAC image was 4.6% and 5.1% more complete to the VMI and MAC images for the Φ 6.5 × 30-mm screws, and 5.0% and 5.1% for the Φ 7.5 × 40-mm screws, respectively. The vertebral body segmented on the VMI was closest to the reference, with only 3.2% and 7.4% overestimation for Φ 6.5 × 30-mm and Φ 7.5 × 40-mm screws, respectively. CONCLUSIONS: Using metal-free reference as the ground truth for comparison, the AI-MAC outperforms VMI in characterizing soft tissue, while VMI is useful in skeletal depiction.

Clinical validation of an AI-based motion correction reconstruction algorithm in cerebral CT.

OBJECTIVES: To evaluate the clinical performance of an artificial intelligence (AI)-based motion correction (MC) reconstruction algorithm for cerebral CT. METHODS: A total of 53 cases, where motion artifacts were found in the first scan so that an immediate rescan was taken, were retrospectively enrolled. While the rescanned images were reconstructed with a hybrid iterative reconstruction (IR) algorithm (reference group), images of the first scan were reconstructed with both the hybrid IR (motion group) and the MC algorithm (MC group). Image quality was compared in terms of standard deviation (SD), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), the mean squared error (MSE), peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), and mutual information (MI), as well as subjective scores. The diagnostic performance for each case was evaluated accordingly by lesion detectability or the Alberta Stroke Program Early CT Score (ASPECTS) assessment. RESULTS: Compared with the motion group, the SNR and CNR of the MC group were significantly increased. The MSE, PSNR, SSIM, and MI with respect to the reference group were improved by 44.1%, 15.8%, 7.4%, and 18.3%, respectively (all p < 0.001). Subjective image quality indicators were scored higher for the MC than the motion group (p < 0.05). Improved lesion detectability and higher AUC (0.817 vs 0.614) in the ASPECTS assessment were found for the MC to the motion group. CONCLUSIONS: The AI-based MC reconstruction algorithm has been clinically validated for reducing motion artifacts and improving diagnostic performance of cerebral CT. KEY POINTS: • An artificial intelligence-based motion correction (MC) reconstruction algorithm has been clinically validated in both qualitative and quantitative manner. • The MC algorithm reduces motion artifacts in cerebral CT and increases the diagnostic confidence for brain lesions. • The MC algorithm can help avoiding rescans caused by motion and improving the efficiency of cerebral CT in the emergency department.

Effects of inhaled JAK inhibitor GDC-4379 on exhaled nitric oxide and peripheral biomarkers of inflammation.

BACKGROUND: Janus Kinases (JAKs) mediate activity of many asthma-relevant cytokines. GDC-0214, an inhaled small molecule JAK1 inhibitor, has previously been shown to reduce fractional exhaled nitric oxide (FeNO) in patients with mild asthma, but required an excessive number of inhalations. AIM: To assess whether GDC-4379, a new inhaled JAK inhibitor, reduces FeNO and peripheral biomarkers of inflammation. METHODS: This study assessed the activity of GDC-4379 in a double-blind, randomized, placebo-controlled, Phase 1 study in patients with mild asthma. Participants included adults (18-65y) with a diagnosis of asthma for ≥6 months, forced expiratory volume in 1 s (FEV1)> 70% predicted, FeNO >40 ppb, using as-needed short-acting beta-agonist medication only. Four sequential, 14-day, ascending-dose cohorts (10 mg QD, 30 mg QD, 40 mg BID, and 80 mg QD) of 12 participants each were randomized 2:1 to GDC-4379 or placebo. The primary activity outcome was percent change from baseline (CFB) in FeNO to Day 14 compared to the pooled placebo group. Safety, tolerability, pharmacokinetics, and pharmacodynamic biomarkers, including blood eosinophils, serum CCL17, and serum CCL18, were also assessed. RESULTS: Of 48 enrolled participants, the mean age was 25 years and 54% were female. Median (range) FeNO at baseline was 79 (41-222) ppb. GDC-4379 treatment led to dose-dependent reductions in FeNO. Compared to placebo, mean (95% CI) percent CFB in FeNO to Day 14 was: -6 (-43, 32) at 10 mg QD, -26 (-53, 2) at 30 mg QD, -55 (-78, -32) at 40 mg BID and -52 (-72, -32) at 80 mg QD. Dose-dependent reductions in blood eosinophils and serum CCL17 were also observed. Higher plasma drug concentrations corresponded with greater FeNO reductions. No serious AEs occurred. The majority of AEs were mild to moderate. The most common AEs were headache and oropharyngeal pain. Minor changes in neutrophils were noted at 80 mg QD, but were not considered clinically meaningful. CONCLUSIONS: In patients with mild asthma, 14-day treatment with GDC-4379 reduced FeNO levels and peripheral biomarkers of inflammation. Treatment was well tolerated without any major safety concerns. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12619000227190.

Improving coverage probabilities for parametric tolerance intervals via bootstrap calibration.

Statistical tolerance intervals are commonly employed in biomedical and pharmaceutical research, such as in lifetime analysis, the assessment of biosimilarity of branded and generic versions of biopharmaceutical drugs, and in quality control of drug products to ensure that a specified proportion of the products are covered within established acceptance limits. Exact two-sided parametric tolerance intervals are only available for the normal distribution, while exact one-sided parametric tolerance limits are available for a limited number of distributions. Approximations to two-sided parametric tolerance intervals often use the Bonferroni correction on the one-sided tolerance interval calculation; however, this often incurs a higher coverage probability than the nominal level. Recently, the usage of a bootstrap calibration has been demonstrated as a way to improve coverage probabilities of tolerance intervals for very specific and complex distributional settings. We present a focused treatment on using a single-layer bootstrap calibration to improve the coverage probabilities of two-sided parametric tolerance intervals. Simulation results clearly demonstrate the improved coverage probabilities towards the nominal level over the uncalibrated setting. Applications to medical data for various parametric distributions also highlight the utility of constructing these calibrated tolerance intervals.

Transcriptomic profiles of the bovine mammary gland during lactation and the dry period.

The initiation and maintenance of lactation are complex phenomena governed by biochemical and endocrine processes in the mammary gland (MG). Although DNA-based approaches have been used to study the onset of lactation, more comprehensive RNA-based techniques may be critical in furthering our understanding of gene alterations that occur to support lactation in the bovine MG. To further determine how gene profiles vary during lactation compared with the dry period, RNA-seq transcriptomic analysis was used to identify differentially expressed genes (DEG) in bovine MG tissues from animals that were lactating and not lactating. A total of 881 DEG (605 upregulated and 276 downregulated) were identified in MG of 3 lactating Chinese Holstein dairy cows versus the 3 dry cows. The subcellular analysis showed that the upregulated genes were most abundantly located in "integral to membrane" and "mitochondrion," and the top number of downregulated genes existed in "nucleus" and "cytoplasm." The functional analysis indicated that the DEG were primarily associated with the support of lactation processes. The genes in higher abundance were most related to "metabolic process," "oxidation-reduction process," "transport" and "signal transduction," protein synthesis-related processes (transcription, translation, protein modifications), and some MG growth-associated processes (cell proliferation/cycle/apoptosis). The downregulated genes were mainly involved in immune-related processes (inflammatory/immune/defense responses). The KEGG analysis suggested that protein synthesis-related pathways (such as protein digestion and absorption; protein processing in endoplasmic reticulum; and glycine, serine, and threonine metabolism) were highly and significantly enriched in the bovine MG of lactating cows compared to dry cows. The results suggested that the dry cows had decreased capacity for protein synthesis, energy generation, and cell growth but enhanced immune response. Collectively, this reduced capacity in dry cows supports the physiological demands of the next lactation and the coordinated metabolic changes that occur to support these demands. A total of 51 identified DEG were validated by RT-PCR, and consistent results were found between RT-PCR and the transcriptomic analysis. This work provides a profile of gene-associated changes that occur during lactation and can be used to facilitate further investigation of the mechanisms underlying lactation in dairy cows.

Lysine Stimulates Protein Synthesis by Promoting the Expression of ATB0,+ and Activating the mTOR Pathway in Bovine Mammary Epithelial Cells.

Background: l-lysine (Lys) is a critical dietary nutrient for mammary gland development and milk production. However, the specific pathways of Lys utilization and how milk protein synthesis is affected in bovine mammary epithelial cells (BMECs) are poorly understood. Objective: We aimed to investigate the effects of Lys on milk protein synthesis and the mechanism of Lys uptake and catabolism in BMECs. Methods: BMECs were cultured in 0, 0.5, 1.0, 1.5, 2.0, 5.0, and 10.0 mmol Lys/L to detect cell viability, or cultured in 0-2.0 mmol Lys/L with l-[ring-3H5] phenylalanine to study the effect of Lys on protein turnover, or cultured in Krebs buffer with [U-14C] l-Lys to quantify Lys metabolism. In some experiments, BMECs were cultured in a conditioned medium alone or including 1.0 mmol Lys/L and 2-amino-endo-bicyclo [2.2.1] heptane-2-carboxylic acid (BCH) for 24 h to analyze the expression of amino acid transporter B (0+) (ATB0,+), mammalian target of rapamycin (mTOR), and Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) pathways. Results: Including 1.0 mmol Lys/L in cultures increased cell viability by 17-47% and protein synthesis by 7-23%, whereas protein degradation was inhibited by 4-64% compared with BMECs cultured with 0, 0.5, or 2.0 mmol Lys/L (all P ≤ 0.05). Studies that used [U-14C] l-Lys showed that most Lys was incorporated into proteins (90%), whereas the remainder was either oxidized into CO2 (4%) or used as a substrate for aspartate (3%) and histidine synthesis (3%). Furthermore, Lys significantly increased expression of ATB0,+ (71% mRNA and 44% protein), STAT5 (27% mRNA and 21% phosphorylated proteins), and mTOR (51% mRNA and 22% phosphorylated proteins) compared with cells without Lys. Conclusions: Lys promoted protein synthesis, mostly through enhancing uptake by ATB0,+ and the mTOR and JAK2-STAT5 pathways. Understanding the utilization of Lys in BMECs provides insights into the role of amino acid nutrition in bovine milk production.

Population pharmacokinetics of exendin-(9-39) and clinical dose selection in patients with congenital hyperinsulinism.

AIMS: Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycaemia in infants and children. Exendin-(9-39), an inverse glucagon-like peptide 1 (GLP-1) agonist, is a novel therapeutic agent for HI that has demonstrated glucose-raising effect. We report the first population pharmacokinetic (PopPK) model of the exendin-(9-39) in patients with HI and propose the optimal dosing regimen for future clinical trials in neonates with HI. METHODS: A total of 182 pharmacokinetic (PK) observations from 26 subjects in three clinical studies were included for constructing the PopPK model using first order conditional estimation (FOCE) with interaction method in nonlinear mixed-effects modelling (NONMEM). Exposure metrics (area under the curve [AUC] and maximum plasma concentration [Cmax ]) at no observed adverse effect levels (NOAELs) in rats and dogs were determined in toxicology studies. RESULTS: Observed concentration-time profiles of exendin-(9-39) were described by a linear two-compartmental PK model. Following allometric scaling of PK parameters, age and creatinine clearance did not significantly affect clearance. The calculated clearance and elimination half-life for adult subjects with median weight of 69 kg were 11.8 l h-1 and 1.81 h, respectively. The maximum recommended starting dose determined from modelling and simulation based on the AUC0-last at the NOAEL and predicted AUC0-inf using the PopPK model was 27 mg kg-1  day-1 intravenously. CONCLUSIONS: This is the first study to investigate the PopPK of exendin-(9-39) in humans. The final PopPK model was successfully used with preclinical toxicology findings to propose the optimal dosing regimen of exendin-(9-39) for clinical studies in neonates with HI, allowing for a more targeted dosing approach to achieve desired glycaemic response.

The all-optical modulator in dielectric-loaded waveguide with graphene-silicon heterojunction structure.

All-optical modulators based on graphene show great promise for on-chip optical interconnects. However, the modulation performance of all-optical modulators is usually based on the interaction between graphene and the fiber, limiting their potential in high integration. Based on this point, an all-optical modulator in a dielectric-loaded waveguide (DLW) with a graphene-silicon heterojunction structure (GSH) is proposed. The DLW raises the waveguide mode, which provides a strong light-graphene interaction. Sufficient tuning of the graphene Fermi energy beyond the Pauli blocking effect is obtained with the presented GSH structure. Under the modulation light with a wavelength of 532 nm and a power of 60 mW, a modulation efficiency of 0.0275 dB µm-1 is achieved for light with a communication wavelength of 1.55 µm in the experiment. This modulator has the advantage of having a compact footprint, which may make it a candidate for achieving a highly integrated all-optical modulator.

Zero-power infrared switch with two-phase microfluidic flow and a 2D material thermal isolation layer.

Wireless sensor nodes (WSNs) play an important role in many fields, including environmental monitoring. However, unattended WSNs face challenges in consuming power continuously even in the absence of useful information, which makes energy supply the bottleneck of WSNs. Here, we realized zero-power infrared switches, which consist of a metasurface and two-phase microfluidic flow. The metasurface can recognize the infrared signal from the target and convert it into heat, which triggers the two-phase microfluidic flow switch. As the target is not present, the switch is turned off. The graphene/MoS2/graphene 2D material heterostructure (thickness <2 nm) demonstrates an exceptionally high thermal resistance of 4.2 K/W due to strong phonon scattering and reduces the heat flow from the metasurface to the supporting substrate, significantly increasing the device sensitivity (the displacement of the two-phase microfluidic flow increases from ~1500 to ~3000 µm). The infrared switch with a pair of symmetric two-phase microfluidic flows can avoid spurious triggering resulting from environmental temperature changes. We realized WSNs with near-zero standby power consumption by integrating the infrared switch, sensors, and wireless communication module. When the target infrared signal appears, the WSNs are woken and show superb visual/auditory sensing performance. This work provides a novel approach for greatly lengthening the lifespan of unattended WSNs.

Self-Assembly in Living Cells: Bottom-Up Syntheses in Natural Factory.

In situ self-assembly in living systems is referred to as the processes that regulate assembly by stimuli-responsive reactions at target sites under physiological conditions. Due to the advantages of precisely forming well-defined nanostructures at pathological lesions, in situ-formed assemblies with tailored bioactivity are promising for the development of next-generation biomedical agents. In this Perspective, we summarize the progress of in situ self-assembly of peptides in living cells with an emphasis on the state-of-the-art strategies regulating assembly processes, establishing complexity within assembly systems, and exploiting their applications in biomedicines. We also provide our forward conceiving perspectives on the challenges in the development of in situ assembly in living cells to demonstrate its great potential in creating biomaterials for healthcare in the future.

Rapid screening and identification of targeted and non-targeted illegal added drugs in functional foods by MRSIT-HRMS based on NIST screening database.

The last few decades have witnessed the increasing consumption of functional foods, leading to the expansion of the worldwide market. However, the illegal addition drugs in functional foods remains incessant despite repeated prohibition, making it a key focus of strict crackdowns by regulatory authorities. Effective analytical tools and procedures are desperately needed to rapidly screen and identify illegally added drugs in a large number of samples, given the growing amount and diversity of these substances in functional foods. The MRSIT-HRMS (Multiple Sample Rapid Introduction combined with High Resolution Mass Spectrometry) without chromatographic separation, after direct sampling, utilizes NIST software (National Institute of Standards and Technology) matching with a home-built library to target identification and non-targeted screen of illegal additives. When applied to 50 batches of suspicious samples, the targeted method detected illegal added drugs in 41 batches of samples, while the non-targeted method screened a new phosphodiesterase-5 (PDE-5) inhibitor type structural derivative. The positive results obtained by the targeted method were consistent with LC-MS/MS (QQQ). The novel MRSIT-HRMS with a limit of quantification (LOD) of 1 µg/mL achieved 100 % correct identification for all 50 batches of actual samples, demonstrating its potential as a highly promising and powerful tool for fast screening of illegally added drugs in functional food, especially when compared to traditional LC-MS/MS methods. This is essential for ensuring drug safety and public health.

Experimental and clinical validation of an artificial intelligence metal artifact correction algorithm for low-dose following up CT of percutaneous vertebroplasty.

Background: Low-dose following up computed tomography (CT) of percutaneous vertebroplasty (PVP) that involves the use of bone cement usually suffers from lightweight metal artifacts, where conventional techniques for CT metal artifact reduction are often not sufficiently effective. This study aimed to validate an artificial intelligence (AI)-based metal artifact correction (MAC) algorithm for use in low-dose following up CT for PVP. Methods: In experimental validation, an ovine vertebra phantom was designed to simulate the clinical scenario of PVP. With routine-dose images acquired prior to the cement introduction as the reference, low-dose CT scans were taken on the cemented phantom and processed with conventional MAC and AI-MAC. The resulting image quality was compared in CT attenuation, image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR), followed by a quantitative evaluation of the artifact correction accuracy based on adaptive segmentation of the paraspinal muscle. In clinical validation, ten cases of low-dose following up CT after PVP were enrolled to test the performance of diagnosing sarcopenia with measured CT attenuation per cemented vertebral segment, via receiver operating characteristic (ROC) analysis. Results: With respect to the reference image, no significant difference was found for AI-MAC in CT attenuation, image noise, SNRs, and CNR (all P>0.05). The paraspinal muscle segmented on the AI-MAC image was 18.6% and 8.3% more complete to uncorrected and MAC images. Higher area under the curve (AUC) of the ROC analysis was found for AI-MAC (AUC =0.92) compared to the uncorrected (AUC =0.61) and MAC images (AUC =0.70). Conclusions: In low-dose following up CT for PVP, the AI-MAC has been fully validated for its superior ability compared to conventional MAC in suppressing artifacts and may be a reliable alternative for diagnosing sarcopenia.

Flexible High-Temperature MoS2 Field-Effect Transistors and Logic Gates.

High-temperature-resistant integrated circuits with excellent flexibility, a high integration level (nanoscale transistors), and low power consumption are highly desired in many fields, including aerospace. Compared with conventional SiC high-temperature transistors, transistors based on two-dimensional (2D) MoS2 have advantages of superb flexibility, atomic scale, and ultralow power consumption. However, MoS2 cannot survive at high temperature and drastically degrades above 200 °C. Here, we report MoS2 field-effect transistors (FETs) with top/bottom hexagonal boron nitride (h-BN) encapsulation and graphene electrodes. With the protection of the h-BN/h-BN structure, the devices can survive at much higher temperature (≥500 °C in air) than those of the MoS2 devices ever reported, which provides us an opportunity to explore the electrical properties and working mechanism of MoS2 devices at high temperature. Unlike the relatively low-temperature situation, the on/off ratio and subthreshold swing of MoS2 FETs show drastic variation at elevated temperature due to the injection of thermal emission carriers. Compared with metal electrode, devices with a graphene electrode demonstrate superior performance at high temperature (∼1-order-larger current on/off ratio, 3-7 times smaller subthreshold swing, and 5-9 times smaller threshold voltage shift). We further realize that the flexible CMOS NOT gate based on the above technique, and demonstrate logic computing at 550 °C. This work may stimulate the fundamental research of properties of 2D materials at high temperature, and also creates conditions for next-generation flexible harsh-environment-resistant integrated circuits.

Diagnostic CT of colorectal cancer with artificial intelligence iterative reconstruction: A clinical evaluation.

OBJECTIVES: To investigate the clinical value of a novel deep-learning based CT reconstruction algorithm, artificial intelligence iterative reconstruction (AIIR), in diagnostic imaging of colorectal cancer (CRC). METHODS: This study retrospectively enrolled 217 patients with pathologically confirmed CRC. CT images were reconstructed with the AIIR algorithm and compared with those originally obtained with hybrid iterative reconstruction (HIR). Objective image quality was evaluated in terms of the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Subjective image quality was graded on the conspicuity of tumor margin and enhancement pattern as well as the certainty in diagnosing organ invasion and regional lymphadenopathy. In patients with surgical pathology (n = 116), the performance of diagnosing visceral peritoneum invasion was characterized using receiver operating characteristic (ROC) analysis. Changes of diagnostic thinking in diagnosing hepatic metastases were assessed through lesion classification confidence. RESULTS: The SNRs and CNRs on AIIR images were significantly higher than those on HIR images (all p < 0.001). The AIIR was scored higher for all subjective metrics (all p < 0.001) except for the certainty of diagnosing regional lymphadenopathy (p = 0.467). In diagnosing visceral peritoneum invasion, higher area under curve (AUC) of the ROC was found for AIIR than HIR (0.87 vs 0.77, p = 0.001). In assessing hepatic metastases, AIIR was found capable of correcting the misdiagnosis and improving the diagnostic confidence provided by HIR (p = 0.01). CONCLUSIONS: Compared to HIR, AIIR offers better image quality, improves the diagnostic performance regarding CRC, and thus has the potential for application in routine abdominal CT.

Advances in Cyclodextrins and Their Derivatives in Nano-Delivery Systems.

The diversity of cyclodextrins and their derivatives is increasing with continuous research. In addition to monomolecular cyclodextrins with different branched chains, cyclodextrin-based polymers have emerged. The aim of this review is to summarize these innovations, with a special focus on the study of applications of cyclodextrins and their derivatives in nano-delivery systems. The areas covered include nanospheres, nano-sponges, nanogels, cyclodextrin metal-organic frameworks, liposomes, and emulsions, providing a comprehensive and in-depth understanding of the design and development of nano-delivery systems.

Evaluation of Patient-Centric Sample Collection Technologies for Pharmacokinetic Assessment of Large and Small Molecules.

Low-volume sampling devices offer the promise of lower discomfort and greater convenience for patients, potentially reducing patient burden and enabling decentralized clinical trials. In this study, we determined whether low-volume sampling devices produce pharmacokinetic (PK) data comparable to conventional venipuncture for a diverse set of monoclonal antibodies (mAbs) and small molecules. We adopted an open-label, non-randomized, parallel-group, single-site study design, with four cohorts of 10 healthy subjects per arm. The study drugs, doses, and routes of administration included: crenezumab (15 mg/kg, intravenous infusion), etrolizumab (210 mg, subcutaneous), GDC-X (oral), and hydroxychloroquine (HCQ, 200 mg, oral). Samples were collected after administration of a single dose of each drug using conventional venipuncture and three low-volume capillary devices: TassoOne Plus for liquid blood, Tasso-M20 for dry blood, both applied to the arm, and Neoteryx Mitra® for dry blood obtained from fingertips. Serum/plasma concentrations from venipuncture and TassoOne Plus samples overlapped and PK parameters were comparable for all drugs, except HCQ. After applying a baseline hematocrit value, the dry blood concentrations and PK parameters for the two monoclonal antibodies were comparable to those obtained from venipuncture. For the two small molecules, two bridging strategies were evaluated for converting dry blood concentrations to equivalent plasma concentrations. A baseline hematocrit correction and/or linear regression-based correction was effective for GDC-X, but not for HCQ. Additionally, the study evaluated the bioanalytical data quality and comparability from the various collection methods, as well as patient preference for the devices.

Evaluation of partial volume correction and analysis of longitudinal [18F]GTP1 tau PET imaging in Alzheimer's disease using linear mixed-effects models.

Purpose: We evaluated the impact of partial volume correction (PVC) methods on the quantification of longitudinal [18F]GTP1 tau positron-emission tomography (PET) in Alzheimer's disease and the suitability of describing the tau pathology burden temporal trajectories using linear mixed-effects models (LMEM). Methods: We applied van Cittert iterative deconvolution (VC), 2-compartment, and 3-compartment, and the geometric transfer matrix plus region-based voxelwise methods to data acquired in an Alzheimer's disease natural history study over 18 months at a single imaging site. We determined the optimal PVC method by comparing the standardized uptake value ratio change (%ΔSUVR) between diagnostic and tau burden-level groups and the longitudinal repeatability derived from the LMEM. The performance of LMEM analysis for calculating %ΔSUVR was evaluated in a natural history study and in a multisite clinical trial of semorinemab in prodromal to mild Alzheimer's disease by comparing results to traditional per-visit estimates. Results: The VC, 2-compartment, and 3-compartment PVC methods had similar performance, whereas region-based voxelwise overcorrected regions with a higher tau burden. The lowest within-subject variability and acceptable group separation scores were observed without PVC. The LMEM-derived %ΔSUVR values were similar to the per-visit estimates with lower variability. Conclusion: The results indicate that the tested PVC methods do not offer a clear advantage or improvement over non-PVC images for the quantification of longitudinal [18F]GTP1 PET data. LMEM offers a robust framework for the longitudinal tau PET quantification with low longitudinal test-retest variability. Clinical trial registration: NCT02640092 and NCT03289143.

Optofluidic crystallithography for directed growth of single-crystalline halide perovskites.

Crystallization is a fundamental phenomenon which describes how the atomic building blocks such as atoms and molecules are arranged into ordered or quasi-ordered structure and form solid-state materials. While numerous studies have focused on the nucleation behavior, the precise and spatiotemporal control of growth kinetics, which dictates the defect density, the micromorphology, as well as the properties of the grown materials, remains elusive so far. Herein, we propose an optical strategy, termed optofluidic crystallithography (OCL), to solve this fundamental problem. Taking halide perovskites as an example, we use a laser beam to manipulate the molecular motion in the native precursor environment and create inhomogeneous spatial distribution of the molecular species. Harnessing the coordinated effect of laser-controlled local supersaturation and interfacial energy, we precisely steer the ionic reaction at the growth interface and directly print arbitrary single crystals of halide perovskites of high surface quality, crystallinity, and uniformity at a high printing speed of 102 µm s-1. The OCL technique can be potentially extended to the fabrication of single-crystal structures beyond halide perovskites, once crystallization can be triggered under the laser-directed local supersaturation.

The endometrial microbiota profile influenced pregnancy outcomes in patients with repeated implantation failure: a retrospective study.

OBJECTIVES: To investigate the association between the pregnancy outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) patients with repeated implantation failure (RIF) and their endometrial microbiota profiles. METHODS: One hundred and forty-one RIF patients were recruited in this retrospective study. Endometrial tissues were sampled using a disposable sterile endometrium sampler. Comprehensive next-generation sequencing techniques were used to detect the endometrial bacteria status, and the pregnancy outcomes were analyzed. RESULTS: Endometrial pathogenic bacteria were detected in 125 patients (88.70%, the pathogenic group) while no relevant pathogen was found in the remaining 16 (11.30%, the no-pathogen group). All the 125 patients received the treatment of oral antibiotics for 14 days. Clinical pregnancy rates and ongoing pregnancy rates were higher in the pathogenic group than in the no-pathogen group without statistical significance (50.40% vs. 37.50%, P＞0.05; 42.40% vs. 25%, P＞0.05). CONCLUSION: In the endometrium of most RIF patients existed pathogenic bacteria, among which Streptococcus, Staphylococcus, Neisseria, and Klebsiella were most frequently observed, and the sensitive antibiotic therapy might improve clinical outcomes of the RIF patients in subsequent embryo transfer cycles.