Benchmarking PathCLIP for Pathology Image Analysis.

Accurate image classification and retrieval are of importance for clinical diagnosis and treatment decision-making. The recent contrastive language-image pre-training (CLIP) model has shown remarkable proficiency in understanding natural images. Drawing inspiration from CLIP, pathology-dedicated CLIP (PathCLIP) has been developed, utilizing over 200,000 image and text pairs in training. While the performance the PathCLIP is impressive, its robustness under a wide range of image corruptions remains unknown. Therefore, we conduct an extensive evaluation to analyze the performance of PathCLIP on various corrupted images from the datasets of osteosarcoma and WSSS4LUAD. In our experiments, we introduce eleven corruption types including brightness, contrast, defocus, resolution, saturation, hue, markup, deformation, incompleteness, rotation, and flipping at various settings. Through experiments, we find that PathCLIP surpasses OpenAI-CLIP and the pathology language-image pre-training (PLIP) model in zero-shot classification. It is relatively robust to image corruptions including contrast, saturation, incompleteness, and orientation factors. Among the eleven corruptions, hue, markup, deformation, defocus, and resolution can cause relatively severe performance fluctuation of the PathCLIP. This indicates that ensuring the quality of images is crucial before conducting a clinical test. Additionally, we assess the robustness of PathCLIP in the task of image-to-image retrieval, revealing that PathCLIP performs less effectively than PLIP on osteosarcoma but performs better on WSSS4LUAD under diverse corruptions. Overall, PathCLIP presents impressive zero-shot classification and retrieval performance for pathology images, but appropriate care needs to be taken when using it.

Influence of different penetrating cryoprotectants and egg yolk level on the post-thaw quality of sperm.

Objective: The Hu sheep is a renowned breed known for its high reproductive rate. It is in estrus all year round, and its breeding population is gradually expanding. However, the current techniques for cryopreserving semen have limited effectiveness, which hinders the continuous development of this species. The purpose of this study is to explore the effects of different penetrating cryoprotectants (CPAs) and egg yolk (EY) concentrations on the cryopreservation of Hu ram semen to determine the most effective combination. Methods: In this study, the effects of glycerol (GLY), ethylene glycol (EG), dimethylacetamide (DMA), dimethyl sulfoxide (DMSO), different proportions of GLY and EG, EY on sperm quality after thawing were investigated by detecting sperm total motility (TM), progressive motility (PM), straight-line velocity (VSL), curvilinear velocity (VCL), average path velocity (VAP), amplitude of lateral head displacement (ALH), wobble movement coefficient (WOB), average motion degree (MAD), functional integrity (plasma membrane integrity, acrosome integrity) and reactive oxygen species (ROS) level. Results: When GLY and EG were added together, compared to other concentration groups, 6% GLY significantly (p < 0.05) increased TM, PM, plasma membrane integrity, and acrosome integrity of thawed sperm. Additionally, it significantly (p < 0.05) decreased the ROS level of sperm. In this study, the TM, PM and membrane integrity of the 6% EG were significantly (p < 0.05) higher than those of the control, 1% GLY+5% EG and 6% GLY+6% EG groups. Compared to other concentration groups, 20% EY significantly (p < 0.05) improved the TM, PM, and plasma membrane integrity of thawed sperm. However, the integrity of the acrosome increased with the higher concentration of EY. Conclusion: In conclusion, the post-thawed Hu ram semen diluted with a diluent containing 6% GLY and 20% EY exhibited higher quality compared to the other groups.

Effects of Different Diluents and Freezing Methods on Cryopreservation of Hu Ram Semen.

The purpose of this study was to investigate the effects of different diluents and freezing methods on the quality of thawed sperm after cryopreservation and find an inexpensive and practical method for freezing Hu ram semen for use in inseminations under farm conditions. Ejaculates were collected from five Hu rams. In experiment I, ejaculates were diluted with eight different freezing diluents (basic diluents A, B, C, D, E, F, G, and H). After dilution and cooling, the samples were loaded into 0.25 mL straws and frozen using the liquid nitrogen fumigation method. In experiment II, diluent C was used as the basic diluent and the semen was frozen using liquid nitrogen fumigation and two program-controlled cooling methods. For analysis, frozen samples were evaluated in terms of motility parameters (total motility (TM), progressive motility (PM)), biokinetic characteristics (straight-line velocity (VSL), average path velocity (VAP), curvilinear velocity (VCL), amplitude of lateral head displacement (ALH), wobble movement coefficient (WOB), average motion degree (MAD)), reactive oxygen species (ROS) level, and membrane and acrosome integrity. In experiment I, diluent C had higher TM, PM, and acrosome and membrane integrity and lower ROS compared to other extenders (p < 0.05) except diluent A. Diluent C exhibited higher (p < 0.05) VCL, VAP, ALH, WOB, and MAD compared to diluents B, D, E, and F. In experiment II, TM and all biokinetic characteristics did not show significant differences (p > 0.05) amongst the three freezing methods. Liquid nitrogen fumigation resulted in higher (p < 0.05) PM, membrane integrity, acrosome integrity, and lower ROS level compared to the program. In conclusion, the thawed semen diluted with diluent C had higher quality compared to other diluents. The liquid nitrogen fumigation demonstrated superior semen cryopreservation effects compared to the program-controlled cooling method using diluent C.

Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104).

The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon's two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro. Infiltration and T cell receptor (TCR) clonal expansion of CCR8+ regulatory T (Treg)hi/CXCL13+ exhausted T (Tex)lo cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC.

Molecular Dynamics Simulation and the Regeneration and Diffusion Effects of Waste Engine Oil in Aged Asphalt Binder.

In recent years, the potential of waste engine oil (WEO) as a rejuvenator for aged asphalt binders has gained significant attention. Despite this interest, understanding WEO's regeneration mechanism within aged asphalt binders, particularly its diffusion behavior when mixed with both aged and virgin asphalt binders, remains limited. This study adopts a molecular dynamics approach to constructing models of virgin, aged, and rejuvenated asphalt binders with different WEO contents (3%, 6%, 9%, and 12%). Key properties such as the density, glass transition temperature, cohesive energy density, solubility parameter, viscosity, surface free energy, fractional free volume, and diffusion coefficient are simulated. Additionally, models of rejuvenated asphalt binder are combined with those of aged asphalt binder to investigate mutual diffusion, focusing on the impact of WEO on the relative concentration and binding energy. The findings reveal that WEO notably decreased the density, viscosity, and glass transition temperature of aged asphalt binders. It also improved the molecular binding within the asphalt binder, enhancing crack resistance. Specifically, a 9% WEO content can restore the diffusion coefficient to 93.17% of that found in virgin asphalt binder. Increasing the WEO content facilitates diffusion toward virgin asphalt binders, strengthens molecular attraction, and promotes the blending of virgin and aged asphalt binders.

Effect of fumigation height and time on cryopreservation of ram semen.

The cooling rate is a crucial factor in the process of freezing semen, influencing the overall freezing effectiveness. The height and time of fumigation can significantly impact the rate of cooling. Appropriate cooling rates can help minimize the formation of ice crystals in spermatozoa and reduce potential damage to them. Therefore, the aim of this study was to evaluate the effect of different fumigation heights and time for the cryopreservation of Hu ram semen. Experiments I-IV assessed the effect of semen cryopreservation by testing the post-thawed spermatozoa total motility (TM), progressive motility (PM) and kinetic parameters fumigated at distances of 2, 4, 6 and 8 cm for durations of 5, 10, 15 and 20 min, respectively. Based on the results of experiments I to IV, experiment V evaluated the effect of semen cryopreservation by testing the post-thawed spermatozoa TM, PM, kinetic parameters, plasma membrane integrity, acrosome integrity and reactive oxygen species (ROS) level fumigated at distances of 2, 4, 6 and 8 cm for duration of 20 min. The results indicated that fumigation at 2 cm for 20 min significantly (P < 0.05) improved spermatozoa TM, PM, mean angular displacement (MAD), plasma membrane integrity and acrosome integrity compared to other groups. Additionally, it significantly (P < 0.05) reduced spermatozoa ROS level compared to the 6 and 8 cm groups. In conclusion, fumigation for 20 min at a distance of 2 cm from the liquid nitrogen surface is the most suitable cooling method for the cryopreservation of Hu ram semen.

Identification of cancer risk groups through multi-omics integration using autoencoder and tensor analysis.

Identifying cancer risk groups by multi-omics has attracted researchers in their quest to find biomarkers from diverse risk-related omics. Stratifying the patients into cancer risk groups using genomics is essential for clinicians for pre-prevention treatment to improve the survival time for patients and identify the appropriate therapy strategies. This study proposes a multi-omics framework that can extract the features from various omics simultaneously. The framework employs autoencoders to learn the non-linear representation of the data and applies tensor analysis for feature learning. Further, the clustering method is used to stratify the patients into multiple cancer risk groups. Several omics were included in the experiments, namely methylation, somatic copy-number variation (SCNV), micro RNA (miRNA) and RNA sequencing (RNAseq) from two cancer types, including Glioma and Breast Invasive Carcinoma from the TCGA dataset. The results of this study are promising, as evidenced by the survival analysis and classification models, which outperformed the state-of-the-art. The patients can be significantly (p-value<0.05) divided into risk groups using extracted latent variables from the fused multi-omics data. The pipeline is open source to help researchers and clinicians identify the patients' risk groups using genomics.

Genetic risk, adherence to healthy lifestyle behaviors, and risk of cholelithiasis: A population-based cohort study.

OBJECTIVE: Genetic and lifestyles contribute to cholelithiasis, but the impact of adhering to healthy lifestyle on cholelithiasis risk remains uncertain. We aimed to assess combined lifestyle factors and a polygenic risk score on incident cholelithiasis. METHODS: We utilized cholelithiasis genome-wide association study (GWAS) data from FinnGen study, constructing varied polygenic risk score (PRS), and applied them to 317,640 UK Biobank participants. The relative and absolute risk of incident cholelithiasis associated with six well-established lifestyle risk factors, was evaluated and stratified by PRS (low risk [quintile 1], intermediate risk [quintiles 2-4] and high risk [quintile 5]). Lifestyle score was also categorized into favorable, intermediate, and unfavorable groups. RESULTS: The PRS derived from 13 single nucleotide polymorphisms (p ≤ 5 × 10-6, r2 < 0.001) showed the best performance. A significant gradient of increase in risk of cholelithiasis was observed across the quintiles of the polygenic risk score (p < 0.001). Compared to participants with low genetic risk, those with intermediate or high genetic risk had a 10% (95% confidence interval [CI] = 1.05-1.17) and 24% (95% CI = 1.16-1.32) higher risk of cholelithiasis. An unfavorable lifestyle was associated with an approximately 50% higher risk of cholelithiasis than a favorable lifestyle. Participants with high genetic risk and an unfavorable lifestyle had 98% (Hazard ratio [HR]: 1.98; 95% CI: 1.67-2.35) higher risk of cholelithiasis than those with low genetic risk and a favorable lifestyle. CONCLUSIONS: Our study highlights the importance of lifestyle behaviors intervention on cholelithiasis risk regardless of the genetic risk in White European population.

New Carbon Materials for Multifunctional Soft Electronics.

Soft electronics are garnering significant attention due to their wide-ranging applications in artificial skin, health monitoring, human-machine interaction, artificial intelligence, and the Internet of Things. Various soft physical sensors such as mechanical sensors, temperature sensors, and humidity sensors are the fundamental building blocks for soft electronics. While the fast growth and widespread utilization of electronic devices have elevated life quality, the consequential electromagnetic interference (EMI) and radiation pose potential threats to device precision and human health. Another substantial concern pertains to overheating issues that occur during prolonged operation. Therefore, the design of multifunctional soft electronics exhibiting excellent capabilities in sensing, EMI shielding, and thermal management is of paramount importance. Because of the prominent advantages in chemical stability, electrical and thermal conductivity, and easy functionalization, new carbon materials including carbon nanotubes, graphene and its derivatives, graphdiyne, and sustainable natural-biomass-derived carbon are particularly promising candidates for multifunctional soft electronics. This review summarizes the latest advancements in multifunctional soft electronics based on new carbon materials across a range of performance aspects, mainly focusing on the structure or composite design, and fabrication method on the physical signals monitoring, EMI shielding, and thermal management. Furthermore, the device integration strategies and corresponding intriguing applications are highlighted. Finally, this review presents prospects aimed at overcoming current barriers and advancing the development of state-of-the-art multifunctional soft electronics.

Effect of Different Dilution Methods and Ratios of Ram Semen on Sperm Parameters after Cryopreservation.

The dilution method and ratio were tested to assess their effects on the Hu ram semen after cryopreservation. Experiment I aimed to explore the effect of various dilution ratios (1:1, 1:2, 1:3, 1:4) of diluent I (Tris-based and egg yolk) under the condition of 1:1 dilution of diluent II (diluent I and glycerol) on the Hu ram semen preserved in liquid nitrogen regarding spermatozoa motility and kinetic parameters. Experiment II aimed to investigate the effect of various dilution ratios (1:1, 1:2, 1:3, 1:4) of diluent I under the condition of 1:2 dilution of diluent II to the Hu ram semen for cryopreservation on spermatozoa motility and kinetic parameters. The purpose of experiment III is to assess the effect of various dilution methods and ratios on the cryopreservation of Hu ram semen by detecting spermatozoa motility, kinetic parameters, plasma membrane integrity, acrosome integrity and reactive oxygen species (ROS) level. Experiment III includes four groups: one-step dilution method and two-step dilution method. The two-step dilution method includes two groups: 1:2, 1:1 and 1:3, 1:2, and the one-step dilution method includes two groups: 1:5 and 1:11. The results indicated that the post-thawed spermatozoa total motility (TM), progressive motility (PM) and average motion degree (MAD) were highest in the 1:2 group and significantly higher (p < 0.05) than those in the 1:1 and 1:4 groups under the condition of 1:1 dilution of diluent II. The post-thawed spermatozoa TM and PM of the 1:3 group were significantly higher (p < 0.05) than those of the other groups under the condition of 1:2 dilution of diluent II. The post-thawed spermatozoa TM, PM, plasma membrane integrity and acrosome integrity of the two-step group (1:3, 1:2) were the highest and significantly higher (p < 0.05) than those in the other groups. Additionally, the post-thawed spermatozoa ROS level of the two-step group (1:3, 1:2) was significantly lower (p < 0.05) than that in the one-step groups (1:5 and 1:11). Therefore, a two-step dilution (1:3, 1:2) was found to be the most suitable method and ratio for diluting the Hu ram semen after cryopreservation.

Magnetically driven capsules with multimodal response and multifunctionality for biomedical applications.

Untethered capsules hold clinical potential for the diagnosis and treatment of gastrointestinal diseases. Although considerable progress has been achieved recently in this field, the constraints imposed by the narrow spatial structure of the capsule and complex gastrointestinal tract environment cause many open-ended problems, such as poor active motion and limited medical functions. In this work, we describe the development of small-scale magnetically driven capsules with a distinct magnetic soft valve made of dual-layer ferromagnetic soft composite films. A core technological advancement achieved is the flexible opening and closing of the magnetic soft valve by using the competitive interactions between magnetic gradient force and magnetic torque, laying the foundation for the functional integration of both drug release and sampling. Meanwhile, we propose a magnetic actuation strategy based on multi-frequency response control and demonstrate that it can achieve effective decoupled regulation of the capsule's global motion and local responses. Finally, through a comprehensive approach encompassing ideal models, animal ex vivo models, and in vivo assessment, we demonstrate the versatility of the developed magnetic capsules and their multiple potential applications in the biomedical field, such as targeted drug delivery and sampling, selective dual-drug release, and light/thermal-assisted therapy.

Latamoxef dosing regimen adjustments and pharmaceutical care in pediatrics.

Latamoxef is a semi-synthetic, broad-spectrum oxacephem antibiotic used primarily to treat infectious diseases, but the adverse drug reactions, such as the risk of fatal bleeding, once caused physicians to use it less frequently. However, with the rise of antibiotic-resistant bacterial strains, latamoxef is being used again to treat infectious diseases, especially in pediatrics. The pharmacokinetic parameters of latamoxef are highly variable, given the changes in body composition, organ maturation, and development that occurs in pediatrics. Therefore, an appropriate dosing regimen is essential. Latamoxef dosing optimization in pediatrics should adequately account for current body weight, postnatal age, postmenstrual age, and different minimum inhibitory concentration (MIC) values. In addition, attention should also be paid to some of the adverse reactions associated with latamoxef, such as coagulation disorders and bleeding risks, disulfiram-like reactions, as well as hypersensitivity and anaphylactic shock. This review summarizes the dosing regimens and some key points of pharmaceutical care for latamoxef in pediatrics in order to provide a better reference for its application in clinical practice.

Punicalagin Protects Ram Sperm from Oxidative Stress by Enhancing Antioxidant Capacity and Mitochondrial Potential during Liquid Storage at 4 °C.

The aim of this study was to investigate the effect of punicalagin, an antioxidant, on ram sperm quality. Semen samples were collected and pooled from five rams, then diluted using a Tris-based diluent containing various concentrations (0, 5, 15, 30 and 45 µM) of punicalagin. Sperm motility, plasma membrane integrity, acrosome integrity, total antioxidant capacity (TAC), reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential (MMP), superoxide dismutase (SOD) and catalase (CAT) were measured and analyzed during liquid storage at 4 °C. The results showed that the Tris-based solution containing punicalagin improved sperm motility, plasma membrane integrity, acrosome integrity, TAC, SOD, CAT and MMP, and decreased ROS content and MDA content. At the same time, the semen sample diluted with the Tris-based solution supplemented with 30 µM punicalagin achieved the best effect. The sperm total motility, progressive motility, plasma membrane integrity, acrosome integrity, TAC, SOD, CAT and MMP of the group supplemented with 30 µM punicalagin were significantly (p < 0.05) higher than those of the other groups on the 5th day during the liquid storage at 4 °C. Meanwhile, the ROS content and MDA content were significantly (p < 0.05) lower than those in the other groups. In conclusion, the optimal concentration of punicalagin in the Hu ram semen diluent was determined to be 30 µM. The results indicated that a diluent supplemented with punicalagin could enhance the quality of ram sperm preserved at 4 °C by increasing antioxidant capacity, mitochondrial potential and reducing oxidative stress.

Masked Conditional Variational Autoencoders for Chromosome Straightening.

Karyotyping is of importance for detecting chromosomal aberrations in human disease. However, chromosomes easily appear curved in microscopic images, which prevents cytogeneticists from analyzing chromosome types. To address this issue, we propose a framework for chromosome straightening, which comprises a preliminary processing algorithm and a generative model called masked conditional variational autoencoders (MC-VAE). The processing method utilizes patch rearrangement to address the difficulty in erasing low degrees of curvature, providing reasonable preliminary results for the MC-VAE. The MC-VAE further straightens the results by leveraging chromosome patches conditioned on their curvatures to learn the mapping between banding patterns and conditions. During model training, we apply a masking strategy with a high masking ratio to train the MC-VAE with eliminated redundancy. This yields a non-trivial reconstruction task, allowing the model to effectively preserve chromosome banding patterns and structure details in the reconstructed results. Extensive experiments on three public datasets with two stain styles show that our framework surpasses the performance of state-of-the-art methods in retaining banding patterns and structure details. Compared to using real-world bent chromosomes, the use of high-quality straightened chromosomes generated by our proposed method can improve the performance of various deep learning models for chromosome classification by a large margin. Such a straightening approach has the potential to be combined with other karyotyping systems to assist cytogeneticists in chromosome analysis.

Non-invasive imaging of pathological scars using a portable handheld two-photon microscope.

BACKGROUND: Pathological scars are a disorder that can lead to various cosmetic, psychological, and functional problems, and no effective assessment methods are currently available. Assessment and treatment of pathological scars are based on cutaneous manifestations. A two-photon microscope (TPM) with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo . This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients. METHODS: Fifteen patients with pathological scars and three healthy controls were recruited. Imaging was performed using a portable handheld TPM. Five indexes were extracted from two dimensional (2D) and three dimensional (3D) perspectives, including collagen depth, dermo-epidermal junction (DEJ) contour ratio, thickness, orientation, and occupation (proportion of collagen fibers in the field of view) of collagen. Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images. We assessed index differences between scar and normal skin and changes before and after treatment. RESULTS: Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers. Five indexes were employed to distinguish between normal skin and scar tissue. Statistically significant differences were found in average depth ( t = 9.917, P <0.001), thickness ( t = 4.037, P <0.001), occupation ( t = 2.169, P <0.050), orientation of collagen ( t = 3.669, P <0.001), and the DEJ contour ratio ( t = 5.105, P <0.001). CONCLUSIONS: Use of portable handheld TPM can distinguish collagen from skin tissues; thus, it is more suitable for scar imaging than reflectance confocal microscopy. Thus, a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.

Downregulation of KCNMA1 in mice accelerates auditory hair cells senescence via ferroptosis.

KCNMA1 encodes the K+ potassium channel α-subunit that plays a significant role in the auditory system. Our previous studies indicated that KCNMA1 is associated with age-related hearing loss(AHL). However, the detailed mechanism of KCNMA1 involvement in auditory age-related degradation has not been fully clarified. Therefore, we explored the expression of KCNMA1 in the peripheral auditory of 2-month-old and 12-month-old mice by Western blotting and immunofluorescence. The results of animal experiments showed that KCNMA1 expression was decreased in 12-month-old mice compared with 2-month-old mice, whereas the ferroptosis level was increased. To verify the role of KCNMA1 in AHL, we downregulated KCNMA1 in HEI-OC1 cells by transfecting shRNA. After downregulation, the ferroptosis level was increased and the aging process was accelerated. Furthermore, the aging process was affected by the expression of ferroptosis. In conclusion, these results revealed that KCNMA1 is associated with the aging process in auditory hair cells by regulating ferroptosis, which deepens our understanding of age-related hearing loss.

A pharmacovigilance study of association between proton-pump inhibitors and rhabdomyolysis event based on FAERS database.

BACKGROUND AND AIM: The association between proton-pump inhibitors (PPIs) and rhabdomyolysis were unclear. The aim of this study was to explore and systematically analyze the potential link between five PPIs and the rhabdomyolysis events using the FDA Adverse Event Reporting System (FAERS) database. METHODS: Suspected rhabdomyolysis events associated with PPIs were identified by data mining with the reporting odds ratio (ROR), proportional reporting ratio (PRR), the information component (IC), and Empirical Bayes Geometric Mean (EBGM). Demographic information, drug administration, and outcomes of PPI-induced rhabdomyolysis events were also analyzed. RESULTS: There were 3311 reports associated with PPI-induced rhabdomyolysis that were identified. After removing duplicates, 1899 cases were determined to contain complete patient demographic data. The average age was 65 ± 18 year and 57% were male. Omeprazole and pantoprazole had the same largest percentage of reports. Lansoprazole had the highest ROR index of 12.67, followed by esomeprazole (11.18), omeprazole (10.27), rabeprazole (10.06), and pantoprazole (9.24). PRR, IC, and EBGM showed similar patterns. This suggested that lansoprazole exhibited the strongest correlation with rhabdomyolysis. In rhabdomyolysis events, PPIs were mainly "concomitant" (>60%), and only a few cases were "primary suspects" (<15%). Rabeprazole showed the lowest death rate while lansoprazole showed the highest. CONCLUSIONS: The study suggested that significant rhabdomyolysis signals were associated with PPIs. Further research should be performed in drug safety evaluation for a more comprehensive association.

Large-Area Soluble Covalent Organic Framework Oligomer Coating for Organic Solution Nanofiltration Membranes.

Covalent organic frameworks (COFs) are a family of engaging membrane materials for molecular separation, which remain challenging to fabricate in the form of thin-film composite membranes due to slow crystal growth and insoluble powder. Here, an additive approach is presented to construct COF-based thin-film composite membranes in 10 min via COF oligomer coating onto poly(ether ether ketone) (PEEK）ultrafiltration membranes. By the virtue of ultra-thin liquid phase and liquid-solid interface-confined assembly, the COF oligomers are fast stacked up and grow along the interface with the solvent evaporation. Benefiting from the low out-plane resistance of COFs, COF@PEEK composite membranes exhibit high solvent permeances in a negative correlation with solvent viscosity. The well-defined pore structures enable high molecular sieving ability (Mw = 300 g mol-1 ). Besides, the COF@PEEK composite membranes possess excellent mechanical integrities and steadily operate for over 150 h in the condition of high-pressure cross flow. This work not only exemplifies the high-efficiency and scale-up preparation of COF-based thin-film composite membranes but also provides a new strategy for COF membrane processing.

Asymmetric conducting route and potential redistribution determine the polarization-dependent conductivity in layered ferroelectrics.

Precise control of the conductivity of layered ferroelectric semiconductors is required to make these materials suitable for advanced transistor, memory and logic circuits. Although proof-of-principle devices based on layered ferroelectrics have been demonstrated, it remains unclear how the polarization inversion induces conductivity changes. Therefore, function design and performance optimization remain cumbersome. Here we combine ab initio calculations with transport experiments to unveil the mechanism underlying the polarization-dependent conductivity in ferroelectric channel field-effect transistors. We find that the built-in electric field gives rise to an asymmetric conducting route formed by the hidden Stark effect and competes with the potential redistribution caused by the external field of the gate. Furthermore, leveraging our mechanistic findings, we control the conductivity threshold in α-In2Se3 ferroelectric channel field-effect transistors. We demonstrate logic-in-memory functionality through the implementation of electrically self-switchable primary (AND, OR) and composite (XOR, NOR, NAND) logic gates. Our work provides mechanistic insights into conductivity modulation in a broad class of layered ferroelectrics, providing foundations for their application in logic and memory electronics.