Short-term usage of proton pump inhibitors during admission was associated with increased risk of rehospitalization in critically ill patients with myocardial infarction: a cohort study.

PURPOSE: Previous studies showed that long-term use of proton pump inhibitors (PPIs) was associated with cardiovascular events. However, the impact of short-term PPI exposure on intensive care unit (ICU) patients with myocardial infarction (MI) remains largely unknown. This study aims to determine the precise correlation between short-term PPI usage during hospitalization and prognostic outcomes of ICU-admitted MI patients using Medical Information Mart for Intensive Care IV database (MIMIC-IV). METHODS: Propensity score matching (PSM) was applied to adjust confounding factors. The primary study outcome was rehospitalization with mortality and length of stay as secondary outcomes. Binary logistic, multivariable Cox, and linear regression analyses were employed to estimate the impact of short-term PPI exposure on ICU-admitted MI patients. RESULTS: A total of 7249 patients were included, involving 3628 PPI users and 3621 non-PPI users. After PSM, 2687 pairs of patients were matched. The results demonstrated a significant association between PPI exposure and increased risk of rehospitalization for MI in both univariate and multivariate [odds ratio (OR) = 1.157, 95% confidence interval (CI) 1.020-1.313] analyses through logistic regression after PSM. Furthermore, this risk was also observed in patients using PPIs > 7 days, despite decreased risk of all-cause mortality among these patients. It was also found that pantoprazole increased the risk of rehospitalization, whereas omeprazole did not. CONCLUSION: Short-term PPI usage during hospitalization was still associated with higher risk of rehospitalization for MI in ICU-admitted MI patients. Furthermore, omeprazole might be superior to pantoprazole regarding the risk of rehospitalization in ICU-admitted MI patients.

Cooperative NHC and Photoredox Catalyzed Radical Aminoacylation of Alkenes to Tetrahydropyridazines.

Tetrahydropyridazines constitute an important structural motif found in numerous natural products and pharmaceutical compounds. Herein, we report an aminoacylation reaction of alkenes that enables the synthesis of 1,4,5,6-tetrahydropyridazines through cooperative N-heterocyclic carbene (NHC) and photoredox catalysis. This approach involves the 6-endo-trig cyclization of N-centered hydrazonyl radicals, generated via single-electron oxidation of hydrazones, followed by a radical-radical coupling step. The mild process tolerates a wide range of common functional groups and affords a variety of tetrahydropyridazines in moderate to high yields. Preliminary investigations using chiral NHC catalysts demonstrate the potential of this protocol for asymmetric radical reactions.

Synthesis of γ-Oxo-phosphonates via N-Heterocyclic Carbene-Catalyzed Acylphosphorylation of Alkenes.

In this study, we present an N-heterocyclic carbene-catalyzed method for the radical acylphosphorylation of alkenes. Electrochemical investigations were employed to identify an appropriate class of oxime phosphonates capable of undergoing a single-electron transfer (SET) with Breslow enolates. The resulting phosphoryl radicals were effectively coupled with diverse styrenes and aldehydes to yield a variety of γ-oxo-phosphonates. Both radical clock experiments and electrochemical studies support our reaction design, and a plausible mechanism for the organocatalytic transformation is proposed.

An Angular Acceleration Based Looming Detector for Moving UAVs.

Visual perception equips unmanned aerial vehicles (UAVs) with increasingly comprehensive and instant environmental perception, rendering it a crucial technology in intelligent UAV obstacle avoidance. However, the rapid movements of UAVs cause significant changes in the field of view, affecting the algorithms' ability to extract the visual features of collisions accurately. As a result, algorithms suffer from a high rate of false alarms and a delay in warning time. During the study of visual field angle curves of different orders, it was found that the peak times of the curves of higher-order information on the angular size of looming objects are linearly related to the time to collision (TTC) and occur before collisions. This discovery implies that encoding higher-order information on the angular size could resolve the issue of response lag. Furthermore, the fact that the image of a looming object adjusts to meet several looming visual cues compared to the background interference implies that integrating various field-of-view characteristics will likely enhance the model's resistance to motion interference. Therefore, this paper presents a concise A-LGMD model for detecting looming objects. The model is based on image angular acceleration and addresses problems related to imprecise feature extraction and insufficient time series modeling to enhance the model's ability to rapidly and precisely detect looming objects during the rapid self-motion of UAVs. The model draws inspiration from the lobula giant movement detector (LGMD), which shows high sensitivity to acceleration information. In the proposed model, higher-order information on the angular size is abstracted by the network and fused with multiple visual field angle characteristics to promote the selective response to looming objects. Experiments carried out on synthetic and real-world datasets reveal that the model can efficiently detect the angular acceleration of an image, filter out insignificant background motion, and provide early warnings. These findings indicate that the model could have significant potential in embedded collision detection systems of micro or small UAVs.

Factors influencing serum calcium levels and the incidence of hypocalcemia after parathyroidectomy in primary hyperparathyroidism patients.

Background: Parathyroidectomy (PTX) is an effective treatment for primary hyperparathyroidism (PHPT) patients. Postoperative hypocalcemia is a common complication after PTX. This study aimed to analyze the factors influencing serum calcium levels and the incidence of hypocalcemia after parathyroidectomy in primary hyperparathyroidism patients. Methods: The retrospective study included 270 PHPT patients treated with PTX and collected their demographic and clinical information and their laboratory indices. Factors influencing serum calcium levels and hypocalcemia after PTX in PHPT patients were analyzed using univariate and multifactorial analyses. Results: First, in patients with normal preoperative serum calcium levels (2.20-2.74 mmol/L), the higher the preoperative alkaline phosphatase and serum phosphorus levels, the lower the postoperative serum calcium levels. Furthermore, the higher the preoperative serum calcium levels and the accompanying clinical symptoms, the higher the postoperative serum calcium levels. Low preoperative serum calcium levels were shown to be a risk factor for postoperative hypocalcemia (OR=0.022), and the optimal preoperative serum calcium threshold was 2.625 mmol/L (sensitivity and specificity were 0.587 and 0.712, respectively). Second, in the mild preoperative hypercalcemia group (2.75-3.00 mmol/L), the older the patient, the higher the preoperative and postoperative serum calcium levels, the higher the postoperative serum calcium; the lower the alkaline phosphatase and calcitonin levels, the higher the postoperative serum calcium levels. On the other hand, the younger the patient was, the more likely hypocalcemia blood was (OR=0.947), with an optimal age threshold of 47.5 years (sensitivity and specificity were 0.543 and 0.754, respectively). Third, in the preoperative moderate to severe hypercalcemia group (>3.0mmol/L), patients undergoing a combined contralateral thyroidectomy and a total thyroidectomy had low postoperative serum calcium levels. Conclusion: Patients with different preoperative serum calcium levels had various factors influencing their postoperative serum calcium levels and postoperative hypocalcemia, which facilitated the assessment of their prognosis.

Synthesis of Pyrroloindolines via N-Heterocyclic Carbene Catalyzed Dearomative Amidoacylation of Indole Derivatives.

Pyrroloindoline is a privileged heterocyclic motif that is widely present in many natural products and pharmaceutical compounds. Herein, we report an amidyl radical-mediated dearomatization for synthesizing a series of pyrroloindolines via N-heterocyclic carbene catalysis. In this organocatalytic process, the Breslow enolate served as both a single electron donor and an acyl radical equivalent to assemble C3a-acyl pyrroloindolines with a broad substrate scope. Sequential reduction of the indole derivatives provided the analogues of (±)-desoxyeseroline, which exhibited potential anticancer activity.

Photocatalytic Phosphine-Mediated Thioesterification of Carboxylic Acids with Disulfides.

Herein, a practical and effective synthesis of thioesters from readily available carboxylic acids and odorless disulfides was developed under photocatalytic conditions. This approach involves phosphoranyl radical-mediated fragmentation to generate acyl radicals and allows for incorporation of both S atoms of the disulfides into the desired products. In addition to batch reactions, a continuous-flow reactor was employed, enabling rapid thioester synthesis on a gram scale. Preliminary experimental mechanistic studies and the rapid synthesis of dalcetrapib are also demonstrated.

Influence of the built environment on taxi travel demand based on the optimal spatial analysis unit.

When discussing the influence of the built environment on taxi travel demand, few studies have considered the effect of the modifiable areal unit problem (MAUP) or the influence of the "5D" dimensions of the built environment (It refers to the consideration of the built environment from five dimensions of density, diversity, design, destination accessibility and distance to transit.) on taxi travel demand. Moreover, discussion of the nonlinear and linear relationships between taxi demand and environment variables is also lacking. To address these gaps, we constructed a "5D" dimension index system of built environment variables. The influence of the MAUP on the model results was discussed using the optimal parameter-based geographical detector (OPGD) model, and the optimal spatial analysis unit was selected. The OPGD and multiscale geographically weighted regression (MGWR) models were used to reveal the influence of different dimensions of the built environment on taxi travel demand from global and local perspectives, respectively. Finally, the central urban area of Xi'an was analyzed as an example. The results show the following: (1) Most built environment variables are sensitive to the influence of MAUP. (2) It is better to divide the space into regular hexagons than squares, and the optimal spatial analysis unit in this study is a regular hexagon grid with sides of 900m. (3) From a global perspective, the distance to the city center, commercial residence POI density, transportation facility POI density, and population density have the greatest influence on the demand for taxi travel. (4) From a local perspective, the MGWR model considering spatial heterogeneity and scale differences is superior to the GWR model, and the influence of built environment variables exhibited spatial heterogeneity. The proposed optimal spatial analysis unit can provide a basis for taxi demand forecasting and scheduling. This study provides a reference for urban planners and traffic managers to offer optimization strategies related to the built environment, promote healthy development of the taxi industry, and solve the problems of the urban transportation system.

Evidence for marine sedimentary rocks in Utopia Planitia: Zhurong rover observations.

Decades of research using remotely sensed data have extracted evidence for the presence of an ocean in the northern lowlands of Mars in the Hesperian (∼3.3 Ga), but these claims have remained controversial due to the lack of in situ analysis of the associated geologic unit, the Vastitas Borealis Formation (VBF). The Tianwen-1/Zhurong rover was targeted to land within the VBF near its southern margin and has traversed almost 2 km southward toward the interpreted shoreline. We report here on the first in situ analysis of the VBF that reveals sedimentary structures and features in surface rocks that suggest that the VBF was deposited in a marine environment, providing direct support for the existence of an ancient (Hesperian) ocean on Mars.

Silylacylation of Alkenes through N-Heterocyclic Carbene Catalysis.

The construction of silicon-containing molecules has received increasing attention in recent years. Herein, we report the generation of silyl radicals through NHC catalysis under mild reaction conditions. This methodology offers a novel and convenient route to a diverse range of ß-silyl ketones with a broad substrate scope and good functional group compatibility. Both the radical clock and electrochemical studies are consistent with the hypothesis of ground-state SET, and a plausible mechanism for the organocatalytic transformation is proposed.

Application of urinary N-acetyl-ß-D-glucosaminidase combined with serum retinol-binding protein in early detection of diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a microangiopathy of type 2 diabetes mellitus (T2DM), which can damage the kidney through various ways and mechanisms due to the nature of the disease, involving the renal interstitium and glomeruli. However, in the early stage of the disease, patients only showed kidney volume increase and glomerular hyperthyroidism, and typical symptoms that are difficult to arouse individual attention were noticed. AIM: To observe the expression of serum retinol-binding protein (RBP) and urinary N-acetyl-ß-D-glucosaminidase (NAG) in patients with DN, and to analyze their value in disease prediction, so as to provide new targets for early diagnosis and treatment of DN. METHODS: The baseline data of 50 T2DM patients treated in our hospital between January 2021 and December 2022 were retrospectively reviewed and included in group A. The baseline data of 50 patients with type 2 DN admitted to our hospital during the same period were collected and included in group B. The baseline data and serum RBP and urine NAG expression were compared between the two groups to analyze their value in the early prediction of DN. RESULTS: There was no significant difference in age, gender, duration of diabetes, combined hyperlipidemia and combined hypertension between the two groups (P > 0.05); the expression of urinary NAG and serum RBP in group B was higher than that in group A, and the difference was statistically significant (P < 0.05); a multiple logistic regression model was established, and the results showed that urinary NAG and serum RBP were related to the presence or absence of injury in diabetic patients, and overexpression of urinary NAG and serum RBP may be risk factors for renal injury in T2DM patients (OR > 1, P < 0.05); receiver operating curve curve was plotted, and the results showed that the area under the curve of urinary NAG and serum RBP expression alone and in combination for predicting DN was > 0.80, and the predictive value was satisfactory; bivariate Spearman linear correlation analysis showed that there was a positive correlation between urinary NAG and serum RBP expression in patients with DN (r = 0.566, P = 0.000). CONCLUSION: The increased expression of urinary NAG and serum RBP may be the risk factors leading to the progression of T2DM to DN. The possibility of DN can be considered in patients with urinary NAG and serum RBP overexpression by examining the expression of urinary NAG and serum RBP in patients with T2DM in clinical practice.

MiR-125 family improves the radiosensitivity of head and neck squamous cell carcinoma.

BACKGROUND: MiRNAs can affect the radiosensitization of head and neck squamous cell carcinoma (HNSCC). We aimed to analyze the function of miR-125 family members in HNSCC using The Cancer Genome Atlas (TCGA) and determine their effect on radiation in laryngeal squamous cell cancer (LSCC). METHODS: First, we systematically analyzed the role of the miR-125 family in HNSCC using the TCGA database and found that miR-125a-5p is associated with radiotherapy. We then performed comprehensive enrichment analysis of miR-125a-5p and predicted target genes. Then, we performed transfection, cell proliferation assays, reverse transcription polymerase chain reaction, apoptosis assays, micronucleus tests, and western blotting on hep-2 cells selected with puromycin. RESULTS: MiR-125 family members exhibited significantly different expression in HNSCC. They were significantly associated with tumor-node-metastasis staging, clinical stages, and histological grades. Radiation therapy had a statistically effect on miR-125 family members, except miR-125a-3p. Moreover, miR-125a-5p was related to overall survival in LSCC. Thus, we predicted 110 target genes and seven hub genes of miR-125a-5p. The proliferation rate of cells transfected with lentivirus vector expressing miR-125a-5p was significantly reduced compared to the other groups. The radiation effect was enhanced in cells transfected with miR-125a-5p. The ratio of apoptotic cells transfected and exposed to X-rays (10 Gy) was distinctly higher than that of the Ad-control group. Western blotting analysis revealed that miR-125a-5p upregulated the apoptotic regulators P53 and rH2AX. Thus, miR-125a-5p may increase radiosensitivity in LSCC via upregulation of pro-apoptotic genes. CONCLUSIONS: MiR-125 family members could be prognostic biomarkers of HNSCC and improve HNSCC sensitivity to radiotherapy by activating P53. Upregulating miR-125a-5p via lentivirus vectors may be a novel strategy to strengthen the effect of radiotherapy on LSCC.

Deoxygenation of oximes for the synthesis of pyrrolines via hydroimination cyclization.

Herein, we report the generation of iminyl radicals through photocatalytic deoxygenation of oximes with trivalent phosphine. The hydroimination reaction proceeded via ß-scission of a phosphoranyl radical, followed by 5-exo-trig cyclization of the resulting iminyl radical. This protocol transforms oximes, including alkyl oximes, into a variety of pyrrolines in moderate to good yields. A radical clock experiment confirmed the formation of a cyclic radical and supported our reaction design.

A Synthetic SARS-CoV-2-Derived T-Cell and B-Cell Peptide Cocktail Elicits Full Protection against Lethal Omicron BA.1 Infection in H11-K18-hACE2 Mice.

Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developing the capacity for immune evasion and resistance to existing vaccines and drugs. To address this, development of vaccines against coronavirus disease 2019 (COVID-19) has focused on universality, strong T cell immunity, and rapid production. Synthetic peptide vaccines, which are inexpensive and quick to produce, show low toxicity, and can be selected from the conserved SARS-CoV-2 proteome, are promising candidates. In this study, we evaluated the effectiveness of a synthetic peptide cocktail containing three murine CD4+ T-cell epitopes from the SARS-CoV-2 nonspike proteome and one B-cell epitope from the Omicron BA.1 receptor-binding domain (RBD), along with aluminum phosphate (Al) adjuvant and 5' cytosine-phosphate-guanine 3' oligodeoxynucleotide (CpG-ODN) adjuvant in mice. The peptide cocktail induced good Th1-biased T-cell responses and effective neutralizing-antibody titers against the Omicron BA.1 variant. Additionally, H11-K18-hACE2 transgenic mice were fully protected against lethal challenge with the BA.1 strain, with a 100% survival rate and reduced pulmonary viral load and pathological lesions. Subcutaneous administration was found to be the superior route for synthetic peptide vaccine delivery. Our findings demonstrate the effectiveness of the peptide cocktail in mice, suggesting the feasibility of synthetic peptide vaccines for humans. IMPORTANCE Current vaccines based on production of neutralizing antibodies fail to prevent the infection and transmission of SARS-CoV-2 Omicron and its subvariants. Understanding the critical factors and avoiding the disadvantages of vaccine strategies are essential for developing a safe and effective COVID-19 vaccine, which would include a more effective and durable cellular response, minimal effects of viral mutations, rapid production against emerging variants, and good safety. Peptide-based vaccines are an excellent alternative because they are inexpensive, quick to produce, and very safe. In addition, human leukocyte antigen T-cell epitopes could be targeted at robust T-cell immunity and selected in the conserved region of the SARS-CoV-2 variants. Our study showed that a synthetic SARS-CoV-2-derived peptide cocktail induced full protection against lethal infection with Omicron BA.1 in H11-K18-hACE2 mice for the first time. This could have implications for the development of effective COVID-19 peptide vaccines for humans.

Attention and Prediction-Guided Motion Detection for Low-Contrast Small Moving Targets.

Small target motion detection within complex natural environments is an extremely challenging task for autonomous robots. Surprisingly, the visual systems of insects have evolved to be highly efficient in detecting mates and tracking prey, even though targets occupy as small as a few degrees of their visual fields. The excellent sensitivity to small target motion relies on a class of specialized neurons, called small target motion detectors (STMDs). However, existing STMD-based models are heavily dependent on visual contrast and perform poorly in complex natural environments, where small targets generally exhibit extremely low contrast against neighboring backgrounds. In this article, we develop an attention-and-prediction-guided visual system to overcome this limitation. The developed visual system comprises three main subsystems, namely: 1) an attention module; 2) an STMD-based neural network; and 3) a prediction module. The attention module searches for potential small targets in the predicted areas of the input image and enhances their contrast against a complex background. The STMD-based neural network receives the contrast-enhanced image and discriminates small moving targets from background false positives. The prediction module foresees future positions of the detected targets and generates a prediction map for the attention module. The three subsystems are connected in a recurrent architecture, allowing information to be processed sequentially to activate specific areas for small target detection. Extensive experiments on synthetic and real-world datasets demonstrate the effectiveness and superiority of the proposed visual system for detecting small, low-contrast moving targets against complex natural environments.

A Time-Delay Feedback Neural Network for Discriminating Small, Fast-Moving Targets in Complex Dynamic Environments.

Discriminating small moving objects within complex visual environments is a significant challenge for autonomous micro-robots that are generally limited in computational power. By exploiting their highly evolved visual systems, flying insects can effectively detect mates and track prey during rapid pursuits, even though the small targets equate to only a few pixels in their visual field. The high degree of sensitivity to small target movement is supported by a class of specialized neurons called small target motion detectors (STMDs). Existing STMD-based computational models normally comprise four sequentially arranged neural layers interconnected via feedforward loops to extract information on small target motion from raw visual inputs. However, feedback, another important regulatory circuit for motion perception, has not been investigated in the STMD pathway and its functional roles for small target motion detection are not clear. In this article, we propose an STMD-based neural network with feedback connection (feedback STMD), where the network output is temporally delayed, then fed back to the lower layers to mediate neural responses. We compare the properties of the model with and without the time-delay feedback loop and find that it shows a preference for high-velocity objects. Extensive experiments suggest that the feedback STMD achieves superior detection performance for fast-moving small targets, while significantly suppressing background false positive movements which display lower velocities. The proposed feedback model provides an effective solution in robotic visual systems for detecting fast-moving small targets that are always salient and potentially threatening.

Enhancing LGMD's Looming Selectivity for UAV With Spatial-Temporal Distributed Presynaptic Connections.

Collision detection is one of the most challenging tasks for unmanned aerial vehicles (UAVs). This is especially true for small or micro-UAVs due to their limited computational power. In nature, flying insects with compact and simple visual systems demonstrate their remarkable ability to navigate and avoid collision in complex environments. A good example of this is provided by locusts. They can avoid collisions in a dense swarm through the activity of a motion-based visual neuron called the Lobula giant movement detector (LGMD). The defining feature of the LGMD neuron is its preference for looming. As a flying insect's visual neuron, LGMD is considered to be an ideal basis for building UAV's collision detecting system. However, existing LGMD models cannot distinguish looming clearly from other visual cues, such as complex background movements caused by UAV agile flights. To address this issue, we proposed a new model implementing distributed spatial-temporal synaptic interactions, which is inspired by recent findings in locusts' synaptic morphology. We first introduced the locally distributed excitation to enhance the excitation caused by visual motion with preferred velocities. Then, radially extending temporal latency for inhibition is incorporated to compete with the distributed excitation and selectively suppress the nonpreferred visual motions. This spatial-temporal competition between excitation and inhibition in our model is, therefore, tuned to preferred image angular velocity representing looming rather than background movements with these distributed synaptic interactions. Systematic experiments have been conducted to verify the performance of the proposed model for UAV agile flights. The results have demonstrated that this new model enhances the looming selectivity in complex flying scenes considerably and has the potential to be implemented on embedded collision detection systems for small or micro-UAVs.

The feasibility and safety of simultaneous bilateral video-assisted thoracic surgery for the treatment of bilateral pulmonary lesions.

Background: The aim of this study was to evaluate the feasibility and safety of simultaneous bilateral video-assisted thoracic surgery (VATS) for the treatment of bilateral pulmonary lesions. Methods: The data of 11 patients who received simultaneous bilateral pulmonary surgery using VATS in the Department of Thoracic Surgery of The Third Affiliated Hospital of Naval Medical University between January 2016 and August 2021 were retrospectively analyzed. Results: The cases of four male and seven female patients, with a mean age of 57.54 ± 8.37 years (range, 44-67 years), were reviewed. Nonanatomic wedge resection, pulmonary segmentectomy or lobectomy via VATS were performed depending on each patient's situation. Mean 1 second forced expiratory volume (FEV1) was 2.55 ± 0.66 L(range, 1.49-3.88 L), mean intraoperative bleeding volume was 91.81 ± 49.56 mL(range, 30-150 mL), mean operating time was 273.72 ± 68.98 min(range, 132-390 min), and mean drainage duration was 5.27 ± 3.60 days(range, 2-14 days), with a mean total drainage volume of 1,515.90 ± 772.75 mL(range, 530-3,225 mL). Only one postoperative complication (air leakage) occurred, with an overall complication rate of 9.09%. The mean postoperative hospital stay was 8.81 ± 3.60 days (range, 5-18 days), and the mean total cost of hospitalization was 67,054.53 ± 20,896.49 RMB (range, 47,578.45-123,530.8 RMB). Conclusions: Simultaneous bilateral pulmonary surgery using VATS for the treatment of bilateral pulmonary lesions is safe and feasible and can therefore be considered after strict preoperative evaluation of the patient.

Diastereoselective Radical Aminoacylation of Olefins through N-Heterocyclic Carbene Catalysis.

There have been significant advancements in radical-mediated reactions through covalent-based organocatalysis. Here, we present the generation of iminyl and amidyl radicals via N-heterocyclic carbene (NHC) catalysis, enabling diastereoselective aminoacylation of trisubstituted alkenes. Different from photoredox catalysis, single electron transfer from the deprotonated Breslow intermediate to O-aryl hydroxylamine generates an NHC-bound ketyl radical, which undergoes diastereocontrolled cross-coupling with the prochiral C-centered radical. This operationally simple method provides a straightforward access to a variety of pyrroline and oxazolidinone heterocycles with vicinal stereocenters (77 examples, up to >19:1 d.r.). Electrochemical studies of the acyl thiazolium salts support our reaction design and highlight the reducing ability of Breslow-type derivatives. A detailed computational analysis of this organocatalytic system suggests that radical-radical coupling is the rate-determining step, in which π-π stacking interaction between the radical intermediates subtly controls the diastereoselectivity.