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1. Scaling and logic in the color code on a superconducting quantum processor

Author

Lacroix, Nathan, Bourassa, Alexandre, Heras, Francisco J. H., Zhang, Lei M., Bausch, Johannes, Senior, Andrew W., Edlich, Thomas, Shutty, Noah, Sivak, Volodymyr, Bengtsson, Andreas, McEwen, Matt, Higgott, Oscar, Kafri, Dvir, Claes, Jahan, Morvan, Alexis, Chen, Zijun, Zalcman, Adam, Madhuk, Sid, Acharya, Rajeev, Beni, Laleh Aghababaie, Aigeldinger, Georg, Alcaraz, Ross, Andersen, Trond I., Ansmann, Markus, Arute, Frank, Arya, Kunal, Asfaw, Abraham, Atalaya, Juan, Babbush, Ryan, Ballard, Brian, Bardin, Joseph C., Bilmes, Alexander, Blackwell, Sam, Bovaird, Jenna, Bowers, Dylan, Brill, Leon, Broughton, Michael, Browne, David A., Buchea, Brett, Buckley, Bob B., Burger, Tim, Burkett, Brian, Bushnell, Nicholas, Cabrera, Anthony, Campero, Juan, Chang, Hung-Shen, Chiaro, Ben, Chih, Liang-Ying, Cleland, Agnetta Y., Cogan, Josh, Collins, Roberto, Conner, Paul, Courtney, William, Crook, Alexander L., Curtin, Ben, Das, Sayan, Demura, Sean, De Lorenzo, Laura, Di Paolo, Agustin, Donohoe, Paul, Drozdov, Ilya, Dunsworth, Andrew, Eickbusch, Alec, Elbag, Aviv Moshe, Elzouka, Mahmoud, Erickson, Catherine, Ferreira, Vinicius S., Burgos, Leslie Flores, Forati, Ebrahim, Fowler, Austin G., Foxen, Brooks, Ganjam, Suhas, Garcia, Gonzalo, Gasca, Robert, Genois, Élie, Giang, William, Gilboa, Dar, Gosula, Raja, Dau, Alejandro Grajales, Graumann, Dietrich, Greene, Alex, Gross, Jonathan A., Ha, Tan, Habegger, Steve, Hansen, Monica, Harrigan, Matthew P., Harrington, Sean D., Heslin, Stephen, Heu, Paula, Hiltermann, Reno, Hilton, Jeremy, Hong, Sabrina, Huang, Hsin-Yuan, Huff, Ashley, Huggins, William J., Jeffrey, Evan, Jiang, Zhang, Jin, Xiaoxuan, Joshi, Chaitali, Juhas, Pavol, Kabel, Andreas, Kang, Hui, Karamlou, Amir H., Kechedzhi, Kostyantyn, Khaire, Trupti, Khattar, Tanuj, Khezri, Mostafa, Kim, Seon, Klimov, Paul V., Kobrin, Bryce, Korotkov, Alexander N., Kostritsa, Fedor, Kreikebaum, John Mark, Kurilovich, Vladislav D., Landhuis, David, Lange-Dei, Tiano, Langley, Brandon W., Laptev, Pavel, Lau, Kim-Ming, Ledford, Justin, Lee, Kenny, Lester, Brian J., Guevel, Loïck Le, Li, Wing Yan, Li, Yin, Lill, Alexander T., Livingston, William P., Locharla, Aditya, Lucero, Erik, Lundahl, Daniel, Lunt, Aaron, Maloney, Ashley, Mandrà, Salvatore, Martin, Leigh S., Martin, Orion, Maxfield, Cameron, McClean, Jarrod R., Meeks, Seneca, Megrant, Anthony, Miao, Kevin C., Molavi, Reza, Molina, Sebastian, Montazeri, Shirin, Movassagh, Ramis, Neill, Charles, Newman, Michael, Nguyen, Anthony, Nguyen, Murray, Ni, Chia-Hung, Niu, Murphy Y., Oas, Logan, Oliver, William D., Orosco, Raymond, Ottosson, Kristoffer, Pizzuto, Alex, Potter, Rebecca, Pritchard, Orion, Quintana, Chris, Ramachandran, Ganesh, Reagor, Matthew J., Resnick, Rachel, Rhodes, David M., Roberts, Gabrielle, Rosenberg, Eliott, Rosenfeld, Emma, Rossi, Elizabeth, Roushan, Pedram, Sankaragomathi, Kannan, Schurkus, Henry F., Shearn, Michael J., Shorter, Aaron, Shvarts, Vladimir, Small, Spencer, Smith, W. Clarke, Springer, Sofia, Sterling, George, Suchard, Jordan, Szasz, Aaron, Sztein, Alex, Thor, Douglas, Tomita, Eifu, Torres, Alfredo, Torunbalci, M. Mert, Vaishnav, Abeer, Vargas, Justin, Vdovichev, Sergey, Vidal, Guifre, Heidweiller, Catherine Vollgraff, Waltman, Steven, Waltz, Jonathan, Wang, Shannon X., Ware, Brayden, Weidel, Travis, White, Theodore, Wong, Kristi, Woo, Bryan W. K., Woodson, Maddy, Xing, Cheng, Yao, Z. Jamie, Yeh, Ping, Ying, Bicheng, Yoo, Juhwan, Yosri, Noureldin, Young, Grayson, Zhang, Yaxing, Zhu, Ningfeng, Zobrist, Nicholas, Neven, Hartmut, Kohli, Pushmeet, Davies, Alex, Boixo, Sergio, Kelly, Julian, Jones, Cody, Gidney, Craig, and Satzinger, Kevin J.

Subjects
Quantum Physics
Abstract

Quantum error correction is essential for bridging the gap between the error rates of physical devices and the extremely low logical error rates required for quantum algorithms. Recent error-correction demonstrations on superconducting processors have focused primarily on the surface code, which offers a high error threshold but poses limitations for logical operations. In contrast, the color code enables much more efficient logic, although it requires more complex stabilizer measurements and decoding techniques. Measuring these stabilizers in planar architectures such as superconducting qubits is challenging, and so far, realizations of color codes have not addressed performance scaling with code size on any platform. Here, we present a comprehensive demonstration of the color code on a superconducting processor, achieving logical error suppression and performing logical operations. Scaling the code distance from three to five suppresses logical errors by a factor of $\Lambda_{3/5}$ = 1.56(4). Simulations indicate this performance is below the threshold of the color code, and furthermore that the color code may be more efficient than the surface code with modest device improvements. Using logical randomized benchmarking, we find that transversal Clifford gates add an error of only 0.0027(3), which is substantially less than the error of an idling error correction cycle. We inject magic states, a key resource for universal computation, achieving fidelities exceeding 99% with post-selection (retaining about 75% of the data). Finally, we successfully teleport logical states between distance-three color codes using lattice surgery, with teleported state fidelities between 86.5(1)% and 90.7(1)%. This work establishes the color code as a compelling research direction to realize fault-tolerant quantum computation on superconducting processors in the near future.

Published
2024

2. Training Language Models to Self-Correct via Reinforcement Learning

Author

Kumar, Aviral, Zhuang, Vincent, Agarwal, Rishabh, Su, Yi, Co-Reyes, John D, Singh, Avi, Baumli, Kate, Iqbal, Shariq, Bishop, Colton, Roelofs, Rebecca, Zhang, Lei M, McKinney, Kay, Shrivastava, Disha, Paduraru, Cosmin, Tucker, George, Precup, Doina, Behbahani, Feryal, and Faust, Aleksandra

Subjects
Computer Science - Machine Learning
Abstract

Self-correction is a highly desirable capability of large language models (LLMs), yet it has consistently been found to be largely ineffective in modern LLMs. Current methods for training self-correction typically depend on either multiple models, a more advanced model, or additional forms of supervision. To address these shortcomings, we develop a multi-turn online reinforcement learning (RL) approach, SCoRe, that significantly improves an LLM's self-correction ability using entirely self-generated data. To build SCoRe, we first show that variants of supervised fine-tuning (SFT) on offline model-generated correction traces are often insufficient for instilling self-correction behavior. In particular, we observe that training via SFT falls prey to either a distribution mismatch between mistakes made by the data-collection policy and the model's own responses, or to behavior collapse, where learning implicitly prefers only a certain mode of correction behavior that is often not effective at self-correction on test problems. SCoRe addresses these challenges by training under the model's own distribution of self-generated correction traces and using appropriate regularization to steer the learning process into learning a self-correction behavior that is effective at test time as opposed to fitting high-reward responses for a given prompt. This regularization process includes an initial phase of multi-turn RL on a base model to generate a policy initialization that is less susceptible to collapse, followed by using a reward bonus to amplify self-correction. With Gemini 1.0 Pro and 1.5 Flash models, we find that SCoRe achieves state-of-the-art self-correction performance, improving the base models' self-correction by 15.6% and 9.1% respectively on MATH and HumanEval.

Published
2024

3. Many-Shot In-Context Learning

Author

Agarwal, Rishabh, Singh, Avi, Zhang, Lei M., Bohnet, Bernd, Rosias, Luis, Chan, Stephanie, Zhang, Biao, Anand, Ankesh, Abbas, Zaheer, Nova, Azade, Co-Reyes, John D., Chu, Eric, Behbahani, Feryal, Faust, Aleksandra, and Larochelle, Hugo

Subjects
Computer Science - Machine Learning, Computer Science - Artificial Intelligence, Computer Science - Computation and Language
Abstract

Large language models (LLMs) excel at few-shot in-context learning (ICL) -- learning from a few examples provided in context at inference, without any weight updates. Newly expanded context windows allow us to investigate ICL with hundreds or thousands of examples -- the many-shot regime. Going from few-shot to many-shot, we observe significant performance gains across a wide variety of generative and discriminative tasks. While promising, many-shot ICL can be bottlenecked by the available amount of human-generated examples. To mitigate this limitation, we explore two new settings: Reinforced and Unsupervised ICL. Reinforced ICL uses model-generated chain-of-thought rationales in place of human examples. Unsupervised ICL removes rationales from the prompt altogether, and prompts the model only with domain-specific questions. We find that both Reinforced and Unsupervised ICL can be quite effective in the many-shot regime, particularly on complex reasoning tasks. Finally, we demonstrate that, unlike few-shot learning, many-shot learning is effective at overriding pretraining biases, can learn high-dimensional functions with numerical inputs, and performs comparably to fine-tuning. We also find that inference cost increases linearly in the many-shot regime, and frontier LLMs benefit from many-shot ICL to varying degrees. Our analysis also reveals the limitations of next-token prediction loss as an indicator of downstream ICL performance., Comment: NeurIPS (Spotlight)

Published
2024

4. Cuprate-like Electronic Structures in Infinite-Layer Nickelates with Substantial Hole Dopings

Author

Ding, X., Fan, Y., Wang, X. X., Li, C. H., An, Z. T., Ye, J. H., Tang, S. L., Lei, M. Y. N., Sun, X. T., Guo, N., Chen, Z. H., Sangphet, S., Wang, Y. L., Xu, H. C., Peng, R., and Feng, D. L.

Subjects
Condensed Matter - Superconductivity, Condensed Matter - Materials Science, Condensed Matter - Strongly Correlated Electrons
Abstract

The superconducting infinite-layer (IL) nickelates offer a new platform for investigating the long-standing problem of high-temperature superconductivity. Many models were proposed to understand its superconducting mechanisms based on the calculated electronic structure, and the multiple Fermi surfaces and multiple orbitals involved create complications and controversial conclusions. Over the past 5 years, the lack of direct measurements of the electronic structure has hindered the understanding of nickelate superconductors. Here we fill this gap by directly resolving the electronic structures of the parent compound LaNiO$_2$ and superconducting La$_{0.8}$Ca$_{0.2}$NiO$_2$ using angle-resolved photoemission spectroscopy (ARPES). We find that their Fermi surfaces consist of a quasi-two-dimensional (quasi-2D) hole pocket and a three-dimensional (3D) electron pocket at the Brillouin zone corner, whose volumes change upon Ca doping. The Fermi surface topology and band dispersion of the hole pocket closely resemble those observed in hole-doped cuprates. However, the cuprate-like band exhibits significantly higher hole doping in superconducting La$_{0.8}$Ca$_{0.2}$NiO$_2$ compared to superconducting cuprates, highlighting the disparities in the electronic states of the superconducting phase. Our observations highlight the novel aspects of the IL nickelates, and pave the way toward the microscopic understanding of the IL nickelate family and its superconductivity., Comment: 12 pages, 4 figures

Published
2024
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6. Empirical Lossless Compression Bound of a Data Sequence

Author

Li, Lei M

Subjects
Computer Science - Information Theory, Mathematics - Statistics Theory, 68P30, 94A15, 62B10, G.0
Abstract

We consider the lossless compression bound of any individual data sequence. If we fit the data by a parametric model, the entropy quantity $nH({\hat \theta}_n)$ obtained by plugging in the maximum likelihood estimate is an underestimate of the bound, where $n$ is the number of words. Shtarkov showed that the normalized maximum likelihood (NML) distribution or code length is optimal in a minimax sense for any parametric family. We show by the local asymptotic normality that the NML code length for the exponential families is $nH(\hat \theta_n) +\frac{d}{2}\log \, \frac{n}{2\pi} +\log \int_{\Theta} |I(\theta)|^{1/2}\, d\theta+o(1)$, where $d$ is the model dimension or dictionary size, and $|I(\theta)|$ is the determinant of the Fisher information matrix. We also demonstrate that sequentially predicting the optimal code length for the next word via a Bayesian mechanism leads to the mixture code, whose pathwise length is given by $nH({\hat \theta}_n) +\frac{d}{2}\log \, \frac{n}{2\pi} +\log \frac{|\, I({\hat \theta}_n)|^{1/2}}{w({\hat \theta}_n)}+o(1) $, where $w(\theta)$ is a prior. The asymptotics apply to not only discrete symbols but also continuous data if the code length for the former is replaced by the description length for the latter. The analytical result is exemplified by calculating compression bounds of protein-encoding DNA sequences under different parsing models. Typically, the highest compression is achieved when the parsing is in phase of the amino acid codons. On the other hand, the compression rates of pseudo-random sequences are larger than 1 regardless parsing models. These model-based results are in consistency with that random sequences are incompressible as asserted by the Kolmogorov complexity theory. The empirical lossless compression bound is particularly more accurate when dictionary size is relatively large., Comment: 3 tables

Published
2023

8. Characteristics of Bacteria in Urine and Stones from Patients Treated with Percutaneous Nephrolithotomy and Association with Postoperative Infection

Author

Lei M, Jiang Z, Xu P, Chang Z, Zhang Y, Zhang S, An L, Li S, Zeng T, Tiselius HG, Zhou Y, Zeng G, and Wu W

Subjects
kidney stones, bacterial spectrum, antibiotic resistance, stone culture, urine culture, Infectious and parasitic diseases, RC109-216
Abstract

Min Lei,1,2,&ast; Zheng Jiang,1,2,&ast; Peng Xu,1,2 Zhenglin Chang,1– 3 Yuyan Zhang,4 Shike Zhang,1,2 Lingyue An,1,2,5 Shujue Li,2,3 Tao Zeng,2,3 Hans-Göran Tiselius,6 Yuhao Zhou,1,2 Guohua Zeng,2,3 Wenqi Wu1,2 1Department of Urology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, People’s Republic of China; 2Guangdong Key Laboratory of Urology, Guangzhou Medical University, Guangzhou, Guangdong, 510260, People’s Republic of China; 3Department of Urology, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, People’s Republic of China; 4Guangzhou Institute of Dermatology, Guangzhou, Guangdong, 510095, People’s Republic of China; 5Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, People’s Republic of China; 6Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, 14186, Sweden&ast;These authors contributed equally to this workCorrespondence: Wenqi Wu; Guohua Zeng, Email 2009681012@gzhmu.edu.cn; gzgyzgh@vip.sina.comBackground: The purpose of this study was to identify bacterial differences between urine cultures (UC) and stone cultures (SC) in patients with complex kidney stones and to determine any correlation with post-percutaneous nephrolithotomy Systemic Inflammatory Response Syndrome (SIRS).Methods: Perioperative data of 1055 patients with complex kidney stones treated with first-stage Percutaneous Nephrolithotomy (PCNL) from September 2016 until September 2021 were included. Preoperative mid-stream urine samples and surgically obtained stone material were subjected to bacterial culture and antibiotic sensitivity tests. Preoperatively, antibiotic usage was determined by the UC or local bacterial resistance patterns. After PCNL treatment, antibiotic selection was guided by stone bacterial culture result and clinical symptoms. The effect of different preoperative antibiotic regimens based on urine cultures and postoperative antibiotic treatment based on stone cultures were assessed.Results: Positive stone cultures (SC+) were significantly more common than positive urine cultures (UC+) (31.9% vs 20.9%, p < 0.05). Escherichia coli (E. coli) was the most common uropathogen in both urine (54.3%) and stones (43.9%). The difference was statistically significant (p < 0.05). Moreover, UC+SC-, UC-SC+, UC+SC+, and preoperative serum creatinine were independent risk factors of postoperative SIRS. The incidence of SIRS in the UC+SC+ patients with different bacteria in stones and urine (51.6%) was higher than that in other culture groups. The antibiotic resistance of E. coli inside the stone was increased when prolonged preoperative antibiotics were administered to UC+ patients.Conclusion: The bacterial spectrum and positive outcome of culture in urine and stones were significantly different. The incidence of postoperative SIRS was highest in patients with UC+SC+ but with different bacteria strains. Prolonged pre-surgical antibiotic treatment apparently induced higher drug resistance for bacteria inside the stone.Keywords: kidney stones, bacterial spectrum, antibiotic resistance, stone culture, urine culture

Published
2024

9. Evaluation of Depression and Its Correlates in Terms of Demographics, Eating Habits, and Exercises Among University Students: A Multicenter Cross-Sectional Analysis

Author

Zheng H, Li C, Zhang L, Wang T, Cai Z, and Lei M

Subjects
depression, eating habits, sports, university students, cross-sectional study., Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Hua Zheng,1 Changqing Li,1 Lirong Zhang,2 Tailin Wang,3 Zengliang Cai,4 Mingxing Lei5,6 1College of Physical Education and Health Science, Chongqing Normal University, Chongqing, 401331, People’s Republic of China; 2Department of Physical Education, Xiamen University of Technology, Xiamen, Fujian, 361024, People’s Republic of China; 3School of Physical Education, North University of China, Taiyuan, Shanxi, 030051, People’s Republic of China; 4Department of Physical Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 5Chinese PLA General School, Beijing, 100853, People’s Republic of China; 6Chinese PLA General Hospital, Beijing, 100853, People’s Republic of ChinaCorrespondence: Mingxing Lei, Department of Orthopedic Surgery, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100039, People’s Republic of China, Tel +8618811772189, Email leimingxing@301hospital.com.cn Zengliang Cai, Department of Physical Education, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai, 201203, People’s Republic of China, Email caizengliang@shutcm.edu.cnBackground: University students are a vulnerable population prone to mental health challenges. This study aimed to investigate depression and its associated factors among university students in terms of demographics, eating habits, and exercises.Methods: A total of 2891 university students from three universities participated in this study between January 2024 and February 2024. An online survey questionnaire was distributed using a snow-ball strategy. The survey collected demographic, lifestyle, and psychological data, including depression and anxiety scores using the PHQ-9 and GAD-7 screening tools. Subgroup analysis was conducted according to sport frequency and sport type using Chi-square test for qualitative data and t-test for quantitative data. Multiple linear regression analysis was performed to identify risk factors for depression.Results: A total of 44.2% and 39.5% of the participants reported symptoms of depression and anxiety, respectively. Significant differences were observed in various characteristics across different sport frequency groups, with participants with higher sport frequency tending to have less depression (P< 0.001) and anxiety (P< 0.001) symptoms. As the frequency of weekly exercise increased, anxiety and depression scores gradually decreased. The mean PHQ-9 and GAD-7 scores were highest in the group with no sports and lowest in the group with a sport frequency of 3– 4 times per week (P< 0.001). Additionally, once exercise frequency reached 5 times per week or more, anxiety and depression scores no longer decreased. Subgroup analysis based on sport type revealed that participants engaging in specific sports, such as basketball, tennis, dance, and running, had lower depression (P< 0.001) and anxiety (P< 0.001) scores compared to the overall average. Based on multiple linear regression analysis, married status (P=0.036), enjoying barbecue food (P< 0.001), prolonged sedentary time (P=0.001), experiencing stress events (P< 0.001), and electronic device usage time (P< 0.001) were positively associated with depression scores, while loving eating vegetables (P=0.007), a relatively longer sport time (P=0.005), a higher exercise frequency (P=0.064), and no chronic disease (P< 0.001) were negatively associated with depression scores.Conclusion: This study highlights the importance of a healthy lifestyle, including regular exercise, limited exposure to electronic screens, and a balanced diet, in preventing and mitigating depression among university students. This study also suggests that exercising 3– 4 times a week is associated with the lowest levels of anxiety and depression. Activities such as basketball, tennis, dance, and running are effective in alleviating these mental health issues through regular exercise.Keywords: depression, eating habits, sports, university students, cross-sectional study

Published
2024

11. An Artificial Intelligence Platform to Stratify the Risk of Experiencing Sleep Disturbance in University Students After Analyzing Psychological Health, Lifestyle, and Sports: A Multicenter Externally Validated Study

Author

Zhang L, Zhao S, Yang Z, Zheng H, and Lei M

Subjects
university students, sleep disturbance, machine learning, artificial intelligence, feature importance., Psychology, BF1-990, Industrial psychology, HF5548.7-5548.85
Abstract

Lirong Zhang,1 Shaocong Zhao,1 Zhongbing Yang,2 Hua Zheng,3 Mingxing Lei4,5 1Department of Physical Education, Xiamen University of Technology, Xiamen, Fujian, 361024, People’s Republic of China; 2School of Physical Education, Guizhou Normal University, Guizhou, 550025, People’s Republic of China; 3College of Physical Education and Health Sciences, Chongqing Normal University, Chongqing, 401331, People’s Republic of China; 4National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation, Beijing, 100039, People’s Republic of China; 5Department of Orthopedic Surgery, Chinese PLA General Hospital, Beijing, 100039, People’s Republic of ChinaCorrespondence: Hua Zheng, College of Physical Education and Health Sciences, Chongqing Normal University, No. 37, Middle Road, University Town, Shapingba District, Chongqing, 401331, People’s Republic of China, Tel +86+15923028254, Email 20130296@cqnu.edu.cn Mingxing Lei, Department of Orthopedic Surgery, Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China, Tel +86+18811772189, Email leimingxing@301hospital.com.cnBackground: Sleep problems are prevalent among university students, yet there is a lack of effective models to assess the risk of sleep disturbance. Artificial intelligence (AI) provides an opportunity to develop a platform for evaluating the risk. This study aims to develop and validate an AI platform to stratify the risk of experiencing sleep disturbance for university students.Methods: A total of 2243 university students were included, with 1882 students from five universities comprising the model derivation group and 361 students from two additional universities forming the external validation group. Six machine learning techniques, including extreme gradient boosting machine (eXGBM), decision tree (DT), k-nearest neighbor (KNN), random forest (RF), neural network (NN), and support vector machine (SVM), were employed to train models using the same set of features. The models’ prediction performance was assessed based on discrimination and calibration, and feature importance was determined using Shapley Additive exPlanations (SHAP) analysis.Results: The prevalence of sleep disturbance was 44.69% in the model derivation group and 49.58% in the external validation group. Among the developed models, eXGBM exhibited superior performance, surpassing other models in metrics such as area under the curve (0.779, 95% CI: 0.728– 0.830), accuracy (0.710), precision (0.737), F1 score (0.692), Brier score (0.193), and log loss (0.569). Calibration and decision curve analyses demonstrated favorable calibration ability and clinical net benefits, respectively. SHAP analysis identified five key features: stress score, severity of depression, vegetable consumption, age, and sedentary time. The AI platform was made available online at https://sleepdisturbancestudents-xakgzwectsw85cagdgkax9.streamlit.app/, enabling users to calculate individualized risk of sleep disturbance.Conclusion: Sleep disturbance is prevalent among university students. This study presents an AI model capable of identifying students at high risk for sleep disturbance. The AI platform offers a valuable resource to guide interventions and improve sleep outcomes for university students.Keywords: university students, sleep disturbance, machine learning, artificial intelligence, feature importance

Published
2024

12. Combined Photosensitive Gene Therapy Effective Against Triple-Negative Breast Cancer in Mice Model

Author

Hu Y, Wang D, Zhang T, Lei M, Luo Y, Chen Z, Li Y, Duan D, Zhang L, and Zhu Y

Subjects
photodynamic therapy, gene therapy, hypoxia, invasion, mitochondrial target, triple-negative breast cancer., Medicine (General), R5-920
Abstract

Yixue Hu,1 Dongna Wang,2 Tianyu Zhang,2 Meng Lei,3 Yingnan Luo,2 Zhimeng Chen,3 Yuting Li,2 Dandan Duan,2 Liefeng Zhang,1 Yongqiang Zhu1,2 1College of Life Science, Nanjing Normal University, Nanjing, People’s Republic of China; 2School of Food and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, People’s Republic of China; 3College of Science, Nanjing Forestry University, Nanjing, People’s Republic of ChinaCorrespondence: Liefeng Zhang; Yongqiang Zhu, College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Qixia District, Nanjing, 210023, People’s Republic of China, Tel/Fax +86-25-85898184; +86-25-85891591, Email lfzhang@njnu.edu.cn; zhyqscu@hotmail.comIntroduction: Tumor hypoxia and invasion present significant challenges for the efficacy of photodynamic therapy (PDT) in triple-negative breast cancer (TNBC). This study developed a mitochondrial targeting strategy that combined PDT and gene therapy to promote each other and address the challenges.Methods: The positively charged amphiphilic material triphenylphosphine-tocopherol polyethylene glycol succinate (TPP-TPGS, TPS) and the photosensitizer chloride e6 (Ce6) formed TPS@Ce6 nanoparticles (NPs) by hydrophobic interaction. They electrostatically condensed microRNA-34a (miR-34a) to form stable TPS@Ce6/miRNA NPs.Results: Firstly, Ce6 disrupted the lysosomal membrane, followed by successful delivery of miR-34a by TPS@Ce6/miRNA NPs. Meanwhile, miR-34a reduced ROS depletion and further enhanced the effectiveness of PDT. Consequently, the mutual promotion between PDT and gene therapy led to enhanced anti-tumor effects. Furthermore, the TPS@Ce6/miRNA NPs promoted apoptosis by down-regulating Caspase-3 and inhibited tumor cell migration and invasion by down-regulating N-Cadherin. In addition, in vitro and in vivo experiments demonstrated that the TPS@Ce6/miRNA NPs achieved excellent anti-tumor effects. These findings highlighted the enhanced anticancer effects and reduced migration of tumor cells through the synergistic effects of PDT and gene therapy.Conclusion: Taken together, the targeted co-delivery of Ce6 and miR-34a will facilitate the application of photodynamic and genic nanomedicine in the treatment of aggressive tumors, particularly TNBC. Keywords: photodynamic therapy, gene therapy, hypoxia, invasion, mitochondrial target, triple-negative breast cancer

Published
2024

13. Learning Robust Real-Time Cultural Transmission without Human Data

Author

Cultural General Intelligence Team, Bhoopchand, Avishkar, Brownfield, Bethanie, Collister, Adrian, Lago, Agustin Dal, Edwards, Ashley, Everett, Richard, Frechette, Alexandre, Oliveira, Yanko Gitahy, Hughes, Edward, Mathewson, Kory W., Mendolicchio, Piermaria, Pawar, Julia, Pislar, Miruna, Platonov, Alex, Senter, Evan, Singh, Sukhdeep, Zacherl, Alexander, and Zhang, Lei M.

Subjects
Computer Science - Machine Learning, Computer Science - Artificial Intelligence, Computer Science - Multiagent Systems
Abstract

Cultural transmission is the domain-general social skill that allows agents to acquire and use information from each other in real-time with high fidelity and recall. In humans, it is the inheritance process that powers cumulative cultural evolution, expanding our skills, tools and knowledge across generations. We provide a method for generating zero-shot, high recall cultural transmission in artificially intelligent agents. Our agents succeed at real-time cultural transmission from humans in novel contexts without using any pre-collected human data. We identify a surprisingly simple set of ingredients sufficient for generating cultural transmission and develop an evaluation methodology for rigorously assessing it. This paves the way for cultural evolution as an algorithm for developing artificial general intelligence.

Published
2022

14. A SPECT/NIR Fluorescence Dual-Modality Imaging Agent Composed of Drugs and Hospital Available Isotope for Preoperative Sentinel Lymph Node Mapping and Intraoperative Biopsy

Author

Zhou M, Liu P, Yin X, Deng C, Xiao Y, Lei M, Hu S, An F, and Zhao M

Subjects
image-guided surgery, indocyanine green, albumin, nuclide imaging, optical imaging, Medicine (General), R5-920
Abstract

Ming Zhou,1,2,&ast; Peng Liu,1,2,&ast; Xiaoqin Yin,1 Caiting Deng,3,4 Yi Xiao,1 Meng Lei,1 Shuo Hu,1 Feifei An,3 Min Zhao1,5,6 1Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Key Laboratory of Biological, Nanotechnology of National Health Commission, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 4Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Science, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 5Department of Nuclear Medicine, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 6National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Zhao; Feifei An, Email mzhao1981@csu.edu.cn; anfeifei@xjtu.edu.cnBackground: Sentinel lymph node (SLN) mapping-guided biopsy is crucial for cancer staging and treatment. Optical/nuclide dual-modality imaging agents for mapping SLN are ideal for preoperative planning and intraoperative biopsy, which are enabled by penetration-depth unlimited nuclide imaging and dynamic real-time optical imaging, respectively. However, commonly reported dual-modality imaging agents are composed of novel but safety-unproven materials, making their quick clinical translation challenging. Herein, we report a novel nanoparticle composed of facile hospital-available drugs and isotope for single-photon emission computed tomography (SPECT)/near-infrared (NIR) fluorescence imaging to detect SLNs.Methods: Indocyanine green-human serum albumin (ICG-HSA) nanoparticles (NPs) were synthesized by ICG-induced HSA self-assembly and further 99mTc-labeling via a one-step, facile hospital-available method. After injecting 99mTc-ICG-HSA into the rats’ forepaw pads, the rats’ draining axillary lymph nodes were visualized by preoperative mapping with SPECT/CT and intraoperative biopsy with NIR fluorescence. The axillary lymph nodes of rats were identified by pathology and fluorescent staining after execution. Additionally, its toxicity testing and comparison with 99mTc-sulfur colloid imaging were also explored.Results: The study reported a self-assembled 99mTc-ICG-HSA with a high radiochemical yield (85.6 ± 3.8%). Compared with conventional 99mTc-sulfur colloid, 99mTc-ICG-HSA NPs showed faster SLN identification, higher renal clearance, and lower hepatic retention. Furthermore, NIRF imaging allowed for the accurate visualization of the SLN and guided SLN biopsy intraoperatively. Notably, the 99mTc-ICG-HSA NPs were composed of hospital-available drugs and isotope, which are safe for acute toxicity evaluation by a certified institute.Conclusion: The proposed 99mTc-ICG-HSA NPs are safe and capable of noninvasive SLN identification and biopsy guidance with multi-modal imaging strategies and could be a promising tool for clinically assisted SLN biopsy. Keywords: image-guided surgery, indocyanine green, albumin, fluorescence imaging, near-infrared, single-photon emission computed tomography

Published
2023

15. Learning few-shot imitation as cultural transmission

Author

Avishkar Bhoopchand, Bethanie Brownfield, Adrian Collister, Agustin Dal Lago, Ashley Edwards, Richard Everett, Alexandre Fréchette, Yanko Gitahy Oliveira, Edward Hughes, Kory W. Mathewson, Piermaria Mendolicchio, Julia Pawar, Miruna Pȋslar, Alex Platonov, Evan Senter, Sukhdeep Singh, Alexander Zacherl, and Lei M. Zhang

Subjects
Science
Abstract

Abstract Cultural transmission is the domain-general social skill that allows agents to acquire and use information from each other in real-time with high fidelity and recall. It can be thought of as the process that perpetuates fit variants in cultural evolution. In humans, cultural evolution has led to the accumulation and refinement of skills, tools and knowledge across generations. We provide a method for generating cultural transmission in artificially intelligent agents, in the form of few-shot imitation. Our agents succeed at real-time imitation of a human in novel contexts without using any pre-collected human data. We identify a surprisingly simple set of ingredients sufficient for generating cultural transmission and develop an evaluation methodology for rigorously assessing it. This paves the way for cultural evolution to play an algorithmic role in the development of artificial general intelligence.

Published
2023
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17. Reconstructing COVID-19 incidences from positive RT-PCR tests by deconvolution

Author

Mengtian Li, Jiachen Li, Ke Wang, and Lei M. Li

Subjects
COVID-19, Daily incidences, RT-PCR test, Delay function, Richard-Lucy deconvolution, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background The emergency of new COVID-19 variants over the past three years posed a serious challenge to the public health. Cities in China implemented mass daily RT-PCR tests by pooling strategies. However, a random delay exists between an infection and its first positive RT-PCR test. It is valuable for disease control to know the delay pattern and daily infection incidences reconstructed from RT-PCR test observations. Methods We formulated the convolution model between daily incidences and positive RT-PCR test counts as a linear inverse problem with positivity restrictions. Consequently, the Richard-Lucy deconvolution algorithm was used to reconstruct COVID-19 incidences from daily PCR tests. A real-time deconvolution was further developed based on the same mathematical principle. The method was applied to an Omicron epidemic data set of a bar outbreak in Beijing and another in Wuxi in June 2022. We estimated the delay function by maximizing likelihood via an E-M algorithm. Results The delay function of the bar-outbreak in 2022 differs from that reported in 2020. Its mode was shortened to 4 days by one day. A 95% confidence interval of the mean delay is [4.43,5.55] as evaluated by bootstrap. In addition, the deconvolved infection incidences successfully detected two associated infection events after the bar was closed. The application of the real-time deconvolution to the Wuxi data identified all explosive incidence increases. The results revealed the progression of the two COVID-19 outbreaks and provided new insights for prevention and control strategies, especially for the role of mass daily RT-PCR testing. Conclusions The proposed deconvolution method is generally applicable to other infectious diseases if the delay model can be assumed to be approximately valid. To ensure a fair reconstruction of daily infection incidences, the delay function should be estimated in a similar context in terms of virus variant and test protocol. Both the delay estimate from the E-M algorithm and the incidences resulted from deconvolution are valuable for epidemic prevention and control. The real-time feedback is particularly useful during the epidemic’s acute phase because it can help the local disease control authorities modify the control measures more promptly and precisely.

Published
2023
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18. Clinical Characteristics of Tracheobronchopathia Osteochondroplastica: A Retrospective Study of 33 Patients

Author

Liu Q, Hu Y, Lei M, Mei C, and Yang C

Subjects
benign tracheobronchial disease, tuberculosis, misdiagnosis, bronchoscopy, Medicine (General), R5-920
Abstract

Qiliang Liu,&ast; Yan Hu,&ast; Mei Lei, Chunlin Mei, Chengqing Yang Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, Wuhan, Hubei, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengqing Yang, Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, Wuhan, Hubei, 430030, People’s Republic of China, Email 147391593@qq.comIntroduction: Tracheobronchopathia osteochondroplastica (TO) is a relatively rare benign tracheobronchial disease, which is often misdiagnosed or missed. To date, there is no specific treatment for TO. The aim of this study was to investigate the clinical manifestations, imaging features, bronchoscopy results, pathological findings, and diagnostic points of TO.Patients and methods: A total of 33 patients diagnosed with TO were enrolled. Clinical data were collected using retrospective methods in the period from January 2021 and November 2022. Descriptive analysis was used.Results: Patients included 17 (51.5%) male and 16 (48.5%) female, with a median age of 54 years. The main clinical manifestations included cough in 15 cases, fever in 6 cases, chest tightness in 4 cases, haemoptysis in 3 cases, and chest pain in 4 cases. The time from the onset of symptoms to diagnosis was 1 week to 96 months. Some patients were diagnosed with other lung diseases, including 16 patients with tuberculosis, 2 patients with lung cancer, 3 patients with nontuberculous mycobacteriosis, 3 patients with tuberculous pleurisy, 2 patients with bronchiectasis, and 1 patient with pneumonia. Chest computed tomography (CT) scan demonstrated calcified nodules in 10 (30.3%) patients. In bronchoscopy, entire tracheal involvement was found in 21 (63.6%) patients, 12 (36.4%) patients were found to have involvement of only part of the trachea. The patients were divided into three groups according to the bronchoscopic presentation, the largest proportion was stage II (19/33), followed by stage I (8/33) and stage III (6/33). Histopathological findings showed squamous metaplasia, cartilaginous, and bony tissues.Conclusion: TO is a slowly progressing disease with non-specific clinical symptoms and a low positive rate of imaging diagnosis, making it susceptible to misdiagnosis and missed diagnosis. The disease needs to be diagnosed by combining imaging features, fiberoptic bronchoscopy, and pathological findings.Keywords: benign tracheobronchial disease, tuberculosis, misdiagnosis, bronchoscopy

Published
2023

19. Learning few-shot imitation as cultural transmission

Author

Bhoopchand, Avishkar, Brownfield, Bethanie, Collister, Adrian, Dal Lago, Agustin, Edwards, Ashley, Everett, Richard, Fréchette, Alexandre, Oliveira, Yanko Gitahy, Hughes, Edward, Mathewson, Kory W., Mendolicchio, Piermaria, Pawar, Julia, Pȋslar, Miruna, Platonov, Alex, Senter, Evan, Singh, Sukhdeep, Zacherl, Alexander, and Zhang, Lei M.

Published
2023
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22. Human-Timescale Adaptation in an Open-Ended Task Space.

Author

Jakob Bauer, Kate Baumli, Feryal M. P. Behbahani, Avishkar Bhoopchand, Nathalie Bradley-Schmieg, Michael Chang, Natalie Clay, Adrian Collister, Vibhavari Dasagi, Lucy Gonzalez, Karol Gregor, Edward Hughes 0001, Sheleem Kashem, Maria Loks-Thompson, Hannah Openshaw, Jack Parker-Holder, Shreya Pathak, Nicolas Perez Nieves, Nemanja Rakicevic, Tim Rocktäschel, Yannick Schroecker, Satinder Singh 0001, Jakub Sygnowski, Karl Tuyls, Sarah York, Alexander Zacherl, and Lei M. Zhang

Published
2023

24. Many-Shot In-Context Learning.

Author

Rishabh Agarwal, Avi Singh, Lei M. Zhang, Bernd Bohnet, Stephanie Chan 0003, Ankesh Anand, Zaheer Abbas, Azade Nova, John D. Co-Reyes, Eric Chu, Feryal M. P. Behbahani, Aleksandra Faust, and Hugo Larochelle

Published
2024
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25. RegCloser: a robust regression approach to closing genome gaps

Author

Shenghao Cao, Mengtian Li, and Lei M. Li

Subjects
Genome assembly, Closing gaps, Robust regression, Tandem repeat, Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Closing gaps in draft genomes leads to more complete and continuous genome assemblies. The ubiquitous genomic repeats are challenges to the existing gap-closing methods, based on either the k-mer representation by the de Bruijn graph or the overlap-layout-consensus paradigm. Besides, chimeric reads will cause erroneous k-mers in the former and false overlaps of reads in the latter. Results We propose a novel local assembly approach to gap closing, called RegCloser. It represents read coordinates and their overlaps respectively by parameters and observations in a linear regression model. The optimal overlap is searched only in the restricted range consistent with insert sizes. Under this linear regression framework, the local DNA assembly becomes a robust parameter estimation problem. We solved the problem by a customized robust regression procedure that resists the influence of false overlaps by optimizing a convex global Huber loss function. The global optimum is obtained by iteratively solving the sparse system of linear equations. On both simulated and real datasets, RegCloser outperformed other popular methods in accurately resolving the copy number of tandem repeats, and achieved superior completeness and contiguity. Applying RegCloser to a plateau zokor draft genome that had been improved by long reads further increased contig N50 to 3-fold long. We also tested the robust regression approach on layout generation of long reads. Conclusions RegCloser is a competitive gap-closing tool. The software is available at https://github.com/csh3/RegCloser . The robust regression approach has a prospect to be incorporated into the layout module of long read assemblers.

Published
2023
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27. α-Mangostin Inhibited M1 Polarization of Macrophages/Monocytes in Antigen-Induced Arthritis Mice by Up-Regulating Silent Information Regulator 1 and Peroxisome Proliferators-Activated Receptor γ Simultaneously

Author

Wu YJ, Zhang SS, Yin Q, Lei M, Wang QH, Chen WG, Luo TT, Zhou P, and Ji CL

Subjects
rheumatoid arthritis, mangosteen, metabolism, inflammation, immune, Therapeutics. Pharmacology, RM1-950
Abstract

Yi-Jin Wu,1– 3,&ast; Sa-Sa Zhang,1,&ast; Qin Yin,1 Ming Lei,2 Qi-Hai Wang,4 Wen-Gang Chen,1 Ting-Ting Luo,1 Peng Zhou,5 Cong-Lan Ji4,6 1Department of Pharmacy, The Second Affiliated Hospital of Wannan Medical College, Wuhu, 241000, People’s Republic of China; 2Xin’an Medical Research Center, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, People’s Republic of China; 3Vascular Diseases Research Center of Wannan Medical College, Wuhu, 241000, People’s Republic of China; 4School of Pharmacy, Anhui College of Traditional Chinese Medicine, Wuhu, Anhui, 241000, People’s Republic of China; 5School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, 230000, People’s Republic of China; 6Research Center of Integration of Traditional Chinese and Western Medicine, Wannan Medical College, Wuhu, 241000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Zhou; Cong-Lan Ji, Email zhoupeng@ahtcm.edu.cn; 37709103@qq.comBackground: α-Mangostin (MG) showed the potentials in alleviating experimental arthritis, inhibiting inflammatory polarization of macrophages/monocytes, and regulating peroxisome proliferators-activated receptor γ (PPAR-γ) and silent information regulator 1 (SIRT1) signals. The aim of this study was to analyze the correlations among the above-mentioned properties.Methods: Antigen-induced arthritis (AIA) was established in mouse, which was treated with MG in combination with SIRT1/PPAR-γ inhibitors to clarify the role of the two signals in the anti-arthritic actions. Pathological changes were systematically investigated. Phenotypes of cells were investigated by flow cytometry. Expression and co-localization of SIRT1 and PPAR-γ proteins in joint tissues were observed by the immunofluorescence method. Finally, clinical implications from the synchronous up-regulation of SIRT1 and PPAR-γ were validated by experiments in vitro.Results: SIRT1 and PPAR-γ inhibitors (nicotinamide and T0070097) reduced the therapeutic effects of MG on AIA mice, and abrogated MG-induced up-regulation of SIRT1/PPAR-γ and inhibition of M1 polarization in macrophages/monocytes. MG has a good binding affinity to PPAR-γ, and MG promoted the co-expression of SIRT1 and PPAR-γ in joints. Synchronously activating SIRT1 and PPAR-γ was revealed to be necessary by MG to repress inflammatory responses in THP-1 monocytes.Conclusion: MG binds PPAR-γ and excites this signaling to initiate ligand-dependent anti-inflammatory activity. Due to certain unspecified signal transduction crosstalk mechanism, it then promoted SIRT1 expression and further limited inflammatory polarization of macrophages/monocytes in AIA mice.Graphical Abstract: Keywords: rheumatoid arthritis, mangosteen, metabolism, inflammation, immune

Published
2023

33. Dupilumab for Chronic Prurigo in Different Backgrounds: A Case Series

Author

Luo N, Wang Q, Lei M, Li T, and Hao P

Subjects
dupilumab, chronic prurigo, therapy, asthma, Dermatology, RL1-803
Abstract

Nana Luo,1,2 Qiuyue Wang,2 Min Lei,2 Tianhao Li,1 Pingsheng Hao1 1Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of ChinaCorrespondence: Tianhao Li; Pingsheng Hao, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, People’s Republic of China, Tel +86-13880986337 ; +86-13881965024, Fax +86-28-87732407, Email litianhao_doctor@163.com; hpswl@126.comAbstract: Chronic prurigo (CPG) is a chronic inflammatory disease characterized by intense pruritus, and therapy is often challenging due to its unclear pathogenesis. Here, we report four patients with refractory CPG from different backgrounds who experienced failure of conventional therapy and were controlled with dupilumab, accompanied by a significant decrease in pruritus numerical rating scale, dermatology life quality index, and investigator global assessment, without adverse effects. Furthermore, dupilumab improved the condition of asthma in CPG patients along with an increase in asthma control test scores.Keywords: dupilumab, chronic prurigo, therapy, asthma

Published
2022

34. Preclinical Pharmacokinetics, Tissue Distribution and in vitro Metabolism of FHND6091, a Novel Oral Proteasome Inhibitor

Author

Yang X, Liu A, Yang L, Wen T, Wang J, Shi J, Zhou H, Chen Z, Lei M, and Zhu Y

Subjects
fhnd6091, active from fhnd6081, proteasome inhibitor, preclinical pharmacokinetics, tissue distribution, drug-availability, Therapeutics. Pharmacology, RM1-950
Abstract

Xu Yang,1 Amin Liu,1 Lin Yang,1 Tiantian Wen,2 Jia Wang,3 Jingmiao Shi,3 Hui Zhou,2 Zhimeng Chen,1 Meng Lei,1 Yongqiang Zhu2 1College of Science, Nanjing Forestry University, Nanjing, People’s Republic of China; 2College of Life Science, Nanjing Normal University, Nanjing, People’s Republic of China; 3Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd, Nanjing, People’s Republic of ChinaCorrespondence: Meng Lei; Yongqiang Zhu, Tel +86 25 85427621 ; +86 25 85891591, Email hk-lm@163.com; zhyqscu@hotmail.comIntroduction: FHND6091, a novel N-capped dipeptidyl boronic acid proteasome inhibitor with promising pharmacological properties, entirely converted into active form FHND6081 under physiological conditions. The proteasome, a key component of the ubiquitin-proteasome pathway (UPP), has emerged as a validated target of multiple myeloma (MM) therapeutics. FHND6091 is a selective oral proteasome inhibitor that binds irreversibly to the β 5 submit of the 20S proteasome and exerts anti-cancer roles.Methods: In this study, we investigated the metabolic stability, metabolite production, metabolic pathways and plasma protein binding (PPB) of FHND6081 along with its absorption, tissue distribution, excretion (ADME) and pharmacokinetics (PK) in animals.Results: Ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) identified a total of nine new metabolites after co-incubation with FHND6091 in hepatocytes from different species. A hypothetical CYP450-metabolic pathway including dehydrogenation, N-dealkylation plus mono-oxygenation and other was proposed. In addition, FHND6081 was highly bound to plasma proteins (> 99%); nevertheless, it preferred to partition to red blood cells (B/P ratio: 4.91). The results of microsomal metabolic stability corroborated that FHND6081 was a moderate-clearance compound. In Caco-2 cell experiments, the compound displayed modest permeability suggesting that it may show limited bioavailability via oral routes. Furthermore, FHND6081 was extensively distributed in rats and the highest exposure was achieved in the stomach followed by the small intestine and adrenal gland. Pharmacokinetic studies were done by using Sprague-Dawley (SD) rats, oral absorption was fast and plasma exposure was dose-dependent and oral bioavailability were low. At the same dose, FHND6081 exposure was severalfold higher in whole blood than in plasma, which was consistent with blood cell partitioning. Moreover, only a small fraction of the parent compound was excreted via feces and urine and oxidative metabolites were detected in feces and plasma.Conclusion: The overall preclinical pharmacokinetic profile supported the selection and development of FHND6091 as a clinical candidate.Keywords: FHND6091, active form FHND6081, proteasome inhibitor, preclinical pharmacokinetics, tissue distribution, drug-availability

Published
2022

35. Burning and Scaling Probably Associated with Dupilumab Therapy: A Case Report

Author

Luo N, Wang Q, Lei M, Li Z, Li T, and Hao P

Subjects
dupilumab, atopic dermatitis, burning, scaling, adverse event, Dermatology, RL1-803
Abstract

Nana Luo,1,2 Qiuyue Wang,1 Min Lei,1 Zhiyong Li,1 Tianhao Li,2 Pingsheng Hao2 1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of ChinaCorrespondence: Tianhao Li; Pingsheng Hao, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, Sichuan Province, People’s Republic of China, Tel +86-13880986337 ; +86-13881965024, Fax +86-28-87732407, Email litianhao_doctor@163.com; hpswl@126.comCase Report: We present the case of a 51-year-old male who experienced temporary desquamation and recurrent burning sensation in primary skin lesions after the injection of dupilumab. The scaling lasted for 1 week and subsided, while the burning became aggravated with each injection of dupilumab, which gradually subsides after 8 weeks, and there was no recurrence since then.Conclusion: Dupilumab is an emerging and efficacious biologics medication for AD. The burning sensation and scaling we report may be the adverse events of dupilumab. Rare adverse reactions to biologics deserve the attention of physicians.Keywords: dupilumab, atopic dermatitis, burning, scaling, adverse event

Published
2022

36. Facial Irritant Contact Dermatitis Caused by Pyraclostrobin

Author

Wang Q, Luo N, Lei M, Zhong L, Li C, and Hao P

Subjects
irritant contact dermatitis, pyraclostrobin, pesticide exposure, pesticides, farming, case report, Dermatology, RL1-803
Abstract

Qiuyue Wang,1,2 Nana Luo,1,2 Min Lei,1,2 Lingyuan Zhong,1,2 Chunxiao Li,2,* Pingsheng Hao2,* 1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunxiao Li; Pingsheng Hao, Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610075, Sichuan, People’s Republic of China, Tel +86-18981937829 ; +86-13881965024, Fax +86-028-87732407, Email chunxiaolee@126.com; hpswl@126.comAbstract: Contact dermatitis and facial contact dermatitis caused by pesticides are not uncommon in China. However, clinically, due to the wide variety of pesticides, they mainly appear in the form of case reports. We reported a 70-year-old male patient developed facial irritant contact dermatitis (ICD) due to pyraclostrobin which was sprayed on his face. Initially, he felt facial burning and tingling, and localized erythematous-edematous and scaly rash appeared on his face as well as front hairline scalp. During the outpatient visit, the main symptoms were a facial burning sensation, itching, and tingling. The patient’s facial lesions improved after treatment. To better protect the skin of agricultural workers, preventive measures should be undertaken, such as personal protective equipment, gas masks, protective clothing and goggles, which are indispensable for manual pesticide spraying. Pyraclostrobin diluted according to the instructions is a potential source of ICD. Agricultural workers should undertake preventive measures during manual pesticide spraying. Safety education and publicity are particularly important. We need dermatologists to spread knowledge and agricultural workers to develop the right protective habits.Keywords: irritant contact dermatitis, pyraclostrobin, pesticide exposure, pesticides, farming, case report

Published
2022

37. A hybrid plasma model for Cr thin film deposition by deep oscillation magnetron sputtering.

Author

Gao, J. Y., Ferreira, F., and Lei, M. K.

Subjects
THIN film deposition, PLASMA chemistry, MAGNETRON sputtering, KINETIC energy, PLASMA diffusion, TWO-dimensional models
Abstract

A time-dependent hybrid plasma model composed of a zero-dimensional global model and a two-dimensional fluid model is proposed for simulation of plasma chemistry and transportation of plasma during Cr thin film deposition by deep oscillation magnetron sputtering (DOMS). The global model deals with plasma reactions in the ionization region near the target with discharge voltage and current waveforms as inputs. The temporal plasma characteristics calculated by the global model are utilized as a boundary condition for the two-dimensional fluid model to simulate high-density plasma transportation in the diffusion region through the entire macropulse period. The full momentum equation taking inertia force into consideration is applied for ion momentum conservation in the fluid model instead of using the drift-diffusion approximation, which ensures validity of the simulation for low-pressure plasmas. The deposition flux as well as the kinetic and potential energy fluxes transferred to the growing films are calculated by the hybrid model. Microstructure evolution of the DOMS deposited Cr thin films from zone I to zone T is attributed to the growing kinetic and potential energies as the charging voltage increases according to the structure zone diagram. The deposition rate loss in DOMS is explained by the back attraction effect, sputtering yield effect, and densification of the films. [ABSTRACT FROM AUTHOR]

Published
2024
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39. Bullous Grover’s Disease in a Chinese Tibetan Adolescent: A Case Report

Author

Wang Q, Luo N, Lei M, Chen X, Li C, and Hao P

Subjects
grover’s disease, chinese, minocycline, methotrexate, adolescent, case report, Dermatology, RL1-803
Abstract

Qiuyue Wang,1,2,&ast; Nana Luo,1,2,&ast; Min Lei,1,2 Xian Chen,3 Chunxiao Li,2 Pingsheng Hao2 1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Department of Pathology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunxiao Li; Pingsheng Hao, Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu 610075, Sichuan, People’s Republic of China, Tel +86-18981937829 ; +86-13881965024, Fax +86-028-87732407, Email chunxiaolee@126.com; hpswl@126.comAbstract: Grover’s disease (GD), also known as Transient acantholytic dermatosis, has no typical clinical rash features. It usually occurs in elderly white men but very rarely in China. This is a disease of acantholysis and dyskeratosis, which is usually considered to be spontaneous remission. The skin lesions of the disease are diverse, and the main symptom is severe itching. We have reported a case of GD in a 14-year-old Chinese Tibetan male whose clinical manifestations were pruritic red papule, generalized red papules, papulo vesicles and blisters ranging from millet rice to soybean size. Skin lesions change rapidly and variously. In order to confirm the diagnosis, we have done skin biopsies, immunofluorescence, dermoscopy, microscopy and other examinations. Pathological skin biopsy showed acantholysis. Intraepidermal blisters and the presence of blisters on the basal cells as well as under the stratum corneum can be observed on the same pathological section. Type IV collagen immunohistochemistry showed blisters in the epidermis. The diagnosis of GD depended on the exclusion of other diseases. After we performed whole exon sequencing (WES) on DNA from the patient’s blood, pathogenic gene mutations were not found. Pustular psoriasis, Subcorneal pustular dermatosis, Herpesvirus infections, Dermatitis herpetiformis, Pemphigus vulgaris, Norwegian scabies, Darier’s disease, and Hailey-Hailey disease were all excluded. We successfully treated adolescent GD with minocycline combined with methotrexate. The patient was followed up for 19 months without recurrence.Keywords: Grover’s disease, Chinese, minocycline, methotrexate, adolescent, case report

Published
2022

43. A data integration approach unveils a transcriptional signature of type 2 diabetes progression in rat and human islets.

Author

Shenghao Cao, Linting Wang, Yance Feng, Xiao-Ding Peng, and Lei M Li

Subjects
Medicine, Science
Abstract

Pancreatic islet failure is a key characteristic of type 2 diabetes besides insulin resistance. To get molecular insights into the pathology of islets in type 2 diabetes, we developed a computational approach to integrating expression profiles of Goto-Kakizaki and Wistar rat islets from a designed experiment with those of the human islets from an observational study. A principal gene-eigenvector in the expression profiles characterized by up-regulated angiogenesis and down-regulated oxidative phosphorylation was identified conserved across the two species. In the case of Goto-Kakizaki versus Wistar islets, such alteration in gene expression can be verified directly by the treatment-control tests over time, and corresponds to the alteration of α/β-cell distribution obtained by quantifying the islet micrographs. Furthermore, the correspondence between the dual sample- and gene-eigenvectors unveils more delicate structures. In the case of rats, the up- and down-trend of insulin mRNA levels before and after week 8 correspond respectively to the top two principal eigenvectors. In the case of human, the top two principal eigenvectors correspond respectively to the late and early stages of diabetes. According to the aggregated expression signature, a large portion of genes involved in the hypoxia-inducible factor signaling pathway, which activates transcription of angiogenesis, were significantly up-regulated. Furthermore, top-ranked anti-angiogenic genes THBS1 and PEDF indicate the existence of a counteractive mechanism that is in line with thickened and fragmented capillaries found in the deteriorated islets. Overall, the integrative analysis unravels the principal transcriptional alterations underlying the islet deterioration of morphology and insulin secretion along type 2 diabetes progression.

Published
2023
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46. Learning Robust Real-Time Cultural Transmission without Human Data.

Author

Avishkar Bhoopchand, Bethanie Brownfield, Adrian Collister, Agustin Dal Lago, Ashley Edwards, Richard Everett 0001, Alexandre Fréchette, Yanko Gitahy Oliveira, Edward Hughes 0001, Kory W. Mathewson, Piermaria Mendolicchio, Julia Pawar, Miruna Pislar, Alex Platonov, Evan Senter, Sukhdeep Singh, Alexander Zacherl, and Lei M. Zhang

Published
2022
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47. Nitrogen Boil-Off Method of Measuring AC Losses in Twisted-Stacked HTS Conductor

Author

Gao, S. Y., Yang, X. S., Shi, S. J., Jiang, J., Zhang, H., Lei, M., Zhang, Y., Huang, M., and Zhao, Y.

Abstract

High-temperature superconducting twisted stacked conductors are one of the promising candidates for fusion magnets and particle acceleration magnets due to their higher critical current density, better mechanical strength, thermal stability, and complete translocation. We investigated the magnetization AC losses of multi-slot stacked twisted conductors without interlayer insulation using calorimetry and measured the losses incurred by the tapes after the removal of the skeleton. The magnetization loss of this conductor was calculated using the three-dimensional T-A equation and compared with the measured results of the calorimetric method. The results of this article will provide magnetization loss data to support the optimal design of multi-slot stacked conductors.

Published
2024
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48. Global model on oscillation discharge characteristics during deep oscillation magnetron sputtering of Cr target.

Author

Gao, J. Y., Ferreira, F., and Lei, M. K.

Subjects
MAGNETRON sputtering, ION bombardment, MICROPLASMAS, WORKING gases, OSCILLATIONS, HIGH voltages, GLOW discharges
Abstract

A time-dependent global model is developed for deep oscillation magnetron sputtering (DOMS) with a Cr target to characterize the plasma using the working Ar gas at a pressure of 0.8 Pa. An input of the global model is the target voltage and current waveforms at charging voltages from 260 to 400 V. The plasma densities vary synchronously with the oscillations of target power. During the on-time of a micropulse, the gas atoms are ionized first to ignite the plasma and subsequently the metal ions follow to sustain the discharge. During the off-time, the gas ions dominate the afterglow. The DOMS possesses a characteristic of alternating gas/metal discharge in the time domain. The peak values of plasma densities increase linearly with charging voltages, which is mainly attributed to the higher Cr+ ion density. The discharge transits from gas dominated to metal dominated at high charging voltage. The working gas rarefaction in DOMS discharge is enhanced at higher charging voltages. At charging voltages higher than 360 V, the metal self-sputtering comes into the runaway regime temporarily as indicated by the self-sputtering parameters exceeding unity, generating the dense and metal-rich plasma. The metal self-sputtering is promoted by gas rarefaction. The electrons tend to ionize the metal atoms after the gas atoms are depleted. The decreased grain size and elevated nano-hardness of the Cr thin films are explained by structure transition from zone I to zone T due to the efficient metal ion bombardment to the growing thin films as the charging voltage increases. [ABSTRACT FROM AUTHOR]

Published
2022
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