Integrating Reinforcement Learning and Monte Carlo Tree Search for enhanced neoantigen vaccine design.

Recent advances in cancer immunotherapy have highlighted the potential of neoantigen-based vaccines. However, the design of such vaccines is hindered by the possibility of weak binding affinity between the peptides and the patient's specific human leukocyte antigen (HLA) alleles, which may not elicit a robust adaptive immune response. Triggering cross-immunity by utilizing peptide mutations that have enhanced binding affinity to target HLA molecules, while preserving their homology with the original one, can be a promising avenue for neoantigen vaccine design. In this study, we introduced UltraMutate, a novel algorithm that combines Reinforcement Learning and Monte Carlo Tree Search, which identifies peptide mutations that not only exhibit enhanced binding affinities to target HLA molecules but also retains a high degree of homology with the original neoantigen. UltraMutate outperformed existing state-of-the-art methods in identifying affinity-enhancing mutations in an independent test set consisting of 3660 peptide-HLA pairs. UltraMutate further showed its applicability in the design of peptide vaccines for Human Papillomavirus and Human Cytomegalovirus, demonstrating its potential as a promising tool in the advancement of personalized immunotherapy.

Fundamentals of the recycling of spent lithium-ion batteries.

This review discusses the critical role of fundamentals of battery recycling in addressing the challenges posed by the increasing number of spent lithium-ion batteries (LIBs) due to the widespread use of electric vehicles and portable electronics, by providing the theoretical basis and technical support for recycling spent LIBs, including battery classification, ultrasonic flaw detection, pretreatment (e.g., discharging, mechanical crushing, and physical separation), electrolyte recovery, direct regeneration, and theoretical calculations and simulations. Physical chemistry principles are essential for achieving effective separation of different components through methods like screening, magnetic separation, and flotation. Electrolyte recovery involves separation and purification of electrolytes through advanced physical and chemical techniques. Direct regeneration technology restores the structure of electrode materials at the microscopic scale, requiring precise control of the physical state and crystal structure of the material. Physical processes such as phase changes, solubility, and diffusion are fundamental to techniques like solid-state sintering, eutectic-salt treatment, and hydrothermal methods. Theoretical calculations and simulations help predict the behaviour of materials during recycling, guiding process optimization. This review provides insights into understanding and improving the recycling process, emphasizing the central role of physical chemistry principles in addressing environmental and energy issues. It is valuable for promoting innovation in spent LIB recycling processes and is expected to stimulate interest among researchers and manufacturers.

Renal outcomes after contrast exposure in patients with diabetes who use sodium-glucose cotransporter 2 inhibitors.

BACKGROUND: Contrast-induced nephropathy has become increasingly prevalent as the age and prevalence of comorbidities in the general population have increased. Most cases of contrast-induced nephropathy are reversible; however, some may progress to acute kidney disease, and subsequently, to chronic kidney disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are known for their renoprotective effects. However, whether the use of these inhibitors affects the risk of contrast-induced kidney injury remains unclear. METHODS: Data were collected from the Taipei Medical University Clinical Research Database. We included patients with diabetes who had contrast exposure between 2016 and 2020 because of computed tomography or coronary angiography. The primary outcome was the risk of a major adverse kidney event (MAKE), which encompassed acute kidney disease, chronic kidney disease progression, and the need for renal replacement therapy. Overlap weighting was performed to reduce the effects of potential confounders. RESULTS: This study included 12 421 patients, who were divided into two groups: SGLT2i users (n = 920) and nonusers (n = 11 501). The follow-up period after contrast exposure was 6 months. The risk of a MAKE was lower in SGLT2i users than in nonusers (incidence, 36.9 vs. 49.9 per 1000 person-months, respectively; P = .0011). Furthermore, the incidence of acute kidney disease or chronic kidney disease progression was significantly lower in the SGLT2i users than in nonusers. However, no significant between-group difference was noted in the incidence of other MAKEs. CONCLUSIONS: SGLT2i may be safely used in diabetic patients needing contrast exposure. The risk of a MAKE may be lower in SGLT2i users than in nonusers.

A partially flipped physiology classroom improves the deep learning approach of medical students.

This study aimed to compare the impact of the partially flipped physiology classroom (PFC) and the traditional lecture-based classroom (TLC) on students' learning approaches. The study was conducted over 5 mo at Xiangya School of Medicine from February to July 2022 and comprised 71 students majoring in clinical medicine. The experimental group (n = 32) received PFC teaching, whereas the control group (n = 39) received TLC. The Revised Two-Factor Study Process Questionnaire (R-SPQ-2F) was used to assess the impact of different teaching methods on students' learning approaches. After the PFC, students got significantly higher scores on deep learning approach (Z = -3.133, P < 0.05). Conversely, after the TLC students showed significantly higher scores on surface learning approach (Z = -2.259, P < 0.05). After the course, students in the PFC group scored significantly higher in deep learning strategy than those in the TLC group (Z = -2.196, P < 0.05). The PFC model had a positive impact on deep learning motive and strategy, leading to an improvement in the deep approach, which is beneficial for the long-term development of students. In contrast, the TLC model only improved the surface learning approach. The study implies that educators should consider implementing PFC to enhance students' learning approaches.NEW & NOTEWORTHY In this article, we compare the impact of the partially flipped classroom (PFC) and the traditional lecture classroom (TLC) in a physiology course on medical students' learning approaches. We found that the PFC benefited students by significantly enhancing their deep learning motive, strategy, and approach, which was good for them. However, the TLC model only improved the surface learning motive and approach.

Optical frequency domain polarimetry based on a self-referenced unbalanced Mach-Zehnder interferometer.

Optical frequency domain polarimetry (OFDP) is an emerging distributed polarization crosstalk rapid measurement method with an ultrawide dynamic range. However, interferometric phase noise induced by the laser source and ambient noise results in a trade-off between measurement length and dynamic range. In this Letter, we solve this problem with a self-referenced unbalanced Mach-Zehnder interferometer. The features of long distance (9.8 km), ultrawide dynamic range (107.8 dB), short measurement time (2 sec), and signal-to-noise ratio improvement against ambient noise are experimentally demonstrated. The method makes it possible to evaluate a long polarization-maintaining fiber in an environment whose state changes rapidly.

Thromboembolic Presentations among Patients Hospitalized to the Intensive Care Unit for Coronavirus Disease 2019 (COVID-19) - A Northern Taiwan Single Center Experience.

Coronavirus Disease 2019 (COVID-19) has been associated with a high thromboembolic risk among patients in intensive care units. Asian populations may share a similar thromboembolic risk, but with a higher prevalence of arterial thromboembolism than venous thromboembolism. To clarify this risk in Taiwan, this single-center retrospective study collected 27 consecutive intensive care unit patients with COVID-19 confirmed by polymerase chain reaction, with a median age of 67.6 years (male 81.5%). Twenty-three patients received prophylactic anticoagulation (85.2%), and there were four bleeding events (14.8%). Nine patients had thromboembolism (33.3%), including three with deep vein thrombosis, two with peripheral artery thromboembolism, and four with ischemic stroke. There were no significant clinical differences between the patients with or without thromboembolism. Initial serum ferritin [adjusted odds ratio (OR): 13.19, 95% confidence interval (CI): 1.01-172.07] and peak serum procalcitonin (adjusted OR: 18.93, 95% CI: 1.08-330.91) were associated with a higher risk of thromboembolism. Furthermore, prophylactic anticoagulation (adjusted OR: 0.01, 95% CI: < 0.001-0.55) was associated with a lower risk of thromboembolism. All cases of deep vein thrombosis and one peripheral artery thromboembolism occurred at intravascular catheter locations. No association between thromboembolism and survival was found (age-adjusted hazard ratio: 0.55, 95% CI: 0.10-2.95). In conclusion, the prevalence of COVID-19 thromboembolism among Taiwanese patients in intensive care units was high, even with prophylactic anticoagulation. Serum ferritin and procalcitonin may identify high-risk populations. Prophylactic anticoagulation may reduce the risk of thromboembolism with a manageable bleeding risk. Larger prospective studies are needed to clarify the risk of COVID-19 thromboembolism and its risk factors in the post-Omicron era.

Pressure-impedance analysis: Assist the diagnosis and classification of ineffective esophageal motility disorder.

BACKGROUND AND AIM: We elucidated the clinical significance of distal contractile integral-to-esophageal impedance integral (EII) ratio (DCIIR) in ineffective esophageal motility (IEM) adult patients. METHODS: We recruited 101 patients with IEM (48.38 ± 1.58 years) and 42 matched healthy volunteers (44.28 ± 1.85 years) in this case-control study. All subjects underwent esophageal high-resolution impedance manometry from October 2014 to May 2018. The diagnosis of IEM was based on the Chicago Classification version 3.0. The EII, EII ratio, and DCIIR were analyzed by matlab software. RESULTS: The EII, EII ratio, and DCIIR calculated at an impedance threshold of 1500 Ω (EII1500, EII ratio1500, and DCIIR1500, respectively) were significantly lower in the IEM group than in healthy controls (P < 0.0001, < 0.0001, and < 0.0001, respectively). Receiver operating characteristic analysis showed that DCIIR1500 < 0.008 mmHg/Ω, EII1500 > 71 000 Ω.s.cm, and EII ratio1500 > 0.43 were all predictive of IEM. Only DCIIR1500 < 0.008 mmHg/Ω remained significant in diagnosing IEM in the multivariate logistic regression analysis (odds ratio = 72.13, P < 0.001). The DCIIR1500 is negatively correlated with Eckardt score and the Reflux Disease Questionnaire (correlation coefficient = -0.2844 and -0.3136; P = 0.0006 and 0.0002, respectively). Receiver operating characteristic analysis further showed that a DCIIR1500 cut-off of 0.002 mmHg/Ω achieved the best differentiation between the IEM-alternans and IEM-persistens subtypes among IEM patients (P < 0.001). CONCLUSIONS: The novel pressure-impedance parameter of high-resolution impedance manometry, DCIIR1500, may assist in the diagnosis and classification of IEM and correlated with clinical symptoms.

[Human activity recognition based on the inertial information and convolutional neural network].

With the rapid improvement of the perception and computing capacity of mobile devices such as smart phones, human activity recognition using mobile devices as the carrier has been a new research hot-spot. The inertial information collected by the acceleration sensor in the smart mobile device is used for human activity recognition. Compared with the common computer vision recognition, it has the following advantages: convenience, low cost, and better reflection of the essence of human motion. Based on the WISDM data set collected by smart phones, the inertial navigation information and the deep learning algorithm-convolutional neural network (CNN) were adopted to build a human activity recognition model in this paper. The K nearest neighbor algorithm (KNN) and the random forest algorithm were compared with the CNN network in the recognition accuracy to evaluate the performance of the CNN network. The classification accuracy of CNN model reached 92.73%, which was much higher than KNN and random forest. Experimental results show that the CNN algorithm model can achieve more accurate human activity recognition and has broad application prospects in predicting and promoting human health.

Quantitative analysis of genetically modified soya using multiple reaction monitoring mass spectrometry with endogenous peptides as internal standards.

A simple label-free method was developed for the quantification of the herbicide-resistant gene-related protein 5-enolpyruvylshikimate-3-phosphate synthase using multiple reaction monitoring liquid chromatography-mass spectrometry. Sample pretreatment procedures including ion exchange chromatography and CaCl2 precipitation were used to purify the 5-enolpyruvylshikimate-3-phosphate synthase protein. Quantification of various percentages of genetically modified soya (0.5-100%) was performed by selecting suitable endogenous soybean peptides as internal standards. Results indicated that Gly P (QGDVFVVPR) and Lec P (LQLNK) are useful internal standards for the quantification of low and high percentages of genetically modified soya, respectively. Linear regression analysis of both calibration curves yielded good linearity with R2 of 0.99. This approach is a convenient and accurate quantification method for genetically modified soya at a level as low as 0.5% (less than the current EU threshold for labeling genetically modified soya).

Distal contractile to impedance integral ratio assist the diagnosis of pediatric ineffective esophageal motility disorder.

OBJECTIVES: We investigated the diagnostic utility of distal contractile integral (DCI) to esophageal impedance integral (EII) ratio (DCIIR) in high-resolution impedance manometry (HRIM) of ineffective esophageal motility (IEM) in children. METHODS: We performed HRIM in 31 children with dysphagia, odynophagia, chronic vomiting, chest pain, or heartburn sensation. Based on the Chicago classification version 3.0, 20 subjects were diagnosed with IEM, and 11 subjects were normal. We analyzed the EII and DCIIR using MATLAB software. RESULTS: The DCIIR calculated at the impedance cutoff at 1500 Ω (DCIIR1500) were significantly lower in IEM group than patients with normal motility (P = 0.007). Receiver operating characteristic (ROC) curve analysis showed that a DCIIR1500 < 0.009 mmHg/Ω best predicted IEM in children (P < 0.001). A DCIIR1500 < 0.008 mmHg/Ω is associated with significant body weight loss > 10% within 6 months in children. (P < 0.001). CONCLUSIONS: The calculation of DCIIR1500 may assist the automatic analysis of bolus transit in HRIM study to diagnose IEM in children. An DCIIR1500 < 0.009 mmHg/Ω may assist in the diagnosis of IEM in children, and DCIIR1500 < 0.008 mmHg/Ω correlated with significant body weight loss. The calculation of DCIIR may serve as possible parameters for HRIM.

Rear interface engineering of hybrid organic-silicon nanowire solar cells via blade coating.

In this work, we investigate blade-coated organic interlayers at the rear surface of hybrid organic-silicon photovoltaics based on two small molecules: Tris(8-hydroxyquinolinato) aluminium (Alq(3)) and 1,3-bis(2-(4-tert-butylphenyl)-1,3,4-oxadiazol-5-yl) benzene (OXD-7). In particular, soluble Alq(3) resulting in a uniform thin film with a root-mean-square roughness < 0.2nm is demonstrated for the first time. Both devices with the Alq(3) and OXD-7 interlayers show notable enhancement in the open-circuit voltage and fill-factor, leading to a net efficiency increase by over 2% from the reference, up to 11.8% and 12.5% respectively. The capacitance-voltage characteristics confirm the role of the small-molecule interlayers resembling a thin interfacial oxide layer for the Al-Si Schottky barrier to enhance the built-in potential and facilitate charge transport. Moreover, the Alq(3) interlayer in optimized devices exhibits isolated phases with a large surface roughness, in contrast to the OXD-7 which forms a continuous uniform thin film. The distinct morphological differences between the two interlayers further suggest different enhancement mechanisms and hence offer versatile functionalities to the advent of hybrid organic-silicon photovoltaics.

Ligand-doped liquid crystal sensor system for detecting mercuric ion in aqueous solutions.

We developed a liquid crystal (LC) sensor system for detecting mercuric ion (Hg(2+)) in aqueous solutions. In this system, 4-cyano-4'-pentyl biphenyl (5CB) was doped with a sulfur- and nitrogen-containing ligand 5-(pyridine-4-yl)-2-(5-(pyridin-4-yl)thiophen-2-yl)thiazole (ZT) as the Hg(2+) specific LCs. When the system was immersed in the solution containing Hg(2+), the complex of ZT and Hg(2+) formed, which disrupted the orientation of LC and lead to a dark-to-bright transition of the image of LCs. From mercuric binding titrations monitored by UV-vis spectroscopy, it was found that 1:1 Hg(2+)/ZT complexes were formed. The limit of detection (LOD) of the system to Hg(2+) is 10 µM, and it did not respond to Cd(2+), Zn(2+), Cu(2+), Pb(2+), Fe(+), Mg(2+), Ca(2+), Na(+), and K(+). Besides, we also demonstrated that this system is capable of detecting Hg(2+) in tap water and pond water. Because the signal of this system is colorful under ambient light, which is readily understood by normal users, it can be used as a portable device to monitor the water quality at any location.

Cingulum correlates of cognitive functions in patients with mild cognitive impairment and early Alzheimer's disease: a diffusion spectrum imaging study.

Diffusion spectrum imaging (DSI) of MRI can detect neural fiber tract changes. We investigated integrity of cingulum bundle (CB) in patients with mild cognitive impairment (MCI) and early Alzheimer's disease (EAD) using DSI tractography and explored its relationship with cognitive functions. We recruited 8 patients with MCI, 9 with EAD and 15 healthy controls (HC). All subjects received a battery of neuropsychological tests to access their executive, memory and language functions. We used a 3.0-tesla MRI scanner to obtain T1- and T2-weighted images for anatomy and used a pulsed gradient twice-refocused spin-echo diffusion echo-planar imaging sequence to acquire DSI. Patients with EAD performed significantly poorer than the HC on most tests in executive and memory functions. Significantly smaller general fractional anisotropy (GFA) values were found in the posterior and inferior segments of left CB and of the anterior segment of right CB of the EAD compared with those of the HC. Spearman's correlation on the patient groups showed that GFA values of the posterior segment of the left CB were significantly negatively associated with the time used to complete Color Trails Test Part II and positively correlated with performance of the logical memory and visual reproduction. GFA values of inferior segment of bilateral CB were positively associated with the performance of visual recognition. DSI tractography demonstrates significant preferential degeneration of the CB on the left side in patients with EAD. The location-specific degeneration is associated with corresponding declines in both executive and memory functions.

Decline in extractable kitasamycin during the composting of kitasamycin manufacturing waste with dairy manure and sawdust.

The aim of this study was to propose a feasible treatment of kitasamycin manufacturing waste by examining extractable kitasamycin and evaluating its compost maturity during the composting of waste with different ratios of dairy manure and sawdust over a 40-day period (volume/volume/volume; M1, 0/80/20; M2, 10/70/20; and M3, 30/50/20). During composting, the concentration of extractable kitasamycin in kitasamycin-contaminated composts declined rapidly, and was undetectable in M2 within 15 days. M2 also achieved the highest fertility compost, which was characterised by the following final parameters: electrical conductivity, 2.34 dS cm(-1); pH, 8.15; total C/N, 22.2; water-soluble NH4(+), P, and K, 0.37, 3.43, and 1.05 g kg(-1), respectively; and plant germination index values, 92%. Furthermore, DGGE analysis showed a dramatic increase in the diversity of bacterial species during composting. In contrast, a high concentration (121 mg kg(-1)) of extractable kitasamycin still remained in the M3 compost, which exerted an inhibitory effect on the composting, resulting in reduced bacterial diversity, high values of electrical conductivity and water-soluble NH4(+), a low C/N ratio, and a low plant germination index value. Furthermore, 3.86 log (CFU g(-1)) kitasamycin-resistant bacteria were still present on day 40, indicating the biological degradation contributed to the decline of extractable kitasamycin.

The emerging role of the cerebellum in neurodegeneration linked to cognitive impairment.

The cerebellum has been largely overlooked in Alzheimer's disease, despite increasing evidence implicating its cognitive capacities and functional networks, which interacts with cerebral cortex to subserve cognition. A study by Lin et al. has indicated that the cerebellum is part of the integrated network in amnestic mild cognitive impairment (aMCI), a prodromal state of Alzheimer's disease. The aMCI patients exhibited weaker cerebello-parietal functional connectivity but stronger cerebellar coupling with precuneus cortex, posterior cingulate gyrus, and caudate nucleus. These alterations in cerebello-cortical connectivity correlated with cognitive performance, suggesting a dynamic change of cerebello-cortical network related to cognitive change in aMCI.

Strategies for developing layered oxide cathodes, carbon-based anodes, and electrolytes for potassium ion batteries.

Lithium-ion batteries (LIBs) have become the most popular portable secondary energy storage facilities. However, the limited lithium resource results in possible unsustainable development. Potassium-ion batteries (PIBs) are considered promising alternatives to LIBs because of their high resource availability, low cost, and environmentally friendly features. In this field, high energy density layered cathodes and carbon-based anodes are also the main research objectives. However, compared to the most appealing alternative sodium-ion batteries (SIBs), despite having various theoretical advantages, PIBs exhibit poorer electrochemical performance in practice. Their poor capacity retention and narrow working voltage range seriously limit their applications. The performance of the electrodes is usually considered an important factor for battery performance, life, and safety. To solve these problems, many significant research studies have been carried out in the last decade, achieving numerous breakthroughs. Nevertheless, there are still many drawbacks and unclear mechanisms. In this comprehensive review, we examine the current state of high-performance layered oxide cathodes, electrolytes, and carbon-based anodes, to identify potential candidates for PIBs. Our focus lies on their structural characteristics, interface properties, underlying mechanisms, and modification techniques. The viewpoints of these advanced strategies are integrated, and concise development suggestions and strategies are subsequently proposed.

Low-dose aspirin for prevention of cardiovascular mortality in patients with type 2 diabetes and chronic kidney disease: A real-world nationwide cohort study.

AIMS/INTRODUCTION: Cardiovascular mortality risk is elevated among patients with diabetes and concurrent chronic kidney disease. However, controversy surrounds the use of aspirin for primary prevention within this population. This study aims to assess the effectiveness and safety of low-dose aspirin for primary prevention in patients with diabetes and pre-end-stage renal disease. MATERIALS AND METHODS: This was a retrospective population-based cohort study using the National Health Insurance Research Database in Taiwan. The study included adults with type 2 diabetes who were enrolled in the pre-end-stage renal disease pay-for-performance program and had no atherosclerotic cardiovascular disease. We used propensity score analysis to control baseline characteristics between the two groups. Clinical outcomes including cardiovascular mortality, all-cause mortality, major bleeding, and renal disease progression were compared between patients who first received aspirin and those who did not. RESULTS: Between January 2012 and December 2015, a total of 2,155 low-dose aspirin users and 6,737 nonaspirin users were identified. Following propensity score adjustment, aspirin use exhibited a comparable risk of cardiovascular death compared with nonaspirin users (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.65-1.95; P = 0.681). The risk of all-cause mortality was similar between the two groups (aHR 1.07; 95% CI 0.92-1.24; P = 0.385). Similar risks were observed in terms of major bleeding and renal disease progression. CONCLUSIONS: In patients with diabetes and pre-end-stage renal disease who lacked atherosclerotic cardiovascular disease, low-dose aspirin did not demonstrate a reduction in mortality. These findings do not support the use of aspirin for primary prevention in this high-risk population.