Prior-free 3D tracking of a fast-moving object at 6667 frames per second with single-pixel detectors.

Real-time tracking and 3D trajectory computation of fast-moving objects is a promising technology, especially in the field of autonomous driving. However, existing image-based tracking methods face significant challenges when it comes to real-time tracking, primarily due to the limitation of storage space and computational resources. Here, we propose a novel approach that enables real-time 3D tracking of a fast-moving object without any prior motion information and at a very low computational cost. To enable 3D coordinate synthesis with a space-efficient optical setup, geometric moment patterns are projected on two non-orthogonal planes with a spatial resolution of 125 µm. Our experiment demonstrates an impressive tracking speed of 6667 frames per second (FPS) with a 20 kHz digital micromirror device (DMD), which is more than 200 times faster than the widely adopted video-based tracking methods. To the best of our knowledge, this is the highest tracking speed record in the field of single-pixel 3D trajectory tracking. This method promotes the development of real-time tracking techniques with single-pixel imaging (SPI).

Discovery of Phenylpyrazole Derivatives as a New Class of Selective Inhibitors of MCL-1 with Antitumor Activity.

MCL-1, an antiapoptotic member of the BCL-2 family, is dysregulated and overexpressed in various tumors. In tumors with MCL-1 overexpression, selective inhibitors of MCL-1 are expected to overcome the drug resistance caused by BCL-2 inhibitors currently used in clinical treatment. Here, we employed docking-based virtual screening to identify an active hit, LC126, with binding affinity around 10 µM for MCL-1 and BCL-2. Under the guidance of structure-based design, we obtained a few selective inhibitors of MCL-1 after three rounds of structural optimization. The representative compound GQN-B37-E exhibited binding affinity for MCL-1 at the submicromolar range (K i = 0.6 µM) without apparent binding to BCL-2 or BCL-XL. 15N-heteronuclear single-quantum coherence NMR spectra suggested that this compound binds to the BH3-domain-binding pocket in the MCL-1 surface. Cellular assays revealed that GQN-B37-Me, the precursor of GQN-B37-E, is effective particularly on leukemia cells (such as H929 and MV-4-11) to induce caspase-dependent apoptosis. Its interaction with MCL-1 in cells was confirmed by coimmunoprecipitation. Administration of GQN-B37-Me to MV-4-11 xenograft mice at 50 mg/kg every 2 days for 20 days led to 43% tumor growth inhibition. GQN-B37-Me also exhibited reasonable in vitro stability in GSH and liver microsomes from several species. This new class of MCL-1 inhibitor may have potential to be further developed into a preclinical candidate for treating leukemia.

Linking active rectal mucosa-attached microbiota to host immunity reveals its role in host-pathogenic STEC O157 interactions.

The rectal anal junction (RAJ) is the major colonization site of Shiga toxin-producing Escherichia coli (STEC) O157 in beef cattle, leading to transmission of this foodborne pathogen from farms to food chains. To date, there is limited understanding on whether mucosa-attached microbiome has a profound impact on host-STEC interactions. In this study, the active RAJ mucosa-attached microbiota and its potential role in host immunity-STEC-commensal interactions were investigated using RAJ mucosal biopsies collected from calves orally challenged with two STEC O157 strains with or without functional stx2a (stx2a + or stx2a-). The results revealed that shifts of microbial diverstives, topological, and assembly patterns were subjected to stx2a production post-challenge and Paeniclostridium and Gallibacterium being the keystone taxa for both microbial interactions and assembly. Additional mucosal transcriptome profiling showed stx2a-dependent host immune responses (i.e. B and T cell signaling, antigen processing and presentation) post-challenge. Further integrated analysis revealed that mucosa-attached beneficial microbes (i.e. Provotella, Faecalibacterium, and Dorea) interacted with host immune genes pre-challenge to maintain host homeostasis, however, opportunistic pathogenic microbes (i.e. Paeniclostridium) could interact with host immune genes after the STEC O157 colonization and interactions were stx2a-dependent. Furthermore, bacterial predicted functions involved in pathogen (O157 and Paeniclostridium) colonization and metabolism were related to host immunities. These findings suggest that host-microbe interactions could shift from beneficial to opportunistic pathogenic bacteria-driven during the pathogen colonization and be dependent on the production of particular virulence factors, highlighting the potential regulatory role of mucosa-attached microbiota in affecting pathogen-commensal-host interactions under STEC O157 infection in calves.

Case Report: Endoluminal removal of a conical retrievable superior vena cava filter with a retraction hook attached to the wall.

We report the case of a 22-year-old male who underwent endoluminal surgery and was implanted an Option Elite filter in the superior vena cava (SVC) while the filter retraction hook was attached to the vessel wall. The patient requested to remove the filter after 155 days. Preoperative ultrasonography and CT examination revealed that the filter retraction hook was very likely to penetrate the SVC wall and its tip was very close to the right pulmonary artery. The SVC was not obstructed, and no thrombus was observed in either upper limb. After the filter retrieval device (ZYLOX, China) failed to capture the filter hook, we introduced a pigtail catheter with its tip partly removed and a loach guidewire, used a modified loop-snare technique to cut the proliferative tissues and free the hook, and finally removed the filter successfully by direct suspension of the guidewire. During this procedure, the patient experienced discomfort, such as chest pain and palpitations, but these symptoms disappeared when procedure completed. Repeated multiangle angiography revealed no contrast medium extravasation, no complications such as pericardial tamponade, pleural effusion, SVC haematoma formation, right pulmonary artery dissecting aneurysm, or intramural haematoma. We initially presented the modified loop-snare technique used to remove a conical superior vena cava filter (SVCF), so this method can be considered a practical and novel auxiliary technique for successful filter retrieval.

The spatial orientation of crista ampullaris: implications for BPPV diagnosis and treatment.

Objective: This study aimed to provide a comprehensive understanding of the spatial orientation of the crista ampullaris within the inner ear and its implications for the diagnosis and management of benign paroxysmal positional vertigo (BPPV). Methods: Using high-resolution MRI scans of 55 normal inner ears, 3D models of the semicircular canals were segmented. These were complemented by detailed membrane labyrinth models from micro-CT scans of human temporal bones, accessed via the Comparative Ear Bank (www.earbank.org). A statistical shape model of inner ears and eyeballs was established, and a standardized 3D spatial coordinate system was created. The horizontal plane was defined using the top of the common crus and the bottom of the eyeballs. This calibrated reference system allowed for precise quantification of crista ampullaris orientations by calculating angles between the defined crista planes and coordinate planes. Results: The plane of the ampulla and the corresponding semicircular canal plane are nearly perpendicular to each other. In the upright position, the posterior semicircular canal crista ampullaris formed an angle of 48.9° with the horizontal plane. The relative orientations of the crista ampullaris of the lateral and superior canals were also defined. Furthermore, we identified "zero-point planes" representing crista orientations perpendicular to gravity, which resulted in minimal ampullary stimulation. A 6.2° tilt to the left in the supine position resulted in the plane of the left lateral semicircular canal crista ampullaris being parallel to the direction of gravity. Conclusion: This study elucidates the precise spatial orientation of the crista ampullaris, thereby providing an anatomical basis for understanding BPPV pathophysiology and improving the accuracy of diagnostic and therapeutic maneuvers. The findings have the potential to significantly enhance the management of BPPV and other inner ear disorders.

Summary of the best evidence on self-management support schemes for patients with inflammatory bowel disease based on mobile health systems.

Objective: Self-management support services can improve patients' self-management ability. This study summarized the best evidence on a self-management support scheme for patients with inflammatory bowel disease based on a mobile health system to accurately describe the current status of the field and provide recommendations for healthcare workers. Methods: Two researchers retrieved studies from computer decision support systems, guideline websites, official association websites, and databases from the establishment of the database until October 2023. The quality of the included studies was independently evaluated by two authors using the Appraisal of Guidelines for Research and Evaluation Instrument II and the 2016 version of the corresponding evaluation standards of the Australian Joanna Briggs Institute Evidence-based Health Care Center. The classification of evidence and recommendation level adopted the 2014 version of the Australian Joanna Briggs Institute evidence pregrading and recommending level system. Results: Fifteen studies were included, comprising one guideline, two expert consensuses, four systematic reviews, four quasi-experimental studies, and four qualitative studies. The overall quality of the included studies was moderate to high. Thirty-six pieces of best evidence were compiled for seven elements, namely, mobile health system type and functional support; mobile health system application preparation; health information recording, uploading, and presentation; zoning management of diseases and early warning of the active period; support related to health education; healthcare support team formation and services; and virtual communities. Conclusions: Our study evaluated the quality of the included studies and summarized a self-management support scheme for patients with inflammatory bowel disease based on a mobile health system. The main scheme was divided into 7 parts and 36 items, which can be used as a reference for healthcare workers so that they can provide more comprehensive and scientific self-management support services for patients with inflammatory bowel disease through mobile health systems.

Effect of 3-Nitropropionic Acid at Different Doses on In Vitro Rumen Fermentation, Digestibility, and Methane Emissions of Grazing Yak and Cattle.

3-nitropropionic acid (3NPA) has been proposed as an useful modifier to mitigate ruminal enteric methane emissions. However, few studies investigated the effects of 3NPA on ruminal fermentation characteristics of grazing ruminants in vitro. Rumen fluid from grazing yak and cattle were collected and incubated with additions of 0, 8, and 16 mM 3NPA. The total gas production, CH4 production, and dry matter digestibility significantly decreased with increasing 3NPA doses in both ruminant species (p < 0.05) and methane production decreased to almost 100% in cattle at 8 mM NPA but not yak, while H2 accumulation showed an opposite trend. The total fatty acid (TVFA) production, acetate concentration, and propionate concentration in cattle decreased as 3NPA doses increased at 12 and 24 h incubation. For yak, the H2 accumulation reached its apex at 8 mM NPA (p < 0.05). The TVFA in yak decreased significantly with increasing 3NPA doses at 12 and 72 h incubation. Moreover, the acetate concentration and propionate concentration in yak decreased as 3NPA doses increased at 12 and 24 h incubation. Overall, these findings demonstrated that 3NPA could be used as a strategy to mitigate methane emissions; although, it negatively affected the dry matter degradability in vitro.

Effect of High Temperature on Abamectin and Thiamethoxam Tolerance in Bemisia tabaci MEAM1 (Hemiptera: Aleyrodidae).

Bemisia tabaci (Gennadius) is one of the most important invasive species in China, with strong insecticide resistance and thermotolerance. In this study, we investigated the effects of elevated temperature on the tolerance of B. tabaci MEMA1 to abamectin (AB) and thianethixam (TH) insecticides. We firstly cloned two new CYP450 genes from B. tabaci MEAM1, including one CYP6 family gene (BtCYP6k1) and one CYP305 family gene (BtCYP305a1). The expression patterns of the two BtCYP450 genes were compared in response to high-temperature stress and insecticide exposure, and RNAi was then used to demonstrate the role that these two genes play in insecticide tolerance. The results showed that expression of the two BtCYP450 genes could be induced by exposure to elevated temperature or insecticide, but this gene expression could be inhibited to a certain extent when insects were exposed to the combined effects of high temperature and insecticide treatment. For AB treatment, the expression of the two BtCYP450 genes reached the lowest level when insects were exposed to a temperature of 41 °C and treated with AB (combined effects of temperature and insecticide). In contrast, TH treatment showed a general decrease in the expression of the two BtCYP450 genes with exposure to elevated temperatures. These findings suggest that insecticide tolerance in B. tabaci MEAM1 could be mediated by high temperatures. This study provides a prospective method for the more effective application of insecticides for the control of B. tabaci in the field.

CD177 on neutrophils engages stress-related behavioral changes in male mice.

Persistent psychological stress can affect immune homeostasis and is a key factor in the development of depression. Many efforts are focused on the identifcation of pathways that link the immune system and mood disorders. Here, we found that psychological stress caused an increase in the frequency of brain-associated neutrophils and the level of neutrophil-specific antigen CD177 on peripheral neutrophils in male mice. Upregulated levels of blood CD177 are associated with depression in humans. Neutrophil depletion or Cd177 deficiency protected mice from stress-induced behavioral deficits. Importantly, adoptive transfer of CD177+ neutrophils from stressed mice increased the frequency of brain-associated leukocytes, including neutrophils, and caused behavioral defects in naive mice. These effects may be related to the endothelial adhesion advantage of CD177+ neutrophils and the interference of serine protease on endothelial junction. Our findings suggest a critical link between circulating CD177+ neutrophils and psychological stress-driven behavioral disorder.

Effects of immune cells on ischemic stroke and the mediating roles of metabolites.

Objective: Previous studies have not shown an association between IgD-CD24-B-cell absolute count (IgD-CD24-AC) and ischemic stroke (IS). Our study aimed to assess the causal effect of IgD-CD24-AC on IS and to explore the role of ascorbic acid 2-sulfate (AA2S) as a potential mediator. Methods: Our study was based on the largest available genome-wide association study (GWAS). Inverse variance weighting (IVW), MR-Egger, weighted median (WMN), simple mode, and weighted mode methods were used to assess causal effects, with IVW as the primary outcome. Subsequently, we further performed a two-step MR analysis to evaluate whether AA2S mediated this causal effect. In addition, several sensitivity analyses were conducted to evaluate heterogeneity, including Cochran's Q test, the MR-Egger intercept test, the MR-PRESSO global test, and the leave-one-out analysis. Results: Using the IVW approach, the risk ratio of IgD-CD24-AC to IS was estimated to be 1.216 (95% CI = 1.079-1.371, p = 0.001). This result was supported by the WMN method (OR = 1.204, 95% CI = 1.020-1.421, p = 0.028) and the MR-Egger method (OR = 1.177, 95% CI = 0.962-1.442, p = 0.133). We also observed the same trend with the simple model and weighted model. Furthermore, the proportion of genetically predicted IgD-CD24-AC mediated through AA2S levels was 3.73%. Conclusion: Our study revealed a causal relationship between IgD-CD24-AC and IS, a small part of which was mediated by AA2S. These findings offer critical insights for developing immune-targeted therapies in the future and lay a strong foundation for advancements in precision medicine.

Topical application of Artemisia annua L. essential oil ameliorates 2,4-dintrochlorobenzene-induced atopic dermatitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Volatile oil is widely used in traditional Chinese medicine owing to its unique hydrophobic and lipophilic properties and rapid skin absorption. Artemisia annua L. (A.annua) essential oil (AAEO), a volatile oil extracted from A. annua, exhibits anti-inflammatory properties. However, few studies have investigated its effects on skin inflammation. AIM OF THE STUDY: To investigate and elucidate the mechanisms of action of AAEO in the treatment of atopic dermatitis (AD). MATERIALS AND METHODS: Network pharmacology was used to predict the targets and pathways of AAEO for the treatment of AD. The AD mouse model was established by topical application of 2,4-dintrochlorobenzene (DNCB), AAEO, and the positive control drug hydrocortisone butyrate cream (HBC). We evaluated the symptoms of AD, SCORAD scores, histological analysis, and serum IgE and TNF-α levels in mice. Immunofluorescence, western blotting, and qPCR were used to investigate the signaling pathways. RESULTS: Network pharmacology analysis indicated that AAEO may exert its effects via the MAPK/NF-κB signaling pathway. Animal experiments demonstrated that topical application of AAEO and HBC significantly ameliorated skin lesions, reduced dermatitis score, and decreased spleen weight compared to DNCB treatment. AAEO reduced skin epidermal thickness and mast cell infiltration. DNCB markedly reduced the protein levels of filaggrin (FLG) and loricrin (LOR), whereas AAEO reversed these changes. Notably, the 5% concentration of AAEO demonstrated substantial improvement in skin barrier function. Compared to the DNCB group, the levels of FLG and LOR remained almost unchanged following HBC treatment. DNCB markedly elevated IgE and TNF-α levels, which were reversed by AAEO and HBC treatment. Among the inflammatory cytokines, DNCB increased mRNA expression of TNF-α, IL-1ß, and IL-6, however, it reduced IL-10, with AAEO and HBC reversing these changes to various degrees. Additionally, DNCB-induced ERK, JNK, and P38 phosphorylation, associated with the upregulation of phosphorylation of NF-κB, whereas, AAEO and HBC exhibited potent inhibition of the MAPK/NF-κB signaling pathway. CONCLUSIONS: This study systematically demonstrated the possible therapeutic effects and mechanisms of AAEO in AD via network pharmacological analysis and experimental confirmation. These results revealed that topical application of AAEO can suppress skin inflammation and restore skin barrier function. These findings provide the potential application of AAEO in synthesizing external preparations for both pharmacological and cosmetic industries.

Dopamine D1 Receptor Agonists Rescue Age-related Decline in Temporal Order Memory.

Dopamine D1 receptor agonists improve spatial working memory, but their effects on temporal order memory, particularly prone to the effects of aging, have not been studied. Two D1 agonists, PF6256142 (PF) and 2-methyldihydrexidine (2MDHX), were examined for their effects in a rodent temporal order recognition task. Our results are consistent with the hypothesis that there is an age-related decline in rodent temporal order memory. The data also show that either agonist rescues the poor memory performance with a large effective size. Interestingly, the optimal effective dose varied among individual rats of different age groups. PF showed greater potency for older rats, whereas 2MDHX showed better overall population effectiveness. Both PF and 2MDHX have high intrinsic activity at rodent D1-mediated cAMP synthesis. Conversely, at D1-mediated ß-arrestin recruitment, PF has essentially no intrinsic activity, whereas 2MDHX is a super-agonist. These findings suggest that D1 agonists have potential to treat age-related cognitive decline, and the pattern of functional selectivity may be useful for developing drugs with an improved therapeutic index.

Retracing from Outcomes to Causes: NRF2-Driven GSTA4 Transcriptional Regulation Controls Chronic Inflammation and Oxidative Stress in Atopic Dermatitis Recurrence.

Atopic dermatitis (AD), a chronic and recurrent inflammatory skin disorder, presents a high incidence and imposes a substantial economic burden. Preventing its recurrence remains a significant challenge in dermatological therapy owing to poorly understood underlying mechanisms. In our study, we adopted a strategy of tracing the mechanisms of recurrence from clinical outcomes. We developed a mouse model of recurrent AD and applied clinically validated treatment regimens. Transcriptomic analyses revealed a pronounced enrichment in the glutathione metabolic pathway in the treated group. Through integrated bioinformatics and in vivo validation, we identified glutathione S-transferase alpha 4 (GSTA4) as a pivotal mediator in AD recurrence. Immunohistochemical analysis demonstrated decreased GSTA4 expression in lesions from patients with AD. Functionally, in vitro overexpression of GSTA4 significantly curtailed AD-like inflammatory responses and ROS production. Moreover, we discovered that NRF2 transcriptional activity regulates GSTA4 expression and function. Our treatment notably augmented NRF2-mediated GSTA4 transcription, yielding pronounced anti-inflammatory and ROS-neutralizing effects. Conclusively, our findings implicate GSTA4 as a critical factor in the recurrence of AD, particularly in the context of oxidative stress and chronic inflammation. Targeting the NRF2-GSTA4 axis emerges as a promising anti-inflammatory and antioxidative strategy for preventing AD recurrence.

The application of the golden-angle radial sparse parallel technique in T restaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy.

PURPOSE: To evaluate the diagnostic performance of Golden-Angle Radial Sparse Parallel (GRASP) MRI in identifying pathological stage T0-1 (ypT0-1) after neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer, compared to T2-weighted imaging (T2WI) combined with Diffusion Weighted Imaging (DWI). METHODS: In this retrospective study, 168 patients were carefully selected based on inclusion criteria that targeted individuals with biopsy-confirmed primary rectal adenocarcinoma, identified via MRI as having locally advanced disease (≥ T3 and/or positive lymph node results) prior to nCRT. Post-nCRT, all MRI images obtained after nCRT were assessed by two observers independently. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for identifying ypT0-1 based on GRASP and T2 + DWI were calculated. Multivariable regression analysis was used to explore the factors independently associated with ypT0-1 tumor. RESULTS: 45 patients out of these cases were ypT0-1, and the accuracy, sensitivity, specificity, PPV, and NPV of GRASP were higher than the T2 + DWI (88% vs 74%, 93% vs 71%, 86% vs 75%, 71% vs 52% and 97% vs 88%), the AUC in identifying ypT0-1 tumor based on GRASP was 0.90 (95% CI:0.84, 0.94), which was better than the T2 + DWI (0.73; 95% CI: 0.66, 0.80). Multivariable logistic regression analysis showed that the yT stage on GRASP scans was the only factor independently associated with ypT0-1 tumor (P < 0.001). CONCLUSION: The GRASP helped distinguish ypT0-1 tumor after nCRT and can select patients who may be suitable for local excision.

Global trends and hotspots in pain associated with bipolar disorder in the last 20 years: a bibliometric analysis.

Purpose: The prevalence of comorbid pain and Bipolar Disorder in clinical practice continues to be high, with an increasing number of related publications. However, no study has used bibliometric methods to analyze the research progress and knowledge structure in this field. Our research is dedicated to systematically exploring the global trends and focal points in scientific research on pain comorbidity with bipolar disorder from 2003 to 2023, with the goal of contributing to the field. Methods: Relevant publications in this field were retrieved from the Web of Science core collection database (WOSSCC). And we used VOSviewer, CiteSpace, and the R package "Bibliometrix" for bibliometric analysis. Results: A total of 485 publications (including 360 articles and 125 reviews) from 66 countries, 1019 institutions, were included in this study. Univ Toront and Kings Coll London are the leading research institutions in this field. J Affect Disorders contributed the largest number of articles, and is the most co-cited journal. Of the 2,537 scholars who participated in the study, Stubbs B, Vancampfort D, and Abdin E had the largest number of articles. Stubbs B is the most co-cited author. "chronic pain," "neuropathic pain," "psychological pain" are the keywords in the research. Conclusion: This is the first bibliometric analysis of pain-related bipolar disorder. There is growing interest in the area of pain and comorbid bipolar disorder. Focusing on different types of pain in bipolar disorder and emphasizing pain management in bipolar disorder are research hotspots and future trends. The study of pain related bipolar disorder still has significant potential for development, and we look forward to more high-quality research in the future.

Raman spectroscopy study on terephthalamide crystal at high pressures.

In this study, we have investigated the structural stability of terephthalamide (TPA) crystal at pressure from ambient to 15 GPa in the diamond anvil cell at room temperature by Raman spectroscopy. Assignment for the Raman vibration modes of TPA crystal at ambient conditions has been performed based on the density functional theory (DFT) calculations. Pressure-induced structural transition was monitored using in-situ Raman spectroscopy. Remarkable changes (including the appearance of new Raman peaks, disappearance of original Raman bands, discontinuous changes in the pressure dependence of some Raman wavenumbers at different pressures) in Raman spectra were observed at approximately 1.3 and 5.2 GPa, provided clear evidences for two pressure-induced phase transitions: phase I to phase II at ∼1.3 GPa, phase II to phase III at ∼5.2 GPa.

Error-compensation network for ringing artifact reduction in holographic displays.

Recent advances in learning-based computer-generated holography (CGH) have unlocked novel possibilities for crafting phase-only holograms. However, existing approaches primarily focus on the learning ability of network modules, often neglecting the impact of diffraction propagation models. The resulting ringing artifacts, emanating from the Gibbs phenomenon in the propagation model, can degrade the quality of reconstructed holographic images. To this end, we explore a diffraction propagation error-compensation network that can be easily integrated into existing CGH methods. This network is designed to correct propagation errors by predicting residual values, thereby aligning the diffraction process closely with an ideal state and easing the learning burden of the network. Simulations and optical experiments demonstrate that our method, when applied to state-of-the-art HoloNet and CCNN, achieves PSNRs of up to 32.47 dB and 29.53 dB, respectively, surpassing baseline methods by 3.89 dB and 0.62 dB. Additionally, real-world experiments have confirmed a significant reduction in ringing artifacts. We envision this approach being applied to a variety of CGH algorithms, paving the way for improved holographic displays.

Advancing precision rheumatology: applications of machine learning for rheumatoid arthritis management.

Rheumatoid arthritis (RA) is an autoimmune disease causing progressive joint damage. Early diagnosis and treatment is critical, but remains challenging due to RA complexity and heterogeneity. Machine learning (ML) techniques may enhance RA management by identifying patterns within multidimensional biomedical data to improve classification, diagnosis, and treatment predictions. In this review, we summarize the applications of ML for RA management. Emerging studies or applications have developed diagnostic and predictive models for RA that utilize a variety of data modalities, including electronic health records, imaging, and multi-omics data. High-performance supervised learning models have demonstrated an Area Under the Curve (AUC) exceeding 0.85, which is used for identifying RA patients and predicting treatment responses. Unsupervised learning has revealed potential RA subtypes. Ongoing research is integrating multimodal data with deep learning to further improve performance. However, key challenges remain regarding model overfitting, generalizability, validation in clinical settings, and interpretability. Small sample sizes and lack of diverse population testing risks overestimating model performance. Prospective studies evaluating real-world clinical utility are lacking. Enhancing model interpretability is critical for clinician acceptance. In summary, while ML shows promise for transforming RA management through earlier diagnosis and optimized treatment, larger scale multisite data, prospective clinical validation of interpretable models, and testing across diverse populations is still needed. As these gaps are addressed, ML may pave the way towards precision medicine in RA.

Utilization of diffusion-weighted derived mathematical models to predict prognostic factors of resectable rectal cancer.

PURPOSE: This study explored models of monoexponential diffusion-weighted imaging (DWI), diffusion kurtosis imaging (DKI), stretched exponential (SEM), fractional-order calculus (FROC), and continuous-time random-walk (CTRW) as diagnostic tools for assessing pathological prognostic factors in patients with resectable rectal cancer (RRC). METHODS: RRC patients who underwent radical surgery were included. The apparent diffusion coefficient (ADC), the mean kurtosis (MK) and mean diffusion (MD) from the DKI model, the distributed diffusion coefficient (DDC) and α from the SEM model, D, ß and u from the FROC model, and D, α and ß from the CTRW model were assessed. RESULTS: There were a total of 181 patients. The area under the receiver operating characteristic (ROC) curve (AUC) of CTRW-α for predicting histology type was significantly higher than that of FROC-u (0.780 vs. 0.671, p = 0.043). The AUC of CTRW-α for predicting pT stage was significantly higher than that of FROC-u and ADC (0.786 vs.0.683, p = 0.043; 0.786 vs. 0.682, p = 0.030), the difference in predictive efficacy of FROC-u between ADC and MK was not statistically significant [0.683 vs. 0.682, p = 0.981; 0.683 vs. 0.703, p = 0.720]; the difference between the predictive efficacy of MK and ADC was not statistically significant (p = 0.696). The AUC of CTRW (α + ß) (0.781) was significantly higher than that of FROC-u (0.781 vs. 0.625, p = 0.003) in predicting pN stage but not significantly different from that of MK (p = 0.108). CONCLUSION: The CTRW and DKI models may serve as imaging biomarkers to predict pathological prognostic factors in RRC patients before surgery.

Pyridine-Bridged Covalent Organic Frameworks with Adjustable Band Gaps as Intelligent Artificial Enzymes for Light-Augmented Biocatalytic Sensing.

One of the biggest challenges in biotechnology and medical diagnostics is finding extremely sensitive and adaptable biosensors. Since metal-based enzyme-mimetic biocatalysts may lead to biosafety concerns on accumulative toxicity, it is essential to synthesize metal-free enzyme-mimics with optimal biocatalytic activity and superior selectivity. Here, the pyridine-bridged covalent organic frameworks (COFs) with specific oxidase-like (OXD-like) activities as intelligent artificial enzymes for light-augmented biocatalytic sensing of biomarkers are disclosed. Because of the adjustable bandgaps of pyridine structures on the photocatalytic properties of the pristine COF structures, the pyridine-bridged COF exhibit efficient, selective, and light-responsive OXD-like biocatalytic activity. Moreover, the pyridine-bridged COF structures show tunable and light-augmented biocatalytic detection capabilities, which outperform the recently reported state-of-the-art OXD-mimics regarding biosensing efficiency. Notably, the pyridine-bridged COF exhibits efficient and multifaceted diagnostic activity, including the extremely low limit of detection (LOD), which enables visual assays for abundant reducibility biomarkers. It is believed that this design will offer unique metal-free biocatalysts for high-sensitive and low-cost colorimetric detection and also provide new insights to create highly efficient enzyme-like COF materials via linkage-modulation strategies for future biocatalytic applications.