Artificial Intelligence-Based Multimodal Prediction of Postoperative Adjuvant Immunotherapy Benefit in Urothelial Carcinoma: Results From the Phase III, Multicenter, Randomized, IMvigor010 Trial.

While circulating tumor DNA (ctDNA) testing has demonstrated utility in identifying muscle-invasive urothelial carcinoma (MIUC) patients likely to benefit from adjuvant immunotherapy, the prognostic value of transcriptome data from surgical specimens remains underexplored. Using transcriptomic and ctDNA data from the IMvigor010 trial, we developed an artificial intelligence (AI)-driven biomarker to predict immunotherapy response in urothelial carcinoma, termed UAIscore. Patients with high UAIscore had significantly better outcomes in the atezolizumab arm versus the observation arm.

Fingernail-based metabolomics reveals a stepwise decline in dodecanoic acid associated with Alzheimer's disease progression.

Background: Fingernail metabolomics provides a novel, non-invasive platform that captures long-term biochemical fluctuations for identifying reliable biomarkers for dementia and mild cognitive impairment (MCI) due to Alzheimer's disease (AD).

Methods: This study enrolled 199 participants stratified by Clinical Dementia Rating (CDR) scores. Fingernail clippings were collected and subjected to gas chromatography-mass spectrometry based metabolomic analysis.

Blood-Brain barrier disruption in long COVID and cognitive correlates: A cross-sectional MRI study.

Disruption of the blood-brain barrier (BBB) may contribute to neuropsychiatric symptoms observed in Long COVID (LC). Using a non-contrast magnetic resonance imaging (MRI) technique, we investigated BBB permeability in individuals with LC and its relationship to cognitive function. We hypothesized that LC individuals would show greater BBB permeability than recovered individuals, and that higher permeability would correlate with poorer cognition.

Evaluating the role of large language models in traditional Chinese medicine diagnosis and treatment recommendations.

Digital health technologies hold significant potential for reducing global healthcare disparities. Large language models (LLMs) offer new opportunities to enhance access to culturally specific healthcare, including traditional Chinese medicine (TCM). This study evaluated the diagnostic and treatment performance of seven publicly available LLMs using a real-world acupuncture case, comparing their outputs with three professional acupuncturists across five domains: Western diagnosis, TCM diagnosis, acupoint selection, needling technique, and herbal medicine.

Surface oxygen concentration differs between dry and ice-snow melting bare lands on the Tibetan Plateau.

The Tibetan Plateau's unique geography has attracted significant research interest in near-surface atmospheric oxygen concentration. Understanding the impacts of elevation, temperature, and precipitation on oxygen concentration patterns in various bare lands is essential for enhancing resilience against hypoxia and promoting sustainable development in high elevation regions. This paper utilized near-surface oxygen content data and systematic field sampling data from the Tibetan Plateau to examine the spatial distribution of oxygen concentration in dry and ice-snow melting bare lands, along with its relationships with altitude, temperature, and precipitation.

Endothelin A receptor in nociceptors is essential for persistent mechanical pain in a chronic pancreatitis of mouse model.

Background: Chronic pancreatitis (CP) accompanied with persistent abdominal pain represents a major clinical challenge for the symptom management in patients. Although with clear involvement of neuropathy, the detailed mechanisms underlying pain hypersensitivity associated with CP are not totally clear. The endothelin system has been reported to contribute to chronic pain and chronic inflammatory settings, and is a potential therapeutic target for the treatment of chronic pain.

PAM-free hairpin target binding activates trans-cleavage activity of Cas12a.

CRISPR-Cas12a has been demonstrated to be activated for its trans-cleavage activity by single- and double-stranded DNA containing a protospacer adjacent motif (PAM), but other types of activators have remained undiscovered. In this work, we found that a hairpin-structured substrate can activate the trans-cleavage activity of Cas12a without a PAM, and the parameters of the hairpin loop obviously affect the activity. Cas12a exhibits sequence preference for proximal loops, preferring to recognize polyadenine hairpin loop activators.

Application of Non-G-Quadruplex Hemin Aptamers to Hemin Detection and Heme Oxygenase 1 Activity Evaluation via Spatial Conformational Constraint.

The correct spatial folding of the aptamer significantly influences its binding performance with the target. By extending the terminal double-stranded domain of the hemin aptamer, we obtained apt71 with a more stable spatial conformation. The catalytic activity of the resulting apt71/hemin DNAzyme reached 200% of that of the original aptamer.

Gait speed as a superior screening indicator for mild cognitive impairment compared to walk ratio and dual-task cost: a cross-sectional study.

Background: The accurate and sensitive quantitative indicator for screening patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) has not yet been established.

Methods: Our study involved the measurement and comparison of clinical features and gait indicators among 96 patients with MCI, 66 patients with SCD, and 50 individuals with normal cognition (NC). Receiver operating characteristic (ROC) curve, multiple logistic regression, correlation clustering heatmap plot, and random forest modeling were used to evaluate the ability of gait indicators to differentiate disease.

PFKFB3 confers cisplatin resistance in gastric cancer by inhibiting ferroptosis through SLC7A11/xCT dephosphorylation.

Cisplatin-based combination chemotherapy is a cornerstone of perioperative and adjuvant therapies for gastric cancer (GC). However, cisplatin resistance resulting from repeated treatment limits its clinical application. PFKFB3 (6-phosphofructo-2-kinase), an isoenzyme of the PFKFB family, functions as a vital regulator of glycolysis and is involved in multiple cancer-related processes, including carcinogenesis, proliferation, metastasis, and drug resistance.

Immunotyping the Tumor Microenvironment Reveals Molecular Heterogeneity for Personalized Immunotherapy in Cancer.

The tumor microenvironment (TME) significantly influences cancer prognosis and therapeutic outcomes, yet its composition remains highly heterogeneous, and currently, no highly accessible, high-throughput method exists to define it. To address this complexity, the TMEclassifier, a machine-learning tool that classifies cancers into three distinct subtypes: immune Exclusive (IE), immune Suppressive (IS), and immune Activated (IA), is developed. Bulk RNA sequencing categorizes patient samples by TME subtype, and in vivo mouse model validates TME subtype differences and differential responses to immunotherapy.

Neutrophil-to-lymphocyte ratio-based prognostic score can predict outcomes in patients with advanced non-small cell lung cancer treated with immunotherapy plus chemotherapy.

Backgroud: Immune checkpoint inhibitor (ICI) plus chemotherapy has become the standard of care for advanced non-small cell lung cancer (NSCLC). Nonetheless, reliable efficacy biomarkers of ICI plus chemotherapy are lacking. In this research, we sought to explore efficacy biomarkers and construct robust prognostic models in NSCLC patients treated with ICI plus chemotherapy.

HTRecNet: a deep learning study for efficient and accurate diagnosis of hepatocellular carcinoma and cholangiocarcinoma.

Background: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represent the primary liver cancer types. Traditional diagnostic techniques, reliant on radiologist interpretation, are both time-intensive and often inadequate for detecting the less prevalent CCA. There is an emergent need to explore automated diagnostic methods using deep learning to address these challenges.

Autistic-like behaviors and impaired chronic inflammatory pain in primary nociceptive neuron-specific deletion of Mecp2 or Fmr1 knockout male mice.

Aims: Recent studies have identified the roles of autism risk genes in primary sensory neurons and their connection to autism spectrum disorder (ASD) etiology. However, further research is needed to determine the specific impact of different sensory neuron populations. The aim of this study was to investigate the actions of Mecp2 or Fmr1 expression in primary nociceptive neurons on ASD and pain perception.

Targeting hypoxia-mediated chemo-immuno resistance by a hybrid NBDHEX-Pt(IV) prodrug via declining nuclear STING1-promoted AhR-CIN in human lung squamous cell carcinoma.

As found in human lung squamous cell carcinoma (LUSC), STING1 involved in ER-Golgi intermediate compartment (ERGIC) could coordinate immune responses to ectopic DNA triggered by DNA-targeted chemotherapy. ERGIC STING1 is considered to compete with nuclear STING1 to decline aryl hydrocarbon receptor (AhR)-chromosomal instability (CIN)-triggered chronic STING activation which could cause therapeutic resistance. Moreover, GSTP1 was proved to inhibit ERGIC-STING1 via promoting S-glutathione modification of STING1.

Hybrid Capture-Based Sequencing Enables Highly Sensitive Zoonotic Virus Detection Within the One Health Framework.

Hybrid capture-based target enrichment prior to sequencing has been shown to significantly improve the sensitivity of detection for genetic regions of interest. In the context of One Health relevant pathogen detection, we present a hybrid capture-based sequencing method that employs an optimized probe set consisting of 149,990 probes, targeting 663 viruses associated with humans and animals. The detection performance was initially assessed using viral reference materials in a background of human nucleic acids.

Study on the interaction mechanism among spatial patterns of traditional villages and tourism attractiveness and accessibility in Guizhou province.

Traditional villages, an important rural cultural heritage, have gradually developed tourism value and become attractive tourism resources with the support of increasingly convenient transportation infrastructure, and there is inevitably a correlation between the spatial pattern distribution and tourism attractiveness as well as transportation accessibility. Therefore, the study adopts ArcGIS, a modified gravity model combined with the research method of transportation accessibility, to investigate the interaction mechanism and influence relationship between 724 traditional villages in 88 districts and counties of Guizhou Province as the research object. The results found that: (1) Traditional villages in Guizhou Province are mainly clustered in Qiandongnan, with an overall clustering distribution.

Clinical Manifestations and Prognosis of Patients With Mucormycosis in Intensive Care Units in Western China: A Multi-Center Retrospective Study.

Background: Mucormycosis is a life-threatening fungal infection with high mortality in critically ill patients. Clinical manifestations and outcomes of mucormycosis in intensive care units (ICUs) remain poorly investigated.

Methods: We conducted a multicenter retrospective study including 43 adult patients with confirmed mucormycosis admitted to 14 tertiary ICUs between January 2014 and May 2022.

Dynamic cross-linked topological network reconciles the longstanding contradictory properties of polymers.

There is usually a trade-off between high-tensile properties and processability in polymers because the mechanisms of these properties are mutually exclusive. Here, we design a chemically coupled four-arm dynamic polymer cross-link site to overcome this challenge. By concurrently increasing cross-link sites and dynamic bond contents, this approach fabricates polymer networks with high cross-link density yet low processing temperature, challenging the conventional structure-property relationship where cross-linking inherently limits plasticity.

Avoiding the Formation of Bubbles and Pits in Buffered Chemical Polishing for the Niobium Superconducting Cavity Through Adjusting the Acid Ratio.

Buffered chemical polishing (BCP) is an important and widely used polishing technique for superconducting radio-frequency (SRF) cavities made of niobium. A common problem encountered during BCP is the formation of bubbles and W-shaped pits on the cavity surface, which may severely limit the RF performance. We report a method to address the problem of W-shaped pits through optimizing the BCP acid ratio.

Mechanism of Pit Formation on Surface of Superconducting Niobium Cavities During Buffered Chemical Polishing.

Superconducting radio-frequency niobium cavities processed using buffered chemical polishing (BCP) sometimes show typical W-shaped pits on their surface, which may greatly limit their performance. However, the causes of such pits and effective solutions are not fully understood. In this study, we reproduced the formation of W-shaped pits on the cavity surface through niobium sample BCP experiments, directly observed the sample surface's evolution during the polishing process and the polished surface's morphology, and analyzed the cause of W-shaped pits in detail: the formation and attachment of bubbles on the niobium surface during the BCP process.

Post-marketing safety surveillance of Amivantamab: a real world study based on the FDA adverse event reporting system.

Background: Amivantamab stands as the pioneering bispecific antibody that targets both EGFR and MET, utilized in the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR ex20ins mutations. Nevertheless, a thorough assessment of its safety characteristics in the real-world remains unknown.

Research Design And Methods: The adverse event (AE) reports were collected through a search of the FDA Adverse Event Reporting System (FAERS) database spanning from 2019 Q1 to 2024 Q1, and then disproportionality analysis was utilized.

Analysis of risk factors for radiation-induced oral mucositis for nasopharyngeal carcinoma and prognostic value of EGF and STREM-1.

Background: This study analyzed the risk factors of radiation-induced oral mucositis (RIOM) for nasopharyngeal carcinoma (NPC) and the correlation between epidermal growth factor (EGF), soluble myeloid cell expression trigger receptor-1 (sTREM-1), and disease severity.

Methods: A total of 124 patients with NPC who received radiotherapy from March 2013 to November 2016 were enrolled and divided into the study group (n=68) and the control group (n=56) regarding the presence of RIOM. The risk factors of RIOM were evaluated by multivariate logistic regression.

Tumor microenvironment assessment-based signatures for predicting response to immunotherapy in non-small cell lung cancer.

Immunotherapy has significantly altered the treatment paradigm of non-small cell lung cancer (NSCLC), but not all patients experience durable benefits. Predictive biomarkers are needed to identify patients who may benefit from immunotherapy. We retrospectively collected tumor tissues from 65 patients with advanced NSCLC before treatment, and performed transcriptomic and genomic analysis.