Rapid and precise treatment selection for antimicrobial-resistant infection enabled by a nano-dilution SlipChip.

Antimicrobial resistance (AMR) has become an increasingly severe threat to global health, and AMR-associated infection is one of the leading causes of death around the world. Due to the long turnaround time and the limited flexibility and availability of current antimicrobial susceptibility testing (AST) methods, a large portion of patients with bacterial infections are still treated empirically, increasing the risk of mistreatment. To address the demand for precision treatment of bacterial infections, we developed a nano-dilution SlipChip (nd-SlipChip)-based systematic evaluation method, which facilitates rapid, logic feedback for the assessment of antibiotics, antibiotic combinations, and phage therapy.

Super-enhancer Activates Master Transcription Factor NR3C1 Expression and Promotes 5-FU Resistance in Gastric Cancer.

Poor response to 5-fluorouracil (5-FU) remains an obstacle in the treatment of gastric cancer (GC). Super enhancers (SEs) are crucial for determining tumor cell survival under drug pressure. SE landscapes related to 5-FU-resistance are mapped to GC using chromatin immunoprecipitation-sequencing (ChIP-Seq).

Diagnostic accuracy of metagenomic next-generation sequencing in pulmonary tuberculosis: a systematic review and meta-analysis.

Background: Metagenomic next-generation sequencing (mNGS) has emerged as a promising tool in clinical practice due to its unbiased approach to pathogen detection. Its diagnostic performance in pulmonary tuberculosis (PTB), however, remains to be fully evaluated.

Objective: This study aims to systematically review and Meta-analyze the diagnostic accuracy of mNGS in patients with PTB.

Chinese guidelines for ultrasound-guided thermal ablation of thyroid nodules (2024 Edition).

The Chinese Guidelines for Ultrasound-guided Thermal Ablation of Thyroid Nodules (2024 edition) were jointly initiated by the Ultrasound Committee of Chinese Medical Association, the Interventional Ultrasound Committee of Chinese Association of Ultrasound in Medicine and Engineering, the Ultrasonic Intervention Committee of Chinese Colleges of Interventionalists, the Oncological Intervention Committee of Chinese Research Hospital Association, 37 multidisciplinary experts in interventional ultrasound, ultrasound medicine, endocrinology and thyroid surgery participated in the compilation of this guide, which expanded the depth and breadth of the perspective and enhanced the authority of the guide. Based on the systematic review of literatures related to ultrasound-guided thermal ablation of thyroid nodules and the professional opinions of experts, the guidelines define the indications and contraindications of thermal ablation, including pre-ablation evaluation and preparation, thermal ablation techniques and operational procedures, post-ablation follow-up, therapeutic effect evaluation, complications prevention and treatment, and the writing of medical documents for ablation. According to the Grading of Recommendations Assessment, Development and Evaluation (GRADE), a total of 17 objective and comprehensive recommendations were given.

Concurrent Severe Fever with Thrombocytopenia Syndrome Virus Outbreaks on Multiple Fox Farms, China, 2023.

The role of farmed animals in the viral spillover from wild animals to humans is of growing importance. Between July and September of 2023 infectious disease outbreaks were reported on six Arctic fox () farms in Shandong and Liaoning provinces, China, which lasted for 2-3 months and resulted in tens to hundreds of fatalities per farm. Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) was identified in tissue/organ and swab samples from all the 13 foxes collected from these farms.

Personalized Vascularized Tumor Organoid-on-a-Chip for Tumor Metastasis and Therapeutic Targeting Assessment.

While tumor organoids have revolutionized cancer research by recapitulating the cellular architecture and behaviors of real tumors in vitro, their lack of functional vasculature hinders their attainment of full physiological capabilities. Current efforts to vascularize organoids are struggling to achieve well-defined vascular networks, mimicking the intricate hierarchy observed in vivo, which restricts the physiological relevance particularly for studying tumor progression and response to therapies targeting the tumor vasculature. An innovative vascularized patient-derived tumor organoids (PDTOs)-on-a-chip with hierarchical, tumor-specific microvasculature is presented, providing a versatile platform to explore tumor-vascular dynamics and antivascular drug efficacy.

Negative valence in Obsessive-Compulsive Disorder: A worldwide mega-analysis of task-based functional neuroimaging data of the ENIGMA-OCD consortium.

Objective: Obsessive-compulsive disorder (OCD) is associated with altered brain function related to processing of negative emotions. To investigate neural correlates of negative valence in OCD, we pooled fMRI data of 633 individuals with OCD and 453 healthy controls from 16 studies using different negatively-valenced tasks across the ENIGMA-OCD Working-Group.

Methods: Participant data were processed uniformly using HALFpipe, to extract voxelwise participant-level statistical images of one common first-level contrast: negative vs.

Driver mutation landscape of acute myeloid leukemia provides insights for neoantigen-based immunotherapy.

Acute myeloid leukemia (AML) has lagged in benefiting from immunotherapies, primarily due to the scarcity of actionable AML-specific antigens. Driver mutations represent promising immunogenic targets, but a comprehensive characterization of the AML neoantigen landscape and their impact on patient outcomes and the AML immune microenvironment remain unclear. Herein, we conducted matched DNA and RNA sequencing on 304 AML patients and extensively integrated data from additional ∼2500 AML cases, identifying 49 driver genes, notably characterized by a significant proportion of insertions and deletions (indels).

The role of heart and neural crest derivatives-expressed protein factors in pregnancy.

Heart and neural crest derivatives-expressed protein 1 (HAND1) and Heart and neural crest derivatives-expressed protein 2 (HAND2), members of the Twist-family of basic Helix-Loop-Helix (bHLH) proteins, act as critical transcription factors that play a key role in various developmental processes, including placental development and fetal growth during pregnancy. This review aims to explore the current understanding of HAND1 and HAND2 in pregnant maintenance and their potential implications for maternal and fetal health. We will summarize the mechanisms of action of HAND1 and HAND2 in pregnancy, their expression regulation and association with pregnancy complications such as preterm birth and preeclampsia.

Heterogeneous blood pressure treatment effects on cognitive decline in type 2 diabetes: A machine learning analysis of a randomized clinical trial.

Aim: We aimed to identify the characteristics of patients with diabetes who can derive cognitive benefits from intensive blood pressure (BP) treatment using machine learning methods.

Materials And Methods: Using data from the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes (ACCORD-MIND) study, 1349 patients with type 2 diabetes who underwent BP treatment (intensive treatment targeting a systolic BP <120 mmHg vs. standard treatment targeting <140 mmHg) were included in the machine learning analysis.

Gallstones, cholecystectomy, and cancer risk: an observational and Mendelian randomization study.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations.

mFusion: a multiscale fusion method bridging neuroimages to genes through neurotransmissions in mental health disorders.

Mental health disorders emerge from complex interactions among neurobiological processes across multiple scales, which poses challenges in uncovering pathological pathways from molecular dysfunction to neuroimaging changes. Here, we proposed a multiscale fusion (mFusion) method to evaluate the relevance of each gene to the neuroimaging traits of mental health disorders. We combined gene-neuroimaging associations with gene-positron emission tomography (PET) and PET-neuroimaging associations using protein-protein interaction networks, where various genes traced by PET maps are involved in neurotransmission.

GALNT6 drives lenvatinib resistance in hepatocellular carcinoma through autophagy and cancer-associated fibroblast activation.

Background: Hepatocellular carcinoma (HCC) remains a significant global health challenge with limited treatment options. Lenvatinib, a tyrosine kinase inhibitor, has shown promise but is often undermined by the development of drug resistance.

Methods: Utilizing high-throughput sequencing, we investigated the molecular mechanisms underlying lenvatinib resistance in HCC cells, with a focus on metabolic pathways.

ACE Loss Drives Renal Cell Carcinoma Growth and Invasion by Modulating AKT-FOXO1.

Purpose: Emerging literature links the role of the renin-angiotensin-aldosterone system (RAAS) to the progression of cancers. However, the function of RAAS has not been verified in Clear-cell renal cell carcinoma (ccRCC).

Methods: ACE expression in ccRCC tissues was determined using RT-PCR, Western blot, and immunohistochemistry staining.

Multidimensional Proteomic Landscape Reveals Distinct Activated Pathways Between Human Brain Tumors.

Brain metastases (BrMs) and gliomas are two typical human brain tumors with high incidence of mortalities and distinct clinical challenges, yet the understanding of these two types of tumors remains incomplete. Here, a multidimensional proteomic landscape of BrMs and gliomas to infer tumor-specific molecular pathophysiology at both tissue and plasma levels is presented. Tissue sample analysis reveals both shared and distinct characteristics of brain tumors, highlighting significant disparities between BrMs and gliomas with differentially activated upstream pathways of the PI3K-Akt signaling pathway that have been scarcely discussed previously.

Different Role of PET-CT Evaluation in Newly Diagnosed Follicular Lymphoma Upon Rituximab-Based Chemotherapy and Chemo-Free Immunotherapy.

Newly diagnosed follicular lymphoma (FL) patients usually received first-line rituximab-based immunochemotherapy (R-chemo). Recently, rituximab plus lenalidomide (R2) emerged as an alternative chemo-free immunotherapy. We performed a comparative analysis of positron emission tomography/computed tomography (PET/CT) in FL undergoing R-chemo or R2.

JMJD3 deficiency disturbs dopamine biosynthesis in midbrain and aggravates chronic inflammatory pain.

Midbrain dopamine (mDA) neurons participate in a wide range of brain functions through an intricate regulation of DA biosynthesis. The epigenetic factors and mechanisms in this process are not well understood. Here we report that histone demethylase JMJD3 is a critical regulator for DA biosynthesis in adult mouse mDA neurons.

Robust and interpretable deep learning system for prognostic stratification of extranodal natural killer/T-cell lymphoma.

Purpose: Extranodal natural killer/T-cell lymphoma (ENKTCL) is an hematologic malignancy with prognostic heterogeneity. We aimed to develop and validate DeepENKTCL, an interpretable deep learning prediction system for prognosis risk stratification in ENKTCL.

Methods: A total of 562 patients from four centers were divided into the training cohort, validation cohort and test cohort.

Comparative analysis of sleep physiology using qualitative and quantitative criteria for insomnia symptoms.

Despite decades of research, defining insomnia remains challenging due to its complex and variable nature. Various diagnostic systems emphasize the chronic nature of insomnia and its impact on daily functioning, relying heavily on patient self-reporting due to limitations in objective measures like polysomnography (PSG). Discrepancies between subjective experiences and objective PSG results highlight the need for more nuanced approaches, such as electroencephalogram (EEG) spectral analysis, which reveals distinct patterns of high-frequency activity in individuals with insomnia.