Pooled data from phase 3 clinical trials comparing the clinical activity of ceftolozane/tazobactam versus meropenem for the treatment of complicated intra-abdominal infections.

Background: Ceftolozane/tazobactam (C/T) in combination with metronidazole is an active antimicrobial therapy used to treat complicated intra-abdominal infections (cIAIs).

Methods: A comparison of the clinical efficacy of C/T plus metronidazole vs. meropenem for the treatment of cIAIs using pooled data from four phase 3 clinical studies (CXA-cIAI-10-08, CXA-cIAI-10-09, NCT02739997 and NCT03830333).

Pseudouridine synthase 1-targeted therapy activates antiviral immunity to boost cancer immunotherapy.

Pseudouridine is the most abundant epitranscriptomic modification, but its cellular functions remain poorly understood. Here, we identify pseudouridine synthase 1 (PUS1) as a key driver of tumor immune evasion. Specifically, we find that PUS1 is aberrantly overexpressed in tumors and correlates with tumor malignant progression.

Associations of Physical Frailty, Social Deficits, and Cognitive Impairment with Risk of 45 Incident Non-Communicable Diseases: The Mediating Role of Accelerated Biological Aging-A Prospective Cohort Study.

Objectives: Frailty extends beyond a physical construct to encompass cognitive and social functioning. We aimed to assess the associations of these impairments, individually and in combination, with the risk of 45 non-communicable diseases (NCDs), and explore the role of accelerated biological aging.

Design And Setting: A prospective cohort study was conducted using data from the UK Biobank.

Association of cerebrospinal fluid FGF21 with sleep quality in Chinese adults.

Objective: This study aimed to examine whether FGF21 levels in cerebrospinal fluid (CSF) and plasma are associated with sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI) scores, and to assess the correlation between FGF21 levels and sleep disorder severity.

Methods: We recruited 90 Chinese adult males undergoing anterior cruciate ligament reconstruction surgery, gathering sociodemographic and clinical characteristics. Sleep quality was assessed using the PSQI, and CSF samples were obtained for FGF21 analysis.

ICMC: An Interpretable Cross-domain Multi-modal Classification model for grading teaching plan.

Multi-modal classification aims to extract pertinent information from various modalities to assign labels to instances. The advent of deep neural networks has significantly advanced this task. However, the majority of current deep neural networks lack interpretability, leading to skepticism.

Genome-wide selection signal analysis reveals the adaptability of Tibetan sheep to high altitudes.

Altitude adaptation is a complex process involving multiple physiological and biochemical responses to hypoxia and other environmental stresses. In-depth genetic analysis of Tibetan sheep, which exhibit significant adaptations to high-altitude hypoxia, promises to elucidate hypoxia-tolerance mechanisms in plateau animals. Here, we conducted a genome-wide selection scan on three Tibetan sheep populations: low-altitude Tao (TS; 2887 m), medium-altitude Tianjun white (WT; 3331 m), and high-altitude Huoerba (HB; 4614 m).

Exploring Novel Biomarkers for Rosacea Through Cohort Study and Mendelian Randomisation.

The current therapeutic landscape for rosacea is notably deficient in targeted medications, underscoring an urgent need for the identification of novel biomarkers. Utilising a longitudinal cohort of 54 306 individuals from the UK Biobank (UKB), we conducted a comprehensive assessment of the associations between 2923 serum proteins and the risk for rosacea. Our cohort analysis identified 18 proteins significantly associated with rosacea risk.

Theileria luwenshuni and Novel Babesia spp. Infections in Humans, Yunnan Province, China.

Piroplasmid parasites such as Theileria luwenshuni protozoa pose a global threat to both animal and human health. However, human theileriosis remains underexplored compared to infections caused by Plasmodium and Babesia species parasites. We investigated potential hemoparasite infections among 1,721 persons with fever, anemia, or both in Yunnan Province, China.

Psychological experiences of family caregivers of patients with chronic obstructive pulmonary disease (COPD) from the perspective of perceived benefit finding: a qualitative study in Shenzhen, China.

Objective: This study aims to explore and investigate the positive experiences and the benefit finding among family caregivers of patients with chronic obstructive pulmonary disease (COPD) during the caregiving process.

Design: A semi-structured interview was conducted with eight caregivers of individuals diagnosed with COPD, employing a phenomenological approach typical of qualitative research. The interview data were analysed using the Colaizzi's 7-step method, which facilitated a systematic examination, summarisation and identification of themes within the data.

Nanoshield Architecture Harnessing Neoantigen-Targeting Peptides Enables Durable Post-surgical Glioma Immunotherapy.

Despite advances in immunotherapy, its efficacy against postoperative glioma recurrence remains limited. Here, we present a neoantigen-targeting peptide nanoshield that synergizes with glioma resection to eliminate residual tumor cells and prevent relapse. The nanoshield architecture is constructed using a multicationic protein (MCP) as the structural scaffold, which is assembled with the mutated isocitrate dehydrogenase 1 (muIDH1) neoantigen.

The difference in the effect of methadone and protracted abstinence on the coupling among key large-scale brain networks of individuals with heroin use disorder: A resting-state fMRI study.

Background: Methadone maintenance treatment (MMT) and protracted abstinence (PA) effectively reduce the craving for heroin among individuals with heroin use disorder (HUD). However, the difference in their effects on brain function, especially the coupling among the large-scale brain networks (default mode [DMN], salience [SN], and executive control [ECN] networks), remains unclear. This study analyzed the effects of the MMT and PA on these networks and the predictive value of the bilateral resource allocation index (RAI) for craving for heroin.

Genetic Contribution to Treatment-Related Dyslipidemia in Adult Survivors of Childhood Cancer: Findings from the CCSS, SJLIFE, and DCCSS-LATER Cohorts.

BACKGROUND Dyslipidemia can occur as a long-term side effect of childhood cancer treatment. The difference in prevalence among children receiving comparable treatment suggests a role for genetic variation. We conducted the first genome-wide association study on dyslipidemia in a large childhood cancer survivor cohort, using three additional cohorts for replication.

Ultrahigh Energy Density in Dielectric Polymers Near Glass Transition Temperature by Molecular Twisting Conformation Locking.

Dielectric polymers with high operating temperatures (T) for capacitive energy storage applications are urgently needed in new energy vehicles and power electronics. Polymers with high glass transition temperatures (T), such as Kapton polyimide (T≈360 °C), suffer low T (< 150 °C) due to electron delocalization between donor and acceptor units. Here, a molecular twisting conformation-locking strategy is proposed for high-temperature dielectric polymers to block intrachain and interchain electron migration pathways.

Integrating multi-omics proteomic approaches in deciphering the tumor microenvironment and therapeutic resistance mechanisms in prostate cancer.

Prostate cancer (PCa) is one of the main causes of cancer-related mortality. The tumor microenvironment (TME) and the development of drug resistance pose significant challenges to effective cancer therapy. This review explores the integration of multi-omics proteomic approaches to decipher the complex interactions within the TME and the mechanisms driving resistance in PCa.

HWI encoding/decoding of a non-invasive HWI-BCI paradigm based on temporal variation abundance scale.

The performance of non-invasive Handwriting Imagery (HWI) input in Brain-computer interface (BCI) systems is highly dependent on the paradigms employed, yet there is limited research on interpretable scales to measure how HWI-BCI paradigms and neural encoding designs affect performance. This study introduces the "Temporal Variation Abundance" metric and utilizes it to design two classes of handwriting imagery paradigms: Low Temporal Variation Abundance (LTVA) and High Temporal Variation Abundance (HTVA). A dynamic time warping algorithm based on random templates (rt-DTW) is proposed to align HWI velocity fluctuations using EEG.

Deep learning-based spatial analysis on tumor and immune cells of pathology images predicts MIBC prognosis.

Objective: Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease with a poor prognosis. This study aims to explore the correlation between the spatial distribution of lymphocyte aggregates and the prognosis of MIBC using deep learning.

Methods: Whole-slide images (WSIs) and clinical information of MIBC patients were collected from The Cancer Genome Atlas (TCGA) and the HBlaU079Su01 microarray.

Biotransformation and disposition of C-labeled sonrotoclax ([C]BGB-11417) in preclinical safety species and characterization of unique contribution from gut microbiome.

Introduction: Sonrotoclax (BGB-11417), a second-generation B-cell lymphoma-2 (BCL-2) inhibitor currently in clinical development, requires comprehensive verification of its biotransformation and disposition profiles in safety species.

Methods: [C]BGB-11417 was employed to assess its pharmacokinetics, excretion, tissue distribution and metabolite profiles in mice and dogs. Radioactivity in plasma and excreta were analyzed to determine pharmacokinetics and mass balance.

Projection of ENSO using observation-informed deep learning.

The El Niño-Southern Oscillation (ENSO) profoundly impacts global climate, but its sea surface temperature (SST) variability projected by climate models remains uncertain, with a substantial inter-model spread in 21st-century projections. Model-observation discrepancies in ENSO physics contribute to this uncertainty, necessitating observational constraints to refine projections. However, methods to achieve this constraint remain unclear.

Synthetic biology-driven design and bioproduction of mechanical proteins.

Structural proteins, with exceptional structural versatility and tailored properties, have inspired the design of mechanically robust biomaterials with diverse applications. Nevertheless, the heterologous biosynthesis of high-performance structural proteins faces inherent challenges due to their characteristic high molecular weight, highly repetitive sequences, and intricate folding patterns, frequently leading to reduced production yields, structural defects, and compromised mechanical properties. To overcome these limitations, researchers have adopted various strategies to refine sequence architectures and optimize heterologous expression systems of recombinant structural proteins.

Association Between Soy Product Intake and Insomnia in Chinese Middle-Aged and Older Adults: A Cross-Sectional Study.

Background And Objective: Insomnia has various adverse effects on middle-aged and older adults. Improving insomnia by adjusting diet has attracted attention. This study investigated the relationship between soy product intake and insomnia in middle-aged and older adults and explored the role of inflammatory factors.

Cost-Effectiveness and Cost-Utility Analysis of Tongxinluo Capsules Compared With Conventional Therapy for the Treatment of Acute Myocardial Infarction.

Aim: Tongxinluo (TXL) capsule, a traditional Chinese medicine compound, has proven effective in acute myocardial infarction (AMI), but its cost-effectiveness is unclear.

Methods: This economic evaluation utilized individual data from clinical trials to compare major adverse cardiac and cerebrovascular events (MACCEs) at 30 days and quality-adjusted life years (QALYs) at 1 year between an intervention group (TXL combined with conventional therapy) and the control group (placebo plus conventional therapy), from a healthcare perspective. A lifetime cost-utility analysis (CUA) was conducted using a Markov model, and sensitivity analyses were performed to evaluate the robustness of the results.

Baicalin Induces Mesenchymal-Epithelial Transition in Chronic Pancreatitis Through Upregulation of E-Cadherin.

Introduction: Baicalin has achieved the potential in the treatment of chronic pancreatitis (CP).To explore the potential of Baicalin on the induction of mesenchymal-epithelial transition (MET) in chronic pancreatitis.

Materials: To explore the causal association between CP and E-cadherin through bidirectional Mendelian randomization (MR).

Perfluoroalkyl Substance (PFAS) Mixtures Drive Rheumatoid Arthritis Risk Through Immunosuppression: Integrating Epidemiology and Mechanistic Evidence.

Perfluoroalkyl substances (PFASs) possess immunosuppressive properties. However, their association with rheumatoid arthritis (RA) risk remains inconclusive across epidemiological studies. This study integrates population-based and mechanistic evidence to clarify the relationship between PFAS exposure and RA.

ELF6 mutation suppresses the dwarf phenotype of Arabidopsis ino80 mutant by modulating cell cycle progression.

The chromatin-remodeling factor INO80 is conserved across eukaryotes and plays important roles in various biological processes. However, its upstream regulators remain unclear. This study aimed to identify new regulators of INO80 in Arabidopsis and to uncover its molecular mechanism in plant growth.

Asymmetric point-spread function in the tilted plane.

In this article, we focus on the problem of sampling a point spread function (PSF) in a tilted plane for computational wave optics and holography. Conventionally, the PSF represents a symmetric wavefield distribution expressed in an orthogonal plane to the target hologram. In contrast, we reveal the wavefield for a point-spread function over a tilted plane, showing an asymmetric structure depending on the tilt angle.