Molecular Profiling of Mouse Models of Loss or Gain of Function of the KCNT1 (Slack) Potassium Channel and Antisense Oligonucleotide Treatment.

The potassium sodium-activated channel subtype T member 1 () gene encodes the Slack channel K1.1, which is expressed in neurons throughout the brain. Gain-of-function variants in are associated with a spectrum of epilepsy syndromes, and mice carrying those variants exhibit a robust phenotype similar to that observed in patients.

Falling Detection of Toddlers Based on Improved YOLOv8 Models.

If toddlers are not promptly checked and rescued after falling from relatively high locations at homes, they are at risk of severe health complications. We present a toddler target extraction method and real-time falling alarm. The procedure is executed in two stages: In stage I, a GELAN-integrated YOLOv8 model is used to extract the body features.

Real-world impact of emicizumab and immunosuppression on acquired hemophilia A: a multicenter US cohort.

Acquired hemophilia A (AHA) is an autoimmune bleeding disorder that is caused by factor VIII (FVIII) autoantibodies with high morbidity and mortality due to bleeding and complications from immunosuppression (IST). To address the real-world implications of the FVIII mimetic antibody, emicizumab, and the role of IST, we retrospectively collected de-identified data on 62 patients with AHA who were treated off-label with emicizumab for a median of 10 weeks at 12 US-based hemophilia treatment centers. Most patients (95.

ATP-dependent remodeling of chromatin condensates uncovers distinct mesoscale effects of two remodelers.

ATP-dependent chromatin remodeling enzymes mobilize nucleosomes, but how such mobilization affects chromatin condensation is unclear. Here, we investigate effects of two major remodelers, ACF and RSC using chromatin condensates and single-molecule footprinting. We find that both remodelers inhibit the formation of condensed chromatin.

Chinese Society of Clinical Oncology (CSCO) Breast Cancer guidelines 2024.

Background: Developing guidelines for the diagnosis and treatment of common cancers in China based on the evidence-based practice, the availability of diagnosis and treatment products, and the up-to-date advances in precision medicine is one of the basic tasks of the Chinese Society of Clinical Oncology Breast Cancer (CSCO BC) Committee.

Methods: Protocols with high evidence level and good availability are used as the Level I recommendations; protocols with relatively high evidence level but slightly lower expert consensus or with poor availability are used as the Level II recommendations; and protocols that are clinically applicable but with low evidence level are regarded as the Level III recommendations. Based on the findings of clinical research at home and abroad and the opinions of CSCO BC experts, the CSCO BC guidelines determine the levels of recommendations for clinical application.

The INVISION Talar Component in Revision Total Ankle Arthroplasty: Analysis of Early Outcomes.

Introduction: Launched in 2018 for revision total ankle arthroplasty (rTAA), the INVISION talar component addresses subsidence when poor talar bone stock is present. Due to the recency of the market-availability of the INVISION, studies evaluating its efficacy are lacking. This study presents the first analysis of early-term outcomes of patients undergoing rTAA with the INVISION talar component.

Metabolic reprogramming in hepatocellular carcinoma: a bibliometric and visualized study from 2011 to 2023.

Background And Aims: Metabolic reprogramming has been found to be a typical feature of tumors. Hepatocellular carcinoma (HCC), a cancer with high morbidity and mortality, has been extensively studied for its metabolic reprogramming-related mechanisms. Our study aims to identify the hotspots and frontiers of metabolic reprogramming research in HCC and to provide guidance for future scientific research and decision-making in HCC metabolism.

Top-down proteomics.

Proteoforms, which arise from post-translational modifications, genetic polymorphisms and RNA splice variants, play a pivotal role as drivers in biology. Understanding proteoforms is essential to unravel the intricacies of biological systems and bridge the gap between genotypes and phenotypes. By analysing whole proteins without digestion, top-down proteomics (TDP) provides a holistic view of the proteome and can decipher protein function, uncover disease mechanisms and advance precision medicine.

Postoperative Nausea and Vomiting in Female Patients Undergoing Laparoscopic Gastrointestinal Surgery with Double Prophylactic Therapy.

 Postoperative nausea and vomiting (PONV) is a major problem after surgery. This study aimed to demonstrate the incidence of PONV and the potential associated factors in female patients undergoing laparoscopic gastrointestinal surgery against the background of double prophylactic therapy.  Our retrospective study recruited 109 female patients undergoing laparoscopic gastrointestinal surgery with double prophylactic therapy, combining palonosetron with dexamethasone, from October 2020 to March 2021, at the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Scanning the aged to minimize missed injury: An Eastern Association for the Surgery of Trauma multicenter study.

Background: Despite the high incidence of blunt trauma in older adults, there is a lack of evidence-based guidance for computed tomography (CT) imaging in this population. We aimed to identify an algorithm to guide use of a pan-scan (head/cervical spine [C-spine]/torso) or a selective scan (head/C-spine ± torso). We hypothesized that a patient's initial history and examination could be used to guide imaging.

Alectinib in Resected -Positive Non-Small-Cell Lung Cancer.

Background: Platinum-based chemotherapy is the recommended adjuvant treatment for patients with resectable, -positive non-small-cell lung cancer (NSCLC). Data on the efficacy and safety of adjuvant alectinib as compared with chemotherapy in patients with resected -positive NSCLC are lacking.

Methods: We conducted a global, phase 3, open-label, randomized trial in which patients with completely resected, -positive NSCLC of stage IB (tumors ≥4 cm), II, or IIIA (as classified according to the seventh edition of the of the American Joint Committee on Cancer and Union for International Cancer Control) were randomly assigned in a 1:1 ratio to receive oral alectinib (600 mg twice daily) for 24 months or intravenous platinum-based chemotherapy in four 21-day cycles.

Diisoprenyl Cyclohexene-Type Meroterpenoids with Cytotoxic Activity from a Mangrove Endophytic Fungus sp. GXNU-Y85.

Five new diisoprenyl cyclohexene-type meroterpenoids, aspergienynes J-N (-), along with three known analogues (-), were obtained from the mangrove endophytic fungal strain sp. GXNU-Y85. The chemical structures, including their absolute configurations, were established via spectroscopic data and comparison of experimental and calculated ECD spectra.

A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings.

Obesity is a major public health crisis. Multi-specific peptides have emerged as promising therapeutic strategies for clinical weight loss. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are endogenous incretins that regulate weight through their receptors (R).

A phase Ib trial of pembrolizumab plus paclitaxel or flat-dose capecitabine in 1st/2nd line metastatic triple-negative breast cancer.

Chemoimmunotherapy with anti-programmed cell death 1/ligand 1 and cytotoxic chemotherapy is a promising therapeutic modality for women with triple-negative breast cancer, but questions remain regarding optimal chemotherapy backbone and biomarkers for patient selection. We report final outcomes from a phase Ib trial evaluating pembrolizumab (200 mg IV every 3 weeks) with either weekly paclitaxel (80 mg/m weekly) or flat-dose capecitabine (2000 mg orally twice daily for 7 days of every 14-day cycle) in the 1st/2nd line setting. The primary endpoint is safety (receipt of 2 cycles without grade III/IV toxicities requiring discontinuation or ≥21-day delays).

Glioblastoma Stem Cell Targeting Peptide Isolated Through Phage Display Binds Cadherin 2.

Glioblastoma stem cells (GSCs) have unique properties of self-renewal and tumor initiation that make them potential therapeutic targets. Development of effective therapeutic strategies against GSCs requires both specificity of targeting and intracranial penetration through the blood-brain barrier. We have previously demonstrated the use of in vitro and in vivo phage display biopanning strategies to isolate glioblastoma targeting peptides.

An MRI Deep Learning Model Predicts Outcome in Rectal Cancer.

Background Deep learning (DL) models can potentially improve prognostication of rectal cancer but have not been systematically assessed. Purpose To develop and validate an MRI DL model for predicting survival in patients with rectal cancer based on segmented tumor volumes from pretreatment T2-weighted MRI scans. Materials and Methods DL models were trained and validated on retrospectively collected MRI scans of patients with rectal cancer diagnosed between August 2003 and April 2021 at two centers.

Early-Life Cardiovascular Risk Factor Trajectories and Vascular Aging in Midlife: A 30-Year Prospective Cohort Study.

Background: Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular outcomes. We aimed to explore the associations of individual cardiovascular risk factors from childhood to midlife and their accumulation over a 30-year span with vascular aging in midlife.

Methods: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 2180 participants aged 6 to 18 years at baseline were followed for over 30 years.