Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer's disease in humans.

Background: Alzheimer's disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear.

Method: In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform.

The sequence-structure-function relationship of intrinsic ERα disorder.

The oestrogen receptor (ER or ERα), a nuclear hormone receptor that drives most breast cancer, is commonly activated by phosphorylation at serine 118 within its intrinsically disordered N-terminal transactivation domain. Although this modification enables oestrogen-independent ER function, its mechanism has remained unclear despite ongoing clinical trials of kinase inhibitors targeting this region. By integration of small-angle X-ray scattering and nuclear magnetic resonance spectroscopy with functional studies, we show that serine 118 phosphorylation triggers an unexpected expansion of the disordered domain and disrupts specific hydrophobic clustering between two aromatic-rich regions.

Host metabolism balances microbial regulation of bile acid signalling.

Metabolites derived from the intestinal microbiota, including bile acids (BA), extensively modulate vertebrate physiology, including development, metabolism, immune responses and cognitive function. However, to what extent host responses balance the physiological effects of microbiota-derived metabolites remains unclear. Here, using untargeted metabolomics of mouse tissues, we identified a family of BA-methylcysteamine (BA-MCY) conjugates that are abundant in the intestine and dependent on vanin 1 (VNN1), a pantetheinase highly expressed in intestinal tissues.

A vision-language foundation model for precision oncology.

Clinical decision-making is driven by multimodal data, including clinical notes and pathological characteristics. Artificial intelligence approaches that can effectively integrate multimodal data hold significant promise in advancing clinical care. However, the scarcity of well-annotated multimodal datasets in clinical settings has hindered the development of useful models.

Artificial intelligence for body composition assessment focusing on sarcopenia.

This study aimed to address the limitations of conventional methods for measuring skeletal muscle mass for sarcopenia diagnosis by introducing an artificial intelligence (AI) system for direct computed tomography (CT) analysis. The primary focus was on enhancing simplicity, reproducibility, and convenience, and assessing the accuracy and speed of AI compared with conventional methods. A cohort of 3096 cases undergoing CT imaging up to the third lumbar (L3) level between 2011 and 2021 were included.

Microglia depletion reduces neurodegeneration and remodels extracellular matrix in a mouse Parkinson's disease model triggered by α-synuclein overexpression.

Chronic neuroinflammation with sustained microglial activation occurs in Parkinson's disease (PD), yet the mechanisms and exact contribution of these cells to the neurodegeneration remains poorly understood. In this study, we induced progressive dopaminergic neuron loss in mice via rAAV-hSYN injection to cause the neuronal expression of α-synuclein, which produced neuroinflammation and behavioral alterations. We administered PLX5622, a colony-stimulating factor 1 receptor inhibitor, for 3 weeks prior to rAAV-hSYN injection, maintaining it for 8 weeks to eliminate microglia.

Influence of ESBL colonization status on gut microbiota composition during allogenic hematopoietic stem cell transplantation.

After allogeneic HSCT (allo-HSCT), the diversity of the intestinal microbiota significantly decreases. The changes can be rapid and are thought to be caused by chemotherapy, antibiotics, or intestinal inflammation. Most patients are exposed to prophylactic and therapeutic antibiotics during neutropenia and several patients are colonized by ESBL bacteria.

Stereo-seq of the prefrontal cortex in aging and Alzheimer's disease.

Aging increases the risk for Alzheimer's disease (AD), driving pathological changes like amyloid-β (Aβ) buildup, inflammation, and oxidative stress, especially in the prefrontal cortex (PFC). We present the first subcellular-resolution spatial transcriptome atlas of the human prefrontal cortex (PFC), generated with Stereo-seq from six male AD cases at varying neuropathological stages and six age-matched male controls. Our analyses revealed distinct transcriptional alterations across PFC layers, highlighted disruptions in laminar structure, and exposed AD-related shifts in layer-to-layer and cell-cell interactions.

CCR5-ligand decorated rilpivirine lipid-based nanoparticles for sustained antiretroviral responses.

Antiretroviral therapy (ART) improves the quality of life for those living with the human immunodeficiency virus type one (HIV-1). However, poor compliance reduces ART effectiveness and leads to immune compromise, viral mutations, and disease co-morbidities. Here we develop a drug formulation in which a lipid-based nanoparticle (LBNP) carrying rilpivirine (RPV) is decorated with the C-C chemokine receptor type 5 (CCR5) targeting peptide.

Qualitative assessment of primary care providers' attitudes toward genetic services and genetics education.

As the role of primary care providers (PCPs) in genetic medicine increases, there is a need for training related to the integration of genetics into primary care. However, little is known about PCPs' attitudes towards and perceived needs for such training. We conducted semi-structured interviews with nine PCPs to capture information about their perceptions of their role in genetics and their continuing medical educational needs related to genetics in primary care, and we conducted thematic analysis.

PET Imaging of Sphingosine-1-Phosphate Receptor 1 with [F]TZ4877 in Nonhuman Primates.

Purpose: The sphingosine-1-phosphate receptor-1 (S1PR) is involved in regulating responses to neuroimmune stimuli. There is a need for S1PR-specific radioligands with clinically suitable brain pharmcokinetic properties to complement existing radiotracers. This work evaluated a promising S1PR radiotracer, [F]TZ4877, in nonhuman primates.

Mortality, Hepatic Decompensation, and Cardiovascular Outcomes in Lean vs. Non-lean MASLD Cirrhosis: A Veterans Affairs Cohort Study.

Background And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) has a global prevalence of 25%. Studies on incident liver and cardiovascular outcomes in lean (Body mass index: BMI < 25 kg/m, or < 23 kg/m for Asians) vs. non-lean individuals with MASLD have reported mixed results.

Early outcomes of robotic vs open living donor right hepatectomy in a US Center.

Background: Robotic living donor hepatectomy offers potential advantages but has been limited to high-volume centers, primarily in Asia and the Middle East. We report our experience establishing a robotic living donor right hepatectomy program in a U.S.

SLC10A7 regulates O-GalNAc glycosylation and Ca homeostasis in the secretory pathway: insights into SLC10A7-CDG.

Glycans are known to be fundamental for many cellular and physiological functions. Congenital disorders of glycosylation (CDG) currently encompassing over 160 subtypes, are characterized by glycan synthesis and/or processing defects. Despite the increasing number of CDG patients, therapeutic options remain very limited as our knowledge on glycan synthesis is fragmented.

The beneficial effect of adding belimumab in severe and refractory IgA nephropathy: a case report.

IgA nephropathy (IgAN) is one of the most common primary glomerular diseases worldwide and is the most common cause of chronic kidney disease (CKD) in China. It lacks recommended treatment in refractory IgAN after conventional therapy. Belimumab, a recombinant human IgG-1λ monoclonal antibody that inhibits the B lymphocyte stimulator, is recommended to treat active lupus nephritis.

Large language models for the mental health community: framework for translating code to care.

Large language models (LLMs) offer promising applications in mental health care to address gaps in treatment and research. By leveraging clinical notes and transcripts as data, LLMs could improve diagnostics, monitoring, prevention, and treatment of mental health conditions. However, several challenges persist, including technical costs, literacy gaps, risk of biases, and inequalities in data representation.

Continuous vital sign monitoring of patients recovering from surgery on general wards: a narrative review.

Most postoperative deaths occur on general wards, often linked to complications associated with untreated changes in vital signs. Monitoring in these units is typically intermittent checks each shift or maximally every 4-6 h, which misses prolonged periods of subtle changes in physiology that can herald a critical downstream event. Continuous monitoring of vital signs is therefore intuitively necessary for patient safety.

Effectiveness of 4-dimensional maximum intensity projection (4D-MIP) for respiratory motion management with uncertain interobserver delineation.

This study was conducted to evaluate the use of 4-dimensional (4D) maximum intensity projection (4D-MIP) to compensate for the disadvantages of average intensity projection (AIP), which is used to determine the internal target volume (ITV) in lung tumors. A respiratory motion phantom with a simulated tumor was imaged using 4D computed tomography (4D-CT). AIP and 4D-MIP were generated based on 10 phases of 4D-CT, followed by contouring of the ITV and ITV; these were compared with the ITV contoured in 10 phases of 4D-CT (ITV).

Preoperative frailty in oesophageal cancer: postoperative outcomes and overall survival - meta-analysis and systematic review.

Purpose: To assess the prevalence of preoperative frailty in patients with oesophageal cancer and its impact on postoperative outcomes and overall survival.

Methods: A comprehensive computer-based search of the CNKI, Wanfang, VIP, CBM, PubMed, Embase, Cochrane Library, Web of Science and CINAHL databases was conducted for articles related to preoperative frailty in patients with oesophageal cancer. The search was carried out from the time of the construction of the database to 20 April 2024.

Airway associated inflammation in post-transplant cystic fibrosis patients as a predictor of chronic lung allograft dysfunction (CLAD).

Aims: In cystic fibrosis lung transplant recipients (LTRs), graft dysfunction due to acute infections, rejection or chronic lung allograft dysfunction (CLAD) is difficult to distinguish. Characterisation of the airway inflammatory milieu could help detect and prevent graft dysfunction. We speculated that an eosinophil or neutrophil-rich milieu is associated with higher risk of CLAD.

Deciphering risk factors for severe postherpetic neuralgia in patients with herpes zoster: an interpretable machine learning approach.

Introduction: Postherpetic neuralgia (PHN) is a common complication of herpes zoster (HZ). This study aimed to use a large real-world electronic medical records database to determine the optimal machine learning model for predicting the progression to severe PHN and to identify the associated risk factors.

Methods: We analyzed the electronic medical records of 23,326 patients diagnosed with HZ from January 2010 to June 2020.

[Disseminated toxoplasmosis after cord blood transplantation diagnosed at autopsy].

A 54-year-old woman underwent cord blood transplantation in second remission of acute myeloid leukemia. She tested positive for anti-toxoplasma IgG antibody before transplantation. After neutrophil engraftment, she complained of foggy vision, but brain MRI showed no abnormality.

Hypertriglyceridemia and younger age are associated with effectiveness of growth hormone therapy on hepatic steatosis.

Adult growth hormone deficiency (AGHD) is often accompanied with metabolic dysfunction-associated steatotic liver disease (MASLD). Although some studies reported that MASLD is ameliorated by growth hormone replacement therapy (GHRT), the characteristics of AGHD that are associated with an improvement of hepatic steatosis by GHRT remain unknown. We aimed to investigate whether GHRT affects hepatic lipid accumulation as well as biochemical parameters, and investigated the association between these parameters (UMIN000044989).