targeted

BACKGROUND: Aging-related processes contribute to neurodegeneration and disability in multiple sclerosis (MS). Biomarkers of biological aging such as leukocyte telomere length (LTL) could help personalise prognosis. Pregnancy has been shown to be protective against disability accumulation in women with MS, though it is unclear if this effect relates to aging mechanisms or LTL. OBJECTIVES: This study aimed to cross-sectionally characterise LTL in a cohort of individuals with MS, and to correlate LTL with disability severity and pregnancy history...

Traditional Chinese Medicine (TCM) is a supremely valuable resource for the development of drug discovery. Few methods are capable of hunting for potential molecule ligands from TCM towards more than one single protein target. In this study, a novel dual-target surface plasmon resonance (SPR) biosensor was developed to perform targeted compound screening of two key proteins involved in the cellular invasion process of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): the spike (S) protein receptor binding domain (RBD) and the angiotensin-converting enzyme 2 (ACE2)...

Purpose: Continuous exposure to ionizing radiation at a low dose rate poses significant health risks to humans on deep space missions, prompting the need for mechanistic studies to identify countermeasures against its deleterious effects. Mitochondria are a major subcellular locus of radiogenic injury, and may trigger secondary cellular responses through the production of reactive oxygen species (mtROS) with broader biological implications. Methods and Materials: To determine the contribution of mtROS to radiation-induced cellular responses, we investigated the impacts of protracted γ-ray exposures (IR; 1...

BACKGROUND: Social media is essential in the lives of adolescents, with 97% of US teenagers engaging daily. While it facilitates communication, learning, and identity development, it also poses risks like harmful content exposure and psychological distress, particularly for adolescents in their critical developmental stage. Teaching digital life skills innovatively counters these risks, adapting traditional competencies such as decision-making, problem-solving, creative and critical thinking, communication, interpersonal skills, self-awareness, empathy, and emotional and stress management to digital challenges...

Storage is important for the garlic cloves industry because it is critical to enabling a year-round supply. This study aimed to investigate the changes in biochemical and metabolic profiles in garlic cloves in terms of different temperatures and cultivars during storage using nontargeted and targeted metabolomics. The results showed that the storage temperatures and times were important factors affecting the composition and metabolite content of garlic cloves. In detail, the metabolic profiling of garlic cloves changed significantly at 22 °C, which was mainly related to sprouting...

BACKGROUND: Healthy Davis Together was a program launched in September 2020 in the city of Davis, California, to mitigate the spread of COVID-19 and facilitate the return to normalcy. The program involved multiple interventions, including free saliva-based asymptomatic testing, targeted communication campaigns, education efforts, and distribution of personal protective equipment, community partnerships, and investments in the local economy. OBJECTIVE: This study identified demographic characteristics of individuals that underwent testing and assessed adherence to testing over time in a community pandemic-response program launched in a college town in California, United States...

BACKGROUND: Particle mini-beam therapy exhibits promise in sparing healthy tissue through spatial fractionation, particularly notable for heavy ions, further enhancing the already favorable differential biological effectiveness at both target and entrance regions. However, breathing-induced organ motion affects particle mini-beam irradiation schemes since the organ displacements exceed the mini-beam structure dimensions, decreasing the advantages of spatial fractionation. PURPOSE: In this study, the impact of breathing-induced organ motion on the dose distribution was examined at the target and organs at risk(OARs) during carbon ion mini-beam irradiation for pancreatic cancer...

In preparation for 90Y radioembolization for hepatic malignancies, hepatic angiography is performed with intra-arterial delivery of 99mTc-macroaggregated albumin (MAA), known as premapping. This initial procedure allows for evaluation of standard/variant hepatic arterial anatomy using MAA as a surrogate marker for the delivery of 90Y to visualize the likely distribution of 90Y. Premapping allows for the assessment of at-risk extrahepatic targets and for the quantification of hepatopulmonary shunting. We present cases where MAA scintigraphic images reveal unusual perfusion patterns in hepatic cancers, treated with 90Y glass microspheres (Therasphere; Boston Scientific, Marlborough, MA)...

An 83-year-old woman with newly diagnosed multiple myeloma (MM) was enrolled in our 68Ga-pentixather and 68Ga-pentixafor PET/CT trial for evaluation of tumor burden. 68Ga-pentixather PET/CT detected more focal bone lesions, and the uptake levels of focal bone lesions on 68Ga-pentixather PET/CT were higher than those on 68Ga-pentixafor PET/CT. This suggests that 68Ga-pentixather PET/CT may be an alternative imaging modality and more sensitive in detecting MM lesions than 68Ga-pentixafor PET/CT.

Perioperative neurocognitive disorder (PND) is a common complication in surgical patients. While many interventions to prevent PND have been studied, the availability of treatment methods is limited. Thus, it is crucial to delve into the mechanisms of PND, pinpoint therapeutic targets, and develop effective treatment approaches. In this study, reduced dorsal tenia tecta (DTT) neuronal activity was found to be associated with tibial fracture surgery-induced PND, indicating that a neuronal excitation-inhibition (E-I) imbalance could contribute to PND...

BACKGROUND AND OBJECTIVES: Clinical heterogeneity of patients with Parkinson disease (PD) is well recognized. PD with REM sleep behavior disorder (RBD) is a more malignant phenotype with faster motor progression and higher nonmotor symptom burden. However, the neural mechanisms underlying this clinical divergence concerning imbalances in neurotransmitter systems remain elusive. METHODS: Combining magnetic resonance (MR) spectroscopy and [11 C]ABP688 PET on a PET/MR hybrid system, we simultaneously investigated two different mechanisms of glutamate signaling in patients with PD...

Amidst the present healthcare issues, diabetes is unique as an emerging class of affliction with chronicity in a majority of the population. To check and control its effects, there have been huge turnover and constant development of management strategies, and though a bigger part of the health care area is involved in achieving its control and the related issues such as the effect of diabetes on wound healing and care and many of the works have reached certain successful outcomes, still there is a huge lack in managing it, with maximum effect yet to be attained...

PURPOSE OF THE REPORT: 18F-PBR06-PET targeting 18-kDa translocator protein can detect abnormal microglial activation (MA) in multiple sclerosis (MS). The objectives of this study are to develop individualized mapping of MA using 18F-PBR06, to determine the effect of disease-modifying treatment (DMT) efficacy on reducing MA, and to determine its clinical, radiological, and serological correlates in MS patients. PATIENTS AND METHODS: Thirty 18F-PBR06-PET scans were performed in 22 MS patients (mean age, 46 ± 13 years; 16 females) and 8 healthy controls (HCs)...

Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous disease with distinct molecular subtypes described as classical/progenitor and basal-like/squamous PDAC. We hypothesized that integrative transcriptome and metabolome approaches can identify candidate genes whose inactivation contributes to the development of the aggressive basal-like/squamous subtype. Using our integrated approach, we identified endosome-lysosome associated apoptosis and autophagy regulator 1 (ELAPOR1/KIAA1324) as a candidate tumor suppressor in both our NCI-UMD-German cohort and additional validation cohorts...

No abstract text is available yet for this article.

PURPOSE: Several recurring pathogenic variants (PVs) in BRCA1/BRCA2 and additional cancer susceptibility genes are described in the ethnically diverse Israeli population. Since 2019, testing for these recurring PVs is reimbursed unselectively for all patients with breast cancer (BC) in Israel. The aim was to evaluate the yield of genotyping for these PVs in non-Ashkenazi Jewish (AJ) patients with BC diagnosed ≥age 50 years. METHODS: Clinical and genotyping data of all patients with BC undergoing oncogenetic counseling at the Oncology Institute at Sheba Medical Center from June 2017 to December 2023 were reviewed...

Cucumber (Cucumis sativus, Cs) tendrils are slender vegetative organs that typically require manual removal to ensure orderly growth during greenhouse cultivation. Here, we identified cucumber tendril-less (tl), a Tnt1 retrotransposon-induced insertion mutant lacking tendrils. Map-based cloning identified the mutated gene, CsaV3_3G003590, which we designated as CsTL, which is homologous to Arabidopsis thaliana LATERAL SUPPRESSOR (AtLAS). Knocking out CsTL repressed tendril formation but did not affect branch initiation, whereas overexpression of CsTL resulted in the formation of two or more tendrils in one leaf axil...

Pathomechanisms that activate oncogenic B-cell receptor (BCR) signaling in diffuse large B-cell lymphoma (DLBCL), are largely unknown. Kelch-like family member 6 (KLHL6) encoding a substrate-adapter for Cullin-3-RING E3 ubiquitin-ligase (CRL) with poorly established targets is recurrently mutated in DLBCL. By applying high-throughput protein interactome screens and functional characterization, we discovered that KLHL6 regulates BCR by targeting its signaling subunits CD79A and CD79B. Loss of physiological KLHL6 expression pattern was frequent among the MCD/C5-like activated B-cell DLBCLs and was associated with higher CD79B levels and dismal outcome...

Follicular helper T (TFH) cells are essential for inducing germinal center (GC) reactions to mediate humoral adaptive immunity in tumors, but the mechanisms underlying TFH cell differentiation remain unclear. Here, we found that the metabolism sensor sirtuin 3 (SIRT3) is critical for TFH cell differentiation and GC formation during tumor and viral infection. SIRT3 deficiency in CD4+ T cells intrinsically enhanced TFH cell differentiation and GC reactions during tumor and virus infection. Mechanistically, damaged oxidative phosphorylation (OXPHOS) compensatively triggered the NAD+-glycolysis pathway to provide a cellular energy supply, which was necessary for SIRT3 deficiency-induced TFH cell differentiation...

BACKGROUND: The treatment of carbapenem-resistant Acinetobacter baumannii/calcoaceticus complex (CRAB) presents significant treatment challenges. METHODS: We report the case of a 42-year-old woman with CRAB meningitis who experienced persistently positive cerebrospinal fluid (CSF) cultures for 13 days despite treatment with high-dose ampicillin-sulbactam and cefiderocol. On day 13, she was transitioned to sulbactam-durlobactam and meropenem; four subsequent CSF cultures remained negative...