Advantages of single high-dose radiation therapy compared with conventional fractionated radiation therapy in overcoming radioresistance.

Background: Radioresistance is a major clinical challenge in cancer treatment, as it reduces the effectiveness of radiation therapy (RT). While advances in radiation delivery have enabled the clinical use of high-dose hypofractionated RT, its impact on radioresistant tumors remains unclear. This study aimed to compare the effects of single high-dose RT with conventional fractionated RT on radioresistant breast cancer cells and explore the underlying mechanisms.

Overcoming radioresistance of breast cancer cells with MAP4K4 inhibitors.

Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) has recently emerged as a promising therapeutic target in cancer. In this study, we explored the biological function of MAP4K4 in radioresistant breast cancer cells using two MAP4K4 inhibitors, namely PF06260933 and GNE-495. Radioresistant SR and MR cells were established by exposing SK-BR-3 and MCF-7 breast cancer cells to 48-70 Gy of radiation delivered at 4-5 Gy twice a week over 10 months.

Toward Digital Twin Development for Implant Placement Planning Using a Parametric Reduced-Order Model.

Real-time stress distribution data for implants and cortical bones can aid in determining appropriate implant placement plans and improving the post-placement success rate. This study aims to achieve these goals via a parametric reduced-order model (ROM) method based on stress distribution data obtained using finite element analysis. For the first time, the finite element analysis cases for six design variables related to implant placement were determined simultaneously via the design of experiments and a sensitivity analysis.

Physicochemical Properties of Yanggaeng with Added Tempeh Powder.

In this study, we investigated the physicochemical and antioxidative properties of the traditional Korean confectionery, Yanggaeng, when various amounts of tempeh powder (TP) were added. We replaced a portion of the white bean paste in Yanggaeng with TP at percentages of 0% (CON), 2% (TP2), 4% (TP4), and 6% (TP6) by total weight. The proximate composition results showed that TP6 exhibited the highest crude ash and crude protein contents, but its moisture content and carbohydrate content were the lowest compared to the CON.

Discovery of proteolysis-targeting chimera targeting undruggable proteins using a covalent ligand screening approach.

Targeted protein degradation (TPD) technology, such as proteolysis-targeting chimera (PROTAC), has become a new therapeutic modality. However, the degradation of undruggable proteins, such as those involved in protein-protein interactions (PPIs), using PROTAC is still limited owing to the difficulties in finding small-molecule binders of these proteins. To identify new chemical moieties that bind to the target sites of the protein of interest (POI), we conducted a site-specific and fragment-based covalent ligand screening using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Stress induces behavioral abnormalities by increasing expression of phagocytic receptor MERTK in astrocytes to promote synapse phagocytosis.

Childhood neglect and/or abuse can induce mental health conditions with unknown mechanisms. Here, we identified stress hormones as strong inducers of astrocyte-mediated synapse phagocytosis. Using in vitro, in vivo, and human brain organoid experiments, we showed that stress hormones increased the expression of the Mertk phagocytic receptor in astrocytes through glucocorticoid receptor (GR).

Serum and glucocorticoid-regulated kinase 1: Structure, biological functions, and its inhibitors.

Serum and glucocorticoid-regulated kinase 1 (SGK1) is a serine/threonine kinase belonging to the protein kinase A, G, and C (AGC) family. Upon initiation of the phosphoinositide 3-kinase (PI3K) signaling pathway, mammalian target of rapamycin complex 2 (mTORC2) and phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylate the hydrophobic motif and kinase domain of SGK1, respectively, inducing SGK1 activation. SGK1 modulates essential cellular processes such as proliferation, survival, and apoptosis.

Quality of life and caregiver burden in pediatric glaucoma: A systematic review.

Pediatric conditions can lead to significant caregiver burden and poor quality of life (QoL). This systematic review describes research relating to caregiver burden and QoL of caregivers of pediatric glaucoma patients. A systematic database search of Embase, Medline, PsycINFO, CINAHL, Web of Science, and the three journals within the Association for Research in Vision and Ophthalmology (ARVO) was conducted in October 2021.

Enhancement of Thermoplasmonic Neural Modulation Using a Gold Nanorod-Immobilized Polydopamine Film.

Photothermal neural activity inhibition has emerged as a minimally invasive neuromodulation technology with submillimeter precision. One of the techniques involves the utilization of plasmonic gold nanoparticles (AuNPs) to modulate neural activity by photothermal effects ("thermoplasmonics"). A surface modification technique is often required to integrate AuNPs onto the neural interface.

Engineering Brain Organoids: Toward Mature Neural Circuitry with an Intact Cytoarchitecture.

The emergence of brain organoids as a model system has been a tremendously exciting development in the field of neuroscience. Brain organoids are a gateway to exploring the intricacies of human-specific neurogenesis that have so far eluded the neuroscience community. Regardless, current culture methods have a long way to go in terms of accuracy and reproducibility.

links the development and function of a sleep-regulatory circuit.

Although many genes are known to influence sleep, when and how they impact sleep-regulatory circuits remain ill-defined. Here, we show that (), a conserved adaptor for the autism-associated Cul3 ubiquitin ligase, acts in a restricted period of neuronal development to impact sleep in adult . The loss of causes structural and functional alterations within the mushroom body (MB), a center for sensory integration, associative learning, and sleep regulation.

Effective Organs-at-Risk Dose Sparing in Volumetric Modulated Arc Therapy Using a Half-Beam Technique in Whole Pelvic Irradiation.

Background: Although there are some controversies regarding whole pelvic radiation therapy (WPRT) due to its gastrointestinal and hematologic toxicities, it is considered for patients with gynecological, rectal, and prostate cancer. To effectively spare organs-at-risk (OAR) doses using multi-leaf collimator (MLC)'s optimal segments, potential dosimetric benefits in volumetric modulated arc therapy (VMAT) using a half-beam technique (HF) were investigated for WPRT.

Methods: While the size of a fully opened field (FF) was decided to entirely include a planning target volume in all beam's eye view across arc angles, the HF was designed to use half the FF from the isocenter for dose optimization.

Acyl-CoA synthetase-4 mediates radioresistance of breast cancer cells by regulating FOXM1.

The development of radioresistance during radiotherapy is a major cause of tumor recurrence and metastasis. To provide new insights of the mechanisms underlying radioresistance, we established radioresistant cell lines derived from two different subtypes of breast cancer cells, HER2-positive SK-BR-3 and ER-positive MCF-7 breast cancer cells, by exposing cells to 48 ~ 70 Gy of radiation delivered at 4-5 Gy twice weekly over 9 ~ 10 months. The established radioresistant SK-BR-3 (SR) and MCF-7 (MR) cells were resistant not only to a single dose of radiation (2 Gy or 4 Gy) but also to fractionated radiation delivered at 2 Gy/day for 5 days.

Aggravation of Hemorrhoids in Patients With Cervical Cancer Undergoing Radiotherapy: A Nationwide Population-based Study.

Background/aim: Anal canal toxicity tends to be ignored in pelvic radiotherapy (RT). However, patients with hemorrhoids can be troubled by lower radiation dose. We tried to determine whether a correlation exists between hemorrhoids and anal symptoms in patients with cervical cancer undergoing RT.

Chaga mushroom extract induces autophagy via the AMPK-mTOR signaling pathway in breast cancer cells.

Ethnopharmacological Relevance: Chaga mushrooms (Inonotus obliquus) are commonly used in traditional treatments in Eastern Europe and Asia due to their diverse pharmacological effects, including anti-tumor and immunologic effects. Thus, many cancer patients take Chaga mushrooms as a complementary medicine, even during chemotherapy or radiotherapy. However, few studies have investigated the effects or molecular targets of Chaga mushrooms in breast cancer.

Evaluation of Radiotherapy-Induced Systemic Antitumor Effects in Mice Bearing 4T1 Mouse Breast Cancer Cells.

Recently, several clinical studies have reported that combination treatments of radiation therapy (RT) and immunotherapy in patients with multiple lesions can improve tumor regression at a distance from the irradiated site, known as the abscopal effect. However, when RT and immunotherapy are concurrently applied, it is hard to distinguish the pure systemic effects of RT from those of the immunotherapy drug. In this preclinical study, the authors investigated the systemic antitumor effects of RT alone according to fraction dose size and splitting schedules.

Assessment of portal image resolution improvement using an external aluminum target and polystyrene electron filter.

Background: In this study, an external 8 mm thick aluminum target was installed on the upper accessory tray mount of a medical linear accelerator head. The purpose of this study was to determine the effects of the external aluminum target beam (Al-target beam) on the portal image quality by analyzing the spatial and contrast resolutions. In addition, the image resolutions with the Al-target beams were compared with those of conventional 6 megavoltage (MV) images.

Characterization and comparative expression analysis of CUL1 genes in rice.

Cullin-RING E3 ubiquitin ligase (CRL) complex is known as the largest family of E3 ligases. The most widely characterized CRL, SCF complex (CRL1), utilizes CUL1 as a scaffold protein to assemble the complex components. To better understand CRL1-mediated cellular processes in rice, three CUL1 genes (OsCUL1s) were isolated in Oryza sativa.

Investigation of the use of external aluminium targets for portal imaging in a medical accelerator using Geant4 Monte Carlo simulation.

Objective: To install a low-Z target on the wedge tray mount of a medical linear accelerator to create a new image beam and to confirm image contrast enhancement.

Methods: Experimental low-energy photon beams were produced with the linac running in the 6 MeV electron mode and with a low-Z target installed on the wedge tray mount [denoted 6 MeV (low-Z target)]. Geant4 Monte Carlo simulation was performed to analyse the energy spectrum and image contrast of a 6 MeV (low-Z target) beam.

Determination of the optimal time for tamoxifen treatment in combination with radiotherapy.

Although radiotherapy and tamoxifen have been extensively used to treat estrogen receptor α (ERα)-positive breast cancers, it is still questionable when tamoxifen should be started to maximize clinical benefits in combination with radiotherapy. Generally, clinician's opinion and experience are major determinants in scheduling concurrent or sequential tamoxifen and radiotherapy. Thus, we attempted to determine an optimal time to start tamoxifen treatment by analyzing tamoxifen responses at different times after irradiating MCF-7 cells to cumulative doses of 10 or 20-30 Gy.

Comparison of Treatment Outcomes between Breast Conserving Surgery Followed by Radiotherapy and Mastectomy Alone in Patients with T1-2 Stage and 1-3 Axillary Lymph Nodes in the Era of Modern Adjuvant Systemic Treatments.

Purpose: The role of postmastectomy radiotherapy in the treatment of T1-2 primary tumor with 1-3 positive lymph nodes is controversial. We compared treatment outcomes between breast conserving surgery followed by radiotherapy (BCS+RT) and total mastectomy alone (TM) in the setting of modern adjuvant systemic treatments.

Methods: Patients with T1-2 primary breast cancer and 1-3 positive lymph nodes who were treated between 2001 and 2011 were divided into 2 groups based on the treatment approach: BCS+RT (n = 169) and TM (n = 117).