Comparative crystal structure analysis of the human EP300 and CBP KIX domains.

Small-cell lung cancer (SCLC) is highly lethal because the tumors grow and metastasize rapidly. Effective treatments for SCLC are lacking currently. A recent study demonstrated that the E1A binding protein P300 (EP300) KIX domain has pro-tumorigenic activity and is selectively involved in the development and growth of SCLC.

Activatable near-infrared fluorescence probe for real-time imaging of PD-L1 expression in tumors.

In clinical practice, determining programmed death-ligand 1 (PD-L1) expression is crucial for selecting patients and monitoring immune checkpoint blockade therapies. Currently, PD-L1 expression is quantified using immunohistochemistry (IHC). However, IHC-based methods do not capture the heterogeneous and dynamic nature of PD-L1 expression.

Quantitative Assessment of Condylar Remodeling After Open Reduction and Internal Fixation in Mandibular Condylar Head Fractures.

Open reduction and internal fixation (OR/IF) and closed treatments are viable options, with OR/IF gaining popularity in mandibular condylar head fracture (CHF). Sufficient research is lacking on long-term condylar morphologic changes. This study quantitatively evaluated the morphologic changes in the condylar head in patients who underwent OR/IF for CHF without the removal of osteosynthesis material.

PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature in C9orf72 ALS/FTD neurons.

Dipeptide repeat proteins are a major pathogenic feature of C9orf72 amyotrophic lateral sclerosis (C9ALS)/frontotemporal dementia (FTD) pathology, but their physiological impact has yet to be fully determined. Here we generated C9orf72 dipeptide repeat knock-in mouse models characterized by expression of 400 codon-optimized polyGR or polyPR repeats, and heterozygous C9orf72 reduction. (GR)400 and (PR)400 knock-in mice recapitulate key features of C9ALS/FTD, including cortical neuronal hyperexcitability, age-dependent spinal motor neuron loss and progressive motor dysfunction.

An Analysis of the Demographics and Clinical Characteristics of Transgender and Intersex Populations in Korea: A Retrospective Study Using HIRA Database.

Background: Transgender and intersex populations have long remained under-documented in South Korea, largely due to the absence of comprehensive epidemiological data. With increasing societal acknowledgment, there's an urgent need to understand the demographics and health challenges faced by these communities.

Methods: This retrospective, large-scale data study included people who received the F64 codes from the Korean Health Insurance Review & Assessment Service between January 2007 and December 2021.

Crystal structure of [1,2,4]triazolo[4,3-b]pyridazine derivatives as BRD4 bromodomain inhibitors and structure-activity relationship study.

BRD4 contains two tandem bromodomains (BD1 and BD2) that recognize acetylated lysine for epigenetic reading, and these bromodomains are promising therapeutic targets for treating various diseases, including cancers. BRD4 is a well-studied target, and many chemical scaffolds for inhibitors have been developed. Research on the development of BRD4 inhibitors against various diseases is actively being conducted.

Discovery of BET specific bromodomain inhibitors with a novel scaffold.

Bromodomain and extra-terminal domain (BET) proteins have been considered as potent candidates for anti-cancer drug development. As epigenetic readers, they modulate gene expression by recognizing acetylated lysine residues on histones. Therefore, the pharmacological inhibition of BET proteins has been extensively studied.

The structure of Deinococcus radiodurans transcriptional regulator HucR retold with the urate bound.

HucR is a MarR family protein of Deinococcus radiodurans, which binds tightly to the intergenic region of HucR and the uricase gene to inhibit their expression. Urate (or uric acid) antagonizes the repressor function of HucR by binding to HucR to impede its association with the cognate DNA. The previously reported crystal structure of HucR was without the bound urate showing significant structural homology to other MarR structures.

Osteogenic Capacity of the Prefabricated Periosteofascial Flap using Vascular Induction with Skeletonized Pedicle Transfer in Rabbit Calvarium.

The study investigated the osteogenic capacity of a prefabricated periosteal flap created using only skeletonized pedicle transfer without fascia or muscle for vascular induction in rabbit calvarium. A critical-sized bone defect was made in the parietal bone centered on the sagittal suture, and the demineralized bone matrix was implanted. The periosteofascia over the defect was used as a form of prefabricated periosteofascial flap (PPF group, N=10), conventional periosteofascial flap (CPF group, N=10), and nonvascularized free periosteofascial graft (FPG group, N=6).

The Reciprocal Interaction Between Sleep and Alzheimer's Disease.

It is becoming increasingly recognized that patients with a variety of neurodegenerative diseases exhibit disordered sleep/wake patterns. While sleep impairments have typically been thought of as sequelae of underlying neurodegenerative processes in sleep-wake cycle regulating brain regions, including the brainstem, hypothalamus, and basal forebrain, emerging evidence now indicates that sleep deficits may also act as pathophysiological drivers of brain-wide disease progression. Specifically, recent work has indicated that impaired sleep can impact on neuronal activity, brain clearance mechanisms, pathological build-up of proteins, and inflammation.

Phosphorylation of OGFOD1 by Cell Cycle-Dependent Kinase 7/9 Enhances the Transcriptional Activity of RNA Polymerase II in Breast Cancer Cells.

2-oxoglutarate and iron-dependent oxygenase domain-containing protein 1 (OGFOD1) expression is upregulated in a variety of cancers and has been related to poor prognosis. However, despite this significance to cancer progression, the precise oncogenic mechanism of OGFOD1 is not understood. We demonstrated that OGFOD1 plays a role in enhancing the transcriptional activity of RNA polymerase II in breast cancer cells.

Phospholipid transfer function of PTPIP51 at mitochondria-associated ER membranes.

In eukaryotic cells, mitochondria are closely tethered to the endoplasmic reticulum (ER) at sites called mitochondria-associated ER membranes (MAMs). Ca ion and phospholipid transfer occurs at MAMs to support diverse cellular functions. Unlike those in yeast, the protein complexes involved in phospholipid transfer at MAMs in humans have not been identified.

Synthesis and Structure-Activity Relationships of Aristoyagonine Derivatives as Brd4 Bromodomain Inhibitors with X-ray Co-Crystal Research.

Epigenetic regulation is known to play a key role in progression of anti-cancer therapeutics. Lysine acetylation is an important mechanism in controlling gene expression. There has been increasing interest in bromodomain owing to its ability to modulate transcription of various genes as an epigenetic 'reader.

Crystal Structure of the Kinase Domain of MerTK in Complex with AZD7762 Provides Clues for Structure-Based Drug Development.

Aberrant tyrosine-protein kinase Mer (MerTK) expression triggers prosurvival signaling and contributes to cell survival, invasive motility, and chemoresistance in many kinds of cancers. In addition, recent reports suggested that MerTK could be a primary target for abnormal platelet aggregation. Consequently, MerTK inhibitors may promote cancer cell death, sensitize cells to chemotherapy, and act as new antiplatelet agents.

Phosphorylation of OCT4 Serine 236 Inhibits Germ Cell Tumor Growth by Inducing Differentiation.

Octamer-binding transcription factor 4 (Oct4) plays an important role in maintaining pluripotency in embryonic stem cells and is closely related to the malignancies of various cancers. Although posttranslational modifications of Oct4 have been widely studied, most of these have not yet been fully characterized, especially in cancer. In this study, we investigated the role of phosphorylation of serine 236 of OCT4 [OCT4 (S236)] in human germ cell tumors (GCTs).

Volumetric lung nodule segmentation using adaptive ROI with multi-view residual learning.

Accurate quantification of pulmonary nodules can greatly assist the early diagnosis of lung cancer, enhancing patient survival possibilities. A number of nodule segmentation techniques, which either rely on a radiologist-provided 3-D volume of interest (VOI) or use the constant region of interests (ROIs) for all the slices, are proposed; however, these techniques can only investigate the presence of nodule voxels within the given VOI. Such approaches restrain the solutions to freely investigate the nodule presence outside the given VOI and also include the redundant structures (non-nodule) into VOI, which limits the segmentation accuracy.

Outcome Differences of Remnant- Preserving versus Non-Preserving Methods in Arthroscopic Anterior Cruciate Ligament Reconstruction: A Meta-analysis with Subgroup analysis.

Purpose: To analyze differences in clinical outcomes of arthroscopic anterior cruciate ligament reconstruction between remnant-preserving and non-preserving methods.

Methods: International electronical databases PubMed, Embase, and the Cochrane central database from January 1966 to December 2017 were searched for randomized controlled trials (RCTs) and observational studies that compared differences of clinical outcomes of ACL reconstruction with and without remnant preservation. A meta-analysis of these studies was performed to compare clinical outcomes.

Comparison of the Outcomes of Closed Reduction Nasal Bone Fractures With a Surgical Navigation System.

Background: The most prevalent form of facial bone fractures is nasal fractures. The surgical procedures used for these fractures are relatively simple, but complete correction is not easy because the nasal bone is small and identifying the fracture site by palpation is difficult. This study aimed to investigate the efficacy of intraoperative surgical navigation systems in nasal bone fracture surgery through a prospective analysis.

Use of a biopsy punch for end-to-side anastomosis in free-tissue transfer.

In end-to-side vessel-anastomoses, a side fenestration should be made by a slit incision or partial excision of the vessel wall. However, a slit incision might restrict blood flow across the anastomosis, and a partial vessel wall excision using micro-scissors may be time-consuming and result in irregular edges, which may weaken the vessel wall and cause flow disturbances. We used a biopsy punch for end-to-side anastomosis, and obtained satisfactory results.

Intraoral temporalis transposition for facial reanimation: A novel technique in facial nerve palsy.

Background: Facial palsy patients require reconstructive surgery because they suffer from an expressionless and deformed appearance especially during smiling. To gain a natural smile, various dynamic procedures rather than static procedures are performed. Through cadaveric studies with clinical implications on temporalis muscle and intraoral transposition, we were able to come up with a more effective and less invasive procedure than the conventional temporalis muscle transposition or lengthening temporalis myoplasty.

Comparison of Harmonic scalpel and monopolar cautery for capsulectomy at the second stage of expander/implant breast reconstruction.

Background: Capsular contracture is a common complication of two-stage expander/implant breast reconstruction. To minimize the risk of this complication, capsulectomy is performed using monopolar cautery or ultrasonic surgical instrumentation, the latter of which can be conducted with a Harmonic scalpel. To date, there is disagreement regarding which of the two methods is superior.

Ultrasonographic Evaluation of a Patient With a Successful Digital Sympathectomy in Raynaud Phenomenon: A Case Report.

Selective periarterial sympathectomy in Raynaud phenomenon (RP) has not been adequately studied as there was no reliable method to evaluate outcomes. However, dynamic Doppler ultrasonography may have clinical value in the management and follow-up of patients with RP; but few reports describe using the device to assess surgical outcomes. Here, we report a case of successful digital sympathectomy in a single digit and the postoperative evaluation using ultrasonography.