Autophosphorylation of the Tousled-like kinases TLK1 and TLK2 regulates recruitment to damaged chromatin via PCNA interaction.

Tousled-like kinases 1 and 2 (TLK1 and 2) are cell cycle-regulated serine/threonine kinases that are involved in multiple biological processes. Mutation of TLK1 and 2 confer neurodegenerative diseases. Recent studies demonstrate that TLK1 and 2 are involved in DNA repair.

Outcomes of Adjunct Emergent Stenting Versus Mechanical Thrombectomy Alone: The RESCUE-ICAS Registry.

Background: Underlying intracranial stenosis is the most common cause of failed mechanical thrombectomy in acute ischemic stroke patients with large vessel occlusion. Adjunct emergent stenting is sometimes performed to improve or maintain reperfusion, despite limited data regarding its safety or efficacy.

Methods: We conducted a prospective multicenter observational international cohort study.

Prolonged intracranial catheter dwell time exacerbates penumbral stress and worsens stroke thrombectomy outcomes.

Background: The duration of mechanical thrombectomy (MT) is a negative predictor of outcomes in acute ischemic stroke (AIS), yet the precise mechanisms are unclear. We investigated whether the placement of large-bore catheters intracranially reduces blood flow to the ischemic penumbra and diminishes the efficacy of MT.

Methods: We investigated the impact of different catheter sizes on flow through the intracranial circulation using an in vitro model.

Anatomical Approach for the Evaluation of the Nipple-Areolar Complex.

The nipple-areolar complex (NAC) is an anatomically unique region from which several normal variants and pathologies arise. Understanding its anatomy is crucial for accurate clinical and imaging assessments, aiding with differential diagnosis, and ensuring radiologic-pathologic concordance. Mammography and US are commonly used for NAC evaluation; however, these are susceptible to technical limitations such as tissue superimposition and artifacts, compromising visualization of abnormalities in this area.

Validating the porcine model for microsurgical perforator training: Can surgeons trained on pig perforator dissection successfully perform human DIEP flap procedures? A pilot study.

Autologous breast reconstruction, especially using the deep inferior epigastric artery perforator (DIEP) flap, is increasingly seen as a reliable, safe, and long-term alternative to implant-based reconstruction. Despite the recognized advantages of the DIEP flap for breast reconstruction, successful realization demands excellent anatomical knowledge, a thorough understanding of autologous breast reconstruction concepts and advanced microsurgical skills. Given that the porcine model is widely employed in microsurgical training, our study aims to assess this model using validated outcomes, with the objective of evaluating the enhancement in a surgeon's learning curve following training with this model.

DOT1L: orchestrating methylation-dependent radiotheRAPy responses via BRCA1.

Breast Cancer Type 1 Susceptibility Protein (BRCA)-1 existing in several functionally distinct complexes, promotes DNA repair of DNA double-strand breaks (DSBs). A recent study by Tang and colleagues identifies the lysine methyltransferase Disruptor of Telomeric Silencing 1-Like (DOT1L) involved in modifying Receptor-Associated Protein 80 (RAP80) to promote BRCA1-A complex localization and repair functions at DNA breaks. This study illuminates a potential therapeutic target for cancer radiotherapy.

Improved technical outcomes with converting thrombectomy techniques after failed first pass recanalization.

Background: A higher number of recanalization attempts reduces the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke secondary to large vessel occlusion (LVO). We assessed the impact of switching EVT techniques after a failed first pass on procedural and clinical outcomes.

Methods: This multicenter international study, conducted between January 2013 and December 2022, included patients undergoing EVT for anterior circulation LVO (internal carotid artery or M1 segments) with failed first pass recanalization.

DSS1 restrains BRCA2's engagement with dsDNA for homologous recombination, replication fork protection, and R-loop homeostasis.

DSS1, essential for BRCA2-RAD51 dependent homologous recombination (HR), associates with the helical domain (HD) and OB fold 1 (OB1) of the BRCA2 DSS1/DNA-binding domain (DBD) which is frequently targeted by cancer-associated pathogenic variants. Herein, we reveal robust ss/dsDNA binding abilities in HD-OB1 subdomains and find that DSS1 shuts down HD-OB1's DNA binding to enable ssDNA targeting of the BRCA2-RAD51 complex. We show that C-terminal helix mutations of DSS1, including the cancer-associated R57Q mutation, disrupt this DSS1 regulation and permit dsDNA binding of HD-OB1/BRCA2-DBD.

Evolved histone tail regulates 53BP1 recruitment at damaged chromatin.

The master DNA damage repair histone protein, H2AX, is essential for orchestrating the recruitment of downstream mediator and effector proteins at damaged chromatin. The phosphorylation of H2AX at S139, γH2AX, is well-studied for its DNA repair function. However, the extended C-terminal tail is not characterized.

Autophosphorylation of the Tousled-like kinases TLK1 and TLK2 regulates recruitment to damaged chromatin via PCNA interaction.

Tousled-like kinases 1 and 2 (TLK1 and 2) are cell cycle-regulated serine/threonine kinases that are involved in multiple biological processes. Mutation of TLK1 and 2 confer neurodegenerative diseases. Recent studies demonstrate that TLK1 and 2 are involved in DNA repair.

Microsurgical Clipping of Unruptured Anterior Circulation Aneurysms-A Global Multicenter Investigation of Perioperative Outcomes.

Background And Objectives: Microsurgical aneurysm repair by clipping continues to be highly important despite increasing endovascular treatment options, especially because of inferior occlusion rates. This study aimed to present current global microsurgical treatment practices and to identify risk factors for complications and neurological deterioration after clipping of unruptured anterior circulation aneurysms.

Methods: Fifteen centers from 4 continents participated in this retrospective cohort study.

The protein phosphatase EYA4 promotes homologous recombination (HR) through dephosphorylation of tyrosine 315 on RAD51.

Efficient DNA repair and limitation of genome rearrangements rely on crosstalk between different DNA double-strand break (DSB) repair pathways, and their synchronization with the cell cycle. The selection, timing and efficacy of DSB repair pathways are influenced by post-translational modifications of histones and DNA damage repair (DDR) proteins, such as phosphorylation. While the importance of kinases and serine/threonine phosphatases in DDR have been extensively studied, the role of tyrosine phosphatases in DNA repair remains poorly understood.

Evaluation of collagen turnover biomarkers as an objective measure for efficacy of treatment with rurioctocog alfa pegol in patients with hemophilia A: a secondary analysis of a randomized controlled trial.

Background: Patients with hemophilia who have recurrent hemarthroses develop hemophilic arthropathy (HA). Regular prophylaxis with factor (F) VIII (FVIII) can reduce HA, but there is a need for objective outcome measures to evaluate treatment efficacy.

Objectives: Evaluate and assess collagen turnover biomarkers in patients with hemophilia A to determine the efficacy of rurioctocog alfa pegol treatment and understand their potential as tools for guiding treatment decisions and monitoring outcomes.

Initial oral microbiota and the impact of delivery mode and feeding practices in 0 to 2 month-old infants.

The aim of this study was to describe the initial oral microbiota and how delivery mode and feeding practices impact its diversity in 0-2-month-old infants. This was a cross-sectional study that consisted of one collection of saliva samples from 0-2-month infants at baseline. Ten pairs of mothers and infants were selected.

Pediatric Thromboprophylaxis of Large Coronary Artery Aneurysm Using Rivaroxaban.

Giant or large coronary artery aneurysms (CAA) are rare in children, most often secondary to Kawasaki disease, and anticoagulation is recommended to prevent thromboembolism. There are no published pediatric reports on the use of a direct oral anticoagulant for this indication. We describe the anticoagulation management of an 8-year-old boy with a dilated right CAA secondary to Kawasaki disease that has remained stable on rivaroxaban and aspirin, following bleeding complications on enoxaparin and challenges on warfarin.

Once-daily Compared With Twice-daily Enoxaparin Maintenance Therapy Appears Safe and Efficacious in Pediatric Venous Thromboembolism.

Introduction: Once-daily enoxaparin (ODE), considered standard of care for venous thromboembolism (VTE) treatment in adults, has been infrequently assessed in children. To contribute available data to a limited field, we reviewed our center's experience with ODE in treating pediatric VTE compared with twice-daily enoxaparin (TDE).

Materials And Methods: A retrospective analysis of children and adolescents 18 years of age or below diagnosed with VTE and treated at our institution with ODE or TDE maintenance therapy between April 2015 and December 2020 was performed.

Deep Learning Mechanism for Predicting the Axillary Lymph Node Metastasis in Patients with Primary Breast Cancer.

The second largest cause of mortality worldwide is breast cancer, and it mostly occurs in women. Early diagnosis has improved further treatments and reduced the level of mortality. A unique deep learning algorithm is presented for predicting breast cancer in its early stages.

National Survey on Flow-Diverting Stents for Intracranial Aneurysms in the United States.

Background: The Pipeline Embolization Device (PED) has been the only flow-diverting device (FDD) approved by the Food and Drug Administration (FDA) in the U.S. market for nearly a decade, with more FDD choices in the United States following recent FDA approval of the Flow Redirection Endoluminal Device and Surpass.

Treating phantom limb pain: cryoablation of the posterior tibial nerve.

Phantom limb pain (PLP) is a complex pathophysiologic process involving both the central and peripheral nervous system for which there is no definitive treatment. The number of individuals living with amputated limbs is predicted to increase to 3.5 million by 2050, and up to 80% of these patients will have PLP.

Machine Learning Approach for Cardiovascular Risk and Coronary Artery Calcification Score.

Coronary artery calcification (CAC) could assist in the discovery of new risk elements for coronary artery disorder. CAC evaluation, on the other hand, is difficult due to the wide range of CAC in the populations. As a reason, evaluating and analysing data among research have become complicated.

A Deep Learning Framework for Earlier Prediction of Diabetic Retinopathy from Fundus Photographs.

Diabetic patients can also be identified immediately utilizing retinopathy photos, but it is a challenging task. The blood veins visible in fundus photographs are used in several disease diagnosis approaches. We sought to replicate the findings published in implementation and verification of a deep learning approach for diabetic retinopathy identification in retinal fundus pictures.

Stent retriever versus direct aspiration thrombectomy for acute large vessel occlusion: A meta-analysis including 17,556 patients, from MR CLEAN to present.

Objective: Stent retriever (SR) and direct aspiration (DA) mechanical thrombectomy (MT) improve clinical outcomes for stroke secondary to large vessel occlusion. The purpose is to perform an updated meta-analysis comparing the two techniques.

Methods: PubMed database was searched for studies between January 1, 2015, and July 5th, 2021 with mechanical thrombectomy to treat acute ischemic stroke.