Design and Optimization of Novel Benzimidazole- and Imidazo[4,5-]pyridine-Based ATM Kinase Inhibitors with Subnanomolar Activities.

The ATM kinase is a promising target in cancer treatment as an important regulator of the cellular response to DNA double-strand breaks. In this work, we present a new class of specific benzimidazole-based ATM inhibitors with picomolar potency against the isolated enzyme and favorable selectivity within relative PIKK and PI3K kinases. We could identify two promising inhibitor subgroups with significantly different physicochemical properties, which we developed simultaneously.

Psychophysics of Pain: A Methodological Introduction.

For over 100 years, psychophysics ..÷ the scientific study between physical stimuli and sensation .

Empathy in Healthcare Professionals during the Coronavirus Pandemic.

Background: Empathy is important for successful interactions. The aim of the present study was to determine whether the cognitive component (Perspective taking) and affective components (Empathic concern and Personal distress) of empathy in health professionals were related to the degree of perceived threat of coronavirus, difficulties in doing work, difficulties in getting along with people, the health condition (current or past coronavirus disease), as well as with some socio-demographic characteristics. Fantasy as the cognitive component of empathy was not the focus of the present study as more irrelevant to clinical practice.

Incidence and Predictors of Inadvertent Dural Puncture After Percutaneous Spinal Cord Stimulation: A Retrospective Database Analysis.

Objectives: Inadvertent dural puncture (IDP) is a known complication associated with traditional neuraxial procedures; however, its characterization after percutaneous spinal cord stimulation (SCS) lead placement has yet to be clearly established in large population studies. This retrospective analysis aims to understand the incidence and associated characteristics of patients with IDP after percutaneous SCS lead placement.

Materials And Methods: The PearlDiver Mariner database of national all-payer claims was used to identify patients who received percutaneous SCS leads and had a claim for IDP (intraoperative IDP or postdural puncture headache [PDPH] claim) within 45 days.

Development of novel urea-based ATM kinase inhibitors with subnanomolar cellular potency and high kinome selectivity.

The ATM kinase is a key molecule regulating DNA damage response and can be targeted resulting in efficient radio- or chemosensitization. Due to the enormous size of this protein and the associated difficulties in obtaining high-quality crystal structures, we sought to develop an accurate in silico model to identify new targeting possibilities. We identified a urea group as the most beneficial chemical anchor point, which could undergo multiple interactions in the aspartate-rich hydrophobic region I of the atypical ATM kinase domain.

I-CARE-An Interaction System for the Individual Activation of People with Dementia.

I-CARE is a hand-held activation system that allows professional and informal caregivers to cognitively and socially activate people with dementia in joint activation sessions without special training or expertise. I-CARE consists of an easy-to-use tablet application that presents activation content and a server-based backend system that securely manages the contents and events of activation sessions. It tracks various sources of explicit and implicit feedback from user interactions and different sensors to estimate which content is successful in activating individual users.

Sleep spindles comprise a subset of a broader class of electroencephalogram events.

Study Objectives: Sleep spindles are defined based on expert observations of waveform features in the electroencephalogram (EEG) traces. This is a potentially limiting characterization, as transient oscillatory bursts like spindles are easily obscured in the time domain by higher amplitude activity at other frequencies or by noise. It is therefore highly plausible that many relevant events are missed by current approaches based on traditionally defined spindles.

The Year in Electrophysiology: Selected Highlights from 2019.

This article is the second in an annual series for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the Editor-in-Chief, Dr. Kaplan, the Associate Editor-in-Chief, Dr.

Autonomous Molecular Design: Then and Now.

The success of deep machine learning in processing of large amounts of data, for example, in image or voice recognition and generation, raises the possibilities that these tools can also be applied for solving complex problems in materials science. In this forum article, we focus on molecular design that aims to answer the question on how we can predict and synthesize molecules with tailored physical, chemical, or biological properties. A potential answer to this question could be found by using intelligent systems that integrate physical models and computational machine learning techniques with automated synthesis and characterization tools.

[Comparative Clinical and Ultrastructural Analysis of the Results from Ranibizumab and Aflibercept in Patients with PDR].

Purpose: Diabetic retinopathy is one of the worst complications of diabetes and can threaten sight. The aim of our study is to compare the clinical outcomes and ultrastructural changes in diabetic retinopathy patients after intravitreal admission of either ranibizumab (Lucentis) or aflibercept (Eylea).

Methods: In our prospective study, 27 patients with PDR were enrolled.

Increased Conductivity and Reduced Settling Time of Carbon-Based Electrodes By Addition of Sea Salt for Wearable Application.

A carbon-based dry electrode is designed to measure bio-potential from skin surface without hydrogel. Consequently, unlike Ag/AgCl electrodes, the carbon-based electrodes require some settling time before a high-fidelity signal is obtained due to the process for impedance matching among skin surface, electrode and amplifiers in biometric system. Besides, especially, when electrocardiogram (ECG) is measured at some distance away from the chest using carbon-based electrodes for wearable application, the settling time could be a critical concern for immediate data collection due to the smaller bio-potential and bigger motion artifact noises.

Development, Optimization, and Structure-Activity Relationships of Covalent-Reversible JAK3 Inhibitors Based on a Tricyclic Imidazo[5,4- d]pyrrolo[2,3- b]pyridine Scaffold.

Janus kinases are major drivers of immune signaling and have been the focus of anti-inflammatory drug discovery for more than a decade. Because of the invariable colocalization of JAK1 and JAK3 at cytokine receptors, the question if selective JAK3 inhibition is sufficient to effectively block downstream signaling has been highly controversial. Recently, we discovered the covalent-reversible JAK3 inhibitor FM-381 (23) featuring high isoform and kinome selectivity.

[OurPuppet - Caring support with an interactive puppet for informal caregivers : Opportunities and challenges in the social and technical developmental process].

Background: The "OurPuppet" project comprises a sensor-based, interactive puppet that will be developed to communicate with people in need of care during a short period of absence of the informal caregiver. Specially qualified puppet guides will support the use of the new technical development. They instruct people with dementia and caregivers on how to use the puppet and supervise the (informal) care relationship through discussions on a regular basis.

Characterization of a CC1153 PVL-producing community-acquired methicillin-resistant Staphylococcus aureus from a dog bite wound.

The isolation of a rare community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strain from an infected dog bite wound is here reported. A 27-year old man presented with a deep open wound on his right hand caused by his dog's bite at the outpatient clinic of Infectious Disease Hospital (IDH), Kuwait. A wound swab was obtained for bacteriological culture and susceptibility testing.

[THE ROLE OF THE CYTOKINE PROFILE IN TREATMENT IN WOMEN WITH ENDOMETRIAL CANCER FIRST STAGE].

Endometrial canceris the most common gynecological cancer. It is positive that more than 53% of diagnosed cases of endometrial cancer are in first stage when the therapeutic options are more successive. More and more gynecologists in addition to the normal clinical and histological tests expand the information for the neoplastic process with biochemical and immunological markers-tumor markers, hormones, lymphocyte population, cytokines, markers for lesion-inflammatory processes, etc.

[A Case of Isolated Massive Pre-sacral Lymph Node Metastasis in 1B1 Stage Cervical Cancer - Case Report.].

The article presents a rare case of isolated massive pre-sacral metastasis in first stage cervical cancer. A 64 year old patient, which on occasion genital bleeding is made D&CI and histologically proven a "cancer of the cervix." Last period - 6 years ago.

[Ultrasound Examination and Management of Twin Pregnancy.].

Unlabelled: Twin pregnancies are found in about 3 % of all pregnancies and 2/3 are dizygotic and 1/3 are monozygotic. In the last 30 years after the introduction of assisted conception and increasing maternal age the rate of twin pregnancies dramatically increased. Compared to singletons, twins have more complications such as intrauterine demise, intrauterine selective fetal growth reStriction, congenital anomalies, miscarriage and preterm labour.

[DIFFICULTIES IN DISSECTION OF URINARY BLADDER IN TOTAL LAPAROSCOPIC HYSTERECTOMY.].

The dissection of urinary bladder is a crucial phase of the laparoscopic operation of hysterectomy. The latter dissection may become even more difficult in the context of history of operative interventions as cesarean section or cervical conization, presence of cervical or isthmic myomatous nodes, as well as upon a bad operative technique. The obeying of some basic principles (knowledge of pelvic anatomy and topographic interrelations; considering of present risk factors; intraoperative screening for complications and their early treatment) results in the optimal performance of laparoscopic hysterectomy.

Association of rs172378 C1q gene cluster polymorphism with lupus nephritis in Bulgarian patients.

Introduction: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that can affect substantially any organ in the body. One of its most severe manifestations is lupus nephritis. Hereditary C1q deficiency is strongly related to SLE but there are very few and inconsistent studies exploring the single nucleotide polymorphisms (SNPs) of the C1q gene cluster in relation to the pathogenesis of SLE.

[Investigation of S100A1 expression in normal ovarian tissues].

The S100 protein family includes low-molecular weight (16-26 kDa) calcium-binding proteins. During the last decade data demonstrating the increased S100A 1 expression in several types of tumors was published. The authors of the basic studies, concerning the role of S100A1 expression in ovarian carcinomas emphasize the insignificant rate of S100A1 expression in normal ovarian tissues.

[Evaluation of the expression of S100A1 protein in serous, mucinous and endometroid ovarian carcinoma].

According to literature approximately 60% from all ovarian malignances express epithelial phenotype. According to their histomorphological characteristics, epithelial ovarian tumors are divided into eight groups. In some particular cases, separate histological types are hard to distinguish one from another.

Oncofetal gene SALL4 in aggressive hepatocellular carcinoma.

Background: Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis. The oncofetal gene SALL4, a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment.

Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex.

An exciting recent approach to targeting transcription factors in cancer is to block formation of oncogenic complexes. We investigated whether interfering with the interaction of the transcription factor SALL4, which is critical for leukemic cell survival, and its epigenetic partner complex represents a novel therapeutic approach. The mechanism of SALL4 in promoting leukemogenesis is at least in part mediated by its repression of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) through its interaction with a histone deacetylase (HDAC) complex.