Geometric deep learning-guided Suzuki reaction conditions assessment for applications in medicinal chemistry.

Suzuki cross-coupling reactions are considered a valuable tool for constructing carbon-carbon bonds in small molecule drug discovery. However, the synthesis of chemical matter often represents a time-consuming and labour-intensive bottleneck. We demonstrate how machine learning methods trained on high-throughput experimentation (HTE) data can be leveraged to enable fast reaction condition selection for novel coupling partners.

Enabling late-stage drug diversification by high-throughput experimentation with geometric deep learning.

Late-stage functionalization is an economical approach to optimize the properties of drug candidates. However, the chemical complexity of drug molecules often makes late-stage diversification challenging. To address this problem, a late-stage functionalization platform based on geometric deep learning and high-throughput reaction screening was developed.

Deposition chamber technology as building blocks for a standardized brain-on-chip framework.

The in vitro modeling of human brain connectomes is key to exploring the structure-function relationship of the central nervous system. Elucidating this intricate relationship will allow better studying of the pathological mechanisms of neurodegeneration and hence result in improved drug screenings for complex neurological disorders, such as Alzheimer's and Parkinson diseases. However, currently used in vitro modeling technologies lack the potential to mimic physiologically relevant neural structures.

[Mission (im)possible : Setting up a neurological center 12,000 km away with telemedicine].

Background: Specialized neurological treatment decreases the mortality and morbidity of stroke patients. In many regions of the world an extensive coverage is not available. The cooperation between the Krankenhaus Nordwest (KHNW, Frankfurt, Germany) and the Government of Brunei Darussalam describes the set-up process of a specialized neurological center, including stroke unit, science and rehabilitation center.

Treatment of breast cancer with simultaneous integrated boost in hybrid plan technique : Influence of flattening filter-free beams.

Objective: The present study compares in silico treatment plans using hybrid plan technique during hypofractionated radiation of mammary carcinoma with simultaneous integrated boost (SIB). The influence of 6 MV photon radiation in flattening filter free (FFF) mode against the clinical standard flattening filter (FF) mode is to be examined.

Patients And Methods: RT planning took place with FF and FFF radiation plans for 10 left-sided breast cancer patients.

Heart dose reduction in breast cancer treatment with simultaneous integrated boost: Comparison of treatment planning and dosimetry for a novel hybrid technique and 3D-CRT.

Objective: The present study compares in silico treatment plans of clinically established three-dimensional conformal radiotherapy (3D-CRT) with a hybrid technique consisting of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc radiotherapy (VMAT) during normally fractionated radiation of mammary carcinomas with simultaneous integrated boost on the basis of dose-volume histogram (DVH) parameters.

Patients And Methods: Radiation treatment planning was performed with a hybrid and a 3D-CRT treatment plan for 20 patients. Hybrid plans were implemented with two tangential IMRT fields and a VMAT field in the angular range of the tangents.

Motility patterns of ex vivo intestine segments depend on perfusion mode.

Aim: To evaluate and characterize motility patterns from small intestinal gut segments depending on different perfusion media and pressures.

Methods: Experiments were carried out in a custom designed perfusion chamber system to validate and standardise the perfusion technique used. The perfusion chamber was built with a transparent front wall allowing for optical motility recordings and a custom made fastener to hold the intestinal segments.

Influence of plasticiser on the barrier, mechanical and grease resistance properties of alginate cast films.

Alginate cast films were plasticised by two plasticisers--glycerol and sorbitol--in different concentrations. As a function of the plasticiser type and concentration, the following parameters were investigated: equilibrium moisture content (EMC), colour measurement, microscopic analysis by SEM, grease resistance, oxygen permeability (OP), water vapour transmission rate (WVTR) and the mechanical properties. Both plasticisers have a positive influence on the mechanical properties but differ in their effect on the barrier properties.

Changes of the enteric nervous system in amyloid-β protein precursor transgenic mice correlate with disease progression.

In Alzheimer's disease (AD), fatal neuronal cell loss occurs long before relevant evidence can lead to a reliable diagnosis. If characteristic pathological alterations take place in the enteric nervous system (ENS), it could be one of the most promising targets for an early diagnosis, using submucosal biopsies from the gut. We therefore investigated time- and spatial-dependent changes in an amyloid-β protein precursor (AβPP) overexpressing transgenic mouse model to examine early changes within the ENS.

Efficacy and safety of a Butcher's broom preparation (Ruscus aculeatus L. extract) compared to placebo in patients suffering from chronic venous insufficiency.

Extracts from Butcher's broom rhizome (Ruscus aculeatus) have been widely used in the oral treatment of lower leg edema in patients with chronic venous insufficiency. The aim of the present multi-center, double-blind, randomized, placebo-controlled trial was to confirm the efficacy and safety of a ruscus extract (Fagorutin Ruscus Kapseln) according to the latest scientific standards. 166 women suffering from chronic venous insufficiency (Widmer grade I and II, CEAP (Clinical signs, Etiological classification, Anatomic distribution, Pathophysiology) 3-4) were included.

Single dose, dose-escalating trial with fozivudine tidoxil (BM 21.1290).

Background And Objectives: In vitro and in vivo experimental data for fozivudine tidoxil [BM21.1290 (FZD) an ether-lipid conjugate of zidovudine] have shown better efficacy, no myelotoxicity and better tolerability compared with zidovudine. Therefore, the objectives of our study were to evaluate the safety of FZD in patients with human immunodeficiency virus (HIV) infection and to establish basic pharmacokinetic data.

Intravenous immunoglobulins in the therapy of paraneoplastic neurological disorders.

The treatment of paraneoplastic neurological syndromes (e.g., tumor therapy, immunosuppressive therapy, plasmapheresis) rarely leads to an improvement in the neurological symptoms.

Changes of cerebral perfusion after osmotherapy in acute cerebral edema assessed with perfusion weighted MRI.

Perfusion is thought to be impaired in brain edema due to reduced perfusion pressure. Brain edema therapy is assumed to improve perfusion. We assessed regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and mean transit time of blood (MTT) using perfusion-weighted magnetic resonance imaging (MRI) in 15 patients showing acute local brain edema due to infarction or intracerebral hematoma.

Femoral injection of echo contrast medium may increase the sensitivity of testing for a patent foramen ovale.

Objective: The diagnosis of a patent foramen ovale (PFO) as a cause of stroke is of increasing interest especially in young (<45 years) patients.

Methods: We studied potential right-to-left shunting using transesophageal echocardiography (TEE) and bilateral transcranial Doppler sonography (TCD) of the middle cerebral artery (MCA) simultaneously in 44 patients. All patients were younger than age 45 years and suffered from an acute ischemic stroke or transient ischemic attack.

[Diffusion-weighted magnetic resonance imaging in the diagnosis of cerebral infarct].

Forty-one patients demonstrating clinical symptoms for cerebral infarction were investigated by magnetic resonance imaging with diffusion-weighted echo-planar imaging (DWI) and T2-weighted imaging (T2WI). In 8 patients only DWI showed the cerebral lesions clearly. One patient with positive DWI and T2WI suffered from HSV encephalitis.

Time course of the acetazolamide effect in patients with extracranial carotid artery disease.

The acetazolamide test of cerebrovascular reserve is performed as a two-point transcranial Doppler (TCD) measurement of the flow velocity in the middle cerebral artery (MCA) before and 15 to 20 minutes after injection of the carbonic anhydrase inhibitor. The time course was evaluated by bilateral TCD monitoring over 45 minutes in 51 patients with extracranial carotid artery disease. Twenty-nine patients in Group 1 showed a unilateral and 22 patients in Group 2, a bilateral stenosis of the internal carotid artery (ICA).

Comparative clinical efficacy and tolerability of oxerutins and horse chestnut extract in patients with chronic venous insufficiency.

Oxerutins (O-(beta-hydroxyethyl)rutosides, HR, Venoruton) and horse chestnut extract (HCE) are active principles of first priority for the pharmacological treatment of chronic venous insufficiency (CVI). The efficacies of both compounds were shown in numerous, double-blind, randomized, placebo controlled clinical trials. Besides the direct comparison of the two compounds the aim of the study was to investigate the initial dose/maintenance dose concept for HR.

Time course of acetazolamide effect in normal persons.

The intravenous injection of the carbonic anhydrase inhibitor acetazolamide causes a sustained increase of blood flow velocity in the middle cerebral artery. This effect is used in the acetazolamide test of the so-called cerebrovascular reserve capacity. The acetazolamide test is performed routinely as a two-point measurement of the blood flow velocity by transcranial Doppler before and 15 to 20 minutes after drug injection.

Pharmacokinetics and relative bioavailability after single dose administration of 25 mg ketoprofen solution as compared to tablets.

The relative bioavailability of ketoprofen from a liquid formulation as compared to a tablet formulation as reference after single oral dose administration was investigated in 16 healthy male subjects. The subjects received in a randomized, crossover design during one study period of 5 days 2.5 mg of ketoprofen as tablet or liquid formulation administered as single dose with a washout interval of 48 h.

[The value of various transcranial color doppler tests for determining cerebrovascular reserve capacity].

One of the techniques for the assessment of the cerebrovascular reserve capacity is the so-called "breath-holding" test. In order to minimise haemodynamic changes following deep inspiration the patients should hold their breath at the end of a normal inspiration. We studied three different ways (breath holding following normal inspiration [NI], deep inspiration [DI], hyperventilation [HV]), of performing this test in 20 healthy volunteers.

Gastric potential difference measurement as a quantification of gastrointestinal tolerability comparing a buffered acetylsalicylic acid formulation versus plain acetylsalicylic acid.

Two different acetylsalicylic acid (ASA, CAS 50-78-2) formulations (Aspirin) were compared regarding their gastric mucosal tolerability. After administration of plain ASA, buffered ASA and ASA placebo the decrease of gastric potential difference (GPD) was measured. Evaluation of the GPD parameters showed a better tolerability of buffered ASA than of plain ASA.

Renal elimination of magnesium as a parameter of bioavailability of oral magnesium therapy.

Magnesium is an important cation in human physiology, especially in the regulation of membrane proteins, as a cofactor for various enzyme systems and in neuromuscular transmission. Magnesium deficiency leads to severe impairment in muscle function, particularly in cardiovascular diseases. Classical bioavailability studies with magnesium cannot be carried out for several reasons.

[A personal computer-based system for online monitoring of neurologic intensive care patients].

In the management of neurological intensive care patients with an intracranial space-consuming process the measurement and recording of intracranial pressure together with arterial blood pressure is of special interest. These parameters can be used to monitor the treatment of brain edema and hypertension. Intracranial pressure measurement is also important in the diagnosis of the various subtypes of hydrocephalus.