On the Importance of Configuration Search to the Predictivity of Lanthanide Selectivity.

The lanthanide elements are crucial components in numerous technologies, yet their industrial production through liquid-liquid extraction continues to be economically and environmentally costly due to the challenge of separating elements with similar physicochemical properties. While computational ligand screening has shown promise toward discovering efficient extractants, the complexity of constructing chemically sensible 3D structures (often by hand), coupled with the high cost of quantum chemistry calculations, often limits exploration of the vast ligand chemical and conformational space in favor of local exploration around known chemistries. Moreover, metal complexes can have many stable configurations whose differences in energies exceed the small energy differences that determine the extractant selectivity for certain lanthanides.

Sub-1-min relaxation-enhanced non-contrast non-triggered cervical MRA using compressed SENSE with deep learning reconstruction in healthy volunteers.

Background: We evaluated the acceleration of a three-dimensional isotropic flow-independent magnetic resonance angiography (MRA) (relaxation-enhanced angiography without contrast and triggering, REACT) of neck arteries using compressed SENSE (CS) combined with deep learning (adaptive intelligence, AI)-based reconstruction (CS-AI).

Methods: Thirty-four volunteers received 3-T REACT MRA, acquired threefold: (i) CS acceleration factor 7 (CS7), scan time 1:20 min:s; (ii) CS acceleration factor 10 (CS10), scan time 0:55 min:s; and (iii) CS-AI acceleration factor 10 (CS10-AI), scan time 0:55 min:s. Two radiologists rated the image quality of seven arterial segments and overall image noise.

Live imaging of excitable axonal microdomains in ankyrin-G-GFP mice.

The axon initial segment (AIS) constitutes not only the site of action potential initiation, but also a hub for activity-dependent modulation of output generation. Recent studies shedding light on AIS function used predominantly post-hoc approaches since no robust murine in vivo live reporters exist. Here, we introduce a reporter line in which the AIS is intrinsically labeled by an ankyrin-G-GFP fusion protein activated by Cre recombinase, tagging the native gene.

Treatment adherence and effectiveness in patients treated with carfilzomib-based therapy combinations for relapsed/refractory multiple myeloma in Germany: interim results from the non-interventional CARO study.

Therapy adherence can significantly influence the outcome of cancer patients. The prospective, non-interventional CARO study (NCT02970747) investigated adherence, effectiveness, and safety of carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) in the German real-world setting. In total, 359 patients were included at 69 sites.

Non-contrast-enhanced MR-angiography of Extracranial Arteries in Acute Ischemic Stroke at 1.5 Tesla Using Relaxation-Enhanced Angiography Without Contrast and Triggering (REACT).

Purpose: To evaluate a novel flow-independent sequence (Relaxation-Enhanced Angiography without Contrast and Triggering (REACT)) for imaging of the extracranial arteries in acute ischemic stroke (AIS) at 1.5 T.

Methods: This retrospective single-center study included 47 AIS patients who received REACT (scan time: 3:01 min) and contrast-enhanced MRA (CE-MRA) of the extracranial arteries at 1.

Live imaging of excitable axonal microdomains in ankyrin-G-GFP mice.

The axon initial segment (AIS) constitutes not only the site of action potential initiation, but also a hub for activity-dependent modulation of output generation. Recent studies shedding light on AIS function used predominantly post-hoc approaches since no robust murine live reporters exist. Here, we introduce a reporter line in which the AIS is intrinsically labeled by an ankyrin-G-GFP fusion protein activated by Cre recombinase, tagging the native gene.

Architector for high-throughput cross-periodic table 3D complex building.

Rare-earth and actinide complexes are critical for a wealth of clean-energy applications. Three-dimensional (3D) structural generation and prediction for these organometallic systems remains a challenge, limiting opportunities for computational chemical discovery. Here, we introduce Architector, a high-throughput in-silico synthesis code for s-, p-, d-, and f-block mononuclear organometallic complexes capable of capturing nearly the full diversity of the known experimental chemical space.

First-line nab-paclitaxel plus carboplatin for patients with advanced non-small cell lung cancer: Final results of the NEPTUN study.

Real-world data on the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) are still limited. The NEPTUN study evaluated effectiveness and safety of first-line nab-paclitaxel (Abraxane) plus carboplatin (nab-P/C) in patients with advanced NSCLC in routine clinical practice in Germany. Patients included in our study were aged ≥18 years, diagnosed with locally advanced or metastatic NSCLC and with decision for first-line nab-P/C in routine clinical practice.

Medication adherence with denosumab in patients with bone metastases from solid tumors treated in routine clinical settings: a retrospective study.

Purpose: To describe (non)adherence with denosumab among patients with solid tumors and bone metastases.

Methods: This retrospective, observational study pooled data from two completed prospective, multicenter cohort studies (X-TREME; Study 240) in adult patients with bone metastases from primary breast, prostate, lung, kidney, or other solid cancer types and administered denosumab 120 mg in routine clinical practice in Germany and Central and Eastern Europe. The studies were conducted between May 2012 and May 2017; pooled analysis was completed in August 2021.

[Disorders of the central lymphatic system].

The central lymphatic system consists of the thoracic duct, cisterna chyli and the retroperitoneal lymphatics through which lymph and chyle flows. Disorders of the central lymphatic system can for instance lead to leakage (chylothorax), accumulation of fluid (lymphedema) and retrograde flow (protein losing enteropathy). Abnormalities in the central lymphatic system were overlooked for years, followed by lack of diagnostic and therapeutic options.

The lymphatic system throughout history: From hieroglyphic translations to state of the art radiological techniques.

A comprehensive lymphatic system is indispensable for a well-functioning body; it is integral to the immune system and is also interrelated with the digestive system and fluid homeostasis. The main difficulty in examining the lymphatic system is its fine-meshed structure. This remains a challenge, leaving patients with uninterpreted symptoms and a dearth of potential therapies.

First-line nab-paclitaxel plus carboplatin for patients with advanced non-small cell lung cancer: Results of the NEPTUN study.

Background: Platinum-based chemotherapy remains a first-line standard of care for approximately 30% of patients with non-small cell lung cancer (NSCLC) not harboring a druggable alteration. Favorable efficacy and safety of the nab-paclitaxel/carboplatin (nab-P/C) combination was shown in the pivotal phase 3 trial. However, information on effectiveness of nab-P/C in a real-world setting in Germany is missing.

Performance evaluation of fifth-generation ultra-high-resolution SPECT system with two stationary detectors and multi-pinhole imaging.

Background: Small-animal single-photon emission computed tomography (SPECT) systems with multi-pinhole collimation and large stationary detectors have advantages compared to systems with moving small detectors. These systems benefit from less labour-intensive maintenance and quality control as fewer prone parts are moving, higher accuracy for focused scans and maintaining high resolution with increased sensitivity due to focused pinholes on the field of view. This study aims to investigate the performance of a novel ultra-high-resolution scanner with two-detector configuration (U-SPECT5-E) and to compare its image quality to a conventional micro-SPECT system with three stationary detectors (U-SPECT).

Capabilities of multi-pinhole SPECT with two stationary detectors for in vivo rat imaging.

We aimed to investigate the image quality of the U-SPECT5/CT E-Class a micro single-photon emission computed tomography (SPECT) system with two large stationary detectors for visualization of rat hearts and bones using clinically available Tc-labelled tracers. Sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR) of the small-animal SPECT scanner were investigated in phantom studies using an ultra-high-resolution rat and mouse multi-pinhole collimator (UHR-RM). Point source, hot-rod, and uniform phantoms with Tc-solution were scanned for high-count performance assessment and count levels equal to animal scans, respectively.

Structural and Functional Maturation of Rat Primary Motor Cortex Layer V Neurons.

Rodent neocortical neurons undergo prominent postnatal development and maturation. The process is associated with structural and functional maturation of the axon initial segment (AIS), the site of action potential initiation. In this regard, cell size and optimal AIS length are interconnected.

Phase II Study of the ALK5 Inhibitor Galunisertib in Very Low-, Low-, and Intermediate-Risk Myelodysplastic Syndromes.

Purpose: Overactivation of TGF-β signaling is observed in myelodysplastic syndromes (MDS) and is associated with dysplastic hematopoietic differentiation. Galunisertib, a first-in-class oral inhibitor of the TGF-β receptor type 1 kinase (ALK5) has shown effectiveness in preclinical models of MDS and acceptable toxicity in phase I studies of solid malignancies.

Patients And Methods: A phase II multicenter study of galunisertib was conducted in patients with very low-, low-, or intermediate-risk MDS by the Revised International Prognostic Scoring System criteria with hemoglobin ≤ 10.

Dynamic Regulation of Synaptopodin and the Axon Initial Segment in Retinal Ganglion Cells During Postnatal Development.

A key component allowing a neuron to function properly within its dynamic environment is the axon initial segment (AIS), the site of action potential generation. In visual cortex, AIS of pyramidal neurons undergo periods of activity-dependent structural plasticity during development. However, it remains unknown how AIS morphology is organized during development for downstream cells in the visual pathway (retinal ganglion cells; RGCs) and whether AIS retain the ability to dynamically adjust to changes in network state.

Restrictive strategy versus usual care for cholecystectomy in patients with gallstones and abdominal pain (SECURE): a multicentre, randomised, parallel-arm, non-inferiority trial.

Background: International guidelines advise laparoscopic cholecystectomy to treat symptomatic, uncomplicated gallstones. Usual care regarding cholecystectomy is associated with practice variation and persistent post-cholecystectomy pain in 10-41% of patients. We aimed to compare the non-inferiority of a restrictive strategy with stepwise selection with usual care to assess (in)efficient use of cholecystectomy.

Rapid infusions of human normal immunoglobulin 50g/l are safe and well tolerated in immunodeficiencies and immune thrombocytopenia.

Intravenous immunoglobulin (IVIg) is accepted as an effective and well-tolerated treatment for primary and secondary immunodeficiencies (ID) and immune thrombocytopenia (ITP). Adverse reactions of IVIg are usually mild, comprising transient flu-like symptoms, change in blood pressure and tachycardia. However IVIg therapy can be burdensome for both patients and healthcare facilities, since the infusion may take up to 4h to administer.

Systemic therapy in metastatic renal cell carcinoma.

Purpose: Current systemic treatment of targeted therapies, namely the vascular endothelial growth factor-antibody (VEGF-AB), VEGF receptor tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitors, have improved progression-free survival and replaced non-specific immunotherapy with cytokines in metastatic renal cell carcinoma (mRCC).

Methods: A panel of experts convened to review currently available phase 3 data for mRCC treatment of approved agents, in addition to available EAU guideline data for a collaborative review as the plurality of substances offers different options of first-, second- and third-line treatment with potential sequencing.

Results: Sunitinib and pazopanib are approved treatments in first-line therapy for patients with favorable- or intermediate-risk clear cell RCC (ccRCC).

Everolimus in metastatic renal cell carcinoma after failure of initial anti-VEGF therapy: final results of a noninterventional study.

Background: Data are limited regarding routine use of everolimus after initial vascular endothelial growth factor (VEGF)-targeted therapy. The aim of this prospective, noninterventional, observational study was to assess efficacy and safety of everolimus after initial VEGF-targeted treatment in patients with metastatic renal cell carcinoma (mRCC) in routine clinical settings.

Methods: Everolimus was administered per routine clinical practice.