Shoring Up Osteoporosis Management: A Fresh Start?

Anabolic bone agents, such as parathyroid hormone receptor agonists (teriparatide and abaloparatide) and sclerostin-inhibiting monoclonal antibody (romosozumab), are superior at preventing clinically significant fractures and/or vertebral fractures in women with and without severe osteoporosis compared with bisphosphonates.

Fragmentation of water clusters formed in helium nanodroplets by charge transfer and Penning ionization.

Helium nanodroplets ("HNDs") are widely used for forming tailor-made clusters and molecular complexes in a cold, transparent, and weakly interacting matrix. The characterization of embedded species by mass spectrometry is often complicated by the fragmentation and trapping of ions in the HNDs. Here, we systematically study fragment ion mass spectra of HND-aggregated water and oxygen clusters following their ionization by charge transfer ionization ("CTI") and Penning ionization ("PEI").

IgG Subclass Switch in Volunteers Repeatedly Immunized with the Full-Length Merozoite Surface Protein 1 (MSP1).

Vaccines are highly effective tools against infectious diseases and are also considered necessary in the fight against malaria. Vaccine-induced immunity is frequently mediated by antibodies. We have recently conducted a first-in-human clinical trial featuring SumayaVac-1, a malaria vaccine based on the recombinant, full-length merozoite surface protein 1 (MSP1) formulated with GLA-SE as an adjuvant.

Isolated melanoma cells in sentinel lymph node in stage IIIA melanoma correlate with a favorable prognosis similar to stage IB.

Background: The American Joint Committee on Cancer 8th edition (AJCC v8) defines sentinel lymph nodes (SLN) containing any tumor cells as positive SLN. Consequently, even thin melanomas with isolated tumor cells (ic) in SLN are classified as stage IIIA, making them candidates for adjuvant therapy.

Objectives And Endpoints: We aimed to evaluate survival outcomes of melanoma stage IIIA (ic) and compare them with stage IIIA with lymph node (LN) metastases > 0.

A Survey on Progressive Visualization.

Currently, growing data sources and long-running algorithms impede user attention and interaction with visual analytics applications. Progressive visualization (PV) and visual analytics (PVA) alleviate this problem by allowing immediate feedback and interaction with large datasets and complex computations, avoiding waiting for complete results by using partial results improving with time. Yet, creating a progressive visualization requires more effort than a regular visualization but also opens up new possibilities, such as steering the computations towards more relevant parts of the data, thus saving computational resources.

Generation of Large Vortex-Free Superfluid Helium Nanodroplets.

Superfluid helium nanodroplets are an ideal environment for the formation of metastable, self-organized dopant nanostructures. However, the presence of vortices often hinders their formation. Here, we demonstrate the generation of vortex-free helium nanodroplets and explore the size range in which they can be produced.

The pH-dependent lactose metabolism of Lactobacillus delbrueckii subsp. bulgaricus: An integrative view through a mechanistic computational model.

The fermentation process of milk to yoghurt using Lactobacillus delbrueckii subsp. bulgaricus in co-culture with Streptococcus thermophilus is hallmarked by the breakdown of lactose to organic acids such as lactate. This leads to a substantial decrease in pH - both in the medium, as well as cytosolic.

Multifunctional IgG/IgM antibodies and cellular cytotoxicity are elicited by the full-length MSP1 SumayaVac-1 malaria vaccine.

Radical control of malaria likely requires a vaccine that targets both the asymptomatic liver stages and the disease-causing blood stages of the human malaria parasite Plasmodium falciparum. While substantial progress has been made towards liver stage vaccines, the development of a blood stage vaccine is lagging behind. We have recently conducted a first-in-human clinical trial to evaluate the safety and immunogenicity of the recombinant, full-length merozoite surface protein 1 (MSP1) formulated with GLA-SE as adjuvant.

Trialkoxysilane Exchange: Scope, Mechanism, Cryptates and pH-Response.

The dynamic covalent chemistry (DCvC) of the Si-O bond holds unique opportunities, but has rarely been employed to assemble discrete molecular architectures. This may be due to the harsh conditions required to initiate exchange reactions at silicon in aprotic solvents. Herein, we provide a comprehensive experimental and computational account on the reaction of trialkoxysilanes with alcohols and identify mild conditions for rapid exchange in aprotic solvents.

Three-dimensional femtosecond snapshots of isolated faceted nanostructures.

The structure and dynamics of isolated nanosamples in free flight can be directly visualized via single-shot coherent diffractive imaging using the intense and short pulses of x-ray free-electron lasers. Wide-angle scattering images encode three-dimensional (3D) morphological information of the samples, but its retrieval remains a challenge. Up to now, effective 3D morphology reconstructions from single shots were only achieved via fitting with highly constrained models, requiring a priori knowledge about possible geometries.

A Two-Compartment Fermentation System to Quantify Strain-Specific Interactions in Microbial Co-Cultures.

To fulfil the growing interest in investigating microbial interactions in co-cultures, a novel two-compartment bioreactor system was developed, characterised, and implemented. The system allowed for the exchange of amino acids and peptides via a polyethersulfone membrane that retained biomass. Further system characterisation revealed a Bodenstein number of 18, which hints at backmixing.

Differential Amino Acid Uptake and Depletion in Mono-Cultures and Co-Cultures of and subsp. in a Novel Semi-Synthetic Medium.

The mechanistic understanding of the physiology and interactions of microorganisms in starter cultures is critical for the targeted improvement of fermented milk products, such as yogurt, which is produced by in co-culture with subsp. . However, the use of complex growth media or milk is a major challenge for quantifying metabolite production, consumption, and exchange in co-cultures.

Reporting of melanoma cell densities in the sentinel node refines outcome prediction.

Introduction: Sentinel node biopsy is a key procedure to predict prognosis in melanoma. In a prospective study we compare reporting on melanoma cell densities in cytospin preparations with semiquantitative histopathology for predicting outcome.

Patients And Methods: Sentinel nodes from 900 melanoma patients were bisected.

Modification of Skin Flaps for Single-Stage Reconstruction of the Nasal Ala Using All-Layer Suture: A Prospective Study.

Background And Objectives: After local flaps, it may be necessary to reconstruct the contour of the nasal ala. This is possible with a single-stage all-layer shaping suture. In the present study, the functional and aesthetic results after single-stage reconstruction of the nasal ala were prospectively evaluated.

Compartment-specific metabolome labeling enables the identification of subcellular fluxes that may serve as promising metabolic engineering targets in CHO cells.

C labeling data are used to calculate quantitative intracellular flux patterns reflecting in vivo conditions. Given that approaches for compartment-specific metabolomics exist, the benefits they offer compared to conventional non-compartmented C flux studies remain to be determined. Using compartment-specific labeling information of IgG1-producing Chinese hamster ovary cells, this study investigated differences of flux patterns exploiting and ignoring metabolic labeling data of cytosol and mitochondria.

The 1-Megapixel pnCCD detector for the Small Quantum Systems Instrument at the European XFEL: system and operation aspects.

The X-ray free-electron lasers that became available during the last decade, like the European XFEL (EuXFEL), place high demands on their instrumentation. Especially at low photon energies below 1 keV, detectors with high sensitivity, and consequently low noise and high quantum efficiency, are required to enable facility users to fully exploit the scientific potential of the photon source. A 1-Megapixel pnCCD detector with a 1024 × 1024 pixel format has been installed and commissioned for imaging applications at the Nano-Sized Quantum System (NQS) station of the Small Quantum System (SQS) instrument at EuXFEL.

Not Recommended, But Done: Breastfeeding with HIV in Germany.

Breastfeeding (BF) in mothers living with HIV (MLWH) is still discussed controversially in resource-rich settings. In Germany, where formula feeding is recommended for MLWH single BF cases have been reported, but no systematic data collection and analysis are available so far. This study, titled HELENE, aims to fill this data gap.

Flow Cytometry for Detection and Quantification of Micrometastases in Sentinel Lymph Nodes from Patients with Primary Melanoma.

Background: Detection of micrometastases in the regional lymph nodes is one of the most important prognostic factors for melanoma patients. Our aim was to evaluate the suitability of flow cytometry for rapid quantification of disseminated melanoma cells in sentinel lymph nodes (SLN).

Methods: 132 SLNs from 104 patients diagnosed with melanoma were analyzed by flow cytometry, utilizing the extracellular marker melanoma-associated chondroitin sulfate proteoglycan, in addition to quantitative immunocytology and conventional histopathology, including immunohistochemistry.

[Sentinel node biopsy and lymph node dissection in the era of new systemic therapies for malignant melanoma].

Background: Recently, adjuvant therapies with checkpoint inhibitors and BRAF/MEK inhibitors have become available for patients with malignant melanoma and microscopic nodal disease. Meanwhile the number of complete nodal dissections for a melanoma-positive sentinel node (SN) have decreased significantly.

Objective: The authors discuss the significance of sentinel node biopsy (SNB) and early lymph node dissection in the era of adjuvant systemic therapy for stage III melanoma.

Appointment completion in pediatric neurology telemedicine clinics serving underserved patients.

Background: To determine whether telemedicine improves access to outpatient neurology care for underserved patients, we compared appointment completion between urban, in-person clinics and telemedicine clinics held in rural and underserved communities where neurology consultations are provided remotely.

Methods: In this retrospective study, we identified patients scheduled for outpatient care from UCDH pediatric neurologists between January 1, 2009, and July 31, 2017, in person and by telemedicine. Demographic and clinical variables were abstracted from electronic medical records.

Hospital Utilization Among Rural Children Served by Pediatric Neurology Telemedicine Clinics.

Importance: Telemedicine is increasingly used to provide outpatient pediatric neurology consultations in underserved communities. Although telemedicine clinics have been shown to improve access, little is known about how they alter patients' utilization of hospital services.

Objective: To evaluate the association between access to telemedicine clinics and hospital utilization among underserved children with neurologic conditions.