[Multimorbid patients in endocrine surgery].

Endocrine surgery in multimorbid, frail and geriatric patients is increasing, is often urgent and characterized by special risk constellations. Successful parathyroid gland surgery nearly always results in a marked improvement, irrespective of the specific risk profile of the patient. Except for critical intubation and mediastinal interventions in the risk profile, surgery of the thyroid glands is predominantly beneficial and justifiable even in frail patients.

Intratumoral or Subcutaneous MK-2118, a Non-Cyclic Dinucleotide STING Agonist, With or Without Pembrolizumab for Advanced or Metastatic Solid Tumors or Lymphomas.

Background: We evaluated the non-cyclic dinucleotide stimulator of interferon genes agonist MK-2118 ± pembrolizumab in patients with advanced solid tumors or lymphomas.

Methods: This first-in-human study (NCT03249792) enrolled patients with refractory, advanced solid tumors or lymphomas. Patients received intratumoral (IT) MK-2118 100-20,000 µg (arm 1), IT MK-2118 900-15,000 µg plus intravenous (IV) pembrolizumab 200 mg every 3 weeks (Q3W; arm 2), or subcutaneous (SC) MK-2118 5000-150,000 µg plus IV pembrolizumab 200 mg Q3W (arm 4); arm 3 (visceral injection of MK-2118) was not pursued.

N-detected TROSY for H-N heteronuclear correlation to study intrinsically disordered proteins: strategies to increase spectral quality.

Intrinsically disordered proteins and protein regions are central to many biological processes but difficult to characterize at atomic resolution. Nuclear magnetic resonance is particularly well-suited for providing structural and dynamical information on intrinsically disordered proteins, but existing NMR methodologies need to be constantly refined to provide greater sensitivity and resolution, particularly to capitalise on the potential of high magnetic fields to investigate large proteins. In this paper, we describe how N-detected 2D NMR experiments can be optimised for better performance.

Utilization of acid whey and oat pomace in succinic acid fermentation.

of this study was to investigate the by-products acid whey and oat pomace as nutrient sources for succinic acid production by Actinobacillus succinogenes. Both by-products provide carbon sources in form of glucose and/or lactose without any pre-treatment. Yields of succinic acid per g total sugars consumed after 24 h were between 0.

The development of cardinal extension: From counting to exact equality.

Numerate adults know that when two sets are equal, they should be labeled by the same number word. We explored the development of this principle-sometimes called "cardinal extension"-and how it relates to children's other numerical abilities. Experiment 1 revealed that 2- to 5-year-old children who could accurately count large sets often inferred that two equal sets should be labeled with the same number word, unlike children who could not accurately count large sets.

Microwave-assisted synthesis of highly photoluminescent core/shell CuInZnSe/ZnS quantum dots as photovoltaic absorbers.

Water-dispersible core/shell CuInZnSe/ZnS (CIZSe/ZnS) quantum dots (QDs) were efficiently synthesized under microwave irradiation using -acetylcysteine (NAC) and sodium citrate as capping agents. The photoluminescence (PL) emission of CIZSe/ZnS QDs can be tuned from 593 to 733 nm with varying the Zn : Cu molar ratio in the CIZSe core. CIZSe/ZnS QDs prepared with a Zn : Cu ratio of 0.

Mapping the spatial transferability of knowledge-guided machine learning: Application to the prediction of drain flow fraction.

Machine learning (ML) methods continue to gain traction in hydrological sciences for predicting variables at large scales. Yet, the spatial transferability of these ML methods remains a critical yet underexamined aspect. We present a metamodel approach to obtain large-scale estimates of drain fraction at 10 m spatial resolution, using a ML algorithm (Gradient Boost Decision Tree).

More Anastomotic Ulcers, Less Dumping, and Equal Weight Loss in Long vs. Short Gastric Pouch in Laparoscopic Roux-en-Y Gastric Bypass.

Background: Anastomotic ulcers (AU) at the gastroenterostomy are a common postoperative complication after laparoscopic Roux-en-Y gastric bypass (LRYGB). Possible risk factors for ulcer formation include active smoking, the use of non-steroidal anti-inflammatory drugs, increased tension or ischemia at the anastomosis, or factors that increase the acid secretion of the gastric pouch. Therefore, a longer gastric pouch may increase risk of AU formation after LRYGB.

Targeted deletion of the pancreatic β-cell oxytocin receptor and its effects on metabolic regulation and β-cell health.

The neuropeptide oxytocin (OXT) and its receptor (OXTR) have been shown to play an important role in glucose metabolism, and pancreatic islets express this ligand and receptor. In the current study, OXTR expression was identified in α-, β-, and δ-cells of the pancreatic islet by RNA hybridization, and OXT protein expression was observed only in β-cells. In order to examine the contribution of islet OXT/OXTR in glycemic control and islet β-cell heath, we developed a β-cell specific OXTR knock-out (β-KO) mouse.

Macrophage-induced enteric neurodegeneration leads to motility impairment during gut inflammation.

Current studies pictured the enteric nervous system and macrophages as modulators of neuroimmune processes in the inflamed gut. Expanding this view, we investigated the impact of enteric neuron-macrophage interactions on postoperative trauma and subsequent motility disturbances, i.e.

Variation of gene ratios in mock communities constructed with purified 16S rRNA during processing.

16S ribosomal nucleic acid (16S rRNA) analysis allows to specifically target the metabolically active members of microbial communities. The stability of the ratios between target genes in the workflow, which is essential for the bioprocess-relevance of the data derived from this analysis, was investigated using synthetic mock communities constructed by mixing purified 16S rRNA from Bacillus subtilis (Bs), Staphylococcus aureus (Sa), Pseudomonas aeruginosa (Pa), Klebsiella pneumoniae (Kp) and Burkholderia cepacia (Bc) in different proportions. The RT reaction yielded one copy of cDNA per rRNA molecule for Pa, Bc and Sa but only 2/3 of the expected cDNA from 16S rRNAs of Bs and Kp.

Transforming waste wood into pure L-(+)-lactic acid: Efficient use of mixed sugar media through cell-recycled continuous fermentation.

Lignocellulosic media, containing diverse sugars and growth inhibitor compounds, pose great challenges to fermentation processes. This study tested thermophile Heyndrickxia coagulans strains for the production of L-(+)-lactic acid from waste wood hydrolysate. H.

MoA Studies of the TEAD P-Site Binding Ligand MSC-4106 and Its Optimization to TEAD1-Selective Amide M3686.

Taking the structural information into account, we were able to tune the TEAD selectivity for a specific chemotype. However, different TEAD selectivity profiles did not affect the compound potency or efficacy in the NCI-H226 viability assay. Amides based on or analogues showed improved viability efficacy compared with the corresponding acids.

A spheroid whole mount drug testing pipeline with machine-learning based image analysis identifies cell-type specific differences in drug efficacy on a single-cell level.

Background: The growth and drug response of tumors are influenced by their stromal composition, both in vivo and 3D-cell culture models. Cell-type inherent features as well as mutual relationships between the different cell types in a tumor might affect drug susceptibility of the tumor as a whole and/or of its cell populations. However, a lack of single-cell procedures with sufficient detail has hampered the automated observation of cell-type-specific effects in three-dimensional stroma-tumor cell co-cultures.

A dormant overmassive black hole in the early Universe.

Recent observations have found a large number of supermassive black holes already in place in the first few hundred million years after the Big Bang, many of which seem to be overmassive relative to their host galaxy stellar mass when compared with local relation. Several different models have been proposed to explain these findings, ranging from heavy seeds to light seeds experiencing bursts of high accretion rate. Yet, current datasets are unable to differentiate between these various scenarios.

Improvement of Transmural Inflammation With Adalimumab Versus Immunomodulator Maintenance Therapy in Pediatric Crohn's Disease: Single-Center Prospective Evaluation Using the Pediatric Inflammatory Crohn's Magnetic Resonance Enterography Index.

Background And Aims: Transmural healing, including as assessed by magnetic resonance enterography (MRE) has been associated with long-term favorable outcomes in Crohn's Disease (CD), but data concerning MRE improvement and normalization with therapy are sparse. We performed a prospective longitudinal study utilizing the recently developed pediatric MRE-based multi-item measure of inflammation (PICMI) to examine the efficacy of adalimumab (ADA) and immunomodulator (IM) in attaining improvement of transmural inflammation of the small intestine.

Methods: Pediatric patients with CD involving small bowel and initiating ADA or IM were prospectively enrolled and followed with repeat MRE at 1 year.

Eight weeks of Pilates Method improves physical fitness and sleep quality of individuals with post-COVID-19 syndrome: A randomized clinical trial blinded.

Objectives: To evaluate the impact of eight weeks of Pilates Method on physical fitness and sleep quality of individuals with post-COVID-19 syndrome.

Methods: Randomized clinical trial blinded conducted with fifty-nine individuals with post-COVID-19 syndrome. The participants were randomly allocated to the Pilates group (PG; n = 20), supervised physical exercise group (SPEG; n = 20) and control group (CG; n = 19).

Using interactive platforms to encode, manage and explore immune-related adverse outcome pathways.

This work focuses on the need for modeling and predicting adverse outcomes in immunotoxicology to improve nonclinical assessments of the safety of immunomodulatory therapies. The integrated approach includes, first, the adverse outcome pathway concept established in the toxicology field, and, second, the systems medicine disease map approach for describing molecular mechanisms involved in a particular pathology. The proposed systems immunotoxicology workflow is illustrated with chimeric antigen receptor (CAR) T cell treatment as a use case.

Evaluation of a new soluble transferrin receptor assay and comparison to three measurement procedures.

Background: Soluble transferrin receptor (sTfR) is a useful marker in the differentiation of anemia. Clinical utility is limited by lack of standardization between measurement procedures and interpretative recommendations. Our objective was to evaluate the analytical performance of a research sTfR immunoturbidimetric assay (Alinity c, Abbott Diagnostics) and compare it to three established measurement procedures.

Return of individual research results to participants with and at risk for Parkinson's disease.

In a prospective, remote natural history study of 277 individuals with (60) and genetically at risk for (217) Parkinson's disease (PD), we examined interest in the return of individual research results (IRRs) and compared characteristics of those who opted for versus against the return of IRRs. Most ( = 180, 65%) requested sharing of IRRs with either a primary care provider, neurologist, or themselves. Among individuals without PD, those who requested sharing of IRRs with a clinician reported more motor symptoms than those who did not request any sharing (mean (SD) 2.

Interferon-α as a biomarker to predict renal outcomes in lupus nephritis.

Objective: To determine if serum interferon (IFN)-α levels at the time of a lupus nephritis (LN) flare are associated with renal outcomes.

Methods: Patients with an LN flare who had a preflare estimated glomerular filtration rate (eGFR) ≥60 mL/min were included in the study. The following outcomes were ascertained: (1) Time to first and second LN flares during follow-up, (2) Time to a sustained decline in eGFR by 30% and 50%, and progression to end-stage renal disease (ESRD, <15 mL/min), and (3) Time to an adverse renal event (≥2 renal flares and/or at least a 30% sustained decline in eGFR during follow-up).

Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study.

Allergen-specific immunotherapy (AIT) induces immune tolerance, showing the highest success rate (>95%) for insect venom while a much lower chance for pollen allergy. However, the molecular switches leading to successful durable tolerance restoration remain elusive. The primary outcome of this observational study is the comprehensive immunological cellular characterization during the AIT initiation phase, whereas the secondary outcomes are the serological and Th2-cell-type-specific transcriptomic analyses.

Parent-Specific Transgenerational Immune Priming Enhances Offspring Defense-Unless Heat Stress Negates It All.

Transgenerational immune priming (TGIP) adjusts offspring's immune responses based on parental immunological experiences. It is predicted to be adaptive when parent-offspring environmental conditions match, while mismatches negate those advantages, rendering TGIP potentially costly. We tested these cost-benefit dynamics in the pipefish (Syngnathidae).

Graph databases in systems biology: a systematic review.

Graph databases are becoming increasingly popular across scientific disciplines, being highly suitable for storing and connecting complex heterogeneous data. In systems biology, they are used as a backend solution for biological data repositories, ontologies, networks, pathways, and knowledge graph databases. In this review, we analyse all publications using or mentioning graph databases retrieved from PubMed and PubMed Central full-text search, focusing on the top 16 available graph databases, Publications are categorized according to their domain and application, focusing on pathway and network biology and relevant ontologies and tools.