Sulfuric Acid Baking and Fe(III)-Cl-HSO Leaching Behavior of Ni- and Cu-Containing Sulfide and Silicate Rich Suhanko Concentrate.

Ni- and Cu-rich concentrate from a new site in Suhanko, Finland, was investigated. Mineral phases identified included talc, chalcopyrite, kaolinite, and pyrrhotite with 3.2% Cu and 1.

International Union of Basic and Clinical Pharmacology CXIV: Orexin Receptor Function, Nomenclature and Pharmacology.

The orexin system consists of the peptide transmitters orexin-A and -B and the G protein-coupled orexin receptors OX and OX Orexin receptors are capable of coupling to all four families of heterotrimeric G proteins, and there are also other complex features of the orexin receptor signaling. The system was discovered 25 years ago and was immediately identified as a central regulator of sleep and wakefulness; this is exemplified by the symptomatology of the disorder narcolepsy with cataplexy, in which orexinergic neurons degenerate. Subsequent translation of these findings into drug discovery and development has resulted to date in three clinically used orexin receptor antagonists to treat insomnia.

Characterization of a putative orexin receptor in Ciona intestinalis sheds light on the evolution of the orexin/hypocretin system in chordates.

Tunicates are evolutionary model organisms bridging the gap between vertebrates and invertebrates. A genomic sequence in Ciona intestinalis (CiOX) shows high similarity to vertebrate orexin receptors and protostome allatotropin receptors (ATR). Here, molecular phylogeny suggested that CiOX is divergent from ATRs and human orexin receptors (hOX).

Novel uses of ensiled biomasses as feedstocks for green biorefineries.

Perennial forage plants are efficient utilizers of solar radiation and nutrients so that there is a lot of scope to increase the production of green biomass in many areas. Currently, grasses are mainly used as feeds for ruminants and equines, but there could be higher added value use for several components of the green biomass. Interest in green biorefining has risen recently motivated by the increased sustainability pressures and need to break the reliance on fossil fuels.

Phase Ib study of sabatolimab (MBG453), a novel immunotherapy targeting TIM-3 antibody, in combination with decitabine or azacitidine in high- or very high-risk myelodysplastic syndromes.

The safety and efficacy of sabatolimab, a novel immunotherapy targeting T-cell immunoglobulin domain and mucin domain-3 (TIM-3), was assessed in combination with hypomethylating agents (HMAs) in patients with HMA-naive revised International Prognostic System Score (IPSS-R) high- or very high-risk myelodysplastic syndromes (HR/vHR-MDS) or chronic myelomonocytic leukemia (CMML). Sabatolimab + HMA had a safety profile similar to that reported for HMA alone and demonstrated durable clinical responses in patients with HR/vHR-MDS. These results support the ongoing evaluation of sabatolimab-based combination therapy in MDS, CMML, and acute myeloid leukemia.

Neuromuscular exercise and counseling for treating recurrent low back pain in female healthcare workers-Findings from a 24-month follow-up study of a randomized controlled trial.

Background: Female healthcare workers have a high prevalence of low back pain (LBP)-related sickness absence. Here, we report findings of a 24-month follow-up of a previously published 6-month randomized controlled trial (RCT).

Methods: By adopting an RCT with 6 months of intervention and follow-up at 6, 12, and 24 months, we assessed the maintenance of changes in the effectiveness (LBP and fear of pain) of the interventions (neuromuscular exercise [NME], back-care counseling, both combined) using a generalized linear mixed model adjusted for baseline covariates.

Effects of faba bean, blue lupin and rapeseed meal supplementation on amino acid metabolism of dairy cows fed grass silage-based diets.

Information about the amino acid (AA) supply of locally produced protein supplements to dairy cow metabolism is needed to design sustainable diets for milk production. In this dairy cow experiment, grass silage and cereal-based diets supplemented with isonitrogenous amounts of rapeseed meal (RSM), faba beans (FB) and blue lupin seeds (BL) were compared with a control diet (CON) without protein supplementation. The diets were arranged as a 4 × 4 Latin Square using periods of 21 days, and four rumen-cannulated Nordic Red dairy cows were used in the experiment.

Processing of a Zinc Leach Residue by a Non-Fossil Reductant.

The suitability of a non-fossil reductant in high-temperature treatment of a zinc leach residue was studied in laboratory-scale experiments. The pyrometallurgical experiments carried out at temperatures of 1200-1350 °C consisted of melting the residue under an oxidizing atmosphere to produce an intermediate, desulfurized slag, which was further cleaned of metals such as Zn, Pb, Cu, and Ag, using renewable biochar as a reductant. The aim was to recover valuable metals and produce a clean, stable slag for use as construction material, for example.

Sabatolimab (MBG453) model-informed drug development for dose selection in patients with myelodysplastic syndrome/acute myeloid leukemia and solid tumors.

Sabatolimab is a novel immunotherapy with immuno-myeloid activity that targets T-cell immunoglobulin domain and mucin domain-3 (TIM-3) on immune cells and leukemic blasts. It is being evaluated for the treatment of myeloid malignancies in the STIMULUS clinical trial program. The objective of this analysis was to support the sabatolimab dose-regimen selection in hematologic malignancies.

Neck-Shoulder Region Training for Chronic Headache in Women: A Randomized Controlled Trial.

Objectives: We investigated whether a specific exercise program for the neck-shoulder region reduces headache intensity, frequency, and duration, and how it influences neck disability among women with chronic headache compared to a control group.

Design: Two-center randomized controlled trial.

Subjects: 116 working-age women.

Preservation characteristics and bacterial communities of crimped ensiled barley grains modulated by moisture content and additive application.

Information about the relationships between preservation characteristics and main bacterial communities of fermented feeds can guide decision making during feed preservation and silage additive development. The objective was to evaluate fermentation quality, aerobic stability, microbial quality and bacterial profile of crimped barley grains ensiled under three moisture contents (MC): 228 (low MC), 287 (medium MC) and 345 (high MC) g/kg fresh matter; and using four additive treatments: 1. Control (CONT), 2.

Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor.

Objectives: Sabatolimab is a humanized monoclonal antibody (hIgG4, S228P) directed against human T-cell immunoglobulin domain and mucin domain-3 (TIM-3). Herein, we describe the development and characterization of sabatolimab.

Methods: Sabatolimab was tested for binding to its target TIM-3 and blocking properties.

Photogrammetric Method to Determine Physical Aperture and Roughness of a Rock Fracture.

Rock discontinuities play an important role in the behavior of rock masses and have a high impact on their mechanical and hydrological properties, such as strength and permeability. The surfaces roughness and physical aperture of rock joints are vital characteristics in joint shear strength and fluid flow properties. This study presents a method to digitally measure the physical aperture of a rock fracture digitized using photogrammetry.

Effects of faba bean, blue lupin and rapeseed meal supplementation on nitrogen digestion and utilization of dairy cows fed grass silage-based diets.

There is increasing interest in using locally produced protein supplements in dairy cow feeding. The objective of this experiment was to compare rapeseed meal (RSM), faba beans (FBs) and blue lupin seeds (BL) at isonitrogenous amounts as supplements of grass silage and cereal based diets. A control diet (CON) without protein supplement was included in the experiment.

Activity of PD-1 blockade with nivolumab among patients with recurrent atypical/anaplastic meningioma: phase II trial results.

Background: Programmed death ligand 1 (PD-L1) contributes to tumor immunosuppression and is upregulated in aggressive meningiomas. We performed a phase II study of nivolumab, a programmed death 1 (PD-1) blocking antibody among patients with grade ≥2 meningioma that recurred after surgery and radiation therapy.

Methods: Twenty-five patients received nivolumab (240 mg biweekly) until progression, voluntary withdrawal, unacceptable toxicity, or death.

A phase I, dose-escalation study of oral PIM447 in Japanese patients with relapsed and/or refractory multiple myeloma.

PIM447, a pan-proviral integration site for Moloney leukemia (PIM) kinase inhibitor, has shown preclinical activity in multiple myeloma (MM). This phase I, open-label, multicenter, dose-escalation study aimed to determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE) of PIM447 in Japanese patients with relapsed and/or refractory (R/R) MM. The study included 13 patients (250 mg once daily (QD), [n = 7]; 300 mg QD, [n = 6]).

Prolyl oligopeptidase inhibition by KYP-2407 increases alpha-synuclein fibril degradation in neuron-like cells.

Growing evidence emphasizes insufficient clearance of pathological alpha-synuclein (αSYN) aggregates in the progression of Parkinson's disease (PD). Consequently, cellular degradation pathways represent a potential therapeutic target. Prolyl oligopeptidase (PREP) is highly expressed in the brain and has been suggested to increase αSYN aggregation and negatively regulate the autophagy pathway.

Mitoxantrone, pixantrone and mitoxantrone (2-hydroxyethyl)piperazine are toll-like receptor 4 antagonists, inhibit NF-κB activation, and decrease TNF-alpha secretion in primary microglia.

Toll-like receptor 4 (TLR4) recognizes various endogenous and microbial ligands and is an essential part in the innate immune system. TLR4 signaling initiates transcription factor NF-κB and production of proinflammatory cytokines. TLR4 contributes to the development or progression of various diseases including stroke, neuropathic pain, multiple sclerosis, rheumatoid arthritis and cancer, and better therapeutics are currently sought for these conditions.

The bacterial community and metabolome dynamics and their interactions modulate fermentation process of whole crop corn silage prepared with or without inoculants.

Multi-omics approach was adopted to investigate the modulation of bacterial microbiota and metabolome as well as their interactions in whole crop corn ensiling systems by inoculating homofermentative Lactobacillus plantarum or heterofermentative Lactobacillus buchneri. Inoculations of the two different inoculants resulted in substantial differences in microbial community and metabolic composition as well as their dynamics in ensiled corn. Inoculants also altered the correlations of microbiota in different manners, and various keystone species were identified in corn silages with different treatments.

Fear-avoidance beliefs are associated with exercise adherence: secondary analysis of a randomised controlled trial (RCT) among female healthcare workers with recurrent low back pain.

Background: Exercise is recommended for the treatment and management of low back pain (LBP) and the prevention of chronicity. Exercise adherence has been only modest in intervention studies among people with musculoskeletal pain. Fear-avoidance beliefs (FABs) are known to affect exercise adherence.

Fibrolytic enzyme treatment prior to ensiling increased press-juice and crude protein yield from grass silage.

Grass is a versatile raw material for green biorefineries and preserving it as silage provides a year-round feedstock. The objective of the current study was to evaluate the effect of fibrolytic enzyme application on silage as a feedstock for a biorefinery. Two batches of grass (mixture of timothy and meadow fescue) silages were ensiled in pilot scale after fibrolytic enzyme was applied to them at four levels.