Optimizing the use of technology to support people with diabetes: research recommendations from Diabetes UK's 2019 diabetes and technology workshop.

AIMS: To identify key gaps in the research evidence base that could help improve how technology supports people with diabetes, and provide recommendations to researchers and research funders on how best to address them. METHODS: A research workshop was conducted, bringing together research experts in diabetes, research experts in technology, people living with diabetes and healthcare professionals. RESULTS: The following key areas within this field were identified, and research recommendations for each were developed: Matching the pace of research with that of technology development Time in range as a measure Health inequalities and high-risk groups How to train people to use technology most effectively Impact of technology usage on mental health CONCLUSIONS: This position statement outlines recommendations through which research could improve how technology is employed to care for and support people living with diabetes, and calls on the research community and funders to address them in future research programmes and strategies.

Risk of Pneumonitis with the Use of Different Immune Checkpoint Inhibitors in a Mexican Population.

PURPOSE: The incidence of pneumonitis reported in previous trials in patients with advanced cancer and use of programmed cell death protein 1 (PD-1) immunotherapy inhibitors was 2.7-3.6%. However, none of these trials included Mexican populations. METHODS: This was a retrospective analysis involving 87 patients with advanced cancer who received PD-1 inhibitors as part of their therapy. The primary outcome was the incidence of pneumonitis after using PD-1 inhibitors. The secondary outcomes were major risk factors and radiological patterns of pneumonitis. RESULTS: We found 13 cases of pneumonitis, giving an overall incidence of 15%; three of the cases were high-grade (grade 3). A ground-glass pattern was the major form found by chest computed tomography scans. We did not find any significant risk factor for pneumonitis. CONCLUSION: The incidence of pneumonitis secondary to treatment with PD-1 inhibitors in our Mexican population was 15%, which is 5 times higher than that found in other studies. No risk factor was identified for this increased incidence of drug-induced pneumonitis following the use of PD-1 inhibitors.

A high number of co-occurring genomic alterations detected by NGS is associated with worse clinical outcomes in advanced EGFR-mutant lung adenocarcinoma: Data from LATAM population.

BACKGROUND: Co-occurring genomic alterations identified downstream main oncogenic drivers have become more evident since the introduction of next-generation sequencing (NGS) analyses at diagnosis and progression. Emerging evidence has stated that co-occurring genomic alterations at diagnosis might represent de novo and primary resistance mechanisms to tyrosine kinase inhibitors (TKIs) in advanced EGFR-mutant (EGFRm) non-small lung cancer (NSCLC). In this study, we assessed the prognostic role of co-occurring genomic alterations in advanced EGFRm NSCLC. METHODS: A cohort of 111 patients with advanced NSCLC harboring EGFR-sensitive mutations detected by PCR was analyzed in 5 Latin American oncological centers from January 2019 to December 2020. All eligible patients received upfront therapy with EGFR-TKI. Co-occurring genomic alterations were determined at diagnosis in every patient by the NGS (FoundationOneCDx) comprehensive platform, which evaluates 324 known cancer-related genes. RESULTS: EGFR exon19 deletion was the most frequent oncogenic driver mutation (60.4 %) detected by NGS. According to the NGS assay, 31 % and 68.3 % of patients had 1-2 and ≥ 3 co-occurring genomic alterations, respectively. The most frequent co-occurring genomic alterations were TP53 mutations (64.9 %) followed by CDKN2AB alterations (13.6 %), BRCA2 (13.6 %), and PTEN (12.7 %) mutations. Baseline central nervous system disease was present in 42.7 % of patients. First- or second-generation EGFR TKIs (gefitinib, afatinib, or erlotinib) were the most common treatment in 67.5 % of patients, while osimertinib was administered in 27.9 % of cases. The median PFS in all evaluated patients was 13.63 months (95 %CI: 11.79-15.52). Using ≥ 3 co-occurring alterations as the cut-off point, patients with ≥ 3 co-occurring genomic alterations showed a median PFS, of 12.7 months (95 %CI: 9.92-15.5) vs 21.3 months (95 %CI: 13.93-NR) in patients with 2 or less co-occurring genomic alterations [HR 3.06, (95 %CI: 1.55-5.48) p = 0.0001]. Also, patients with a TP53 mutation had a shorter PFS, 13.6 (95 %CI: 10.7-15.5) vs 19.2 months (95 %CI: 12.8-NR); in wild type TP53 [HR 2.01 (95 %CI: 1.18-3.74) p = 0.12]. In the multivariate analysis, the number (≥3) of concurrent genomic alterations and ECOG PS of 2 or more were related to a significant risk factor for progression [HR 2.79 (95 %CI: 1.49-5.23) p = 0.001 and HR 2.42 (95 %CI: 1.22-4.80) p = 0.011 respectively]. CONCLUSION: EGFR-mutant NSCLC is not a single oncogene-driven disease in the majority of cases, harboring a higher number of co-occurring genomic alterations. This study finds the number of co-occurring genomic alterations and the presence of TP53 mutations as negative prognostic biomarkers, which confers potentially earlier resistance mechanisms to target therapy.

Impact of Testicular Germ Cell Tumor Laterality on Recurrence-Free Survival in the Mexican Population.

BACKGROUND: To date, the prognostic value of laterality for testicular germ cell tumors remains unknown. Herein, we describe this prognostic factor in the Mexican population. METHODS: A retrospective single-center study that included 37 patients with primary testicular germ cell tumors was conducted. Primary outcome was recurrence-free survival (RFS) at 2 years. Secondary outcomes were RFS by histology, progression-free survival by laterality, and 2-year overall survival. RESULTS: Thirty-seven patients were included, of which five showed relapses. By laterality, the 2-year RFS rate was 100% for left tumors and 77.3% for right tumors, with a trend toward statistical significance (P = 0.058). By histology, the RFS rate was higher for seminomas than non-seminomas (89% vs. 83%, respectively) without this difference being statistically significant. Progression-free survival was higher for right tumors than left tumors (91% vs. 80%, respectively) but without reaching statistical significance. The overall survival rate for the entire cohort was 94.5%. CONCLUSIONS: Our study shows that patients with primary germ cell tumors of the right testicle have a higher risk of recurrence than those with primary germ cell tumors of the left testicle, with a trend toward statistical significance.

Development of Two Analytical Methods Based on Reverse Phase Chromatographic and SDS-PAGE Gel for Assessment of Deglycosylation Yield in N-Glycan Mapping.

N-lined glycosylation is one of the critical quality attributes (CQA) for biotherapeutics impacting the safety and activity of drug product. Changes in pattern and level of glycosylation can significantly alter the intrinsic properties of the product and, therefore, have to be monitored throughout its lifecycle. Therefore fast, precise, and unbiased N-glycan mapping assay is desired. To ensure these qualities, using analytical methods that evaluate completeness of deglycosylation is necessary. For quantification of deglycosylation yield, methods such as reduced liquid chromatography-mass spectrometry (LC-MS) and reduced capillary gel electrophoresis (CGE) have been commonly used. Here we present development of two additional methods to evaluate deglycosylation yield: one based on LC using reverse phase (RP) column and one based on reduced sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE gel) with offline software (GelAnalyzer). With the advent of rapid deglycosylation workflows in the market for N-glycan profiling replacing overnight incubation, we have aimed to quantify the level of deglycosylation in a selected rapid deglycosylation workflow. Our results have shown well resolved peaks of glycosylated and deglycosylated protein species with RP-LC method allowing simple quantification of deglycosylation yield of protein with high confidence. Additionally a good correlation, ≥0.94, was found between deglycosylation yields estimated by RP-LC method and that of reduced SDS-PAGE gel method with offline software. Evaluation of rapid deglycosylation protocol from GlycanAssure™ HyPerformance assay kit performed on fetuin and RNase B has shown complete deglycosylation within the recommended protocol time when evaluated with these techniques. Using this kit, N-glycans from NIST mAb were prepared in 1.4 hr and analyzed by hydrophilic interaction chromatography (HILIC) ultrahigh performance LC (UHPLC) equipped with a fluorescence detector (FLD). 37 peaks were resolved with good resolution. Excellent sample preparation repeatability was found with relative standard deviation (RSD) of <5% for peaks with >0.5% relative area.

Alkylsulfuric acid ionic liquids: a promising class of strongly acidic room-temperature ionic liquids.

Strongly acidic (pKa ≈ -3.5) room-temperature ionic liquids (ILs) with -OSO3H functionalized cations are introduced. The strong acidity, easy synthesis, and better physical properties of these R-OSO3H ILs make them excellent alternatives to the well-known sulfonic acid (R-SO3H) ILs, especially in the domain of metal processing.

New metal extractants and super-acidic ionic liquids derived from sulfamic acid.

Sulfamic acid (NH3-SO3) is an acidic zwitterion with many applications. N-Alkylated derivatives are introduced, which can be used as a new class of metal extractants R2NH-SO3 and as new super-acidic ionic liquids [R2NH-SO3H][Tf2N]. The synthesis, properties and novel applications of this versatile platform are discussed.

Overview of the effect of salts on biphasic ionic liquid/water solvent extraction systems: anion exchange, mutual solubility, and thermomorphic properties.

Hydrophobic (water-immiscible) ionic liquids (ILs) are frequently used as organic phase in solvent extraction studies. These biphasic IL/water extraction systems often also contain metal salts or mineral acids, which can significantly affect the IL trough (un)wanted anion exchange and changes in the solubility of IL in the aqueous phase. In the case of thermomorphic systems, variations in the cloud point temperature are also observed. All these effects have important repercussions on the choice of IL, suitable for a certain extraction system. In this paper, a complete overview of the implications of metal salts on biphasic IL/water systems is given. Using the Hofmeister series as a starting point, a range of intuitive prediction models are introduced, supported by experimental evidence for several hydrophobic ILs, relevant to solvent extraction. Particular emphasis is placed on the IL betainium bis(trifluoromethylsulfonyl)imide [Hbet][Tf2N]. The aim of this work is to provide a comprehensive interpretation of the observed effects of metal salts, so that it can be used to predict the effect on any given biphasic IL/water system instead of relying on case-by-case reports. These prediction tools for the impact of metal salts can be useful to optimize IL synthesis procedures, extraction systems and thermomorphic properties. Some new insights are also provided for the rational design of ILs with UCST or LCST behavior based on the choice of IL anion.

Sulfonic acid functionalized ionic liquids for dissolution of metal oxides and solvent extraction of metal ions.

New sulfonic acid functionalized ionic liquids (SAFILs) with bis(trifluoromethylsulfonyl)imide anions were synthesized. These ionic liquids are strong Brønsted acids and can solubilize metal oxides. Water-immiscible SAFILs were used as organic phases in solvent extraction studies.

Selective uptake of rare earths from aqueous solutions by EDTA-functionalized magnetic and nonmagnetic nanoparticles.

Magnetic (Fe3O4) and nonmagnetic (SiO2 and TiO2) nanoparticles were decorated on their surface with N-[(3-trimethoxysilyl)propyl]ethylenediamine triacetic acid (TMS-EDTA). The aim was to investigate the influence of the substrate on the behavior of these immobilized metal coordinating groups. The nanoparticles functionalized with TMS-EDTA were used for the adsorption and separation of trivalent rare-earth ions from aqueous solutions. The general adsorption capacity of the nanoparticles was very high (100 to 400 mg/g) due to their large surface area. The heavy rare-earth ions are known to have a higher affinity for the coordinating groups than the light rare-earth ions but an additional difference in selectivity was observed between the different nanoparticles. The separation of pairs of rare-earth ions was found to be dependent on the substrate, namely the density of EDTA groups on the surface. The observation that sterical hindrance (or crowding) of immobilized ligands influences the selectivity could provide a new tool for the fine-tuning of the coordination ability of traditional chelating ligands.

Síndrome hemofagocítico. Reporte de un caso y revisión de la literatura / Hemophagocytic syndrome. Case report and review of the literature

Resumen El síndrome hemofagocítico es una enfermedad caracterizada por fiebre, citopenias, esplenomegalia y otras alteraciones en laboratorios debido a una activación excesiva de los macrófagos, debido a mutaciones genéticas o secundario a infecciones, malignidad o enfermedades reumatológicas. Debido a la poca especificidad de los síntomas, el diagnóstico usualmente se realiza de manera tardía. Su manejo requiere el tratamiento de la causa subyacente, y de ser necesario, medicamentos que disminuyan la respuesta inflamatoria.

Abstract Hemophagocytic syndrome is a disease characterized by fever, cytopenia, splenomegaly and other alterations in laboratories due to excessive activation of macrophages, by genetic mutations or secondary to infections, malignancy or rheumatological diseases. Because of the low specificity of the symptoms, the diagnosis is usually late. Its management requires the treatment of the underlying cause and, if necessary, medications that decrease the inflammatory response.

ABRF-2002ESRG, a difficult sequence: Analysis of a PVDF-bound known protein with a heterogeneous amino-terminus.

The ABRF-2002 Edman Sequencing Research Group (ESRG) sample (ABRF-2002ESRG) was the 14th in a yearly series designed as an education and self-evaluation tool for laboratories performing Edman sequence analysis. This year's study used a known protein with a heterogeneous amino-terminus, and thus was one of the more challenging protein samples distributed by an Association for Biomolecular Resource Facilities (ABRF) research group. The sample was originally submitted to an ESRG member's lab, and after analysis was thought to demonstrate an analytical problem that would be of interest to the general sequencing community. The protein was purified using commercially available, pre-cast sodium dodecyl sulfate-polyacrylamide gels and transferred to polyvinylidene fluoride.Protein bands were distributed to 72 members of the ABRF who requested ABRF-2002ESRG, along with a data instruction sheet and a brief survey. Participating members were requested to report observed raw data, interpret the data as they normally would for an investigator, and identify the protein using a database search. Study results from 31 responses are presented to show how labs fared with a difficult but sequenceable sample.