Modulating Weak Protein-Protein Cross-Interactions by the Addition of Free Amino Acids at Millimolar Concentrations.

In this paper, we quantify weak protein-protein interactions in solution using cross-interaction chromatography (CIC) and surface plasmon resonance (SPR) and demonstrate that they can be modulated by the addition of millimolar concentrations of free amino acids. With CIC, we determined the second osmotic virial cross-interaction coefficient (B23) as a proxy for the interaction strength between two different proteins. We perform SPR experiments to establish the binding affinity between the same proteins. With CIC, we show that the amino acids proline, glutamine, and arginine render the protein cross-interactions more repulsive or equivalently less attractive. Specifically, we measured B23 between lysozyme (Lys) and bovine serum albumin (BSA) and between Lys and protein isolates (whey and canola). We find that B23 increases when amino acids are added to the solution even at millimolar concentrations, corresponding to protein/ligand stoichiometric ratios as low as 1:1. With SPR, we show that the binding affinity between proteins can change by 1 order of magnitude when 10 mM glutamine is added. In the case of Lys and one whey protein isolate (WPI), it changes from the mM to the M range, thus by 3 orders of magnitude. Interestingly, this efficient modulation of the protein cross-interactions does not alter the protein's secondary structure. The capacity of amino acids to modulate protein cross-interactions at mM concentrations is remarkable and may have an impact across fields in particular for specific applications in the food or pharmaceutical industries.

Phylodynamic Insights into Global Emergence and Diversification of the Tomato Pathogen Xanthomonas hortorum pv. gardneri.

The emergence of plant pathogens is often associated with waves of unique evolutionary and epidemiological events. Xanthomonas hortorum pv. gardneri is one of the major pathogens causing bacterial spot disease of tomatoes. After its first report in the 1950s, there were no formal reports on this pathogen until the 1990s, despite active global research on the pathogens that cause tomato and pepper bacterial spot disease. Given the recently documented global distribution of X. hortorum pv. gardneri, our objective was to examine genomic diversification associated with its emergence. We sequenced the genomes of X. hortorum pv. gardneri strains collected in eight countries to examine global population structure and pathways of emergence using phylodynamic analysis. We found that strains isolated post-1990 group by region of collection and show minimal impact of recombination on genetic variation. A period of rapid geographic expansion in X. hortorum pv. gardneri is associated with acquisition of a large plasmid conferring copper tolerance by horizontal transfer and coincides with the burgeoning hybrid tomato seed industry through the 1980s. The ancestry of X. hortorum pv. gardneri is consistent with introduction to hybrid tomato seed production and dissemination during the rapid increase in trade of hybrid seeds.

Investigating the Associations between Patient-Reported Quality of Care and Perceived Coercion: A Norwegian Cross-Sectional Study.

Patient perspectives on the quality of care received are fundamental to mental health care. This study aimed to investigate the association between patient-reported mental health care quality, perceived coercion, and various demographic, clinical, and ward-related factors. Using a cross-sectional design, data were collected from 169 patients in Norwegian mental health wards using the quality in psychiatric care-inpatient (QPC-IP) instrument and experienced coercion scale (ECS). The analysis revealed a consistent pattern in which patients with higher perceived coercion consistently rated lower quality on all QPC-IP dimensions. The significant findings of the multiple regression models further supported this association. Beyond coercion, the factors influencing quality ratings include self-reported treatment results, participation in treatment planning, and knowledge of complaint procedures. Emphasizing the pivotal role of coercion in enhancing mental health care quality, these findings contribute to a nuanced understanding of patient experiences and underscore the importance of patient participation in mental health care improvement efforts.

Use of Upadacitinib as Salvage Therapy for Ulcerative Colitis in Pregnancy: A Case Report.

Upadacitinib, a selective JAK-1 inhibitor, was used as rescue therapy for ulcerative colitis in the setting of pregnancy following use of mesalamine, vedolizumab, infliximab, and corticosteroids. This resulted in an uncomplicated live full birth without need for surgical intervention.

Improving health system responses when patients are harmed: a protocol for a multistage mixed-methods study.

INTRODUCTION: At least 10% of hospital admissions in high-income countries, including Australia, are associated with patient safety incidents, which contribute to patient harm ('adverse events'). When a patient is seriously harmed, an investigation or review is undertaken to reduce the risk of further incidents occurring. Despite 20 years of investigations into adverse events in healthcare, few evaluations provide evidence of their quality and effectiveness in reducing preventable harm.This study aims to develop consistent, informed and robust best practice guidance, at state and national levels, that will improve the response, learning and health system improvements arising from adverse events. METHODS AND ANALYSIS: The setting will be healthcare organisations in Australian public health systems in the states of New South Wales, Queensland, Victoria and the Australian Capital Territory. We will apply a multistage mixed-methods research design with evaluation and in-situ feasibility testing. This will include literature reviews (stage 1), an assessment of the quality of 300 adverse event investigation reports from participating hospitals (stage 2), and a policy/procedure document review from participating hospitals (stage 3) as well as focus groups and interviews on perspectives and experiences of investigations with healthcare staff and consumers (stage 4). After triangulating results from stages 1-4, we will then codesign tools and guidance for the conduct of investigations with staff and consumers (stage 5) and conduct feasibility testing on the guidance (stage 6). Participants will include healthcare safety systems policymakers and staff (n=120-255) who commission, undertake or review investigations and consumers (n=20-32) who have been impacted by adverse events. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Northern Sydney Local Health District Human Research Ethics Committee (2023/ETH02007 and 2023/ETH02341).The research findings will be incorporated into best practice guidance, published in international and national journals and disseminated through conferences.

Beyond COVID-19: Wastewater-based epidemiology for multipathogen surveillance and normalization strategies.

Wastewater-based epidemiology (WBE) is a critical tool for monitoring community health. Although much attention has focused on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of coronavirus disease 2019 (COVID-19), other pathogens also pose significant health risks. This study quantified the presence of SARS-CoV-2, influenza A virus (Inf-A), and noroviruses of genogroups I (NoV-GI) and II (NoV-GII) in wastewater samples collected weekly (n = 170) from July 2023 to February 2024 from five wastewater treatment plants (WWTPs) in Yamanashi Prefecture, Japan, by quantitative PCR. Inf-A RNA exhibited localized prevalence with positive ratios of 59 %-82 % in different WWTPs, suggesting regional outbreaks within specific areas. NoV-GI (94 %, 160/170) and NoV-GII (100 %, 170/170) RNA were highly prevalent, with NoV-GII (6.1 ± 0.8 log10 copies/L) consistently exceeding NoV-GI (5.4 ± 0.7 log10 copies/L) RNA concentrations. SARS-CoV-2 RNA was detected in 100 % of the samples, with mean concentrations of 5.3 ± 0.5 log10 copies/L in WWTP E and 5.8 ± 0.4 log10 copies/L each in other WWTPs. Seasonal variability was evident, with higher concentrations of all pathogenic viruses during winter. Non-normalized and normalized virus concentrations by fecal indicator bacteria (Escherichia coli and total coliforms), an indicator virus (pepper mild mottle virus (PMMoV)), and turbidity revealed significant positive associations with the reported disease cases. Inf-A and NoV-GI + GII RNA concentrations showed strong correlations with influenza and acute gastroenteritis cases, particularly when normalized to E. coli (Spearman's ρ = 0.70-0.81) and total coliforms (ρ = 0.70-0.81), respectively. For SARS-CoV-2, non-normalized concentrations showed a correlation of 0.61, decreasing to 0.31 when normalized to PMMoV, suggesting that PMMoV is unsuitable. Turbidity normalization also yielded suboptimal results. This study underscored the importance of selecting suitable normalization parameters tailored to specific pathogens for accurate disease trend monitoring using WBE, demonstrating its utility beyond COVID-19 surveillance.

Investigation of UV Light-Promoted Synthesis of α-Sulfonyl Amides from N-Sulfonyl Ynamides.

UV light-promoted synthesis of α-sulfonyl amides from N-sulfonyl ynamides without any additives is reported. The reaction proceeds through a radical chain mechanism involving the photoinduced cleavage of the nitrogen-sulfur bond and addition of an electrophilic sulfonyl radical to the triple bond of the ynamide followed by ß-fragmentation of the sulfonyl group leading to a ketenimine hydrated upon workup. This highly efficient rearrangement leads, after acidic treatment, to a wide range of α-sulfonyl amides in high yields.

Inter domain linker region affects properties of CBM6 in GH5_34 arabinoxylanases and alters oligosaccharide product profile.

Understanding the relation between enzyme domain structure and catalytic activity is crucial for optimal engineering of novel enzymes for lignocellulose bioconversion. Xylanases with varying specificities are commonly used to valorise the hemicellulose arabinoxylan (AX), yet characterization of specific arabinoxylanases remain limited. Two homologous GH5_34 arabinoxylanases, HhXyn5A and CtXyn5A, in which the two domains are connected by a 40-residue linker, exhibit distinct activity on AX, yielding different reaction product patterns, despite high sequence identity, conserved active sites and similar domain composition. In this study, the carbohydrate binding module 6 (CBM6), or the inter domain linker together with CBM6, were swapped to investigate their influence on hydrolytic activity and oligosaccharide product pattern on cereal AXs. The variants, with only CBM6 swapped, displayed reduced activity on commercial wheat and rye AX, as well as on extracted oat fibre, compared to the original enzymes. Additionally, exchange of both linker and CBM6 resulted in a reduced ratio of enzyme produced in soluble form in Escherichia coli cultivations, causing loss of activity of both HhXyn5A and CtXyn5A variants. Analysis of oligosaccharide product patterns applying HPAEC-PAD revealed a decreased number of reaction products for CtXyn5A with swapped CBM6, which resembled the product pattern of HhXyn5A. These findings emphasize the importance of the CBM6 interactions with the linker and the catalytic domain for enzyme activity and specificity, and underlines the role of the linker in enzyme structure organisation and product formation, where alterations in linker interactions with the catalytic and/or CBM6 domains, influence enzyme-substrate association and specificity.

Final nanoparticle size distribution under unusual parameter regimes.

We explore the large-scale behavior of a stochastic model for nanoparticle growth in an unusual parameter regime. This model encompasses two types of reactions: nucleation, where n monomers aggregate to form a nanoparticle, and growth, where a nanoparticle increases its size by consuming a monomer. Reverse reactions are disregarded. We delve into a previously unexplored parameter regime. Specifically, we consider a scenario where the growth rate of the first newly formed particle is of the same order of magnitude as the nucleation rate, in contrast to the classical scenario where, in the initial stage, nucleation dominates over growth. In this regime, we investigate the final size distribution as the initial number of monomers tends to infinity through extensive simulation studies utilizing state-of-the-art stochastic simulation methods with an efficient implementation and supported by high-performance computing infrastructure. We observe the emergence of a deterministic limit for the particle's final size density. To scale up the initial number of monomers to approximate the magnitudes encountered in real experiments, we introduce a novel approximation process aimed at faster simulation. Remarkably, this approximating process yields a final size distribution that becomes very close to that of the original process when the available monomers approach infinity. Simulations of the approximating process further support the conjecture of the emergence of a deterministic limit.

Factors leading to excessive fatigue in nurses - a three-year follow-up study.

BACKGROUND: Global nursing shortages necessitate the identification of mitigatable factors that may reduce nursing absence and turnover. Fatigue has been shown to be associated with these issues. This study aimed to identify factors leading to development of or recovery from excessive fatigue in nurses as these can offer actionable avenues for protecting nurses against fatigue or supporting fatigue recovery. METHODS: A longitudinal study among nurses randomly sampled from the Norwegian Nurse's Organization. The Chalder Fatigue Questionnaire measured fatigue. Dichotomized scoring was used, with scores ≥ 4 considered excessive fatigue. The study included questions on shift work schedules, psychosocial work characteristics, sleep, body mass index, physical activity, caffeine, alcohol, mental health, etc. Two sets of logistic regression analysis were conducted (one for development of and one for recovery from excessive fatigue), evaluating how changes in work, lifestyle and health between baseline (2015) and follow-up (2018) affected first, odds of development of excessive fatigue and second, odds of recovery from excessive fatigue. RESULTS: Among 1,311 included nurses, 21.6% maintained, 13.3% developed, and 18.0% recovered from excessive fatigue (2015-2018). Within work characteristics, increased psychological work demands were associated with development of excessive fatigue OR = 1.77 (CI = 1.11-2.82). Several work characteristics were associated with recovery from excessive fatigue, including decreased decision latitude (OR = 0.39; CI = 0.19-0.82) and increased coworker support (OR = 1.90; CI = 1.11-3.24). Shift work variables were not associated with fatigue outcomes. Amongst lifestyle factors, changes in sleep duration, obesity, and exercise were significant. Notably, developing inappropriate sleep duration (OR = 2.84; CI = 1.47-5.48) increased odds of developing excessive fatigue, while maintaining inappropriate sleep duration (< 6 h or > 8 h) (OR = 0.19; CI = 0.54-0.65) decreased odds of recovering. All assessed health conditions (depression, anxiety, insomnia, and shift work disorder) were related to development of (ORs 2.10-8.07) or recovery from (ORs 0.10-0.50) excessive fatigue. Depression, for example, increased odds of development of (OR = 8.07; CI = 2.35-27.66) and decreased odds of recovery (OR = 0.10; CI = 0.04-0.26) from excessive fatigue. CONCLUSIONS: Changes in lifestyle factors, health conditions, and psychosocial work factors were associated with development of and recovery from excessive fatigue. Sleep and psychosocial work factors played important roles. We found no relationship with shift work schedules.

Roles of Tubulin Concentration during Prometaphase and Ran-GTP during Anaphase of Caenorhabditis elegans Meiosis.

In many animal species, the oocyte meiotic spindle, which is required for chromosome segregation, forms without centrosomes. In some systems, Ran-GEF on chromatin initiates spindle assembly. We found that in Caenorhabditis elegans oocytes, endogenously-tagged Ran-GEF dissociates from chromatin during spindle assembly but re-associates during meiotic anaphase. Meiotic spindle assembly occurred after auxin-induced degradation of Ran-GEF, but anaphase I was faster than controls and extrusion of the first polar body frequently failed. In search of a possible alternative pathway for spindle assembly, we found that soluble tubulin concentrates in the nuclear volume during germinal vesicle breakdown. We found that the concentration of soluble tubulin in the metaphase spindle region is enclosed by ER sheets which exclude cytoplasmic organelles including mitochondria and yolk granules. Measurement of the volume occupied by yolk granules and mitochondria indicated that volume exclusion would be sufficient to explain the concentration of tubulin in the spindle volume. We suggest that this concentration of soluble tubulin may be a redundant mechanism promoting spindle assembly near chromosomes.

Academic orientation and cannabis use-findings from a population-based study of Swedish adolescents in upper secondary school.

AIM: To examine the association between academic orientation and frequent cannabis use among Swedish adolescents in upper secondary school and include pupils from introductory programs (IPs), a large group of adolescents previously overlooked in research on adolescent cannabis use. METHODS: We used cross-sectional data from two anonymous school surveys carried out in upper secondary school in 2021. The samples consisted of pupils from all academic orientations, and the analysis included 3151 pupils in higher education preparatory programs (HEPs), 1010 pupils in vocational programs (VPs), and 819 pupils in IPs. The association between the exposure academic orientation and the outcome frequent (21+ times) cannabis was analyzed using multi-level mixed-effects Poisson regression. RESULTS: Estimates from the first model showed a significant (P < 0.05) 2.45 times higher risk of frequent cannabis use among pupils in IPs compared with in HEPs [incidence rate ratio (IRR) 2.45, 95% confidence interval (CI) 1.28-4.66] and 82% higher in VPs (IRR 1.82, 95% CI 1.09-3.04) compared with in HEPs. However, the associations between academic orientation and frequent (21+ times) cannabis use were attenuated and no longer significant when socioeconomic status, truancy, school dissatisfaction, and early onset of substance use were adjusted for. CONCLUSIONS: There was a higher risk of frequent (21+ times) cannabis use among pupils in IPs, and this differential was explained by higher exposure to risk factors in this group. This result is important from a policy perspective as it provides knowledge of a previously neglected risk group for frequent cannabis use.

Efficacy and Safety of Upadacitinib or Elsubrutinib Alone or in Combination for Systemic Lupus Erythematosus: A Phase 2 Randomized Controlled Trial.

OBJECTIVE: The 48-week, phase 2 SLEek study (NCT03978520) evaluated the efficacy and safety of upadacitinib (Janus kinase inhibitor) and elsubrutinib (Bruton's tyrosine kinase inhibitor) alone or in combination (ABBV-599) in adults with moderately to severely active systemic lupus erythematosus (SLE). METHODS: Patients were randomized 1:1:1:1:1 to once-daily (QD) ABBV-599 high dose (HD; elsubrutinib 60mg + upadacitinib 30mg), ABBV-599 low dose (LD; elsubrutinib 60mg + upadacitinib 15mg), elsubrutinib 60mg, upadacitinib 30mg, or placebo. The primary endpoint was the proportion of patients achieving both SLE Responder Index-4 (SRI-4) and glucocorticoid dose ≤10mg QD at week 24. Additional assessments through week 48 included British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) and Lupus Low Disease Activity State (LLDAS) responses, number of flares, time to first flare, and adverse events. RESULTS: The study enrolled 341 patients. The ABBV-599LD and elsubrutinib arms were discontinued after a planned interim analysis showed lack of efficacy (no safety concerns). More patients achieved the primary endpoint with upadacitinib (54.8%; P=0.028) and ABBV-599HD (48.5%; P=0.081) versus placebo (37.3%). SRI-4, BICLA, and LLDAS response rates were higher for both upadacitinib and ABBV-599HD versus placebo at weeks 24 and 48. Flares were reduced and time to first flare through week 48 was substantially delayed with both upadacitinib and ABBV-599HD versus placebo. No new safety signals were observed beyond those previously reported for upadacitinib or elsubrutinib. CONCLUSIONS: Upadacitinib 30mg alone or in combination with elsubrutinib (ABBV-599HD) demonstrated significant improvements in SLE disease activity, reduced flares and were well tolerated through 48 weeks.

Therapeutic efficiency and safety assessment of intradermal platelet-rich plasma combined with oral tranexamic acid in patients with facial melasma.

BACKGROUND: Melasma is a chronic, acquired hypermelanosis that primarily affects the face. Platelet-rich plasma (PRP) and tranexamic acid (TXA) are promising treatments for melasma. However, only a few randomized clinical trials have examined the efficacy and safety of combining these therapies for melasma. OBJECTIVES: We aimed to compare the efficacy and safety of combining PRP and oral TXA with those of PRP alone in the treatment of facial melasma. MATERIAL AND METHODS: A randomized controlled trial was conducted at Walailak University Hospital, Nakhon Si Thammarat, Thailand, between March and September 2023. Participants with mixed-type melasma were randomly allocated in a 1:1 ratio to either group A (PRP injection alone without placebo) or group B (PRP injection with oral TXA). Therapeutic efficacy and safety assessments were performed over a 12-week follow-up period. RESULTS: The study included 26 participants (mean age: 45.9 years, standard deviation (±SD): 5.0) who were predominantly female (84.6%). In group A, the modified Melasma Area and Severity Index (mMASI) scores significantly decreased from a median of 4.30 interquartile range (IQR): 4.10) to 3.60 (IQR: 3.10) between week 0 and week 12, respectively. In group B, the median mMASI decreased from 6.40 (IQR: 7.80) to 3.60 (IQR: 3.70) over the same period. The median change in mMASI scores in group B (2.90, IQR: 2.40) was significantly larger than in group A (0.90, IQR: 0.60) (p < 0.001, U = 160.50). However, there were no significant differences in the physicians' global assessment (PGA), melasma quality of life scale (MelasQoL) or patient satisfaction during follow-up. Four patients (15.4%) experienced transient erythema and swelling. In group B, 1 participant (7.7%) experienced transient mild gastrointestinal discomfort after receiving oral TXA. CONCLUSIONS: The combination of intradermal PRP injection and oral TXA is effective for melasma, even in patients with poor prognostic treatment response factors. No serious adverse reactions were observed in either group.

Long-Term Impact of Deep Brain Stimulation in Parkinson's Disease: Does It Affect Rehabilitation Outcomes?

Background and Objectives: Although the growing literature is now focusing on the long-term effects of Deep Brain Stimulation (DBS) in Parkinson's disease (PD), there is still a large gap of knowledge about its long-term implications in rehabilitation. Therefore, this study aimed at investigating the effects of rehabilitation in PD patients years after DBS implantation. Materials and Methods: This retrospective case-control study analyzed records from Moriggia-Pelascini Hospital, Italy from September 2022 to January 2024. Data of PD patients (n = 47) with (DBS group, n = 22) and without (control group, n = 25) DBS were considered. All study participants underwent a daily rehabilitation program lasting four weeks, including warm-up, aerobic exercises, strength training, postural exercises, and proprioceptive activities. The outcomes assessed were the Unified Parkinson's Disease Rating Scale (UPDRS), Berg Balance Scale (BBS), Timed Up and Go (TUG), 6 Min Walk Test (6MWT), and Self-Assessment Parkinson Disease Scale (SPDDS). Results: DBS group showed significant improvements in terms of all outcome measures after the rehabilitation intervention (UPDRS III: -7.0 (-11.5 to -1.0); p = 0.001; UPDRS I II IV: -12.0 (-19.0 to -4.5); p = 0.001; BBS: 7.0 (3.8 to 10.3); p < 0.001; TUG (s): -2.8 (-5.7 to -1.1); p < 0.001; SPDDS: -8 (-13.0 to -4.0); p < 0.001; 6MWT (m): 81 (37.3 to 132.3); p < 0.001). No differences were reported in the between-group analysis (p: NS). Conclusions: This study emphasizes positive rehabilitation effects on PD patients irrespective of DBS status. Further research is essential to elucidate long-term effects of DBS on rehabilitation outcomes of PD patients.

Impact of whole-genome duplications on structural variant evolution in Cochlearia.

Polyploidy, the result of whole-genome duplication (WGD), is a major driver of eukaryote evolution. Yet WGDs are hugely disruptive mutations, and we still lack a clear understanding of their fitness consequences. Here, we study whether WGDs result in greater diversity of genomic structural variants (SVs) and how they influence evolutionary dynamics in a plant genus, Cochlearia (Brassicaceae). By using long-read sequencing and a graph-based pangenome, we find both negative and positive interactions between WGDs and SVs. Masking of recessive mutations due to WGDs leads to a progressive accumulation of deleterious SVs across four ploidal levels (from diploids to octoploids), likely reducing the adaptive potential of polyploid populations. However, we also discover putative benefits arising from SV accumulation, as more ploidy-specific SVs harbor signals of local adaptation in polyploids than in diploids. Together, our results suggest that SVs play diverse and contrasting roles in the evolutionary trajectories of young polyploids.

Rare Filaggrin Variants Are Associated with Pustular Skin Diseases in Asians.

Reactive pustular eruptions (RPEs) can manifest in a variety of conditions, including pustular psoriasis (PP) and adult-onset immunodeficiency syndrome due to anti-interferon-γ autoantibody (AOID). These RPEs can be attributed to different causes, one of which is genetic factors. However, the genetic basis for pustular skin diseases remains poorly understood. In our study, we conducted whole-exome sequencing on a cohort of 17 AOID patients with pustular reactions (AOID-PR) and 24 PP patients. We found that 76% and 58% of the AOID-PR and PP patients, respectively, carried rare genetic variations within the filaggrin (FLG) gene family. A total of 12 out of 21 SNPs on FLG had previously received clinical classifications, with only p.Ser2706Ter classified as pathogenic. In contrast, none of the FLG3 SNPs identified in this study had prior clinical classifications. Overall, these variations had not been previously documented in cases of pustular disorders, and two of them were entirely novel discoveries. Immunohistochemical analysis of skin biopsies revealed that FLG variants like p.Ser860Trp, p.Gly3903Ter, p.Gly2440Glu, and p.Glu2133Asp caused reductions in FLG levels similar to the pathogenic FLG p.Ser2706Ter. These results highlight rare FLG variants as potential novel genetic risk factors contributing to pustule formation in both AOID and PP.

Syndromic Gastrointestinal Panel Diagnostic Tests Have Changed our Understanding of the Epidemiology of Yersiniosis-Foodborne Diseases Active Surveillance Network, 2010-2021.

Background: In the US, yersinosis was understood to predominantly occur in winter and among Black or African American infants and Asian children. Increased use of culture-independent diagnostic tests (CIDTs) has led to marked increases in yersinosis diagnoses. Methods: We describe differences in the epidemiology of yersiniosis diagnosed by CIDT versus culture in 10 US sites, and identify determinants of health associated with diagnostic method. Results: Annual reported incidence increased from 0.3/100 000 in 2010 to 1.3/100 000 in 2021, particularly among adults ≥18 years, regardless of race and ethnicity, and during summer months. The proportion of CIDT-diagnosed infections increased from 3% in 2012 to 89% in 2021. An ill person's demographic characteristics and location of residence had a significant impact on their odds of being diagnosed by CIDT. Conclusions: Improved detection due to increased CIDT use has altered our understanding of yersinosis epidemiology, however differential access to CIDTs may still affect our understanding of yersinosis.

Post-functionalization of triamino-phenazinium dyes to reach near-infrared emission.

This study presents the synthesis and characterization of phenazinium dyes with absorption ranging from red to far-red, as well as emission extending into the far-red to near-infrared (NIR) region. The procedure involves the post-functionalization of a triamino-phenazinium that was recently reported as a theranostic agent. The introduction of electron-withdrawing moieties is accomplished through acylation or aromatic nucleophilic substitution. For one of the obtained products, a further substitution step could be achieved with primary amines to tune the electron density of the phenazinium core. The isolated dyes exhibit promising features that hold potential for future applications as biological markers or therapeutic agents.