Discovery of a Potent Triazole-Based Reversible Targeted Covalent Inhibitor of Cruzipain.

Cruzipain (CZP) is an essential cysteine protease of , the etiological agent of Chagas disease, and a promising druggable target. To date, no CZP inhibitors have reached clinical use, with research efforts mostly hampered by insufficient potency, limited target selectivity or lack of bioactivity translation from the isolated enzyme to the parasite in cellular environments. In this study, we report the design of , a 1,2,3-triazole-based targeted covalent inhibitor with nanomolar potency (IC = 28 nM) and null inhibition of human cathepsin L.

Patient and Caregiver Perceptions of Caregiving Contributions During Cancer Clinical Trials: A Mixed-Methods Study.

Objective: Caregivers play crucial roles in cancer treatment and outcomes. However, little is known regarding how caregivers support patients during cancer clinical trials. The aim of this study was to gain insight into the caregiver experience of rural and urban patients enrolled in cancer clinical trials.

The 2023 dengue outbreak in Lombardy, Italy: A one-health perspective.

Introduction: Here we reported the virological, entomological and epidemiological characteristics of the large autochthonous outbreak of dengue (DENV) occurred in a small village of the Lombardy region (Northern Italy) during summer 2023.

Methods: After the diagnosis of the first autochthonous case on August 18, 2023, public health measures, including epidemiological investigation and vector control measures, were carried out. A serological screening for DENV antibodies detection was offered to the population.

Disentangling Sources of Momentum Fluctuations in Xe+Xe and Pb+Pb Collisions with the ATLAS Detector.

High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.

Heterogeneous integration of GaInAsSb-GaSb photodiodes on SOI photonic integrated circuits for SWIR applications.

We demonstrate the heterogeneous integration of GaInAsSb-GaSb photodiodes on 220 nm SOI photonic integrated circuits (PICs) using the micro-transfer-printing (μTP) technology, for operation in the short-wave infrared (SWIR) wavelength region. Utilizing an evanescent coupling scheme between a silicon waveguide and a III-V structure, the device exhibits a room temperature responsivity of 1.23 and 1.

Entomological investigation after an outbreak of dengue at the riverside of Rio Doce, Espírito Santo State, Brazil.

Background: In 2019, a dengue outbreak involving Aedes albopictus occurred in a rural area of Espírito Santo, Brazil, motivating our study in Sooretama and Linhares.

Methods: We set traps to sample immature mosquito larvae at 40 sites, with weekly inspections from July 2022 to January 2023. Adult specimens were collected monthly at 19 sites, each collection lasting 15 min.

DLK1 Is Associated with Stemness Phenotype in Medullary Thyroid Carcinoma Cell Lines.

Medullary thyroid carcinoma (MTC) is a rare and aggressive tumor, often requiring systemic treatment in advanced or metastatic stages, where drug resistance presents a significant challenge. Given the role of cancer stem cells (CSCs) in cancer recurrence and drug resistance, we aimed to identify CSC subpopulations within two MTC cell lines harboring pathogenic variants in the two most common MEN2-associated codons. We analyzed 15 stemness-associated markers, along with well-established thyroid stem cell markers (CD133, CD44, and ALDH1), a novel candidate (DLK1), and multidrug resistance proteins (MRP1 and MRP3).

Reduced expression of in differentiated thyroid cancer, the contribution of CPG methylation, and their clinical relevance.

Introduction: Forkhead box E1 () is a transcription factor with a crucial role in thyroid morphogenesis and differentiation. Promoter hypermethylation downregulates expression in different tumor types; nevertheless, its expression and relationship with methylation status in differentiated thyroid cancer (DTC) remain unclear.

Methods: A total of 33 pairs of matched samples of PTC tumors and non-tumors were included.

Evaluating imatinib in severe COVID-19: a systematic review and meta-analysis.

Background: Considering the potential antiviral and immunomodulatory properties of imatinib, this drug has been investigated in several studies as a potential treatment option for severe cases of COVID-19, given that treatment modalities available remain limited.

Objectives: To evaluate the benefits or otherwise of imatinib for COVID-19 in severely ill patients, we performed a systematic review of studies that tested the efficacy and the safety of imatinib for COVID-19 and executed a meta-analysis.

Methods: We searched Medline, Embase and Cochrane with the following search terms: 'coronavirus', 'SARS-Cov2', 'covid', 'covid-19' and 'imatinib'.

Improved light transmission for III-V lasers monolithically integrated on Si platforms.

We propose a strategy to monolithically integrate active III-V lasers and passive dielectric devices, where the passive waveguides are fabricated after the MBE growth of the III-V semiconductors on a planar Si substrate. This avoids any airgap at the active/passive interface, replaced by a thin dielectric interface layer which improves the light coupling efficiency. We demonstrate GaSb DLs butt-coupled to SiN waveguides with ∼23% transmission after 2 mm SiN, corresponding to ∼35% transmission at the active/passive interface.

Immunomolecular and reactivity landscapes of gut IgA subclasses in homeostasis and inflammatory bowel disease.

The human gut includes plasma cells (PCs) expressing immunoglobulin A1 (IgA1) or IgA2, two structurally distinct IgA subclasses with elusive regulation, function, and reactivity. We show here that intestinal IgA1+ and IgA2+ PCs co-emerged early in life, comparably accumulated somatic mutations, and were enriched within short-lived CD19+ and long-lived CD19- PC subsets, respectively. IgA2+ PCs were extensively clonally related to IgA1+ PCs and a subset of them presumably emerged from IgA1+ precursors.

Liver Transplantation and the Older Adults Candidate: Perioperative Considerations.

Pioneered by Thomas Starzl in the early 1970s, liver transplant (LT) is nowadays often considered a final intervention and standard of care to cure many forms of acute and chronic end-stage liver diseases. Started in recipients younger than 60 years old, LT indications are now much broader, and at least, one-fifth of the candidates are older than 65 years. Problems associated with ageing and frailty in LT recipients and their impact on the entire perioperative course are discussed according to a modern anesthesiological perspective and the anesthesiologist covering the role of the perioperative (transplant) physician.

Comparative Analysis of Quantitative Methods for spp. Quantification: ISO 10272-2:2017, Tempo and Real-Time PCR in Refrigerated and Frozen Turkey Cuts.

New technologies for more effective microbiological assays are being adopted by the food industry to intervene more rapidly in its production chain. The aim of this study was to evaluate the alternative methods of TEMPO CAM and real-time PCR (rtPCR) Biotecon in comparison with the ISO 10272-2:2017 reference method for spp. quantification in turkey meat, aiming to validate a quick and easily replicable method in these meat matrices.

The triglyceride-glucose index, blood glucose levels, and metabolic syndrome are associated with all-cause mortality in obesity.

Background: The Triglyceride-Glucose Index (TYG) has been proposed as a prognostic index for mortality in the general population, in T2DM, and in patients with cardiovascular diseases. However, data on the respective predictive roles of TYG, glucose tolerance (GT), and metabolic syndrome (MS) for mortality in obesity are lacking.

Methods: We analyzed 1359 obese patients (371 men and 988 women), aged 44.

Invisible burden: Prevalence of Chagas disease in Latin American migrants in Turin, North-Western Italy - A STROBE compliant-cross-sectional study.

Objectives: Chagas disease (CD), or American trypanosomiasis, is a parasitic disease caused by Trypanosoma cruzi, primarily transmitted by triatomine bugs. Increased travels and migrations introduced CD to non-endemic regions, including Europe. In Italy, the disease has raised public attention mainly in northern regions, where Latin American migrant population is larger.

Structures and pH-dependent dimerization of the sevenless receptor tyrosine kinase.

Sevenless (Sev) is a Drosophila receptor tyrosine kinase (RTK) required for the specification of the R7 photoreceptor. It is cleaved into α and β subunits and binds the ectodomain of the G-protein-coupled receptor bride of sevenless (Boss). Previous work showed that the Boss ectodomain could bind but not activate Sev; rather, the whole seven-pass transmembrane Boss was required.

Ginkgo biloba extract modulates astrocytic and microglial recruitment in the hippocampus and hypothalamus of menopause-induced ovariectomized rats.

Background: Changes in steroid hormone levels associated with menopause are known to affect body composition, with increased accumulation of visceral fat and impaired actions of appetite-regulating neuropeptides. Anti-obesogenic, antioxidant, anti-inflammatory and neuromodulatory properties have been attributed to Ginkgo biloba extract (GbE) oral supplementation.

Hypothesis/purpose: We investigated in menopause-induced ovariectomized rats the effects of GbE oral supplementation on microglial reactivity and astrocyte recruitment in hippocampal and hypothalamic subregions involved in the regulation of feeding behavior and energy homeostasis.

Membrane aerated biological reactors (MABRs) to enhance the biological treatment process at a WWTP.

The goal of climate neutrality, under the provision of the European Green Deal, will require great efforts to wastewater treatment plants (WWTPs) to reduce and optimize their energy consumption. The utilization of membrane aerated biological reactors (MABRs) to renovate existing WWTPs could be an opportunity in this sense. In this study, the control of the flow at the outlet of a pure, open-end MABR was used as a strategy to minimize the oxygen consumption and obtain high oxygen transfer efficiencies (OTEs).

Search for the Exclusive W Boson Hadronic Decays W^{±}→π^{±}γ, W^{±}→K^{±}γ and W^{±}→ρ^{±}γ with the ATLAS Detector.

A search for the exclusive hadronic decays W^{±}→π^{±}γ, W^{±}→K^{±}γ, and W^{±}→ρ^{±}γ is performed using up to 140  fb^{-1} of proton-proton collisions recorded with the ATLAS detector at a center-of-mass energy of sqrt[s]=13  TeV. If observed, these rare processes would provide a unique test bench for the quantum chromodynamics factorization formalism used to calculate cross sections at colliders. Additionally, at future colliders, these decays could offer a new way to measure the W boson mass through fully reconstructed decay products.

A conceptual data model for IMM: A methodological interpretation of targets and indicators in SDG11.

We are rapidly approaching the midpoint of the period set by the UN Agenda 2030 for transforming our activities on the planet Earth. Yet, many of the global issues we have begun with stand still while some of them took a much more severe course. The Sustainable Development Goals (SDGs) are unambiguous.

Gastrointestinal germinal center B cell depletion and reduction in IgA plasma cells in HIV-1 infection.

Gastrointestinal (GI) B cells and plasma cells (PCs) are critical to mucosal homeostasis and the host response to HIV-1 infection. Here, high-resolution mapping of human B cells and PCs sampled from the colon and ileum during both viremic and suppressed HIV-1 infection identified a reduction in germinal center (GC) B cells and follicular dendritic cells (FDCs) during HIV-1 viremia. Immunoglobulin A-positive (IgA) PCs are the major cellular output of intestinal GCs and were significantly reduced during viremic HIV-1 infection.

Albumin reprograms the B cell transcriptional landscape and improves neutrophil antimicrobial function in patients with decompensated cirrhosis.

Background & Aims: Patients with acutely decompensated (AD) cirrhosis are immunocompromised and particularly susceptible to infections. This study investigated the immunomodulatory actions of albumin by which this protein may lower the incidence of infections.

Methods: Blood immunophenotyping was performed in 11 patients with AD cirrhosis and 10 healthy volunteers (HV).