Browse Articles

Parameters for one health genomic surveillance of Escherichia coli from Australia

Abstract Genomics is a cornerstone of modern pathogen epidemiology yet demonstrating transmission in a One Health context is challenging, as strains circulate and evolve within and between diverse hosts and environments. To identify phylogenetic linkages and better define relevant measures of genomic relatedness in a One Health context, we collated 5471 Escherichia coli genome sequences from Australia originating from humans (n = 2996), wild animals (n = 870), livestock (n = 649), companion animals (n = 375), environmental sources (n = 292) and food (n = 289) spanning over 36 years. Of the 827 multi-locus sequence types (STs) identified, 10 STs were commonly associated with cross-source genomic clusters, including the highly clonal ST131, pandemic zoonotic lineages such as ST95, and emerging human ExPEC ST1193. Here, we show that assessing genomic relationships at ≤ 100 SNP threshold enabled detection of cross-source linkage otherwise obscured when applying typical outbreak-oriented relatedness thresholds ( ≤ 20 SNPs) and should be considered in interrogation of One Health genomic datasets.

How I treat adult Ph+ ALL

Abstract The Philadelphia (Ph) chromosome is one of the few genetic aberrations in which a casualty has been proven and, as such, represents a success in the history of medicine. This is also evident in the setting of Ph+ acute lymphoblastic leukemia (ALL), the most frequent genetic subgroup in adult ALL, whose incidence increases with age and whose prognosis, before the advent of tyrosine kinase inhibitors (TKIs), was particularly poor. The outcome and management of patients with Ph+ ALL have greatly improved since the incorporation of first-, second-, and third-generation TKIs in the therapeutic backbone and is further changing with the more recent introduction of immunotherapy. This allows for long-term survival rates currently ranging between 75% and 80%. The clinical scenario of adult Ph+ ALL has thus changed profoundly, and new challenges are emerging. In this article, illustrative clinical cases are used to discuss the current role of systemic chemotherapy and allogeneic stem cell transplant, the difficulty in treating central nervous system relapses and, more in general, relapses in the current therapeutic era, and the possibility of stopping TKIs. Finally, the challenges related to an optimal management of these patients are discussed.

U-shaped associations between body mass index and serum liver enzyme levels

Congestion avoidance in 6G networks with V Gradient Geocast Routing Protocol

AbstractThis is a moment of heavy necessity for a dependable internet connection in the modern world, which is used to engage in business dealings, communicate with other people, entertain oneself, and lead a daily life. Therefore, a Wi-Fi 6 router must have an internal wire-free connection within a house or business. However, as they depend on the weather and are installed in ways that expose them to infiltration, they are vulnerable. The increased demand for Internet services for business, communication, and leisure activities due to poor weather puts added stress on the network, slowing down the speeds and increasing congestion. The bottom line is to prioritize traffic and lower latency and convergence time to improve network performance under less-than-ideal weather conditions. This will be realized using highly technical approaches such as the mini-batch gradient descent optimization algorithm for network optimization and the V Gradient Geocast Routing Protocol for effective routing. The proposed enhanced congestion avoidance model with V Gradient Geocast Routing Protocol in 6G networks under unfavorable weather conditions attains an accuracy of 98.85%.

Efficient biodiesel production from waste cooking oil using a bifunctional Ce/Mn/γ-Al₂O₃ catalysts

Multiscale integral synchronous assembly of cuttlebone-inspired structural materials by predesigned hydrogels

Cost-effectiveness of iptacopan for paroxysmal nocturnal hemoglobinuria

Abstract Iptacopan, a novel oral factor B inhibitor, recently obtained US Food and Drug Administration approval for treating paroxysmal nocturnal hemoglobinuria, a rare blood disorder characterized by persistent complement-mediated hemolytic anemia. The standard-of-care (SOC) has traditionally relied on complement C5 inhibitors eculizumab and ravulizumab, which are limited by persistent anemia from extravascular hemolysis and requirement for intravenous infusion. Recent publication of phase 3 studies in this arena reinforces iptacopan as an effective anticomplement monotherapy compared with SOC. Given ongoing price negotiations and limited literature showing its cost-ineffectiveness in the anti-C5–treated population, we conducted a comprehensive cost-effectiveness analysis of iptacopan monotherapy in anti-C5–treated patients from the societal perspective, as compared with C5 inhibition. The primary outcomes were the incremental net monetary benefit across a lifetime horizon and the cost-effective maximum monthly threshold price of iptacopan monotherapy compared with the SOC. The secondary outcome was time saved for patients and nurses with the use of oral iptacopan therapy. Iptacopan monotherapy and SOC accrued 12.6 and 10.8 quality-adjusted life-years at costs of $9.52 million and $13.5 million, respectively. Iptacopan monotherapy remained cost saving across extensive sensitivity and all scenario analyses, including alternative parameterization for anemia resolution and aggregated individual-level utilities and transition probability matrix. Across all probabilistic sensitivity analyses, iptacopan monotherapy was favored over SOC in 100% of 10 000 Monte Carlo iterations. Cost-saving thresholds for iptacopan vs anti-C5 are ∼1.1, 1.4, and 1.4 in Brazil, Japan, and the United States, respectively. Iptacopan monotherapy can improve quality-adjusted life expectancy for patients while saving health care costs across jurisdictions.

The prognostic and immunomodulatory role of the MMR system in patients with stomach adenocarcinoma

Association between serum bicarbonate and 28-day mortality in critically ill patients with infective endocarditis: a cohort study from MIMIC-IV

Non-uniform failure mechanism and stability control of mining roadway under deviatoric stress field

Optimizing surface active sites via burying single atom into subsurface lattice for boosted methanol electrooxidation

How I treat postimmunotherapy relapsed B-ALL

Abstract Despite significant advancements in single-antigen targeted therapies for B-cell acute lymphoblastic leukemia (B-ALL), nonresponse and relapse persist as major challenges. Antigen escape after blinatumomab or CD19-directed chimeric antigen receptor (CAR) T cells (CD19-CAR), as CD19-negative B-ALL or lineage switch (LS) to acute myeloid leukemia, present diagnostic and treatment complexities. Given the poor outcomes for patients experiencing a postinfusion relapse, particularly those with loss of the target antigen, a strategic approach to diagnosis and treatment is imperative. In this discussion, we outline a systematic approach to managing postimmunotherapy events, categorized by CD19-positive relapse, CD19-negative relapse, and LS. We explore treatment modalities including CD19-CAR reinfusions, humanized CAR constructs, combinatorial strategies, and alternative antigen-targeted therapies, such as blinatumomab and inotuzumab. Challenges in diagnosis, particularly with antigen-escape, are addressed, highlighting the role of next-generation sequencing and multiparameter flow cytometry for myeloid marker monitoring.

Patterns of object play behaviour and its functional implications in free-flying common ravens

AbstractObject play has been proposed to provide individuals with information about their environment, facilitating foraging skills and tool use. In species where object play co-occurs with locomotor or social play, it may have additional functional implications, such as facilitating the evaluation of peers or forming social bonds. For instance, ravens judge others’ competitiveness via play caching and engage in social play by exchanging objects. However, most raven studies were conducted on a restricted number of individuals and under controlled captive settings. To validate these findings and to gauge the functional scope of object play under field conditions, we investigated the patterns and characteristics of object play in individually marked free-flying ravens in the Austrian Alps. Using two large data sets, we show a decrease in object play with age and a preference for playing longer with novel objects, supporting findings from captivity. We also find adults occasionally playing with objects and no difference in the duration of social or non-social object play bouts across age classes. Taken together, our findings are in line with the assumption that raven object play likely has more than one function and serves to gain information about the individual’s physical and social environment.

Evaluation of windproof and sand fixation effect of protective system in the Desert oasis ecotone of Mingsha Mountain Dunhuang

Combination of morphological and multiparametric MR neurography enhances carpal tunnel syndrome diagnosis and evaluation

The protein circPETH-147aa regulates metabolic reprogramming in hepatocellular carcinoma cells to remodel immunosuppressive microenvironment

An erythroid-specific lentiviral vector improves anemia and iron metabolism in a new model of XLSA

Abstract X-linked sideroblastic anemia (XLSA) is a congenital anemia caused by mutations in ALAS2, a gene responsible for heme synthesis. Treatments are limited to pyridoxine supplements and blood transfusions, offering no definitive cure except for allogeneic hematopoietic stem cell transplantation, only accessible to a subset of patients. The absence of a suitable animal model has hindered the development of gene therapy research for this disease. We engineered a conditional Alas2-knockout (KO) mouse model using tamoxifen administration or treatment with lipid nanoparticles carrying Cre-mRNA and conjugated to an anti-CD117 antibody. Alas2-KOBM animals displayed a severe anemic phenotype characterized by ineffective erythropoiesis (IE), leading to low numbers of red blood cells, hemoglobin, and hematocrit. In particular, erythropoiesis in these animals showed expansion of polychromatic erythroid cells, characterized by reduced oxidative phosphorylation, mitochondria’s function, and activity of key tricarboxylic acid cycle enzymes. In contrast, glycolysis was increased in the unsuccessful attempt to extend cell survival despite mitochondrial dysfunction. The IE was associated with marked splenomegaly and low hepcidin levels, leading to iron accumulation in the liver, spleen, and bone marrow and the formation of ring sideroblasts. To investigate the potential of a gene therapy approach for XLSA, we developed a lentiviral vector (X-ALAS2-LV) to direct ALAS2 expression in erythroid cells. Infusion of bone marrow (BM) cells with 0.6 to 1.4 copies of the X-ALAS2-LV in Alas2-KOBM mice improved complete blood cell levels, tissue iron accumulation, and survival rates. These findings suggest our vector could be curative in patients with XLSA.

Evaluating the relationship between news source sharing and political beliefs

Evaluating body roundness index and systemic immune inflammation index for mortality prediction in MAFLD patients

Cows that are less active in the chute have more optimal grazing distribution

AbstractIndividual grazing patterns among cattle can contribute to sustainability of land use, however, little is known about the consistency of these grazing patterns. To address this knowledge gap, fifty Angus x Hereford cows were observed in repeated assays: A management assay (handling procedure, narrow chute, hydraulic squeeze), a social-feed trade-off assay (SFTA; choice between social mates and feed item), and novel approach assay (choice between social mates and feed item with novel pattern). The same cattle were tracked with GPS collars over two grazing seasons (June-August 2021 and 2022) and average grazing-related metrics (e.g., elevation used, distance traveled) were calculated within each season. Cows with a more passive response in the chute were found at higher elevation (p = 0.017), further from water (p = 0.043), and closer to supplement sites (p = 0.029). Cows that had higher latency to supplement in the SFTA traveled shorter distances on rangeland (p = 0.035). Thus, there was some evidence that cows with a more passive response to isolation and management had more optimal grazing patterns (grazed underutilized areas of the range at higher elevations and further from water sources). Selecting cattle with more optimal foraging patterns based on observable behaviors during handling and isolation could improve the sustainability of rangeland grazing.