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A data-driven group retrosynthesis planning model inspired by neurosymbolic programming
Introduction to a How I Treat series on acute lymphoblastic leukemia
Edited by Associate Editor Hervé Dombret, this How I Treat series highlights the clinical approach to high-risk subgroups of acute lymphoblastic leukemia (ALL). These include adult Philadelphia chromosome (Ph)–positive ALL, Ph-like ALL, infant acute ALL, early T-cell precursor ALL, Ph-negative ALL in older patients, and postimmunotherapy relapsed B-cell ALL. Using illustrative cases, the authors outline the approach to these patients, with recommendations with regard to targeted therapies, novel therapeutic approaches, and the changing role of allogeneic stem cell transplantation.
First report on comprehensive genomic analysis of a multidrug-resistant Enterobacter asburiae isolated from diabetic foot infection from Bangladesh
Narrative mobile video game-based cognitive training to enhance frontal function in patients with mild cognitive impairment
Abstract Although cognitive training has been proposed as a possible therapeutic modality for mild cognitive impairment (MCI), most serious games focus on specific tasks. This study aimed to investigate the feasibility and efficacy of narrative video game-based cognitive intervention for MCI. A four-week (± 1-week) mobile game intervention was given to 17 MCI participants (mean age (SD) = 72.8(4.75)). At baseline and post-intervention, the participants received neuropsychological tests and a depression scale. Frontal function was assessed using the Corsi block-tapping test, Color Word Stroop Test, Controlled Oral Word Association Test, Digit Symbol Coding, and Trail Making Test-Elderly’s Version; depression was assessed using the Geriatric Depression Scale. User’s compliance and gaming experience were also evaluated. MCI patients showed significant improvements in frontal function, particularly in Digit Symbol Coding (mean ± SD, 0.47 ± 0.49, p = 0.007) and phonemic fluency (mean ± SD, 0.39 ± 0.55, p = 0.024). Each frontal subtest’s mean z-score was increased (mean ± SD, 0.44 ± 0.38, p = 0.008). Block span and depression scale remained unchanged. High adherence rates (122.35%) and favorable feedback on the gaming experience indicated that the game intervention’s usability boosted patients’ motivation and engagement. Our findings demonstrate that narrative game-based cognitive intervention was not only beneficial but also enjoyable for elderly MCI.
A novel approach for agricultural carbon emission reduction by integrating fermatean neutrosophic set with WINGS and AHP-EWM
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.