Dengue, an Aedes mosquito-borne viral infection, is on the rise with climate and demographic change. In 2023, WHO declared dengue its highest grade of emergency, following the largest number of cases and deaths in recorded history. This emergency highlighted the absence of safe and effective dengue-specific treatments as a gap in the product landscape for care for people with dengue. To accelerate development of dengue-specific treatments for wide implementation and access in all dengue-endemic countries, WHO conducted a landscape analysis of the dengue therapeutics pipeline and convened a global expert and public consultation to develop target product profiles for treatments for non-severe and severe dengue. These target product profiles provide strategic guidance for product developers, regulators, procurement agencies, and funders on the intended use, target populations, and key product characteristics of dengue-specific treatments required to meet public health needs, setting clear targets to drive development of dengue drugs accessible to those who need them the most.
Background: Older adults with acute myeloid leukemia (AML) represent a cancer population in which disease-based risk factors, comorbidities, patient goals, and treatment risks and benefits influence treatment recommendations. Objective: These evidence-based guidelines from the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health professionals in their decisions about management of AML in older adults. Methods: ASH formed a multidisciplinary guideline panel, including patient representatives, that minimized bias from conflicts of interest. Clarity Research Group at McMaster University supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized questions and outcomes according to their importance for clinicians and patients. The panel used the grading of recommendations assessment, development and evaluation approach, including evidence-to-decision frameworks, to assess evidence and make recommendations. Results: The panel agreed on 9 critical clinical recommendations for managing AML in older adults, mirroring real-time practitioner-patient conversations: the decision to pursue antileukemic treatment vs best supportive management; traditional induction and postremission therapy vs hypomethylating agent or low-dose cytarabine, or combinations with venetoclax; the role and duration of postremission therapy; combinations with venetoclax vs monotherapy; the use of targeted therapy, including isocitrate dehydrogenase and FMS-like tyrosine kinase 3 (FLT3) inhibitors, in appropriate patients; the role of hematopoietic stem cell transplantation in nonfavorable prognosis AML; and the role of transfusion support for patients no longer receiving antileukemic therapy. Conclusions: Key recommendations of these guidelines include treatment over best supportive care; venetoclax-based regimens over monotherapies; and incorporation of FLT3 inhibitors into traditional induction and postremission therapy.
A sample of patients with amyotrophic lateral sclerosis (ALS) and another with the SPG4 variant of hereditary spastic paraplegia (HSP-SPG4), affecting specifically lower limbs, were tested with two tasks employing upper-limb and lower-limb motion verbs either as literal isolated words or in literal and metaphorical sentences, controlling for cognitive impairment. At the group level, the expected disadvantage for action language emerged only in HSP-SPG4 patients, restricted to literal language, with no limb differences. At the single-case level, literal action-language impairment affected up to 50% of HSP-SPG4 patients, with the expected disadvantage for lower-limb verbs, but was negligible in ALS. Figurative action language was impaired in 20% of ALS and 40% of HSP-SPG4 patients, but somatotopic effects were limited. Findings support the motor simulation account at literal and figurative levels. Yet they also highlight the gradual nature of motor grounding disruption in motor neuron diseases, depending on linguistic contexts and clinical profiles.
The structure of LaxSr1-xTiO3 single-phase perovskites (0.10 <= x <= 0.30) was studied using synchrotron X-ray Powder Diffraction for Rietveld and Pair Distribution Function analysis. Electron Spin Resonance and X-ray Raman Scattering Spectroscopy confirmed that Sr substitution by La is charge compensated via electron injection into the conduction band. High-resolution diffraction (110-490 K) revealed phase transitions to a tetragonal phase with antiferrodistortive tilting (a 0 a 0 c - , in Glazer notation). Fitting the Ginzburg-Landau mean field equation indicated a transition regime between second-order and tricritical. The critical temperature (TC) and tilt order parameter (Phi 0) increase with La content up to x = 0.20, then decrease at x = 0.30. This non-monotonic behavior reflects an emerging local symmetry lowering toward Cmcm, supported by increased octahedral tilting and Bond Valence Sum analysis. The enhanced tilting offsets compensate for reduced thermal contraction of Ti3+-rich TiO6 octahedra below TC.
The present work introduces a sustainable strategy for biowaste valorization through the extraction and functionalization of biopolymers from Citrus limetta (bergamot) peel using natural deep eutectic solvents (NADES). A green NADES system composed of citric acid, glucose, and water (1:1:2 molar ratio) enabled an efficient extraction of polysaccharides, achieving a maximum yield of 28.11
