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Despite its high prevalence among dementias, Lewy body dementia (LBD) remains poorly understood with a limited, albeit growing, evidence base. The public-health burden that LBD imposes is worsened by overlapping pathologies, which contribute to misdiagnosis, and lack of treatments. For this report, we gathered and analyzed public-domain information on advocacy, funding, research outputs, and the therapeutic pipeline to identify gaps in each of these key elements. To further understand the current gaps, we also conducted interviews with leading experts in regulatory/governmental agencies, LBD advocacy, academic research, and biopharmaceutical research, as well as with funding sources. We identified wide gaps across the entire landscape, the most critical being in research. Many of the experts participated in a workshop to discuss the prioritization of research areas with a view to accelerating therapeutic development and improving patient care. This white paper outlines the opportunities for bridging the major LBD gaps and creates the framework for collaboration in that endeavor. HIGHLIGHTS: A group representing academia, government, industry, and consulting expertise was convened to discuss current progress in Dementia with Lewy Body care and research. Consideration of expert opinion,natural language processing of the literature as well as publicly available data bases, and Delphi inspired discussion led to a proposed consensus document of priorities for the field.

We demonstrated an ultra-sensitive terahertz virus detection method combined with virus-sized gold nanogaps filled with Al2O3. Large-area high-density 20 nm-gap rectangular loop structures, containing a resonant frequency in the terahertz range, were fabricated on a 4-inch wafer using atomic layer lithography. When target viruses with a 60 nm diameter were located on the nanogaps, we observed a significant redshift of the resonant peak already with an average number of about 100 viruses per unit loop due to the strong field confinement and enhancement near the gap. Furthermore, when the virus was tightly attached to an etched gap like a bridge connecting metals, its sensitivity is doubled compared to the unetched gap, which resulted in 400% more resonance frequency shift per single virus particle than our previous work. Full-wave simulations and theoretical calculations based on modal expansions were in good agreement with the experiments, revealing that the resonant transmission spectrum was mostly determined by the change in refractive index in a two-dimensional-like optical hotspot near the nanogap. A further step could be taken to increase sensitivity by tuning nanogap-loops to the absorption frequencies associated with the intermolecular vibrational modes of the viruses and fingerprinting them as well.

Site disorder between S and Cl anions at Wyckoff 4a and 4d sites is a key structural feature of the argyrodite Li6PS5Cl solid electrolyte in all-solid-state batteries. This first-principles study of the Li5.75PS4.75ClBr0.25 system is the first to report that S/Cl/Br anion disorder leads to an unexpected segregation of two anion sublattice domains, one composed of S anions and the other composed of Cl/Br anions. Increasing the degree of anion disorder enhances the stability of Li5.75PS4.75ClBr0.25, resulting in the formation of the most stable structure with anion segregation when the highest degree of anion disorder is reached. The anion segregation causes a greater distribution of Li ions in the S domain than in the Cl/Br domain, which greatly reduces the repulsion between S2− ions compared to the repulsion between Cl−/Br− ions and effectively stabilizes Li5.75PS4.75ClBr0.25. Li ions in the S domain move with difficulty due to the strong Li–S bonds, whereas Li ions in the Cl/Br domain can move relatively freely due to the weak Li–Cl (Li–Br) bonds, resulting in a high conductivity of 10.1 mS cm−1. This study suggests that domain-dependent Li migration due to anion segregation is the fundamental ion transport mechanism in Li6−xPS5−xClBrx and offers a new perspective for understanding superionic conductivity in Li6PS5Cl-based argyrodite solid electrolytes. [ABSTRACT FROM AUTHOR]

In this report, a tumor exhibited EWSR1 :: RORß gene fusion, to our knowledge, is the first such reported case. The Ewing sarcoma breakpoint region 1 gene (EWSR1) is known to be associated with several soft tissue tumors although its specific role remains unclear. Its fusion with a member of the ETS family, including FLI1 and ERG , results in Ewing sarcoma, and its fusion with other genes unrelated to the ETS family, including NFATC2 and PATZ1 , results in round cell sarcoma with EWSR1-non-ETS fusions, previously referred to as Ewing-like sarcoma. RORß encodes retinoic acid-related orphan receptor ß, a nuclear receptor (NR), and is involved in circadian rhythm modulation and cancer regulation. The specific role of ROR ß in tumorigenesis remains unclear; however, this case report suggests that it may form part of a new tumorigenic entity. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii primarily invades the central nervous system, causing latent infections. Cysts persist in the host for life and there is currently no effective treatment. T. gondii infects human hosts through contaminated meat, invading the intestinal tissue and leading to changes in the number and composition of the gut microbiota. Since probiotic ingestion modulates intestinal microbiota changes, we hypothesized that intestinal microbiota dysbiosis caused by T. gondii infection would be restored following probiotic supplementation. To this end, we orally infected C57BL/6 mice with 10 T. gondii cysts and administered supplemental probiotics daily. We analyzed the levels of T. gondii B1 gene DNA, indicative of T. gondii infection, in brain tissue. We investigated alterations in the gut microbiota composition and functional pathways between the probiotic and non-probiotic treatment groups via next-generation sequencing analysis of each fecal sample. The infection level in the probiotic-treated group was significantly reduced after 4 weeks (P<0.05). Probiotic supplementation notably changed the gut microbiota after 2 weeks of infection, increasing the relative abundance of Intestinimonas massiliensis and Lawsonibacter asaccharolyticus. Probiotic supplements appear to modulate the gut microbiota, activating functional pathways involved in intestinal short-chain fatty acid production and strengthening the intestinal barrier, thereby impeding T. gondii infection and subsequent proliferation. Our findings provide valuable insights into T. gondii infection control and future study directions. [ABSTRACT FROM AUTHOR]

Clonorchis sinensis, which causes clonorchiasis, is prevalent in East Asian countries and poses notable health risks, including bile duct complications. Although praziquantel is the primary treatment for the disease, the emerging resistance among trematodes highlights the need for alternative strategies. Understanding the nutrient uptake mechanisms in trematodes, including C. sinensis, is crucial for developing future effective treatments. This study aimed to characterize the function of C. sinensis glucose transporter 4 (CsGTP4) and determine its role in nutrient uptake employing synthesized cDNA of adult C. sinensis worms. The functional characterization of CsGTP4 involved injecting its cRNA into Xenopus laevis oocytes and analyzing the deoxy-D-glucose uptake levels. The results demonstrated that deoxy-D-glucose uptake depended on the deoxy-D-glucose incubation and CsGTP4 expression time, but not sodium-dependent. The concentration-dependent uptake followed the Michaelis–Menten equation, with a Km value of 2.7 mM and a Vmax value of 476 pmol/oocyte/h based on the Lineweaver–Burk analysis. No uptake of radiolabeled α-ketoglutarate, p-aminohippurate, taurocholate, arginine, or carnitine was observed. The uptake of deoxy-D-glucose by CsGTP4 was significantly inhibited by unlabeled glucose and galactose in a concentration-dependent manner. It was significantly inhibited under strongly acidic and basic conditions. These insights into the glucose uptake kinetics and pH dependency of CsGTP4 provide a deeper understanding of nutrient acquisition in trematodes. This study contributes to the development of novel antiparasitic agents, addressing a considerable socioeconomic challenge in affected regions. [ABSTRACT FROM AUTHOR]