A novel entomopathogenic nematode (EPN) species, Steinernema tarimense n. sp., was isolated from soil samples collected in a Populus euphratica forest located in Yuli County within the Tarim Basin of Xinjiang, China. Integrated morphological and molecular analyses consistently place S. tarimense n. sp. within the ‘kushidai-clade’. The infective juvenile (IJ) of new species is characterized by a body length of 674–1010 μm, excretory pore located 53–80 μm from anterior end, nerve ring positioned 85–131 μm from anterior end, pharynx base situated 111–162 μm from anterior end, a tail length of 41–56 μm, and the ratios D% = 42.0–66.6, E% = 116.2–184.4, and H% = 25.5–45.1. The first-generation male of the new species is characterized by a curved spicule length of 61–89 μm, gubernaculum length of 41–58 μm, and ratios D% = 36.8–66.2, SW% = 117.0–206.1, and GS% = 54.8–82.0. Additionally, the tail of first-generation female is conoid with a minute mucron. Phylogenetic analyses of ITS, 28S, and mt12S sequences demonstrated that the three isolates of S. tarimense n. sp. are conspecific and form a sister clade to members of the ‘kushidai-clade’ including S. akhursti, S. anantnagense, S. kushidai, and S. populi. Notably, the IJs of the new species exhibited faster development at 25°C compared to other Steinernema species. This represents the first described of an indigenous EPN species from Xinjiang, suggesting its potential as a novel biocontrol agent against local pests.

Background: Deep brain stimulation (DBS) in Parkinson’s disease (PD) requires extensive trial-and-error programming, often taking over a year to optimize. An objective, rapid biomarker of stimulation success is needed. Our team developed a functional magnetic resonance imaging (fMRI)-based algorithm to identify optimal DBS settings. This study prospectively compared fMRI-guided programming with standard-of-care (SoC) clinical programming in a double-blind, crossover, non-inferiority trial. Methods: Twenty-two PD-DBS patients were prospectively enrolled for fMRI using a 30-sec DBS-ON/OFF cycling paradigm. Optimal settings were identified using our published classification algorithm. Subjects then underwent >1 year of SoC programming. Clinical improvement was assessed under SoC and fMRI-determined stimulation conditions. Results: fMRI optimization significantly reduced the time required to determine optimal settings (1.6 vs. 5.6 months, p<0.001). Unified Parkinson’s Disease Rating Scale (UPDRSIII) improved comparably with both approaches (23.8 vs. 23.6, p=0.9). Non-inferiority was demonstrated within a predefined margin of 5 points (p=0.0018). SoC led to greater tremor improvement (p=0.019), while fMRI showed greater bradykinesia improvement (p=0.040). Conclusions: This is the first prospective evaluation of an algorithm able to suggest stimulation parameters solely from the fMRI response to stimulation. It suggests that fMRI-based programming may achieve equivalent outcomes in less time than SoC, reducing patient burden while potentially enhancing bradykinesia response.

Objectives/Goals: Large-scale tumor sequencing efforts have led to annotations of novel cancer hotspot mutations that may underlie driver or cooperative function. We have sought to define the molecular consequences of such hotspots associated with pediatric DICER1 syndrome cancers, with the ultimate goal of revealing novel targets that may inform new standards of care. Methods/Study Population: We have performed genomic analysis to identify tumor types (in TCGA and MSK-IMPACT patient data) for which mutations in the Dicer1 gene (encoding Dicer protein) emerge as the dominant signature of driver function. As Dicer is a critical RNA processing factor responsible for the generation of microRNAs, which are posttranscriptional gene regulatory molecules, we have modeled these mutations in human embryonic stem cells in order to study the direct effects on miRNAs and their target genes in an isogenic background. In addition to providing the required setting for unambiguous attribution of function to specific mutations, clonal human ES cells offer an opportunity for modeling of both developmental and cancer requirements associated with altered Dicer function. Results/Anticipated Results: Through generation of genomics and functional datasets from matched genotypes in Dicer mutated human ES cells, we have identified specific alterations in miRNAs and their effects on target genes. Unexpectedly, we found direct evidence for both loss of function and gain of function attributable to Dicer mutations. In addition, through integrated analysis of genomic data from tumor sequencing datasets and our human ES cell models, we have identified potential miRNA and target gene alterations that underlie tumorigenic potential, nominating gene candidates for targeted therapy in DICER1 syndrome. Direct mouse modeling of such candidate gene targets has revealed evidence for driver function of identified miRNA and their targets. Discussion/Significance of Impact: DICER1 syndrome cancers comprise a wide variety of rare pediatric tumor types. Presently, we still lack an effective standard of care. Furthermore, the previous lack of molecular profiling precluded targeted therapy opportunities. Our precise knock-in modeling of Dicer hotspots and deep profiling of relevant tumors now provide candidate targets.

Brown dwarfs are failed stars with very low mass (13–75 Jupiter mass) and an effective temperature lower than 2 500 K. Their mass range is between Jupiter and red dwarfs. Thus, they play a key role in understanding the gap in the mass function between stars and planets. However, due to their faint nature, previous searches are inevitably limited to the solar neighbourhood (20 pc). To improve our knowledge of the low mass part of the initial stellar mass function and the star formation history of the Milky Way, it is crucial to find more distant brown dwarfs. Using James Webb Space Telescope (JWST) COSMOS-Web data, this study seeks to enhance our comprehension of the physical characteristics of brown dwarfs situated at a distance of kpc scale. The exceptional sensitivity of the JWST enables the detection of brown dwarfs that are up to 100 times more distant than those discovered in the earlier all-sky infrared surveys. The large area coverage of the JWST COSMOS-Web survey allows us to find more distant brown dwarfs than earlier JWST studies with smaller area coverages. To capture prominent water absorption features around 2.7 ${\unicode{x03BC}}$m, we apply two colour criteria, $\text{F115W}-\text{F277W}+1\lt\text{F277W}-\text{F444W}$ and $\text{F277W}-\text{F444W}\gt\,0.9$. We then select point sources by CLASS_STAR, FLUX_RADIUS, and SPREAD_MODEL criteria. Faint sources are visually checked to exclude possibly extended sources. We conduct SED fitting and MCMC simulations to determine their physical properties and associated uncertainties. Our search reveals 25 T-dwarf candidates and 2 Y-dwarf candidates, more than any previous JWST brown dwarf searches. They are located from 0.3 to 4 kpc away from the Earth. The spatial number density of 900–1 050 K dwarf is $(2.0\pm0.9) \times10^{-6}\text{ pc}^{-3}$, 1 050–1 200 K dwarf is $(1.2\pm0.7) \times10^{-6}\text{ pc}^{-3}$, and 1 200–1 350 K dwarf is $(4.4\pm1.3) \times10^{-6}\text{ pc}^{-3}$. The cumulative number count of our brown dwarf candidates is consistent with the prediction from a standard double exponential model. Three of our brown dwarf candidates were detected by HST, with transverse velocities $12\pm5$, $12\pm4$, and $17\pm6$ km s$^{-1}$. Along with earlier studies, the JWST has opened a new window of brown dwarf research in the Milky Way thick disk and halo.

In 2023 all Supplemental Nutrition Assistance Program (SNAP) participants were allowed to start grocery shopping online. This paper provides the first answer to the question: What is online shopping worth to the SNAP participant in dollars? Using meal-kit pricing and time-use data, an implicit wage rate and dollar value distribution are estimated for time saved in home food production from online grocery shopping. We report the 95th, 75th, 50th, 25th, and 5th percentile results. We simulate saving 50%, 75%, and 90% of grocery shopping time and estimate the savings per hour per meal. For example, if online shopping saved 75% of shopping time, the median saving per hour per meal would be $2.59. If a family of four made 15 to 30 meals a month, this corresponds to an implicit 5% to 11% increase in the benefits per month due to the time saved. The implicit wage rate provides simple and elegant economic insights into many aspects of food production and consumption not obtainable by just considering the money price.

Most people with mental illness in low and middle-income countries (LMICs) do not receive biomedical treatment, though many seek care from traditional healers and faith healers. We conducted a qualitative study in Buyende District, Uganda, using framework analysis. Data collection included interviews with 24 traditional healers, 20 faith healers, and 23 biomedical providers, plus 4 focus group discussions. Interviews explored treatment approaches, provider relationships, and collaboration potential until theoretical saturation was reached. Three main themes emerged: (1) Biomedical providers’ perspectives on traditional and faith healers; (2) Traditional and faith healers’ views on biomedical providers; and (3) Collaboration opportunities and barriers. Biomedical providers viewed faith healers positively but traditional healers as potentially harmful. Traditional and faith healers valued biomedical approaches while feeling variably accepted. Interest in collaboration existed across groups but was complicated by power dynamics, economic concerns, and differing mental illness conceptualizations. Traditional healers and faith healers routinely referred patients to biomedical providers, though reciprocal referrals were rare. The study reveals distinct dynamics among providers in rural Uganda, with historical colonial influences continuing to shape relationships and highlighting the need for integrated, contextually appropriate mental healthcare systems.

The cyst nematodes, subfamily Heteroderinae, are plant pathogens of worldwide economic significance. A new cyst nematode of the genus Cactodera within the Heteroderinae, Cactodera xinanensis n. sp., was isolated from rhizospheres of crops in the Guizhou and Sichuan provinces of southwest China. The new species was characterized by having the cyst with a length/width = 1.3 ± 0.1 (1.1–1.6), a fenestral diameter of 28.1 ± 4.3 (21.3–38.7) μm, vulval denticles present; second-stage juvenile with stylet 21.5 ± 0.5 (20.3–22.6) μm long, tail 59.4 ± 2.0 (55.9–63.8) μm long and hyaline region 28.7 ± 2.7 (25.0–36.3) μm long, lateral field with four incisures; the eggshell with punctations. The new species can be differentiated from other species of Cactodera by a longer tail and hyaline region of second-stage juveniles. Phylogenetic relationships within populations and species of Cactodera are given based on the analysis of the internal transcribed spacer (ITS-rRNA), the large subunit of the nuclear ribosomal RNA (28S-rRNA) D2-D3 region and the partial cytochrome oxidase subunit I (COI) gene sequences here. The ITS-rRNA, 28S-rRNA and COI gene sequences clearly differentiated Cactodera xinanensis n. sp. from other species of Cactodera. A key and a morphological identification characteristic table for the species of Cactodera are included in the study.