University of Missouri–St. Louis

The incidence and endemic range of human babesiosis are expanding. Standard therapy for human babesiosis consists of antimicrobials developed for other indications. While these treatments are adequate in immunocompetent hosts, infections in the immunocompromised can be severe, relapsing, and drug-resistant despite the use of multi-drug regimens. Existing drugs are ineffective in the immunocompromised because they cannot achieve and maintain adequate serum concentrations to inhibit Babesia . Discovery of improved agents against Babesia spp. is of growing importance, and efficient techniques for high-throughput compound screening can assist in this effort. We developed a high-throughput in vitro drug screening assay for Babesia duncani that is conducted in 384-well plates and makes use of the fluorescent DNA stain propidium iodide (PI) with relative fluorescence measured by a microplate reader. A Z′ factor of 0.82 was calculated, which suggests an excellent ability to detect inhibitory compounds. A screen of the 41-compound library Structural Genomics Consortium Bug Box was conducted, yielding five hits: trimethoprim, atovaquone, SDDC M7, diphenyleneiodonium chloride, and panobinostat. Panobinostat, a histone deacetylase complex (HDAC) inhibitor, was selected for further evaluation given that its target had not been previously explored in B. duncani . Dose-response testing of structurally related compounds revealed multiple potential leads, including nanatinostat and quisinostat, both of which were potent at the nanomolar level and showed favorable selectivity index in cytotoxicity studies. High-throughput screening using PI and 384-well plates is an advance in drug discovery for babesiosis, and HDAC inhibitors show promise as lead compounds worthy of further investigation.

Soybean (Glycine max L. Merr.) is a critical crop for food security and economic development in tropical regions, particularly in Indonesia. Despite its importance, the productivity of soybean in these areas is hindered by challenging climatic conditions, leading to a reliance on imports from temperate regions. Here, we identify genotypes that exhibit superior agronomic traits and stability, thereby contributing to improved soybean productivity in tropical environments. The multi‐trait genotype‐ideotype distance index (MGIDI) and multi‐trait stability index (MTSI) were employed to evaluate the genotypes' performance in relation to an ideal ideotype and their stability across the environments. Additionally, the Genotype Main Effect Plus G × E Interaction (GGE) Biplot analysis was utilised to examine genotype‐by‐environment interactions and to identify the most suitable environments for soybean cultivation. The MGIDI index analysis identified the 100‐seed weight (W100) as a key trait with the highest selection gain. The MTSI identified genotypes G11, G18 and G14 as the most stable across all environments. The GGE Biplot analysis indicated E2 (Upland, rainy season) as the most ideal environment for selecting superior soybean genotypes, suggesting it is the optimal setting for future breeding efforts. This study highlighted the importance of multi‐trait selection and stability analysis in identifying soybean genotypes with both desirable traits and environmental stability for diverse tropical conditions. These findings offer strategic insights for future soybean breeding and cultivation in tropical regions.

Sphingolipids are important and abundant lipids in the plasma membrane, and their homeostasis plays a key role in plant growth, development, and stress responses. We previously found that non-specific phospholipase C4 (NPC4) hydrolyzes sphingophospholipids upon phosphate starvation. Here, we defined the downstream steps of sphingolipid remodeling by identifying glucosylceramide synthase (GCS) and its regulatory mechanisms in Arabidopsis thaliana. Phosphate deficiency induces the expression of GCS, and the encoded GCS enzyme mediates glucosylceramide biosynthesis. Down-regulation of GCS severely affects sphingolipid homeostasis and hinders plant growth under phosphate starvation. Accordingly, GCS over-expression promotes sphingolipid remodeling to maintain plant growth. In addition, PHOSPHATE STARVATION RESPONSE1 (PHR1), a key regulator of phosphate homeostasis, directly affects the expression of NPC4 and GCS to regulate sphingolipid remodeling during phosphate starvation. Together, these results identify the PHR1–NPC4–GCS module as a regulatory mechanism that fine-tunes sphingolipid homeostasis and reveal the importance of sphingolipid homeostasis in the plant response to phosphate deficiency.

Abstract Innovations in 3D tissue imaging have revolutionized research, but limitations stemming from lengthy protocols and equipment accessibility persist. Widefield microscopy is fast and accessible but often excluded from 3D imaging workflows due to its lack of optical sectioning. Here we combine tissue clearing with a depth-variant deconvolution approach customized for large-volume widefield imaging to achieve subnuclear axial resolution in tissues to a depth of 500 µm. We illustrate the utility of this method in a model of ileitis and to gain a 3D perspective in thick brain slices from a model of cerebral amyloid angiopathy, where we resolved amyloid deposits along small blood vessels, attaining resolution that compared favorably to confocal microscopy. Finally, we leveraged our approach for richer pathological evaluation of human kidney biopsies. Our approach produced hundreds of consecutive z-planes in five minutes of imaging for 3D visualization of winding arterioles entering glomeruli. This perspective afforded straightforward identification of atrophic tubes in kidney biopsies prepared in 2 hours to simulate donor kidney evaluation before transplant. Having achieved subnuclear z-resolution in sections hundreds of microns thick, widefield microscopy coupled to robust deconvolution now emerges as an accessible and viable method to gain 3D insight in research or clinical evaluations.

Instead of a scholarly paper, we decided to write a brief, personal remembrance of our friend and colleague Jim Moor. We briefly touch on his personal kindnesses to us, his significant influence on legitimizing computer ethics as an object of study, and why we think Jim was so effective in reaching scholars across disciplinary divides.

With the increasing food demands of a global population projected to reach 9.6 billion by 2050, there is an urgent need to increase crop productivity. Bioengineering approaches to boost crop yields include enhancing photosynthetic capacity, though relatively few efforts focus on C4 crop species despite their significant presence in agriculture. Multiple photosynthesis engineering examples utilize overexpression of components of the nuclear‐encoded machinery, while work on chloroplast‐encoded photosynthetic genes is limited to the few dicot species where plastid transformation technology exists. We present here a novel approach to photosynthetic gene engineering in maize using a nuclear‐encoded, chloroplast‐targeted TALE‐cytidine deaminase enzyme to create non‐photosynthetic knockout mutants of the chloroplast rbcL gene. An off‐target mutation in the adjacent atpB gene, encoding the β subunit of ATP synthase, was consistently found in all edited lines, identified as pigment‐deficient in tissue culture. These double mutants, carrying mutations in both genes, were purified to homoplasmy using unique leaf‐base regeneration techniques. To test mutation complementation and identify the causal gene, nuclear transgenic lines overexpressing chloroplast‐targeted RbcL and AtpB proteins were generated. The results show that nuclear expression of AtpB restores chlorophyll accumulation and supports wild‐type growth in tissue culture. Nonphotochemical quenching (NPQ) function was restored, and the maximum quantum yield of photosystem II (Fv/Fm) reached about 30% of wild‐type levels in the nuclear‐transformed lines. This is the first demonstration in a monocot plant that complementation of a photosynthetic mutant via nuclear gene expression is possible, providing a facile method for future photosynthetic engineering.

This article investigates the implications that theater role-taking has on identity transformation for individuals recently released from prison in the United States. Drawing upon 15 in-depth and semistructured interviews with individuals recently released from prison involved in a theater program, this study finds that theater role-taking provides the gateway to personal identity role-taking at three levels: the self, the family, and the broader society. At each level individuals are simultaneously accessing the roles of the “agentic self,” “the responsible family member,” and “the productive citizen.” These personal identity role-taking opportunities have implications for how individuals engage in “performing rehabilitation” or the presentation of self, which identifies reentering individuals as “changed.” As individuals engage in a presentation of self that are aligned with the rehabilitative ideas of the state, the theater program extends notions of rehabilitation that mirror those found across the reentry landscape.

Background Kidney disease significantly increases the risk of dementia, including among kidney transplant (KTx) recipients. To date, the cost implications of dementia after KTx are not well described. Methods We performed a retrospective cohort study of US Renal Data System (USRDS) data (2006–2020) to estimate cost of care for ≥65‐year‐old Medicare insured KTx recipients (2006–2020) with newly diagnosed dementia ( n = 3285), compared to propensity‐matched controls without dementia ( n = 6570). KTx recipients age 65+ years with post‐KTx dementia were identified by diagnosis codes, and costs were computed based on payments on Medicare claims. Average costs per month, marginal costs per month, and cumulative costs were compared after dementia diagnosis versus after the equivalent time post‐KTx in controls. Results Dementia was diagnosed at a mean of 5.1 ± 3.4 years post‐KTx. Patients' characteristics were well matched in cases versus controls, including age (mean: 70.1 vs. 69.9 years), sex (38.4% vs. 37.9% women), race (23.7% vs. 22.2% African American), and cause of ESKD (45.4% vs. 43.7% diabetes). Over 4 years post‐KTx, dementia was associated with reduced survival (27% vs. 68%) along with $66 145 (95$51 560‐$78 489) higher Medicare spending. Average monthly costs in dementia patients reached a maximum of$12 713 and exceeded the cost of unaffected patients by up to $9789 per month. Conclusions Post‐KTx dementia dramatically increased resource utilization and reduced post‐KTx surivival. These findings highlight the need for care pathways that better integrate cognitive health assessment and management into the care of KTx candidates and recipients.

Relapsed/refractory T-cell acute lymphoblastic leukemia (ALL)/lymphoma (LBL) represent a significant unmet medical need. WU-CART-007 is a CD7-targeting, allogeneic, fratricide-resistant chimeric antigen receptor T cell product generated from healthy donor T cells. WU-CART-007 was evaluated in a phase 1/2 study with a 3+3 dose-escalation design followed by cohort expansion in relapsed/refractory T-ALL/LBL. Patients received one infusion of WU-CART-007 after standard or enhanced lymphodepleting chemotherapy. The primary objectives, to characterize safety and assess the composite complete remission rate, were met. Of 28 patients enrolled, 13 received the recommended phase 2 dose (RP2D) of 900 million cells of WU-CART-007 with enhanced lymphodepletion. The most common treatment-related adverse event was cytokine release syndrome (88.5%; 19.2% grade 3-4). Two grade 1 immune effector cell-associated neurotoxicity syndrome events (7.7%) and one grade 2 acute graft-vs-host disease event occurred (3.8%). One grade 2 immune effector cell associated HLH-like syndrome (IEC-HS) was observed. Among the 11 patients evaluable for response at the RP2D who received enhanced lymphodepleting chemotherapy, the overall response rate was 90.9% and composite complete remission rate was 72.7%. WU-CART-007 at the RP2D demonstrated a high response rate in patients with relapsed/refractory T-ALL/LBL and has the potential to provide a new treatment option. ClinicalTrials.gov registration: NCT04984356.

Throughout sub‐Saharan Africa and the African diaspora, there is documented oppression of girls and women. While many policies and laws have been created to improve the well‐being of this population, many of them are ineffective, oftentimes due to harmful cultural practices enshrined by systems of oppression. This paper conducts a cross‐cultural comparative analysis using the framework of intersectionality to explore the unique oppression that girls and women experience in sub‐Saharan Africa and the African diaspora. Specific cultural practices and policies will be analyzed using Ghana and the United States. In Ghana, we explore the Trokosi system as a cultural practice which negatively influences the well‐being of girls and women. In the United States, we explore the child welfare system, which we argue also negatively influences the well‐being of Black girls and Black women. Similarities and differences related to the underlying oppression that both groups experience are explored in detail utilizing both contextual intersectionality and situated intersectionality.

Research on sentencing typically measures the sentence with either a dichotomous in/out variable that combines prison and jail sentences, or with a continuous variable of the length of the sentence. Holleran and Spohn called this into question, arguing that combining prison and jail into a “total incarceration” measure can lead to overly simplistic findings. We use data from Miami-Dade County, Florida ( N = 40,240) to replicate and extend Holleran and Spohn’s research, with additional model flexibility for both in/out and sentence length. We find that not only are there distinct disparities that would have been undetected using the total incarceration variable, but these disparities also vary across the sentence length distribution.

Background Magnetic Resonance‐guided Radiation Therapy (MRgRT) systems are increasingly used in clinical practice, necessitating a dedicated dosimetry protocol to address the challenges posed by the presence of strong magnetic fields. Purpose AAPM TG351 introduces a reference dosimetry protocol for external beam MRgRT systems, aligning with AAPM TG51 reports and incorporating elements from the IAEA TRS398 code of practice. Methods The protocol offers practical guidance on beam quality and dosimetry setup in the presence of strong magnetic fields. It reviews relevant literature to identify reference‐class chambers suitable for external beam MRgRT systems and determines their beam quality conversion and other relevant correction factors through a detailed analysis of available data and associated uncertainties. Results AAPM TG351 offers a comprehensive dosimetry protocol for external beam MRgRT systems, addressing the unique challenges posed by the presence of magnetic fields. It includes detailed guidance for measurement setups, a list of reference‐class chambers appropriate for reference dosimetry in MRgRT systems, and updated beam quality conversion and correction factors. Additionally, the protocol presents an in‐depth analysis of the uncertainty budget, identifying key contributors and providing strategies to minimize uncertainties, thereby enhancing clinical accuracy and reliability. Conclusions This protocol provides a practical, evidence‐based reference for medical physicists conducting reference dosimetry in external beam MRgRT systems.

While semi‐autonomous drones are increasingly used for road infrastructure inspection, their insufficient ability to independently handle complex scenarios beyond initial job planning hinders their full potential. To address this, the paper proposes a human–drone collaborative inspection approach leveraging flexible surface electromyography (sEMG) for conveying inspectors' speech guidance to intelligent drones. Specifically, this paper contributes a new data set, sEMG Commands for Piloting Drones (sCPD), and an sEMG‐based Cross‐subject Classification Network (sXCNet), for both command keyword recognition and inspector identification. sXCNet acquires the desired functions and performance through a synergetic effort of sEMG signal processing, spatial‐temporal‐frequency deep feature extraction, and multitasking‐enabled cross‐subject representation learning. The cross‐subject design permits deploying one unified model across all authorized inspectors, eliminating the need for subject‐dependent models tailored to individual users. sXCNet achieves notable classification accuracies of 98.1% on the sCPD data set and 86.1% on the public Ninapro db1 data set, demonstrating strong potential for advancing sEMG‐enabled human–drone collaboration in road infrastructure inspection.

Introduction Lipedema is a chronic and progressive disease that predominantly affects women, characterized by a disproportionate increase in subcutaneous adipose tissue (AT), particularly in the lower limbs. It is associated with significant physical disability, chronic pain, thromboembolism, and psychosocial distress. Despite its profound impact on women's health and quality of life, lipedema remains underrecognized and insufficiently studied, with an estimated prevalence of approximately 10% among women worldwide. Although the exact etiology of lipedema remains unclear, emerging evidence suggests a multifactorial origin involving genetic predisposition, hormonal influences, and vascular dysfunction—all contributing to its development and progression. Current therapeutic options provide only partial symptom relief and remain noncurative, highlighting the urgent need for expanded research and improved management strategies. Methods A systematic review was conducted to assess the current understanding of lipedema pathophysiology and current treatment options. Research articles were sourced from PubMed, Web of Science, ScienceDirect, and Scopus databases. Over 100 studies were incorporated. Results This review provides a comprehensive overview of lipedema, encompassing its clinical features, pathophysiological mechanisms, diagnostic challenges, and current treatment modalities. Additionally, the review discusses whether the molecular and metabolic differences between abdominal and femoral AT depots mirror those observed in classical obesity. Conclusions Multidisciplinary, research‐informed care is essential for managing lipedema, combining conservative therapies, tailored exercise, and liposuction for advanced cases. More research to better understand the underlying pathophysiology is critical to developing targeted treatments, improving diagnostic accuracy, and informing standardized, evidence‐based care.

Malaria is a major global health burden, yet its associated pain manifestations—headache, myalgia, abdominal pain, back pain, and joint pain—are often overlooked and poorly understood. In this narrative review, the prevalence, clinical presentation, mechanisms, and management of malaria-related pain are explored. Pain may arise from inflammatory responses triggered by cytokine release, endothelial dysfunction, ischemia due to microvascular obstruction, and, in severe cases such as cerebral malaria, neuroinflammation. Despite its clinical significance, pain management in malaria remains suboptimal, with limited research guiding treatment. Analgesics, such as acetaminophen and nonsteroidal anti-inflammatory drugs, may provide relief but could influence disease progression. Addressing malaria-associated pain is crucial for improving patient outcomes, particularly in endemic regions where pain assessment is often inadequate. A better understanding of its’ underlying mechanisms is essential for developing evidence-based treatment strategies and improving clinical care.