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Inducing antigen-specific tolerance during an established immune response typically requires non-specific immunosuppressive signalling molecules. Hence, standard treatments for autoimmunity trigger global immunosuppression. Here we show that established antigen-specific responses in effector T cells and memory T cells can be suppressed by a polymer glycosylated with N-acetylgalactosamine (pGal) and conjugated to the antigen via a self-immolative linker that allows for the dissociation of the antigen on endocytosis and its presentation in the immunoregulatory environment. We show that pGal–antigen therapy induces antigen-specific tolerance in a mouse model of experimental autoimmune encephalomyelitis (with programmed cell-death-1 and the co-inhibitory ligand CD276 driving the tolerogenic responses), as well as the suppression of antigen-specific responses to vaccination against a DNA-based simian immunodeficiency virus in non-human primates. Our findings show that pGal–antigen therapy invokes mechanisms of immune tolerance to resolve antigen-specific inflammatory T-cell responses and suggest that the therapy may be applicable across autoimmune diseases. Established antigen-specific T-cell responses can be suppressed by conjugating the antigen to a glycosylated polymer, as shown in a mouse model of multiple sclerosis and with the suppression of responses to vaccination in non-human primates.

Soil health can differ across cropping systems because of variation in edaphic and management factors. We evaluated how biological indicators of soil health (soil organic matter [SOM], permanganate oxidizable carbon [POXC], mineralizable carbon [MinC], autoclaved‐citrate‐extractable [ACE] protein, and potentially mineralizable nitrogen [PMN]) compared across four common Wisconsin cropping systems: grazed cool‐season pastures, forage‐based rotations that included perennial legumes or grasses, annual rotations receiving manure, and annual rotations receiving synthetic fertilizers. Biological indicators of soil health were up to 195% greater in pastures than other cropping systems. MinC, POXC and PMN were 10%–90% greater in forage‐based rotations than annual cropping systems, but only MinC and POXC were greater in annual systems with manure compared to those without manure by 35% and 7%, respectively. Perennial vegetation and livestock integration offer the greatest potential to increase biological indicators of soil health in agricultural lands. Core ideas Wisconsin soil health assessment of 624 fields found that biological indicators were sensitive to cropping system. Mineralizable carbon (MinC), permanganate oxidizable carbon (POXC), and potentially mineralizable nitrogen (PMN) differed among cropping systems more than soil organic matter (SOM) or autoclaved‐citrate‐extractable (ACE) protein. Pastures were associated with greater SOM and biological indicators than annual rotations. Manure use in annual cropping systems was associated with greater POXC and MinC. Combining all five soil health principles is the key to healthier soils.

Uncontrolled hemorrhage from junctional wounds that cannot be controlled by traditional tourniquets accounts for one in five preventable battlefield exsanguination deaths. Products for treating these wounds are costly and require special training. However, chemically treated gauze products are inexpensive, potentially effective, and require only minimal training. This study was designed to assess the efficacy of three hemostatic gauze products following brief training, using a consensus swine groin injury model. After viewing a 15-minute PowerPoint presentation, without demonstration or practice, 24 U.S. Navy Corpsmen, most with little to no live tissue or hemostatic agent experience, applied one of three hemostatic agents: QuikClot Combat Gauze, Celox Trauma Gauze, or Hemcon ChitoGauze. Animals were resuscitated and monitored for 150 minutes to assess initial hemostasis, blood loss, rebleeding, and survival. Participants completed a survey before training and following testing. Products were similar in initial hemostasis, blood loss, and rebleeding. Twenty-three swine survived (96%). Ease of use and perceived efficacy of training ratings were high. Comfort level with application improved following training. Hemostatic gauze can potentially be effective for treating junctional wounds following minimal training, which has important implications for corpsmen, self-aid/buddy-aid, civilian providers, and Tactical Combat Casualty Care guidelines.

A urinary tract infection (UTI) can be diagnosed via urinalysis, consisting of a dipstick test and manual microscopic examination. Point-of-care (POC) image-based systems have been designed to automate the microscopic examination for low-volume laboratories or low-resource clinics. In this pilot study, acridine orange (AO) was evaluated as a fluorescence-based contrast agent to aid in detecting and enumerating urine sediment specific for diagnosing a UTI. Acridine orange staining of epithelial cells, leukocytes, and bacteria provided sufficient contrast to successfully implement image segmentation techniques, which enabled the extraction of classifiable morphologic features. Surface area bounded by each cell border was used to differentiate the sediment; epithelial cells were larger than 500μm2, bacteria were less than 30μm2, and leukocytes in between. This image-based semi-automated technique using AO resulted in similar cell counts to the clinical results, which demonstrates the feasibility of AO as an aid for POC urinalysis systems.

BackgroundDespite advances in therapy, sarcomas remain a significant unmet need.1 2 Median OS among patients with treatment-refractory soft tissue sarcomas (STS) treated with either trabectedin, pazopanib, or eribulin has been reported to range from 12.5 to 13.6 months.3 4 AXL, a cell-surface receptor tyrosine kinase, is highly expressed in several STS subtypes and has been shown to drive increased metastasis, resistance to chemotherapy, and poor outcomes.5 Mecbotamab vedotin (Mec-V, BA3011, Conditionally Active Biologic CAB-AXL-ADC) is designed to reduce off-tumor toxicity and improve pharmacokinetics by conditionally binding to AXL under low-pH conditions (pH<6.7) of the tumor microenvironment.6 7 MethodsA phase 2 open-label study evaluated Mec-V among adult and adolescent patients with AXL-expressing locally advanced, unresectable, or metastatic STS with measurable disease by RECIST v1.1. Patients received either Mec-V monotherapy 1.8 mg/kg every 2 weeks (Q2W) or Mec-V + nivo combination therapy.ResultsPhase 1 and 2 included 44 patients with STS, of whom 33 received Q2W and 11 received Q2W Mec-V + nivo. This report focuses upon the long term follow up among patients with leiomyosarcoma (LMS, n=27), liposarcoma (LPS, n=9), or undifferentiated pleomorphic sarcoma (UPS, n=8). Patients had a median of 2 prior lines of treatment. Most TEAEs were low grade and reversible; related grade 3/4 TEAE of special interest were neutropenia (21%), hepatic transaminase elevations (16%), and hyperglycemia (3%). No grade 5 TEAE were observed and 9% of related TEAE led to treatment discontinuation. 5% and 52% experienced partial response or disease control respectively. As of March 24, 2025, the OS with Mec-V in LMS, LPS, and UPS was 21.5 months (table 1). Landmark OS at 1 year was 73%. Median OS in Mec-V monotherapy vs. Mec-V + nivo combination therapy was 18.4 vs 22.9 months, respectively (table 1), across STS subtypes with 45% of events recorded.ConclusionsPatients with heavily pretreated leiomyosarcoma, liposarcoma, and undifferentiated mean pleomorphic sarcoma had a median OS of 21.5 months after treatment with Mec-V, a conditionally binding, AXL-targeting ADC. The manageable safety profile remained consistent with previous reports. Further evaluation of Mec-V, potentially in novel combinations, is justified.Trial RegistrationNCT03425279ReferencesZhang G, Liu Z, Xu H, Yang Q, et al. miR-124-3p inhibits cell growth and enhances chemosensitivity of osteosarcoma cells by targeting STAT3. Oncol Lett. 2018;15:2726–2734.Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2017. National Cancer Institute. Bethesda, MD. https://seer.cancer.gov/csr/1975_2017/. Based on November 2019 SEER data submission, posted April 2020.Italiano A, Delva F, Mathoulin-Pélissier S, et al. Frequency, characteristics, and management of gastrointestinal stromal tumors in daily practice. Cancer. 2011;117:1049-1054.Isakoff MS, Bielack SS, Meltzer P, Gorlick R, et al. Osteosarcoma: current treatment and a collaborative pathway to success. J Clin Oncol. 2015;33:3029-3035.Gay CM, Balaji AK, Byers LA, et al. Giving AXL the axe: targeting AXL in human malignancy. Br J Cancer. 2017;116:415-423.Chang HW, et al. Proc Natl Acad Sci USA. 2021;118(9):e2020606118.Dy GK, Yau E, Rotow J, et al. Exploratory analysis of overall survival among non-small cell lung cancer (NSCLC) patients with mutated KRAS in a phase 2 trial of mecbotamab vedotin (CAB-AXL-ADC). Presented at: European Lung Cancer Congress; 2025 Mar 26–29; Paris, France. Poster 98P.Ethics ApprovalThe study was performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and are consistent with ICH/GCP.Abstract 523 Table 1Best overall response

Foliar diseases, such as soybean rust (Phakopsora pachyrhizi) can cause severe defoliation and yield loss in soybean [Glycine max (L.) Merr.] and can be managed with an effective fungicide applied during the reproductive growth stages. The impact of soybean row spacing and fungicide application timing on canopy penetration and grain yield are unknown. The objectives of this experiment were (i) to quantify the impact of crop row spacing and spray application timing on penetration and coverage with a fungicide and (ii) to quantify the impact of sprayer wheel traffic during fungicide application on crop yield. The experiment was a split plot design with three replications conducted at the Northeast, Southeast, and Davis–Purdue Agricultural Centers (NEPAC, SEPAC, DPAC) in 2005 and 2006. The whole‐plot treatments were crop row spacing (19, 38, and 76 cm) and fungicide (azoxystrobin + propiconazole) [(methyl (E)‐2‐[2‐[6‐(2‐cyanophenoxy)pyrimidin‐4‐yl]oxyphenyl]‐3‐methoxy‐prop‐2‐enoate) + (1‐[[2‐(2,4‐dichlorophenyl)‐4‐propyl‐1,3‐dioxolan‐2‐yl]methyl]‐1,2,4‐triazole)] application timing (unsprayed or applications at growth stages R1, R3, R5, R3 + R5, or R1 + R3 + R5). Spray canopy coverage was quantified at 30‐cm increments within the soybean canopy. Crop row spacing affected spray canopy coverage at the R3 growth stage at the NEPAC location only. Application timing did not affect canopy coverage or spray penetration. Coverage decreased with depth in the canopy. Grain yield averaged 9% greater in the 19‐ and 38‐cm row spacing than in the 76‐cm row spacing. Fungicide application timing did not influence yield. Our research shows that fungicide application timing should not influence row spacing decisions. Growers should consider the effects of wheel‐track damage when planning spray applications during the reproductive growth stages of soybean.

Ten consecutive patients with failure of urinary bladder augmentation (UBA) performed either prior to or after reaching end-stage renal disease (ESRD) were studied. Seven patients developed increased hydroureteronephrosis, infectious complications, and advanced to ESRD after UBA. The mean time to development of ESRD in patients who had UBA performed with moderate chronic renal failure (CRF) was 1.8 years. The UBAs in all seven patients were taken down prior to transplantation. Subsequently, five of these UBA-takedown patients have received kidney grafts and all have stable, good renal function. Three patients had their UBA performed after they reached ESRD, in preparation for renal transplantation. All three of these patients experienced recurrent urosepsis following transplantation, resulting in death in one patient and loss of graft in another. The third patient will undergo takedown of the UBA. This study suggests that UBA may possibly not be the best option for patients with moderate CRF and those awaiting transplantation.