Growing concern about the quantity of available freshwater around the world has led to interest in surveying groundwater total dissolved solids (TDS) below water well depths. Deep TDS has not been systematically mapped, and there is much to learn about the distribution and controls on deeper groundwater. In sedimentary basins across the United States, groundwater resources often overlie hydrocarbon resources, providing an opportunity to use borehole geophysical data collected for hydrocarbons to characterize groundwater and pore space resources. This study adapts a recently developed subsurface geostatistical and geophysical modeling approach to continuously map groundwater TDS, porosity, and temperature in the Dakota Group of the Williston Basin-an undercharacterized regional aquifer system overlying deeper hydrocarbon reservoirs. Groundwater TDS in the Dakota Group ranges from approximately 4800 to 26,900 mg/L. TDS patterns are stratified with higher TDS in the lower and upper Dakota Group, and relatively lower TDS in the middle Dakota Group. The lower TDS in the middle zone may represent a preferential regional flow path for lower-TDS meteoric recharge from the west. The alternating pattern of TDS may also be evidence of higher-TDS inflows into the Dakota Group from underlying and potentially from overlying aquifers. Porosity is lower near the center of the Williston Basin and tends to be higher to the east, which may be related to grain size distributions. The new regional TDS and porosity modeling serves as a quantitative reference for water users and provides supporting evidence for hypotheses on Dakota Group recharge.
The Chicxulub asteroid impact at the Cretaceous-Paleogene (K-Pg) boundary triggered a mass extinction 66 million years ago. Ferns thrived in the aftermath of the extinction, evidenced by the well-documented "fern spore spike." However, fern macrofossil records across the K-Pg boundary are less understood. We analyzed 698 fern macrofossils from 19 Cretaceous and 83 Paleogene localities in the Raton (Colorado and New Mexico), Denver (Colorado), and Williston basins (North Dakota and Montana), grouping specimens into morphotypes using a newly developed descriptive schema. We examined familial affiliations and documented taxonomic and morphological turnover across the boundary. Additionally, herbivory and pathogen damage were categorized on each specimen. We identified 33 morphotypes: eight were found only in the Cretaceous, 12 in both the Cretaceous and Paleogene, and 13 only in the Paleogene. Two fern families were in the Cretaceous only, nine in both the Cretaceous and Paleogene, and five in the Paleogene only. Taxa that occur in both the Cretaceous and Paleogene occupied less morphospace than taxa that occur only in the Cretaceous or the Paleogene. Sixty-three specimens had herbivory or pathogen damage; one damage type was found in the Cretaceous only, nine in both the Cretaceous and Paleogene, and seven in the Paleogene only. Our data indicate possible changes in morphotype composition, family representations, morphological disparity, and insect herbivory across the K-Pg boundary. This research is important for understanding K-Pg recovery dynamics, fern adaptation, and their relation to deep time and modern catastrophic events.
Yellow fever (YF) is an infectious disease caused by the yellow fever virus (YFV), an arbovirus of the Flaviviridae family. It is transmitted through the bite of infected mosquitoes of the Culicidae family and affects both humans and non-human primates (NHPs). This study aimed to investigate the sylvatic Culicidae fauna and the occurrence of natural YFV infection in a microregion of southern Santa Catarina, Brazil, an area recently affected by a sylvatic YF outbreak. Entomological collections were conducted between January and February 2023 in five municipalities with confirmed viral circulation. Natural YFV infection was assessed using RT-LAMP. A total of 4352 female culicids were collected, representing at least 32 species, including several key sylvatic YFV vectors. Haemagogus leucocelaenus was identified in all sampled municipalities, whereas Haemagogus (Haemagogus) janthinomys Dyar, 1921, historically considered the primary vector of sylvatic YFV in Brazil, was not detected. Mosquitoes from the genera Aedes Meigen, 1818; Haemagogus Williston, 1896; Psorophora Robineau-Desvoidy, 1827; and Sabethes Robineau-Desvoidy, 1827 were tested for YFV. Only one pool, composed of Sabethes albiprivus, tested positive, yielding a minimum infection rate (MIR) of 11.6. This is the first record of natural YFV infection in Sa. albiprivus in southern Brazil, and only the third record globally, highlighting its potential role as a secondary vector in maintaining viral circulation in sylvatic environments. Based on species presence and abundance, Hg. leucocelaenus is likely to have acted as the primary YFV vector in the study area. The composition of the culicid fauna, coupled with the detection of YFV in sylvatic vectors, indicates an ongoing epidemiological risk. These findings underscore the need to strengthen entomological surveillance and expand YF vaccination coverage in affected and neighbouring regions.
Understanding the sensory nervous system's precise innervation of visceral organs remains a major challenge in systems neuroscience, particularly for designing neuromodulatory therapies. Here, we introduce a digital twin of the rodent stomach that combines high-resolution structural images and nerve-specific mapping onto a common coordinate scaffold. Using a pipeline developed within the NIH SPARC (Stimulate Peripheral Activity to Relieve Conditions) framework, we used immunohistochemistry (fluorescence and chromogenic) and anterograde tracing to label Calcitonin gene-related peptide (CGRP) axons and tracer-labeled spinal afferents in the whole stomach flat-mounts, digitized the axons, and registered axon data from nerve tracing experiments. These datasets were integrated into a standard scaffold, enabling cross-specimen alignment and annotation. The scaffold promotes integration of topographically anatomical and physiological metadata into the scaffold to enable simulation of neuromodulatory input effects, advances research on targeted nerve stimulation to improve organ function, and supports iterative development of closed-loop bioelectronic devices. The scaffold is publicly available via the SPARC Portal and supports modular extension to other species and organ systems. Our methodology contributes to a better understanding of the visceral afferent nervous system and multi-organ connectome, as well as establishing a reproducible computational framework for mapping and manipulating autonomic pathways in visceral organs, with applications spanning basic neuroanatomy to translational clinical intervention.
Mantle cell lymphoma (MCL) is a rare, aggressive form of non-Hodgkin lymphoma that arises from cells within the mantle zone (the outer ring of lymphocytes surrounding the center of a lymphatic nodule). Recent treatment advances, such as the introduction of Bruton tyrosine kinase inhibitors and chimeric antigen receptor T-cell therapies, have improved outcomes for many patients. Development of resistance is common, though, and relapse rates are high in MCL. The molecular mechanisms that contribute to resistance remain unclear, and the clinical heterogeneity of MCL can make it difficult to predict how patients will respond to treatment. Thus, there remains an urgent need for continued research on the molecular drivers of MCL pathogenesis, mechanisms of resistance, and novel strategies for targeting these pathways to improve outcomes for patients across the spectrum of disease. In April 2025, researchers gathered for the Lymphoma Research Foundation's 21st Mantle Cell Lymphoma Scientific Consortium and Workshop to discuss recent developments in the characterization and treatment of MCL. This report, which includes a summary of each presentation, aims to review the findings presented at the workshop and highlight new opportunities and unanswered questions in the care of patients with MCL, paving the way for novel treatments to improve outcomes and experiences in the years to come.
Explore modern metastatic breast cancer care: longer survival, smarter symptom control, caregiver support, and steps to close racial treatment gaps.
Bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CAR) T-cell therapies have transformed the management of hematologic malignancies, including relapsed/refractory multiple myeloma (RRMM), lymphomas, and leukemias. These approaches enable targeted cytotoxicity through T-cell redirection and engineered cellular activity, achieving high response rates in heavily pretreated populations. Data presented at the 2025 Immune Cell Effector Therapies (ICE-T) Symposium highlighted expansion beyond B-cell maturation antigen (BCMA) to additional targets such as GPRC5D and FcRH5, alongside emerging multitarget and next-generation constructs aimed at improving durability and overcoming resistance. This narrative review summarizes key findings from the 2025 ICE-T Symposium, integrating data from clinical trials, real-world studies, and contemporary guideline-based management, with a focus on efficacy, safety, sequencing, and emerging therapeutic platforms. Across hematologic malignancies, immune-based therapies demonstrated substantial and clinically meaningful activity, with outcomes varying by disease subtype, target antigen, and therapeutic platform. In multiple myeloma, BCMA-directed bispecific antibodies, including teclistamab and elranatamab, achieved overall response rates (ORRs) of approximately 63% and 61%, respectively, in heavily pretreated populations, with median progression-free survival (PFS) of approximately 11 to 17 months across pivotal studies. Talquetamab demonstrated ORR of approximately 73% to 74% in the MonumenTAL-1 study (NCT03399799), supporting efficacy in post-BCMA settings. Cevostamab has shown promising early-phase activity, with response rates of approximately 55% to 60% at higher dose levels, reflecting the expansion of therapeutic targets beyond BCMA. In B-cell lymphomas, CD19-directed CAR T-cell therapies, including axicabtagene ciloleucel and lisocabtagene maraleucel, produced high response rates with durable remissions in relapsed/refractory large B-cell lymphoma, with long-term follow-up demonstrating sustained survival in a subset of patients. Among bispecific antibodies, epcoritamab achieved an ORR of approximately 60% to 65%, whereas glofitamab demonstrated an ORR of approximately 45% to 50% in heavily pretreated populations, supporting their role as effective off-the-shelf therapeutic options. In acute lymphoblastic leukemia, CD19-directed CAR T-cell therapies, including tisagenlecleucel and brexucabtagene autoleucel, achieved high rates of remission with deep measurable residual disease negativity, supporting their role as definitive or bridging strategies in relapsed disease. Beyond hematologic malignancies, early-phase data highlighted the expansion of T cell-redirecting therapies into solid tumors. The DLL3-directed bispecific antibody tarlatamab demonstrated clinically meaningful activity in relapsed small cell lung cancer and has received accelerated regulatory approval based on response rate and durability. Safety profiles were broadly consistent across platforms. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were frequent but predominantly low grade and manageable with IL-6 blockade and corticosteroids. Infections and prolonged cytopenias represented the principal drivers of morbidity, emphasizing the need for structured supportive care. Contemporary recommendations from the NCCN and International Myeloma Working Group support proactive toxicity mitigation, antimicrobial prophylaxis, and multidisciplinary management. Emerging strategies, including trispecific antibodies, dual-target CAR T-cell constructs, and allogeneic "off-the-shelf" cellular therapies, demonstrated promising early efficacy and represent key approaches to improving durability, overcoming resistance, and expanding access across hematologic malignancies. T cell-redirecting therapies represent a central pillar in modern oncology, delivering high response rates across hematologic malignancies with expanding roles in earlier treatment settings. Future progress will depend on improving durability, optimizing sequencing, mitigating toxicity, and enhancing real-world deliverability through next-generation and multitarget platforms.
This study aims to understand the degree of influence of the severity of lymphedema on quality of life (QOL) in patients with breast cancer-related lymphedema (BCRL) during the maintenance phase, and to understand the influencing factors of QOL to identify targeted interventions to improve QOL for patients with BCRL. This cross-sectional study was conducted among patients with BCRL who underwent complete decongestive therapy during the intensive phase of BCRL treatment from January 2022 to December 2024 at the lymphedema outpatient clinic. General information and the specific QOL scale for upper limb lymphedema were collected. One-way ANOVA and multiple linear regression were used in IBM SPSS (Statistical Package for Social Sciences) version 25to analyze factors affecting QOL. This study included a total of 153 patients, with an overall QOL score of 48.52 plus or minus 12.112. Multivariate linear analysis indicated that the time from discovery of lymphedema to treatment and the severity of lymphedema affected the QOL of patients with BCRL during the maintenance phase. Long-term monitoring and timely treatment are necessary for patients with BCRL. Before the start of the maintenance phase, it is important for lymphedema therapists to treat BCRL disease as soon as possible.
This study compares the effect of virtual reality (VR) and pranayama breathing technique on preoperative anxiety in patients undergoing coronary artery bypass graft (CABG) surgery. The design was a three-arm parallel randomized controlled trial conducted across three open heart centers in Baghdad, Iraq. A sample of 122 patients were randomly assigned to VR (n = 45), pranayama (n = 40), and control (n = 37) groups. Anxiety was measured in pre- and postintervention using the Amsterdam Preoperative Anxiety and Information Scale (APAIS). The results were that there were no significant differences between the two active interventions, although the largest effect size was observed in the pranayama breathing technique intervention group (η2 = 0.381). Thus, both VR and pranayama breathing technique reduce preoperative anxiety among patients having CABG surgery and can be incorporated into routine preoperative nursing care.
The affordability of health care will be the top issue in the upcoming midterm elections. However, the discussion about health care affordability began more than 15 years ago with the passage of the Affordable Care Act (ACA), which was dubbed Obamacare. Under the ACA, every American was to have health insurance and access to care. Citing PolitiFact, Mark Memmott of National Public Radio in December 2013 reported that President Barack Obama told the "lie of the year," publicly claiming more than 35 times that "if you like your health care plan, you can keep it." The ACA was also supposed to allow patients to "keep their doctor" and save each family of 4 about $2500 per year, which never occurred.
Shared decision making (SDM) is an approach in which patients and healthcare providers simultaneously work to make decisions about tests, treatments, or chronic conditions management. To explore any possible interventions between cancer patients, nurses in the SDM process need to be up to data on the current literature. A global focused literature review of English and Italian language papers on the topic was done. The search included the use of the following terms: shared decision making, cancer patient, and nurse. Fourteen studies that were the best fit with the inclusion criteria were included to create this narrative review. The conclusion was that cancer nurses seemed to be relevant in cancer teams to support patients in their SDM processes. They do this by balancing the evidence on options, preferences, and values through a decision coaching approach to determine the best practices for supporting patients in their decisions.
Many data-driven approaches rely on scalable and affordable three-dimensional (3D) imaging across subcellular to organ scales. Although advances in tissue clearing, expansion microscopy and light-sheet microscopy (LSM) have enabled high-resolution imaging of intact specimens, scalability in sample size, throughput and accessibility remains fundamentally limited by detection optics. Here we introduce hybrid solid-liquid optics (HySIL), a flexible refractive design framework in which a solid optical element and a refractive index (RI)-matched liquid function as a continuous optical system for wavefront correction and numerical aperture enhancement. We implement this framework as SCOPE and Super-SCOPE, enabling submicron-resolution, aberration-corrected LSM using long-working-distance air objectives. We demonstrate high-resolution volumetric imaging across diverse biological contexts, including cleared and expanded mouse, salamander and cavefish brains, human induced pluripotent stem cell (iPSC)-derived brain organoids and large intact human tissues for 3D histopathology. By combining enhanced optical performance with low-cost, long-working-distance and multi-immersion compatibility, HySIL provides an accessible and scalable foundation for next-generation volumetric imaging and data-driven biological discovery.
We describe a unique clinical case of primary melanoma of the ascending colon presenting with intussusception and profuse hemorrhage. A 72-year-old man on anticoagulant therapy was admitted with massive rectal bleeding and hypotension. Colonoscopy revealed an 8-cm obstructing exophytic tumor. CT scan confirmed enteroenteric intussusception via the pathognomonic pseudokidney sign. Diagnosis was established by immunohistochemical analysis, demonstrating positive expression of S100 protein and melanoma-associated antigens, while negative for melanocyte antigen A and BRAF mutations. The patient underwent emergency right-sided hemicolectomy with lymphadenectomy. Pathomorphological evaluation confirmed stage T4aN0M0 (R0 resection). Following an accelerated recovery protocol, the patient started adjuvant immunotherapy with PD-1 inhibitors. This case underscores the need for a multidisciplinary approach and extended immunohistochemical profiling to diagnose rare mucosal pathologies. It highlights the effectiveness of radical surgery combined with modern systemic immunotherapy in emergency settings. Given the aggressive nature of mucosal melanoma, adhering to oncological guidelines and considering early immunotherapy are crucial for optimizing clinical outcomes.
The ability to adhere to mucus-lined tissues underpins a range of biomedical devices and therapies. However, many existing strategies rely on covalent bonding chemistries and can be unstable, cytotoxic, or incompatible with therapeutics. Here, we present a bacteria-mimetic bioadhesion strategy inspired by Vibrio cholerae. A short Bap1-derived adhesion peptide is grafted onto chitosan to strengthen mucus interactions through multivalent, cooperative secondary bonding, while preserving pH-triggered interfacial bridging behavior. Bacterial peptide grafting significantly increases adhesion energy on porcine intestine, and when paired with a tough hydrogel matrix achieves adhesion energies >400 J m-2 without forming covalent bonds to tissue. Confocal imaging reveals deep tissue penetration (∼80 µm) with markedly enhanced mucin binding and no loss of cytocompatibility. Ex vivo intestinal delivery and in vitro drug release tests demonstrate improved drug transport and tissue exposure compared to carbodiimide-mediated covalent bonding strategy. These findings establish a bacteria-mimetic bioadhesion strategy for tissue repair and drug delivery.
This cross-sectional study evaluated the genetic landscape of a cohort of patients with metastatic prostate cancer who were treated at a referral center in Mexico City, Mexico.
The tight adherence (Tad) pilus is a broadly distributed and evolutionarily distinct subclass of type IV pili that mediate cell adhesion, biofilm formation, predation, and surface sensing in many bacteria, including Caulobacter crescentus, Myxococcus xanthus, Vibrio vulnificus, and Bifidobacterium breve. Tad pili undergo cycles of extension and retraction powered by a cell-envelope-embedded nanomachine. Despite their biological importance, the architecture and assembly mechanism of the Tad pilus system remain poorly understood. Although cryo-electron tomography (cryo-ET) has elucidated the in situ architectures of other type IV pilus systems, no intact Tad machine structure has previously been reported. Here, we use cryo-ET and subtomogram averaging to resolve the architecture of the C. crescentus Tad pilus within the bacterial cell envelope. A three-dimensional classification further reveals multiple assembly intermediates, and integrative modeling incorporating AlphaFold3 predictions helps define the spatial arrangement of all core components. The resulting structural framework gives insight into the stepwise assembly process of the C. crescentus Tad pilus machine. Altogether, our results provide an in situ architectural model of the Tad pilus machine, establishing a foundation for understanding homologous systems across a broad range of bacteria. Investigating the Tad pilus nanomachine in a genetically tractable, non-pathogenic organism like Caulobacter crescentus provides a powerful model for elucidating the architecture and functional dynamics of this widespread system. Insights gained from studying the Tad machinery can improve our understanding of related Tad pilus systems in pathogenic bacteria such as Aggregatibacter actinomycetemcomitans, where Tad pili are a key determinant of biofilm formation and chronic infection. Additionally, the remarkable functional diversity of Tad systems, ranging from surface sensing in C. crescentus to bacterial predation in Myxococcus xanthus, highlights their broad biological relevance. By revealing the in situ architecture of the Tad pilus biosynthetic machinery, this study advances our understanding of a major class of bacterial nanomachines and may thus provide structural insights that could inform the development of new therapeutic strategies targeting pilus-mediated virulence.
Persons with spinal cord injury are at high risk of developing pressure injuries, and their caregivers are in a critical position to help prevent them. The objective of this study was to evaluate the effectiveness of an educational program for caregivers of persons with spinal cord injuries to prevent pressure injuries in Iraq. A pre- and post-test design was used and involved 25 caregivers of persons with spinal cord injury during the acute care phase in an SCI-specific unit of a hospital. A scale and questionnaire were used to gather the participants' demographic information, pre- and post-educational program knowledge, and observations of their pre- and post-program performance of pressure injury preventive tasks. Descriptive statistics and inferential statistics were calculated using SPSS (Version 26.0). The educational program effectively increased caregivers' knowledge and improved pressure injury prevention performance. The findings are discussed from a global nursing perspective.
The purpose of this study is to assess the level of moral development, spiritual intelligence, and critical thinking of nurses, and to see if there is a relationship between these constructs for them. A descriptive correlational design was used, with a sample of 102 nurses in Iran. The descriptive statistics and Pearson's correlation were done on the survey results using SPSS (Version 24). The moral development level scores of the nurses were 34 ± 2.17, which is considered average, critical thinking was 25 ± 1.23, which is considered relatively high, and spiritual intelligence scores were 41 ± 2.75, which is considered relatively low. Both spiritual intelligence and critical thinking were positively correlated with the nurses' moral development (R = 0.76, R = 0.48, respectively). The conclusion of the paper is that more attention needs to be paid to raise the level of critical thinking, spiritual intelligence, and moral development in nurses.
Immunotherapy has transformed the treatment of a variety of malignancies, including breast cancer. Given the unmet clinical need, immunotherapy was first studied in advanced-stage, triple-negative breast cancer (TNBC). The anti-PD-1 agent pembrolizumab plus chemotherapy is approved for both advanced and early TNBC, and data from randomized phase 3 trials in high-risk, early-stage, hormone receptor-positive breast cancer have demonstrated promising efficacy. Ongoing trials aim to identify the most appropriate patients for treatment, amount and timing of immunotherapy needed for optimal outcomes, and ideal combination of therapies to maximize survival while minimizing toxicity. The future of immunotherapy in breast cancer will continue to evolve with the advent of novel immunologic agents. In this review, we highlight pivotal trials that have informed current practice and ongoing trials that may inform the therapeutic landscape in the coming years.
Three-dimensional (3D) ex vivo imaging of cleared tissue from intact brains from animal models, human brain surgical specimens, and large postmortem human and non-human primate brain specimens is essential for understanding physiological neural connectivity and pathological alterations underlying neurological and neuropsychiatric disorders. Contemporary light-sheet microscopy enables rapid, high-resolution imaging of large, cleared samples but is limited by the orthogonal arrangement of illumination and detection optics, which constrains specimen size. Light-sheet theta microscopy (LSTM) overcomes this limitation by employing two oblique illumination paths while maintaining a perpendicular detection geometry. Here, we report the development of a next-generation, fully integrated and user-friendly LSTM system that enables uniform subcellular-resolution imaging (with subcellular resolution determined by the lateral performance of the system) throughout large specimens without constraining lateral (XY) dimensions. The system provides a seamless workflow encompassing image acquisition, data storage, pre- and post-processing, enhancement and quantitative analysis. Performance is demonstrated by high-resolution 3D imaging of intact mouse brains and human brain samples, including complete downstream analyses such as digital neuron tracing, vascular reconstruction and design-based stereological analysis. This enhanced and accessible LSTM implementation enables rapid quantitative mapping of molecular and cellular features in very large biological specimens.