The number of orthotopic lung transplants (OLT) has skyrocketed since the 1960s, generating an ever-increasing cohort of post-OLT patients. Many challenges exist in the post-OLT timeframe, including donor graft dysfunction, infection, malignancy, and immunosuppression-related conditions. A rather elusive topic in the posttransplant setting remains the impact of the underlying disease process and donor lungs on other organ systems and the complications arising from the complex physiologic interactions. The liver represents a vital organ often impacted in many ways by the lung transplant procedure. Also, there is a higher likelihood of adverse outcomes in OLT recipients who have significant liver pathology. Yet little is known about the morphologic changes in liver after patients have received an OLT. In this study we retrospectively reviewed liver pathology cases obtained after the patient received an OLT.

To compare a deep learning (DL)-accelerated non-enhanced abbreviated MRI (AMRI) protocol with standard AMRI (AMRI) of the liver in terms of image quality and malignant focal lesion detection.

FOLR1 is heterogeneously overexpressed in epithelial ovarian cancer. We examined the combined effects of the anti-FOLR1 antibody-drug conjugate (IMGN853) with other drugs, including topotecan, anti-VEGF-A antibody, and olaparib. These findings could contribute to the continued development of IMGN853 in the treatment of ovarian cancer.

Pancreatic ductal adenocarcinoma (PDAC) tumor heterogeneity impedes the development of biomarker assays for early disease detection. We hypothesized that PDAC cell subpopulations could be identified by aberrant glycan signatures in both tumor tissue and blood samples. We used multiplexed glycan immunofluorescence to distinguish between PDAC and noncancer cell subpopulations within tumor tissue, and we developed hybrid glycan sandwich assays to determine whether the aberrant glycan signatures could be detected in blood samples. We found that PDAC cells were identified by signatures of glycans detected by four glycan-binding proteins (VVL, CA19-9, sTRA, and GM2) and that there are three types of glycan-defined PDAC tumors: sTRA type, CA19-9 type, and intermixed. In patient-matched tumor and blood samples, the PDAC tumor type could be determined by the aberrant glycans in the blood. As a result, the combined assays of aberrant glycan signatures were more sensitive and specific than any individual assay. Our results demonstrate a methodology to detect and stratify PDAC.

Background Although artificial intelligence is actively being developed for prostate MRI, few studies have prospectively validated these tools. Purpose To compare the diagnostic performance of a commercial deep learning algorithm (DLA) and radiologists' clinical reports for cancer detection in participants from two hospitals using histopathologic findings from biopsy specimens as the reference standard. Materials and Methods This prospective bicenter study enrolled participants suspected of having prostate cancer (PCa) who were scheduled for biopsy based on clinical information, including prostate MRI, from December 2022 to July 2023. Targeted prostate biopsies were performed for lesions with Prostate Imaging Reporting and Data System (PI-RADS) scores of 3 or higher, identified by either radiologists or the DLA. PI-RADS classifications by radiologists (using all imaging sequences), the DLA (using biparametric MRI), and the scenario in which radiologist-based PI-RADS 3 scores were modulated with DLA-based PI-RADS scores were compared using the area under the receiver operating characteristic curve (AUC) with DeLong and McNemar tests. Results A total of 259 lesions, including 117 clinically significant PCas (csPCas) (Gleason grade group ≥2), were evaluated in 205 men (median age, 68 years; age range, 47-90 years). At per-lesion analysis, the DLA had a lower sensitivity (94 of 117; 80%) and higher positive predictive value (PPV) (94 of 163; 58%) for detecting csPCa than did the radiologists (109 of 117 [93%] and 109 of 227 [48%]; = .02 and = .008, respectively). At per-participant analysis, incorporation of the DLA increased specificity from 23 of 108 (21%) to 48 of 108 (44%) ( = .001), with similar sensitivity (96 of 97 [99%] vs 93 of 97 [96%]; = .74). There was no evidence of a difference in the AUC between radiologist-based and DLA-based PI-RADS score (0.77 [95% CI: 0.70, 0.82] vs 0.79 [95% CI: 0.73, 0.85]; = .73). Conclusion The DLA demonstrated lower sensitivity but a greater PPV than radiologists for detecting csPCa in a biopsy setting. Using DLA results when radiologists' interpretations are indeterminate could improve specificity while maintaining sensitivity. International Clinical Trials Registry Platform registration no. KCT0006947 © RSNA, 2025 .

Concussion is a common consequence of engaging in collision sports, with the often mild, transient nature of symptoms posing a considerable diagnostic and management challenge. This challenge is vastly magnified for athletes competing at grassroots/non-professional levels, who lack field side access to medical expertise in the assessment of a player's capacity to continue playing or need for further medical attention. The aim of this pilot study was to evaluate the utility of the BrainEye application and hardware (BrainEye platform) as a concussion screening tool, specifically determining (1) its sensitivity and specificity with respect to identifying an individual with a clinically diagnosed concussion, (2) the stability of the platform through test completion/failure rates, and (3) its usability through operator feedback and uptake/integration into concussion management protocols.

Data on the comparative usefulness of medications commonly prescribed to individuals with alcohol use disorder (AUD) are scarce. This study compared the association between antidepressants, relapse-preventive AUD medication, both, and neither on the risk of subsequent alcohol-related hospitalization in individuals with severe AUD. This retrospective analysis of Swedish nationwide register data used Cox (primary analysis) and logistic (sensitivity analysis) regression models to assess the associations between medication exposure (antidepressants, AUD medication, both, neither) and risk of subsequent alcohol-related hospitalization. The analysis included data on 14,026 individuals who were admitted to the hospital for severe AUD between 2009 and 2020. Antidepressants were not significantly associated with a lower risk of subsequent alcohol-related hospitalization (hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.82-1.08), but AUD medication was (HR = 0.61, 95% CI = 0.54-0.69), as were antidepressants plus AUD medication (HR = 0.63, 95% CI = 0.45-0.87) (reference: exposure to neither). Pairwise comparisons showed that AUD medication was associated with a lower risk of hospitalization than antidepressants (HR = 0.65, 95% CI = 0.54-0.78). Antidepressants alone were associated with a higher risk than antidepressants plus AUD medication (HR = 1.50, 95% CI = 1.05-2.15). The sensitivity analysis confirmed the association between AUD medication and lower hospitalization risk. Antidepressant monotherapy was not associated with a lower risk of subsequent alcohol-related hospitalization, but relapse-preventive medication for AUD was, both alone and in combination with antidepressants. These findings support the use of relapse-preventive medication to reduce hospitalization risk in individuals with severe AUD and raise questions about the benefit of antidepressant monotherapy for this purpose.

Proton exchange membrane water electrolysis (PEMWE) technology commercialization strongly relies on developing efficient and cost-effective anode catalysts. One key challenge is the high cost associated with IrO, which can be mitigated by reducing iridium (Ir) loading. A promising approach to achieving this is using a conductive support material to anchor Ir/IrO. In this study, we explored depositing metallic Ir on antimony-doped tin oxide (ATO) using a solid-state method. This approach is straightforward and time-efficient. Among four samples with 50 wt % Ir loading, one prepared with NaOH in 100% ethanol (Ir/ATO-NE) exhibited the highest specific oxygen evolution reaction (OER) performance. The Ir/ATO-NE catalyst achieved 340 A g at 1.6 V (versus RHE), surpassing a commercial IrO catalyst, which showed 282 A g. Additionally, Ir/ATO-NE demonstrated the lowest Tafel slope, indicating enhanced oxygen evolution kinetics and long-term durability comparable to commercial catalysts. Electron microscopy revealed uniform Ir nanoparticle (NP) sizes and a complete layer of Ir NPs on the support, in contrast to other samples. This study introduces a synthesis protocol for Ir catalysts that is efficient, simple, and effective for oxygen evolution in acidic media.

The use of tramadol and other opioids for pain management has been accompanied by a multitude of challenges and concerns worldwide. The use of tramadol saw a decline in Denmark during 2017-2019 accompanied by a slight increase in the use of morphine and oxycodone. Using the Danish National Prescription Registry and utilizing data until and including 2023, we aimed to provide updated data on the utilization patterns of tramadol and other opioids in Denmark. We found a 35% decline in the use of tramadol from 2017 to 2023 most likely due to media attention, regulatory actions, health campaigns and targeted education of physicians and patients by the Danish health authorities. This decline was accompanied by an increase in the number of new (+90%) and current users of morphine (+57%), which surpassed those of tramadol, oxycodone and other opioids in 2023.

is one of the closest relatives of the highly host-adapted and uncultivable hemotrophic mycoplasma. The complete genome of strain 117C was constructed from long-reads derived from Pacific Biosciences single-molecule, real-time sequencing technology. The genome is organized into one circular, gapless chromosome with a length of 1,034 kb.

Despite the high prevalence of alcohol use disorder (AUD), only a minority of patients receive recommended pharmacological treatments, possibly owing to uncertainty about the real-world effectiveness of these medications. Here, we analyzed nationwide, register-based data to investigate the association between approved AUD medications (naltrexone, acamprosate, disulfiram, and nalmefene) and the risk of alcohol-related hospitalizations among individuals with AUD.

Mitochondria play an essential role in the life cycle of eukaryotic cells. However, we still don't know how their ultrastructure, like the cristae of the inner membrane, dynamically evolves to regulate these fundamental functions, in response to external conditions or during interaction with other cell components. Although high-resolution fluorescent microscopy coupled with recently developed innovative probes can reveal this structural organization, their long-term, fast and live 3D imaging remains challenging. To address this problem, we have developed a CNN, called DeepCristae, to restore mitochondria cristae in low spatial resolution microscopy images. Our network is trained from 2D STED images using a novel loss specifically designed for cristae restoration. To efficiently increase the size of the training set, we also developed a random image patch sampling centered on mitochondrial areas. To evaluate DeepCristae, quantitative assessments are carried out using metrics we derived by focusing on the mitochondria and cristae pixels rather than on the whole image as usual. Depending on the conditions of use indicated, DeepCristae works well on broad microscopy modalities (Stimulated Emission Depletion (STED), Live-SR, AiryScan and LLSM). It is ultimately applied in the context of mitochondrial network dynamics during interaction with endo/lysosome membranes.

Intraductal papillary mucinous neoplasms (IPMN) occur in 5-10% of the population, but only a small minority progress to pancreatic ductal adenocarcinoma (PDAC). The lack of accurate predictors of high-risk disease leads both to unnecessary operations for indolent neoplasms as well as missed diagnoses of PDAC. Digital spatial RNA profiling (DSP-RNA) provides an opportunity to define and associate transcriptomic states with cancer risk.

Changes in psychotropic drug use relative to suicidal behavior could potentially inform the timing of preventive efforts. We aimed to describe the initiation and discontinuation of psychotropic drugs relative to suicide and suicide attempts.

The syndrome "bassess richesses" is a vector-borne disease of sugar beet in Germany. The gammaproteobacterium ' Arsenophonus phytopathogenicus' causes reduced sugar content and biomass, growth abnormalities, and yellowing. Co-infection with the 16SrXII-P stolbur phytoplasmas often leads to more severe symptoms and a risk of complete economic loss. This yellowing agent of the Mollicutes class had not been described before, so its differences from other stolbur phytoplasmas remained unanswered. The genome of strain GOE was sequenced, providing a resource to analyze its characteristics. Phylogenetic position was revised, genome organization was compared, and functional reconstructions of metabolic and virulence factors were performed. Average nucleotide identity analysis indicates that GOE represents a new ' Phytoplasma' species. Our results show that GOE is also distinct from other stolbur phytoplasmas in terms of smaller genome size and G+C content. Its reductive evolution is reflected in conserved membrane protein repertoire and minimal metabolism. The encoding of a riboflavin kinase indicates a lost pathway of phytoplasmas outside the groups 16SrXII and 16SrXIII. GOE shows a complete transposon harboring orthologs of SAP11, SAP54, and SAP05 effectors indicating an original phytoplasma pathogenicity island. Our results deepen the understanding of phytoplasma evolution and reaffirm the heterogeneity of stolbur phytoplasmas.

Ionizing radiation induces various types of DNA damage, and the reparability and lethal effects of DNA damage differ depending on its spatial density. Elucidating the structure of radiation-induced clustered DNA damage and its repair processes will enhance our understanding of the lethal impact of ionizing radiation and advance progress toward precise therapeutics. Previously, we developed a method to directly visualize DNA damage using atomic force microscopy (AFM) and classified clustered DNA damage into simple base damage clusters (BDCs), complex BDCs and complex double-strand breaks (DSBs). This study investigated the repair of each type of damage in DNA-repair-deficient human TK6 cells and elucidated the association between each type of clustered DNA damage and the pathway responsible for its repair postirradiation with low linear energy transfer (LET) radiation (X-rays) and high-LET radiation (Fe-ion beams) in cells. We found that base excision repair and, surprisingly, nucleotide excision repair restored simple and complex BDCs. In addition, the number of complex DSBs in wild-type cells increases 1 h postirradiation, which was most likely caused by BDC cleavage initiated with DNA glycosylases. Furthermore, complex DSBs, which are likely associated with lethality, are repaired by homologous recombination with little contribution from nonhomologous-end joining.

Chronic exposure to manganese (Mn) induces manganism and has been widely implicated as a contributing environmental factor to Parkinson's disease (PD), featuring notable overlaps between the two in motor symptoms and clinical hallmarks. Here, we developed an adult model of Mn toxicity that recapitulated key parkinsonian features, spanning behavioral deficits, neuronal loss, and dysfunctions in lysosomes and mitochondria. Metabolomics analysis of the brain and body tissues of these flies at an early stage of toxicity identified systemic changes in the metabolism of biotin (also known as vitamin B) in Mn-treated groups. Biotinidase-deficient flies showed exacerbated Mn-induced neurotoxicity, parkinsonism, and mitochondrial dysfunction. Supplementing the diet of wild-type flies with biotin ameliorated the pathological phenotypes of concurrent exposure to Mn. Biotin supplementation also ameliorated the pathological phenotypes of three standard fly models of PD. Furthermore, supplementing the culture media of human induced stem cells (iPSCs) differentiated midbrain dopaminergic neurons with biotin protected against Mn-induced mitochondrial dysregulation, cytotoxicity, and neuronal loss. Last, analysis of the expression of genes encoding biotin-related proteins in patients with PD revealed increased amounts of biotin transporters in the substantia nigra compared with healthy controls, suggesting a potential role of altered biotin metabolism in PD. Together, our findings identified changes in biotin metabolism as underlying Mn neurotoxicity and parkinsonian pathology in flies, for which dietary biotin supplementation was preventative.

Distinguishing grade 3 pancreatic neuroendocrine tumors (PanNETs) from neuroendocrine carcinomas (PanNECs) is sometimes challenging. Recently, a diffuse p16-positive pattern was reported in PanNECs but not in grade 3 PanNETs, suggesting that p16 could help differentiate these entities. This study aimed to investigate p16 expression in PanNETs of various grades and its association with clinicopathologic features.

Neurochemical signals like dopamine (DA) play a crucial role in a variety of brain functions through intricate interactions with other neuromodulators and intracellular signaling pathways. However, studying these complex networks has been hindered by the challenge of detecting multiple neurochemicals simultaneously. To overcome this limitation, we developed a single-protein chemigenetic DA sensor, HaloDA1.0, which combines a cpHaloTag-chemical dye approach with the G protein-coupled receptor activation-based (GRAB) strategy, providing high sensitivity for DA, sub-second response kinetics, and an extensive spectral range from far-red to near-infrared. When used together with existing green and red fluorescent neuromodulator sensors, Ca indicators, cAMP sensors, and optogenetic tools, HaloDA1.0 provides high versatility for multiplex imaging in cultured neurons, brain slices, and behaving animals, facilitating in-depth studies of dynamic neurochemical networks.

Capacity-building interventions for health extension workers (HEWs) are key to providing quality health services to the community. Since Ethiopia's Health Extension Program was established, several types of capacity-building interventions have been developed to build HEW competencies. However, no comprehensive study has mapped the types of capacity-building interventions being used or the competencies targeted.

To describe the clinical and radiological parameters of spine malignant tumors.