Citations

Abstract Background Accurate synthesis of computed tomography (CT) images from magnetic resonance imaging (MRI) is clinically valuable for cranial applications such as attenuation correction, radiotherapy planning, and image‐guided interventions. However, the heterogeneity of MRI data across magnetic field strengths and pulse sequences limits the generalizability of existing methods, posing a barrier to clinical translation. Purpose This study aims to reformulate cranial CT synthesis as a modular, structurally coupled problem using a deep learning approach, enhancing adaptability across heterogeneous MRI conditions, including different field strengths and sequence protocols. Methods We implemented a cascaded multitask pipeline that jointly models skull segmentation and Hounsfield Unit (HU) regression in anatomically targeted regions. A 3D patch‐based training paradigm shifts the modeling focus from global image translation to localized bone feature extraction. The backbone leverages a residual Mamba‐based state space model within a 3D U‐Net structure to improve spatial representation, while a Transformer U‐Net serves as a widely recognized reference baseline comparison. The model was trained and evaluated in terms of multi‐modal (T1‐weighted and T2‐FLAIR) and cross‐domain transferability from a public 1.5 Tesla brain dataset ( n = 37) to an independent 7 Tesla clinical brain dataset ( n = 44). Performance was assessed using Dice and Jaccard indices for segmentation accuracy and mean absolute error (MAE) for HU regression. Results Quantitative analysis showed that our multitask pipeline, incorporating both morphological and HU map prediction stages, significantly outperformed conventional direct MRI‐to‐CT mapping across all metrics on the public 1.5T dataset (p < 0.05). Consistent performance on an external 7T clinical dataset (p < 0.001) further demonstrated the method's robustness and adaptability across field strengths. Conclusion These findings support that task‐structured training for modality transformation markedly improves both accuracy and generalizability of cranial CT synthesis across heterogeneous MRI conditions. The observed consistency across field strengths validates the robustness of the proposed methodology.

With limited therapeutic progress despite aggressive multimodal treatment, glioblastoma (GBM) remains one of the deadliest primary brain tumors. Emerging evidence suggests that GSCs are key drivers of tumor initiation, intratumoral heterogeneity, therapeutic resistance, and recurrence. GSCs retain self-renewal capacity, multilineage differentiation potential, and remarkable plasticity, enabling them to adapt to diverse microenvironmental cues. These properties are upheld by dysregulated developmental and oncogenic signaling pathways, including Notch, Wnt/β-catenin, Hedgehog, PI3K/AKT/mTOR, and STAT3, as well as epigenetic and metabolic reprogramming. In addition, dedicated niches such as hypoxic and perivascular microenvironments critically support GSC maintenance and immune evasion. In this review, we summarize the current understanding of the molecular pathways governing GSC biology, examine their interactions with the tumor microenvironment, and discuss emerging therapeutic strategies targeting GSCs, including pathway inhibition, differentiation therapy, immunotherapy, and nanomedicine-based drug delivery. We highlight key challenges and future directions for translating GSC-targeted approaches into effective clinical interventions for GBM.

Background Although clinically framed as a public health concern, the meanings of suicide are fundamentally shaped by cultural narratives and visual representations. Aims To examine the evolution of sculptural representations of suicide from antiquity to the present, and to interpret these works through psychiatric and sociological lenses relevant to contemporary clinical and public health discourse. Method A structured search across PubMed, Scopus and Web of Science (up to August 2025) was integrated with museum archives and art-historical catalogues. Selected sculptural works were analysed as interpretive case studies using iconographic, semiotic and contextual approaches. Interpretation focused on affective and relational processes such as psychological pain (psychache), shame, entrapment and social disconnection prioritising cultural formulation over retrospective diagnostic attribution in historical cases. Results Sculptural representations frame suicide through shifting moral and social logics: from honour-bound self-death in antiquity and virtue-coded narratives in the early-modern period to interiority and estrangement in modernity. Contemporary public installations shift this focus towards visibility, urban space and prevention. These works externalise private suffering and structural conditions (e.g. isolation, stigma), actively shaping collective imaginaries of self-destruction. Conclusions Sculpture provides a unique medium for the translation of individual suffering and the collective meanings of suicide into public form. An interdisciplinary reading of these works supports culturally informed clinical reflection and contributes to ethically attentive public communication and prevention strategies.

Abstract Transcriptional condensates (TCs) are dynamic, membrane-less assemblies of proteins and nucleic acids that form at specific genomic loci to control gene expression. The primary drivers of TC formation and function are long stretches of polypeptide chains that lack well-defined tertiary structure, known as the intrinsically disordered regions (IDRs) of Transcription Factors (TFs). However, the role of well-structured domains such as the DNA-binding domain (DBD) in condensate formation and downstream regulation remains poorly understood. Here, we investigated whether the DBD of the Progesterone Receptor (PR), a model TF regulated by hormone binding, contributes to the formation of PR TCs. By combining Single Particle Tracking (SPT) with deep-learning-based single-trajectory analysis, we demonstrated that both the IDR and the DBD are required for the formation of PR condensates. Furthermore, transcriptomic analysis showed that mutations of either of the two domains result in the expression of a distinct set of genes, with functional assays corroborating these findings and linking domain-specific transcription to differential effects on cell proliferation and migration. Together, our results show that domains beyond IDRs also play a role in TC formation and function and uncover domain-specific regulation of transcriptional and oncogenic programs.

A new systems approach to diseased states and wellness result in a new branch in the healthcare services, namely, Personalized and Precision Medicine (PPM). To achieve the implementation of PPM concept, it is necessary to create a fundamentally new strategy based upon the recogni-tion of biomarkers and thus the targets to secure the grand future of drug design and drug dis-covery.Each decision-maker values the impact of their decision to use PPM on their own budget and well-being, which may not necessarily be optimal for society as a whole. It would be extremely useful to integrate data harvesting from different databanks for applications to provide more tai-lored measures for the patients resulting in improved patient outcomes, reduced adverse events, and more cost-effective use of the latest health care resources including diagnostic (companion ones or theranostics), preventive and therapeutic (targeted molecular and cellular) etc.Meanwhile, along with the impact of genomics and bioinformatics, pathology is the central specialty of PPM-related resources. Coupled with IT, the upgraded tools are ever more efficient and robust within clinical cancer settings. The latest algorithms may be able to identify and vali-date patterns which humans are not capable of quantifying easily, such as slight differences in textures or morphologies. In this sense, the impact of pathology allows a modular approach, as its various aspects are under development in several areas of PPM.Among the above-mentioned medical specialists involved in PPM, the pathologists play an im-portant and key role in the implementation and development of PPM-driven resources that are in the center of decision of many therapeutic choices. Recent advances in systems biology have tremendously affected the practice of precision pathology, gradually transforming it from a morphology-based into a precise molecular-based discipline. The enormous development of precision pathology research (integrating molecular OMICS and digital approaches) has raised great expectations concerning its impact on PPM aiming to custom-ize medical practice with a focus on the individual, based on the use of molecular tests, identifi-cation of genomic biomarkers, and development of targeted drugs.The precision pathology process introduces a new paradigm in pathology by leveraging digital imaging and IT technologies, and provides significant advancements in accuracy, efficiency, and collaboration. Among the latest innovations the precision pathology supported by digital tools, would dictate the implementation of high-resolution imaging, image analysis tools and integra-tion with molecular OMICS data. Integration of the approaches and resources will provide a true challenge for the future, requiring collaboration between oncologists, pathologists, biodesigners and bioengineers and remaining a challenge to precision cancer practice and profiled bioindustry.The latter requires precision pathologists highly trained in pre-analytic processes, tumor area mi-crodissection for tumor cell enrichment, methodology analysis and results. The in-depth study of molecular alterations in patients allows optimizing molecular diagnosis and selecting candidates for receive novel treatments against specific molecular targets. These patients would benefit from multidisciplinary approach and learning. In this sense, molecular diagnostics has a long tradition in pathology, especially in clinical one, where various OMICS-analyses of cancers are incorpo-rated into diagnostic and decision-making algorithms to secure a way where the pathologists con-tinue to play an essential role in developing and implementing molecular profiling tests in practice and communicate the results and their relevance with cancer practitioners.Cancer pathology is the central specialty of personalized and precision oncology (PPO). Meanwhile, the combination of comprehensive biobanking and the next wave of theranostic pathology technologies provides a natural, externally visible infrastructure that now allows pa-thology as a discipline – to engage directly with the biotechnology and pharma sector. We’re at an exciting junction in precision cancer pathology’s growth as a medical specialty, and pathology-driven biobanking is becoming both central to our core expertise and, even more importantly, a powerful enabler for many of the most promising growth areas of our discipline: PPM healthcare, clinical trials and drug development, theranostics, and functional assessment and monitoring of disease. In the context of these changes and challenges, the precision cancer pathology can play a fundamental role in both PPO-guided clinical practice and biodesign-driven cancer research.

ABSTRACT Background Clinical T 2 ‐weighted (T2W) MRI of prostate cancer (PCa) usually implements a 2D fast‐spin‐echo (FSE) sequence, but understanding the echo‐time‐dependent contrast behavior is not straightforward due to the complicated FSE signal evolution. Consequently, consensus‐based recommendations on the optimal effective echo time (TE eff ) to maximize contrast are lacking. Purpose To investigate the effect of TE eff on PCa lesion contrast in prostate T2W MRI. Study Type Phantom and in vivo prospective study. Subjects A standard MRI phantom and 53 prostate cancer patients (29 for image evaluation and 24 for quantitative lesion analysis). Field Strength and Sequence Multi‐slice T2W FSE sequence at 3 T acquired at multiple TE eff values. Assessment Three readers (13, 25, and 27 years' experience) evaluated TE eff = 100 ms versus 150 ms on diagnostic quality and reader preference. The effective T 2 relaxation rates ( T 2,eff ) were measured using FSE sequences in the phantom and used to predict the optimal TE eff maximizing T2W contrasts. From multi‐TE eff scans of subjects with suspected PCa, T 2,eff values of PCa lesions and healthy tissue were measured and used to calculate the optimal TE eff maximizing the lesion contrast. In vivo contrast metrics were measured as a function of TE eff . Statistical Tests Wilcoxon test of reader scores, with p < 0.05 defining statistical significance. Results No statistically significant difference was found in diagnostic quality between TE eff = 150 ms and 100 ms images, but all three readers significantly favored TE eff = 150 ms. Phantom experiments demonstrated that TE eff ‐dependent FSE signal progression can be characterized by T 2,eff values typically 40% longer than actual T 2 values, allowing accurate prediction of optimal TE eff within 2%–5%. Applied to PCa imaging, in vivo measurements indicated that effective T 2 relaxation times of the prostate are on average 1.5× longer than published T 2 values. Data Conclusion The benefits of TE eff = 150 ms versus 100 ms in prostate T2W FSE were supported by reader preference, phantom experiments, in vivo measurements, and analytic optimizations. Evidence Level 2. Technical Efficacy 2.

ABSTRACT Background Chronic megacolon is an uncommon neurogastrointestinal disorder typically characterized by a persistent increase in colonic diameter. Methods Our aim was to identify adults with medical treatment‐refractory constipation without radiographic criteria for megacolon but with increased colonic compliance (refractory constipation with colonic hypercompliance (RCCH)), and to compare the colonic compliance in 7 identified patients with “RCCH” to colonic compliance in 10 patients with chronic megacolon by radiographic criteria (i.e., megacolon) and 40 healthy volunteers. After endoscopic placement, compliance of left or transverse colon was measured using a 10‐cm‐long infinitely compliant balloon connected to an electronically controlled rigid piston barostat. The barostat inflated the balloon from 0 to 44 mmHg in 4‐mmHg steps at 30‐s intervals to measure colonic compliance (pressure‐volume relationship). Eligibility criteria for inclusion were increased colonic compliance based on a functional assessment without meeting radiographic criteria for megacolon (i.e., RCCH). In the three groups, we compared colonic volumes at intra‐balloon pressure of 8, 16, 20, 32, and 44 mmHg, the pressure at half maximum volume, and the slope of the colonic compliance curve using ANOVA on ranks and Dunn's pairwise comparison test. Other features of colonic motility were documented. Results Colonic volumes at all pressures (8‐44 mmHg) and the pressure at half maximum volume were significantly greater in patients with megacolon and RCCH than in healthy controls ( p < 0.001 for both), but compliance was not significantly different between RCCH and megacolon. Conclusion A subset of patients with medically‐refractory chronic constipation has colonic compliance similar to that of patients with megacolon.

ABSTRACT Background Chronic obstructive pulmonary disease (COPD) is associated with musculoskeletal comorbidities, including cachexia. Weight loss (WL) is the major criterion for cachexia and increases risk for mortality in COPD. Risk factors for WL in COPD are incompletely understood. We performed this whole genome sequencing (WGS) analysis to identify genetic risk variants for WL in COPD. Methods We studied 16 972 participants from the Trans‐Omics for Precision Medicine (TOPMed) Initiative and All of Us Research Program. COPD was diagnosed using spirometry in TOPMed, while diagnosis codes were used in All of Us. WL was defined as WL ≥ 5% or a final body mass index (BMI) < 20 kg/m 2 . WGS data came from white blood cells in all cohorts. Single‐variant testing was conducted on both race‐ and study‐stratified cohorts and in a cosmopolitan, ancestry‐independent manner using GENESIS in TOPMed and SAIGE in All of Us. SAIGE‐GENE+ gene‐based analyses were performed on race‐stratified and cosmopolitan cohorts. Single variant meta‐analyses were conducted using METAL within (B/AA and NHW analyses of Black/African–American and non‐Hispanic white participants, respectively) and across racial groups (COSMO). Rare variant gene‐based results were combined using Fisher's method. Transcriptomic effects were predicted using MetaXcan. We used the GWAS Catalogue to analyse for colocalization with other related traits. Results Two single variants were associated with WL in COPD among All of Us participants: one intronic variant in HCN1 in Black/African–American participants (chr5:45271359:TACACAC:T, odds ratio with 95% confidence interval (OR (CI 95 )) = 2.43(1.78–3.31), p = 1.95 × 10 −8 ) and one intergenic variant between PPP4R2 and PDZRN3 in the cosmopolitan and NHW cohorts (chr3:73345901:A:G, OR (CI 95 ) = 0.21(0.12–0.35), p = 8.84 × 10 −9 in cosmopolitan and OR (CI 95 ) = 0.18(0.10–0.33), p = 9.44 × 10 −9 in NHW). Single‐variant meta‐analysis identified two loci associated with WL in COPD: five variants within DRAIC in the B/AA meta‐analysis (lead variant chr15:69571341:A:G, OR (CI 95 ) = 1.37(1.23–1.51), p = 1.29 × 10 −9 ) and two intronic variants within RFX3 in the cosmopolitan meta‐analysis (lead variant chr9:3390983:T:C, OR (CI 95 ) = 1.50(1.31–1.73), p = 1.06 × 10 −8 ). Rare variants within RNU6‐565P (NHW analysis in All of Us; p = 2.83 × 10 −7 ) and LOC339298 (B/AA analysis in All of Us, p = 1.85 × 10 −6 ) were associated with WL in COPD. The RNU‐565P signal remained significant after combination with TOPMed results (p combined = 1.23 × 10 −6 ). MetaXcan predicted differential expression of LNC00959 in visceral adipose tissue ( p = 1.16 × 10 −6 in COSMO analysis). Colocalization analyses identified genomic associations between BMI and variants in or near DRAIC , RFX3 , PDZRN3 , and LINC00959 . Conclusions In the first WGS analysis of WL in COPD, we have identified seven novel loci. Further characterization of these loci will validate our findings and improve our understanding of the molecular pathophysiology of this condition.

Background: Candidemia is a serious complication after gastrointestinal (GI) perforation and/or ischemia, yet most evidence pools candidemia with intra-abdominal candidiasis (IAC). We sought candidemia-specific risk factors after GI perforation and/or ischemia and evaluated associated outcomes. Methods: We conducted a single-center, retrospective matched case–control study of adults undergoing emergency surgical procedure for GI perforation and/or ischemia and admitted to a surgical intensive care unit. Cases with candidemia during index admission were matched 4:1 to controls by age, Charlson Comorbidity Index, and surgical procedure year. Conditional logistic regression assessed pre-specified risk factors, and exploratory outcomes included mortality, length of stay, and days on invasive ventilation. Results: Twenty-four cases were matched to 99 controls. Factors identified to be independently associated with candidemia include the presence of IAC (adjusted OR [aOR]: 5.51, 95% CI: 1.61, 18.89; p = 0.007), upper GI injury (aOR: 4.28, 95% CI: 1.52–12.08; p = 0.006), and diffuse intra-abdominal contamination, compared with contained/none (aOR: 3.21, 95% CI: 1.06–9.74; p = 0.040). Among candidemia cases, species distribution was Candida albicans 41.7%, C. glabrata 33.3%, C. parapsilosis 12.5%, with single cases of C. tropicalis, C. krusei , and C. dubliniensis . Candidemia was associated with a longer hospital length of stay (+13.97 d; 95% CI: 0.90–27.04; p = 0.036), without significant differences in ICU stay, duration of invasive ventilation, or mortality. Conclusions: After GI perforation and/or ischemia, the risk of candidemia is highest in patients with upper GI injury and diffuse contamination, independent of IAC. These readily identifiable operative features may guide targeted surveillance and selective early antifungal strategies. Prospective validation is warranted.

ABSTRACT BACKGROUND Point-of-care (POC) high-sensitivity cardiac troponin (hs-cTn) testing has the potential to expedite decision-making and reduce emergency department (ED) length of stay for patients presenting with possible myocardial infarction (MI) by ensuring that results are consistently available when looked for by clinicians. We assessed the real-life effectiveness and safety of implementing POC hs-cTn testing in the ED. METHODS We conducted a pragmatic, stepped-wedge cluster randomized trial. The control arm was usual care with an accelerated diagnostic pathway utilizing a single-sample rule-out step with a central laboratory hs-cTn assay. The intervention arm used the same pathway with a POC hs-cTnI. The primary effectiveness outcome was ED length of stay assessed using a generalized linear mixed model, and the safety outcome was 30-day MI or cardiac death. RESULTS Six sites participated with 59,980 ED presentations (44,747 individuals, 61±19 years, 49.5% female) from February 2023 to January 2025, in which 31,392 presentations were during the intervention arm. After adjustment for co-variates associated with length of stay, the intervention reduced length of stay by 13% (95% confidence intervals [CI], 9 to 16%. P<0.001), corresponding to a reduction of 47 minutes (95%CI, 33 to 61 minutes) from a mean length of stay in the control arm of 376 minutes. The 30-day MI or cardiac death rate was similar in the control and intervention arms (0.39% and 0.39% respectively, P=0.54). CONCLUSIONS Implementation of whole-blood hs-cTnI testing at the POC into an accelerated diagnostic pathway was safe and reduced length of stay in the ED compared with laboratory testing. (Australia New Zealand Clinical Trials Registry ACTRN12619001189112) Clinical Perspective What is new? Point-of-care troponin assays with good precision have become available and received regulatory approval as high-sensitivity assays. A pragmatic stepped-wedge cluster randomized trial implementing the validated Siemens VTLi high-sensitivity point-of-care assay into 6 emergency departments investigating ∼60,000 patients, was conducted to ascertain if the rapid turnaround time reduced lengths of stay. Introduction of the VTLi high-sensitivity point-of-care assay into clinical pathways reduced emergency department lengths of stay by an average 13% (47 minutes) without compromising safety. What are the clinical implications? Early decision-making using a point-of-care high-sensitivity troponin assay within a structured clinical pathway was safe. Faster turnaround means troponin results are consistently available when clinicians first seek them. This can facilitate earlier decisions and reduce patient length of stay.