tbuckley/cabot-search huggingface dataset:
Primary Effusion Lymphoma Prognostic Score (<scp>PEL</scp>‐<scp>PS</scp>): A Validated International Prognostic Score in <scp>HIV</scp>‐Associated Primary Effusion Lymphoma
Authors: Kathryn Lurain, Ramya Ramaswami, Eric Oksenhendler, David Boutboul, Alessia Dalla Pria, Lara Ulrich, Krithika Shanmugasundaram, Thomas S. Uldrick, Mark Bower, Robert Yarchoan, Laurence Gérard, Seth M. Steinberg
Journal: American Journal of Hematology (2025)

Primary effusion lymphoma (PEL) is an HIV-associated B-cell non-Hodgkin lymphoma (NHL) caused by Kaposi sarcoma herpesvirus (KSHV). There is no validated prognostic model in PEL, and prognosis is thought to be poor compared to other HIV-associated NHL. We derived the PEL-Prognostic score (PEL-PS) from an international real-world training set of 59 patients with HIV-associated PEL who received first-line anthracycline-containing chemotherapy from the HIV and AIDS Malignancy Branch at the National Cancer Institute (NCI) in the United States and the National Center for HIV Malignancy at the Chelsea and Westminster Hospital (CWH) in England from 2000 to 2022. We identified prognostic factors associated with overall survival (OS). In a multivariable Cox model, ECOG ≥ 3 (p = 0.007; hazard ratio [HR] = 4.0 [95% CI: 1.5-11.1]) and hemoglobin < 8 g/dL (p = 0.006; HR = 3.8 [95% CI: 1.5-9.7]) were jointly associated with lower survival probability. The resulting PEL-PS separated patients with no negative prognostic factors (score 0: hemoglobin ≥ 8 g/dL and ECOG ≤ 2, 48.1% of patients) with median OS of 10.6 years versus patients with 1-2 negative prognostic factors (score 1-2: hemoglobin < 8 g/dL and/or ECOG ≥ 3, 51.9% of patients) with median OS of 0.8 years (p < 0.0001). The PEL-PS was then validated in 58 patients with HIV-associated PEL treated with first-line anthracycline-containing chemotherapy at Hôpital Saint-Louis in France over the same period: median OS in patients with PEL-PS 0 was 16.9 years versus 0.6 years in patients with PEL-PS score of 1-2 (p < 0.0001). The PEL-PS identifies patients with good and poor prognosis. Patients with poor prognosis may benefit from novel therapies.
Autophagy regulator ATG5 preserves cerebellar function by safeguarding its glycolytic activity
Authors: Janine Tutas, Marianna Tolve, Ebru Özer-Yildiz, Lotte Ickert, Ines Klein, Quinn Silverman, Filip Liebsch, Frederik Dethloff, Patrick Giavalisco, Heike Endepols, Theodoros Georgomanolis, Bernd Neumaier, Alexander Drzezga, Guenter Schwarz, Bernard Thorens, Graziana Gatto, Christian Frezza, Natalia L. Kononenko
Journal: Nature Metabolism (2025)

Abstract Dysfunctions in autophagy, a cellular mechanism for breaking down components within lysosomes, often lead to neurodegeneration. The specific mechanisms underlying neuronal vulnerability due to autophagy dysfunction remain elusive. Here we show that autophagy contributes to cerebellar Purkinje cell (PC) survival by safeguarding their glycolytic activity. Outside the conventional housekeeping role, autophagy is also involved in the ATG5-mediated regulation of glucose transporter 2 (GLUT2) levels during cerebellar maturation. Autophagy-deficient PCs exhibit GLUT2 accumulation on the plasma membrane, along with increased glucose uptake and alterations in glycolysis. We identify lysophosphatidic acid and serine as glycolytic intermediates that trigger PC death and demonstrate that the deletion of GLUT2 in ATG5-deficient mice mitigates PC neurodegeneration and rescues their ataxic gait. Taken together, this work reveals a mechanism for regulating GLUT2 levels in neurons and provides insights into the neuroprotective role of autophagy by controlling glucose homeostasis in the brain.
Separate orexigenic hippocampal ensembles shape dietary choice by enhancing contextual memory and motivation
Authors: Mingxin Yang, Arashdeep Singh, Alan de Araujo, Molly McDougle, Hillary Ellis, Léa Décarie-Spain, Scott E. Kanoski, Guillaume de Lartigue
Journal: Nature Metabolism (2025)

The hippocampus (HPC) has emerged as a critical player in the control of food intake, beyond its well-known role in memory. While previous studies have primarily associated the HPC with food intake inhibition, recent research suggests a role in appetitive processes. Here we identified spatially distinct neuronal populations within the dorsal HPC (dHPC) that respond to either fats or sugars, potent natural reinforcers that contribute to obesity development. Using activity-dependent genetic capture of nutrient-responsive dHPC neurons, we demonstrate a causal role of both populations in promoting nutrient-specific intake through different mechanisms. Sugar-responsive neurons encoded spatial memory for sugar location, whereas fat-responsive neurons selectively enhanced the preference and motivation for fat intake. Importantly, stimulation of either nutrient-responsive dHPC neurons increased food intake, while ablation differentially impacted obesogenic diet consumption and prevented diet-induced weight gain. Collectively, these findings uncover previously unknown orexigenic circuits underlying macronutrient-specific consumption and provide a foundation for developing potential obesity treatments. Yang et al. identify and characterize distinct sugar- and fat-responsive neuronal populations in the dorsal hippocampus and their contribution to the development of obesity.
Impact of myelodysplasia‐related and additional gene mutations in intensively treated patients with <i>NPM1</i>‐mutated AML
Authors: Sibylle Cocciardi, Maral Saadati, Nina Weiß, Daniela Späth, Silke Kapp‐Schwoerer, Isabelle Schneider, Annika Meid, Verena I. Gaidzik, Sabrina Skambraks, Walter Fiedler, Michael W. M. Kühn, Ulrich Germing, Karin T. Mayer, Michael Lübbert, Elli Papaemmanuil, Felicitas Thol, Michael Heuser, Arnold Ganser, Lars Bullinger, Axel Benner, Hartmut Döhner, Konstanze Döhner
Journal: HemaSphere (2025)

ABSTRACT This study aimed to evaluate the impact of the myelodysplasia‐related gene (MRG) as well as additional gene mutations on outcomes in intensively treated patients with NPM1 ‐mutated ( NPM1 mut ) AML. Targeted DNA sequencing of 263 genes was performed in 568 NPM1 mut AML patients (median age: 59 years) entered into the prospective AMLSG 09‐09 treatment trial. Most commonly co‐mutated genes were DNMT3A (49.8%), FLT3 ‐TKD (25.9%), PTPN11 (24.8%), NRAS (22.7%), TET2 (21.7%), IDH2 (21.3%), IDH1 (18%), and FLT3 ‐ITD (17.3%). MRG mutations were identified in 18.1% of cases (18–60 years: 9.8%; &gt;60 years: 28.7%). When focusing on the 470 patients with 2022 ELN favorable‐risk NPM1 mut AML, multivariable analysis for event‐free survival (EFS) identified age ( p &lt; 0.001), DNMT3A R882 ( p &lt; 0.001), IDH1 ( p = 0.007), and MRG mutations ( p = 0.03) as unfavorable factors, cohesin gene co‐mutations ( p = 0.001) and treatment with gemtuzumab ozogamicin ( p = 0.007) as favorable factors. Restricting the analysis to a subset of CR/CRi patients with available data on NPM1 mut measurable residual disease (MRD) status in blood post cycle 2 in the model, MRG mutations lost their significant effect, whereas DNMT3A R882 , MYC , and cohesin gene mutations retained the adverse and favorable effects. For OS, age ( p &lt; 0.001), DNMT3A R882 ( p = 0.042), IDH1 ( p = 0.045), and KRAS (0.003) mutations were unfavorable factors, sole favorable factor was IDH2 co‐mutation ( p = 0.037). In 2022 ELN favorable‐risk NPM1 mut AML, MRG mutations are associated with inferior EFS; however, this effect is no longer present when considering NPM1 mut MRD status post cycle 2; DNMT3A R882 and MYC mutations remained adverse, and cohesin gene mutations favorable prognostic factors independent of the NPM1 mut MRD status.
An Injectable Multifunctional Nanosweeper Eliminates Cardiac Mitochondrial DNA to Reduce Inflammation
Authors: Yi‐Jing Li, Xiumeng Hua, Yi‐Qi Zhao, Han Mo, Shun Liu, Xiao Chen, Zhe Sun, Weiteng Wang, Qian Zhao, Zeyu Cui, Tao An, Jiangping Song
Journal: Advanced Healthcare Materials (2025)

Myocarditis, a leading cause of sudden cardiac death and heart transplantation, poses significant treatment challenges. The study of clinical samples from myocarditis patients reveals a correlation between the pathogenesis of myocarditis and cardiomyocyte mitochondrial DNA (mtDNA). During inflammation, the concentration of mtDNA in cardiomyocytes increases. Hence, it is hypothesized that the combined clearance of mtDNA and its downstream STING pathway can treat myocarditis. However, clearing mtDNA is problematic. An innovative mtDNA scavenger is introduced, Nanosweeper (NS), which utilizes its nanostructure to facilitate the transport of NS-mtDNA co-assemblies for degradation, achieving mtDNA clearance. The fluorescent mtDNA probe on NS, bound to functional peptides, enhances the stability of NS. NS also exhibits robust stability in human plasma with a half-life of up to 10 hours. In a murine myocarditis model, NS serves as a drug delivery vehicle, targeting the delivery of the STING pathway inhibitor C-176 to the myocardium. This approach synergistically modulates the cGAS-STING axis with NS, effectively attenuating myocarditis- associated inflammatory cascade. This evaluation of NS in porcine models corroborated its superior biosafety profile and cardiac targeting capability. This strategic approach of targeted mtDNA clearance couple with STING pathway inhibition, significantly augments therapeutic efficacy against myocarditis, outperforming the conventional drug C-176, indicating its clinical potential.
The lived experience of postpartum depression and psychosis in women: a bottom‐up review co‐written by experts by experience and academics
Authors: Paolo Fusar‐Poli, Andrés Estradé, Keshnie Mathi, Constance Mabia, Nur Yanayirah, Valentina Floris, Elisa Figazzolo, Cecilia M. Esposito, Milena Mancini, René Rosfort, Ana Catalan, Helen Baldwin, Rashmi Patel, Giovanni Stanghellini, Matthew Ratcliffe, Mario Maj
Journal: World Psychiatry (2025)

This is the first bottom‐up review of the lived experience of postpartum depression and psychosis in women. The study has been co‐designed, co‐conducted and co‐written by experts by experience and academics, drawing on first‐person accounts within and outside the medical field. The material initially identified was shared with all participants in a cloud‐based system, discussed across the research team, and enriched by phenomenological insights. The subjective world of postpartum depression is characterized by a sudden onset (“being hit with a ton of bricks”), unbearable loneliness and sadness that are often suffered in silence, inability to feel positive emotions, grieving over the loss of self, feelings of being bad mothers (haunted by a suffocating burden of guilt due to that), inability to concentrate, lack of control of thoughts (“feeling like a tightrope walker without control over thoughts and emotions”), insecurity (up to needing to be nurtured and mothered themselves), and thoughts of death (“contemplating death as a glimmer of hope to escape the living nightmare”). In addition to these themes, the subjective world of postpartum psychosis is characterized by difficulty in articulating thoughts (“feeling the brain in a centrifuge”); perceptual abnormalities and unusual beliefs disrupting the sense of personal unity (with, in a few cases, thoughts of harming themselves or their baby, so that women may feel that they are “sinking in the depths of hell”); losing trust (“ploughing through the fog and losing trust and safety”), and stripping down relationships. Much of the isolation, guilt and disorientation experienced in these conditions relates to sociocultural and family environments, especially a gulf between how women feel and a web of norms and expectations surrounding motherhood. In most cases, stigma is related to a lack of knowledge of what postpartum depression or psychosis are. Stigma and lack of knowledge are core drivers impacting health care in terms of seeking professional help, accessing mental health services, and receiving pharmacological or psychological treatments. The narratives described in this paper should inform clinical practice, research and public health education. This study brings voice to the unspoken and unheard, and fosters relational connections within which different mothering experiences may be expressed and understood. This is vital to challenging negative sociocultural attitudes towards postpartum depression and psychosis, and providing the most supportive care to women experiencing such pervasive psychiatric disorders at a critical, fragile time in their lives.
The current clinical approach to feeding and eating disorders aimed to increase personalization of management
Authors: Ulrike H. Schmidt, Angelica Claudino, Fernando Fernández‐Aranda, Katrin E. Giel, Jess Griffiths, Phillipa J. Hay, Youl‐Ri Kim, Jane Marshall, Nadia Micali, Alessio Maria Monteleone, Michiko Nakazato, Joanna Steinglass, Tracey D. Wade, Stephen Wonderlich, Stephan Zipfel, Karina L. Allen, Helen Sharpe
Journal: World Psychiatry (2025)

Feeding and eating disorders (FEDs) are a heterogeneous grouping of disorders at the mind-body interface, with typical onset from childhood into emerging adulthood. They occur along a spectrum of disordered eating and compensatory weight management behaviors, and from low to high body weight. Psychiatric comorbidities are the norm. In contrast to other major psychiatric disorders, first-line treatments for FEDs are mainly psychological and/or nutrition-focused, with medications playing a minor adjunctive role. Patients, carers and clinicians all have identified personalization of treatment as a priority. Yet, for all FEDs, the evidence base supporting this personalization is limited. Importantly, disordered eating and related behaviors can have serious physical consequences and may put the patient's life at risk. In these cases, immediate safety and risk management considerations may at least for a period need to be prioritized over other efforts at personalization of care. This paper systematically reviews several key domains that may be relevant to the characterization of the individual patient with a FED aimed at personalization of management. These domains include symptom profile, clinical subtypes, severity, clinical staging, physical complications and consequences, antecedent and concomitant psychiatric conditions, social functioning and quality of life, neurocognition, social cognition and emotion, dysfunctional cognitive schemata, personality traits, family history, early environmental exposures, recent environmental exposures, stigma, and protective factors. Where possible, validated assessment measures for use in clinical practice are identified. The limitations of the current evidence are pointed out, and possible directions for future research are highlighted. These also include novel and emerging approaches aimed at providing more fine-grained and sophisticated ways to personalize treatment of FEDs, such as those that utilize neurobiological markers. We additionally outline remote measurement technologies designed to delineate patients' illness and recovery trajectories and facilitate development of novel intervention approaches.
Socioeconomic inequalities in mortality associated with mental disorders: a population‐based cohort study
Authors: Danni Chen, Natalie C. Momen, Linda Ejlskov, Katrine Bødkergaard, Julie Werenberg Dreier, Henrik Toft Sørensen, Lisbeth Mølgaard Laustsen, Sam Harper, Christian Hakulinen, John J. McGrath, Oleguer Plana‐Ripoll
Journal: World Psychiatry (2025)

Mental disorders are associated with elevated mortality rates and reduced life expectancy. However, it is unclear whether these associations differ by socioeconomic position (SEP). The aim of this study was to explore comprehensively the role of individual‐level SEP in the associations between specific types of mental disorders and mortality (due to all causes, and to natural or external causes), presenting both relative and absolute measures. This was a cohort study including all residents in Denmark on January 1, 2000, following them up until December 31, 2020. Information on mental disorders, SEP (income percentile, categorized into low, &lt;20%; medium, 20‐79%; and high, ≥80%), and mortality was obtained from nationwide registers. We computed the average reduction in life expectancy for those with mental disorders, relative and absolute differences in mortality rates, and proportional attributable fractions. Subgroup analyses by sex and age groups were performed. Overall, 5,316,626 individuals (2,689,749 females and 2,626,877 males) were followed up for 95.2 million person‐years. People with mental disorders had a shorter average life expectancy than the general population regardless of SEP (70.9‐77.0 vs. 77.2‐85.1 years, depending on income percentile). Among individuals with a mental disorder, the subgroup in the top 3% of the income distribution had the longest average life expectancy (77.0 years), and this estimate was lower than the shortest life expectancy in the general Danish population (77.2 years for individuals in the bottom 6% income distribution). The mortality rate differences were larger in the low‐income than the high‐income group (19.6 vs. 13.3 per 1,000 person‐years). For natural causes of death, a socioeconomic gradient for differences in life expectancy and mortality rates was observed across most diagnoses, both sexes, and all age groups. For external causes, no such gradient was observed. In the low‐SEP group, 10.1% of all deaths and 23.7% of those related to external causes were attributable to mental disorders, compared with 3.5% and 8.7% in the high‐SEP group. Thus, our data indicate that people with mental disorders have a shorter life expectancy even than people with the lowest SEP in the general population. The socioeconomic gradients in mortality rates due to natural causes highlight a greater need for coordinated care of physical diseases in people with mental disorders and low SEP.
Excess cardiometabolic risk in children and adolescents initiating antipsychotic treatment compared to young adults: results from a nationwide cohort study
Authors: Mikkel Højlund, Rikke Wesselhoeft, Michella Heinrichsen, Anne Katrine Pagsberg, Christoph U. Correll, Hans‐Christoph Steinhausen
Journal: World Psychiatry (2025)

Antipsychotic treatment is associated with cardiometabolic risks that may be especially detrimental to children and adolescents. In this Danish population‐based cohort study, we included individuals with psychiatric diagnoses who initiated antipsychotics in 2000‐2021 at age 6‐31 years. We assessed the risk of cardiometabolic adverse events up to 10 years following incident exposure to antipsychotics, compared to age‐ and sex‐matched unexposed individuals with psychiatric diagnoses. Cox regression models were used to calculate hazard ratios (HRs) after adjustment using high‐dimensional propensity scores, including age, sex, calendar time, hospital diagnoses, and prescription drug use. HRs were compared between incident exposure in youths (6‐17 years) and young adults (18‐31 years), and between incident exposure in children (6‐11 years) and adolescents (12‐17 years). The total cohort consisted of 335,093 individuals, including 36,092 subjects exposed to antipsychotics (children and adolescents: 8,547, mean follow‐up: 6.8±3.2 years; young adults: 27,545, mean follow‐up: 6.5±3.4 years) and 299,001 age‐, sex‐ and calendar‐matched unexposed subjects. The incidence rate of cardiometabolic events was higher for young adults initiating antipsychotics than for children and adolescents (23.2 vs. 14.1 events/1,000 person‐years). However, the adjusted excess risk of cardiometabolic events was significantly higher in exposed compared to unexposed children and adolescents (HR=1.87, 95% CI: 1.71‐2.05) than in exposed compared to unexposed young adults (HR=1.46, 95% CI: 1.40‐1.51) (p&lt;0.001). The excess risk of cardiometabolic events was even higher when antipsychotic treatment was initiated before age 12 years (HR=2.44; 95% CI: 1.99‐2.98) than at age 12‐17 years (HR=1.69, 95% CI: 1.52‐1.87) (p=0.012). Concerning specific cardiometabolic outcomes, there was an effect of age at antipsychotic initiation on the risks of metabolic syndrome (p=0.011) and obesity (p&lt;0.001), that were higher among children and adolescents than young adults. Thus, initiation of antipsychotic treatment before age 18 years is associated with an excess risk of cardiometabolic events compared to age‐ and sex‐matched youths with psychiatric disorders but unexposed to antipsychotics. The excess cardiometabolic risk is significantly higher than that of individuals who start antipsychotic treatment in early adulthood, and significantly higher for treatment onset in childhood compared to adolescence. On the basis of these findings, recommendations are provided about the use of antipsychotics in children and adolescents.
Augmenting trauma‐focused cognitive behavior therapy for post‐traumatic stress disorder with memory specificity training: a randomized controlled trial
Authors: Richard A. Bryant, Katie S. Dawson, Srishti Yadav, Jenny Tran, Jasmine Choi‐Christou, Natasha Rawson, Julia Tockar, Eileen Stech, Benjamin Garber, Catherine Broomfield, Anthony Harrison, Dharani Keyan, Suzanna Azevedo
Journal: World Psychiatry (2025)

Although trauma‐focused cognitive behavior therapy (TF‐CBT) is the recommended treatment for post‐traumatic stress disorder (PTSD), up to one‐half of patients do not respond to this intervention. There is an urgent need to develop new strategies to improve treatment response. Training people to recall specific positive memories may augment treatment gains in TF‐CBT. We conducted a controlled trial in Australia with current or former first responders (including police, firefighters and paramedics) with PTSD, who were randomized on a 1:1 basis to 12 weekly 90‐min individual sessions of either TF‐CBT combined with memory specificity training (TF‐CBT/MT) or TF‐CBT alone. The primary outcome was change in PTSD severity independently assessed at baseline, post‐treatment, and six months after treatment (primary outcome timepoint). Secondary outcomes included measures of depression, trauma‐related cognitions, alcohol use, and quality of life. Between October 2021 and May 2023, fifty participants were randomized to TF‐CBT/MT, and fifty to TF‐CBT alone. Most participants were males (71.0%) and the mean age was 46.8±9.9 years. At the 6‐month assessment, participants receiving TF‐CBT/MT showed a greater reduction of PTSD severity than those randomized to TF‐CBT alone (mean difference: 9.2, 95% CI: 3.2‐15.1, p=0.003), indicating a large effect size (0.9, 95% CI: 0.1‐1.6). Participants receiving TF‐CBT/MT also had greater reductions in alcohol use (mean difference: 5.3, 95% CI: 1.5‐9.2, p=0.007; effect size: 0.8, 95% CI: 0.2‐1.4) and self‐blame cognitions (mean difference: 0.8, 95% CI: 0.2‐1.4, p=0.008; effect size: 0.5, 95% CI: 0.1‐0.9). These data suggest that memory specificity training adds significantly to the effect of standard TF‐CBT in reducing PTSD severity. This approach can offer a simple and easy to implement strategy to augment treatment for PTSD patients.
Improving authenticity and provenance in digital biomarkers: the case for digital watermarking
Authors: Arjun Mahajan, Dylan Powell
Journal: npj Digital Medicine (2025)

Enabled by the rapid rise in data collected by technologies, Digital Biomarkers (DBx) have emerged as a novel mechanism for assessment, diagnosis, and monitoring. However, the exponential growth and ability to generate new data has also raised questions about ways of ensuring the authenticity and accuracy of digital data. A recent study highlights how Large Language Models (LLMs) generating human-like content amplify these risks, and propose watermarking as a scalable solution to ensure data integrity. This article examines the potential of digital watermarking to help safeguard the reliability and provenance of DBx data, whilst also addressing broader challenges in health systems.