tbuckley/cabot-search huggingface dataset:
Reducing Distress from Auditory Verbal Hallucinations: A Multicenter, Parallel, Single-Blind, Randomized Controlled Feasibility Trial of Relating Therapy
Authors: Tania Marie Lincoln, Björn Schlier, Rebecca Müller, Mark Hayward, Anne-Katharina Fladung, Niklas Bergmann, Kerem Böge, Jürgen Gallinat, Candelaria Mahlke, Uwe Gonther, Thomas Lang, Cornelia Exner, Anika Buchholz, Katharina Stahlmann, Antonia Zapf, Geraldine Rauch, Matthias Pillny
Journal: Psychotherapy and Psychosomatics (2024)

Introduction: There is a significant demand for interventions that reduce distress related to auditory verbal hallucinations (AVHs). AVH distress is associated with the way voice hearers relate with AVHs. We aimed to establish the feasibility of a randomized controlled trial to demonstrate that adding “Relating Therapy” (RT) to treatment as usual (TAU) is superior to TAU in reducing AVH distress. Methods: We conducted a multicenter, parallel, single-blind, randomized controlled feasibility trial in five mental health centers in Germany. Participants were ≥19 years of age, had persistent and distressing AVHs, and had a diagnosis of a schizophrenia-spectrum disorder. RT was delivered over a maximum of 16 sessions within 5 months. Blind assessments were conducted at baseline and at 5 and 9 months. Feasibility outcomes were the number of patients recruited and retained, and safety and therapist adherence. The primary endpoint was the distress factor score of the AVH subscale of the Psychotic Symptoms Rating Scales at 9 months. Results: Eighty-five of 177 enrolled participants were randomized into RT + TAU (n = 43) or TAU (n = 42). Feasibility was excellent with 87% retention at 9 months, 86% reaching treatment uptake criteria, 98% therapist adherence, and no unexpected serious adverse reactions. Compared to TAU, RT + TAU showed nonsignificant trends toward less AVH distress (b = −2.40, SE = 1.52, p = 0.121, 90% CI (−4.94 to 0.15) and stronger improvement on all but one of the secondary outcomes. Conclusion: A randomized controlled trial of RT is feasible, safe, and well accepted. Our results provide an encouraging basis to further test the efficacy of RT in a definitive multicenter trial.
A bimodal taxonomy of adult human brain sulcal morphology related to timing of fetal sulcation and trans-sulcal gene expression gradients
Authors: William E Snyder, Petra E Vértes, Vanessa Kyriakopoulou, Konrad Wagstyl, Logan Z J Williams, Dustin Moraczewski, Adam G Thomas, Vyacheslav R Karolis, Jakob Seidlitz, Denis Rivière, Emma C Robinson, Jean-Francois Mangin, Armin Raznahan, Edward T Bullmore
Journal: Neuron (2024)

We developed a computational pipeline (now provided as a resource) for measuring morphological similarity between cortical surface sulci to construct a sulcal phenotype network (SPN) from each magnetic resonance imaging (MRI) scan in an adult cohort (n = 34,725; 45-82 years). Networks estimated from pairwise similarities of 40 sulci on 5 morphological metrics comprised two clusters of sulci, represented also by the bimodal distribution of sulci on a linear-to-complex dimension. Linear sulci were more heritable and typically located in unimodal cortex, and complex sulci were less heritable and typically located in heteromodal cortex. Aligning these results with an independent fetal brain MRI cohort (n = 228; 21-36 gestational weeks), we found that linear sulci formed earlier, and the earliest and latest-forming sulci had the least between-adult variation. Using high-resolution maps of cortical gene expression, we found that linear sulcation is mechanistically underpinned by trans-sulcal gene expression gradients enriched for developmental processes.
Transcriptional function of E2A, Ebf1, Pax5, Ikaros and Aiolos analyzed by in vivo acute protein degradation in early B cell development
Authors: Anna S. Fedl, Hiromi Tagoh, Sarah Gruenbacher, Qiong Sun, Robyn L. Schenk, Kimon Froussios, Markus Jaritz, Meinrad Busslinger, Tanja A. Schwickert
Journal: Nature Immunology (2024)
Ventral attention network connectivity is linked to cortical maturation and cognitive ability in childhood
Authors: Hao-Ming Dong, Xi-Han Zhang, Loïc Labache, Shaoshi Zhang, Leon Qi Rong Ooi, B. T. Thomas Yeo, Daniel S. Margulies, Avram J. Holmes, Xi-Nian Zuo
Journal: Nature Neuroscience (2024)
Role of anticoagulation therapy in modifying stroke risk associated with new-onset atrial fibrillation after non-cardiac surgery
Authors: Omid Azimaraghi, Maíra I. Rudolph, Karuna Wongtangman, Felix Borngaesser, Maya Doehne, Pauline Y. Ng, Dario von Wedel, Annika Eyth, Fengwei Zou, Christopher Tam, William J. Sauer, Michael E. Kiyatkin, Timothy T. Houle, Ibraheem M. Karaye, Ling Zhang, Maximilian S. Schaefer, Simon T. Schaefer, Carina P. Himes, Aline M. Grimm, Olubukola O. Nafiu, Christian Mpody, Aiman Suleiman, Brendon M. Stiles, Luigi Di Biase, Mario J. Garcia, Annika Bald, Luigi Di Biase, Joseph J. DeRose, Stephen J. Forest, Fran Ganz-Lord, Jay J. Im, M. Azeem Latib, Jonathan Leff, Can M. Luedeke, Timothy Pulverenti, Tina Ramishvili, Flora T. Scheffenbichler, Dario von Wedel, Sujatha Ramachandran, Deepak L. Bhatt, Matthias Eikermann
Journal: Nature Medicine (2024)
Chromosome 9p trisomy increases stem cells clonogenic potential and fosters T-cell exhaustion in JAK2-mutant myeloproliferative neoplasms
Authors: Chiara Carretta, Sandra Parenti, Matteo Bertesi, Sebastiano Rontauroli, Filippo Badii, Lara Tavernari, Elena Genovese, Marica Malerba, Elisa Papa, Samantha Sperduti, Elena Enzo, Margherita Mirabile, Francesca Pedrazzi, Anita Neroni, Camilla Tombari, Barbara Mora, Margherita Maffioli, Marco Mondini, Marco Brociner, Monica Maccaferri, Elena Tenedini, Silvia Martinelli, Niccolò Bartalucci, Elisa Bianchi, Livio Casarini, Leonardo Potenza, Mario Luppi, Enrico Tagliafico, Paola Guglielmelli, Manuela Simoni, Francesco Passamonti, Ruggiero Norfo, Alessandro Maria Vannucchi, Rossella Manfredini
Journal: Leukemia (2024)

JAK2V617F is the most recurrent genetic mutation in Philadelphia-negative chronic Myeloproliferative Neoplasms (MPNs). Since the JAK2 locus is located on Chromosome 9, we hypothesized that Chromosome 9 copy number abnormalities may be a disease modifier in JAK2V617F-mutant MPN patients. In this study, we identified a subset of MPN patients with partial or complete Chromosome 9 trisomy (+9p patients), who differ from JAK2V617F-homozygous MPN patients as they carry three JAK2 alleles as well as three copies of all neighboring gene loci, including CD274, encoding immunosuppressive Programmed death-ligand 1 (PD-L1) protein. Investigation of the clonal hierarchy revealed that the JAK2V617F occurs first, followed by +9p. Functionally, CD34+ cells from +9p MPN patients demonstrated increased clonogenicity, generating a greater number of primitive colonies, due to high OCT4 and NANOG expression, with knock-down of these genes leading to a genotype-specific decrease in colony numbers. Moreover, our analysis revealed increased PD-L1 surface expression in malignant monocytes from +9p patients, while analysis of the T cell compartment unveiled elevated levels of exhausted cytotoxic T cells. Overall, here we identify a distinct novel subgroup of MPN patients, who feature a synergistic interplay between +9p and JAK2V617F that shapes immune escape characteristics and increased stemness in CD34+ cells.
Effect of a digital school-based intervention on adolescent family planning and reproductive health in Rwanda: a cluster-randomized trial
Authors: Rebecca Hémono, Emmyson Gatare, Laetitia Kayitesi, Lauren A. Hunter, Laura Packel, Nicole Ippoliti, Diego Cerecero-García, David Contreras-Loya, Paola Gadsden, Sergio Bautista-Arredondo, Felix Sayinzoga, Michael Mugisha, Stefano M. Bertozzi, Rebecca Hope, Sandra I. McCoy
Journal: Nature Medicine (2024)
Causal inference on human behaviour
Authors: Drew H. Bailey, Alexander J. Jung, Adriene M. Beltz, Markus I. Eronen, Christian Gische, Ellen L. Hamaker, Konrad P. Kording, Catherine Lebel, Martin A. Lindquist, Julia Moeller, Adeel Razi, Julia M. Rohrer, Baobao Zhang, Kou Murayama
Journal: Nature Human Behaviour (2024)
BRD-810 is a highly selective MCL1 inhibitor with optimized in vivo clearance and robust efficacy in solid and hematological tumor models
Authors: Ulrike Rauh, Guo Wei, Michael Serrano-Wu, Georgios Kosmidis, Stefan Kaulfuss, Franziska Siegel, Kai Thede, James McFarland, Christopher T. Lemke, Nicolas Werbeck, Katrin Nowak-Reppel, Sabine Pilari, Stephan Menz, Matthias Ocker, Weiqun Zhang, Kyle Davis, Guillaume Poncet-Montange, Jennifer Roth, Douglas Daniels, Virendar K. Kaushik, Brian Hubbard, Karl Ziegelbauer, Todd R. Golub
Journal: Nature Cancer (2024)

The MCL1 gene is frequently amplified in cancer and codes for the antiapoptotic protein myeloid cell leukemia 1 (MCL1), which confers resistance to the current standard of care. Therefore, MCL1 is an attractive anticancer target. Here we describe BRD-810 as a potent and selective MCL1 inhibitor and its key design principle of rapid systemic clearance to potentially minimize area under the curve-driven toxicities associated with MCL1 inhibition. BRD-810 induced rapid cell killing within 4 h in vitro but, in the same 4-h window, had no impact on cell viability or troponin I release in human induced pluripotent stem cell-derived cardiomyocytes, even at suprapharmacologic concentrations. In vivo BRD-810 induced efficacy in xenograft hematological and solid tumor models despite the short residence time of BRD-810 in plasma. In totality, our data support the hypothesis that short-term inhibition of MCL1 with BRD-810 can induce apoptosis in tumor cells while maintaining an acceptable safety profile. We, therefore, intend to advance BRD-810 to clinical trials.
Mapping spatial organization and genetic cell-state regulators to target immune evasion in ovarian cancer
Authors: Christine Yiwen Yeh, Karmen Aguirre, Olivia Laveroni, Subin Kim, Aihui Wang, Brooke Liang, Xiaoming Zhang, Lucy M. Han, Raeline Valbuena, Michael C. Bassik, Young-Min Kim, Sylvia K. Plevritis, Michael P. Snyder, Brooke E. Howitt, Livnat Jerby
Journal: Nature Immunology (2024)

The drivers of immune evasion are not entirely clear, limiting the success of cancer immunotherapies. Here we applied single-cell spatial and perturbational transcriptomics to delineate immune evasion in high-grade serous tubo-ovarian cancer. To this end, we first mapped the spatial organization of high-grade serous tubo-ovarian cancer by profiling more than 2.5 million cells in situ in 130 tumors from 94 patients. This revealed a malignant cell state that reflects tumor genetics and is predictive of T cell and natural killer cell infiltration levels and response to immune checkpoint blockade. We then performed Perturb-seq screens and identified genetic perturbations—including knockout of PTPN1 and ACTR8—that trigger this malignant cell state. Finally, we show that these perturbations, as well as a PTPN1/PTPN2 inhibitor, sensitize ovarian cancer cells to T cell and natural killer cell cytotoxicity, as predicted. This study thus identifies ways to study and target immune evasion by linking genetic variation, cell-state regulators and spatial biology. Here the authors provide a resource for ovarian cancer combining spatial transcriptomics, genomics, CRISPR Perturb-seq screens and in silico methods to focus on T cells and natural killer cells in the tumor and their role in immune evasion.
Gut microbiome structure and function in asymptomatic diverticulosis
Authors: Xinwei Hua, Jessica McGoldrick, Nour Nakrour, Kyle Staller, Daniel Chulyong Chung, Ramnik Joseph Xavier, Hamed Khalili
Journal: Genome Medicine (2024)

Abstract Background Colonic diverticulosis, the most common lesion found in routine colonoscopy, affects more than 50% of individuals aged ≥ 60 years. Emerging evidence suggest that dysbiosis of gut microbiota may play an important role in the pathophysiology of diverticular disease. However, specific changes in microbial species and metabolic functions in asymptomatic diverticulosis remain unknown. Methods In a cohort of US adults undergoing screening colonoscopy, we analyzed the gut microbiota using shotgun metagenomic sequencing. Demographic factors, lifestyle, and medication use were assessed using a baseline questionnaire administered prior to colonoscopy. Taxonomic structures and metabolic pathway abundances were determined using MetaPhlAn3 and HUMAnN3. We used multivariate association with linear models to identify microbial species and metabolic pathways that were significantly different between asymptomatic diverticulosis and controls, while adjusting for confounders selected a priori including age at colonoscopy, sex, body mass index (BMI), and dietary pattern. Results Among 684 individuals undergoing a screening colonoscopy, 284 (42%) had diverticulosis. Gut microbiome composition explained 1.9% variation in the disease status of asymptomatic diverticulosis. We observed no significant differences in the overall diversity of gut microbiome between asymptomatic diverticulosis and controls. However, microbial species Bifidobacterium pseudocatenulatum and Prevotella copri were significantly enriched in controls ( q value = 0.19 and 0.14, respectively), whereas Roseburia intestinalis , Dorea sp. CAG:317, and Clostridium sp. CAG: 299 were more abundant in those with diverticulosis ( q values = 0.17, 0.24, and 0.10, respectively). We observed that the relationship between BMI and diverticulosis appeared to be limited to carriers of Bifidobacterium pseudocatenulatum and Roseburia intestinalis ( P interaction = 0.09). Conclusions Our study provides the first large-scale evidence supporting taxonomic and functional shifts of the gut microbiome in individuals with asymptomatic diverticulosis. The suggestive interaction between gut microbiota and BMI on prevalent diverticulosis deserves future investigations.
Jim Simons (1938–2024)
Authors: Gerald D. Fischbach
Journal: Nature Neuroscience (2024)

What follows is not a detailed biography of Jim Simons, whose diversity of talents and activities as a mathematician, educator, administrator, life scientist, philanthropist and visionary in this country and abroad would fill several volumes. It is simply a glance at this wonderful man as I knew him in connection with his growing interest in life sciences and as a friend.
Clonal succession after prolonged antiretroviral therapy rejuvenates CD8+ T cell responses against HIV-1
Authors: Eoghann White, Laura Papagno, Assia Samri, Kenji Sugata, Boris Hejblum, Amy R. Henry, Daniel C. Rogan, Samuel Darko, Patricia Recordon-Pinson, Yasmine Dudoit, Sian Llewellyn-Lacey, Lisa A. Chakrabarti, Florence Buseyne, Stephen A. Migueles, David A. Price, Marie-Aline Andreola, Yorifumi Satou, Rodolphe Thiebaut, Christine Katlama, Brigitte Autran, Daniel C. Douek, Victor Appay
Journal: Nature Immunology (2024)
Early warning COVID-19 outbreak in long-term care facilities using wastewater surveillance: correlation, prediction, and interaction with clinical and serological statuses
Authors: Xiaoli Pang, Bonita E Lee, Tiejun Gao, Rhonda J Rosychuk, Linnet Immaraj, Judy Y Qiu, Jiabi Wen, Nathan Zelyas, Krista Howden, Janelle Wallace, Eleanor Risling, Lorie A Little, John Kim, Heidi Wood, Alyssia Robinson, Michael Parkins, Casey R J Hubert, Kevin Frankowski, Steve E Hrudey, Christopher Sikora
Journal: The Lancet Microbe (2024)

The unprecedented COVID-19 pandemic has highlighted the strategic value of wastewater-based surveillance (WBS) of SARS-CoV-2. This multisite 28-month-long study focused on WBS for older residents in 12 long-term care facilities (LTCFs) in Edmonton (AB, Canada) by assessing relationships between COVID-19, WBS, and serostatus during the pandemic.
Intestinal Lymphatic Biology, Drug Delivery and Therapeutics: Current status and Future directions
Authors: Sanjeevini Babu Reddiar, Yining Xie, Mohammad Abdallah, Sifei Han, Luojuan Hu, Orlagh M. Feeney, Gracia Gracia, Abel Anshabo, Zijun Lu, Muhammad Asim Farooq, Ian K. Styles, Anthony R.J. Phillips, John A. Windsor, Christopher J.H. Porter, Enyuan Cao, Natalie L. Trevaskis
Journal: Pharmacological Reviews (2024)

Historically, the intestinal lymphatics were considered passive conduits for fluids, immune cells, dietary lipids, lipid soluble vitamins and lipophilic drugs. Studies of intestinal lymphatic drug delivery in the late 20<sup>th</sup> century focussed primarily on the drug physicochemical properties, especially high lipophilicity, that resulted in intestinal lymphatic transport. More recent discoveries have changed our traditional view by demonstrating that the lymphatics are active, plastic and tissue-specific players in a range of biological and pathological processes, including within the intestine. These findings have, in turn, inspired exploration of lymph-specific therapies for a range of diseases, as well as the development of more sophisticated strategies to actively deliver drugs or vaccines to the intestinal lymph, including a range of nanotechnologies, lipid prodrugs and lipid-conjugated materials that 9hitchhike9 on lymphatic transport pathways. With the increasing development of novel biological therapeutics there has been interest in whether these novel therapeutics are absorbed and transported through intestinal lymph after oral administration. Here we review the current state of understanding of the anatomy and physiology of the gastrointestinal lymphatic system in health and disease, with a focus on aspects relevant to drug delivery. We summarise the current state-of-the-art approaches to deliver drugs and quantify their uptake into the intestinal lymphatic system. Finally, and excitingly, we discuss recent examples of significant pharmacokinetic and therapeutic benefits achieved via intestinal lymphatic drug delivery. We also propose approaches to advance the development and clinical application of intestinal lymphatic delivery strategies into the future. <b>Significance Statement</b> This comprehensive review details understanding of the anatomy and physiology of the intestinal lymphatic system in health and disease, with a focus on aspects relevant to drug delivery. It highlights current state-of-the-art approaches to deliver drugs to the intestinal lymphatics and the shift toward the use of these strategies to achieve pharmacokinetic and therapeutic benefits for patients.
Approach to Mycosis Fungoides in children (ARMFUL study): consensus-based recommendations
Authors: Alex Zvulunov, Holly Neale, Jonah Stern, Pasqualina Santaguida, Amy Buros Stein, Mark Koh, Lawrence F. Eichenfield, Joan Guitart, Matthias Goebeler, Julia Scarisbrick, Rein Willemze, Carrie C. Coughlin, Renu George, Valeria Brazzelli, Márta Marschalkó, Irena Belousova, Christiane Querfeld, Martine Bagot, Jacek C. Szepietowski, Evangelina Papadavid, Pietro Quaglino, Peter Hoeger, Pablo L. Ortiz-Romero, Vasiliki Nikolaou, Reinhard Dummer, Phyu P. Aung, Leslie Lawley, Kimberly D. Morel, Bo Ngan, Mary Wain, Ana Gameiro, Rosa María Lacy-Niebla, Elena Pope
Journal: Journal of the American Academy of Dermatology (2024)
Ancestral diversity in pharmacogenomics affects treatment for Hispanic/Latine populations with inflammatory bowel disease
Authors: Stephanie Ioannou, Ashley Beecham, Lissette Gomez, Ryan Dauer, Nidah Khakoo, Lauren Pascual, Maria Quintero, Joanna Lopez, James S Leavitt, Norma Solis, Mailenys Ortega, Amar R Deshpande, David H Kerman, Siobhan Proksell, Esther A Torres, Talin Haritunians, Dalin Li, Maria T Abreu, Dermott P B McGovern, Jacob L McCauley, Oriana M Damas
Journal: Clinical Gastroenterology and Hepatology (2024)
Induction of circulating ABCB1 transcripts under platinum-based chemotherapy indicates poor prognosis and a bone micrometastatic phenotype in ovarian cancer patients
Authors: Franziska Maria Schwarz, Jan Dominik Kuhlmann, Jorrin Kämpfer, Anna Klimova, Daniel Martin Klotz, Lisa Freitag, Pia Herrmann, Viktoria Zinnow, Janice Smith, Theresia Scheller, Wolfgang Walther, Pauline Wimberger, Ulrike Stein
Journal: Molecular Cancer (2024)

The drug efflux transporter P-glycoprotein, encoded by the ABCB1 gene, promotes acquired chemoresistance. We explored the presence and clinical relevance of circulating cell-free ABCB1 transcripts (cfABCB1tx) in ovarian cancer patients (173 longitudinal serum samples from 79 cancer patients) using digital droplet PCR. cfABCB1tx were readily detectable at primary diagnosis (median 354 mRNA copies/20 µl serum), paralleled FIGO-stage and predicted surgical outcome (p = 0.023, p=0.022, respectively). Increased cfABCB1tx levels at primary diagnosis indicated poor PFS (HR = 2.329, 95%CI:1.374–3.947, p = 0.0017) and OS (HR = 2.074, 95%CI:1.194–3.601, p = 0.0096). cfABCB1tx induction under platinum-based chemotherapy was an independent predictor for poor OS (HR = 2.597, 95%CI: 1.218–5.538, p = 0.013) and paralelled a micrometastatic phenotype, shaped by the presence of disseminated tumor cells in the bone marrow. A strong correlation was observed between cfABCB1tx and circulating transcripts of the metastasis-inducer MACC1, which is the transcriptional activator of ABCB1. Combined assessment of cfABCB1tx and circulating cell-free MACC1 transcripts (cfMACC1tx) resulted in an improved prognostic prediction, with the cfABCB1tx-high/cfMACC1tx-high phenotype bearing the highest risk for relapse and death. Conclusively, we provide proof of principle, that ABCB1 transcripts are readily traceable in the liquid-biopsy of ovarian cancer patients, advancing a new dimension for systemic monitoring of ABCB1/P-glycoprotein expression dynamics.
IL-1 Signal Inhibition in Alcohol-Related Hepatitis: A Randomized, Double-Blind, Placebo-Controlled Trial of Canakinumab
Authors: Nikhil Vergis, Vishal Patel, Karolina Bogdanowicz, Justyna Czyzewska-Khan, Rosemary Keshinro, Francesca Fiorentino, Emily Day, Paul Middleton, Stephen Atkinson, Thomas Tranah, Mary Cross, Daphne Babalis, Neil Foster, Emma Lord, Alberto Quaglia, Josephine Lloyd, Robert Goldin, William Rosenberg, Richard Parker, Paul Richardson, Steven Masson, Gavin Whitehouse, Cyril Sieberhagan, David Patch, Nikolai Naoumov, Ashwin Dhanda, Ewan Forrest, Mark Thursz
Journal: Clinical Gastroenterology and Hepatology (2024)

Short-term mortality in alcohol-related hepatitis (AH) is high, and no current therapy results in durable benefit. A role for interleukin (IL)-1β has been demonstrated in the pathogenesis of alcohol-induced steatohepatitis. This study explored the safety and efficacy of canakinumab (CAN), a monoclonal antibody targeting IL-1β, in the treatment of patients with AH.
Role of early on-treatment serum HBV RNA declines in predicting hepatocellular carcinoma risk in patients with chronic hepatitis B
Authors: Shi Liu, Grace Lai-Hung Wong, Rong Fan, Junqi Niu, Hong Ma, Wanying Liang, Xingyu Lu, Jianping Xie, Jia Shang, Dongying Xie, Yali Liu, Bin Zhou, Qing Xie, Jie Peng, Hongbo Gao, Huiying Rao, Jinjun Chen, Jifang Sheng, Sheng Shen, Song Yang, Xiaoguang Dou, Zhengang Zhang, Vincent Wai-Sun Wong, Jinlin Hou, Jian Sun
Journal: Clinical Gastroenterology and Hepatology (2024)