tbuckley/cabot-search huggingface dataset:
Recipient microbiome-related features predicting metabolic improvement following fecal microbiota transplantation in adults with severe obesity and metabolic syndrome: a secondary analysis of a phase 2 clinical trial
Authors: Zhengxiao Zhang, Valentin Mocanu, Edward C. Deehan, Naomi Hotte, Yuanyuan Zhu, Shanshan Wei, Dina H. Kao, Shahzeer Karmali, Daniel W. Birch, Jens Walter, Karen L. Madsen
Journal: Gut Microbes (2024)

Microbial-based therapeutics in clinical practice are of considerable interest, and a recent study demonstrated fecal microbial transplantation (FMT) followed by dietary fiber supplements improved glucose homeostasis. Previous evidence suggests that donor and recipient compatibility and FMT protocol are key determinants, but little is known about the involvement of specific recipient factors. Using data from our recent randomized placebo-control phase 2 clinical trial in adults with obesity and metabolic syndrome, we grouped participants that received FMT from one of 4 donors with either fiber supplement into HOMA-IR responders (n = 21) and HOMA-IR non-responders (n = 8). We further assessed plasma bile acids using targeted metabolomics and performed subgroup analyzes to evaluate the effects of recipient parameters and gastrointestinal factors on microbiota engraftment and homeostatic model assessment of insulin resistance (HOMA2-IR) response. The baseline fecal microbiota composition at genus level of recipients could predict the improvements in HOMA2-IR at week 6 (ROC-AUC = 0.70). Prevotella was identified as an important predictor, with responders having significantly lower relative abundance than non-responders (p = .02). In addition, recipients displayed a highly individualized degree of microbial engraftment from donors. Compared to the non-responders, the responders had significantly increased bacterial richness (Chao1) after FMT and a more consistent engraftment of donor-specific bacteria ASVs (amplicon sequence variants) such as Faecalibacillus intestinalis (ASV44), Roseburia spp. (ASV103), and Christensenellaceae spp. (ASV140) (p < .05). Microbiota engraftment was strongly associated with recipients' factors at baseline including initial gut microbial diversity, fiber and nutrient intakes, inflammatory markers, and bile acid derivative levels. This study identified that responders to FMT therapy had a higher engraftment rate in the transplantation of specific donor-specific microbes, which were strongly correlated with insulin sensitivity improvements. Further, the recipient baseline gut microbiota and related factors were identified as the determinants for responsiveness to FMT and fiber supplementation. The findings provide a basis for the development of precision microbial therapeutics for the treatment of metabolic syndrome.
Efficacy of an inulin-based treatment on intestinal colonization by multidrug-resistant E. coli: insight into the mechanism of action
Authors: Murad Ishnaiwer, Quentin Le Bastard, Maxime Naour, Michal Zeman, Eric Dailly, Emmanuel Montassier, Eric Batard, Michel Dion
Journal: Gut Microbes (2024)

Inulin, an increasingly studied dietary fiber, alters intestinal microbiota. The aim of this study was to assess whether inulin decreases intestinal colonization by multidrug resistant
Pharmacogenomic Clinical Support Tools for the Treatment of Depression
Authors: Matthew L. Baum, Alik S. Widge, Linda L. Carpenter, William M. McDonald, Bruce M. Cohen, Charles B. Nemeroff
Journal: American Journal of Psychiatry (2024)

Objective: In this review, the authors update the 2018 position statement of the American Psychiatric Association Council of Research Workgroup on Biomarkers and Novel Treatments on pharmacogenomic (PGx) tools for treatment selection in depression. Methods: The literature was reviewed for new clinical trials and meta-analyses, published from 2017 to 2022, of studies using PGx tools for treatment selection in depression. The blinding and control conditions, as well as primary and secondary outcomes and post hoc analyses, were summarized. Results: Eleven new clinical trials and five meta-analyses were identified; all studies had primary outcome measures related to speed or efficacy of treatment response. Three trials (27%) demonstrated efficacy on the primary outcome measure with statistical significance; the three studies used different PGx tools; one study was open-label and the other two were small single-blind trials. Five trials (45%) did not detect efficacy with statistical significance on either primary or secondary outcome measures. Only one trial (9%) used adverse events as a primary outcome measure. All studies had significant limitations; for example, none adopted a fully blinded study design, only two studies attempted to blind the treating clinician, and none incorporated measures to estimate the effectiveness of the blinds or the influence of lack of blinding on the study results. Conclusions: The addition of these new data do not alter the recommendations of the 2018 report, or the advice of the U.S. Food and Drug Administration, that the evidence does not support the use of currently available combinatorial PGx tools for treatment selection in major depressive disorder. Priority efforts for future studies and the development and testing of effective tools include fully blinded study designs, inclusion of promising genetic variants not currently included in any commercially available tests, and investigation of other uses of pharmacogenomics, such as estimating the likelihood of rare adverse drug effects, rather than increasing the speed or magnitude of drug response.
Shared and Specific Neural Correlates of Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder: A Meta-Analysis of 243 Task-Based Functional MRI Studies
Authors: Hiroki Tamon, Junya Fujino, Takashi Itahashi, Lennart Frahm, Valeria Parlatini, Yuta Y. Aoki, Francisco Xavier Castellanos, Simon B. Eickhoff, Samuele Cortese
Journal: American Journal of Psychiatry (2024)

Objective: To investigate shared and specific neural correlates of cognitive functions in attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), the authors performed a comprehensive meta-analysis and considered a balanced set of neuropsychological tasks across the two disorders. Methods: A broad set of electronic databases was searched up to December 4, 2022, for task-based functional MRI studies investigating differences between individuals with ADHD or ASD and typically developing control subjects. Spatial coordinates of brain loci differing significantly between case and control subjects were extracted. To avoid potential diagnosis-driven selection bias of cognitive tasks, the tasks were grouped according to the Research Domain Criteria framework, and stratified sampling was used to match cognitive component profiles. Activation likelihood estimation was used for the meta-analysis. Results: After screening 20,756 potentially relevant references, a meta-analysis of 243 studies was performed, which included 3,084 participants with ADHD (676 females), 2,654 participants with ASD (292 females), and 6,795 control subjects (1,909 females). ASD and ADHD showed shared greater activations in the lingual and rectal gyri and shared lower activations in regions including the middle frontal gyrus, the parahippocampal gyrus, and the insula. By contrast, there were ASD-specific greater and lower activations in regions including the left middle temporal gyrus and the left middle frontal gyrus, respectively, and ADHD-specific greater and lower activations in the amygdala and the global pallidus, respectively. Conclusions: Although ASD and ADHD showed both shared and disorder-specific standardized neural activations, disorder-specific activations were more prominent than shared ones. Functional brain differences between ADHD and ASD are more likely to reflect diagnosis-related pathophysiology than bias from the selection of specific neuropsychological tasks.
Association of Lower Rostral Anterior Cingulate GABA+ and Dysregulated Cortisol Stress Response With Altered Functional Connectivity in Young Adults With Lifetime Depression: A Multimodal Imaging Investigation of Trait and State Effects
Authors: Maria Ironside, Jessica M. Duda, Amelia D. Moser, Laura M. Holsen, Chun S. Zuo, Fei Du, Sarah Perlo, Christine E. Richards, Xi Chen, Lisa D. Nickerson, Kaylee E. Null, Shiba M. Esfand, Madeline M. Alexander, David J. Crowley, Meghan Lauze, Madhusmita Misra, Jill M. Goldstein, Diego A. Pizzagalli
Journal: American Journal of Psychiatry (2024)

Objective: Preclinical work suggests that excess glucocorticoids and reduced cortical γ-aminobutyric acid (GABA) may affect sex-dependent differences in brain regions implicated in stress regulation and depressive phenotypes. The authors sought to address a critical gap in knowledge, namely, how stress circuitry is functionally affected by glucocorticoids and GABA in current or remitted major depressive disorder (MDD). Methods: Multimodal imaging data were collected from 130 young adults (ages 18–25), of whom 44 had current MDD, 42 had remitted MDD, and 44 were healthy comparison subjects. GABA+ (γ-aminobutyric acid and macromolecules) was assessed using magnetic resonance spectroscopy, and task-related functional MRI data were collected under acute stress and analyzed using data-driven network modeling. Results: Across modalities, trait-related abnormalities emerged. Relative to healthy comparison subjects, both clinical groups were characterized by lower rostral anterior cingulate cortex (rACC) GABA+ and frontoparietal network amplitude but higher amplitude in salience and stress-related networks. For the remitted MDD group, differences from the healthy comparison group emerged in the context of elevated cortisol levels, whereas the MDD group had lower cortisol levels than the healthy comparison group. In the comparison group, frontoparietal and stress-related network connectivity was positively associated with cortisol level (highlighting putative top-down regulation of stress), but the opposite relationship emerged in the MDD and remitted MDD groups. Finally, rACC GABA+ was associated with stress-induced changes in connectivity between overlapping default mode and salience networks. Conclusions: Lifetime MDD was characterized by reduced rACC GABA+ as well as dysregulated cortisol-related interactions between top-down control (frontoparietal) and threat (task-related) networks. These findings warrant further investigation of the role of GABA in the vulnerability to and treatment of MDD.
Spatiotemporal ATF3 Expression Determines VSMC Fate in Abdominal Aortic Aneurysm
Authors: Ying Wen, Yingying Liu, Qiang Li, Jinlin Tan, Xing Fu, Yiwen Liang, Yonghua Tuo, Luhao Liu, Xueqiong Zhou, Dongkai LiuFu, Xuejiao Fan, Chaofei Chen, Zheng Chen, Zhouping Wang, Shunyang Fan, Renjing Liu, Lei Pan, Yuan Zhang, Wai Ho Tang
Journal: Circulation Research (2024)

Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. ATF3 (activating transcription factor 3) has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 in AAA development and progression remains elusive.
Medical algorithm: Diagnosis and management of adult food protein‐induced enterocolitis syndrome
Authors: Purificación Gonzalez‐Delgado, Sara Anvari, Ana Entrala, Sonsoles Infante
Journal: Allergy (2024)

Purificacion Gonzalez-Delgado and Sara Anvari serve on the Medical Advisory Board of the International FPIES Association (iFPIES).
Concomitant moderate-to-severe cutaneous lesions have marked impact on quality of life in patients with active systemic lupus erythematosus: a cross-sectional insight from two phase III randomized clinical trials in adults
Authors: Mischa J Mallbris, Bochao Jia, Youna Zhao, J  Michelle Kahlenberg, Johann E Gudjonsson
Journal: British Journal of Dermatology (2024)

For the first time and in a large study we have shown that in patients with active systemic lupus erythematosus (SLE), health-related quality of life was negatively affected by the presence of moderate-to-severe skin lesions compared with patients with active SLE who had no/mild skin lesions.
Comparing advanced hybrid closed loop therapy and standard insulin therapy in pregnant women with type 1 diabetes (CRISTAL): a parallel-group, open-label, randomised controlled trial
Authors: Katrien Benhalima, Kaat Beunen, Nancy Van Wilder, Dominique Ballaux, Gerd Vanhaverbeke, Youri Taes, Xavier-Philippe Aers, Frank Nobels, Joke Marlier, Dahae Lee, Joke Cuypers, Vanessa Preumont, Sarah E Siegelaar, Rebecca C Painter, Annouschka Laenen, Pieter Gillard, Chantal Mathieu
Journal: The Lancet Diabetes & Endocrinology (2024)
Specialized connectivity of molecular layer interneuron subtypes leads to disinhibition and synchronous inhibition of cerebellar Purkinje cells
Authors: Elizabeth P. Lackey, Luis Moreira, Aliya Norton, Marie E. Hemelt, Tomas Osorno, Tri M. Nguyen, Evan Z. Macosko, Wei-Chung Allen Lee, Court A. Hull, Wade G. Regehr
Journal: Neuron (2024)
Tumor mitochondrial oxidative phosphorylation stimulated by the nuclear receptor RORγ represents an effective therapeutic opportunity in osteosarcoma
Authors: Jianwei Zheng, Qianqian Wang, Jianghe Chen, Guodi Cai, Zhenhua Zhang, Hongye Zou, June X. Zou, Qianqian Liu, Shufeng Ji, Guoli Shao, Hong Li, Sheng Li, Hong-Wu Chen, LinLin Lu, Yanqiu Yuan, Peiqing Liu, Junjian Wang
Journal: Cell Reports Medicine (2024)

Osteosarcoma (OS) is the most common malignant bone tumor with a poor prognosis. Here, we show that the nuclear receptor RORγ may serve as a potential therapeutic target in OS. OS exhibits a hyperactivated oxidative phosphorylation (OXPHOS) program, which fuels the carbon source to promote tumor progression. We found that RORγ is overexpressed in OS tumors and is linked to hyperactivated OXPHOS. RORγ induces the expression of PGC-1β and physically interacts with it to activate the OXPHOS program by upregulating the expression of respiratory chain component genes. Inhibition of RORγ strongly inhibits OXPHOS activation, downregulates mitochondrial functions, and increases ROS production, which results in OS cell apoptosis and ferroptosis. RORγ inverse agonists strongly suppressed OS tumor growth and progression and sensitized OS tumors to chemotherapy. Taken together, our results indicate that RORγ is a critical regulator of the OXPHOS program in OS and provides an effective therapeutic strategy for this deadly disease.
A systems biology-based identification and in vivo functional screening of Alzheimer’s disease risk genes reveal modulators of memory function
Authors: Adam D. Hudgins, Shiyi Zhou, Rachel N. Arey, Michael G. Rosenfeld, Coleen T. Murphy, Yousin Suh
Journal: Neuron (2024)

Genome-wide association studies (GWASs) have uncovered over 75 genomic loci associated with risk for late-onset Alzheimer's disease (LOAD), but identification of the underlying causal genes remains challenging. Studies of induced pluripotent stem cell (iPSC)-derived neurons from LOAD patients have demonstrated the existence of neuronal cell-intrinsic functional defects. Here, we searched for genetic contributions to neuronal dysfunction in LOAD using an integrative systems approach that incorporated multi-evidence-based gene mapping and network-analysis-based prioritization. A systematic perturbation screening of candidate risk genes in Caenorhabditis elegans (C. elegans) revealed that neuronal knockdown of the LOAD risk gene orthologs vha-10 (ATP6V1G2), cmd-1 (CALM3), amph-1 (BIN1), ephx-1 (NGEF), and pho-5 (ACP2) alters short-/intermediate-term memory function, the cognitive domain affected earliest during LOAD progression. These results highlight the impact of LOAD risk genes on evolutionarily conserved memory function, as mediated through neuronal endosomal dysfunction, and identify new targets for further mechanistic interrogation.
3D-Printed proangiogenic patches of photo-crosslinked gelatin and polyurethane hydrogels laden with vascular cells for treating vascular ischemic diseases
Authors: Yu-Tsung Shih, Kun-Chih Cheng, Yi-Ju Ko, Chia-Yu Lin, Mei-Cun Wang, Chih-I Lee, Pei-Ling Lee, Rong Qi, Jeng-Jiann Chiu, Shan-hui Hsu
Journal: Biomaterials (2024)
Safety of empirical antibiotic therapy discontinuing for fever of unknown origin during high-risk neutropenia in children
Authors: Lemaigre Clément, Deutch Hélène, Meligne Maud, Dupraz Chrystelle, Bridonneau Constance, Millot Fréderic, Roblot France, Gallego-Hernanz Maria Pilar, Torregrosa-Diaz José-Miguel, Rammaert Blandine
Journal: Journal of Infection (2024)

ECIL-2021 recommends discontinuing empirical antibiotic therapy (EAT) in febrile-neutropenic children after 72 h of treatment and at least 24-48 h of apyrexia in the case of fever of unknown origin (FUO). These guidelines are rarely applied to high-risk children's neutropenia.
Echocardiography-Guided Radiofrequency Ablation for Cardiac Tumors
Authors: Junzhe Huang, Changhui Lei, David H. Hsi, Minjuan Zheng, Hui Ma, Shengjun Ta, Rui Hu, Chao Han, Wenxia Li, Jing Li, Dong Qu, Fangqi Ruan, Jing Wang, Bo Wang, Xueli Zhao, Jiao Liu, Lina Zhao, Zhe Wang, Jian Yang, Liwen Liu
Journal: JACC CardioOncology (2024)

Patients with cardiac tumors may present challenges for surgical resection due to poor clinical condition. Echocardiography-guided transapical radiofrequency ablation for cardiac tumors (TARFACT) potentially offers a less invasive palliative therapy option.
Hydroxyurea dose optimisation for children with sickle cell anaemia in sub-Saharan Africa (REACH): extended follow-up of a multicentre, open-label, phase 1/2 trial
Authors: Banu Aygun, Adam Lane, Luke R Smart, Brígida Santos, Léon Tshilolo, Thomas N Williams, Peter Olupot-Olupot, Susan E Stuber, George Tomlinson, Teresa Latham, Russell E Ware
Journal: The Lancet Haematology (2024)
Prognostic impact and causality of age on oncological outcomes in women with endometrial cancer: a multimethod analysis of the randomised PORTEC-1, PORTEC-2, and PORTEC-3 trials
Authors: Famke C Wakkerman, Jiqing Wu, Hein Putter, Ina M Jürgenliemk-Schulz, Jan J Jobsen, Ludy C H W Lutgens, Marie A D Haverkort, Marianne A de Jong, Jan Willem M Mens, Bastiaan G Wortman, Remi A Nout, Alicia Léon-Castillo, Melanie E Powell, Linda R Mileshkin, Dionyssios Katsaros, Joanne Alfieri, Alexandra Leary, Naveena Singh, Stephanie M de Boer, Hans W Nijman, Vincent T H B M Smit, Tjalling Bosse, Viktor H Koelzer, Carien L Creutzberg, Nanda Horeweg
Journal: The Lancet Oncology (2024)
Effectiveness and impact of universal prophylaxis with nirsevimab in infants against hospitalisation for respiratory syncytial virus in Galicia, Spain: initial results of a population-based longitudinal study
Authors: Sonia Ares-Gómez, Narmeen Mallah, María-Isolina Santiago-Pérez, Jacobo Pardo-Seco, Olaia Pérez-Martínez, María-Teresa Otero-Barrós, Nuria Suárez-Gaiche, Rolf Kramer, Jing Jin, Leticia Platero-Alonso, Rosa-María Alvárez-Gil, Olga-María Ces-Ozores, Victoria Nartallo-Penas, Susana Mirás-Carballal, Marta Piñeiro-Sotelo, Alberto Malvar-Pintos, Juan-Manuel González-Pérez, Carmen Rodríguez-Tenreiro-Sánchez, Irene Rivero-Calle, Antonio Salas, Carmen Durán-Parrondo, Federico Martinón-Torres
Journal: The Lancet Infectious Diseases (2024)
Long-acting transdermal drug delivery formulations: Current developments and innovative pharmaceutical approaches
Authors: Tanvi Karve, Amruta Dandekar, Vivek Agrahari, M. Melissa Peet, Ajay K. Banga, Gustavo F. Doncel
Journal: Advanced Drug Delivery Reviews (2024)

Transdermal administration remains an active research and development area as an alternative route for long-acting drug delivery. It avoids major drawbacks of conventional oral (gastrointestinal side effects, low bioavailability, and multiple dosing) or parenteral routes (invasiveness, pain, and psychological stress and bio-hazardous waste generated from needles), thereby increasing patient appeal and compliance. This review focuses on the current state of long-acting transdermal drug delivery, including adhesive patches, microneedles, and molecularly imprinted polymeric systems. Each subsection describes an approach including key considerations in formulation development, design, and process parameters with schematics. An overview of commercially available conventional (adhesive) transdermal patches for long-acting drug delivery (longer than 24 h), as well as advanced formulations in development, such as the core-shell, nanoformulations-incorporated and stimuli-responsive microneedles, and 3D-printed and molecularly imprinted polymers is also provided. Finally, we elaborated on translational aspects, challenges in patch formulation development, and future directions for the clinical advancement of new long-acting transdermal products
pH-responsive bioadhesive with robust and stable wet adhesion for gastric ulcer healing
Authors: Ruilin Xie, Xueli Yan, Jing Yu, Kaixiang Shen, Mengyuan Zhang, Meng Li, Zhuting Lv, Yuchen Zhang, Zixi Zhang, Yi Lyu, Yilong Cheng, Dake Chu
Journal: Biomaterials (2024)
Oxylipin profiling for clinical research: Current status and future perspectives
Authors: Karol Parchem, Sophia Letsiou, Toni Petan, Olga Oskolkova, Isabel Medina, Ondrej Kuda, Valerie B O'Donnell, Anna Nicolaou, Maria Fedorova, Valery Bochkov, Cécile Gladine
Journal: Progress in Lipid Research (2024)

Oxylipins are potent lipid mediators with increasing interest in clinical research. They are usually measured in systemic circulation and can provide a wealth of information regarding key biological processes such as inflammation, vascular tone, or blood coagulation. Although procedures still require harmonization to generate comparable oxylipin datasets, performing comprehensive profiling of circulating oxylipins in large studies is feasible and no longer restricted by technical barriers. However, it is essential to improve and facilitate the biological interpretation of complex oxylipin profiles to truly leverage their potential in clinical research. This requires regular updating of our knowledge about the metabolism and the mode of action of oxylipins, and consideration of all factors that may influence circulating oxylipin profiles independently of the studied disease or condition. This review aims to provide the readers with updated and necessary information regarding oxylipin metabolism, their different forms in systemic circulation, the current limitations in deducing oxylipin cellular effects from in vitro bioactivity studies, the biological and technical confounding factors needed to consider for a proper interpretation of oxylipin profiles.
STINGing away the pain: the role of interferon-stimulated genes
Authors: Erick J. Rodriguez-Palma, Heather N. Allen, Rajesh Khanna
Journal: Journal of Clinical Investigation (2024)

Pain and inflammation are biologically intertwined responses that warn the body of potential danger. In this issue of the JCI, Defaye, Bradaia, and colleagues identified a functional link between inflammation and pain, demonstrating that inflammation-induced activation of stimulator of IFN genes (STING) in dorsal root ganglia nociceptors reduced pain-like behaviors in a rodent model of inflammatory pain. Utilizing mice with a gain-of-function STING mutation, Defaye, Bradaia, and colleagues identified type I IFN regulation of voltage-gated potassium channels as the mechanism of this pain relief. Further investigation into mechanisms by which proinflammatory pathways can reduce pain may reveal druggable targets and insights into new approaches for treating persistent pain.