tbuckley/cabot-search huggingface dataset:
The All of Us Research Program is an opportunity to enhance the diversity of US biomedical research
Authors: Diana W Bianchi, Patricia Flatley Brennan, Michael F Chiang, Lindsey A Criswell, Rena N D'Souza, Gary H Gibbons, James K Gilman, Joshua A Gordon, Eric D Green, Susan Gregurick, Richard J Hodes, Peter H Kilmarx, George F Koob, Walter J Koroshetz, Helene M Langevin, Jon R Lorsch, Jeanne M Marrazzo, Eliseo J Pérez-Stable, W Kimryn Rathmell, Griffin P Rodgers, Joni L Rutter, Jane M Simoni, Bruce J Tromberg, Debara L Tucci, Nora D Volkow, Rick Woychik, Shannon N Zenk, Elyse Kozlowski, Rachele S Peterson, Geoffrey S Ginsburg, Joshua C Denny
Journal: Nature Medicine (2024)
Cell-type-specific expression of tRNAs in the brain regulates cellular homeostasis
Authors: Mridu Kapur, Michael J. Molumby, Carlos Guzman, Sven Heinz, Susan L. Ackerman
Journal: Neuron (2024)

Defects in tRNA biogenesis are associated with multiple neurological disorders, yet our understanding of these diseases has been hampered by an inability to determine tRNA expression in individual cell types within a complex tissue. Here, we developed a mouse model in which RNA polymerase III is conditionally epitope tagged in a Cre-dependent manner, allowing us to accurately profile tRNA expression in any cell type in vivo. We investigated tRNA expression in diverse nervous system cell types, revealing dramatic heterogeneity in the expression of tRNA genes between populations. We found that while maintenance of levels of tRNA isoacceptor families is critical for cellular homeostasis, neurons are differentially vulnerable to insults to distinct tRNA isoacceptor families. Cell-type-specific translatome analysis suggests that the balance between tRNA availability and codon demand may underlie such differential resilience. Our work provides a platform for investigating the complexities of mRNA translation and tRNA biology in the brain.
Unraveling the Therapeutic Benefit of Sequenced Chemo-immunotherapy
Authors: Paolo D.A. Vignali, Jason J. Luke
Journal: Clinical Cancer Research (2024)

Combination immune-checkpoint inhibition with chemotherapy is a clinical standard, yet concurrent administration may limit the full benefit of immunotherapy by blunting the proliferation and differentiation of CD8 T cells. Identifying patients in whom sequential chemo-immunotherapy or immunotherapy alone is feasible should be a priority to optimize long-term outcomes. See related article by Mariniello et al., p. 1833.
Therapeutic effect of dietary ingredients on cellular senescence in animals and humans: A systematic review
Authors: Lihuan Guan, Anna Eisenmenger, Karen C Crasta, Elena Sandalova, Andrea B Maier
Journal: Ageing Research Reviews (2024)

Cellular senescence has been regarded as a therapeutic target for ageing and age-related diseases. Several senotherapeutic agents have been proposed, including compounds derived from natural products which hold the translational potential to promote healthy ageing. This systematic review examined the association of dietary ingredients with cellular senescence in animals and humans, with an intent to identify dietary ingredients with senotherapeutic potential.
Evaluating the relationship between ciprofloxacin prescription and non-susceptibility in Salmonella Typhi in Blantyre, Malawi: an observational study
Authors: Philip M Ashton, Angeziwa Chunga Chirambo, James E Meiring, Priyanka D Patel, Maurice Mbewe, Niza Silungwe, Kenneth Chizani, Happy Banda, Robert S Heyderman, Zoe A Dyson, Peter MacPherson, Marc Y R Henrion, Prasanta Kumar Biswas, Md Amiruli Islam Bhuiyan, Christoph Blohmke, Thomas C Darton, Christiane Dolecek, Sabina Dongol, Yama Farooq, Jennifer Hill, Nhu Tran Hoang, Tikhala Makhaza Jere, Harrison Msuku, Tran Vu Thieu Nga, Rose Nkhata, Sadia Isfat Ara Rahman, Nazia Rahman, Neil J Saad, Trinh Van Tan, Deus Thindwa, Merryn Voysey, Richard Wachepa, Andrew Pollard, Kathryn E Holt, Melita A Gordon
Journal: The Lancet Microbe (2024)

Ciprofloxacin is the first-line drug for treating typhoid fever in many countries in Africa with a high disease burden, but the emergence of non-susceptibility poses a challenge to public health programmes. Through enhanced surveillance as part of vaccine evaluation, we investigated the occurrence and potential determinants of ciprofloxacin non-susceptibility in Blantyre, Malawi.
Intra‐Articular Mineralization on Computerized Tomography of the Knee and Risk of Cartilage Damage: The Multicenter Osteoarthritis Study
Authors: Jean W. Liew, Mohammed Jarraya, Ali Guermazi, John Lynch, David Felson, Michael Nevitt, Cora E. Lewis, James Torner, Frank W. Roemer, Michel D. Crema, Na Wang, Fabio Becce, Gabriela Rabasa, Tristan Pascart, Tuhina Neogi
Journal: Arthritis & Rheumatology (2024)

Intra-articular (IA) mineralization may contribute to osteoarthritis (OA) structural progression. We studied the association of IA mineralization on knee computed tomography (CT) with cartilage damage worsening on knee magnetic resonance imaging (MRI), with a focus on location- and tissue-specific effects.
Author Correction: COVID-19 vaccination coverage for half a million non-EU migrants and refugees in England
Authors: Rachel Burns, Sacha Wyke, Max T Eyre, Yamina Boukari, Tina B Sørensen, Camille Tsang, Colin N J Campbell, Sarah Beale, Dominik Zenner, Sally Hargreaves, Ines Campos-Matos, Katie Harron, Robert W Aldridge
Journal: Nature Human Behaviour (2024)
Biomimetic Corneal Stroma for Scarless Corneal Wound Healing via Structural Restoration and Microenvironment Modulation (Adv. Healthcare Mater. 5/2024)
Authors: Jianan Huang, Tuoying Jiang, Jinying Li, Jiqiao Qie, Xiaoyu Cheng, Yiyao Wang, Tinglian Zhou, Jia Liu, Haijie Han, Ke Yao, Luyang Yu
Journal: Advanced Healthcare Materials (2024)
Recent advances in generative biology for biotherapeutic discovery
Authors: Marissa Mock, Christopher James Langmead, Peter Grandsard, Suzanne Edavettal, Alan Russell
Journal: Trends in Pharmacological Sciences (2024)

Generative biology combines artificial intelligence (AI), advanced life sciences technologies, and automation to revolutionize the process of designing novel biomolecules with prescribed properties, giving drug discoverers the ability to escape the limitations of biology during the design of next-generation protein therapeutics. Significant hurdles remain, namely: (i) the inherently complex nature of drug discovery, (ii) the bewildering number of promising computational and experimental techniques that have emerged in the past several years, and (iii) the limited availability of relevant protein sequence-function data for drug-like molecules. There is a need to focus on computational methods that will be most practically effective for protein drug discovery and on building experimental platforms to generate the data most appropriate for these methods. Here, we discuss recent advances in computational and experimental life sciences that are most crucial for impacting the pace and success of protein drug discovery.
Antimicrobial, Antioxidant, and Anti‐Inflammatory Nanoplatform for Effective Management of Infected Wounds (Adv. Healthcare Mater. 5/2024)
Authors: Huining Su, Yang Chen, Xunan Jing, Xiaoping Zhao, Heng Sun, Zhicheng Liu, Yao Qiu, Zuoliang Zhang, Hao Guan, Lingjie Meng
Journal: Advanced Healthcare Materials (2024)
First total synthesis, antitumor evaluation and target identification of mornaphthoate E: A new tubulin inhibitor template acting on PI3K/Akt signaling pathway
Authors: Peipei Shan, Tao Ye, Ying-De Tang, Hui Song, Chao Wang, Kongkai Zhu, Feifei Yang, Shi-Lei Zhang, Pei-Wen Su, Shuanhu Gao, Hua Zhang
Journal: Acta Pharmaceutica Sinica B (2024)

Mornaphthoate E (MPE) is a prenylated naphthoic acid methyl ester isolated from the roots of a famous Chinese medicinal plant
Airway epithelial cell cilia transcriptomic dysregulation is associated with the inflammatory phenotype in asthma
Authors: Maëva A. Devilliers, Audrey Brisebarre, Laure M. G. Petit, Myriam Polette, Gaëtan Deslée, Ratko Djukanović, Valérian Dormoy, Jeanne‐Marie Perotin
Journal: Allergy (2024)
Detection of a historic reservoir of bedaquiline/clofazimine resistance-associated variants in Mycobacterium tuberculosis
Authors: Camus Nimmo, Arturo Torres Ortiz, Cedric C. S. Tan, Juanita Pang, Mislav Acman, James Millard, Nesri Padayatchi, Alison D. Grant, Max O’Donnell, Alex Pym, Ola B. Brynildsrud, Vegard Eldholm, Louis Grandjean, Xavier Didelot, François Balloux, Lucy van Dorp
Journal: Genome Medicine (2024)

Abstract Background Drug resistance in tuberculosis (TB) poses a major ongoing challenge to public health. The recent inclusion of bedaquiline into TB drug regimens has improved treatment outcomes, but this advance is threatened by the emergence of strains of Mycobacterium tuberculosis ( Mtb ) resistant to bedaquiline. Clinical bedaquiline resistance is most frequently conferred by off-target resistance-associated variants (RAVs) in the mmpR5 gene ( Rv0678 ), the regulator of an efflux pump, which can also confer cross-resistance to clofazimine, another TB drug. Methods We compiled a dataset of 3682 Mtb genomes, including 180 carrying variants in mmpR5 , and its immediate background (i.e. mmpR5 promoter and adjacent mmpL5 gene), that have been associated to borderline (henceforth intermediate) or confirmed resistance to bedaquiline. We characterised the occurrence of all nonsynonymous mutations in mmpR5 in this dataset and estimated, using time-resolved phylogenetic methods, the age of their emergence. Results We identified eight cases where RAVs were present in the genomes of strains collected prior to the use of bedaquiline in TB treatment regimes. Phylogenetic reconstruction points to multiple emergence events and circulation of RAVs in mmpR5 , some estimated to predate the introduction of bedaquiline. However, epistatic interactions can complicate bedaquiline drug-susceptibility prediction from genetic sequence data. Indeed, in one clade, Ile67fs (a RAV when considered in isolation) was estimated to have emerged prior to the antibiotic era, together with a resistance reverting mmpL5 mutation. Conclusions The presence of a pre-existing reservoir of Mtb strains carrying bedaquiline RAVs prior to its clinical use augments the need for rapid drug susceptibility testing and individualised regimen selection to safeguard the use of bedaquiline in TB care and control.
Materials and Device Designs for Wireless Monitoring of Temperature and Thermal Transport Properties of Wound Beds during Healing (Adv. Healthcare Mater. 5/2024)
Authors: Hanjun Ryu, Joseph W. Song, Haiwen Luan, Youngmin Sim, Sung Soo Kwak, Hokyung Jang, Young Jin Jo, Hong‐Joon Yoon, Hyoyoung Jeong, Jaeho Shin, Do Yun Park, Kyeongha Kwon, Guillermo Antonio Ameer, John A. Rogers
Journal: Advanced Healthcare Materials (2024)
Correction to Lancet Rheumatol 2022; 4: e351–61
Journal: The Lancet Rheumatology (2024)

In this Article, the concentration units in a sentence in the Results section should have read μg/mL rather than mg/mL.The sentence should now read "In the pharmacokinetic analysis for both treatment groups, C trough geometric mean values were 11•59 μg/mL (%CV 134•5%) for the reference tocilizumab group and 11•97 μg/mL (113•3%) for the BAT1806/BIIB800 group at week 12, and 12•26 μg/mL (140•3%) and 12•88 μg/mL (121•3%), respectively, at week 24".These corrections have been made as of Feb 5, 2024.
Oleic acid-PPARγ-FABP4 loop fuels cholangiocarcinoma colonization in lymph node metastases microenvironment
Authors: Honghua Zhang, Ke Zhu, Rui Zhang, Yabin Guo, Jin Wang, Chaoqun Liu, Xinjun Lu, Ziyu Zhou, Wenrui Wu, Fapeng Zhang, Zhixiao Song, Shusheng Lin, Caini Yang, Xiuxian Li, Yang Liu, Qibin Tang, Xianhuan Yu, Leibo Xu, Chao Liu
Journal: Hepatology (2024)

Background and Aims: Lymph node metastasis is a significant risk factor for patients with cholangiocarcinoma, but the mechanisms underlying cholangiocarcinoma colonization in the lymph node microenvironment remain unclear. We aimed to determine whether metabolic reprogramming fueled the adaptation and remodeling of cholangiocarcinoma cells to the lymph node microenvironment. Approach and Results: Here, we applied single-cell RNA sequencing of primary tumor lesions and paired lymph node metastases from patients with cholangiocarcinoma and revealed significantly reduced intertumor heterogeneity and syntropic lipid metabolic reprogramming of cholangiocarcinoma after metastasis to lymph nodes, which was verified by pan-cancer single-cell RNA sequencing analysis, highlighting the essential role of lipid metabolism in tumor colonization in lymph nodes. Metabolomics and in vivo CRISPR/Cas9 screening identified PPARγ as a crucial regulator in fueling cholangiocarcinoma colonization in lymph nodes through the oleic acid-PPARγ-fatty acid–binding protein 4 positive feedback loop by upregulating fatty acid uptake and oxidation. Patient-derived organoids and animal models have demonstrated that blocking this loop impairs cholangiocarcinoma proliferation and colonization in the lymph node microenvironment and is superior to systemic inhibition of fatty acid oxidation. PPARγ-regulated fatty acid metabolic reprogramming in cholangiocarcinoma also contributes to the immune-suppressive niche in lymph node metastases by producing kynurenine and was found to be associated with tumor relapse, immune-suppressive lymph node microenvironment, and poor immune checkpoint blockade response. Conclusions: Our results reveal the role of the oleic acid-PPARγ-fatty acid–binding protein 4 loop in fueling cholangiocarcinoma colonization in lymph nodes and demonstrate that PPARγ-regulated lipid metabolic reprogramming is a promising therapeutic target for relieving cholangiocarcinoma lymph node metastasis burden and reducing further progression.
Serum aryl hydrocarbon receptor activity is associated with survival in patients with alcohol-associated hepatitis
Authors: Tomoo Yamazaki, Tetsuya Kouno, Cynthia L. Hsu, Phillipp Hartmann, Susan Mayo, Xinlian Zhang, Peter Stärkel, Francisco Bosques-Padilla, Elizabeth C. Verna, Juan G. Abraldes, Robert S. Brown, Victor Vargas, Jose Altamirano, Juan Caballería, Debbie L. Shawcross, Alexandre Louvet, Michael R. Lucey, Philippe Mathurin, Guadalupe Garcia-Tsao, Ramon Bataller, Bernd Schnabl
Journal: Hepatology (2024)

Background and Aims: Patients with alcohol-associated hepatitis (AH) have an altered fecal metabolome, including reduced microbiota-derived tryptophan metabolites, which function as ligands for aryl hydrocarbon receptor (AhR). The aim of this study was to assess serum AhR ligand activity in patients with AH. Approach and Results: The study included 74 controls without AUD, 97 patients with AUD, and 330 patients with AH from 2 different multicenter cohorts (InTeam: 134, AlcHepNet: 196). Serum AhR activity was evaluated using an AhR reporter assay with HepG2-Lucia cells incubated with serum for 24 hours. Serum AhR activity was significantly higher in patients with AH compared with both controls (1.59 vs. 0.96-fold change, p &lt; 0.001) and patients with AUD (1.59 vs. 0.93, p &lt; 0.001). In both AH cohorts, patients with AhR activity ≥ 2.09 had significantly lower cumulative survival rates at 30, 60, 90, and 180 days compared to those with AhR activity &lt; 2.09. When serum AhR activity was used to further stratify patients with severe AH, the cumulative 30, 60, 90, and 180-day survival rates for patients with severe AH and the AhR activity ≥ 2.09 group were all significantly lower than those with an AhR activity &lt; 2.09 group. Conclusions: Serum AhR activity was significantly higher in patients with AH compared with controls and individuals with AUD, and this increased activity was associated with higher mortality. Consequently, serum AhR activity holds potential as a prognostic marker.
Identifying Preferred Features of Weight Loss Programs for Adults With or at Risk of Type 2 Diabetes: A Discrete Choice Experiment With 3,960 Adults in the U.K.
Authors: John Buckell, Caroline A. Mitchell, Kate Fryer, Carolyn Newbert, Alan Brennan, Jack Joyce, Susan A. Jebb, Paul Aveyard, Nicola Guess, Elizabeth Morris
Journal: Diabetes Care (2024)

OBJECTIVE To understand preferences for features of weight loss programs among adults with or at risk of type 2 diabetes in the U.K. RESEARCH DESIGN AND METHODS We conducted a discrete choice experiment with 3,960 U.K. adults living with overweight (n = 675 with type 2 diabetes). Preferences for seven characteristics of weight loss programs were analyzed. Simulations from choice models using the experimental data predicted uptake of available weight loss programs. Patient groups comprising those who have experience with weight loss programs, including from minority communities, informed the experimental design. RESULTS Preferences did not differ between individuals with and without type 2 diabetes. Preferences were strongest for type of diet. Healthy eating was most preferred relative to total diet replacement (odds ratio [OR] 2.24; 95% CI 2.04–2.44). Individual interventions were more popular than group interventions (OR 1.40; 95% CI 1.34–1.47). Participants preferred programs offering weight loss of 10–15 kg (OR 1.37; 95% CI 1.28–1.47) to those offering loss of 2–4 kg. Online content was preferred over in-person contact (OR 1.24; 95% CI 1.18–1.30). There were few differences in preferences by gender or ethnicity, although weight loss was more important to women than to men, and individuals from ethnic minority populations identified more with programs where others shared their characteristics. Modeling suggested that tailoring programs to individual preferences could increase participation by ∼17 percentage points (68% in relative terms). CONCLUSIONS Offering a range of weight loss programs targeting the preferred attributes of different patient groups could potentially encourage more people to participate in weight loss programs and support those living with overweight to reduce their weight.
Eosinophilic Fasciitis Illustrated by 18F-FDG PET/CT
Authors: Agathe Fevrier, Pierre-Alban Dufour
Journal: Clinical Nuclear Medicine (2024)

Abstract Eosinophilic fasciitis is a rare sclerodermiform disease characterized by upper and lower limb edema. We present the case of a 71-year-old woman currently hospitalized for painful lower limb edema. Laboratory tests reveal moderate eosinophilia (0.8 g/L) and an inflammatory syndrome. Abdominopelvic ultrasound reveals no abnormalities. In light of the unexplained inflammatory syndrome, a 18 F-FDG PET/CT scan currently shows intense hypermetabolism of the fasciae in the lower and upper limbs. Following an MRI, a biopsy is performed, and the anatomopathology currently confirms eosinophilic fasciitis.
Diffuse Bone Uptake of 131I and Effect on Blood Counts in a Patient With Papillary Thyroid Carcinoma and Chronic Lymphocytic Leukemia
Authors: Adrien Latgé, Mehdi Krim, Lavinia Vija, Loïc Ysebaert, Slimane Zerdoud
Journal: Clinical Nuclear Medicine (2024)

Abstract A 57-year-old woman with history of chronic lymphocytic leukemia was referred to our center for adjuvant 131 I therapy following complete thyroidectomy for differentiated thyroid cancer. Posttherapeutic scintigraphy revealed atypical diffuse osteomedullar uptake. A major drop in lymphocyte count was observed, from 117.7 g/L to 4.8 g/L 8 weeks after 131 I therapy. Bone marrow uptake is presumed to be related to tracer sequestration in leukemic cells. White blood cell count normalization suggests a high sensitivity of leukemic cells to beta emission. This scintigraphic pattern may act as a pitfall for nuclear medicine physician.
177Lu-Microspheres Selective Intra-arterial Radionuclide Therapy
Authors: Jaya Shukla, Sejal Chopra, Komalpreet Kaur, Sudipta Chakraborty, Harmandeep Singh, Ajay Duseja, Naveen Kalra, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2024)

Abstract Hepatocellular carcinoma (HCC) is an aggressive malignancy with a poor prognosis. Surgical resection is limited. Selective intra-arterial radionuclide therapy (SIRT) emerged as a potential cure for intermediate HCC with portal vein thrombosis. We report a pilot study of a 48-year-old man with recurrent HCC who underwent 177 Lu-microsphere SIRT (2.2 GBq) in segment III. Posttherapy SPECT/CT images (24 hours to 3 months) demonstrated excellent localization and prolonged retention within the tumor. Pre- and 3-month post-SIRT CECT showed a notable decrease in arterial enhancement and tumor size. Time-activity curve of the standard and the lesion demonstrated similar decay pattern indicating that 177 Lu-microspheres act as permanent implant.
Elevated FAPI Activity in an Adult Brodie Abscess
Authors: Yang Xie, Wenxin Tang, Huipan Liu, Yudi Wang, Yue Chen
Journal: Clinical Nuclear Medicine (2024)

Abstract We report an adult Brodie abscess with elevated activity of 18 F-FDG and 68 Ga-FAPI (fibroblast activating protein inhibitor), mimicking bone metastasis. Our case illustrates that Brodie abscess should also be contemplated in the differential diagnosis of osteolytic lesions with increased 68 Ga-FAPI uptake.
Cutaneous Metastasis of Ovarian Cancer on 68Ga-FAPI PET/CT
Authors: Haoyuan Ding, Dan Li, Yue Chen, Wenfeng He, Liang Cai
Journal: Clinical Nuclear Medicine (2024)

Abstract Ovarian cancer with cutaneous metastases is quite rare. We report the findings of cutaneous metastases from ovarian cancer on 68 Ga-FAPI PET/CT imaging. A 53-year-old woman with cutaneous metastases from ovarian cancer was enrolled in 68 Ga-FAPI PET/CT clinical trial. The images showed intense FAPI activity in the known cutaneous metastases.
Reversibility of Bicalutamide PSMA PET-Positive Gynecomastia With Androgen Deprivation Therapy
Authors: Miguel Muniz, Daniel S. Childs, Jacob J. Orme, Geoffrey B. Johnson, Oliver Sartor
Journal: Clinical Nuclear Medicine (2024)

Abstract A 78-year-old man receiving bicalutamide for prostate cancer was referred for a PSMA PET/CT scan to evaluate his gradually rising prostate-specific antigen level. The PSMA PET/CT revealed gynecomastia with radiotracer uptake in bilateral breast parenchyma, a known but rarely reported effect of bicalutamide monotherapy. This scan also demonstrated metastatic progression of his disease in bone and lymph nodes, and he was started on leuprolide injections. Three months after a decrease in his testosterone level, the radiotracer uptake in his breast tissue had resolved, demonstrating that PSMA-avid bicalutamide-induced gynecomastia is reversible.