tbuckley/cabot-search huggingface dataset:
Supplier-origin gut microbiomes affect host body weight and select autism-related behaviors
Authors: Zachary L McAdams, Kevin L Gustafson, Amber L Russell, Rachel Self, Amy L Petry, Teresa E Lever, Aaron C Ericsson
Journal: Gut Microbes (2024)

Autism spectrum disorders (ASD) are complex human neurodiversities increasing in prevalence within the human population. In search of therapeutics to improve quality-of-life for ASD patients, the gut microbiome (GM) has become a promising target as a growing body of work supports roles for the complex community of microorganisms in influencing host behavior via the gut-brain-axis. However, whether naturally-occurring microbial diversity within the host GM affects these behaviors is often overlooked. Here, we applied a model of population-level differences in the GM to a classic ASD model – the BTBR T+ Itpr3tf/J mouse – to assess how complex GMs affect host behavior. Leveraging the naturally occurring differences between supplier-origin GMs, our data demonstrate that differing, complex GMs selectively effect host ASD-related behavior – especially neonatal ultrasonic communication – and reveal a male-specific effect on behavior not typically observed in this strain. We then identified that the body weight of BTBR mice is influenced by the postnatal GM which was potentially mediated by microbiome-dependent effects on energy harvest in the gut. These data provide insight into how variability within the GM affects host behavior and growth, thereby emphasizing the need to incorporate microbial diversity within the host GM as an experimental factor in biomedical research.
Phage lysins for intestinal microbiome modulation: current challenges and enabling techniques
Authors: Iris Pottie, Roberto Vázquez Fernández, Tom Van de Wiele, Yves Briers
Journal: Gut Microbes (2024)

The importance of the microbiota in the intestinal tract for human health has been increasingly recognized. In this perspective, microbiome modulation, a targeted alteration of the microbial composition, has gained interest. Phage lysins, peptidoglycan-degrading enzymes encoded by bacteriophages, are a promising new class of antibiotics currently under clinical development for treating bacterial infections. Due to their high specificity, lysins are considered microbiome-friendly. This review explores the opportunities and challenges of using lysins as microbiome modulators. First, the high specificity of endolysins, which can be further modulated using protein engineering or targeted delivery methods, is discussed. Next, obstacles and possible solutions to assess the microbiome-friendliness of lysins are considered. Finally, lysin delivery to the intestinal tract is discussed, including possible delivery methods such as particle-based and probiotic vehicles. Mapping the hurdles to developing lysins as microbiome modulators and identifying possible ways to overcome these hurdles can help in their development. In this way, the application of these innovative antimicrobial agents can be expanded, thereby taking full advantage of their characteristics.
Closed-Loop Insulin Therapy for People With Type 2 Diabetes Treated With an Insulin Pump: A 12-Week Multicenter, Open-Label Randomized, Controlled, Crossover Trial
Authors: Anne-Laure Borel, Sandrine Lablanche, Christine Waterlot, Eloïse Joffray, Céline Barra, Nathalie Arnol, Hafid Amougay, Pierre-Yves Benhamou
Journal: Diabetes Care (2024)

Continuous glucose monitoring (CGM) combined with continuous subcutaneous insulin infusion (CSII) achieves better glycemic control than multi-injection therapy in people with type 2 diabetes. The effectiveness of closed-loop therapy needs to be further evaluated in this population. The study objective was to measure the impact of a hybrid closed-loop device (DBLG1) compared with CSII + CGM on glycemic control in people with type 2 diabetes previously treated with CSII. The randomized, controlled, crossover, two-period, open-label, and multicenter study was conducted from August 2022 to July 2023 in 17 individuals (9 to receive 6 weeks of CSII + CGM first and 8 to receive 6 weeks of closed-loop therapy first). The primary end point was the percentage time in range (TIR: 70-180 mg/dL). Secondary outcomes were other CGM-glucose metrics, physical activity, and sleep objectively measured using 1-week actimetry. Data were analyzed using a modified intention-to-treat approach. Mean age was 63 (SD 9) years and 35% were women. Mean HbA1c at inclusion was 7.9% (SD 0.9). TIR increased to 76.0% (interquartile range 69.0-84.0) during the closed-loop condition vs. 61.0% (interquartile range 55.0-70.0) during the CSII + CGM condition; mean difference was 15.0 percentage points (interquartile range 8.0-22.0; P < 0.001). Analyses of secondary end points showed a decrease in time above range, in glucose management indicator, in glucose variability, and an increase in daily insulin dose. Actimetric sleep analysis showed an improvement in sleep fragmentation during closed-loop treatment. Closed-loop therapy improved glycemic control more than did CSII + CGM in people with type 2 diabetes.
Real-World Use of Semaglutide for Weight Management: Patient Characteristics and Dose Titration—A Danish Cohort Study
Authors: Louise Ladebo, Martin T. Ernst, Aurélie Mailhac, Carsten Dirksen, Kirstine N. Bojsen-Møller, Anton Pottegård
Journal: Diabetes Care (2024)

To determine patient characteristics and dose titration patterns of real-world semaglutide (Wegovy) users.
Do autoantigens drive MASH progression?
Authors: Lucía Valenzuela-Pérez, Hyun Se Kim Lee, Petra Hirsova
Journal: Hepatology (2024)

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA Correspondence Petra Hirsova, Assistant Professor of Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905. Email: [email protected]
Metabolomic prediction of breast cancer treatment induced neurological and metabolic toxicities
Authors: Max Piffoux, Jérémie Jacquemin, Mélanie Pétéra, Stephanie Durand, Angélique Abila, Delphine Centeno, Charlotte Joly, Bernard lyan, Anne-Laure Martin, Sibille Everhard, Sandrine Boyault, Barbara Pistilli, Marion Fournier, Philippe Rouanet, Julie Havas, Baptiste Sauterey, Mario Campone, Carole Tarpin, Marie-Ange Mouret-Reynier, Olivier Rigal, Thierry Petit, Christine Lasset, Aurélie Bertaut, Paul Cottu, Fabrice Andre, Ines Vaz-Luis, Estelle Pujos-Guillot, Youenn Drouet, Olivier Trédan
Journal: Clinical Cancer Research (2024)

Long-term treatment-related toxicities, such as neurologic and metabolic toxicities, are major issues in breast cancer. We investigated the interest of metabolomic profiling to predict toxicities.
Decoding Patient Heterogeneity Influencing Radiation-Induced Brain Necrosis
Authors: Ibrahim Chamseddine, Keyur Shah, Hoyeon Lee, Felix Ehret, Jan Schuemann, Alejandro Bertolet, Helen A. Shih, Harald Paganetti
Journal: Clinical Cancer Research (2024)

In radiotherapy (RT) for brain tumors, patient heterogeneity masks treatment effects, complicating the prediction and mitigation of radiation-induced brain necrosis. Therefore, understanding this heterogeneity is essential for improving outcome assessments and reducing toxicity.
Dopaminylation of endothelial TPI1 suppresses ferroptotic angiocrine signals to promote lung regeneration over fibrosis
Authors: Chunheng Mo, Hui Li, Mengli Yan, Shiyu Xu, Jinyan Wu, Jiachen Li, Xinchun Yang, Yuanyuan Li, Jian Yang, Xingping Su, Jie Liu, Chuan Wu, Yuan Wang, Haohao Dong, Lu Chen, Lunzhi Dai, Ming Zhang, Qiang Pu, Liming Yang, Tinghong Ye, Zhongwei Cao, Bi-Sen Ding
Journal: Cell Metabolism (2024)
The PI3Kδ inhibitor zandelisib on intermittent dosing in relapsed/refractory follicular lymphoma: Results from a global phase 2 study
Authors: Andrew D. Zelenetz, Wojciech Jurczak, Vincent Ribrag, Kim Linton, Graham P. Collins, Javier L. Jiménez, Mark Bishton, Bhagirathbhai Dholaria, Andrea Mengarelli, Tycel J. Phillips, Nagendraprasad Sungala, Gerardo Musuraca, Oonagh Sheehy, Eric Van Den Neste, Mitsuhiko Odera, Lu Miao, Daniel P. Gold, Richard G. Ghalie, Pier L. Zinzani
Journal: HemaSphere (2024)

Abstract In this global phase 2 study in patients with relapsed/refractory follicular lymphoma (FL), zandelisib was administered on intermittent dosing to mitigate immune‐related adverse events and infections that have been reported with oral PI3Kδ inhibitors administered daily continuously. Eligible patients with measurable disease and progression after at least two prior therapies were administered zandelisib until disease progression or intolerability. The primary efficacy endpoint was objective response rate (ORR) and the key secondary efficacy endpoint was duration of response (DOR). We report on 121 patients with FL administered zandelisib on intermittent dosing after 8 weeks of daily dosing for tumor debulking. The median number of prior therapies was 3 (range, 2–8) and 45% of patients had refractory disease. The ORR was 73% (95% confidence interval [CI], 63.9–80.4), the complete response (CR) rate was 38% (95% CI, 29.3–47.3), and the median DOR was 16.4 months (95% CI, 9.5–not reached). With a median follow‐up of 14.3 months (range, 1–30.5), the median progression‐free survival was 11.6 months (95% CI, 8.3–not reached). Twenty‐one patients (17%) discontinued therapy due to an adverse event. Grade 3–4 class‐related toxicities included 6% diarrhea, 5% lung infections, 3% colitis (confirmed by biopsy or imaging), 3% rash, 2% AST elevation, and 1% non‐infectious pneumonitis. Zandelisib achieved a high rate of durable responses in heavily pretreated patients with relapsed/refractory FL. The intermittent dosing resulted in a relatively low incidence of severe class‐related toxicities, which supports the evaluation of zandelisib as a single agent and in combination with indolent B‐cell malignancies.
SLC25A48 controls mitochondrial choline import and metabolism
Authors: Anthony R.P. Verkerke, Xu Shi, Mark Li, Yusuke Higuchi, Tadashi Yamamuro, Daisuke Katoh, Hiroshi Nishida, Christopher Auger, Ichitaro Abe, Robert E. Gerszten, Shingo Kajimura
Journal: Cell Metabolism (2024)

Choline is an essential nutrient for the biosynthesis of phospholipids, neurotransmitters, and one-carbon metabolism with a critical step being its import into mitochondria. However, the underlying mechanisms and biological significance remain poorly understood. Here, we report that SLC25A48, a previously uncharacterized mitochondrial inner-membrane carrier protein, controls mitochondrial choline transport and the synthesis of choline-derived methyl donors. We found that SLC25A48 was required for brown fat thermogenesis, mitochondrial respiration, and mitochondrial membrane integrity. Choline uptake into the mitochondrial matrix via SLC25A48 facilitated the synthesis of betaine and purine nucleotides, whereas loss of SLC25A48 resulted in increased production of mitochondrial reactive oxygen species and imbalanced mitochondrial lipids. Notably, human cells carrying a single nucleotide polymorphism on the SLC25A48 gene and cancer cells lacking SLC25A48 exhibited decreased mitochondrial choline import, increased oxidative stress, and impaired cell proliferation. Together, this study demonstrates that SLC25A48 regulates mitochondrial choline catabolism, bioenergetics, and cell survival.
Advancements and challenges in CAR T cell therapy in autoimmune diseases
Authors: Georg Schett, Fabian Müller, Jule Taubmann, Andreas Mackensen, Wei Wang, Rich A. Furie, Ralf Gold, Aiden Haghikia, Peter A. Merkel, Roberto Caricchio, Maria-Antonietta D’Agostino, Franco Locatelli, Carl H. June, Dimitrios Mougiakakos
Journal: Nature Reviews Rheumatology (2024)
Artificial Intelligence for Early Detection of Pediatric Eye Diseases Using Mobile Photos
Authors: Qin Shu, Jiali Pang, Zijia Liu, Xiaoyi Liang, Moxin Chen, Zhuoran Tao, Qianwen Liu, Yonglin Guo, Xuefeng Yang, Jinru Ding, Ruiyao Chen, Sujing Wang, Wenjing Li, Guangtao Zhai, Jie Xu, Lin Li
Journal: JAMA Network Open (2024)

IMPORTANCE Identifying pediatric eye diseases at an early stage is a worldwide issue. Traditional screening procedures depend on hospitals and ophthalmologists, which are expensive and time-consuming. Using artificial intelligence (AI) to assess children’s eye conditions from mobile photographs could facilitate convenient and early identification of eye disorders in a home setting. OBJECTIVE To develop an AI model to identify myopia, strabismus, and ptosis using mobile photographs. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study was conducted at the Department of Ophthalmology of Shanghai Ninth People’s Hospital from October 1, 2022, to September 30, 2023, and included children who were diagnosed with myopia, strabismus, or ptosis. MAIN OUTCOMES AND MEASURES A deep learning–based model was developed to identify myopia, strabismus, and ptosis. The performance of the model was assessed using sensitivity, specificity, accuracy, the area under the curve (AUC), positive predictive values (PPV), negative predictive values (NPV), positive likelihood ratios (P-LR), negative likelihood ratios (N-LR), and the F1-score. GradCAM++ was utilized to visually and analytically assess the impact of each region on the model. A sex subgroup analysis and an age subgroup analysis were performed to validate the model’s generalizability. RESULTS A total of 1419 images obtained from 476 patients (225 female [47.27%]; 299 [62.82%] aged between 6 and 12 years) were used to build the model. Among them, 946 monocular images were used to identify myopia and ptosis, and 473 binocular images were used to identify strabismus. The model demonstrated good sensitivity in detecting myopia (0.84 [95% CI, 0.82-0.87]), strabismus (0.73 [95% CI, 0.70-0.77]), and ptosis (0.85 [95% CI, 0.82-0.87]). The model showed comparable performance in identifying eye disorders in both female and male children during sex subgroup analysis. There were differences in identifying eye disorders among different age subgroups. CONCLUSIONS AND RELEVANCE In this cross-sectional study, the AI model demonstrated strong performance in accurately identifying myopia, strabismus, and ptosis using only smartphone images. These results suggest that such a model could facilitate the early detection of pediatric eye diseases in a convenient manner at home.
Intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function
Authors: Binsheng Wang, Lichao Wang, Nathan S. Gasek, Chia-Ling Kuo, Jia Nie, Taewan Kim, Pengyi Yan, Junyu Zhu, Blake L. Torrance, Yueying Zhou, Lisa C. Flores, Colton Allen, Allison M. Andrade, Chun Guo, Rachel L. Cohn, Evan R. Jellison, Jenna M. Bartley, George A. Kuchel, Sheng Li, Tamar Pirtskhalava, Tamar Tchkonia, Sumit Yadav, Laura Haynes, James L. Kirkland, Yuji Ikeno, Ming Xu
Journal: Cell Metabolism (2024)
NABNEC: A randomised phase II study of <i>nab</i>-paclitaxel in combination with carboplatin as first line treatment of gastrointestinal neuroendocrine carcinomas (GI-NECs).
Authors: Lorraine A. Chantrill, David Ransom, David Chan, Adnan Nagrial, Nick Pavlakis, Ben Markman, Christos Stelios Karapetis, Katrin Marie Sjoquist, John Simes, Val Gebski, Michael S Hofman, Pablo Gonzalez Ginestet, Anthony J. Gill, Sonia Yip, Michael Michael, Anthony Jaworski, Ho Wai Derrick Siu, Mustafa Khasraw
Journal: Journal of Clinical Oncology (2024)

589 Background: Neuroendocrine carcinomas (NEC) are rare and aggressive cancers. There are no randomised trials to date to establish standard therapy for advanced G3 gastrointestinal (GI) NENs. Extrapolating from small cell lung cancer data, standard practice is to treat G3 GI-NENs with etoposide and carboplatin. Paclitaxel is also active in NECs however there is no data on the role of nab -paclitaxel. NABNEC (ANZCTR # 12616000958482) aimed to determine the activity, safety and tolerability of carboplatin and nab -paclitaxel in advanced G3 GI-NENs and to enhance our understanding of the biology and imaging characteristics of such NENs. Methods: NABNEC was designed as a randomised non-comparative phase II study, evaluating the activity of nab- paclitaxel in patients with advanced and/or metastatic non-resectable G3 GI-NENs. The statistical plan was that 46 evaluable patients in the experimental arm would give 80% power and 95% confidence to rule out a 30% RR in favour of a more interesting RR of 50% at 6 months. Protocol version 3.0 was amended and randomisation to the control arm was suspended after 12 patients. Primary endpoint was objective response rate (RR) by RECIST 1.1. Secondary endpoints were progression free survival, overall survival, adverse events by NCI-CTCAE V4.03 and quality of life (EORTC QLQC30, QLQ-GINET21 questionnaires). Translational research endpoints include blood and tissue biomarkers including circulating tumour cells profiling, mutation profile (whole exome sequencing) and DNA methylation profile correlated with clinical endpoints. Correlation of 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) to early response has also been evaluated. Results: 60 patients were accrued between Sep 2016 and Dec 2021 from 16 centres, resulting in 58 evaluable patients, 12 (control arm), 46 (experimental arm). 43 patients (75%) had tumours with Ki-67&gt;55%; the remainder had Ki-67 between 20 and 55%. About 20% had pancreatic primaries; more than half had liver metastases. The NABNEC trial met its primary endpoint. RR was 53% (38-69%) in the experimental treatment arm compared to 42% (16-71%) in the control group. Progression free survival was not different between the 2 treatments. 24m overall survival was 25% in the experimental group compared to 17% in the control. Grade 3 toxicity was worse in the nab-paclitaxel arms (52% v 42%). Quality of life and tertiary outcomes are being analysed. Conclusions: The combination of carboplatin and nab-paclitaxel is an active regimen for G3 GI-NENs. Further evaluation in a Phase III study is warranted. Clinical trial information: ACTRN12616000958482.
Use of Respiratory Syncytial Virus Vaccines in Adults Aged ≥60 Years: Updated Recommendations of the Advisory Committee on Immunization Practices — United States, 2024
Authors: Amadea Britton, Lauren E. Roper, Camille N. Kotton, David W. Hutton, Katherine E. Fleming-Dutra, Monica Godfrey, Ismael R. Ortega-Sanchez, Karen R. Broder, H. Keipp Talbot, Sarah S. Long, Fiona P. Havers, Michael Melgar
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Respiratory syncytial virus (RSV) is a major cause of respiratory illness and hospitalization in older adults during fall and winter in the United States. The 2023-2024 RSV season was the first during which RSV vaccination was recommended for U.S. adults aged ≥60 years, using shared clinical decision-making. On June 26, 2024, the Advisory Committee on Immunization Practices voted to update this recommendation as follows: a single dose of any Food and Drug Administration-approved RSV vaccine (Arexvy [GSK]; Abrysvo [Pfizer]; or mResvia [Moderna]) is now recommended for all adults aged ≥75 years and for adults aged 60-74 years who are at increased risk for severe RSV disease. Adults who have previously received RSV vaccine should not receive another dose. This report summarizes the evidence considered for these updated recommendations, including postlicensure data on vaccine effectiveness and safety, and provides clinical guidance for the use of RSV vaccines in adults aged ≥60 years. These updated recommendations are intended to maximize RSV vaccination coverage among persons most likely to benefit, by clarifying who is at highest risk and by reducing implementation barriers associated with the previous shared clinical decision-making recommendation. Continued postlicensure monitoring will guide future recommendations.
Outcomes and Mechanisms Associated With Selective Thalamic Neuronal Loss in Chronic Traumatic Brain Injury
Authors: Rebecca E. Woodrow, Julia Grossac, Young T. Hong, Stefan Winzeck, Thomas Geeraerts, Sudhin A. Shah, Alexander R. D. Peattie, Anne E. Manktelow, Joanne G. Outtrim, Nicolas A. Karakatsanis, Nicholas D. Schiff, Tim D. Fryer, David K. Menon, Jonathan P. Coles, Emmanuel A. Stamatakis
Journal: JAMA Network Open (2024)

The chronic neuronal burden of traumatic brain injury (TBI) is not fully characterized by routine imaging, limiting understanding of the role of neuronal substrates in adverse outcomes.
Type 2 Diabetes and Fracture Risk in Older Women
Authors: Michail Zoulakis, Lisa Johansson, Henrik Litsne, Kristian Axelsson, Mattias Lorentzon
Journal: JAMA Network Open (2024)

Importance The reasons for the increased fracture risk in type 2 diabetes (T2D) are not fully understood. Objective To determine if poorer skeletal characteristics or worse physical function explain the increased fracture risk in T2D. Design, Setting, and Participants This prospective observational study is based on the population-based Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures study cohort of older women, performed in the Gothenburg area between March 2013 and May 2016. Follow-up of incident fracture data was completed in March 2023. Data analysis was performed between June and December 2023. Exposures Data were collected from questionnaires and through examination of anthropometrics, physical function, and bone measurements using bone densitometry (dual-energy x-ray absorptiometry), and high-resolution peripheral computed tomography. A subsample underwent bone microindentation to assess bone material strength index (BMSi). Main Outcomes and Measures Baseline assessment of bone characteristics and physical function and radiograph verified incident fractures. Results Of 3008 women aged 75 to 80 years, 294 women with T2D (mean [SD] age, 77.8 [1.7] years) were compared with 2714 women without diabetes (mean [SD] age, 77.8 [1.6] years). Women with T2D had higher bone mineral density (BMD) at all sites (total hip, 4.4% higher; femoral neck (FN), 4.9% higher; and lumbar spine, 5.2% higher) than women without. At the tibia, women with T2D had 7.4% greater cortical area and 1.3% greater density, as well as 8.7% higher trabecular bone volume fraction. There was no difference in BMSi (T2D mean [SD], 78.0 [8.3] vs controls, 78.1 [7.3]). Women with T2D had lower performance on all physical function tests. The study found 9.7% lower grip strength, 9.9% slower gait speed, and 13.9% slower timed up-and-go time than women without diabetes. During a median (IQR) follow-up of 7.3 (4.4-8.4) years, 1071 incident fractures, 853 major osteoporotic fractures (MOF), and 232 hip fractures occurred. In adjusted (for age, body mass index, clinical risk factors, and FN BMD) Cox regression models, T2D was associated with an increased risk of any fracture (HR, 1.26; 95% CI, 1.04-1.54) and MOF (HR, 1.25; 95% CI, 1.00-1.56). Conclusions and Relevance In this cohort study of older women, T2D was associated with higher BMD, better bone microarchitecture, and no different BMSi but poorer physical function, suggesting that poor physical function is the main reason for the increased fracture risk in T2D women.