tbuckley/cabot-search huggingface dataset:
Comparison of gnotobiotic communities reveals milk-adapted metabolic functions and unexpected amino acid metabolism by the pre-weaning microbiome
Authors: Jean-Bernard Lubin, Michael A. Silverman, Paul J. Planet
Journal: Gut Microbes (2024)

The intestinal microbiome during infancy and childhood has distinct metabolic functions and microbial composition compared to adults. We recently published a gnotobiotic mouse model of the pre-weaning microbiome (PedsCom), which retains a pre-weaning configuration during the transition from a milk-based diet to solid foods, leads to a stunted immune system, and increases susceptibility to enteric infection. Here, we compared the phylogenetic and metabolic relationships of the PedsCom consortium to two adult-derived gnotobiotic communities, Altered Schaedler Flora and Oligo-Mouse Microbiota 12 (Oligo-MM12). We find that PedsCom contains several unique functions relative to these adult-derived mouse consortia, including differences in carbohydrate and lipid metabolism genes. Notably, amino acid degradation metabolic modules are more prevalent among PedsCom isolates, which is in line with the ready availability of these nutrients in milk. Indeed, metabolomic analysis revealed significantly lower levels of total free amino acids and lower levels of specific amino acids abundant in milk (e.g. glutamine and glutamic acid) in the intestinal contents of adult PedsCom colonized mice compared to Oligo-MM12 controls. Metabolomic analysis of pre-weaning intestinal contents also showed lower levels of amino acids that are replete in milk compared to germ-free controls. Thus, enhanced amino acid metabolism is a prominent feature of the pre-weaning microbiome that may facilitate design of early-life microbiome interventions.
Dysfunctional mucus structure in cystic fibrosis increases vulnerability to colibactin-mediated DNA adducts in the colon mucosa
Authors: Amanda Mandarino Alves, Chiara Lecchi, Sharon Lopez, Alessia Stornetta, Prince P. Mathai, Peter W. Villalta, Satoshi Ishii, Emily P. Balskus, Silvia Balbo, Alexander Khoruts
Journal: Gut Microbes (2024)

Colibactin is a recently characterized pro-carcinogenic genotoxin produced by
Corrigendum to “Plasmatic BRAF-V600E allele fraction as a prognostic factor in metastatic colorectal cancer treated with BRAF combinatorial treatments”
Authors: J. Ros, J. Matito, G. Villacampa, R. Comas, A. Garcia, G. Martini, I. Baraibar, N. Saoudi, F. Salvà, Á. Martin, M. Antista, R. Toledo, E. Martinelli, F. Pietrantonio, A. Boccaccino, C. Cremolini, R. Dienstmann, J. Tabernero, A. Vivancos, E. Elez
Journal: Annals of Oncology (2024)

The authors regret that in the original publication Dr Dienstmann's name was given incorrectly in the author listing. The correct author listing is now given above. The authors would like to apologise for any inconvenience caused. Plasmatic BRAF-V600E allele fraction as a prognostic factor in metastatic colorectal cancer treated with BRAF combinatorial treatmentsAnnals of OncologyVol. 34Issue 6
Digital solutions in paediatric sepsis: current state, challenges, and opportunities to improve care around the world
Authors: L Nelson Sanchez-Pinto, María Del Pilar Arias López, Halden Scott, Kristen Gibbons, Michael Moor, R Scott Watson, Matthew O Wiens, Luregn J Schlapbach, Tellen D Bennett
Journal: The Lancet Digital Health (2024)
CCL19-producing fibroblasts promote tertiary lymphoid structure formation enhancing anti-tumor IgG response in colorectal cancer liver metastasis
Authors: Yifan Zhang, Guangjian Liu, Qianwen Zeng, Wenrui Wu, Kai Lei, Chuankai Zhang, Miaoling Tang, Yuting Zhang, Xiao Xiang, Li Tan, Rui Cui, Si Qin, Xinming Song, Changjun Yin, Zhihang Chen, Ming Kuang
Journal: Cancer Cell (2024)

Tertiary lymphoid structures (TLSs) are associated with enhanced immunity in tumors. However, their formation and functions in colorectal cancer liver metastasis (CRLM) remain unclear. Here, we reveal that intra- and peri-tumor mature TLSs (TLS+) are associated with improved clinical outcomes than TLS- tumors. Using single-cell-RNA-sequencing and spatial-enhanced-resolution-omics-sequencing (Stereo-seq), we reveal that TLS+ tumors are enriched with IgG
Single-session endoscopic ultrasound-guided tissue acquisition followed by choledochoduodenostomy in a patient with Roux-en-Y reconstruction
Authors: Tesshin Ban, Yoshimasa Kubota, Naoto Imura, Shun Sasoh, Takashi Joh
Journal: Endoscopy (2024)

Endoscopic ultrasound-guided tissue acquisition (EUS-TA) through the afferent limb of a Roux-en-Y reconstruction is possible but challenging [1] [2]. In reconstructed patients with subsequent distal malignant biliary obstruction, EUS-TA with endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) potentially achieves both pathological diagnosis and biliary drainage in a single session.
Kidney and Cardiovascular Effectiveness of SGLT2 Inhibitors vs GLP-1 Receptor Agonists in Type 2 Diabetes
Authors: Daniel Edmonston, Hillary Mulder, Elizabeth Lydon, Karen Chiswell, Zachary Lampron, Christina Shay, Keith Marsolo, Raj C Shah, W Schuyler Jones, Howard Gordon, Wenke Hwang, Isabella Ayoub, Daniel Ford, Alanna Chamberlain, Ajaykumar Rao, Vivian Fonseca, Alexander Chang, Faraz Ahmad, Adriana Hung, Kelly Hunt, Javed Butler, Hayden B Bosworth, Neha Pagidipati
Journal: Journal of the American College of Cardiology (2024)
Clinical Significance of Diffusion-Weighted Brain MRI Lesions After TAVR
Authors: Alexandra J. Lansky, Daniel Grubman, Michael G. Dwyer, Robert Zivadinov, Helen Parise, Jeffrey W. Moses, Tayyab Shah, Cody Pietras, Daniela Tirziu, Louise Gambone, Martin B. Leon, Tamim M. Nazif, Steven R. Messé
Journal: Journal of the American College of Cardiology (2024)
Optimizing Management of Stable Angina
Authors: Rocco A Montone, Riccardo Rinaldi, Giampaolo Niccoli, Giuseppe Andò, Felice Gragnano, Raffaele Piccolo, Francesco Pelliccia, Elisabetta Moscarella, Marco Zimarino, Enrico Fabris, Salvatore de Rosa, Paolo Calabrò, Italo Porto, Francesco Burzotta, Francesco Grigioni, Emanuele Barbato, Alaide Chieffo, Davide Capodanno, Rasha Al-Lamee, Tom J Ford, Salvatore Brugaletta, Ciro Indolfi, Gianfranco Sinagra, Pasquale Perrone Filardi, Filippo Crea
Journal: Journal of the American College of Cardiology (2024)
Prescription Patterns for Sodium-Glucose Cotransporter 2 Inhibitors in U.S. Health Systems
Authors: Jung-Im Shin, Yunwen Xu, Alexander R. Chang, Juan J. Carrero, Carina M. Flaherty, Amrita Mukhopadhyay, Lesley A. Inker, Saul B. Blecker, Leora I. Horwitz, Morgan E. Grams
Journal: Journal of the American College of Cardiology (2024)
Clinical and Analytical Performance of a Novel Point-of-Care High-Sensitivity Cardiac Troponin I Assay
Authors: Luca Koechlin, Jasper Boeddinghaus, Pedro Lopez-Ayala, Cornelia Reber, Thomas Nestelberger, Karin Wildi, Carlos C Spagnuolo, Ivo Strebel, Jonas Glaeser, Paolo Bima, Luca Crisanti, Lourdes Herraiz-Recuenco, Elisa Dubach, Òscar Miró, F Javier Martin-Sanchez, Damian Kawecki, Dagmar I Keller, Michael Christ, Andreas Buser, Maria Rubini Giménez, Gro Leite Størvold, Marianne Nordlund Broughton, Torbjørn Omland, Magnus N Lyngbakken, Helge Røsjø, Christian Mueller
Journal: Journal of the American College of Cardiology (2024)
Quality improvement programmes in paediatric sepsis from a global perspective
Authors: Daniela C de Souza, Raina Paul, Rebeca Mozun, Jhuma Sankar, Roberto Jabornisky, Emma Lim, Amanda Harley, Samirah Al Amri, Maha Aljuaid, Suyun Qian, Luregn J Schlapbach, Andrew Argent, Niranjan Kissoon
Journal: The Lancet Child & Adolescent Health (2024)
Susceptibility to childhood sepsis, contemporary management, and future directions
Authors: Michael J Carter, Enitan D Carrol, Suchitra Ranjit, Rebeca Mozun, Niranjan Kissoon, R Scott Watson, Luregn J Schlapbach
Journal: The Lancet Child & Adolescent Health (2024)

Sepsis disproportionally affects children across all health-care settings and is one of the leading causes of morbidity and mortality in neonatal and paediatric age groups. As shown in the first paper in this Series, the age-specific incidence of sepsis is highest during the first years of life, before approaching adult incidence rates during adolescence. In the second paper in this Series, we focus on the unique susceptibility of paediatric patients to sepsis and how the underlying dysregulated host response relates to developmental aspects of children's immune system, genetic, perinatal, and environmental factors, and comorbidities and socioeconomic determinants of health, which often differ between children and adults. State-of-the-art clinical management of paediatric sepsis is organised around three treatment pillars-diagnosis, early resuscitation, and titration of advanced care-and we examine available treatment guidelines and the limitations of their supporting evidence. Serious evidence gaps remain in key areas of paediatric sepsis care, especially surrounding recognition, common interventions, and survivor support, and to this end we offer a research roadmap for the next decade that could accelerate targeted diagnostics and personalised use of immunomodulation. However, improving outcomes for children with sepsis relies fundamentally on systematic quality improvement in both recognition and treatment, which is the theme of the third paper in this Series. Digital health, as shown in the fourth and final paper of this Series, holds promising potential in breaking down the barriers that hinder progress in paediatric sepsis care and, ultimately, global child health.
Results of International, Double-Blind, Randomized, Placebo-Controlled, Phase IIa Study of Interleukin-1 Blockade With RPH-104 (Goflikicept) in Patients With ST-Segment–Elevation Myocardial Infarction (STEMI)
Authors: Antonio Abbate, Benjamin Van Tassell, Vlad Bogin, Roshanak Markley, Dmitry V. Pevzner, Paul C. Cremer, Imad Meray, Dmitry V. Privalov, Angela Taylor, Sergey A. Grishin, Alina N. Egorova, Ekaterina G. Ponomar, Yan Lavrovsky, Mikhail Yu Samsonov, Alexandra Pisaryuk, Lala Babaeva, Ilya Zyuryaev, Denis Kalimulin, Oleg Lapin, Sergei Mekhriakov, Nikolay Popov, Igor Kalashnikov, Ekaterina Duhanina, Samra Osmanova, Egor Kornilov, Ekaterina Zubova, Vakhtang Safarian, Natalia Selezneva, Ekaterina Savelieva, Olga Privalova, Zaur Shogenov, Vladimir Novosadov, Murat Agirov, Rostislav Nilk, Andrey Fedash, Andrey Yurkovskiy, Anastasia Kotova, Ilya Staroverov, Vyacheslav Mayorov, Oxana Lonchakova, Denis Rozanov, Sergey Yakushin, Sergey Seleznev, Ekaterina Pravkina, Kristina Pereverzeva, Galina Ivanova, Jeremy S. Turlington, Georgia Thomas, Azita H. Talasaz, Michele Golino, Marco Giuseppe Del Buono, Amr Marawan, Juan Ignacio Damonte
Journal: Circulation (2024)
Individual and neighborhood-level social and deprivation factors impact kidney health in the GLOMMS-CORE study
Authors: Simon Sawhney, Iain Atherton, Thomas Blakeman, Corri Black, Eilidh Cowan, Catherine Croucher, Simon D.S. Fraser, Audrey Hughes, Mintu Nath, Dorothea Nitsch, Nicole Scholes-Robertson, Magdalena Rzewuska Diaz
Journal: Kidney International (2024)

Prospective cohort studies of kidney equity are limited by a focus on advanced rather than early disease and selective recruitment. Whole population studies frequently rely on area-level measures of deprivation as opposed to individual measures of social disadvantage. Here, we linked kidney health and individual census records in the North of Scotland (Grampian area), 2011-2021 (GLOMMS-CORE) and identified incident kidney presentations at thresholds of estimated glomerular filtration rate (eGFR) under 60 (mild/early), under 45 (moderate), under 30 ml/min/1.73m2(advanced), and acute kidney disease (AKD). Household and neighborhood socioeconomic measures, living circumstances, and long-term mortality were compared. Case-mix adjusted multivariable logistic regression (living circumstances), and Cox models (mortality) incorporating an interaction between the household and the neighborhood were used. Among census respondents, there were 48546, 29081, 16116, 28097 incident presentations of each respective eGFR cohort and AKD. Classifications of socioeconomic position by household and neighborhood were related but complex, and frequently did not match. Compared to households of professionals, people with early kidney disease in unskilled or unemployed households had increased mortality (adjusted hazard ratios: 95% confidence intervals) of (1.26: 1.19-1.32) and (1.77: 1.60-1.96), respectively with adjustment for neighborhood indices making little difference. Those within either a deprived household or deprived neighborhood experienced greater mortality, but those within both had the poorest outcomes. Unskilled and unemployed households frequently reported being limited by illness, adverse mental health, living alone, basic accommodation, lack of car ownership, language difficulties, visual and hearing impairments. Thus, impacts of deprivation on kidney health are spread throughout society, complex, serious, and not confined to those living in deprived neighborhoods.
Abstract 4341: Dyssynchrony is a Prerequisite condition for Beta Reserve Upregulation By Cardiac Resynchronization Therapy
Authors: Khalid Chakir, Richard S Tunin, Takeshi Aiba, Gordon Tomaselli, David A Kass
Journal: Circulation (2008)

Background Dyssynchronous Heart failure (DHF) versus synchronous is characterized by unique cellular and molecular substrates involving stress kinase and cell survival signaling ( Chakir et al. Circulation 2008 ; 117 : 1369 –77 ). Hypothesis The impact of CRT may depend upon whether there was a preceding dyssynchrony. Here, we tested such dyssynchrony dependence on basal and beta-adrenergic stimulated myocyte function in a canine HF model. Methods Adult dogs (n=8) underwent LBB radio-frequency ablation; half then subjected to atrial tachypacing-induced dyssynchronous HF (DHF) for 6wks, while the others had 3 weeks DHF followed by 3-wks bi-ventricular tachypacing (CRT). 5 additional dogs were subjected to RV freewall tachypacing for 3wks (dyssynchrony) followed by 3 weeks right atrial tachypacing (resynchronization; V3A3), and 3 more were subjected to synchronous heart failure (RA tachypacing for 6 wks; A6). 3 non-paced dogs served as controls. Myocytes were enzymatically isolated from the LV free wall and field stimulated in a perfusion chamber. Sarcomere shortening and calcium transient were determined with and without 10 −7 M isoproterenol. Results: DHF, V3A3, A6 and CRT hearts had similar global failure, with dP/dtmax 1190.2±139.8 vs. 1111.8±131.6 vs. 1333.0±205.2 vs. 1195.3±137.6 mmHg/s, respectively (1900.3±176.8 in control). However, there were marked differences in basal and β-stimulated myocyte calcium transients and sarcomere shortening (Table , n=8 –30 cells/ group). Intriguingly, both DHF and A6 cells had reduced basal and β-AR stimulated sarcomere shortening and Ca transients versus control. In contrast, both V3A3 and CRT displayed enhanced rest and β-AR responses. Conclusion: HF resynchronization improves rest and β-AR cellular function over those never dyssynchronous. A particular substrate develops with DHF that when offset by CRT enhances cellular function beyond that with synchronous HF; explaining the CRT impact in targeted patients.
Abstract 1364: Impact of the ApoB/A1-Ratio on the Prediction of the Elevation of Left Ventricular Filling Pressure After a First STEMI
Authors: Noriaki Iwahashi, Masami Kosuge, Jun Okuda, Kengo Tsukahara, Yoshio Tahara, Yoshio Tahara, Kiyoshi Hibi, Toshiaki Ebina, Shinichi Sumita, Toshiaki Ishikawa, Kazuaki Uchino, Satoshi Umemura, Kazuo Kimura
Journal: Circulation (2009)

Background The non-fasting ApoB/ApoA1-ratio was superior to any of the cholesterol ratios for estimation of the risk of acute myocardial infarction (AMI) ( Lancet 2008 ; 32 . 224 ). The AMORIS study prospectively revealed that the strongest single lipoprotein-related risk factor for fatal AMI was the Apo-B/Apo-A-I ratio in a large cohort by 10.3 years follow up. ( AJC 2006 ; 97 . 243 ). The aim of this study was to explore the impact of ApoB/A1 on the damage to cardiac function after a first ST-elevation AMI (STEMI). Methods 241 consecutive patients (age=63.8±11.9 years, male=197 patients, culprit lesions: LMT=3, LAD=109, RCA=103, LCx=26) underwent successful emergent PCI within 12 hours of onset. Blood sampling, including apolipoproteins, was obtained at their emergent admission. They underwent echocardiography 2 weeks after onset. We examined the tissue Doppler imaging, then calculated the early transmitral flow velocity (E) divided by the early diastolic velocity of the mitral valve annulus (e′) - a ratio that strongly correlates with mean left ventricular filling pressure. Exclusion criteria were those with chronic kidney disease (CKD) at Stage 4 and 5 (eGFR &lt;30 ml/min), anemia (Hemoglobin&lt;10g/dl), significant valvular heart disease, prior MI, non-STEMI, A-C bypass and atrial fibrillation. Patients were followed up for 36 months. Results There were significant relationships between the Apo-B/Apo-A-1 ratio and E/e′ (r=0.20, p&lt;0.001) and between Apo-B and E/e′ (r=0.15, p&lt;0.05). However, the other apolipoproteins and conventional lipid profiles did not show associations with echocardiographical parameters, including E/e′. Furthermore, the Apo-B/Apo-A-1 ratio was the most powerful predictor of the progression of CKD (when eGFR decreased from baseline &gt;20%) after 36 months(Odds ratio=3.55,95%CI:1.22–10.37). Conclusion The value of the Apo-B/A-1-ratio on admission could predict the elevation of LV filling pressure 2 weeks after a first STEMI onset. The higher the Apo-B/A-1-ratio on admission, the greater the LV damage from STEMI, despite patients having successfully received early reperfusion therapy. These results might explain why the higher Apo-B/Apo-A-I ratio is frequently followed by fatal AMI.
Abstract 3731: Overlapping Patterns of Gene Expression in Experimental and Clinical Models of Myocardial Recovery
Authors: Veli K Topkara, Wei Wang, Feng Gao, Jeffrey Robbins, Natarajan Sivasubramanian, Douglas L Mann
Journal: Circulation (2009)

Background: Similar patterns of myocardial gene expression occur following beneficial pharmacological and/or device therapies for heart failure, suggesting that there may be specific ensembles of genes that promote myocardial recovery (MyoRec). Purpose/Methods: We previously developed and characterized a tetracycline responsive transgenic model (ttA-MHCmin TetO -TRAF2 mice) that allows for conditional cardiac restricted over expression of tumor necrosis factor receptor associated factor 2 (TRAF2), which we have shown is responsible for progressive left ventricular (LV) remodeling in cardiac inflammation. The ttA-MHCmin TetO -TRAF2 mice develop LV remodeling by 8 weeks of age. Oral administration of dox for 4 weeks allows for complete LV reverse remodeling (MyoRec) in the ttA-TRAF2 mice (age 12 weeks), whereas “no dox” mice undergo progressive LV dilation (age 12 weeks). We performed a gene array in the hearts of wild-type and ttA-MHCmin TetO -TRAF2 mice that were given dox or no dox. Changes in the patterns of gene expression were then compared to published ( Circ. Res. 2005 ; 96 : 592 –599 ) changes in the human gene expression before and after support with a left ventricular assist device (LVAD). Results: There were 748 genes that were differentially expressed (403 upregulated, 345 downregulated) in the ttA-MHCmin TetO -TRAF2/no dox (LV remodeling) compared to ttA-MHCmin TetO -TRAF2/dox mice (MyocRec). Gene Ontology (GO) classification of the genes that were involved in MyoRec showed remarkable overlap with the patterns observed in human LVAD samples (table ). Conclusions: These data suggest that there are specific ensembles of genes may be responsible for myocardial recovery, which opens the possibility for developing therapeutic approaches that are specifically designed to promote myocardial recovery. Gene Ontology Classification of Myocardial Recovery Genes
Pustular mycosis fungoides has a poor outcome: a multicentric clinico-pathological and molecular case series study
Authors: Christophe Bontoux, Marine Badrignans, Sivem Afach, Emilie Sbidian, Diana-Laure Mboumba, Saskia Ingen-Housz-Oro, Alexis Claudel, Marie-Hélène Aubriot-Lorton, Arnaud Chong-Si-Tsaon, Gilles Le Masson, Christophe Attencourt, Romain Dubois, Fanny Beltzung, Wafa Koubaa, Helmut Beltraminelli, Nathalie Cardot-Leccia, Brigitte Balme, Anh tuan Nguyen, Kelly Bagny, Delphine Legoupil, Ibtissam Moustaghfir, Juliette Denamps, Laurent Mortier, Houda Hammami-Ghorbel, Sergey Skrek, Mostefa Rafaa, Anne-Claire Fougerousse, Thibaut Deschamps, Stéphane Dalle, Michel D’incan, Guillaume Chaby, Marie Beylot-Barry, Sophie Dalac, Nicolas Ortonne
Journal: British Journal of Dermatology (2024)

Abstract Background Mycosis fungoides (MF) usually has an indolent course. However, some patients develop more aggressive disease and few prognostic parameters have been identified. Isolated cases of pustular MF (pMF) suggest an unfavourable prognosis. Objectives To describe the clinicopathological characteristics and prognostic value of pMF. Methods We retrospectively collected data from all patients with MF with histological pustules diagnosed from 2009 to 2020. The outcomes and clinicopathological characteristics of pMF at diagnosis (pMFD) were compared with those of a cohort of patients with nonpustular MF (NpMF). Results Thirty-three patients with pMF (including 22 with pMFD) and 86 with NpMF were included. Median age at diagnosis of pMF was 61 years [interquartile range (IQR) 50–75]. The median duration of follow-up for patients with pMFD was 32 months (IQR 14–49). Clinically, 33% of patients with pMF had pustules. Large cell transformation (LCT) occurred in 17 patients. Patients with pMFD had significantly more advanced-stage disease and showed more LCT at diagnosis than those with NpMF [50% vs. 7% (P &amp;lt; 0.001) and 23% vs. 0% (P &amp;lt; 0.001), respectively]. On multivariate Cox analysis, the presence of histological pustules at diagnosis was associated with shorter overall survival (OS) in all patients [hazard ratio (HR) 13.90, 95% confidence interval (CI) 2.40–79.00); P = 0.003] and in patients with early-stage disease (HR 11.09, 95% CI 1.56–78.82; P = 0.02). In multivariate Fine and Gray model analysis, pMFD was associated with a higher cumulative incidence of LCT (subdistribution HR 13.90, 95% CI 2.43–79.00; P = 0.003) in all patients. Median OS after the occurrence of histological pustules during follow-up in all patients with pMF was 37 months, with a 5-year OS rate of 25% (95% CI 0.06–0.50). Conclusions pMF often follows an aggressive course, with a high risk of LCT and shorter survival, even for patients with early-stage disease. Histological pustules at diagnosis of MF might represent an independent poor prognostic factor, to be confirmed by further studies. As pustules are not always identified clinically, pustules found on histology should be mentioned in MF pathology reports and should prompt discussion of closer follow-up.