tbuckley/cabot-search huggingface dataset:
Measuring congestion with a non‐invasive monitoring device in heart failure and haemodialysis: <scp>CONGEST‐HF</scp>
Authors: James P. Curtain, Atefeh Talebi, Alasdair McIntosh, Alex McConnachie, Joanne O'Donnell, Paul Welsh, Joanna Osmanska, Matthew M.Y. Lee, Piotr Sonecki, Tony Akl, Joohyun Seo, Venugopal Gopinathan, Jed Hurwitz, Srikanth Thiagarajan, Stephen Pettit, Paul R. Kalra, Rajan K. Patel, Patrick B. Mark, Ninian N. Lang, John J.V. McMurray, Mark C. Petrie, Roy S. Gardner, Pardeep S. Jhund
Journal: European Journal of Heart Failure (2024)

Aims We examined the effectiveness of a novel cardiopulmonary management wearable sensor (worn for less than 5 mins) at measuring congestion and correlated the device findings with established clinical measures of congestion. Methods and results We enrolled three cohorts of patients: (1) patients with heart failure (HF) receiving intravenous diuretics in hospital; (2) patients established on haemodialysis, and (3) HF patients undergoing right heart catheterization (RHC). The primary outcomes in the respective cohorts were a Spearman correlation between (1) change in weight and change in thoracic impedance (TI) (from enrolment, 24 h after admission to discharge) in patients hospitalized for HF; (2) lung ultrasound B‐lines and volume removed during dialysis with device measured TI, and (3) pulmonary capillary wedge pressure (PCWP) and sub‐acoustic diastolic, third heart sound (S3) in the patients undergoing RHC. A total of 66 patients were enrolled. In HF patients ( n = 25), change in weight was correlated with both change in device TI (Spearman correlation [r sp ] = −0.64, p = 0.002) and change in device S3 (r sp = −0.53, p = 0.014). In the haemodialysis cohort ( n = 21), B‐lines and TI were strongly correlated before (r sp = −0.71, p &lt; 0.001) and after (r sp = −0.77, p &lt; 0.001) dialysis. Volume of fluid removed by dialysis was correlated with change in device TI (r sp = 0.49, p = 0.024). In the RHC cohort ( n = 20), PCWP measured at one time point and device S3 were not significantly correlated (r sp = 0.230, p = 0.204). There were no device‐related adverse events. Conclusions A non‐invasive device was able to detect changes in congestion in patients with HF receiving decongestion therapy and patients having fluid removed at haemodialysis. The cardiopulmonary management device, which measures multiple parameters, is a potentially useful tool to monitor patients with HF to prevent hospitalizations.
Health insurance among survivors of childhood cancer following Affordable Care Act implementation
Authors: Anne C Kirchhoff, Austin R Waters, Qi Liu, Xu Ji, Yutaka Yasui, K Robin Yabroff, Rena M Conti, I -Chan Huang, Tara Henderson, Wendy M Leisenring, Gregory T Armstrong, Paul C Nathan, Elyse R Park
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background The Affordable Care Act (ACA) increased private nonemployer health insurance options, expanded Medicaid eligibility, and provided preexisting health condition protections. We evaluated insurance coverage among long-term adult survivors of childhood cancer pre- and post-ACA implementation. Methods Using the multicenter Childhood Cancer Survivor Study, we included participants from 2 cross-sectional surveys: pre-ACA (2007-2009; survivors: n = 7505; siblings: n = 2175) and post-ACA (2017-2019; survivors: n = 4030; siblings: n = 987). A subset completed both surveys (1840 survivors; 646 siblings). Multivariable regression models compared post-ACA insurance coverage and type (private, public, uninsured) between survivors and siblings and identified associated demographic and clinical factors. Multinomial models compared gaining and losing insurance vs staying the same among survivors and siblings who participated in both surveys. Results The proportion with insurance was higher post-ACA (survivors pre-ACA 89.1% to post-ACA 92.0% [+2.9%]; siblings pre-ACA 90.9% to post-ACA 95.3% [+4.4%]). Post-ACA insurance increase in coverage was higher among those aged 18-25 years (survivors: +15.8% vs +2.3% or less ages 26 years and older; siblings +17.8% vs +4.2% or less ages 26 years and older). Survivors were more likely to have public insurance than siblings post-ACA (18.4% vs 6.9%; odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.1 to 2.6). Survivors with severe chronic conditions (OR = 4.7, 95% CI = 3.0 to 7.3) and those living in Medicaid expansion states (OR = 2.4, 95% CI = 1.7 to 3.4) had increased odds of public insurance coverage post-ACA. Among the subset completing both surveys, low- and mid-income survivors (&amp;lt;$40 000 and &amp;lt;$60 000, respectively) experienced insurance losses and gains in reference to highest household income survivors (≥$100 000), relative to odds of keeping the same insurance status. Conclusions Post-ACA, more childhood cancer survivors and siblings had health insurance, although disparities remain in coverage.
Associations of essential metals with the risk of aortic arch calcification: a cross‐sectional study in a mid‐aged and older population of Shenzhen, China
Authors: Mingxing Mo, Li Yin, Tian Wang, Ziquan Lv, Yadi Guo, Jiangang Shen, Huanji Zhang, Ning Liu, Qiuling Wang, Suli Huang, Hui Huang
Journal: MedComm (2024)

Abstract Vascular calcification is a strong predictor of cardiovascular events. Essential metals play critical roles in maintaining human health. However, the association of essential metal levels with risk of aortic arch calcification (AoAC) remains unclear. We measured the plasma concentrations of nine essential metals in a cross‐sectional population and evaluated their individual and combined effects on AoAC risk using multiple statistical methods. We also explored the mediating role of fasting glucose. In the logistic regression model, higher quartiles of magnesium and copper were associated with the decreased AoAC risk, while higher quartile of manganese was associated with higher AoAC risk. The least absolute shrinkage and selection operator penalized regression analysis identified magnesium, manganese, calcium, cobalt, and copper as key metals associated with AoAC risk. The weighted quantile sum regression suggested a combined effect of metal mixture. A linear and positive dose–response relationship was found between manganese and AoAC in males. Moreover, blood glucose might mediate a proportion of 9.38% of the association between manganese exposure and AoAC risk. In summary, five essential metal levels were associated with AoAC and showed combined effect. Fasting glucose might play a significant role in mediating manganese exposure‐associated AoAC risk.
Efficacy and Safety of Ustekinumab for Chronic Pouchitis: A Prospective Open-label Multicenter Study
Authors: An Outtier, Edouard Louis, Olivier Dewit, Catherine Reenaers, Ganel Schops, Matthias Lenfant, Emilie Pontus, Gert De Hertogh, Bram Verstockt, João Sabino, Séverine Vermeire, Marc Ferrante
Journal: Clinical Gastroenterology and Hepatology (2024)
Reply to the letter regarding the article ‘Subclinical systolic dysfunction in genotype‐positive phenotype‐negative relatives of dilated cardiomyopathy patients: A systematic review and meta‐analysis’
Authors: Andrea Faggiano, Elisa Gherbesi, Eleonora Gnan, Alessia Paldino, Marco Merlo, Gianfranco Sinagra, Stefano Carugo
Journal: European Journal of Heart Failure (2024)
404‐error “Disease not found”: Unleashing the translational potential of ‐omics approaches beyond traditional disease classification in heart failure research
Authors: Antonio Esquivel Gaytan, Nils Bomer, Niels Grote Beverborg, Peter van der Meer
Journal: European Journal of Heart Failure (2024)

Abstract The emergence of personalized medicine, facilitated by the progress in ‐omics technologies, has initiated a new era in medical diagnostics and treatment. This review examines the potential of ‐omics approaches in heart failure, a condition that has not yet fully capitalized on personalized strategies compared to other medical fields like cancer therapy. Here, we argue that integrating multi‐omics technology with systems medicine approaches could fundamentally transform heart failure management, moving away from the traditional paradigm of ‘one size fits all’. Our review examines how omics can enhance understanding of heart failure's molecular foundations and contribute to a more comprehensive disease classification. We draw attention to the current state of medical practice that only relies on clinical evidence and a number of standard laboratory tests. At the same time, we propose a shift towards a universal approach that uses quantitative data from multi‐omics to unravel complex molecular interactions. The discussion centres around the potential of the transition as a means to enhance individual risk assessment and emphasizes management within clinical settings. While the use of omics in cardiovascular research is not recent, many past studies have focused only on a single omics approach. In order to achieve a better understanding of disease mechanisms, we explore more holistic approaches using genomics, transcriptomics, epigenomics, and proteomics. This review concludes with a call to action to adopt multi‐omics in clinical trials and practice to pave the way for more personalized disease management and more effective heart failure interventions.
Why Kidney Cancer Rates Differ Globally
Authors: Elie Dolgin
Journal: Cancer Discovery (2024)

An international genomics study has revealed distinct mutational signatures in kidney cancer that vary across different regions, illuminating the reasons behind global disparities in incidence rates. Highlighting the effect of both recognized and unidentified mutation-inducing agents, the research underscores the need for targeted public health interventions and further studies into the environmental factors linked to renal cell carcinoma.
Loss of the TRPM4 channel in humans causes immune dysregulation with defective monocyte migration
Authors: Fang Yu, Satanay Hubrack, Christophe M Raynaud, Asha Elmi, Rafah Mackeh, Nourhen Agrebi, Gaurav Thareja, Abdelaziz Belkadi, Hesham Al Saloos, Ayeda Abdulsalam Ahmed, Saleema C Purayil, Yasmin A Mohamoud, Karsten Suhre, Charbel Abi Khalil, Frank Schmidt, Bernice Lo, Amel Hassan, Khaled Machaca
Journal: Journal of Allergy and Clinical Immunology (2024)

TRPM4 is a broadly expressed, calcium-activated, monovalent cation channel that regulates immune cell function in mice and cell lines. Clinically, however, partial loss- or gain-of-function mutations in TRPM4 lead to arrhythmia and heart disease, with no documentation of immunologic disorders.
Human milk oligosaccharide 2’-fucosyllactose protects against high-fat diet-induced obesity by changing intestinal mucus production, composition and degradation linked to changes in gut microbiota and faecal proteome profiles in mice
Authors: Paola Paone, Dimitris Latousakis, Romano Terrasi, Didier Vertommen, Ching Jian, Valentina Borlandelli, Francesco Suriano, Malin E V Johansson, Anthony Puel, Caroline Bouzin, Nathalie M Delzenne, Anne Salonen, Nathalie Juge, Bogdan I Florea, Giulio G Muccioli, Herman Overkleeft, Matthias Van Hul, Patrice D Cani
Journal: Gut (2024)

To decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2'-fucosyllactose (2'FL), can affect body weight and fat mass gain on high-fat diet (HFD) feeding in mice. We wanted to elucidate whether 2'FL metabolic effects are linked with changes in intestinal mucus production and secretion, mucin glycosylation and degradation, as well as with the modulation of the gut microbiota, faecal proteome and endocannabinoid (eCB) system.
The landscape of rare genetic variation associated with inflammatory bowel disease and Parkinson’s disease comorbidity
Authors: Meltem Ece Kars, Yiming Wu, Peter D Stenson, David N Cooper, Johan Burisch, Inga Peter, Yuval Itan
Journal: Genome Medicine (2024)

Inflammatory bowel disease (IBD) and Parkinson's disease (PD) are chronic disorders that have been suggested to share common pathophysiological processes. LRRK2 has been implicated as playing a role in both diseases. Exploring the genetic basis of the IBD-PD comorbidity through studying high-impact rare genetic variants can facilitate the identification of the novel shared genetic factors underlying this comorbidity.
Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction
Authors: Mehrangiz Dezhbord, Seong Ho Kim, Soree Park, Da Rae Lee, Nayeon Kim, Juhee Won, Ah Ram Lee, Dong-Sik Kim, Kyun-Hwan Kim
Journal: Clinical and Molecular Hepatology (2024)

Background/Aims: The major histocompatibility class II (MHC II) transactivator, known as CIITA, is induced by Interferon gamma (IFN-γ) and plays a well-established role in regulating the expression of class II MHC molecules in antigen-presenting cells.Methods: Primary human hepatocytes (PHH) were isolated via therapeutic hepatectomy from two donors. The hepatocellular carcinoma (HCC) cell lines HepG2 and Huh7 were used for the mechanistic study, and HBV infection was performed in HepG2-NTCP cells. HBV DNA replication intermediates and secreted antigen levels were measured using Southern blotting and ELISA, respectively.Results: We identified a non-canonical function of CIITA in the inhibition of hepatitis B virus (HBV) replication in both HCC cells and patient-derived PHH. Notably, in vivo experiments demonstrated that HBV DNA and secreted antigen levels were significantly decreased in mice injected with the CIITA construct. Mechanistically, CIITA inhibited HBV transcription and replication by suppressing the activity of HBV-specific enhancers/promoters. Indeed, CIITA exerts antiviral activity in hepatocytes through ERK1/2-mediated down-regulation of the expression of hepatocyte nuclear factor 1α (HNF1α) and HNF4α, which are essential factors for virus replication. In addition, silencing of CIITA significantly abolished the IFN-γ-mediated anti-HBV activity, suggesting that CIITA mediates the anti-HBV activity of IFN-γ to some extent. HBV X protein (HBx) counteracts the antiviral activity of CIITA via direct binding and impairing its function.Conclusions: Our findings reveal a novel antiviral mechanism of CIITA that involves the modulation of the ERK pathway to restrict HBV transcription. Additionally, our results suggest the possibility of a new immune avoidance mechanism involving HBx.
Letter regarding the article ‘Subclinical systolic dysfunction in <scp>genotype‐positive</scp> p<scp>henotype‐negative</scp> relatives of dilated cardiomyopathy patients: A systematic review and <scp>meta‐analysis</scp>’
Authors: Arif Albulushi, Ghalib Al Hinai, Nadya Al Matrooshi
Journal: European Journal of Heart Failure (2024)
Resistance, rebound, and recurrence regrowth patterns in pediatric low-grade glioma treated by MAPK inhibition: A modified Delphi approach to build international consensus-based definitions—International Pediatric Low-Grade Glioma Coalition
Authors: Patricia O’Hare, Tabitha Cooney, Peter de Blank, David H Gutmann, Mark Kieran, Till Milde, Jason Fangusaro, Michael Fisher, Shivaram Avula, Roger Packer, Kohei Fukuoka, Kshitij Mankad, Sabine Mueller, Angela J Waanders, Enrico Opocher, Eric Bouffet, Eric Raabe, Natacha Entz Werle, Amedeo A Azizi, Nathan J Robison, Pablo Hernáiz Driever, Mark Russo, Netteke Schouten, Cornelis M van Tilburg, Astrid Sehested, Jacques Grill, Pratiti Bandopadhayay, John-Paul Kilday, Olaf Witt, David M Ashley, Birgit Betina Ertl-Wagner, Uri Tabori, Darren R Hargrave
Journal: Neuro-Oncology (2024)

Abstract Pediatric low-grade glioma (pLGG) is the most common childhood brain tumor group. The natural history, when curative resection is not possible, is one of a chronic disease with periods of tumor stability and episodes of tumor progression. While there is a high overall survival rate, many patients experience significant and potentially lifelong morbidities. The majority of pLGGs have an underlying activation of the RAS/MAPK pathway due to mutational events, leading to the use of molecularly targeted therapies in clinical trials, with recent regulatory approval for the combination of BRAF and MEK inhibition for BRAFV600E mutated pLGG. Despite encouraging activity, tumor regrowth can occur during therapy due to drug resistance, off treatment as tumor recurrence, or as reported in some patients as a rapid rebound growth within 3 months of discontinuing targeted therapy. Definitions of these patterns of regrowth have not been well described in pLGG. For this reason, the International Pediatric Low-Grade Glioma Coalition, a global group of physicians and scientists, formed the Resistance, Rebound, and Recurrence (R3) working group to study resistance, rebound, and recurrence. A modified Delphi approach was undertaken to produce consensus-based definitions and recommendations for regrowth patterns in pLGG with specific reference to targeted therapies.
Targeting squalene epoxidase restores anti-PD-1 efficacy in metabolic dysfunction-associated steatohepatitis-induced hepatocellular carcinoma
Authors: Jun Wen, Xiang Zhang, Chi Chun Wong, Yating Zhang, Yasi Pan, Yunfei Zhou, Alvin Ho-Kwan Cheung, Yali Liu, Fenfen Ji, Xing Kang, Dabin Liu, Jun Yu
Journal: Gut (2024)

Squalene epoxidase (SQLE) promotes metabolic dysfunction-associated steatohepatitis-associated hepatocellular carcinoma (MASH-HCC), but its role in modulating the tumour immune microenvironment in MASH-HCC remains unclear.
Correction: Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340
Authors: Xiangyu Jian, Han He, Jiehong Zhu, Qi Zhang, Zhongxin Zheng, Xiangjing Liang, Liuyan Chen, Meiling Yang, Kaiyue Peng, Zhaowen Zhang, Tengfei Liu, Yaping Ye, Hongli Jiao, Shuyang Wang, Weijie Zhou, Yanqing Ding, Tingting Li
Journal: Molecular Cancer (2024)
Analysis of measurable residual disease by IG/TR gene rearrangements: quality assurance and updated EuroMRD guidelines
Authors: Vincent H J van der Velden, Isabel Dombrink, Julia Alten, Giovanni Cazzaniga, Emmanuelle Clappier, Daniela Drandi, Cornelia Eckert, Eva Fronkova, Jeremy Hancock, Michaela Kotrova, Rebekka Kraemer, Mirkka Montonen, Heike Pfeifer, Christiane Pott, Thorsten Raff, Heiko Trautmann, Hélène Cavé, Beat W Schäfer, Jacques J M van Dongen, Jan Trka, Monika Brüggemann
Journal: Leukemia (2024)

Abstract Minimal/measurable residual disease (MRD) diagnostics using real-time quantitative PCR analysis of rearranged immunoglobulin and T-cell receptor gene rearrangements are nowadays implemented in most treatment protocols for patients with acute lymphoblastic leukemia (ALL). Within the EuroMRD Consortium, we aim to provide comparable, high-quality MRD diagnostics, allowing appropriate risk-group classification for patients and inter-protocol comparisons. To this end, we set up a quality assessment scheme, that was gradually optimized and updated over the last 20 years, and that now includes participants from around 70 laboratories worldwide. We here describe the design and analysis of our quality assessment scheme. In addition, we here report revised data interpretation guidelines, based on our newly generated data and extensive discussions between experts. The main novelty is the partial re-definition of the “positive below quantitative range” category by two new categories, “MRD low positive, below quantitative range” and “MRD of uncertain significance”. The quality assessment program and revised guidelines will ensure reproducible and accurate MRD data for ALL patients. Within the Consortium, similar programs and guidelines have been introduced for other lymphoid diseases (e.g., B-cell lymphoma), for new technological platforms (e.g., digital droplet PCR or Next-Generation Sequencing), and for other patient-specific MRD PCR-based targets (e.g., fusion genes).
Defining Biomarkers in Stem Cell‐Derived Tissue Constructs for Drug and Disease Screening
Authors: Alexander R. Harris, Patrick McGivern, Frederic Gilbert, Nicole Van Bergen
Journal: Advanced Healthcare Materials (2024)

The development of stem cell-derived tissue constructs (SCTCs) for clinical applications, including regenerative medicine, drug and disease screening offers significant hope for detecting and treating intractable disorders. SCTCs display a variety of biomarkers that can be used to understand biological mechanisms, assess drug interactions, and predict disease. Although SCTCs can be derived from patients and share the same genetic make-up, they are nevertheless distinct from human patients in many significant ways, which can undermine the clinical significance of measurements in SCTCs. This study defines biomarkers, how they apply to SCTCs, and clarifies specific ethical issues associated with the use of SCTCs for drug and disease screening.
T cells with high BCL-2 expression induced by venetoclax impact anti-leukemic immunity “graft-versus-leukemia effects”
Authors: Joji Nagasaki, Mitsutaka Nishimoto, Hideo Koh, Hiroshi Okamura, Mika Nakamae, Kazuki Sakatoku, Kentaro Ido, Masatomo Kuno, Yosuke Makuuchi, Teruhito Takakuwa, Yasuhiro Nakashima, Masayuki Hino, Hirohisa Nakamae
Journal: Blood Cancer Journal (2024)
Efficacy and Toxicity Analysis of mFOLFIRINOX in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms
Authors: Michele Borghesani, Anna Reni, Eleonora Lauricella, Alice Rossi, Viola Moscarda, Elena Trevisani, Irene Torresan, Taymeyah Al-Toubah, Elisabetta Filoni, Claudio Luchini, Riccardo De Robertis, Luca Landoni, Aldo Scarpa, Camillo Porta, Michele Milella, Jonathan Strosberg, Mauro Cives, Sara Cingarlini
Journal: Journal of the National Comprehensive Cancer Network (2024)

High-grade neuroendocrine neoplasms (NENs) comprise both well-differentiated grade 3 neuroendocrine tumors (G3 NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) nearly always include poorly differentiated NEC as the neuroendocrine component. The efficacy and safety of frontline mFOLFIRINOX chemotherapy has never been investigated in patients with high-grade NENs.