tbuckley/cabot-search huggingface dataset:
Reasons for unmet care needs in older adults with cancer: Analyses from the 2015–2019 National Health and Aging Trends Study.
Authors: Ying Wang, AnnaLynn Williams, Marielle Jensen-Battaglia, Kah Poh Loh, Sally Norton, Christopher Seplaki
Journal: Journal of Clinical Oncology (2024)

11112 Background: Despite extensive research on unmet care needs in older adults (ages ≥65) with cancer, few studies explore the reasons for unmet care needs, knowledge of which can inform future interventions. We aimed to identity reasons for unmet care needs in older adults with cancer and associated factors. Methods: Our analyses included community-dwelling older adults with cancer from the 2015–2019 National Health and Aging Trends Study (NHATS). NHATS captures unmet care needs in 12 activities from three domains: activities of daily living (ADL), instrumental ADL (IADL), and mobility. We separately evaluated two categories of reasons for unmet care needs: “difficulty performing activities independently” (for participants without a caregiver), and “caregivers’ inability to help” (for those receiving caregiver assistance). Personal characteristics included demographic (gender, age, marital status, race, ethnicity, educational level), clinical (cancer type, years since cancer diagnosis), and health variables (physical function, nutritional status, cognition, psychological status). We built logistic models to assess characteristics associated with unmet care needs, adjusting for NHATS year and cancer type. In exploratory analyses, we further evaluated associations of years since cancer diagnosis with unmet care needs. All models were built separately for participants with and without a caregiver. Results: Our analysis included 1829 participants. In 2015, participants had a mean age of 81 years; more than half were female (55%), White (79%), non-Hispanic (96%), had impaired physical function (92%), and received caregiver assistance (51%). From 2015 to 2019, 29% to 32% participants without a caregiver reported any unmet care needs due to difficulty with performing the activity independently, with toileting (45-53%) and managing medications (27-31%) being the most prevalent. Between 18% and 20% participants with a caregiver reported any unmet care needs due to caregivers’ inability to help, with toileting (26-44%) and going around inside home (20-29%) being the most prevalent. Hispanic ethnicity, being separated/divorced, living alone or with non-spouses, and worse health status were independently associated with unmet care needs due to either reason. Compared to pre-diagnosis, being 1-2, [odds ratio (OR) 1.7], 3-4 (OR 1.8) and 5+ (OR 2.2) years from cancer diagnosis was significantly associated with higher odds of unmet care needs among those without a caregiver, but not those with a caregiver. Conclusions: Unmet care needs due to difficulty performing activities independently are common among older adults with cancer. Caregivers generally meet care recipients’ needs in IADLs, but may face challenges in toileting and mobility needs. Tailored interventions addressing specific reasons for unmet needs are needed, particularly for those at greater risk.
Neuropathy trajectory informed by algorithm-based alerts from remote symptom monitoring (RSM) tool in breast cancer practice.
Authors: Joel N. Saltzman, Emelly Rusli, Aaron Galaznik, Debra Wujcik
Journal: Journal of Clinical Oncology (2024)

11114 Background: The prevalence of chemotherapy-induced peripheral neuropathy (CIPN) ranges from 19% to over 85% 1 . In breast cancer (BC) adjuvant treatment, 40% of women report numbness and tingling after two years with 10% stating the symptoms are severe 2 . Risk factors include age, pre-existing neuropathy (PN), and treatment with taxanes and platinum-based drugs. This study explored the trajectory of neuropathy in data from remote symptom monitoring (RSM) in breast cancer practice. Methods: Women undergoing BC treatment who enrolled in Carevive PROmPT, an RSM tool, between 9/1/2020 and 11/29/2023 were included. A composite score (derived from PRO-CTCAE) using presence, severity, and interference reports symptoms as mild, moderate or severe. Mild symptoms are discussed at the next clinical visit while moderate/severe symptoms trigger an alert to the care team for immediate evaluation and mitigation. Analysis of neuropathy trajectory was conducted in patients who did not have PN at baseline, examining time to first neuropathy report and time to alert trigger due to severity. Age at first neuropathy, duration of therapy, cancer stage, race, CIPN drugs use, and the level of neuropathy interference was explored. Results: A total of 519 BC patients with one or more alerts were included, of whom 177 (34.1%) reported moderate/severe neuropathy at least once. Of 7,641 total alerts generated, 10.5% were associated with neuropathy. Nearly 40% (n=74) of patients had PN, with median age was 58.5, 31% late stage, 32% Black/African American, and 61% having prior CIPN treatment. About 58.2% of patients (n=103) did not have PN at baseline; of whom neuropathy was first reported over a median of 42 days (IQR: 17.5, 70.5) from baseline and 53.4% of patients (n=55) had mild neuropathy at first report, which then progressed to moderate/severe at a median of 28 days (IQR: 14, 79). About half of patients (52%) described the first neuropathy interference to be a little bit or somewhat. Patients with mild first occurrence of neuropathy (n=55) were then stratified by time to first neuropathy alert (moderate/severe) from first report: 0-28 days (n=28) and &gt;28 days (n=27). For the two groups, median age at first neuropathy was 51 and 49, duration of treatment was 2.4 and 4.4 months, late stage was 18% and 15%, Black/African American 32% and 22%, and receiving CIPN drugs at alert was 24% and 29%, respectively. The most prevalent level of interference upon alert was described as somewhat (32% vs. 28%, respectively). Conclusions: Breast cancer patients are at risk for developing severe and sustained neuropathy. Patients without PN whose first report of neuropathy was mild, quickly progressed to moderate/severe neuropathy. Physician notification at first report of neuropathy rather than with an alert of moderate/severe neuropathy provides opportunity for earlier intervention and better outcomes.
Nitric Oxide Signaling and Regulation in the Cardiovascular System: Recent Advances
Authors: Mattias Carlström, Eddie Weitzberg, Jon O. Lundberg
Journal: Pharmacological Reviews (2024)

Nitric oxide (NO) from endothelial NO synthase (eNOS) importantly contributes to vascular homeostasis. Reduced NO production or increased scavenging during disease conditions with oxidative stress contribute to endothelial dysfunction and NO deficiency. In addition to the classical enzymatic NOS system, NO can also be generated via the nitrate-nitrite-NO pathway. Dietary and pharmacological approaches aimed at increasing NO bioactivity, especially in the cardiovascular system, have been the focus of much research since the discovery of this small gaseous signaling molecule. Despite wide appreciation of the biological role of NOS/NO signaling, questions still remain about the chemical nature of NOS-derived bioactivity. Recent studies show that NO-like bioactivity can be efficiently transduced by mobile NO-ferroheme species which can transfer between proteins, partition into a hydrophobic phase, and directly activate the sGC-cGMP-PKG pathway without intermediacy of free NO. Moreover, interaction between red blood cells and the endothelium in the regulation of vascular NO homeostasis have gained much attention, especially in conditions with cardiometabolic disease. In this review we discuss both classical and non-classical pathways for NO generation in the cardiovascular system, and how these can be modulated for therapeutic purposes. <b>Significance Statement</b> After four decades of intensive research, questions persist about the transduction and control of NO synthase bioactivity. Here we discuss NO signaling in cardiovascular health and disease, highlighting new findings, such as the important role of red blood cells in cardiovascular NO homeostasis. Non-classical signaling modes, like the nitrate-nitrite-NO pathway, and therapeutic opportunities related to the NO system are discussed. Existing and potential pharmacological treatments/strategies, as well as dietary components influencing NO generation and signaling are covered.
Response, resistance, and recovery of gut bacteria to human-targeted drug exposure
Authors: Jacobo de la Cuesta-Zuluaga, Leonardo Boldt, Lisa Maier
Journal: Cell Host & Microbe (2024)

Survival strategies of human-associated microbes to drug exposure have been mainly studied in the context of bona fide pathogens exposed to antibiotics. Less well understood are the survival strategies of non-pathogenic microbes and host-associated commensal communities to the variety of drugs and xenobiotics to which humans are exposed. The lifestyle of microbial commensals within complex communities offers a variety of ways to adapt to different drug-induced stresses. Here, we review the responses and survival strategies employed by gut commensals when exposed to drugs-antibiotics and non-antibiotics-at the individual and community level. We also discuss the factors influencing the recovery and establishment of a new community structure following drug exposure. These survival strategies are key to the stability and resilience of the gut microbiome, ultimately influencing the overall health and well-being of the host.
A cerebellar granule cell-climbing fiber computation to learn to track long time intervals
Authors: Martha G. Garcia-Garcia, Akash Kapoor, Oluwatobi Akinwale, Lina Takemaru, Tony Hyun Kim, Casey Paton, Ashok Litwin-Kumar, Mark J. Schnitzer, Liqun Luo, Mark J. Wagner
Journal: Neuron (2024)

In classical cerebellar learning, Purkinje cells (PkCs) associate climbing fiber (CF) error signals with predictive granule cells (GrCs) that were active just prior (∼150 ms). The cerebellum also contributes to behaviors characterized by longer timescales. To investigate how GrC-CF-PkC circuits might learn seconds-long predictions, we imaged simultaneous GrC-CF activity over days of forelimb operant conditioning for delayed water reward. As mice learned reward timing, numerous GrCs developed anticipatory activity ramping at different rates until reward delivery, followed by widespread time-locked CF spiking. Relearning longer delays further lengthened GrC activations. We computed CF-dependent GrC→PkC plasticity rules, demonstrating that reward-evoked CF spikes sufficed to grade many GrC synapses by anticipatory timing. We predicted and confirmed that PkCs could thereby continuously ramp across seconds-long intervals from movement to reward. Learning thus leads to new GrC temporal bases linking predictors to remote CF reward signals—a strategy well suited for learning to track the long intervals common in cognitive domains.
Mechanisms of bacterial immunity, protection, and survival during interbacterial warfare
Authors: Nolan W. Kennedy, Laurie E. Comstock
Journal: Cell Host & Microbe (2024)

Most bacteria live in communities, often with closely related strains and species with whom they must compete for space and resources. Consequently, bacteria have acquired or evolved mechanisms to antagonize competitors through the production of antibacterial toxins. Similar to bacterial systems that combat phage infection and mechanisms to thwart antibiotics, bacteria have also acquired and evolved features to protect themselves from antibacterial toxins. Just as there is a large body of research identifying and characterizing antibacterial proteins and toxin delivery systems, studies of bacterial mechanisms to resist and survive assault from competitors' weapons have also expanded tremendously. Emerging data are beginning to reveal protective processes and mechanisms that are as diverse as the toxins themselves. Protection against antibacterial toxins can be acquired by horizontal gene transfer, receptor or target alteration, induction of protective functions, physical barriers, and other diverse processes. Here, we review recent studies in this rapidly expanding field.
Intestinal colonization resistance in the context of environmental, host, and microbial determinants
Authors: Simon Woelfel, Marta Salvado Silva, Bärbel Stecher
Journal: Cell Host & Microbe (2024)

Microbial communities that colonize the human gastrointestinal (GI) tract defend against pathogens through a mechanism known as colonization resistance (CR). Advances in technologies such as next-generation sequencing, gnotobiotic mouse models, and bacterial cultivation have enhanced our understanding of the underlying mechanisms and the intricate microbial interactions involved in CR. Rather than being attributed to specific microbial clades, CR is now understood to arise from a dynamic interplay between microbes and the host and is shaped by metabolic, immune, and environmental factors. This evolving perspective underscores the significance of contextual factors, encompassing microbiome composition and host conditions, in determining CR. This review highlights recent research that has shifted its focus toward elucidating how these factors interact to either promote or impede enteric infections. It further discusses future research directions to unravel the complex relationship between host, microbiota, and environmental determinants in safeguarding against GI infections to promote human health.
Birthmode and environment-dependent microbiota transmission dynamics are complemented by breastfeeding during the first year
Authors: Marta Selma-Royo, Léonard Dubois, Serena Manara, Federica Armanini, Raúl Cabrera-Rubio, Mireia Valles-Colomer, Sonia González, Anna Parra-Llorca, Ramon Escuriet, Lars Bode, Cecilia Martínez-Costa, Nicola Segata, Maria Carmen Collado
Journal: Cell Host & Microbe (2024)

The composition and maturation of the early-life microbiota are modulated by a number of perinatal factors, whose interplay in relation to microbial vertical transmission remains inadequately elucidated. Using recent strain-tracking methodologies, we analyzed mother-to-infant microbiota transmission in two different birth environments: hospital-born (vaginal/cesarean) and home-born (vaginal) infants and their mothers. While delivery mode primarily explains initial compositional differences, place of birth impacts transmission timing-being early in homebirths and delayed in cesarean deliveries. Transmission patterns vary greatly across species and birth groups, yet certain species, like Bifidobacterium longum, are consistently vertically transmitted regardless of delivery setting. Strain-level analysis of B. longum highlights relevant and consistent subspecies replacement patterns mainly explained by breastfeeding practices, which drive changes in human milk oligosaccharide (HMO) degrading capabilities. Our findings highlight how delivery setting, breastfeeding duration, and other lifestyle preferences collectively shape vertical transmission, impacting infant gut colonization during early life.
Host stress drives tolerance and persistence: The bane of anti-microbial therapeutics
Authors: Sophie Helaine, Brian P. Conlon, Kimberly M. Davis, David G. Russell
Journal: Cell Host & Microbe (2024)

Antibiotic resistance, typically associated with genetic changes within a bacterial population, is a frequent contributor to antibiotic treatment failures. Antibiotic persistence and tolerance, which we collectively term recalcitrance, represent transient phenotypic changes in the bacterial population that prolong survival in the presence of typically lethal concentrations of antibiotics. Antibiotic recalcitrance is challenging to detect and investigate-traditionally studied under in vitro conditions, our understanding during infection and its contribution to antibiotic failure is limited. Recently, significant progress has been made in the study of antibiotic-recalcitrant populations in pathogenic species, including Mycobacterium tuberculosis, Staphylococcus aureus, Salmonella enterica, and Yersiniae, in the context of the host environment. Despite the diversity of these pathogens and infection models, shared signals and responses promote recalcitrance, and common features and vulnerabilities of persisters and tolerant bacteria have emerged. These will be discussed here, along with progress toward developing therapeutic interventions to better treat recalcitrant pathogens.
Bacterial esterases reverse lipopolysaccharide ubiquitylation to block host immunity
Authors: Magdalena Szczesna, Yizhou Huang, Rachel E. Lacoursiere, Francesca Bonini, Vito Pol, Fulya Koc, Beatrice Ward, Paul P. Geurink, Jonathan N. Pruneda, Teresa L.M. Thurston
Journal: Cell Host & Microbe (2024)

Aspects of how Burkholderia escape the host's intrinsic immune response to replicate in the cell cytosol remain enigmatic. Here, we show that Burkholderia has evolved two mechanisms to block the activity of Ring finger protein 213 (RNF213)-mediated non-canonical ubiquitylation of bacterial lipopolysaccharide (LPS), thereby preventing the initiation of antibacterial autophagy. First, Burkholderia's polysaccharide capsule blocks RNF213 association with bacteria and second, the Burkholderia deubiquitylase (DUB), TssM, directly reverses the activity of RNF213 through a previously unrecognized esterase activity. Structural analysis provides insight into the molecular basis of TssM esterase activity, allowing it to be uncoupled from its isopeptidase function. Furthermore, a putative TssM homolog also displays esterase activity and removes ubiquitin from LPS, establishing this as a virulence mechanism. Of note, we also find that additional immune-evasion mechanisms exist, revealing that overcoming this arm of the host's immune response is critical to the pathogen.
Paternal and induced gut microbiota seeding complement mother-to-infant transmission
Authors: Léonard Dubois, Mireia Valles-Colomer, Alise Ponsero, Otto Helve, Sture Andersson, Kaija-Leena Kolho, Francesco Asnicar, Katri Korpela, Anne Salonen, Nicola Segata, Willem M. de Vos
Journal: Cell Host & Microbe (2024)

Microbial colonization of the neonatal gut involves maternal seeding, which is partially disrupted in cesarean-born infants and after intrapartum antibiotic prophylaxis. However, other physically close individuals could complement such seeding. To assess the role of both parents and of induced seeding, we analyzed two longitudinal metagenomic datasets (health and early life microbiota [HELMi]: N = 74 infants, 398 samples, and SECFLOR: N = 7 infants, 35 samples) with cesarean-born infants who received maternal fecal microbiota transplantation (FMT). We found that the father constitutes a stable source of strains for the infant independently of the delivery mode, with the cumulative contribution becoming comparable to that of the mother after 1 year. Maternal FMT increased mother-infant strain sharing in cesarean-born infants, raising the average bacterial empirical growth rate while reducing pathogen colonization. Overall, our results indicate that maternal seeding is partly complemented by that of the father and support the potential of induced seeding to restore potential deviations in this process.
SAT-090-YI Improvement of liver frailty, hand grip strength and mid-upper arm circumference in cirrhotic patients after TIPS insertion
Authors: Martin Kabelitz, Anja Tiede, Hannah Schneider, Jim Benjamin Mauz, Alena Friederike Ehrenbauer, Liv Grete Ahl, Lea Wagner, Heiner Wedemeyer, Benjamin Maasoumy, Lisa Sandmann
Journal: Journal of Hepatology (2024)
THU-533 MCPIP1 RNase inhibits liver fibrosis by targeting TGF-β1 mRNA
Authors: Natalia Pydyn, Anna Ferenc, Katarzyna Trzos, Mateusz Wilamowski, Pedro Miguel Rodrigues, Jesus Maria Banales, José María Herranz, Matías A. Avila, Jolanta Jura, Jerzy Kotlinowski
Journal: Journal of Hepatology (2024)
THU-192 Liver steatosis assessed by controlled attenuation parameter in patients with primary biliary cholangitis
Authors: Francesca Bueti, Maria Stella Franzè, Concetta Pitrone, Gaia Caccamo, Irene Cacciola, Roberto Filomia, Sergio Maimone, Giovanni Raimondo, Carlo Saitta
Journal: Journal of Hepatology (2024)
FRI-213 Low-to-moderate alcohol consumption is associated with increased fibrosis in subjects with metabolic dysfunction-associated steatotic liver disease
Authors: David Marti-Aguado, José Luis Calleja Panero, Eduardo Vilar Gomez, Paula Iruzubieta, Juan Carlos Rodriguez Duque, María Del Barrio, Laura Puchades, Jesùs Rivera, Christie Perelló, Angela Puente, Concepción Gómez, Desamparados Escudero-García, Miguel Serra, Ramon Bataller, Javier Crespo, María Teresa Arias Loste
Journal: Journal of Hepatology (2024)
THU-454 Induction of systemic immune activation by liver transplant and effects of previous VEGF/PD-L1 blockade in HCC patients
Authors: Sherrie Bhoori, Michela Dosi, Valentina Bellia, Marco Bongini, Maria Flores, Luca Lalli, Giovanni Di Maio, Jeanette Salsetta, Marta Zorza, Agata Cova, Martina Stroscia, Licia Rivoltini, Vincenzo Mazzaferro
Journal: Journal of Hepatology (2024)
THU-137 Ulcerative colitis-associated anti-integrin αVß6 antibodies are highly prevalent in primary sclerosing cholangitis
Authors: Dominik Roth, Miriam M. Düll, Aylin Lindemann, Peter Dietrich, Ludwig J. Horst, Markus F. Neurath, Juergen Siebler, Christoph Schramm, Andreas E. Kremer, Moritz Leppkes
Journal: Journal of Hepatology (2024)
THU-171 Recurrence of primary sclerosing cholangitis after living donor liver transplantation: experience from turkish registry
Authors: Gupse Adali, Murat Harputluoglu, Meral Akdogan Kayhan, Dilara Turan Gökçe, Mesut Akarsu, Nilay Daniş, Dinc Dincer, Haydar Adanir, Ilker Turan, Elvan Isik, Hale Gokcan, Volkan Yılmaz, Zülal İstemihan, Sabahattin Kaymakoğlu, Ramazan Idilman, Zeki Karasu
Journal: Journal of Hepatology (2024)
THU-126 Metabolomic signature in autoimmune hepatitis discriminates disease activity and predicts response to treatment
Authors: Kalliopi Zachou, Aikaterini Dimou, Christina Kostara, Kalliopi Azariadis, George Giannoulis, Angeliki Lyberopoulou, Eleni Bairaktari, George Dalekos
Journal: Journal of Hepatology (2024)
THU-101 Non-invasive tests for ruling out high-risk esophageal varices in patients with primary biliary cholangitis based on the cholestasis degree
Authors: Vincenza Calvaruso, Ciro Celsa, Laura Cristoferi, Miki Scaravaglio, Eugenia Nofit, Rachel Smith, Senamjit Kaur, Gabriele Di Maria, Luigi Capodicasa, Luca Cadamuro, Alessio Gerussi, Federica Malinverno, Pietro Lampertico, Nora Cazzagon, Marco Marzioni, Umberto Vespasiani-Gentilucci, Francesca Colapietro, Pietro Andreone, Ana Lleo, Cristina Rigamonti, Mauro Viganò, Edoardo Giannini, Maurizio Russello, Ester Vanni, Federica Cerini, Alessandra Orlandini, Maurizia Brunetto, Grazia Anna Niro, Giovanni Vettori, Antonino Castellaneta, Vincenzo Cardinale, Domenico Alvaro, Andrea Mega, Valeria Pace Palitti, Francesco Bellanti, Vito Di Marco, George Mells, Emma Culver, Pietro Invernizzi, Calogero Camma, Marco Carbone
Journal: Journal of Hepatology (2024)
FRI-116 Prognostic significance of HDL-associated apolipoproteins in patients with decompensated cirrhosis and spontaneous bacterial peritonitis
Authors: Mohamad Murad, Johanna Reising, Majda El Hassani, Mick Frissen, Oluwatomi Ibidapo-Obe, Karsten Grose, Theresa Hildegard Wirtz, Christian Trautwein, Philipp Reuken, Tony Bruns
Journal: Journal of Hepatology (2024)
THU-547 Ex-vivo translational assay of hepatic stellate cells using patientderived serum characterizes the anti-fibrotic activity of CM-101
Authors: Johnny Amer, Ahmad Salhab, Raanan Greenman, Tom Snir, Avi Katav, Revital Aricha, Matthew Frankel, John Lawler, Francesca Saffioti, Douglas Thorburn, Massimo Pinzani, Ilan Vaknin, Adi Mor, Rifaat Safadi
Journal: Journal of Hepatology (2024)
TOP-149-YI Plasmatic expression of miR122-5p and miR21-5p predicts relapse of autoimmune hepatitis after treatment withdrawal
Authors: Pinelopi Arvaniti, Olga Millán, Ignasi Olivas, Mar Riveiro Barciela, Montserrat García-Retortillo, Mercé Roget, Thais Leonel, Sergio Rodriguez-Tajes, Judit Julian, Merceè Brunet, María Carlota Londono
Journal: Journal of Hepatology (2024)