tbuckley/cabot-search huggingface dataset:
Successful management of fecalith impaction in the distal ileum using a transendoscopic enteral tube for targeted drug delivery
Authors: Quan Wen, Bota Cui, You Yu, Faming Zhang
Journal: Endoscopy (2024)

A 69-year-old man presented after 1 week of abdominal pain and distension, accompanied by nausea and vomiting for 1 day. Computed tomography identified wall thickening of the distal small intestine, with a 3.4 × 2.8 cm high-density intraluminal foreign body ([Fig. 1]) and proximal intestinal dilation with air/fluid levels. Despite conservative treatments, including intravenous hydration, feeding tubes, stool softeners, and enema, the patient's symptoms persisted. Intestinal ultrasound confirmed a strong echo mass in the distal ileum.
Objective and subjective experiences of childhood maltreatment and their relationships with cognitive deficits: a cohort study in the USA
Authors: Andrea Danese, Cathy Spatz Widom
Journal: The Lancet Psychiatry (2024)

Cognitive deficits might contribute to the elevated risk of life-course psychopathology observed in maltreated children. Leading theories about the links between childhood maltreatment and cognitive deficits focus on documented exposures (objective experience), but empirical research has largely relied on retrospective self-reports of these experiences (subjective experience), and the two measures identify largely non-overlapping groups. We aimed to test the associations of objective and subjective measures of maltreatment with cognitive abilities within the same individuals.
Drug delivery strategies for local immunomodulation in transplantation: Bridging the translational gap
Authors: Afsana Naaz, Heth R Turnquist, Vijay S Gorantla, Steven R Little
Journal: Advanced Drug Delivery Reviews (2024)

Drug delivery strategies for local immunomodulation hold tremendous promise compared to current clinical gold-standard systemic immunosuppression as they could improve the benefit to risk ratio of life-saving or life-enhancing transplants. Such strategies have facilitated prolonged graft survival in animal models at lower drug doses while minimizing off-target effects. Despite the promising outcomes in preclinical animal studies, progression of these strategies to clinical trials has faced challenges. A comprehensive understanding of the translational barriers is a critical first step towards clinical validation of effective immunomodulatory drug delivery protocols proven for safety and tolerability in pre-clinical animal models. This review overviews the current state-of-the-art in local immunomodulatory strategies for transplantation and outlines the key challenges hindering their clinical translation.
The expanded French compassionate programme for elexacaftor–tezacaftor–ivacaftor use in people with cystic fibrosis without a F508del CFTR variant: a real-world study
Authors: Pierre-Régis Burgel, Isabelle Sermet-Gaudelus, Emmanuelle Girodon, Isabelle Durieu, Véronique Houdouin, Camille Audousset, Julie Macey, Dominique Grenet, Michele Porzio, Marlène Murris-Espin, Philippe Reix, Mélisande Baravalle, Chantal Belleguic, Laurent Mely, Juliette Verhille, Laurence Weiss, Martine Reynaud-Gaubert, Marie Mittaine, Rebecca Hamidfar, Sophie Ramel, Laure Cosson, Benoit Douvry, Isabelle Danner-Boucher, Pierre Foucaud, Charlotte Roy, Espérie Burnet, Caroline Raynal, Marie-Pierre Audrezet, Jennifer Da Silva, Clémence Martin, Reem Kanaan, Nicolas Carlier, Isabelle Honoré, Frédérique Chedevergne, Elise Dreano, Aurélie Hatton, Alexandre Hinzpeter, Iwona Pranke, Laurence Le Clainche-Viala, Sophie Mayer, Harriet Corvol, Guillaume Thouvenin, Sandra de Miranda, Natascha Remus, Benoit Douvry, Louise Duthoit, Thierry Perez, Olivier Le Rouzic, Nathalie Wizla, Claire Bon, Stéphanie Bui, Nora Poey, Nathalie Stremler, Bérengère Coltey, Nadine Dufeu, Jean Lebihan, Asma Gabsi, Delphine Pouradier, Claire Andrejak, Cinthia Rames, Magali Dupuy-Grasset, Jeanne Languepin, Christophe Marguet, Stéphanie Pramil, Baptiste Arnouat, Annlyse Fanton, Michel Abely, Bruno Ravoninjatovo, Aurore Blondé, Anne Guillaumot, Sebastien Kieffer, Aurélie Tatopoulos, Raphaële Nove-Josserand, Camille Ohlmann, Thomas Perrin, Quitterie Reynaud, Catherine Llerena, Sébastien Quétant, Sophie Valois, Marie-Laure Dalphin, Bénédicte Richaud-Thiriez, Eric Deneuville, Raphael Chiron, Floriane Socchi, Tiphaine Bihouée, Julie Mankikian, Thomas Flament, Nathalie Coolen-Allou, Elsa Gachelin, Caroline Périsson, Constance Vuillard, Marion Dupuis, Wael Alkoussa, Sarah Marchal, Sylvie Leroy, Manuela Scalbert, Karine Campbell, Muriel Laurans, Guillaume Labbé, Sylvie Montcouquiol, Pascaline Priou, Paola de Carli, Lydie Lemonnier, Clémence Dehillotte, Thierry Nouvel
Journal: The Lancet Respiratory Medicine (2024)
Trends in infection incidence and antimicrobial resistance in the US Veterans Affairs Healthcare System: a nationwide retrospective cohort study (2007–22)
Authors: Thi Mui Pham, Yue Zhang, McKenna Nevers, Haojia Li, Karim Khader, Yonatan H Grad, Marc Lipsitch, Matthew Samore
Journal: The Lancet Infectious Diseases (2024)
Investigating the effect of enhanced cleaning and disinfection of shared medical equipment on health-care-associated infections in Australia (CLEEN): a stepped-wedge, cluster randomised, controlled trial
Authors: Katrina Browne, Nicole M White, Philip L Russo, Allen C Cheng, Andrew J Stewardson, Georgia Matterson, Peta E Tehan, Kirsty Graham, Maham Amin, Maria Northcote, Martin Kiernan, Jennie King, David Brain, Brett G Mitchell
Journal: The Lancet Infectious Diseases (2024)
Indocyanine green near-infrared fluorescence bowel perfusion assessment to prevent anastomotic leakage in minimally invasive colorectal surgery (AVOID): a multicentre, randomised, controlled, phase 3 trial
Authors: Robin A Faber, Ruben P J Meijer, Daphne H M Droogh, Jasmijn J Jongbloed, Okker D Bijlstra, Fran Boersma, Jeffrey P B M Braak, Elma Meershoek-Klein Kranenbarg, Hein Putter, Fabian A Holman, J Sven D Mieog, Peter A Neijenhuis, Esther van Staveren, Johanne G Bloemen, Jacobus W A Burger, Tjeerd S Aukema, Mark A M Brouwers, Andreas W K S Marinelli, Marinke Westerterp, Pascal G Doornebosch, Annelies van der Weijde, Koop Bosscha, Henricus J M Handgraaf, Esther C J Consten, Daan J Sikkenk, Jacobus Burggraaf, Stijn Keereweer, Joost R van der Vorst, Merlijn Hutteman, Koen C M J Peeters, Alexander L Vahrmeijer, Denise E Hilling
Journal: The Lancet. Gastroenterology & hepatology (2024)
Scoping review of withdrawal's role in contemporary gaming disorder research: Conceptualizations and operationalizations
Authors: Sylwia Starzec, Jolanta Starosta, Aleksandra Zajas, Patrycja Kiszka, Sławomir Śpiewak, Paweł Strojny
Journal: Clinical Psychology Review (2024)

The global gaming community now exceeds 3 billion players, prompting increased attention from social and medical sciences regarding gaming-related disorders. Internet Gaming Disorder (IGD) was incorporated into DSM-5 in 2013, and Gaming Disorder (GD) found its place in ICD-11 in 2019. A contentious criterion in IGD, not present in GD, revolves around withdrawal symptoms. This paper offers a theoretical foundation on gaming withdrawal symptoms in gaming-related disorders and conducts a scoping review of withdrawal operationalization and conceptualization in 40 selected studies, following PRISMA-ScR guidelines. Most studies employed a correlation framework, relying on convenience samples and self-assessment questionnaires. A smaller portion focused on clinical samples and case studies. Withdrawal was predominantly conceptualized in terms of affective components, with less emphasis on behavioural, cognitive, physical, or neurological aspects. The prevailing terminology for gaming-related disorders was IGD, with only three studies referencing GD as defined in ICD-11. Notably, just six experimental studies included abstinence control. We advocate for an expansion of research on withdrawal symptoms, particularly through experimental studies that implement abstinence within experimental groups and offer alternative operationalizations beyond dominant self-assessment measures.
Traumatic pancreatic duct injury successfully treated with endoscopic retrograde cholangiopancreatography and stent placement in a 6-year-old boy
Authors: Huma Asmat, Usama Al Farsi, Phillip Harrison, Deepak Joshi
Journal: Endoscopy (2024)

Pancreatic injury in children is rare, accounting for less than 1% of all pediatric traumas, but it does carry significant morbidity and mortality [1].
Extending limits: the longest recorded duodenojejunal bypass implant
Authors: Jan Kral, Pavel Drastich, Manoel P. Galvão, Katerina Knotkova, Martin Haluzik, Evzen Machytka
Journal: Endoscopy (2024)

A 59-year-old patient with type 2 diabetes, dyslipidemia, and hypertension underwent the placement of a duodenojejunal bypass (EndoBarrier; GI Dynamics, Boston, Massachusetts, USA). At the time of the endoscopy procedure, the patient weighed 110 kg and was 172 cm tall, resulting in a body mass index (BMI) of 37.3 kg/m2. The procedure, performed under general anesthesia, concluded without complications. Postoperatively, the patient was prescribed 40 mg of proton pump inhibitors (PPIs) twice daily and advised to avoid fiber. Early side effects included daily nausea (five to eight episodes), and epigastric pain was managed with antiemetics and ongoing PPI use. One month later, an endoscopy confirmed the duodenojejunal bypass was correctly positioned but revealed ulcers at the device's sharp edges. Despite initial challenges, symptoms improved significantly within three weeks. After 12 months, the patient had lost 30 kg, reducing their (BMI) to 27.3 kg/m2. The patient chose to keep the bypass despite the conclusion of the study and against medical advice about potential risks.
COVID-19 vaccination and birth outcomes of 186,990 women vaccinated before pregnancy: an England-wide cohort study
Authors: Arun K Suseeladevi, Rachel Denholm, Matthew Retford, Elena Raffetti, Christy Burden, Katherine Birchenall, Victoria Male, Venetia Walker, Christopher Tomlinson, Angela M Wood, Luisa Zuccolo
Journal: The Lancet Regional Health - Europe (2024)

COVID-19 vaccination in pregnancy is recommended by the World Health Organisation as effective and safe. However, there remains a lack of robust evidence to inform vaccination choices for women of childbearing potential in relation to their future pregnancies. Here we investigated the association between starting a course of COVID-19 vaccination before pregnancy and birth outcomes. We analysed England-wide linked electronic health records for all pregnancies reaching at least 24 weeks gestation between 25th May 2021 and 28th October 2022. We estimated incidence rates and hazard ratios for birth and pregnancy outcomes by pre-pregnancy COVID-19 vaccination status. Based on 186,990 women, compared to starting a pregnancy unvaccinated, receiving COVID-19 vaccination within 12 months before pregnancy was associated with lower risks of very and extremely preterm birth and small-for-gestational age in term babies for any vaccine type (adjusted hazard ratio and 95% confidence interval: 0.74 [0.63, 0.88] and 0.94 [0.88, 1.00], respectively), and lower stillbirth risk in those receiving an mRNA vaccine (0.72 [0.52, 1.00]). Incidence of venous thromboembolism during pregnancy was higher amongst women receiving a viral-vector, but not an mRNA vaccine (1.54 [1.10, 2.16] and 1.02 [0.70, 1.50], respectively). Results were generally consistent for different dose regimens and across sensitivity analyses. We found evidence that pregnancies starting within 12 months from a first COVID-19 vaccination, compared to those in unvaccinated women, experienced fewer adverse birth outcomes, overall or in selected subgroups of the general population, accounting for potential confounders. An mRNA vaccine should be preferred to a viral-vector vaccine, to minimise safety issues, but where the latter is the only choice, it is still to be preferred to starting a pregnancy unvaccinated. The venous thromboembolism risk of the viral-vector vaccine was substantially lower compared to that attributable to SARS-CoV-2 infection in pregnancy or to commonly used medications such as hormone replacement therapy and oral contraceptives in the non-pregnant population. UK National Institute for Health and Care Research (NIHR), UKRIMedical Research Council, UK Research and Innovation, The Alan Turing Institute, Health Data Research UK, the Department of Health and Social Care.
Association of genetic ancestry with molecular tumor profiles in colorectal cancer
Authors: Brooke Rhead, David M. Hein, Yannick Pouliot, Justin Guinney, Francisco M. De La Vega, Nina N. Sanford
Journal: Genome Medicine (2024)

There are known disparities in incidence and outcomes of colorectal cancer (CRC) by race and ethnicity. Some of these disparities may be mediated by molecular changes in tumors that occur at different rates across populations. Genetic ancestry is a measure complementary to race and ethnicity that can overcome missing data issues and better capture genetic similarity in admixed populations. We aimed to identify somatic mutations and tumor gene expression differences associated with both genetic ancestry and imputed race and ethnicity. Sequencing was performed with the Tempus xT NGS 648-gene panel and whole exome capture RNA-Seq for 8454 primarily late-stage CRC patients. Genetic ancestry proportions for five continental groups—Africa (AFR), American indigenous (AMR), East Asia (EAS), Europe (EUR), and South Asia (SAS)—were estimated using ancestry informative markers. To address data gaps, race and ethnicity categories were imputed, resulting in assignments for 952 Hispanic/Latino, 420 non-Hispanic (NH) Asian, 1061 NH Black, and 5763 NH White individuals. We assessed association of genetic ancestry proportions and imputed race and ethnicity categories with somatic mutations in relevant CRC genes and in 2608 expression profiles, as well as 1957 consensus molecular subtypes (CMS). Increased AFR ancestry was associated with higher odds of somatic mutations in APC, KRAS, and PIK3CA and lower odds of BRAF mutations. Additionally, increased EAS ancestry was associated with lower odds of mutations in KRAS, EUR with higher odds in BRAF, and the Hispanic/Latino category with lower odds in BRAF. Greater AFR ancestry and the NH Black category were associated with higher rates of CMS3, while a higher proportion of Hispanic/Latino patients exhibited indeterminate CMS classifications. Molecular differences in CRC tumor mutation frequencies and gene expression that may underlie observed differences by race and ethnicity were identified. The association of AFR ancestry with increased KRAS mutations aligns with higher CMS3 subtype rates in NH Black patients. The increase of indeterminate CMS in Hispanic/Latino patients suggests that subtype classification methods could benefit from enhanced patient diversity.
Spatial multiomics reveals a subpopulation of fibroblasts associated with cancer stemness in human hepatocellular carcinoma
Authors: Si-yu Jing, Dan Liu, Na Feng, Hui Dong, He-qi Wang, Xi Yan, Xu-feng Chen, Min-cheng Qu, Ping Lin, Bin Yi, Feiling Feng, Lei Chen, Hong-yang Wang, Hong Li, Yu-fei He
Journal: Genome Medicine (2024)

Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear.
YAP1 Inhibition Induces Phenotype Switching of Cancer-Associated Fibroblasts to Tumor Suppressive in Prostate Cancer
Authors: Hongtao Song, Tong Lu, Donghui Han, Jiayu Zhang, Lunbiao Gan, Chao Xu, Shaojie Liu, Peng Li, Keying Zhang, Zhihao Hu, Hongji Li, Yu Li, Xiaolong Zhao, Jingliang Zhang, Nianzeng Xing, Changhong Shi, Weihong Wen, Fa Yang, Weijun Qin
Journal: Cancer Research (2024)

Prostate cancer rarely responds to immune-checkpoint blockade (ICB) therapies. Cancer-associated fibroblasts (CAF) are critical components of the immunologically "cold" tumor microenvironment and are considered a promising target to enhance the immunotherapy response. In this study, we aimed to reveal the mechanisms regulating CAF plasticity to identify potential strategies to switch CAFs from protumorigenic to antitumor phenotypes and to enhance ICB efficacy in prostate cancer. Integration of four prostate cancer single-cell RNA sequencing datasets defined protumorigenic and antitumor CAFs, and RNA-seq, flow cytometry, and a prostate cancer organoid model demonstrated the functions of two CAF subtypes. Extracellular matrix-associated CAFs (ECM-CAF) promoted collagen deposition and cancer cell progression, and lymphocyte-associated CAFs (Lym-CAF) exhibited an antitumor phenotype and induced the infiltration and activation of CD8+ T cells. YAP1 activity regulated the ECM-CAF phenotype, and YAP1 silencing promoted switching to Lym-CAFs. NF-κB p65 was the core transcription factor in the Lym-CAF subset, and YAP1 inhibited nuclear translocation of p65. Selective depletion of YAP1 in ECM-CAFs in vivo promoted CD8+ T-cell infiltration and activation and enhanced the therapeutic effects of anti-PD-1 treatment on prostate cancer. Overall, this study revealed a mechanism regulating CAF identity in prostate cancer and highlighted a therapeutic strategy for altering the CAF subtype to suppress tumor growth and increase sensitivity to ICB. Significance: YAP1 regulates cancer-associated fibroblast phenotypes and can be targeted to switch cancer-associated fibroblasts from a protumorigenic subtype that promotes extracellular matrix deposition to a tumor-suppressive subtype that stimulates antitumor immunity and immunotherapy efficacy.
LTβR Agonism Promotes Anti-Tumor Immune Responses via Modulation of the Tumor Microenvironment
Authors: Disi An, Guoying Chen, Wei-Yi Cheng, Katja Mohrs, Christina Adler, Namita T. Gupta, Gurinder S. Atwal, David J. DiLillo, Christopher Daly, John C. Lin, Frank Kuhnert
Journal: Cancer Research (2024)

Abstract The presence of high endothelial venules (HEV) and tertiary lymphoid structures (TLS) in solid tumors is correlated with favorable prognosis and better responses to immune checkpoint blockade in many cancer types. Elucidation of the molecular mechanisms underlying intratumoral HEV and TLS formation and their contribution to antitumor responses may facilitate the development of improved treatment strategies. Lymphotoxin β receptor (LTβR) signaling is a critical regulator of lymph node organogenesis and can cooperate with antiangiogenic and immune checkpoint blockade treatment to augment tumor-associated HEV formation. In this study, we demonstrated that LTβR signaling modulates the tumor microenvironment via multiple mechanisms to promote antitumor T-cell responses. Systemic activation of the LTβR pathway via agonistic antibody treatment induced tumor-specific HEV formation, upregulated the expression of TLS-related chemokines, and enhanced dendritic cell (DC) and T-cell infiltration and activation in syngeneic tumor models. In vitro studies confirmed direct effects of LTβR agonism on DC activation and maturation and associated DC-mediated T-cell activation. Single-agent LTβR agonist treatment inhibited syngeneic tumor growth in a CD8+ T-cell–dependent and HEV-dependent manner, and the LTβR agonist enhanced antitumor effects of anti-PD-1 and CAR T-cell therapies. An in vivo tumor screen for TLS-inducing cytokines revealed that the combination of LTβR agonism and lymphotoxin ⍺ expression promoted robust intratumoral TLS induction and enhanced tumor responses to anti-CTLA4 treatment. Collectively, this study highlights crucial functions of LTβR signaling in modulating the tumor microenvironment and could inform future HEV/TLS-based strategies for cancer treatments. Significance: LTβR mediates tumor-specific high endothelial venule formation and immunomodulation of the tumor microenvironment that promotes antitumor immune responses, supporting LTβR agonism as an approach to enhance the antitumor efficacy of immunotherapies.
H3K18 Lactylation Potentiates Immune Escape of Non-Small Cell Lung Cancer
Authors: Cai Zhang, Lijie Zhou, Mingyuan Zhang, Yue Du, Cai Li, Huijun Ren, Lu Zheng
Journal: Cancer Research (2024)

Abstract Recently discovered epigenetic modification lysine lactylation contributes to tumor development and progression in several types of cancer. In addition to the tumor-intrinsic effects, histone lactylation may mediate tumor microenvironment remodeling and immune evasion. In this study, we observed elevated pan–lysine lactylation and histone H3 lysine 18 lactylation (H3K18la) levels in non–small cell lung cancer (NSCLC) tissues, which was positively correlated with poor patient prognosis. Interruption of glycolysis by 2-deoxy-D-glucose and oxamate treatment and silencing of lactate dehydrogenase A and lactate dehydrogenase B reduced H3K18la levels and circumvented immune evasion of NSCLC cells by enhancing CD8+ T-cell cytotoxicity. Mechanistically, H3K18la directly activated the transcription of pore membrane protein 121 (POM121), which enhanced MYC nuclear transport and direct binding to the CD274 promoter to induce PD-L1 expression. In a mouse NSCLC xenograft model, combination therapy with a glycolysis inhibitor and an anti-PD-1 antibody induced intratumoral CD8+ T-cell function and exhibited strong antitumor efficacy. Overall, this work revealed that H3K18la potentiates the immune escape of NSCLC cells by activating the POM121/MYC/PD-L1 pathway, which offers insights into the role of posttranslational modifications in carcinogenesis and provides a rationale for developing an epigenetic-targeted strategy for treating NSCLC. Significance: H3K18 lactylation supports immunosuppression in non-small cell lung cancer by inducing POM121 to increase MYC activity and PD-L1 expression, which can be reversed by metabolic reprogramming and immunotherapy treatment.
Targeting BCL2 with Venetoclax Enhances the Efficacy of the KRASG12D Inhibitor MRTX1133 in Pancreatic Cancer
Authors: Jeffrey H. Becker, Anastasia E. Metropulos, Christina Spaulding, Alejandra M. Marinelarena, Mario A. Shields, Daniel R. Principe, Thao D. Pham, Hidayatullah G. Munshi
Journal: Cancer Research (2024)

Abstract MRTX1133 is currently being evaluated in patients with pancreatic ductal adenocarcinoma (PDAC) tumors harboring a KRASG12D mutation. Combination strategies have the potential to enhance the efficacy of MRTX1133 to further promote cell death and tumor regression. In this study, we demonstrated that MRTX1133 increased the levels of the proapoptotic protein BIM in PDAC cells and conferred sensitivity to the FDA-approved BCL2 inhibitor venetoclax. Combined treatment with MRTX1133 and venetoclax resulted in cell death and growth suppression in 3D cultures. BIM was required for apoptosis induced by the combination treatment. Consistently, BIM was induced in tumors treated with MRTX1133, and venetoclax enhanced the efficacy of MRTX1133 in vivo. Venetoclax could also resensitize MRTX1133-resistant PDAC cells to MRTX1133 in 3D cultures, and tumors established from resistant cells responded to the combination of MRTX1133 and venetoclax. These results provide a rationale for the clinical testing of MRTX1133 and venetoclax in patients with PDAC. Significance: The combination of MRTX1133 and the FDA-approved drug venetoclax promotes cancer cell death and tumor regression in pancreatic ductal adenocarcinoma, providing rationale for testing venetoclax with KRASG12D inhibitors in patients with pancreatic cancer.