tbuckley/cabot-search huggingface dataset:
Trem2-expressing multinucleated giant macrophages are a biomarker of good prognosis in head and neck squamous cell carcinoma
Authors: Grégoire Gessain, Ahmed-Amine Anzali, Marvin Lerousseau, Kevin Mulder, Mathilde Bied, Anne Auperin, Daniel Stockholm, Nicolas Signolle, Farah Sassi, Maria Eugenia Marques Da Costa, Antonin Marchais, Alexandre Sayadi, Daniela Weidner, Stefan Uderhardt, Quentin Blampey, Sumanth Reddy Nakkireddy, Sophie Broutin, Charles-Antoine Dutertre, Pierre Busson, Thomas Walter, Alix Marhic, Antoine Moya-Plana, Johanne Guerlain, Ingrid Breuskin, Odile Casiraghi, Philippe Gorphe, Marion Classe, Jean-Yves Scoazec, Camille Blériot, Florent Ginhoux
Journal: Cancer Discovery (2024)

Abstract Patients with head and neck squamous cell carcinomas (HNSCC) often have poor outcomes due to suboptimal risk management and treatment strategies; yet integrating novel prognostic biomarkers into clinical practice is challenging. Here, we report the presence of multinucleated giant cells (MGC)—a type of macrophages—in tumors from patients with HNSCC, which are associated with a favorable prognosis in treatment-naive and preoperative chemotherapy–treated patients. Importantly, MGC density increased in tumors following preoperative therapy, suggesting a role of these cells in the antitumoral response. To enable clinical translation of MGC density as a prognostic marker, we developed a deep-learning model to automate its quantification on routinely stained pathological whole slide images. Finally, we used spatial transcriptomic and proteomic approaches to describe the MGC-related tumor microenvironment and observed an increase in central memory CD4 T cells. We defined an MGC-specific signature resembling to TREM2-expressing mononuclear tumor-associated macrophages, which colocalized in keratin tumor niches. Significance: Novel individual biomarkers are needed to guide therapeutic decisions for patients with head and neck cancer. We report for the first time, granulomas of TREM2-expressing multinucleated giant macrophages in keratin-rich tumor niches, as a biomarker of favorable prognosis and developed a deep-learning model to automate its quantification on routinely stained pathological slides.
Commentary on ‘Molecular characteristics of early-onset compared with late-onset colorectal cancer: a case–controlled study’
Authors: Nathnael A. Woldehana, Amogh Verma, Prakasini Satapathy, Rakesh K. Sharma, Mahalaqua N. Khatib, Sarvesh Rustagi, Endalkachew B. Melese
Journal: International Journal of Surgery (2024)
Commentary on ‘The role of coagulopathy and subdural hematoma thickness at admission in predicting the prognoses of patients with severe traumatic brain injury: a multicenter retrospective cohort study from China’
Authors: Yiacob T. Kibret, Abass O. Ajayi, Mahendra P. Singh, Mahalaqua N. Khatib, Quazi S. Zahiruddin, Sarvesh Rustagi, Ayush Anand
Journal: International Journal of Surgery (2024)
Environmental surveillance of a circulating vaccine-derived poliovirus type 2 outbreak in Israel between 2022 and 2023: a genomic epidemiology study
Authors: Neta S Zuckerman, Efrat Bucris, Hagar Morad-Eliyahu, Leah Weiss, Rinat Vasserman, Ilana S Fratty, Ira Aguvaev, Zvi Cohen-Said, Rua Matar, Oran Erster, Lester M Shulman, Ruth Yishai, Lior Hecht-Sagie, Sharon Alroy-Preis, Ella Mendelson, Yaniv Lustig, Danit Sofer, Itay Bar-Or, Merav Weil
Journal: The Lancet Microbe (2024)
Climate change and Trypanosoma cruzi transmission in North and central America
Authors: Colin Forsyth, Nelson Ivan Agudelo Higuita, Sarah A Hamer, Carlos N Ibarra-Cerdeña, Alba Valdez-Tah, Paula Stigler Granados, Gabriel L Hamer, Michael Vingiello, Norman L Beatty
Journal: The Lancet Microbe (2024)
A simplified approach to discriminate between healthy subjects and patients with heart failure using CMR myocardial deformation imaging
Authors: Undine Ella Witt, Maximilian Leo Müller, Rebecca Elisabeth Beyer, Johannes Wieditz, Susanna Salem, Djawid Hashemi, Wensu Chen, Mina Cvetkovic, Anna Clara Nolden, Patrick Doeblin, Moritz Blum, Gisela Thiede, Alexander Huppertz, Henning Steen, Bjoern Andrew Remppis, Volkmar Falk, Tim Friede, Sebastian Kelle
Journal:  (2024)

Abstract Aims Left ventricular global longitudinal strain (LV-GLS) shows promise as a marker to detect early heart failure (HF). This study sought to (i) establish cardiac magnetic resonance imaging (CMR)–derived LV-GLS cut-offs to differentiate healthy from HF for both acquisition-based and post-processing techniques, (ii) assess agreement, and (iii) provide a method to convert LV-GLS between both techniques. Methods and results A secondary analysis of a prospective study enrolling healthy subjects (n = 19) and HF patients (n = 56) was conducted. LV-GLS was measured using fast strain–encoded imaging (fSENC) and feature tracking (FT). Receiver operating characteristic (ROC) analyses were performed to derive and evaluate LV-GLS cut-offs discriminating between healthy, HF with mild deformation impairment (DI), and HF with severe DI. Linear regression and Bland–Altman analyses assessed agreement. Cut-offs discriminating between healthy and HF were identified at −19.3% and −15.1% for fSENC and FT, respectively. Cut-offs of −15.8% (fSENC) and −10.8% (FT) further distinguished mild from severe DI. No significant differences in area under ROC curve were identified between fSENC and FT. Bland–Altman analysis revealed a bias of −4.01%, 95% CI −4.42, −3.50 for FT, considering fSENC as reference. Linear regression suggested a factor of 0.76 to rescale fSENC-derived LV-GLS to FT. Using this factor on fSENC-derived cut-offs yielded rescaled FT LV-GLS cut-offs of −14.7% (healthy vs. HF) and −12% (mild vs. severe DI). Conclusion LV-GLS distinguishes healthy from HF with high accuracy. Each measurement technique requires distinct cut-offs, but rescaling factors facilitate conversion. An FT-based LV-GLS ≥ −15% simplifies HF detection in clinical routine.
Impact of abdominal drainage on outcomes after uncomplicated laparoscopic cholecystectomy: a comparative clinical study
Authors: Waseem Ahmed El Katib, Nasser Madhlom Meazher, Afrah Hasan Jaddoa, Abdul Rahman Kadhim Abdul Razaq, Alaa Jumaah Manji Nasrawi
Journal: GASTROENTEROLOGY (2024)

Background. The most common laparoscopic procedure worldwide is laparoscopic cholecystectomy (LC), which has become the gold standard in the treatment of symptomatic calculous and acalculous cholecystitis. However, there is still considerable disagreement about the effectiveness of regular drainage after LC in reducing postoperative morbidity. Materials and methods. This cross-sectional study was conducted on 200 randomly selected patients. Out of 200, 100 were chosen with a drain (group A) and 100 with no drain (group B). The same antibiotics were given to both groups postoperatively. Every patient has undergone LC using the standard four-port method. The post-surgical complications were noted and compared. Results. The results of this study showed that there was a statistically significant difference between group A and B in terms of length of hospital stay (P = 0.000), with group A length of stay being more extended. Nausea and vomiting were slightly more often in group A than in group B (P = 0.482, 0.153). Regarding abdominal pain, the distribution is as follows: 48.8 % in group A and 51.2 % in group B. For the moderate level of discomfort, it was recorded in 44.4 % of patients in group B and in 55.6 % of group A (P = 0.462). The current study also showed that using a drain significantly affected shoulder symptoms, which were more frequent in group B (P = 0.000). Regarding port site infection, there was no significant difference between two groups (P = 0.234). Finally, no patients developed deep vein thrombosis or postoperative ileus. Conclusions. In this study, there is no practical benefit from routine subhepatic drain insertion during laparoscopic cholecystectomy.
Recurrent variceal bleeding in alcoholic liver cirrhosis (a case report)
Authors: M.I. Tutchenko, D.V. Rudyk, S.A. Aslanian, S.L. Chub, M.S. Besedinskyi
Journal: GASTROENTEROLOGY (2024)

Alcoholic liver cirrhosis is widely known to doctors for its complications, including variceal bleeding from the esophagus and/or stomach. Recurrent variceal bleeding is considered a sign of decompensated portal hypertension. As fibrosis in the liver progresses, the gradient of portal pressure increases steadily, and each subsequent bleeding indicates a worsening survival prognosis. There are variety of measures available now to prevent upper gastrointestinal variceal bleeding. In the clinical case, the methods used to prevent repeated bleeding are described. Despite their use, numerous variceal bleedings were registered, which demonstrated the exceptional compensatory capabilities of the patient. In addition, long-term abstinence from the harmful factor, an alcohol, seems to be the most effective measure in this case.
Fedir Hlazunov — teacher and Latinist with a Ukrainian soul
Authors: M.P. Chaban, Z.I. Shevtsova, V.V. Gaponov
Journal: GASTROENTEROLOGY (2024)

The article considers the origin and education of candidate of theology Fedir Hlazunov. It highlights his teaching career in various religious and medical educational institutions. A special attention is paid to his collaboration with the historian and academician Dmytro Yavornytskyi, particularly in the scientific archival commission. The article also explores Hlazunov’s friendship with church historian Vasyl Bidnov and his family, as well as with the artist Mykola Pohribniak. It includes the memoirs of Oleksandra Serafimova (daughter of the enlightener Ivan Truba) about Fedir Hlazunov and his wife, Anastasiia Harkavtseva. The article brings attention to the revival of Fedir Hlazunov, a representative of pe­dagogical science in the Dnieper region, whose Ukrainian spirit had long been unjustly forgotten.
Transient elastography, ultrasound imaging and liver enzymes in diagnosis of cystic fibrosis-related liver disease in children
Authors: Yu.G. Tsyunchyk, I.M. Shevchenko, A.V. Tsyunchyk, G.F. Stepanov
Journal: GASTROENTEROLOGY (2024)

Background. Liver disease is responsible for relevant morbidity and mortality in children with cystic fibrosis. We aimed to assess the predictive value of a combination of transient elastography, ultrasound imaging and serum liver enzymes for diagnosis of cystic fibrosis-related liver disease. Materials and methods. A total of 108 children aged 0–17 years with cystic fibrosis were examined. The fibrosis stage was determined using transient elastography. The activity of enzymes (alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase-5), ultrasound parameters of the liver at different stages of liver fibrosis have been investigated. Results. Liver fibrosis of varying severity (F1-F4) was detected in 29.6 % of patients with cystic fibrosis. Liver cirrhosis was observed in 14.8 % of children with cystic fibrosis. The association between an elevated activity of alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase-5, an enlargement of the left lobe of the liver and the degree of fibrosis F1-F4 was found. Moreover, a significant increase in the size of the left lobe corresponded to a higher degree of fibrosis. A reverse correlation was detected between the k coefficient (the ratio of the sizes of the right and left lobes of the liver) and the degree of fibrosis, with a greater degree of fibrosis corresponding to a lower value of this parameter. The maximum enlargement of the left lobe of the liver, the lowest value of the k coefficient, and the dilation of the portal and splenic veins were observed in patients with liver cirrhosis. Conclusions. The transient elastography, changing of ultrasound liver parameters with elevated activity of the alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase-5 could be used for early diagnosis of cystic fibrosis-related liver disease.
Muramyl peptide blend ameliorates intestinal inflammation and barrier integrity in cell culture model
Authors: D.M. Masiuk, V.S. Nedzvetsky
Journal: GASTROENTEROLOGY (2024)

Background. The intestinal barrier is a crucial structure for maintaining the balance in permeability of digested food and restriction of microbial invasion from internal environment. Imbalance in these functions closely related to the initiation of intestinal epithelium reactivity and inflammation. Inflammation is the most common cause of intestinal dysfunction. Muramyl peptides (MPs) are small signaling molecules which stimulate intracellular receptors of pathogens and are potent regulators of cell response. However, molecular mechanisms of MP effect on intestinal cells remain unknown. The study of MP application to maintain viability of Caco-2 cells was aimed to explore the cytoprotective effect of MP-based probiotic on gut inflammation and intestinal barrier integrity. Materials and methods. Caco-2 cells were treated with 10–100 µg/ml lipopolysaccharide (LPS), 5–50 µg/ml MPs and combination of LPS + MPs. Cell viability was measured with MTT assay. Occludin content was detected with Western blotting. Enzyme-linked immunosorbent assay was applied to assess interleukin-8 (IL-8) production. Results. Obtained results have shown that LPS treatment with doses of 10–100 µg/ml induced in a decrease in cell viability and occludin content. On the contrary, IL-8 content was increased in LPS treatment that evidence the dose-dependent proinflammatory changes in Caco-2 cells. No significant changes were detected in the cells exposed to 5–50 µg/ml doses of MPs. However, application of 50 µg/ml of MPs inhibited IL-8 upregulation in LPS-exposed cells. Besides, MPs exhibited a dose-dependent cytoprotective effect in respect to cell viability at a dose of 20 and 50 µg/ml. Furthermore, MP dose of 50 µg/ml helped restore occludin content in LPS-exposed cells. Conclusions. Taking into the account that occludin is one of major components of tight junctions, MPs can restore epithelial barrier integrity in compromised gut. Observed results demonstrated that MPs is a promising agent in inflammation-induced intestinal injury and maintaining gut barrier function.
Disparity landscapes of viral-induced structural variations in hepatocellular carcinoma: Mechanistic characterization and functional implications
Authors: Xueying Lyu, Karen Man-Fong Sze, Joyce Man-Fong Lee, Abdullah Husain, Lu Tian, Sandrine Imbeaud, Jessica Zucman-Rossi, Irene Oi-Lin Ng, Daniel Wai-Hung Ho
Journal: Hepatology (2024)

Background and Aims: HCC is the most common type of primary liver cancer and is a common malignancy worldwide. About half of all new liver cancers worldwide each year occur in China, including Hong Kong, due to a high prevalence of HBV infection. HBV DNA integrates into the human genome, disrupting the endogenous tumor suppressors/regulatory genes or enhancing the activity of proto-oncogenes. It would be useful to examine the different NGS-based databases to provide a more unbiased and comprehensive survey of HBV integration. Approach and Results: We aimed to take advantage of publicly available data sets of different regional cohorts to determine the disparity landscapes of integration events among sample cohorts, tissue types, chromosomal positions, individual host, and viral genes, as well as genic locations. By comparing HCC tumors with non tumorous livers, the landscape of HBV integration was delineated in gene-independent and gene-dependent manners. Moreover, we performed mechanistic investigations on how HBV-TERT integration led to TERT activation and derived a score to predict patients’ prognostication according to their clonal disparity landscape of HBV integration. Conclusions: Our study uncovered the different levels of clonal enrichment of HBV integration and identified mechanistic insights and prognostic biomarkers. This strengthens our understanding of HBV-associated hepatocarcinogenesis.
Features of the claudin 1 and 7 expression in the mucous membrane of the large intestine in symptomatic uncomplicated diverticular disease and acute uncomplicated diverticulitis
Authors: H.A. Dorohavtseva, A.E. Dorofieiev, O.O. Dyadyk, M.S. Myroshnychenko, V.O. Bibichenko
Journal: GASTROENTEROLOGY (2024)

Background. Diverticular disease is one of the most common gastrointestinal pathologies, which mainly damages the large intestine and is manifested morphologically by the formation of sac-like protrusions (diverticula) of the intestinal wall. Today, the etiopathogenesis of diverticular disease remains debatable and needs to be fully understood. Changes in the claudin expression in the colonic mucosa and, accordingly, their structural instability may play a certain role in the development of both diverticular disease and its complications. The study aimed to determine the features of claudin 1 and 7 expression in the colonic mucosa of patients with symptomatic uncomplicated diverticular disease (SUDD) and acute uncomplicated diverticulitis (AUD). Materials and methods. Fragments of the colonic mucosa of 12 individuals without gastrointestinal pathology (group 1), biopsies of the colo­nic mucosa from the diverticular orifice of 34 patients with SUDD (group 2) and 26 patients with AUD (group 3) were analyzed. An immunohistochemical study used rabbit polyclonal antibodies to claudins 1 and 7. The PAST program was applied to process digi­tal indicators. The average indicators in groups were compared using the Student’s t-test and Mann-Whitney U-test. Results. A comprehensive morphological study revealed a decrease in the expression of claudins 1 and 7 in the colonic mucosa of patients with SUDD and AUD, more pronounced in those with AUD. In the large intestine mucosa of people without gastrointestinal pathology and patients with SUDD and AUD, firstly, the content of claudins 1 and 7 was higher in the surface epithelium compared to the epithelium of the intestinal glands, secondly, the content of claudin 1 predominated over claudin 7 content. Conclusions. The detected changes in claudin 1 and 7 expression in the colonic mucosa biopsies may underlie the development of diverticular disease and its complications.
Post-translational histone modifications associated with the development of metabolic dysfunction-associated fatty liver disease. Part 1. General provisions
Authors: O.E. Abaturov, A.O. Nikulina
Journal: GASTROENTEROLOGY (2024)

Based on the analysis of literary sources of PubMed, MedLine, The Cochrane Library, EMBASE database, the authors of the article give general provisions regarding post-translational modifications of histones (small proteins with a molecular weight of 10–15 kDa, which make up the largest part of nuclear proteins), which are associated with the development of metabolic dysfunction-associated fatty liver disease. The authors emphasize that post-translational histone modifications regulate the activity of gene expression, and each of these types differently changes the structure of chromatin and, as a result, gene expression. Currently, more than 20 types of histone protein modifications have been identified (acetylation, biotinylation, butyrylation, 2-hydroxybutyrylation, ADP-ribosylation, N-formylation, hydroxylation, glycosylation, glutarylation, dopaminylation, proline isomerization and aspartic acid carbonylation, crotonylation, lactylation, malonylation, methylation, propionylation, succinylation, SUMOylation, ubiquitination, phosphorylation, citrullination). Epigenetic and epitranscriptomic changes are induced by lifestyle, especially the nature of diet and physical activity, by the influence of exogenous and endogenous factors. Prolonged epigenetic changes that determine the expression of target genes can be accompanied by the development of metabolic disorders and the progression of metabolic dysfunction-associated fatty liver disease. Histone modification is carried out by site-specific enzymes: writers, which identify a marker, and erasers, which “erase” a marker. Post-translational histone modifications change the local physicochemical environment and, based on this, directly affect the structure of the nucleosome and chromatin. Also, post-translational modifications of the N- and C-terminal tails of histone proteins act as “docking sites” that recruit specific molecular readers. Readers of histone modifications can act both in the intranucleosomal space, modifying adjacent histone sites or recruiting transcription factors, transcription activators and repressors, and in the internucleosomal space. The authors also describe the pathophysiological significance of post-translational histone modifications in the development of metabolic dysfunction-associated fatty liver disease, the diagnostic value of epigenetic biomarkers, and the potential of pharmacological management of histone modifications to achieve inhibition of the activity of the pathological process.
Expansion of tumor-reactive CD8 <sup>+</sup> T cell clonotypes occurs in the spleen in response to immune checkpoint blockade
Authors: Duncan M. Morgan, Brendan L. Horton, Vidit Bhandarkar, Richard Van, Teresa Dinter, Maria Zagorulya, J. Christopher Love, Stefani Spranger
Journal: Science Immunology (2024)

Immune checkpoint blockade (ICB) enhances T cell responses against cancer, leading to long-term survival in a fraction of patients. CD8 + T cell differentiation in response to chronic antigen stimulation is highly complex, and it remains unclear precisely which T cell differentiation states at which anatomic sites are critical for the response to ICB. We identified an intermediate-exhausted population in the white pulp of the spleen that underwent substantial expansion in response to ICB and gave rise to tumor-infiltrating clonotypes. Increased systemic antigen redirected differentiation of this population toward a more circulatory exhausted KLR state, whereas a lack of cross-presented tumor antigen reduced its differentiation in the spleen. An analogous population of exhausted KLR CD8 + T cells in human blood samples exhibited diminished tumor-trafficking ability. Collectively, our data demonstrate the critical role of antigen density within the spleen for the differentiation and expansion of T cell clonotypes in response to ICB.
CD4 <sup>+</sup> T cells with convergent TCR recombination reprogram stroma and halt tumor progression in adoptive therapy
Authors: Steven P. Wolf, Matthias Leisegang, Madeline Steiner, Veronika Wallace, Kazuma Kiyotani, Yifei Hu, Leonie Rosenberger, Jun Huang, Karin Schreiber, Yusuke Nakamura, Andrea Schietinger, Hans Schreiber
Journal: Science Immunology (2024)

Cancers eventually kill hosts even when infiltrated by cancer-specific T cells. We examined whether cancer-specific T cell receptors of CD4