tbuckley/cabot-search huggingface dataset:
Patients with stage IV colorectal carcinoma selected for palliative primary tumor resection and systemic therapy survive longer compared with systemic therapy alone – A retrospective comparative cohort study
Authors: Rene Mantke, Constanze Schneider, Anne von Ruesten, Michael Hauptmann
Journal: International Journal of Surgery (2024)

Objective: To compare the survival of palliative stage IV colorectal cancer patients selected for primary tumor resection and systemic treatment (PTR+SYST) to patients with systemic treatment only (SYST). Background: About 20–25% of all colorectal cancer patients are diagnosed with stage IV disease. The benefit of primary tumor resection in the palliative situation is therefore of high concern. However, empirical evidence from randomized and observational studies is inconsistent. Methods: Mortality after PTR+SYST was compared to systemic treatment alone in a retrospective observational cohort of patients diagnosed 2012–2020 from the cancer registry in the federal state of Brandenburg (Germany), excluding patients with rectal cancer of the lower two-thirds, emergency procedures, unknown ECOG status, ECOG greater than 2, unknown metastatic status or unclear grading. Results: Of 480 patients, 416 died during an average follow-up of 23 months in mean. Twelve-month survival was 75% after PTR+SYST compared with 49% after SYST [hazard ratio (HR)=0.39, 95% CI 0.29–0.53, P &lt;0.001]. The difference persisted to 36 months (28% vs. 13%, HR=0.53, 95% CI 0.43–0.66, P &lt;0.001). Results were similar after multivariate adjustment, propensity score matching and delayed entry. Conclusion and relevance: Patients with stage IV colorectal carcinoma who are selected for primary tumor resection in combination with systemic therapy and who receive such treatment survive longer compared with patients who receive only systemic treatment. Whether the difference is due to the selection of patients or PTR remains unclear. At present, the current practice of selecting patients for PTR appears to do no harm.
Epidemiologic and survival analysis of malignant peripheral nerve sheath tumors: a retrospective cohort study
Authors: Jingxuan Huang, Haoting Shi, Lingling Ge, Beiyao Zhu, Jun Liu, Xue Wang, Zheshen Han, Qingfeng Li, Zhichao Wang
Journal: International Journal of Surgery (2024)

Huang, Jingxuan MD; Shi, Haoting MD; Ge, Lingling MD; Zhu, Beiyao MD; Liu, Jun MD; Wang, Xue; Han, Zheshen PhD; Li, Qingfeng MD; Wang, Zhichao MD Author Information
The microbiota and the host organism switch between cooperation and competition based on dietary iron levels
Authors: Marie-Louise Noordine, Yohannes Seyoum, Aurélia Bruneau, Kaleab Baye, Thibaud Lefebvre, Claire Cherbuy, François Canonne-Hergaux, Gaël Nicolas, Christèle Humblot, Muriel Thomas
Journal: Gut Microbes (2024)

The microbiota significantly impacts digestive epithelium functionality, especially in nutrient processing. Given the importance of iron for both the host and the microbiota, we hypothesized that host-microbiota interactions fluctuate with dietary iron levels. We compared germ-free (GF) and conventional mice (SPF) fed iron-containing (65 mg/Kg) or iron-depleted (<6 mg/Kg) diets. The efficacy of iron privation was validated by iron blood parameters. Ferritin and Dmt1, which represent cellular iron storage and transport respectively, were studied in tissues where they are abundant: the duodenum, liver and lung. When the mice were fed an iron-rich diet, the microbiota increased blood hemoglobin and hepcidin and the intestinal ferritin levels, suggesting that the microbiota helps iron storage. When iron was limiting, the microbiota inhibited the expression of the intestinal Dmt1 transporter, likely via the pathway triggered by Hif-2α. The microbiota assists the host in storing intestinal iron when it is abundant and competes with the host by inhibiting Dmt1 in conditions of iron scarcity. Comparison between duodenum, liver and lung indicates organ-specific responses to microbiota and iron availability. Iron depletion induced temporal changes in microbiota composition and activity, reduced α-diversity of microbiota, and led to
Harnessing Bacterial Membrane Components for Tumor Vaccines: Strategies and Perspectives
Authors: Zhenxin Bai, Xuanyu Wang, Tianming Liang, Guangyu Xu, Jinzhou Cai, Wei Xu, Kai Yang, Lin Hu, Pei Pei
Journal: Advanced Healthcare Materials (2024)

Tumor vaccines stand at the vanguard of tumor immunotherapy, demonstrating significant potential and promise in recent years. While tumor vaccines have achieved breakthroughs in the treatment of cancer, they still encounter numerous challenges, including improving the immunogenicity of vaccines and expanding the scope of vaccine application. As natural immune activators, bacterial components offer inherent advantages in tumor vaccines. Bacterial membrane components, with their safer profile, easy extraction, purification, and engineering, along with their diverse array of immune components, activate the immune system and improve tumor vaccine efficacy. This review systematically summarizes the mechanism of action and therapeutic effects of bacterial membranes and its derivatives (including bacterial membrane vesicles and hybrid membrane biomaterials) in tumor vaccines. Subsequently, the authors delve into the preparation and advantages of tumor vaccines based on bacterial membranes and hybrid membrane biomaterials. Following this, the immune effects of tumor vaccines based on bacterial outer membrane vesicles are elucidated, and their mechanisms are explained. Moreover, their advantages in tumor combination therapy are analyzed. Last, the challenges and trends in this field are discussed. This comprehensive analysis aims to offer a more informed reference and scientific foundation for the design and implementation of bacterial membrane-based tumor vaccines.
Restricted intake of sulfur-containing amino acids reversed the hepatic injury induced by excess <i>Desulfovibrio</i> through gut–liver axis
Authors: Lingxi Zhou, Gexue Lu, Yawen Nie, Yilin Ren, Jin-Song Shi, Yuzheng Xue, Zheng-Hong Xu, Yan Geng
Journal: Gut Microbes (2024)

Diet is a key player in gut–liver axis. However, the effect of different dietary patterns on gut microbiota and liver functions remains unclear. Here, we used rodent standard chow and purified diet to mimic two common human dietary patterns: grain and plant-based diet and refined-food-based diet, respectively and explored their impacts on gut microbiota and liver. Gut microbiota experienced a great shift with notable increase in Desulfovibrio, gut bile acid (BA) levels elevated significantly, and liver inflammation was observed in mice fed with the purified diet. Liver inflammation and elevated gut BA levels also occurred in mice fed with the chow diet after receiving Desulfovibrio desulfuricans ATCC 29,577 (DSV). Restriction of sulfur-containing amino acids (SAAs) prevented liver injury mainly through higher hepatic antioxidant and detoxifying ability and reversed the elevated BA levels due to excess Desulfovibrio. Ex vivo fermentation of human fecal microbiota with primary BAs demonstrated that DSV enhanced production of secondary BAs. Higher concentration of both primary and secondary BAs were found in the gut of germ-free mice after receiving DSV. In conclusion, Restriction of SAAs in diet may become an effective dietary intervention to prevent liver injury associated with excess Desulfovibrio in the gut.
The Effects of Biomimetic Surface Topography on Vascular Cells: Implications for Vascular Conduits
Authors: Abigail A. Conner, Dency David, Evelyn K.F. Yim
Journal: Advanced Healthcare Materials (2024)

Abstract Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide and represent a pressing clinical need. Vascular occlusions are the predominant cause of CVD and necessitate surgical interventions such as bypass graft surgery to replace the damaged or obstructed blood vessel with a synthetic conduit. Synthetic small‐diameter vascular grafts (sSDVGs) are desired to bypass blood vessels with an inner diameter &lt;6 mm yet have limited use due to unacceptable patency rates. The incorporation of biophysical cues such as topography onto the sSDVG biointerface can be used to mimic the cellular microenvironment and improve outcomes. In this review, the utility of surface topography in sSDVG design is discussed. First, the primary challenges that sSDVGs face and the rationale for utilizing biomimetic topography are introduced. The current literature surrounding the effects of topographical cues on vascular cell behavior in vitro is reviewed, providing insight into which features are optimal for application in sSDVGs. The results of studies that have utilized topographically‐enhanced sSDVGs in vivo are evaluated. Current challenges and barriers to clinical translation are discussed. Based on the wealth of evidence detailed here, substrate topography offers enormous potential to improve the outcome of sSDVGs and provide therapeutic solutions for CVDs.
Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab for Stage I Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: 5-Year Results and Correlative Analyses From ATEMPT
Authors: Paolo Tarantino, Nabihah Tayob, Guillermo Villacampa, Chau Dang, Denise A. Yardley, Steven J. Isakoff, Vicente Valero, Meredith Faggen, Therese Mulvey, Ron Bose, Douglas Weckstein, Antonio C. Wolff, Katherine Reeder-Hayes, Hope S. Rugo, Bhuvaneswari Ramaswamy, Dan Zuckerman, Lowell Hart, Vijayakrishna K. Gadi, Michael Constantine, Kit Cheng, Audrey Merrill Garrett, P. Kelly Marcom, Kathy Albain, Patricia DeFusco, Nadine Tung, Blair Ardman, Rita Nanda, Rachel C. Jankowitz, Mothaffar Rimawi, Vandana Abramson, Paula R. Pohlmann, Catherine Van Poznak, Andres Forero-Torres, Minetta C. Liu, Kathryn J. Ruddy, Adrienne G. Waks, Michelle DeMeo, Harold J. Burstein, Ann H. Partridge, Patrizia Dell'Orto, Leila Russo, Emma Krause, Daniel J. Newhouse, Busem Binboğa Kurt, Elizabeth A. Mittendorf, Bryan Schneider, Aleix Prat, Eric P. Winer, Ian E. Krop, Sara M. Tolaney, Romualdo Barroso-Sousa, Giuseppe Curigliano, Molly DiLullo, Winnie Hui, Christian Kirkup, Giuseppe Viale, Yue Zheng
Journal: Journal of Clinical Oncology (2024)

Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need.
Sleep-disordered breathing in children and adults with intellectual disability: mind the gap!
Authors: Renata L Riha, Ankur Singh, Elizabeth A Hill, Hazel Evans, David O'Regan
Journal: Thorax (2024)

Background In adults and children with intellectual disability (ID), sleep -disordered breathing (SDB) is thought to be common. However, large epidemiological studies are lacking, and there are few studies on optimal methods of investigation and even fewer randomised, controlled intervention trials of treatment. Method Peer-reviewed publications from various databases were examined in line with search terms relevant to ID and SDB spanning the years 200-2024. Results Findings suggest that, due to comorbid conditions, children and adults with ID may experience both an increased risk of SDB, as well as lower frequency of diagnosis. SDB can compromise the emotional, physical and mental health of individuals with ID. Appropriate treatment when tolerated leads to an improvement in health and well-being and several studies emphasized the importance of consistent follow-up of people with ID - something that is not universally occurring during childhood, in the transition to adulthood and during adulthood itself. As the most frequently occurring form of ID worldwide, we use Down syndrome as a specific example of how diagnosing and treating SDB can lead to improved outcomes. Conclusions This review highlights the importance of identifying SDB in this heterogenous population, recognising the multi-faceted, deleterious consequences of untreated SDB in people with ID, and presents some strategies that can be harnessed to improve diagnosis and management. Until further ID-specific research is available, we urge flexibility in the approach to people with ID and SDB based in guidelines and standard practice developed for the typically developing population.
Dysanapsis Genetic Risk Predicts Lung Function Across the Lifespan
Authors: Catherine L. Debban, Amirthagowri Ambalavanan, Auyon Ghosh, Zhonglin Li, Kristina L. Buschur, Yanlin Ma, Elizabeth George, Carrie Pistenmaa, Alain G. Bertoni, Elizabeth C. Oelsner, Erin D Michos, Theo J Moraes, David R. Jacobs, Stephanie Christenson, Surya P Bhatt, Robert J Kaner, Elinor Simons, Stuart E Turvey, Motahareh Vameghestahbanati, James C Engert, Miranda Kirby, Jean Bourbeau, Wan C Tan, Stacey B Gabriel, Namrata Gupta, Prescott G. Woodruff, Padmaja Subbarao, Victor E. Ortega, Eugene R. Bleecker, Deborah A. Meyers, Stephen S. Rich, Eric A. Hoffman, R. Graham Barr, Michael H Cho, Yohan Bossé, Qingling Duan, Ani Manichaikul, Benjamin M. Smith
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale Dysanapsis refers to a mismatch between airway tree caliber and lung size arising early in life. Dysanapsis assessed by computed tomography (CT) is evident by early adulthood and associated with chronic obstructive pulmonary disease (COPD) risk later in life. Objective By examining the genetic factors associated with CT-assessed dysanapsis, we aimed to elucidate its molecular underpinnings and physiological significance across the lifespan. Methods We performed a genome-wide association study (GWAS) of CT-assessed dysanapsis in 11,951 adults, including individuals from two population-based and two COPD-enriched studies. We applied colocalization analysis to integrate GWAS and gene expression data from whole blood and lung. Genetic variants associated with dysanapsis were combined into a genetic risk score that was applied to examine association with lung function in children from a population-based birth cohort (n=1,278) and adults from the UK Biobank (n=369,157). Measurements and Main Results CT-assessed dysanapsis was associated with genetic variants from 21 independent signals in 19 gene regions, implicating
Long-term impact of ivacaftor on mortality rate and health outcomes in people with cystic fibrosis
Authors: Christian A Merlo, Teja Thorat, Maral DerSarkissian, Lisa J McGarry, Catherine Nguyen, Yuqian M Gu, Joe Healy, Jaime L Rubin, M Alan Brookhart
Journal: Thorax (2024)

Background Ivacaftor (IVA) has been shown to improve lung function and other clinical outcomes in people with cystic fibrosis (CF). A decade of real-world IVA availability has enabled the examination of long-term outcomes with this treatment. This retrospective, longitudinal cohort study investigated the impact of IVA on mortality rate and health outcomes among people with CF in the US. Methods Data from the US CF Foundation Patient Registry from January 2010 to December 2019 were analysed. The IVA-treated cohort included people with a CF transmembrane conductance regulator ( CFTR ) gating mutation (excluding R117H ); age-matched comparator cohort included people with a F508del and a minimal function CFTR mutation who had no prior CFTR modulator treatment. Baseline characteristics were balanced between cohorts using standardised mortality ratio weighting generated from propensity scores. Outcomes of interest were overall survival, lung transplant, percent predicted forced expiratory volume in 1 s (ppFEV 1 ), body mass index (BMI), pulmonary exacerbations (PEx), outpatient visits and hospitalisations. Findings Over a maximum follow-up of 7.9 years, the IVA-treated cohort (N=736) had lower rates of mortality (hazard ratio [HR] (95% CI): 0.22 (0.09 to 0.45)), lung transplant (HR: 0.11 (95% CI 0.02 to 0.28)), PEx (rate ratio: 0.49 (95% CI 0.42 to 0.55)) and all-cause hospitalisations (rate ratio: 0.50 (95% CI 0.43 to 0.56)) as well as better lung function (mean difference in ppFEV 1 : 8.46 (95% CI 7.34 to 9.75)) and higher BMI/BMI z -scores (mean difference 1.20 (95% CI 0.92 to 1.71) kg/m 2 and 0.27 (95% CI 0.25 to 0.40), respectively) than the comparator cohort (N=733). Interpretation Our analysis suggests that IVA provides sustained clinical benefits in people with CF over a follow-up period of approximately 8 years. These findings reinforce the existing real-world evidence that IVA can slow disease progression and decrease the healthcare burden of CF over the long term.
Lung Transcriptomics Links Emphysema to Barrier Dysfunction and Macrophage Subpopulations
Authors: Robin Lu, Andrew Gregory, Rahul Suryadevara, Zhonghui Xu, Dhawal Jain, Jarrett D Morrow, Brian D Hobbs, Jeong H Yun, Noah Lichtblau, Robert Chase, Jeffrey L. Curtis, Maor Sauler, Brian J. Bartholmai, Edwin K. Silverman, Craig P. Hersh, Peter J Castaldi, Adel Boueiz
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale: While many studies have examined gene expression in lung tissue, the gene regulatory processes underlying emphysema are still not well understood. Finding efficient non-imaging screening methods and disease-modifying therapies has been challenging, but knowledge of the transcriptomic features of emphysema may help in this effort. Objectives: Our goals were to identify emphysema-associated biological pathways through transcriptomic analysis of bulk lung tissue, to determine the lung cell types in which these emphysema-associated pathways are altered, and to detect unique and overlapping transcriptomic signatures in blood and lung samples. Methods: Using RNA-sequencing data from 446 samples in the Lung Tissue Research Consortium (LTRC) and 3,606 blood samples from the COPDGene study, we examined the transcriptomic features of chest computed tomography-quantified emphysema. We also leveraged publicly available lung single-cell RNA-sequencing data to identify cell types showing COPD-associated differential expression of the emphysema pathways found in the bulk analyses. Measurements and Main Results: In the bulk lung RNA-seq analysis, 1,087 differentially expressed genes and 34 dysregulated pathways were significantly associated with emphysema. We observed alternative splicing of several genes and increased activity in pluripotency and cell barrier function pathways. Lung tissue and blood samples shared differentially expressed genes and biological pathways. Multiple lung cell types displayed dysregulation of epithelial barrier function pathways, and distinct pathway activities were observed among various macrophage subpopulations. Conclusions: This study identified emphysema-related changes in gene expression and alternative splicing, cell-type specific dysregulated pathways, and instances of shared pathway dysregulation between blood and lung.
Deep learning to quantify care manipulation activities in neonatal intensive care units
Authors: Abrar Majeedi, Ryan M. McAdams, Ravneet Kaur, Shubham Gupta, Harpreet Singh, Yin Li
Journal: npj Digital Medicine (2024)

Abstract Early-life exposure to stress results in significantly increased risk of neurodevelopmental impairments with potential long-term effects into childhood and even adulthood. As a crucial step towards monitoring neonatal stress in neonatal intensive care units (NICUs), our study aims to quantify the duration, frequency, and physiological responses of care manipulation activities, based on bedside videos and physiological signals. Leveraging 289 h of video recordings and physiological data within 330 sessions collected from 27 neonates in 2 NICUs, we develop and evaluate a deep learning method to detect manipulation activities from the video, to estimate their duration and frequency, and to further integrate physiological signals for assessing their responses. With a 13.8% relative error tolerance for activity duration and frequency, our results were statistically equivalent to human annotations. Further, our method proved effective for estimating short-term physiological responses, for detecting activities with marked physiological deviations, and for quantifying the neonatal infant stressor scale scores.
DDX41 haploinsufficiency causes inefficient hematopoiesis under stress and cooperates with p53 mutations to cause hematologic malignancy
Authors: Emily Stepanchick, Andrew Wilson, Analise M. Sulentic, Kwangmin Choi, Kathleen Hueneman, Daniel T. Starczynowski, Timothy M. Chlon
Journal: Leukemia (2024)

Germline heterozygous mutations in DDX41 predispose individuals to hematologic malignancies in adulthood. Most of these DDX41 mutations result in a truncated protein, leading to loss of protein function. To investigate the impact of these mutations on hematopoiesis, we generated mice with hematopoietic-specific knockout of one Ddx41 allele. Under normal steady-state conditions, there was minimal effect on lifelong hematopoiesis, resulting in a mild yet persistent reduction in red blood cell counts. However, stress induced by transplantation of the Ddx41+/- BM resulted in hematopoietic stem/progenitor cell (HSPC) defects and onset of hematopoietic failure upon aging. Transcriptomic analysis of HSPC subsets from the transplanted BM revealed activation of cellular stress responses, including upregulation of p53 target genes in erythroid progenitors. To understand how the loss of p53 affects the phenotype of Ddx41+/- HSPCs, we generated mice with combined Ddx41 and Trp53 heterozygous deletions. The reduction in p53 expression rescued the fitness defects in HSPC caused by Ddx41 heterozygosity. However, the combined Ddx41 and Trp53 mutant mice were prone to developing hematologic malignancies that resemble human myelodysplastic syndrome and acute myeloid leukemia. In conclusion, DDX41 heterozygosity causes dysregulation of the response to hematopoietic stress, which increases the risk of transformation with a p53 mutation.
Uncertainty-aware multiple-instance learning for reliable classification: Application to optical coherence tomography
Authors: Coen de Vente, Bram van Ginneken, Carel B. Hoyng, Caroline C.W. Klaver, Clara I. Sánchez
Journal: Medical Image Analysis (2024)

Deep learning classification models for medical image analysis often perform well on data from scanners that were used to acquire the training data. However, when these models are applied to data from different vendors, their performance tends to drop substantially. Artifacts that only occur within scans from specific scanners are major causes of this poor generalizability. We aimed to enhance the reliability of deep learning classification models using a novel method called Uncertainty-Based Instance eXclusion (UBIX). UBIX is an inference-time module that can be employed in multiple-instance learning (MIL) settings. MIL is a paradigm in which instances (generally crops or slices) of a bag (generally an image) contribute towards a bag-level output. Instead of assuming equal contribution of all instances to the bag-level output, UBIX detects instances corrupted due to local artifacts on-the-fly using uncertainty estimation, reducing or fully ignoring their contributions before MIL pooling. In our experiments, instances are 2D slices and bags are volumetric images, but alternative definitions are also possible. Although UBIX is generally applicable to diverse classification tasks, we focused on the staging of age-related macular degeneration in optical coherence tomography. Our models were trained on data from a single scanner and tested on external datasets from different vendors, which included vendor-specific artifacts. UBIX showed reliable behavior, with a slight decrease in performance (a decrease of the quadratic weighted kappa (κ