bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laparoscopic surgery for the diagnosis of abdominal effusion in the modern era of imaging – a retrospective study in a low-to-middle-income country
Authors: Quoc Ai Dang , Thi Thuy Hang Ha , Que Son Tran 
Published: April 2023

Introduction:
Intraperitoneal ascites is a consequence or combination of many different underlying diseases. Laparoscopy with peritoneal biopsy is a tool for rapid and accurate diagnosis.

Methods:
We retrospectively identified patients who could not be diagnosed by clinical examination, laboratory investigations, and imaging tests.

Results:
A total of 103 (55 male and 48 female) patients were selected. The median age of the study group was 54 years (range 38–64 years). Typical clinical symptoms included fever (58.2%), abdominal pain (56.3%), and digestive disorders (62.1%). Fever and digestive disorders were higher in the peritoneal tuberculosis (TB) group than in the metastatic cancer group [(62.1% vs. 12.5%, P=0.009) and (66.3% vs. 12.5%, P=0.004)]. Abdominal pain was more common in the metastatic cancer group than in the other groups (100% vs. 55.8%, P=0.020). Patients in the TB and chronic inflammation groups had lower red blood cell counts and blood albumin (41 vs. 42, P=0.039) than those in the metastatic cancer group, respectively. The rate of intestinal wall thickening on ultrasound and peritoneal thickening on computed tomography was higher in the cancer group than in the benign group (87.5% vs. 7.4%, P=0.000) (75% vs. 23.2%, P=0.005), respectively. There was no difference in the median peritoneal fluid volume between the two groups (390 vs. 340, P=0.058). Pathological results showed 88.3%, 7.8%, and 3.9% of peritoneal TB, metastatic cancer, and chronic inflammatory lesions, respectively. The median hospital stay did not differ between the two groups (4 vs. 3 days, P=0.051). Both groups of patients had no morbidity or mortality.

Conclusion:
Unidentified ascites and peritonitis must be difficult for making diagnose by conventional methods. Laparoscopy might be supportive of making a rapid diagnosis and starting early treatment.
TGF-β induces matrisome pathological alterations and EMT in patient-derived prostate cancer tumoroids
Authors: Fernandes Soraia , La Cruz Jorge Oliver-De , Cassani Marco , Morazzo Sofia , Ďuríková Helena , Caravella Alessio , Fiore Piergiuseppe , Azzato Giulia , De Marco Giuseppe , Lauria Agostino , Izzi Valerio , Bosáková Veronika , Fric Jan , Filipensky Petr , Forte Giancarlo 
Published: April 2023

AbstractExtracellular matrix (ECM) tumorigenic alterations resulting in high matrix deposition and stiffening are hallmarks of adenocarcinomas and are collectively defined asdesmoplasia. Here, we thoroughly analysed primary prostate cancer tissues obtained from numerous patients undergoing radical prostatectomy to highlight reproducible structural changes in the ECM leading to the loss of the glandular architecture. Starting from patient cells, we established prostate cancer tumoroids (PCTs) and demonstrated they require TGF-β signalling pathway activity to preserve phenotypical and structural similarities with the tissue of origin. By modulating TGF-β signalling pathway in PCTs, we unveiled its role in ECM accumulation and remodelling in prostate cancer. We also found that TGF-β-induced ECM remodelling is responsible for the initiation of prostate cell epithelial-to-mesenchymal transition (EMT) and the acquisition of a migratory, invasive phenotype. Our findings highlight the cooperative role of TGF-β signalling and ECMdesmoplasiain prompting prostate cell EMT and promoting tumour progression and dissemination
Spatio-temporal dynamics of the proton motive force on single bacterial cells
Authors: Biquet-Bisquert Anaïs , Carrio Baptiste , Meyer Nathan , Fernandes Thales F.D. , Abkarian Manouk , Seduk Farida , Magalon Axel , Nord Ashley L. , Pedaci Francesco 
Published: April 2023

AbstractElectrochemical gradients established across biological membranes are fundamental in the bioenergetics of all forms of life. In bacteria, the proton motive force (PMF), the electrochemical potential associated to protons, powers an impressive array of fundamental processes, from ATP production to motility. While far from equilibrium, it has classically been considered homeostatic in time and space. Yet, recent experiments have revealed rich temporal dynamics at the single cell level and functional spatial dynamics at the scale of multicellular communities. Lateral segregation of supramolecular respiratory complexes begs the question of whether spatial heterogeneity of the PMF exists even at the single cell level. By using a light-activated proton pump as a spatially and temporally modulatable source, and the bacterial flagellar motor as a local electro-mechanical gauge, we both perturb and probe the PMF on single cells. Using global perturbations, we resolve temporal dynamics on the ms time scale and observe an asymmetrical capacitive response of the cell. Using localized perturbations, we find that the PMF is rapidly homogenized along the entire cell, faster than proton diffusion can allow. Instead, the electrical response can be explained in terms of electrotonic potential spread, as found in passive neurons and described by cable theory. This implies a global coupling between PMF sources and consumers in the bacterial membrane, excluding a sustained spatial heterogeneity while allowing for fast temporal dynamics.SignificanceStoring energy in the form of a proton gradient across a membrane is a fundamental feature of living systems. In mitochondria, spatial compartmentalization separates electrically distinct regions. In bacteria, it is unclear how this energy reservoir, the proton motive force, behaves at the single cell level: can it be heterogeneous in space as in mitochondria? How fast can it change in time? Using a light-driven proton pump and the flagellar motor as a local electro-mechanical gauge, we find that the bacterial proton motive force can change in a few tens of milliseconds, and that it is instantaneously homogenized along the membrane. This electrophysiological response is surprisingly similar to electrotonic voltage spread in passive neurons.
Reconstruction Set Test (RESET): a computationally efficient method for single sample gene set testing based on randomized reduced rank reconstruction error
Authors: Frost H. Robert 
Published: April 2023

AbstractWe have developed a new, and analytically novel, single sample gene set testing method called Reconstruction Set Test (RESET). RESET quantifies gene set importance at both the sample-level and for the entire dataset based on the ability of set genes to reconstruct values for all measured genes. RESET addresses four important limitations of current techniques: 1) existing single sample methods are designed to detect mean differences and struggle to identify differential correlation patterns, 2) computationally efficient techniques are self-contained methods and cannot directly detect competitive scenarios where set genes differ from non-set genes in the same sample, 3) the scores generated by current methods can only be accurately compared across samples for a single set and not between sets, and 4) the computational performance of even the fastest existing methods be significant on very large datasets. RESET is realized using a computationally efficient randomized reduced rank reconstruction algorithm (available via the RESET R package on CRAN) that can effectively detect patterns of differential abundance and differential correlation for self-contained and competitive scenarios. As demonstrated using real and simulated scRNA-seq data, RESET provides superior accuracy at a lower computational cost relative to other single sample approaches.
Colorectal cancer detection and treatment with engineered probiotics
Authors: Gurbatri Candice R. , Radford Georgette , Vrbanac Laura , Coker Courtney , Im Jong-won , Taylor Samuel R. , Jang YoungUk , Sivan Ayelet , Rhee Kyu , Saleh Anas A. , Chien Tiffany , Zandkarimi Fereshteh , Lia Ioana , Lannagan Tamsin RM , Wang Tongtong , Wright Josephine A , Thomas Elaine , Kobayashi Hiroki , Ng Jia Q , Lawrence Matt , Sammour Tarik , Thomas Michelle , Lewis Mark , Papanicolas Lito , Perry Joanne , Fitzsimmons Tracy , Kaazan Patricia , Lim Amanda , Marker Julie , Ostroff Cheri , Rogers Geraint , Arpaia Nicholas , Worthley Daniel L , Woods Susan L , Danino Tal 
Published: April 2023

AbstractBioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment strategies. Here, we demonstrate the phenomenon of selective, long-term colonization of colorectal adenomas after oral delivery of probioticE. coliNissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition. We show that, after oral administration, adenomas can be monitored over time by recovering EcN from stool. We also demonstrate specific colonization of EcN to solitary neoplastic lesions in an orthotopic murine model of CRC. We then exploit this neoplasia-homing property of EcN to develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate, and demonstrate that oral delivery of this strain results in significantly increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. We also assess EcN engineered to locally release immunotherapeutics at the neoplastic site. Oral delivery to mice bearing adenomas, reduced adenoma burden by ∼50%, with notable differences in the spatial distribution of T cell populations within diseased and healthy intestinal tissue, suggesting local induction of robust anti-tumor immunity. Together, these results support the use of EcN as an orally-delivered platform to detect disease and treat CRC through its production of screening and therapeutic molecules.
In vitrolymph node-mimicking 3D model displays long-term T cell-dependent CLL proliferation and survival
Authors: Haselager Marco Vincent , van Driel Bianca Francisca , Perelaer Eduard , de Rooij Dennis , Lashgari Danial , Loos Remco , Kater Arnon P. , Moerland Perry D. , Eldering Eric 
Published: April 2023

AbstractChronic lymphocytic leukemia (CLL) cells are highly dependent on microenvironmental cells and signals. The lymph node (LN) is the critical site ofin vivoCLL proliferation and development of resistance to both chemotherapy and targeted agents. We present a new model that incorporates key aspects of the CLL LN which enables investigation of CLL cells in the context of a protective niche. We describe a 3Din vitroculture system utilizing ultra-low attachment (ULA) plates to create spheroids of CLL cells derived from peripheral blood (PB). Starting from CLL:T cell ratios as observed in LN samples, CLL activation was induced by either direct stimulation and/or indirectly via T cells. Compared to 2D cultures, 3D cultures promoted CLL proliferation in a T cell-dependent manner, and enabled expansion for up to 7 weeks, including the formation of follicle-like structures after several weeks of culture. Addition of LN-derived stromal cells further enhanced the proliferative capacity. This model enables high-throughput drug screening, of which we describe response to Btk inhibition, venetoclax resistance, and T cell-mediated cytotoxicity as examples. In summary, we present the first LN-mimickingin vitro3D culture for primary CLL, which enables readouts such as real-time drug screens, kinetic growth assays and spatial localization. This is the firstin vitroCLL system that allows testing of response and resistance to venetoclax and Btk inhibitors in the context of the tumor microenvironment, thereby opening up new possibilities for clinically useful applications.
Potential Immunomodulatory Role of Lead in Monocyte/Macrophage Differentiation
Authors: Nicholson Stacia M. , Schanne Francis A.X. 
Published: April 2023

AbstractLead (Pb) is a pernicious toxic metal and public health hazard, as it persists in the environment contaminating soil, food, and drinking water. Lead exerts its toxic effect on numerous organ systems, with the abundance of focus on the red blood cells and neurons of the hematopoietic and central nervous systems. However, insufficient investigation has been conducted on the effect of Pb on immune cells. In the current study, the toxic effects of Pb on immune cells of monocyte/macrophage lineage are described. Pb exerts a dose-dependent alteration in differentiation of monocyte/macrophage cells that retain some plasticity in development. Pb induces a bifurcation in differentiation of monocyte/macrophage cells, resulting in inhibition of osteoclastogenesis and induction of dendritic cells (DC). This phenomenon was demonstrated in RAW 264.7 murine monocyte/macrophage cell line and was consistent with response in rat bone-marrow derived macrophage (Sprague-Dawley). Pb primarily produced this response through induction of GM-CSF production and inhibition of p38/MAPK activity. Long-term exposure to physiologically relevant concentrations of Pb has the potential to modulate the immune system through altering the cell-lineage commitment of monocyte/macrophage lineage cells in a dose-dependent manner. Thus, Pb may function as an immunomodulator.
Pelvic spine reduction affects diet but not gill raker morphology in two polymorphic brook stickleback (Culaea inconstans) populations
Authors: Mee Jonathan A. , Yap Emily , Wuitchik Daniel M. 
Published: April 2023

AbstractPelvic spine polymorphism occurs in several species in the stickleback family (Gasterosteidae). Given the similar phenotypic polymorphisms in multiple stickleback species, we sought to determine the extent of parallelism in the ecological correlates of pelvic spine reduction. Based on a metabarcoding analysis of brook stickleback gut contents in two polymorphic populations, we found significant diet differences were associated with pelvic spine reduction, but we found no clear or consistent trend supporting a tendency for benthic feeding in pelvic-reduced brook stickleback. These results contrast with those found in threespine stickleback where pelvic spine reduction is often associated with a benthic diet. Hence, we found non-parallel consequences of spine polymorphism across species. Furthermore, a difference in gill raker morphology has been frequently observed between ecomorphs with differen diets in many fish species. But, we found no evidence of any difference in gill raker morphology associated with pelvic spine polymorphism in brook stickleback.
Circulating exosomes from Alzheimer’s disease suppress VE-cadherin expression and induce barrier dysfunction in recipient brain microvascular endothelial cell
Authors: Bei Jiani , Miranda-Morales Ernesto G. , Gan Qini , Qiu Yuan , Husseinzadeh Sorosh , Liew Jia Yi , Chang Qing , Krishnan Balaji , Gaitas Angelo , Yuan Subo , Felicella Michelle , Qiu Wei Qiao , Fang Xiang , Gong Bin 
Published: April 2023

AbstractBackgroundBlood-brain barrier (BBB) breakdown is a component of the progression and pathology of Alzheimer’s disease (AD). BBB dysfunction is primarily caused by reduced or disorganized tight junction or adherens junction proteins of brain microvascular endothelial cell (BMEC). While there is growing evidence of tight junction disruption in BMECs in AD, the functional role of adherens junctions during BBB dysfunction in AD remains unknown. Exosomes secreted from senescent cells have unique characteristics and contribute to modulating the phenotype of recipient cells. However, it remains unknown if and how these exosomes cause BMEC dysfunction in AD.ObjectivesThis study aimed to investigate the potential roles of AD circulating exosomes and their RNA cargos in brain endothelial dysfunction in AD.MethodsWe isolated exosomes from sera of five cases of AD compared with age- and sex-matched cognitively normal controls using size-exclusion chromatography technology. We validated the qualities and particle sizes of isolated exosomes with nanoparticle tracking analysis and atomic force microscopy. We measured the biomechanical natures of the endothelial barrier of BMECs, the lateral binding forces between live BMECs, using fluidic force miscopy. We visualized the paracellular expressions of the key adherens junction protein VE-cadherin in BMEC cultures and a 3D BBB model that employs primary human BMECs and pericytes with immunostaining and evaluated them using confocal microscopy. We also examined the VE-cadherin signal in brain tissues from five cases of AD and five age- and sex-matched cognitively normal controls.ResultsWe found that circulating exosomes from AD patients suppress the paracellular expression levels of VE-cadherin and impair the barrier function of recipient BMECs. Immunostaining analysis showed that AD circulating exosomes damage VE-cadherin integrity in a 3D model of microvascular tubule formation. We found that circulating exosomes in AD weaken the BBB depending on the RNA cargos. In parallel, we observed that microvascular VE-cadherin expression is diminished in AD brains compared to normal controls.ConclusionUsingin vitroandex vivomodels, our study illustrates that circulating exosomes from AD patients play a significant role in mediating the damage effect on adherens junction of recipient BMEC of the BBB in an exosomal RNA-dependent manner. This suggests a novel mechanism of peripheral senescent exosomes for AD risk.
Detecting Anomalous Proteins Using Deep Representations
Authors: Michael-Pitschaze Tomer , Cohen Niv , Ofer Dan , Hoshen Yedid , Linial Michal 
Published: April 2023

ABSTRACTMany advances in biomedicine can be attributed to identifying unusual proteins and genes. Many of these proteins’ unique properties were discovered by manual inspection, which is becoming infeasible at the scale of modern protein datasets. Here, we propose to tackle this challenge using anomaly detection methods that automatically identify unexpected properties. We adopt a state-of-the-art anomaly detection paradigm from computer vision, to highlight unusual proteins. We generate meaningful representations without labeled inputs, using pretrained deep neural network models. We apply these protein language models (pLM) to detect anomalies in function, phylogenetic families, and segmentation tasks. We compute protein anomaly scores to highlight human prion-like proteins, distinguish viral proteins from their host proteome, and mark non-classical ion/metal binding proteins and enzymes. Other tasks concern segmentation of protein sequences into folded and unstructured regions. We provide candidates for rare functionality (e.g., prion proteins). Additionally, we show the anomaly score is useful in 3D folding-related segmentation. Our novel method shows improved performance over strong baselines and has objectively high performance across a variety of tasks. We conclude that the combination of pLM and anomaly detection techniques is a valid method for discovering a range of global and local protein characteristics.
SFyNCS detects oncogenic fusions involving non-coding sequences in cancer
Authors: Zhong Xiaoming , Luan Jingyun , Yu Anqi , Lee-Hassett Anna , Miao Yuxuan , Yang Lixing 
Published: April 2023

AbstractFusion genes are well-known cancer drivers. However, very few known oncogenic fusions involve non-coding sequences. We develop SFyNCS with superior performance to detect fusions of both protein-coding genes and non-coding sequences from transcriptomic sequencing data. We validate fusions using somatic structural variations detected from the genomes. This allows us to comprehensively evaluate various fusion detection and filtering strategies and parameters. We detect 165,139 fusions in 9,565 tumor samples across 33 tumor types in the Cancer Genome Atlas cohort. Among them, 72% of the fusions involve non-coding sequences and many are recurrent. We discover two long non-coding RNAs recurrently fused with various partner genes in 32% of dedifferentiated liposarcomas and experimentally validated the oncogenic functions in mouse model.
Implementation considerations for deep learning with diffusion MRI streamline tractography
Authors: Cai Leon Y. , Lee Ho Hin , Newlin Nancy R. , Kim Michael E. , Moyer Daniel , Rheault François , Schilling Kurt G. , Landman Bennett A. 
Published: April 2023

AbstractOne area of medical imaging that has recently experienced innovative deep learning advances is diffusion MRI (dMRI) streamline tractography with recurrent neural networks (RNNs). Unlike traditional imaging studies which utilize voxel-based learning, these studies model dMRI features at points in continuous space off the voxel grid in order to propagate streamlines, or virtual estimates of axons. However, implementing such models is nontrivial, and an open-source implementation is not yet widely available. Here, we describe a series of considerations for implementing tractography with RNNs and demonstrate they allow one to approximate a deterministic streamline propagator with comparable performance to existing algorithms. We release this trained model and the associated implementations leveraging popular deep learning libraries. We hope the availability of these resources will lower the barrier of entry into this field, spurring further innovation.
Automated tumor immunophenotyping predicts clinical benefit from anti-PD-L1 immunotherapy
Authors: Li Xiao , Eastham Jeffrey , Giltnane Jennifer M. , Zou Wei , Zijlstra Andries , Tabatsky Evgeniy , Banchereau Romain , Chang Ching-Wei , Nabet Barzin , Patil Namrata , Molinero Luciana , Chui Steve , Peterson Maureen , Lau Shari , Rangell Linda , Waumans Yannick , Kockx Mark , Orlova Darya , Koeppen Hartmut 
Published: April 2023

AbstractBackgroundCancer immunotherapy has transformed the clinical approach to patients with malignancies as profound benefits can be seen in a subset of patients. To identify this subset, biomarker analyses increasingly focus on phenotypic and functional evaluation of the tumor microenvironment (TME) to determine if density, spatial distribution, and cellular composition of immune cell infiltrates can provide prognostic and/or predictive information. Attempts have been made to develop standardized methods to evaluate immune infiltrates in the routine assessment of certain tumor types; however, broad adoption of this approach in clinical decision-making is still missing.MethodsWe developed approaches to categorize solid tumors into “Desert”, “Excluded” and “Inflamed” types according to the spatial distribution of CD8+ immune effector cells to determine the prognostic and/or predictive implications of such labels. To overcome the limitations of this subjective approach we incrementally developed four automated analysis pipelines of increasing granularity and complexity for density and pattern assessment of immune effector cells.ResultsWe show that categorization based on “manual” observation is predictive for clinical benefit from anti-programmed cell death ligand-1 (PD-L1) therapy in two large cohorts of patients with non-small cell lung cancer (NSCLC) or triple-negative breast cancer (TNBC). For the automated analysis we demonstrate that a combined approach outperforms individual pipelines and successfully relates spatial features to pathologist-based read-outs and patient response to therapy.ConclusionsOur findings suggest tumor immunophenotype (IP) generated by automated analysis pipelines should be evaluated further as potential predictive biomarkers for cancer immunotherapy.What is already known on this topicClinical benefit from checkpoint inhibitor-targeted therapies is realized only in a subset of patients. Robust biomarkers to identify patients who may respond to such therapies are needed.What this study addsWe have developed manual and automated approaches to categorize tumors into immunophenotypes based on the spatial distribution of CD8+ T effector cells that predict clinical benefit from anti-PD-L1 immunotherapy for patients with advanced non-small cell lung cancer or triple-negative breast cancer.How this study might affect research, practice or policyTumor immunophenotypes should be further validated as predictive biomarker for checkpoint inhibitor-targeted therapies in prospective clinical studies.