tbuckley/cabot-search huggingface dataset:
Comment on ‘Effectiveness and safety of central pancreatectomy in benign or low-grade malignant pancreatic body lesions: a systematic review and meta-analysis’
Authors: Hsiu-Lan Weng, Ying-Jen Chang, Ming Yew, Kuo-Chuan Hung
Journal: International Journal of Surgery (2024)

Weng, Hsiu-Lan MSc; Chang, Ying-Jen MD; Yew, Ming MD; Hung, Kuo-Chuan MD Author Information
Self‐Propelled Nanomotor for Cancer Precision Combination Therapy
Authors: Yijie Lu, Shikang Liu, Jiarong Liang, Zhiyi Wang, Yanglong Hou
Journal: Advanced Healthcare Materials (2024)

The emergence of nanomotor provides an innovative concept for tumor treatment strategies. Conventional chemotherapeutic agents for tumors exit various therapeutic constraints due to the unique microenvironment of the tumor itself. Calcium overload, the aberrant accumulation of free calcium ions in the cytoplasm, is a well-recognized contributor to damage and even cell death in numerous cell types. Such undesired destructive processes can be a novel means applicable to cancer ion interference therapy. Herein, the chemotherapeutic drug doxorubicin (DOX) and calcium peroxide as the driving force into nanomotors through a facile and understandable experimental scheme are successfully assembled. The modification of nucleic acid aptamer and NIR-II fluorescent molecules on its surface simultaneously strengthens both the active targeting and imaging capability of tumor loci. Therefore, by a comprehensive assessment of nanomotors both in vitro and in vivo experiments, CaO
Apolipoprotein E secreted by astrocytes forms antiparallel dimers in discoidal lipoproteins
Authors: Michael R. Strickland, Michael J. Rau, Brock Summers, Katherine Basore, John Wulf, Hong Jiang, Yun Chen, Jason D. Ulrich, Gwendalyn J. Randolph, Rui Zhang, James A.J. Fitzpatrick, Anil G. Cashikar, David M. Holtzman
Journal: Neuron (2024)
ACCORD (ACcurate COnsensus Reporting Document): A reporting guideline for consensus methods in biomedicine developed via a modified Delphi
Authors: William T. Gattrell, Patricia Logullo, Esther J. van Zuuren, Amy Price, Ellen L. Hughes, Paul Blazey, Christopher C. Winchester, David Tovey, Keith Goldman, Amrit Pali Hungin, Niall Harrison
Journal: PLoS Medicine (2024)

Background In biomedical research, it is often desirable to seek consensus among individuals who have differing perspectives and experience. This is important when evidence is emerging, inconsistent, limited, or absent. Even when research evidence is abundant, clinical recommendations, policy decisions, and priority-setting may still require agreement from multiple, sometimes ideologically opposed parties. Despite their prominence and influence on key decisions, consensus methods are often poorly reported. Our aim was to develop the first reporting guideline dedicated to and applicable to all consensus methods used in biomedical research regardless of the objective of the consensus process, called ACCORD (ACcurate COnsensus Reporting Document). Methods and findings We followed methodology recommended by the EQUATOR Network for the development of reporting guidelines: a systematic review was followed by a Delphi process and meetings to finalize the ACCORD checklist. The preliminary checklist was drawn from the systematic review of existing literature on the quality of reporting of consensus methods and suggestions from the Steering Committee. A Delphi panel ( n = 72) was recruited with representation from 6 continents and a broad range of experience, including clinical, research, policy, and patient perspectives. The 3 rounds of the Delphi process were completed by 58, 54, and 51 panelists. The preliminary checklist of 56 items was refined to a final checklist of 35 items relating to the article title ( n = 1), introduction ( n = 3), methods ( n = 21), results ( n = 5), discussion ( n = 2), and other information ( n = 3). Conclusions The ACCORD checklist is the first reporting guideline applicable to all consensus-based studies. It will support authors in writing accurate, detailed manuscripts, thereby improving the completeness and transparency of reporting and providing readers with clarity regarding the methods used to reach agreement. Furthermore, the checklist will make the rigor of the consensus methods used to guide the recommendations clear for readers. Reporting consensus studies with greater clarity and transparency may enhance trust in the recommendations made by consensus panels.
Temporal Trends in Mortality of Critically Ill Patients with Sepsis in the United Kingdom, 1988–2019
Authors: Hallie C. Prescott, David A. Harrison, Kathryn M. Rowan, Manu Shankar-Hari, Hannah Wunsch
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale: Sepsis is a frequent cause of ICU admission and mortality. Objectives: To evaluate temporal trends in the presentation and outcomes of patients admitted to the ICU with sepsis and to assess the contribution of changing case mix to outcomes. Methods: We conducted a retrospective cohort study of patients admitted to 261 ICUs in the United Kingdom during 1988–1990 and 1996–2019 with nonsurgical sepsis. Measurements and Main Results: A total of 426,812 patients met study inclusion criteria. The patients had a median (interquartile range) age of 66 (53–75) years, and 55.6% were male. The most common sites of infection were respiratory (60.9%), genitourinary (11.5%), and gastrointestinal (10.3%). Compared with patients in 1988–1990, patients in 2017–2019 were older (median age, 66 vs. 63 yr), were less acutely ill (median Acute Physiology and Chronic Health Evaluation II acute physiology score, 14 vs. 20), and more often had genitourinary sepsis (13.4% vs. 2.0%). Hospital mortality decreased from 54.6% (95% confidence interval [CI], 51.0–58.1%) in 1988–1990 to 32.4% (95% CI, 32.1–32.7%) in 2017–2019, with an adjusted odds ratio of 0.64 (95% CI, 0.54–0.75). The adjusted absolute hospital mortality reduction from 1988–1990 to 2017–2019 was 8.8% (95% CI, 5.6–12.1). Thus, of the observed 22.2–percentage point reduction in hospital mortality, 13.4 percentage points (60% of total reduction) were explained by case mix changes, whereas 8.8 percentage points (40% of total reduction) were not explained by measured factors and may be a result of improvements in ICU management. Conclusions: Over a 30-year period, mortality for ICU admissions with sepsis decreased substantially. Although changes in case mix accounted for the majority of observed mortality reduction, there was an 8.8–percentage point reduction in mortality not explained by case mix.
Geo-economic Influence on the Effect of Fluid Volume for Sepsis Resuscitation: A Meta-Analysis
Authors: Ségolène Gendreau, Thomas Frapard, Guillaume Carteaux, Arthur Kwizera, Neill K. J. Adhikari, Mervyn Mer, Glenn Hernandez, Armand Mekontso Dessap
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale: Sepsis management relies on fluid resuscitation avoiding fluid overload and its related organ congestion. Objectives: To explore the influence of country income group on risk–benefit balance of fluid management strategies in sepsis. Methods: We searched e-databases for all randomized controlled trials on fluid resuscitation in patients with sepsis or septic shock up to January 2023, excluding studies on hypertonic fluids, colloids, and depletion-based interventions. The effect of fluid strategies (higher versus lower volumes) on mortality was analyzed per income group (i.e., low- and middle-income countries [LMICs] or high-income countries [HICs]). Measurements and Main Results: Twenty-nine studies (11,798 patients) were included in the meta-analysis. There was a numerically higher mortality in studies of LMICs as compared with those of HICs: median, 37% (interquartile range [IQR]: 26–41) versus 29% (IQR: 17–38; P = 0.06). Income group significantly interacted with the effect of fluid volume on mortality: Higher fluid volume was associated with higher mortality in LMICs but not in HICs: odds ratio (OR), 1.47; 95% confidence interval (95% CI): 1.14–1.90 versus 1.00 (95% CI: 0.87–1.16), P = 0.01 for subgroup differences. Higher fluid volume was associated with increased need for mechanical ventilation in LMICs (OR, 1.24 [95% CI: 1.08–1.43]) but not in HICs (OR, 1.02 [95% CI: 0.80–1.29]). Self-reported access to mechanical ventilation also significantly influenced the effect of fluid volume on mortality, which increased with higher volumes only in settings with limited access to mechanical ventilation (OR: 1.45 [95% CI: 1.09–1.93] vs. 1.09 [95% CI: 0.93–1.28], P = 0.02 for subgroup differences). Conclusions: In sepsis trials, the effect of fluid resuscitation approach differed by setting, with higher volume of fluid resuscitation associated with increased mortality in LMICs and in settings with restricted access to mechanical ventilation. The precise reason for these differences is unclear and may be attributable in part to resource constraints, participant variation between trials, or other unmeasured factors.
Analysis of autophagy in DLBCL reveals subtype-specific differences and the preferential targeting of ULK1 inhibition in GCB-DLBCL provides a rationale as a new therapeutic approach
Authors: Harpreet K. Mandhair, Ramin Radpour, Mira Westerhuis, Yara Banz, Magali Humbert, Miroslav Arambasic, Jörn Dengjel, Andrew Davies, Mario P. Tschan, Urban Novak
Journal: Leukemia (2024)

Diffuse large B-cell lymphomas (DLBCL) represent approximately 30% of all non-Hodgkin lymphomas [1].The recognised cell-oforigin (COO) has classified two major DLBCL subtypes: Germinal B-cell (GCB) and Activated B-cell (ABC) lymphomas.Between 20-50% of patients experience relapse and refractory disease following first-line therapy R-CHOP [2].The recognised molecular heterogeneity contributes to varied clinical outcomes of patients following chemotherapy and targeted agents including ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor [2, 3].Ibrutinib preferentially targets ABC-DLBCL exhibiting reliance on chronic B-cell receptor (BCR) engagement and hyper NF-κB signalling [3].Phase I/II trial elucidated that BTK-activity is driven through BCR-dependent signalling with concomitant MYD88 L265P mutations [3].In contrast, GCB-DLBCL exerts BCR "tonic" activity that is independent of antigen and NF-κB signalling [4, 5].COO DLBCL subtypes exhibit dependence on phosphatidylinositol-3kinase (PI3K)/protein kinase-B (AKT) leading to mammalian target of rapamycin complex-1 (mTORC1) activity [5].Macroautophagy (herein autophagy) maintains cellular homeostasis through the degradation of damaged organelles [6].Suppression of PI3K-AKT-mTORC1 initiates autophagy through the phosphorylation of unc-51-like kinase-1 (ULK1) [6, 7].The ULK1 kinase and its complex activation is critical for triggering the autophagic cascade and recruiting microtubule-associated protein 1 light chain-3 (LC3) for the formation of the autophagosome, a double-membraned vesicle [8].Atypical autophagy facilitates metabolic adaptation in cancer cells [7].Lysosomotropic autophagy inhibitors including hydroxychloroquine lack potency and efficacy in clinical trials [9].ULK1 is a druggable serine/threonine kinase [7].Immunohistochemistry of primary lymphoma entities stained for cytoplasmic-LC3B was significant in 70.6% of aggressive compared
Peri-transplant flow-MRD assessment of cells with leukemic stem cells (LSC) associated phenotype in AML patients undergoing allogeneic stem cell transplantation in CR
Authors: Evgeny Klyuchnikov, Anita Badbaran, Radwan Massoud, Petra Freiberger, Christine Wolschke, Francis Ayuk, Boris Fehse, Ulrike Bacher, Nicolaus Kröger
Journal: Leukemia (2024)
FMRP-mediated spatial regulation of physiologic NMD targets in neuronal cells
Authors: Tatsuaki Kurosaki, Xavier Rambout, Lynne E. Maquat
Journal: Genome biology (2024)

Abstract In non-polarized cells, nonsense-mediated mRNA decay (NMD) generally begins during the translation of newly synthesized mRNAs after the mRNAs are exported to the cytoplasm. Binding of the FMRP translational repressor to UPF1 on NMD targets mainly inhibits NMD. However, in polarized cells like neurons, FMRP additionally localizes mRNAs to cellular projections. Here, we review the literature and evaluate available transcriptomic data to conclude that, in neurons, the translation of physiologic NMD targets bound by FMRP is partially inhibited until the mRNAs localize to projections. There, FMRP displacement in response to signaling induces a burst in protein synthesis followed by rapid mRNA decay.
Male patients with inflammatory joint diseases are less likely than controls to be childless: results from a Norwegian population-based cohort study of 10 865 patients
Authors: Gudrun David Sigmo, Solveig Hauge, Karl Ove Hufthammer, Marianne Wallenius, Kjell Åsmund Salvesen, Anne Kjersti Nesje Daltveit, Gunnstein Bakland, Bjorg-Tilde Svanes Fevang
Journal: Annals of the Rheumatic Diseases (2024)

Objectives To investigate the number of children per man and the proportion of childless men as a proxy of fertility in a national cohort of men with inflammatory joint diseases (IJDs), compared with matched controls from the general population. Methods This is a nationwide, population-based retrospective cohort study. Male patients with IJDs (n = 10 865) in the Norwegian Arthritis Registry were individually matched 1:5 on birth year and county of residence with men without IJDs obtained from the National Population Register (n = 54 325). Birth data were obtained from the Medical Birth Registry of Norway. We compared the mean number of children per man and the proportion of childless men and analysed the impact of age and year of diagnosis. Results The mean number of children per man in the patient group was 1.80 versus 1.69 in the comparison group (p &lt;0.001), and 21% of the patients in the patient group were childless versus 27% in the comparison group (p &lt;0.001). The finding of less childlessness and higher number of children per man remained consistent across age at diagnosis, except for those diagnosed at age 0–19 years. The difference in childlessness was most pronounced for men diagnosed after year 2000, especially when diagnosed at 30–39 years of age (22% vs 32%, p&lt;0.001). Conclusion In this large cohort study we found that patients with IJD have a higher number of children and are less likely to be childless compared with controls. Factors associated with developing or having an IJD might influence fertility and this requires further investigation.
Unraveling the phylogenomic diversity of Methanomassiliicoccales and implications for mitigating ruminant methane emissions
Authors: Fei Xie, Shengwei Zhao, Xiaoxiu Zhan, Yang Zhou, Yin Li, Weiyun Zhu, Phillip B. Pope, Graeme T. Attwood, Wei Jin, Shengyong Mao
Journal: Genome biology (2024)

Abstract Background Methanomassiliicoccales are a recently identified order of methanogens that are diverse across global environments particularly the gastrointestinal tracts of animals; however, their metabolic capacities are defined via a limited number of cultured strains. Results Here, we profile and analyze 243 Methanomassiliicoccales genomes assembled from cultured representatives and uncultured metagenomes recovered from various biomes, including the gastrointestinal tracts of different animal species. Our analyses reveal the presence of numerous undefined genera and genetic variability in metabolic capabilities within Methanomassiliicoccales lineages, which is essential for adaptation to their ecological niches. In particular, gastrointestinal tract Methanomassiliicoccales demonstrate the presence of co-diversified members with their hosts over evolutionary timescales and likely originated in the natural environment. We highlight the presence of diverse clades of vitamin transporter BtuC proteins that distinguish Methanomassiliicoccales from other archaeal orders and likely provide a competitive advantage in efficiently handling B 12 . Furthermore, genome-centric metatranscriptomic analysis of ruminants with varying methane yields reveal elevated expression of select Methanomassiliicoccales genera in low methane animals and suggest that B 12 exchanges could enable them to occupy ecological niches that possibly alter the direction of H 2 utilization. Conclusions We provide a comprehensive and updated account of divergent Methanomassiliicoccales lineages, drawing from numerous uncultured genomes obtained from various habitats. We also highlight their unique metabolic capabilities involving B 12 , which could serve as promising targets for mitigating ruminant methane emissions by altering H 2 flow.
Apolipoprotein E-ε2 and Resistance to Atherosclerosis in Midlife: The PESA Observational Study
Authors: Raquel Toribio-Fernández, Catarina Tristão-Pereira, Juan Carlos Silla-Castro, Sergio Callejas, Belen Oliva, Irene Fernandez-Nueda, Ines Garcia-Lunar, Cristina Perez-Herreras, José María Ordovás, Pilar Martin, Fiona Blanco-Kelly, Carmen Ayuso, Enrique Lara-Pezzi, Antonio Fernandez-Ortiz, Ana Garcia-Alvarez, Ana Dopazo, Fatima Sanchez-Cabo, Borja Ibanez, Marta Cortes-Canteli, Valentin Fuster
Journal: Circulation Research (2024)

APOE is a known genetic contributor to cardiovascular disease, but the differential role
AVCAPIR: A Novel Procalcific PIWI-Interacting RNA in Calcific Aortic Valve Disease
Authors: Dong Han, Tingwen Zhou, Lifu Li, Yan Ma, Shiqi Chen, Chunguang Yang, Ning Ma, Moshi Song, Shaoshao Zhang, Jie Wu, Feng Cao, Yongjun Wang
Journal: Circulation (2024)

Calcification of the aortic valve leads to increased leaflet stiffness and consequently results in the development of calcific aortic valve disease (CAVD). However, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified a novel aortic valve calcification-associated PIWI-interacting RNA (piRNA; AVCAPIR) that increases valvular calcification and promotes CAVD progression.
Pharmacological Improvement of Cystic Fibrosis Transmembrane Conductance Regulator Function Rescues Airway Epithelial Homeostasis and Host Defense in Children with Cystic Fibrosis
Authors: Jennifer Loske, Mirjam Völler, Sören Lukassen, Mirjam Stahl, Loreen Thürmann, Anke Seegebarth, Jobst Röhmel, Sebastian Wisniewski, Marey Messingschlager, Stephan Lorenz, Sven Klages, Roland Eils, Irina Lehmann, Marcus A. Mall, Simon Y. Graeber, Saskia Trump
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Pharmacological improvement of cystic fibrosis transmembrane conductance regulator (CFTR) function with elexacaftor/tezacaftor/ivacaftor (ETI) provides unprecedented improvements in lung function and other clinical outcomes in patients with cystic fibrosis (CF). However, ETI effects on impaired mucosal homeostasis and host defense at the molecular and cellular levels in the airways of patients with CF remain unknown.
Pindel-TD: A Tandem Duplication Detector Based on A Pattern Growth Approach
Authors: Xiaofei Yang, Gaoyang Zheng, Peng Jia, Songbo Wang, Kai Ye
Journal: Genomics Proteomics & Bioinformatics (2024)

Tandem duplication (TD) is a major type of structural variations (SVs) that plays an important role in novel gene formation and human diseases. However, TDs are often missed or incorrectly classified as insertions by most modern SV detection methods due to the lack of specialized operation on TD-related mutational signals. Herein, we developed a TD detection module for the Pindel tool, referred to as Pindel-TD, based on a TD-specific pattern growth approach. Pindel-TD is capable of detecting TDs with a wide size range at single nucleotide resolution. Using simulated and real read data from HG002, we demonstrated that Pindel-TD outperforms other leading methods in terms of precision, recall, F1-score, and robustness. Furthermore, by applying Pindel-TD to data generated from the K562 cancer cell line, we identified a TD located at the seventh exon of SAGE1, providing an explanation for its high expression. Pindel-TD is available for non-commercial use at https://github.com/xjtu-omics/pindel.
Leveraging Oriented Lateral Walls of Nerve Guidance Conduit with Core–Shell MWCNTs Fibers for Peripheral Nerve Regeneration
Authors: Renyuan Sun, Yuna Lang, Ming‐Wei Chang, Mingkang Zhao, Chao Li, Shiheng Liu, Baolin Wang
Journal: Advanced Healthcare Materials (2024)

Abstract Peripheral nerve regeneration and functional recovery rely on the chemical, physical, and structural properties of nerve guidance conduits (NGCs). However, the limited support for long‐distance nerve regeneration and axonal guidance has hindered the widespread use of NGCs. This study introduces a novel nerve guidance conduit with oriented lateral walls, incorporating multi‐walled carbon nanotubes (MWCNTs) within core‐shell fibers prepared in a single step using a modified electrohydrodynamic (EHD) printing technique to promote peripheral nerve regeneration. The structured conduit demonstrated exceptional stability, mechanical properties, and biocompatibility, significantly enhancing the functionality of NGCs. In vitro cell studies revealed that RSC96 cells adhered and proliferated effectively along the oriented fibers, demonstrating a favorable response to the distinctive architectures and properties. Subsequently, a rat sciatic nerve injury model demonstrated effective efficacy in promoting peripheral nerve regeneration and functional recovery. Tissue analysis and functional testing highlighted the significant impact of MWCNT concentration in enhancing peripheral nerve regeneration and confirming well‐matured aligned axonal growth, muscle recovery, and higher densities of myelinated axons. These findings demonstrate the potential of oriented lateral architectures with coaxial MWCNT fibers as a promising approach to support long‐distance regeneration and encourage directional nerve growth for peripheral nerve repair in clinical applications.
An intriguing vision for transatlantic collaborative health data use and artificial intelligence development
Authors: Daniel C. Baumgart
Journal: npj Digital Medicine (2024)

Our traditional approach to diagnosis, prognosis, and treatment, can no longer process and transform the enormous volume of information into therapeutic success, innovative discovery, and health economic performance. Precision health, i.e., the right treatment, for the right person, at the right time in the right place, is enabled through a learning health system, in which medicine and multidisciplinary science, economic viability, diverse culture, and empowered patient's preferences are digitally integrated and conceptually aligned for continuous improvement and maintenance of health, wellbeing, and equity. Artificial intelligence (AI) has been successfully evaluated in risk stratification, accurate diagnosis, and treatment allocation, and to prevent health disparities. There is one caveat though: dependable AI models need to be trained on population-representative, large and deep data sets by multidisciplinary and multinational teams to avoid developer, statistical and social bias. Such applications and models can neither be created nor validated with data at the country, let alone institutional level and require a new dimension of collaboration, a cultural change with the establishment of trust in a precompetitive space. The Data for Health (#DFH23) conference in Berlin and the Follow-Up Workshop at Harvard University in Boston hosted a representative group of stakeholders in society, academia, industry, and government. With the momentum #DFH23 created, the European Health Data Space (EHDS) as a solid and safe foundation for consented collaborative health data use and the G7 Hiroshima AI process in place, we call on citizens and their governments to fully support digital transformation of medicine, research and innovation including AI.