tbuckley/cabot-search huggingface dataset:
Stereotactic Body Radiotherapy for Centrally Located Inoperable Early-Stage NSCLC: EORTC 22113–08113 LungTech Phase II Trial Results
Authors: Antonin Levy, Sonja Adebahr, Coen Hurkmans, Merina Ahmed, Shahreen Ahmad, Matthias Guckenberger, Xavier Geets, Yolande Lievens, Maarten Lambrecht, Nicolas Pourel, Victor Lewitzki, Krzysztof Konopa, Kevin Franks, Rafal Dziadziuszko, Fiona McDonald, Catherine Fortpied, Enrico Clementel, Béatrice Fournier, Stefania Rizzo, Christian Fink, Oliver Riesterer, Heike Peulen, Nicolaus Andratschke, Alan McWilliam, Eleni Gkika, Tanja Schimek-Jasch, Anca-Ligia Grosu, Cécile Le Pechoux, Corinne Faivre-Finn, Ursula Nestle
Journal: Journal of Thoracic Oncology (2024)
Epigenome–metabolism nexus in the retina: implications for aging and disease
Authors: Anupam K. Mondal, Mohita Gaur, Jayshree Advani, Anand Swaroop
Journal: Trends in Genetics (2024)

Intimate links between epigenome modifications and metabolites allude to a crucial role of cellular metabolism in transcriptional regulation. Retina, being a highly metabolic tissue, adapts by integrating inputs from genetic, epigenetic, and extracellular signals. Precise global epigenomic signatures guide development and homeostasis of the intricate retinal structure and function. Epigenomic and metabolic realignment are hallmarks of aging and highlight a link of the epigenome–metabolism nexus with aging-associated multifactorial traits affecting the retina, including age-related macular degeneration and glaucoma. Here, we focus on emerging principles of epigenomic and metabolic control of retinal gene regulation, with emphasis on their contribution to human disease. In addition, we discuss potential mitigation strategies involving lifestyle changes that target the epigenome-metabolome relationship for maintaining retinal function.
Bone transport induces the release of factors with multi-tissue regenerative potential for diabetic wound healing in rats and patients
Authors: Jing Xie, Xuhua Liu, Biaoliang Wu, Bochong Chen, Qiancheng Song, Yuan Guan, Yuanxun Gong, Chengliang Yang, Jinbo Lin, Mingfeng Huang, Xinyu Tan, Ruijun Lai, Xiaozhen Lin, Sheng Zhang, Xiaoling Xie, Xiaoli Chen, Chunyuan Zhang, Mei Yang, Huijiao Nong, Xiaoyang Zhao, Laixin Xia, Weijie Zhou, Guozhi Xiao, Qing Jiang, Weiguo Zou, Di Chen, Di Lu, Jia Liu, Xiaochun Bai
Journal: Cell Reports Medicine (2024)

Tibial cortex transverse distraction is a surgical method for treating severe diabetic foot ulcers (DFUs), but the underlying mechanism is unclear. We show that antioxidant proteins and small extracellular vesicles (sEVs) with multiple-tissue regenerative potential are released during bone transport (BT) in humans and rats. These vesicles accumulate in diabetic wounds and are enriched with microRNAs (miRNAs) (e.g., miR-494-3p) that have high regenerative activities that improve the circulation of ischemic lower limbs while also promoting neovascularization, fibroblast migration, and nerve fiber regeneration. Deletion of miR-494-3p in rats reduces the beneficial effects of BT on diabetic wounds, while hydrogels containing miR-494-3p and reduced glutathione (GSH) effectively repair them. Importantly, the ginsenoside Rg1 can upregulate miR-494-3p, and a randomized controlled trial verifies that the regimen of oral Rg1 and GSH accelerates wound healing in refractory DFU patients. These findings identify potential functional factors for tissue regeneration and suggest a potential therapy for DFUs.
Salvaging donated kidneys from prolonged warm ischemia during ex vivo hypothermic oxygenated perfusion
Authors: Peng Zhang, Chao Sun, Shuyong Mo, Chaoyu Hu, Yuxiang Ning, Han Liang, Zhongzhong Liu, Xiaoli Fan, Yanfeng Wang
Journal: Kidney International (2024)

Prolonged warm ischemic is the main cause discarding donated organs after cardiac death. Here, we identified that prolonged warm ischemic time induced disseminated intravascular coagulation and severe capillary vasospasm after cardiac death of rat kidneys. Additionally, we found a significant accumulation of fibrinogen in a hypoxic cell culture of human umbilical vein epithelial cells and in isolated kidneys exposed to prolonged warm ischemic following flushing out of blood. However, pre-flushing the kidney with snake venom plasmin in a 90-minute warm ischemic model maximized removal of micro thrombi and facilitated the delivery of oxygen and therapeutic agents. Application of carbon monoxide releasing CORM-401 during ex vivo hypothermic oxygenated perfusion achieved multipath protective effects in prolonged warm ischemic kidneys. This led to significant improvements in perfusion parameters, restoration of the microcirculation, amelioration of mitochondrial injury, oxidative stress, and apoptosis. This benefit resulted in significantly prolonged warm ischemic kidney recipient survival rates of 70%, compared with none in those receiving ex vivo hypothermic oxygenated perfusion alone. Significantly, ex vivo hypothermic oxygenated perfusion combined with cytoprotective carbon monoxide releasing CORM-401 treatment meaningfully protected the donated kidney after cardiac death from ischemia-reperfusion injury by reducing inflammation, oxidative stress, apoptosis, and pathological damage. Thus, our study suggests a new combination treatment strategy to potentially expand the donor pool by increasing use of organs after cardiac death and salvaging prolonged warm ischemic kidneys.
Health-care workforce implications of the Dobbs v Jackson Women's Health Organization decision
Authors: Claire D Brindis, Melissa H Laitner, Ellen Wright Clayton, Susan C Scrimshaw, Barbara J Grosz, Lisa A Simpson, Sara Rosenbaum, Corale L Brierley, Melissa A Simon, Yvette Roubideaux, Bruce N Calonge, Paula A Johnson, Laura DeStefano, Ashley Bear, Kavita S Arora, Victor J Dzau
Journal: The Lancet (2024)
Diagnostic Value of Aortic Valve Calcification Levels in the Assessment of Low-Gradient Aortic Stenosis
Authors: Rik Adrichem, Thijmen W Hokken, Sjoerd Bouwmeester, Ola Abdelkarim, Birgit Vogel, David I Blusztein, Verena Veulemans, Jurrien H Kuneman, Marcel L Geleijnse, Sarah Verhemel, Mark M P Van den Dorpel, Isabella Kardys, Pim A L Tonino, Su Min Chang, Nadeen N Faza, Stephanie Jou, Hiroki A Ueyama, Joanna Bartkowiak, Tobias Zeus, Jeroen J Bax, Philippe B Bertrand, Rebecca T Hahn, Susheel K Kodali, Stamatios Lerakis, Roxana Mehran, Stephen H Little, Patrick Houthuizen, Nicolas M Van Mieghem
Journal: JACC. Cardiovascular imaging (2024)

In patients with low-gradient aortic stenosis (AS) and low transvalvular flow, dobutamine stress echocardiography (DSE) is recommended to determine AS severity, whereas the degree of aortic valve calcification (AVC) supposedly correlates with AS severity according to current European and American guidelines. The purpose of this study was to assess the relationship between AVC and AS severity as determined using echocardiography and DSE in patients with aortic valve area <1 cm2 and peak aortic valve velocity <4.0 m/s. All patients underwent DSE to determine AS severity and multislice computed tomography to quantify AVC. Receiver-operating characteristics curve analysis was used to assess the diagnostic value of AVC for AS severity grading as determined using echocardiography and DSE in men and women. A total of 214 patients were included. Median age was 78 years (25th-75th percentile: 71-84 years) and 25% were women. Left ventricular ejection fraction was reduced (<50%) in 197 (92.1%) patients. Severe AS was diagnosed in 106 patients (49.5%). Moderate AS was diagnosed in 108 patients (50.5%; in 77 based on resting transthoracic echocardiography, in 31 confirmed using DSE). AVC score was high (≥2,000 for men or ≥1,200 for women) in 47 (44.3%) patients with severe AS and in 47 (43.5%) patients with moderate AS. AVC sensitivity was 44.3%, specificity was 56.5%, and positive and negative predictive values for severe AS were 50.0% and 50.8%, respectively. Area under the receiver-operating characteristics curve was 0.508 for men and 0.524 for women. Multi-slice computed tomography–derived AVC scores showed poor discrimination between grades of AS severity using DSE and cannot replace DSE in the diagnostic work-up of low-gradient severe AS.
The glycolytic enzyme PFKFB3 drives kidney fibrosis through promoting histone lactylation-mediated NF-κB family activation
Authors: Yating Wang, Hongyu Li, Simin Jiang, Dongying Fu, Xiaohui Lu, Miaoqing Lu, Yi Li, Dan Luo, Kefei Wu, Yiping Xu, Guanglan Li, Yi Zhou, Yiming Zhou, Wei Chen, Qinghua Liu, Haiping Mao
Journal: Kidney International (2024)

Persistently elevated glycolysis in kidney has been demonstrated to promote chronic kidney disease (CKD). However, the underlying mechanism remains largely unclear. Here, we observed that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key glycolytic enzyme, was remarkably induced in kidney proximal tubular cells (PTCs) following ischemia-reperfusion injury (IRI) in mice, as well as in multiple etiologies of patients with CKD. PFKFB3 expression was positively correlated with the severity of kidney fibrosis. Moreover, patients with CKD and mice exhibited increased urinary lactate/creatine levels and kidney lactate, respectively. PTC-specific deletion of PFKFB3 significantly reduced kidney lactate levels, mitigated inflammation and fibrosis, and preserved kidney function in the IRI mouse model. Similar protective effects were observed in mice with heterozygous deficiency of PFKFB3 or those treated with a PFKFB3 inhibitor. Mechanistically, lactate derived from PFKFB3-mediated tubular glycolytic reprogramming markedly enhanced histone lactylation, particularly H4K12la, which was enriched at the promoter of NF-κB signaling genes like Ikbkb, Rela, and Relb, activating their transcription and facilitating the inflammatory response. Further, PTC-specific deletion of PFKFB3 inhibited the activation of IKKβ, I κ B α, and p65 in the IRI kidneys. Moreover, increased H4K12la levels were positively correlated with kidney inflammation and fibrosis in patients with CKD. These findings suggest that tubular PFKFB3 may play a dual role in enhancing NF-κB signaling by promoting both H4K12la-mediated gene transcription and its activation. Thus, targeting the PFKFB3-mediated NF-κB signaling pathway in kidney tubular cells could be a novel strategy for CKD therapy.
Targeted next-generation sequencing to diagnose drug-resistant tuberculosis: a systematic review and meta-analysis
Authors: Tiana Carina Schwab, Lisa Perrig, Pauline Carlotta Göller, Freddy Fernando Guebely De la Hoz, Adrien Philippe Lahousse, Beatrice Minder, Gunar Günther, Orestis Efthimiou, Shaheed Vally Omar, Matthias Egger, Lukas Fenner
Journal: The Lancet Infectious Diseases (2024)
Tuning up the chords of consensus research with the ACcurate COnsensus Reporting Document (ACCORD)
Authors: Esther J van Zuuren
Journal: British Journal of Dermatology (2024)

Tuning up the chords of consensus research with the ACcurate COnsensus Reporting Document (ACCORD)The BJD receives a substantial number of consensus-based papers, yet their quality varies considerably.To address this, the BJD now requires authors to adhere to the ACcurate COnsensus Reporting Document (ACCORD) and include the completed checklist with their submissions.2][3] In dermatology, consensus methods are applied for several purposes such as developing clinical practice guidelines, disease classification, core outcome sets and establishing research priorities. 1,4][3] These differ in terms of anonymity, number of participants, face-to-face meetings and required timeframes.Consensus obtained through formal methods involving a group of experts is generally seen as being more reliable than relying solely on individual opinions and experiences. 1,2hese formal methods mitigate challenges inherent in group decision making by fostering interactions, stimulating critical thinking and questioning conventional viewpoints.Structured approaches minimize risks associated with unstructured group dynamics, such as one individual monopolizing discussions, misrepresenting unanimous agreement when dissenting opinions exist, or allowing group biases to influence decision making. 1 Despite the frequent application of consensus methods, shortcomings in their reporting have been well documented, such as a lack of adequate detail and transparency. 2,3Many study designs have established reporting guidelines to ensure consistency and quality in research publications. 4xamples in the BJD author guidance include the PRISMA and CONSORT guidelines.Until recently there was no universal reporting guideline applicable to all consensus methods.Two reporting guidelines offer some guidance: Appraisal of Guidelines, Research and Evaluation (AGREE)-II, used for clinical practice guidelines, containing one item on consensus, 5 and Core Outcome Set-STAndards for Reporting (COS-STAR), for core outcome set development, with three items. 6Furthermore, the Conducting and Reporting Delphi Studies (CREDES) guideline is designed for Delphi studies, with a focus on palliative care. 7However, ACCORD goes further than just Delphi methods, encompassing all consensus techniques in different health-related domains.The ACCORD checklist comprises 35 items, with the majority focusing on methodological aspects (Table 1). 1,8
Differential Culprit Plaque Morphology in Acute Coronary Syndrome: A Comparison Between Very Young Patients (&amp;lt;=35 Years) and Older Counterparts Using Optical Coherence Tomography
Authors: Gaurav Chaudhary, Basant Gupta, Shubhajeet Roy, Sharad Chandra, Akhil Sharma, Akshyaya Pradhan, Monika Bhandari, Pravesh Vishwakarma, Rishi Sethi, Sudhanshu Kumar Dwivedi, Vinit Baliyan, Prachi Sharma, Vikash Jaiswal, Abhishek Singh, Ayush Shukla, Sajina Shrestha, Alessia Gimelli
Journal:  (2024)

Abstract Aims Underlying mechanisms responsible for acute coronary syndrome (ACS) in young patients compared with older counterparts are yet to be explored with optical coherence tomography (OCT). This study aims to explore underlying mechanisms of ACS in ≤35- (very young) and &amp;gt;35-year-old (older counterparts) ACS patients using OCT. Methods and results This was a prospective, single-centre, investigational study. Patients were divided into groups according to age (≤35 and &amp;gt;35 years) and further subdivided according to the underlying mechanism i.e. plaque rupture (PR) and plaque erosion (PE). A total of 93 patients were analysed. Thin-cap fibroatheroma (TCFA) was significantly higher among older counterparts than very young patients for both PR (80.0% vs. 31.8%, P = 0.002) and PE (66.7% vs. 6.3%, P &amp;lt; 0.001) groups. Microchannels were also significantly more prevalent among older than very young patients for both PR (65.0% vs. 18.2%, P = 0.004) and PE groups (55.6% vs.12.5%, P = 0.013). Macrophages were significantly higher in older than very young patients for both PR (25.0% vs. 0%, P = 0.018) and PE (44.4% vs. 0%, P = 0.003) groups. In contrast, fibrous cap thickness was greater in very young than older patients for both PR (105.71 ± 48.02 vs. 58.00 ± 15.76 µm, P &amp;lt; 0.001) and PE (126.67 ± 48.22 vs. 54.38 ± 24.21 µm, P &amp;lt; 0.001) groups. Intimal thickness was greater in older than very young patients for both PR (728.00 ± 313.92 vs. 342.27 ± 142.02 µm, P &amp;lt; 0.001) and PE (672.78 ± 334.57 vs. 295.00 ± 99.60 µm, P &amp;lt; 0.001) groups. Conclusion Frequency of TCFA, microchannels, macrophages, and intimal thickness was significantly higher in older ACS patients compared with very young patients. However, fibrous cap thickness was significantly greater in very young ACS patients compared with older patients.
The relative vaccine effectiveness of high-dose vs standard-dose influenza vaccines in preventing hospitalization and mortality: A meta-analysis of evidence from randomized trials
Authors: Kristoffer Grundtvig Skaarup, Mats Christian Højbjerg Lassen, Daniel Modin, Niklas Dyrby Johansen, Matthew M. Loiacono, Rebecca C. Harris, Jason K.H. Lee, Marine Dufournet, Orly Vardeny, Alexander Peikert, Brian Claggett, Scott D. Solomon, Jens Ulrik Stæhr Jensen, Tor Biering-Sørensen
Journal: Journal of Infection (2024)

ObjectivesTo summarize current evidence of high-dose influenza vaccine (HD-IV) vs standard-dose (SD-IV) regarding severe clinical outcomes.MethodsA prespecified meta-analysis was conducted to assess relative vaccine effectiveness (rVE) of HD-IV vs SD-IV in reducing the rates of (1) pneumonia and influenza (P&I) hospitalization, (2) all hospitalizations, and (3) all-cause death in adults ≥65 years in randomized controlled trials. Pooled effect sizes were estimated using fixed-effects models with the inverse variance method.ResultsFive randomized trials were included encompassing 105,685 individuals. HD-IV vs SD-IV reduced P&I hospitalizations (rVE: 23.5%, [95%CI: 12.3 to 33.2]). HD-IV vs SD-IV also reduced rate of all-cause hospitalizations (rVE: 7.3%, [95%CI: 4.5 to 10.0]). No significant differences were observed in death rates (rVE = 1.6% ([95%CI: -2.0 to 5.0]) in HD-IV vs SD-IV. Sensitivity analyses omitting trials with participants sharing the same comorbidity, trials with ≥100 events, and random-effects models provided comparable estimates for all outcomes.ConclusionsHD-IV reduced the incidence of P&I and all-cause hospitalization vs SD-IV in adults ≥65 years in randomized trials, through no significant difference was observed in all-cause death rates. These findings, supported by evidence from several randomized studies, can benefit from replication in a fully powered, individually randomized trial.FundingThe Danish Cardiovascular Academy.
The evolution of transglutaminases underlies the origin and loss of cornified skin appendages in vertebrates
Authors: Attila Placido Sachslehner, Marta Surbek, Karin Brigit Holthaus, Julia Steinbinder, Bahar Golabi, Claudia Hess, Leopold Eckhart
Journal: Molecular Biology and Evolution (2024)

Transglutaminases (TGMs) cross-link proteins by introducing covalent bonds between glutamine and lysine residues. These cross-links are essential for epithelial cornification which enables tetrapods to live on land. Here, we investigated which evolutionary adaptations of vertebrates were associated with specific changes in the family of TGM genes. We determined the catalog of TGMs in the main clades of vertebrates, performed a comprehensive phylogenetic analysis of TGMs, and localized the distribution of selected TGMs in tissues. Our data suggest that TGM1 is the phylogenetically oldest epithelial TGM, with orthologs being expressed in the cornified teeth of the lamprey, a basal vertebrate. Gene duplications led to the origin of TGM10 in stem vertebrates, the origin of TGM2 in jawed vertebrates, and an increasing number of epithelium-associated TGM genes in the lineage leading to terrestrial vertebrates. TGM9 is expressed in the epithelial egg tooth, and its evolutionary origin in stem amniotes coincided with the evolution of embryonic development in eggs that are surrounded by a protective shell. Conversely, viviparous mammals have lost both the epithelial egg tooth and TGM9. TGM3 and TGM6 evolved as regulators of cornification in hair follicles and underwent pseudogenization upon the evolutionary loss of hair in cetaceans. Taken together, this study reveals the gain and loss of vertebrate TGM genes in association with the evolution of cornified skin appendages and suggests an important role of TGM9 in the evolution of amniotes.
Hidradenitis suppurativa, systemic inflammatory response syndrome and sepsis: a database study
Authors: Edigin Ehizogie, Ibrahim Maghari, Serigne Lo, Joerg Albrecht
Journal: British Journal of Dermatology (2024)

Hidradenitis suppurativa (HS) has unclear pathophysiology and aetiology, but it is not an infectious disease. However, HS is frequently mistaken for an infection and patients with HS are treated for recurrent bacterial abscesses or admitted for sepsis. A systematic literature search that is published as a separate paper did not identify an index case that demonstrates that sepsis can originate in an HS lesion. However, because patients with HS get admitted for sepsis anyway, we wanted to characterize them.
Early adverse physiological event detection using commercial wearables: challenges and opportunities
Authors: Jesse Phipps, Bryant Passage, Kaan Sel, Jonathan Martinez, Milad Saadat, Teddy Koker, Natalie Damaso, Shakti Davis, Jeffrey Palmer, Kajal Claypool, Christopher Kiley, Roderic I. Pettigrew, Roozbeh Jafari
Journal: npj Digital Medicine (2024)

Abstract Data from commercial off-the-shelf (COTS) wearables leveraged with machine learning algorithms provide an unprecedented potential for the early detection of adverse physiological events. However, several challenges inhibit this potential, including (1) heterogeneity among and within participants that make scaling detection algorithms to a general population less precise, (2) confounders that lead to incorrect assumptions regarding a participant’s healthy state, (3) noise in the data at the sensor level that limits the sensitivity of detection algorithms, and (4) imprecision in self-reported labels that misrepresent the true data values associated with a given physiological event. The goal of this study was two-fold: (1) to characterize the performance of such algorithms in the presence of these challenges and provide insights to researchers on limitations and opportunities, and (2) to subsequently devise algorithms to address each challenge and offer insights on future opportunities for advancement. Our proposed algorithms include techniques that build on determining suitable baselines for each participant to capture important physiological changes and label correction techniques as it pertains to participant-reported identifiers. Our work is validated on potentially one of the largest datasets available, obtained with 8000+ participants and 1.3+ million hours of wearable data captured from Oura smart rings. Leveraging this extensive dataset, we achieve pre-symptomatic detection of COVID-19 with a performance receiver operator characteristic (ROC) area under the curve (AUC) of 0.725 without correction techniques, 0.739 with baseline correction, 0.740 with baseline correction and label correction on the training set, and 0.777 with baseline correction and label correction on both the training and the test set. Using the same respective paradigms, we achieve ROC AUCs of 0.919, 0.938, 0.943 and 0.994 for the detection of self-reported fever, and 0.574, 0.611, 0.601, and 0.635 for detection of self-reported shortness of breath. These techniques offer improvements across almost all metrics and events, including PR AUC, sensitivity at 75% specificity, and precision at 75% recall. The ring allows continuous monitoring for detection of event onset, and we further demonstrate an improvement in the early detection of COVID-19 from an average of 3.5 days to an average of 4.1 days before a reported positive test result.