bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiologic Manifestations of Mycobacterium chimaera Infection After Open Heart Surgery
Authors: Moore Andrew E. , Ngo Tuan , Donald Joseph , Shorey Samira , Sivakumar Ram , Velagapudi Vivek , Walker Christopher M. 
Published: April 2024

Purpose:
The objective of this study is to identify and detail the radiologic manifestations of surgical site and disseminated Mycobacterium chimaera (MC) infection. The aim is to facilitate early identification and diagnosis of MC, considering its indolent nature and the challenges involved in clinically and pathologically establishing the diagnosis.

Patients and Methods:
This was a retrospective cohort study reviewing computed tomography (CT), positron emission tomography (PET)/CT, and magnetic resonance imaging examinations in patients over the age of 18 years with a history of open heart surgery and a clinical or pathologic diagnosis of MC. Two radiology residents, a fellowship-trained nuclear medicine radiologist, and a fellowship-trained cardiothoracic radiologist performed consensus reads to determine the imaging findings seen in MC infection.

Results:
Twenty-five patients were included. Localized, surgical site infection was more common than disseminated disease. Typical CT findings included peristernal soft tissue thickening, sinus tracts often extending to the cutaneous surface, slowly enlarging fluid collections, and sternal osteolysis. PET/CT findings demonstrated hypermetabolic activity in nearly all patients localized to sites of infection. Imaging findings for disseminated infection included hepatosplenomegaly, lymphadenopathy, involvement of the central nervous system, discitis/osteomyelitis, and distant abscesses.

Conclusions:
Imaging plays a vital role in suggesting possible surgical sites and disseminated MC infection acquired from open heart surgery. Radiologists must keep a high index of suspicion given the indolent nature and subtle imaging change over time. PET/CT is most useful in diagnosis and helps in differentiating between a sterile postoperative fluid collection or scarring and active MC infection and helps provide a target for debridement.
SALVIANOLIC ACID A ATTENUATES ANGIOTENSIN II-INDUCED CARDIAC FIBROSIS THROUGH REGULATING THE TXNIP SIGNALING PATHWAY
Authors: Ye Huaqing , Wang Kaiyi , Ma Jiaxin , Cui Sumei , Guo Jialin , Yang Kehui , Lyu Linmao 
Published: April 2024

ABSTRACT
Cardiac fibrosis, characterized by excessive collagen accumulation in heart tissues, poses a significant clinical challenge in various heart diseases and complications. Although salvianolic acid A (Sal A) from Danshen (Salvia miltiorrhiza) has shown promise in the treatment of ischemic heart disease, myocardial infarction, and atherosclerosis, its effects on cardiac fibrosis remain unexplored. Our study investigated the efficacy of Sal A in reducing cardiac fibrosis and elucidated its underlying molecular mechanisms. We observed that Sal A demonstrated significant cardioprotective effects against Angiotensin II (Ang II)-induced cardiac remodeling and fibrosis, showing a dose-dependent reduction in fibrosis in mice and suppression of cardiac fibroblast proliferation and fibrotic protein expression in vitro. RNA sequencing revealed that Sal A counteracted Ang II-induced upregulation of Txnip, and subsequent experiments indicated that it acts through the inflammasome and ROS pathways. These findings establish the antifibrotic effects of Sal A, notably attenuated by Txnip overexpression, and highlight its significant role in modulating inflammation and oxidative stress pathways. This underscores the importance of further research on Sal A and similar compounds, especially regarding their effects on inflammation and oxidative stress, which are key factors in various cardiovascular diseases.
Haptoglobin depletion during the first seven days of veno-venous ECMO therapy is associated with increased mortality and adverse outcomes in patients with ARDS
Authors: Bünger Victoria , Hunsicker Oliver , Krannich Alexander , Balzer Felix , Spies Claudia D. , Kuebler Wolfgang M. , Weber-Carstens Steffen , Menk Mario , Graw Jan A. 
Published: April 2024

Abstract

Background
Hemolysis is a frequent complication in patients with sepsis, ARDS, or extracorporeal membrane oxygenation (ECMO). Haptoglobin (Hp) can scavenge released cell-free hemoglobin (CFH). Hemolysis and low plasma concentrations of Hp may be independently associated with mortality in critically ill patients.

Methods
Retrospective analysis of 435 patients with ARDS and veno-venous ECMO therapy, admitted to a tertiary ARDS referral center (01/2007-12/2018). Hp-depletion was defined as decrease in plasma Hp concentration < 0.39 g/l within the first week after ECMO initiation. Patients with Hp depletion were compared to patients without Hp depletion. The primary endpoint was 28-day mortality. Secondary endpoints included organ dysfunction-free, renal replacement therapy (RRT)-free, vasopressor-free, and ECMO-free composites.

Results
Patients with Hp-depletion (n = 269) had a significantly higher mortality 28 days after ECMO initiation compared to patients without Hp-depletion (43.5%, [95% CI: 37.52-49.66] vs. 25.3%, [19.03-32.74], p < 0.001). Furthermore, patients with Hp depletion had fewer organ dysfunction-free days (subdistribution hazard ratio, [SHR] 0.35, [95% CI 0.25-0.50], p < 0.001), lower chances for successful weaning from renal replacement therapy (SHR 0.50, [0.32-0.79], p < 0.001), vasopressor therapy (SHR 0.39, [0.28-0.54], p < 0.001), and ECMO therapy (SHR 0.41, [0.30-0.57], p < 0.001) within 28 days after ECMO initiation. Patients with initial Hp <0.66 g/l had higher risks for Hp-depletion than patients with initial Hp ≥ 0.66 g/l.

Conclusion
Patients with Hp-depletion within the first week of ECMO therapy might benefit from close monitoring of hemolysis with early detection and elimination of the underlying cause. They might be potential candidates for future Hp supplementation therapy to prevent overload of the CFH-scavenger system.
BURNS INDUCE ALTERATIONS IN THE ACYL PROTEOME OF MICE AND HUMANS
Authors: Bieerkehazhi Shayahati , Barayan Dalia , Khalaf Fadi , de Brito Monteiro Lauar , Aijaz Ayesha , Volk Charlotte , Matveev Anna , Saldanha Sean , Faour Sara , Jeschke Marc G. 
Published: April 2024

ABSTRACT
Hypermetabolic reprogramming triggered by thermal injury causes substantial morbidity and mortality. Despite the therapeutic potential of targeting this response, the underlying mechanisms remain poorly understood. Interestingly, protein S-acylation is a reversible posttranslational modification induced by metabolic alterations via DHHC acyltransferases. While this modification aids in the regulation of cellular functions, deregulated S-acylation contributes to various diseases by altering protein structure, stability, and localization. However, whether and how S-acylation may impact morbidity and mortality during postburn hypermetabolism is unknown. In this study, we discovered that alterations in the acyl proteome play a key role in mediating adverse outcomes that occur after burn injury. Using a murine model, we show that burn injury induces profound changes in the expression of various DHHC isoforms in metabolic organs central to regulating postburn hypermetabolism, the adipose tissue, and liver. This was accompanied by increased levels of S-acylated proteins in several pathways involved in mediating the adverse hypermetabolic response, including ER stress, lipolysis, and browning. In fact, similar results were also observed in adipose tissue from severely burned patients, as reflected by increased S-acylation of ERK1/2, eIF2a, ATGL, FGF21, and UCP1 relative to nonburn controls. Importantly, pharmacologically targeting this posttranslational modification using a nonselective DHHC inhibitor effectively attenuated burn-induced ER stress, lipolysis, and browning induction in an ex vivo explant model. Together, these findings suggest that S-acylation may facilitate the protein activation profile that drives burn-induced hypermetabolism and that targeting it could potentially be an effective strategy to restore metabolic function and improve outcomes after injury.
WTAP-MEDIATED M6A MODIFICATION OF KLF6 AGGRAVATES HYPOXIA/REOXYGENATION-INDUCED HUMAN CARDIOMYOCYTE INJURY
Authors: Fang Mingcheng , Li Ting , Wu Zhiyong 
Published: April 2024

ABSTRACT

Background: Myocardial infarction (MI) is a severe condition that typically results from the ischemia and necrosis of heart muscle. Kruppel-like factor 6 (KLF6) can aggravate myocardial ischemia/reperfusion injury. This work aims to reveal its role and mechanism in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. Methods: Human cardiomyocyte (AC16) was exposed to hypoxic treatment to mimic MI-like cell injury. mRNA expression levels of KLF6 and WT1-associated protein (WTAP) were detected by quantitative real-time polymerase chain reaction. Protein expression was detected by western blotting assay. Cell viability was assessed by CCK-8 assay. Cell apoptosis and cell cycle were investigated by flow cytometry. Enzyme-linked immunosorbent assays were conducted to detect IL-1β, TNF-α and IL-6 levels. Fe2+ colorimetric assay kit was used to detect Fe2+ level. MDA Content Assay Kit was used to detect MDA level. Cellular ROS Assay kit was applied to assess ROS level. The association of KLF6 and WTAP was identified by RNA immunoprecipitation assay and dual-luciferase reporter assay. Results: KLF6 and WTAP expression at mRNA and protein levels were significantly upregulated in serum samples of MI patients and H/R-induced AC16 cells when compared with control groups. KLF6 silencing attenuated H/R-induced AC16 cell apoptosis, inflammatory response, oxidative stress, and ferroptosis. Additionally, WTAP stabilized KLF6 mRNA by regulating its m6A modification. Furthermore, WTAP knockdown rescued H/R-induced AC16 cell apoptosis, inflammatory response, oxidative stress, and ferroptosis by decreasing KLF6 expression. Conclusion: WTAP-mediated m6A modification of KLF6 aggravated hypoxia/reoxygenation-induced apoptosis, inflammatory response, oxidative stress, and ferroptosis of human cardiomyocytes, providing a therapeutic strategy for MI.
Impact of Procedure Risk vs Frailty on Outcomes of Elderly Patients Undergoing Emergency General Surgery: Results of a National Analysis
Authors: Zakhary Bishoy , Coimbra Bruno C , Kwon Junsik , Allison-Aipa Timothy , Firek Matthew , Coimbra Raul 
Published: April 2024

BACKGROUND:
The direct association between procedure risk and outcomes in elderly patients who undergo emergency general surgery (EGS) has not been analyzed. Studies only highlight the importance of frailty. A comprehensive analysis of relevant risk factors and their association with outcomes in elderly patients who undergo EGS is lacking. We hypothesized that procedure risk has a stronger association with relevant outcomes in elderly patients who undergo EGS compared with frailty.

STUDY DESIGN:
Elderly patients (age >65 years) undergoing EGS operative procedures were identified in the NSQIP database (2018 to 2020) and stratified based on the presence of frailty calculated by the Modified 5-Item Frailty Index (mFI-5; mFI 0 nonfrail, mFI 1 to 2 frail, and mFI ≥3 severely frail) and based on procedure risk. Multivariable regression models and receiving operative curve analysis were used to determine risk factors associated with outcomes.

RESULTS:
A total of 59,633 elderly patients who underwent EGS were classified into nonfrail (17,496; 29.3%), frail (39,588; 66.4%), and severely frail (2,549; 4.3%). There were 25,157 patients in the low-risk procedure group and 34,476 in the high-risk group. Frailty and procedure risk were associated with increased mortality, complications, failure to rescue, and readmissions. Differences in outcomes were greater when patients were stratified according to procedure risk compared with frailty stratification alone. Procedure risk had a stronger association with relevant outcomes in elderly patients who underwent EGS compared with frailty.

CONCLUSIONS:
Assessing frailty in the population of elderly patients who undergo EGS without adjusting for the type of procedure or procedure risk ultimately presents an incomplete representation of how frailty impacts patient-related outcomes.
biGMamAct: efficient CRISPR/Cas9-mediated docking of large functional DNA cargoes at theACTBlocus
Authors: Pelosse Martin , Marcia Marco 
Published: April 2024

AbstractRecent advances in molecular and cell biology and imaging have unprecedentedly enabled multi-scale structure-functional studies of entire metabolic pathways from atomic to micrometer resolution, and the visualization of macromolecular complexesin situ, especially if these molecules are expressed with appropriately-engineered and easily-detectable tags. However, genome editing in eukaryotic cells is challenging when generating stable cell lines loaded with large DNA cargoes. To address this limitation, here, we have conceived biGMamAct, a system that allows the straightforward assembly of a multitude of genetic modules and their subsequent integration in the genome at theACTBlocus with high efficacy, through standardized cloning steps. Our technology encompasses a set of modular plasmids for mammalian expression, which can be efficiently docked into the genome in tandem with a validated Cas9/sgRNA pair through homologous-independent targeted insertion (HITI). As a proof of concept, we have generated a stable cell line loaded with an 18.3-kilobase-long DNA cargo to express 6 fluorescently-tagged proteins and simultaneously visualize 5 different subcellular compartments. Our protocol leads from thein-silicodesign to the genetic and functional characterization of single clones within 6 weeks and can be implemented by any researcher with familiarity with molecular biology and access to mammalian cell culturing infrastructure.
Information theory for data-driven model reduction in physics and biology
Authors: Schmitt Matthew S. , Koch-Janusz Maciej , Fruchart Michel , Seara Daniel S. , Rust Michael , Vitelli Vincenzo 
Published: April 2024

Model reduction is the construction of simple yet predictive descriptions of the dynamics of many-body systems in terms of a few relevant variables. A prerequisite to model reduction is the identification of these relevant variables, a task for which no general method exists. Here, we develop a systematic approach based on the information bottleneck to identify the relevant variables, defined as those most predictive of the future. We elucidate analytically the relation between these relevant variables and the eigenfunctions of the transfer operator describing the dynamics. Further, we show that in the limit of high compression, the relevant variables are directly determined by the slowest-decaying eigenfunctions. Our information-based approach indicates when to optimally stop increasing the complexity of the reduced model. Furthermore, it provides a firm foundation to construct interpretable deep learning tools that perform model reduction. We illustrate how these tools work in practice by considering uncurated videos of atmospheric flows from which our algorithms automatically extract the dominant slow collective variables, as well as experimental videos of cyanobacteria colonies in which we discover an emergent synchronization order parameter.Significance StatementThe first step to understand natural phenomena is to intuit which variables best describe them. An ambitious goal of artificial intelligence is to automate this process. Here, we develop a framework to identify these relevant variables directly from complex datasets. Very much like MP3 compression is about retaining information that matters most to the human ear, our approach is about keeping information that matters most to predict the future. We formalize this insight mathematically and systematically answer the question of when to stop increasing the complexity of minimal models. We illustrate how interpretable deep learning tools built on these ideas reveal emergent collective variables in settings ranging from satellite recordings of atmospheric fluid flows to experimental videos of cyanobacteria colonies.
Genome-wide profiling of highly similar paralogous genes using HiFi sequencing
Authors: Chen Xiao , Baker Daniel , Dolzhenko Egor , Devaney Joseph M , Noya Jessica , Berlyoung April S , Brandon Rhonda , Hruska Kathleen S , Lochovsky Lucas , Kruszka Paul , Newman Scott , Farrow Emily , Thiffault Isabelle , Pastinen Tomi , Kasperaviciute Dalia , Gilissen Christian , Vissers Lisenka , Hoischen Alexander , Berger Seth , Vilain Eric , Délot Emmanuèle ,   UCI Genomics Research to Elucidate the Genetics of Rare Diseases (UCI GREGoR) Consortium, Eberle Michael A 
Published: April 2024

AbstractVariant calling is hindered in segmental duplications by sequence homology. We developed Paraphase, a HiFi-based informatics method that resolves highly similar genes by phasing all haplotypes of a gene family. We applied Paraphase to 160 long (>10 kb) segmental duplication regions across the human genome with high (>99%) sequence similarity, encoding 316 genes. Analysis across five ancestral populations revealed highly variable copy numbers of these regions. We identified 23 families with exceptionally low within-family diversity, where extensive gene conversion and unequal-crossing over have resulted in highly similar gene copies. Furthermore, our analysis of 36 trios identified 7de novoSNVs and 4de novogene conversion events, 2 of which are non-allelic. Finally, we summarized extensive genetic diversity in 9 medically relevant genes previously considered challenging to genotype. Paraphase provides a framework for resolving gene paralogs, enabling accurate testing in medically relevant genes and population-wide studies of previously inaccessible genes.
Sanger validation of WGS variants - when to?
Authors: Kopernik Arina , Zobkova Gaukhar , Doroschuk Natalia , Smirnova Anna , Molodtsova-Zolotukhina Daria , Sagaydak Olesya , Ryzhkova Oxana , Kutsev Sergey , Groznova Olga , Melikyan Lyusya , Bondarchuk Elizaveta , Woroncow Mary , Albert Eugene , Bogdanov Viktor , Volchkov Pavel 
Published: April 2024

AbstractWith the development of Next-Generation Sequencing (NGS) technologies it became possible to simultaneously analyze millions of variants. Despite the quality improvement it is generally still required to confirm the variants before reporting. However, in recent years the dominant idea is that one could define the quality thresholds for “high quality” variants which do not require orthogonal validation. Despite that, no works to date report the concordance between variants from whole genome sequencing and their gold-standard Sanger validation. In this study we analyzed the concordance for 1756 WGS variants in order to establish the appropriate thresholds for high-quality variants filtering. Resulting thresholds allowed us to drastically reduce the number of variants which require validation, to 5,6% and 1.2% of the initial set for caller-agnostic thresholds and caller-dependent QUAL threshold respectively.
Homeostatic Control on the Thought: a Comprehensive Explanation of Mind Wandering
Authors: Shinagawa Kazushi , Yamada Kota 
Published: April 2024

AbstractOur thoughts are inherently dynamic, often wandering far from the current situation. Mind-wandering (MW), which is these thought transitions, is crucial for understanding the nature of human thought. Although previous research has identified various factors influencing MW, a comprehensive framework integrating these findings remains absent. Here, we propose that homeostasis has the potential to explain MW and validate the idea through simulations by replicating previous findings. We employed a homeostatic reinforcement learning model where independent drives for the task and others were assigned, and drive reduction became a reward and trained under sustained attention to the response task. We confirmed that the model behaves consistently with the empirical results reported in human experiments, suggesting that the model accurately captures the underlying mechanism of MW. Finally, we discuss the behavioral and neurobiological commonality between human thought and animal behavior and the possibility that the same principle, homeostasis, controls these phenomena.
TINNiK: Inference of the Tree of Blobs of a Species Network Under the Coalescent
Authors: Allman Elizabeth S. , Baños Hector , Mitchell Jonathan D. , Rhodes John A. 
Published: April 2024

AbstractThe tree of blobs of a species network shows only the tree-like aspects of relationships of taxa on a network, omitting information on network substructures where hybridization or other types of lateral transfer of genetic information occur. By isolating such regions of a network, inference of the tree of blobs can serve as a starting point for a more detailed investigation, or indicate the limit of what may be inferrable without additional assumptions. Building on our theoretical work on the identifiability of the tree of blobs from gene quartet distributions under the Network Multispecies Coalescent model, we develop an algorithm, TINNiK, for statistically consistent tree of blobs inference. We provide examples of its application to both simulated and empirical datasets, utilizing an implementation in theMSCquartets 2.0R package.MSC Classification92D15, 92D20
Safety and long-term performance of the Medtronic 3830 lead in His-bundle vs. Left bundle branch area pacing: A single-center 5-year experience
Authors: Sarkar Abdullah , Sanchez-Nadales Alejandro , Sleiman Jose , Lewis-Camargo Antonio , Alonso Mileydis , Seijo Yelenis , Sanchez-Nadales Andres , Bibawy John , Helguera Marcelo , Pinski Sergio L. , Baez-Escudero Jose L. 
Published: April 2024

AbstractBACKGROUNDThe short-term safety, feasibility, and performance of the Medtronic SelectSecure 3830-69 cm pacing lead for conduction system pacing (CSP) has been reported; however, its longer-term performance is not well established.OBJECTIVEThe purpose of this study is to examine the long-term performance of the 3830 lead for His Bundle Pacing (HBP) and Left Bundle Branch Area Pacing (LBBAP).METHODSWe retrospectively reviewed all cases of CSP performed with the Medtronic SelectSecure 3830-69 cm pacing lead at Cleveland Clinic Florida between May 2016 and October 2021.RESULTSOf 515 attempts, HBP achieved an 85% success rate (340 cases), while LBBAP demonstrated a higher success rate of 97.4% (150 cases). The mean follow-up was 28 months for HBP and 14 months for LBBAP, with patient ages averaging 75 and 77 years, respectively. Only 7% of the cohort had an ejection fraction below 50%. The primary indications for HBP were sick sinus syndrome (35.5%), atrioventricular block (35.2%), cardiac resynchronization therapy (10%), and refractory atrial fibrillation (18.8%), with similar distributions for LBBAP. The HBP group’s capture threshold at implant was 1.3 ± 0.8 V at 0.8 ± 0.2 ms, which significantly increased at chronic follow-up to 1.68 ± 1.3 V at 0.7 ± 0.3 ms (p <0.001), whereas the LBBAP group’s capture threshold remained stable from 0.8 ± 0.5 V at 0.5 ± 0.3 ms to to 0.9 ± 0.5 V at 0.5 ± 0.3 ms, (p= 0.35). Lead revisions were more common in the HBP group (50 cases) than in the LBBAP group (5 cases), with exit block rates of 11.7% and 3%, respectively.CONCLUSIONUsing the 3830 lead for HBP can result in significantly elevated thresholds, loss of His-bundle capture, and frequent lead revision rates at long-term follow-up. These issues are less commonly seen when the lead is used for LBBAP.