bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological inhibition of adipose tissue adipose triglyceride lipase by Atglistatin prevents catecholamine-induced myocardial damage
Authors: Thiele Arne , Luettges Katja , Ritter Daniel , Beyhoff Niklas , Smeir Elia , Grune Jana , Steinhoff Julia S , Schupp Michael , Klopfleisch Robert , Rothe Michael , Wilck Nicola , Bartolomaeus Hendrik , Migglautsch Anna K , Breinbauer Rolf , Kershaw Erin E , Grabner Gernot F , Zechner Rudolf , Kintscher Ulrich , Foryst-Ludwig Anna 
Published: May 2021

Abstract

Aims
Heart failure (HF) is characterized by an overactivation of β-adrenergic signalling that directly contributes to impairment of myocardial function. Moreover, β-adrenergic overactivation induces adipose tissue lipolysis, which may further worsen the development of HF. Recently, we demonstrated that adipose tissue-specific deletion of adipose triglyceride lipase (ATGL) prevents pressure-mediated HF in mice. In this study, we investigated the cardioprotective effects of a new pharmacological inhibitor of ATGL, Atglistatin, predominantly targeting ATGL in adipose tissue, on catecholamine-induced cardiac damage.

Methods and results
Male 129/Sv mice received repeated injections of isoproterenol (ISO, 25 mg/kg BW) to induce cardiac damage. Five days prior to ISO application, oral Atglistatin (2 mmol/kg diet) or control treatment was started. Two and twelve days after the last ISO injection cardiac function was analysed by echocardiography. The myocardial deformation was evaluated using speckle-tracking-technique. Twelve days after the last ISO injection, echocardiographic analysis revealed a markedly impaired global longitudinal strain, which was significantly improved by the application of Atglistatin. No changes in ejection fraction were observed. Further studies included histological-, WB-, and RT-qPCR-based analysis of cardiac tissue, followed by cell culture experiments and mass spectrometry-based lipidome analysis. ISO application induced subendocardial fibrosis and a profound pro-apoptotic cardiac response, as demonstrated using an apoptosis-specific gene expression-array. Atglistatin treatment led to a dramatic reduction of these pro-fibrotic and pro-apoptotic processes. We then identified a specific set of fatty acids (FAs) liberated from adipocytes under ISO stimulation (palmitic acid, palmitoleic acid, and oleic acid), which induced pro-apoptotic effects in cardiomyocytes. Atglistatin significantly blocked this adipocytic FA secretion.

Conclusion
This study demonstrates cardioprotective effects of Atglistatin in a mouse model of catecholamine-induced cardiac damage/dysfunction, involving anti-apoptotic and anti-fibrotic actions. Notably, beneficial cardioprotective effects of Atglistatin are likely mediated by non-cardiac actions, supporting the concept that pharmacological targeting of adipose tissue may provide an effective way to treat cardiac dysfunction.
Ultrasound contrast agent hypersensitivity in patients allergic to polyethylene glycol: position statement by the European Association of Cardiovascular Imaging
Authors: Senior Roxy , Lindner Jonathan R. , Edvardsen Thor , Cosyns Bernard 
Published: May 2021

Abstract
The Food and Drug Administration alert enhances our understanding of the mechanism of severe reactions to ultrasound-enhancing agents (UEAs). The known incidence of these reactions remains low and unchanged (1 in 10 000 administrations). Because the risk-to-benefit ratio for ultrasound contrast agents (UCAs) remains extremely low, we do not advise any changes to laboratory policy regarding indications for their use. The use of these agents should continue in situations where they have been shown to be impactful. Lipid-based UCAs (SonoVue and Luminity) are contraindicated in patients who have a history of prior hypersensitivity to these UEAs, to polyethylene glycol (PEG) (macrogol), or to PEG-containing products, such as certain bowel preps for colonoscopy or laxatives.
mRNA and long non-coding RNA expression profiling of human periodontal ligament cells under tension loading
Authors: Lin Yifan , Cheng Tianfan , Zhu Shaoyue , Gu Min , Jin Lijian , Yang Yanqi 
Published: May 2021

SummaryObjectiveThis study explored the expression profiles of messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) in human periodontal ligament (PDL) cells subjected to tensile loading.MethodsPDL cells were isolated from the teeth of five healthy individuals, cultured and then exposed to tensile loading. RNA sequencing was performed to explore the mRNA and lncRNA expression profiles with or without tensile loading. Differential expression, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to reveal enriched biological functions and signal transduction pathways. Quantitative polymerase chain reaction (qPCR) was performed to validate the expression of specific mRNAs and lncRNAs associated with the enriched pathways.ResultsTensile loading significantly enhanced the osteogenic potential of PDL cells. Overall, 1438 mRNAs (860 up- and 578 down-regulated) and 195 lncRNAs (107 up- and 88 down-regulated) were differentially expressed (adjusted P-value &lt;0.05) in the tensile loading group versus the control group. GO and KEGG analyses of the differentially expressed genes indicated significant enrichment in osteogenesis-related biological processes and intracellular signal transduction pathways (e.g. the PI3K–Akt pathway), respectively. The qPCR analysis validated the expression levels of five selected mRNAs (EGFR, FGF5, VEGFA, HIF1A, and FOXO1) and three selected lncRNAs (CYTOR, MIR22HG, and SNHG3).LimitationFurther studies are warranted to validate the mechanisms regulating tension-induced bone remodelling in PDL cells and potential regulation by the identified lncRNAs.ConclusionThe notably altered mRNA and lncRNA expression profiles in PDL cells under tensile loading enhance our mechanistic understanding of tension-induced osteogenesis.
Leadless left ventricular endocardial pacing for CRT upgrades in previously failed and high-risk patients in comparison with coronary sinus CRT upgrades
Authors: Sidhu Baldeep Singh , Sieniewicz Benjamin , Gould Justin , Elliott Mark K , Mehta Vishal S , Betts Timothy R , James Simon , Turley Andrew J , Butter Christian , Seifert Martin , Boersma Lucas V A , Riahi Sam , Neuzil Petr , Biffi Mauro , Diemberger Igor , Vergara Pasquale , Arnold Martin , Keane David T , Defaye Pascal , Deharo Jean-Claude , Chow Anthony , Schilling Richard , Behar Jonathan M , Leclercq Christophe , Auricchio Angelo , Niederer Steven A , Rinaldi Christopher A 
Published: May 2021

Abstract

Aims
Cardiac resynchronization therapy (CRT) upgrades may be less likely to improve following intervention. Leadless left ventricular (LV) endocardial pacing has been used for patients with previously failed CRT or high-risk upgrades. We compared procedural and long-term outcomes in patients undergoing coronary sinus (CS) CRT upgrades with high-risk and previously failed CRT upgrades undergoing LV endocardial upgrades.

Method and results
Prospective consecutive CS upgrades between 2015 and 2019 were compared with those undergoing WiSE-CRT implantation. Cardiac resynchronization therapy response at 6 months was defined as improvement in clinical composite score (CCS) and a reduction in LV end-systolic volume (LVESV) ≥15%. A total of 225 patients were analysed; 121 CS and 104 endocardial upgrades. Patients receiving WiSE-CRT tended to have more comorbidities and were more likely to have previous cardiac surgery (30.9% vs. 16.5%; P = 0.012), hypertension (59.2% vs. 34.7%; P &lt; 0.001), chronic obstructive airways disease (19.4% vs. 9.9%; P = 0.046), and chronic kidney disease (46.4% vs. 21.5%; P &lt; 0.01) but similar LV ejection fraction (30.0 ± 8.3% vs. 29.5 ± 8.6%; P = 0.678). WiSE-CRT upgrades were successful in 97.1% with procedure-related mortality in 1.9%. Coronary sinus upgrades were successful in 97.5% of cases with a 2.5% rate of CS dissection and 5.6% lead malfunction/displacement. At 6 months, 91 WiSE-CRT upgrades and 107 CS upgrades had similar improvements in CCS (76.3% vs. 68.5%; P = 0.210) and reduction in LVESV ≥15% (54.2% vs. 56.3%; P = 0.835).

Conclusion
Despite prior failed upgrades and high-risk patients with more comorbidities, WiSE-CRT upgrades had high rates of procedural success and similar improvements in CCS and LV remodelling with CS upgrades.
Genomic Rearrangements and Sequence Evolution across Brown Algal Organelles
Authors: Starko Samuel , Bringloe Trevor T , Soto Gomez Marybel , Darby Hayley , Graham Sean W , Martone Patrick T 
Published: May 2021

Abstract
Organellar genomes serve as useful models for genome evolution and contain some of the most widely used phylogenetic markers, but they are poorly characterized in many lineages. Here, we report 20 novel mitochondrial genomes and 16 novel plastid genomes from the brown algae. We focused our efforts on the orders Chordales and Laminariales but also provide the first plastid genomes (plastomes) from Desmarestiales and Sphacelariales, the first mitochondrial genome (mitome) from Ralfsiales and a nearly complete mitome from Sphacelariales. We then compared gene content, sequence evolution rates, shifts in genome structural arrangements, and intron distributions across lineages. We confirm that gene content is largely conserved in both organellar genomes across the brown algal tree of life, with few cases of gene gain or loss. We further show that substitution rates are generally lower in plastid than mitochondrial genes, but plastomes are more variable in gene arrangement, as mitomes tend to be colinear even among distantly related lineages (with exceptions). Patterns of intron distribution across organellar genomes are complex. In particular, the mitomes of several laminarialean species possess group II introns that have T7-like ORFs, found previously only in mitochondrial genomes of Pylaiella spp. (Ectocarpales). The distribution of these mitochondrial introns is inconsistent with vertical transmission and likely reflects invasion by horizontal gene transfer between lineages. In the most extreme case, the mitome of Hedophyllum nigripes is ∼40% larger than the mitomes of close relatives because of these introns. Our results provide substantial insight into organellar evolution across the brown algae.
Robustness and repeatability of GlycoWorks RapiFluor-MS IgG N-glycan profiling in a long-term high-throughput glycomic study
Authors: Deriš Helena , Cindrić Ana , Lauber Matthew , Petrović Tea , Bielik Alicia , Taron Christopher H , van Wingerden Marleen , Lauc Gordan , Trbojević-Akmačić Irena 
Published: May 2021

Abstract
Protein glycosylation is the attachment of a carbohydrate moiety to a protein backbone affecting both structure and function of the protein. Abnormal glycosylation is associated with various diseases, and some of the changes in glycosylation are detectable even before symptom development. As such, glycans have emerged as compelling new biomarker candidates. A wide range of analytical methods exist for small-scale glycan analyses. However, there is a growing need for highly robust and reproducible high-throughput techniques that allow for large-scale glycoprofiling. Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates. The data was collected over a 5-month period using multiple UHPLC systems and chromatographic columns. Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%. The highest CVs ranging from 16 to 29% accompanied low abundance glycan peaks with the individual relative peak area below 1% that together made up for &lt;2% of the detected IgG N-glycome. These results show that the tested method is very robust and repeatable, making it suitable for the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time.
Strategies of inorganic and organic trace mineral supplementation in gestating hyperprolific sow diets: effects on the offspring performance and fetal programming
Authors: Villagómez-Estrada Sandra , Pérez José F , van Kuijk Sandra , Melo-Durán Diego , Forouzandeh Asal , Gonzalez-Solè Francesc , D’Angelo Matilde , Pérez-Cano Francisco J , Solà-Oriol David 
Published: May 2021

AbstractThe aim of the present study was to evaluate the effect of trace mineral nutrition on sow performance, mineral content, and intestinal gene expression of neonate piglets when inorganic mineral sources (ITM) were partially replaced by their organic mineral (OTM) counterparts. At 35 d postmating, under commercial conditions, a total of 240 hyperprolific multiparous sows were allocated into three experimental diets: 1) ITM: with Zn, Cu, and Mn at 80, 15, and 60 mg/kg, respectively; 2) partial replacement trace mineral source (Replace): with a 30 % replacement of ITM by OTM, resulting in ITM + OTM supplementation of Zn (56 + 24 mg/kg), Cu (10.5 + 4.5 mg/kg), and Mn (42 + 18 mg/kg); and 3) Reduce and replace mineral source (R&R): reducing a 50% of the ITM source of Zn (40 + 24 mg/kg), Cu (7.5 + 4.5 mg/kg), and Mn (30 + 18 mg/kg). At farrowing, 40 piglets were selected, based on birth weight (light: &lt;800 g, and average: &gt;1,200 g), for sampling. Since the present study aimed to reflect results under commercial conditions, it was difficult to get an equal parity number between the experimental diets. Overall, no differences between experimental diets on sow reproductive performance were observed. Light piglets had a lower mineral content (P &lt; 0.05) and a downregulation of several genes (P &lt; 0.10) involved in physiological functions compared with their average littermates. Neonate piglets born from Replace sows had an upregulation of genes involved in functions like immunity and gut barrier, compared with those born from ITM sows (P &lt; 0.10), particularly in light piglets. In conclusion, the partial replacement of ITM by their OTM counterparts represents an alternative to the totally inorganic supplementation with improvements on neonate piglet gene expression, particularly in the smallest piglets of the litter. The lower trace mineral storage together with the greater downregulation of gut health genes exposed the immaturity and vulnerability of small piglets.
Minimal Effects of Intravenous Administration of Xenogeneic Adipose Derived Stem Cells on Organ Function in a Porcine 40% TBSA Burn Model
Authors: Heard Tiffany C , Gómez Belinda I , Saathoff Micaela E , Duarte Jamila , Dubick Michael A , Bynum James A , Christy Robert J , Burmeister David M 
Published: May 2021

Abstract
Adipose stem cells (ASCs) have shown therapeutic promise for various conditions, including burn injury. While ASCs have immunomodulatory properties, concerns exist over pro-coagulant activity after intravenous (IV) administration. In the present study, we examined IV human ASC delivery in terms of coagulation, organ function, and inflammation in a 40% total body surface area (TBSA) swine burn model. Anesthetized female Yorkshire swine were burned and randomized to receive 15 ml/kg Lactated Ringer’s containing: no ASCs; a low dose (5 × 105 ASCs/kg); or a high dose (5 × 106 ASCs/kg). For biochemical analysis, blood was collected at baseline (BL), 3, 6, 12, and 24 h post-burn, while kidney and liver tissue was collected post-euthanasia. A significant, but transient, effect of ASCs was seen on prothrombin times and INR, wherein low doses revealed slight hypercoagulation. Burns increased partial thromboplastin time, fibrinogen, and d-dimer levels, which was unchanged with ASC administration. ASCs tended to exacerbate increases in bilirubin at 3 h, but this didn’t reach statistical significance. A significant effect of ASCs on creatinine and BUN was seen, wherein low doses elevated levels at 24 h (creatinine, P = 0.0012; BUN, P = 0.0195). Hepatic and renal TUNEL staining were similar for all groups. A dose-dependent decrease in IL-8 was observed, while low doses significantly increased IL-1RA at 3h (P = 0.050), IL-12 at 12h (P = 0.021) and IL-6 at 24 h post-burn (P = 0.035). IV administration of xenogeneic ASCs slightly increased coagulation, but effects on burn-induced renal and hepatic dysfunction effects were minimal. Despite some significant immunomodulation, organ dysfunction effects were modest. Collectively, this study provides evidence to be skeptical about xenogeneic ASC administration in regards to burns.
Homeless Tent Fires: A Descriptive Analysis of Tent Fires in the Homeless Population
Authors: Huang Samantha , Choi Katherine J , Pham Christopher H , Collier Zachary J , Dang Justin M , Kiwanuka Harriet , Sheckter Clifford C , Yenikomshian Haig A , Gillenwater Justin 
Published: May 2021

Abstract
Tent fires are a growing issue in regions with large homeless populations given the rise in homelessness within the United States and existing data that suggest worse outcomes in this population. The aim of this study was to describe the characteristics and outcomes of tent fire burn injuries in the homeless population. A retrospective review was conducted involving two verified regional burn centers with patients admitted for tent fire burns between January 2015 and December 2020. Variables recorded include demographics, injury characteristics, hospital course, and patient outcomes. Sixty-nine patients met the study inclusion criteria. The most common mechanisms of injury were by portable stove accident, assault, and tobacco or methamphetamine related. Median percent total body surface area (%TBSA) burned was 6% (interquartile range [IQR] 9%). Maximum depth of injury was partial thickness in 65% (n = 45) and full thickness in 35% (n = 24) of patients. Burns to the upper and lower extremities were present in 87% and 54% of patients, respectively. Median hospital length of stay (LOS) was 10 days (IQR = 10.5) and median ICU LOS was 1 day (IQR = 5). Inhalation injury was present in 14% (n = 10) of patients. Surgical intervention was required in 43% (n = 30) of patients, which included excision, debridement, skin grafting, and escharotomy. In-hospital mortality occurred in 4% (n = 3) of patients. Tent fire burns are severe enough to require inpatient and ICU level of care. A high proportion of injuries involved the extremities and pose significant barriers to functional recovery in this vulnerable population. Strategies to prevent these injuries are paramount.
Combined endoscopic and mini-open repair of chronic complete proximal hamstring tendon avulsion: a novel approach and short-term outcomes
Authors: Factor Shai , Khoury Amal , Atzmon Ran , Vidra Matias , Amar Eyal , Rath Ehud 
Published: May 2021

Abstract
To evaluate the outcome of a novel, combined endoscopic and mini-open repair (CEMR) of a chronic complete retracted proximal hamstring tendon avulsion (PHA). A retrospective case series of a single-surgeon database for all patients, with a minimum of 1-year follow-up, who underwent CEMR between July 2015 and September 2019 was performed. Patients were evaluated for their functional outcome using the Perth Hamstring Assessment Tool (PHAT). At the latest follow-up, patients were evaluated for their muscle strength, subjective satisfaction and post-operative complications. Twelve patients who underwent endoscopic surgery for chronic PHA were identified, of which seven patients underwent CEMR. After exclusion of one patient from the study due to an open claim for health insurance, six patients (five males) with a mean age of 48 years (range 20–61 years) were evaluated. The mean time from injury to surgery was 12 months (range 2–43 months). At a mean follow-up of 28 months (range 12–55 months), the average PHAT score was 73 (range 70–80). The mean subjective activity level percentage improved from 34 (range 20–50) pre-surgery to 81 (range 75–90) post-surgery. The mean strength of the quadriceps, hamstring at 30°, and hamstring at 90° of the operated leg compared to the uninjured leg did not differ significantly. One patient underwent adhesiolysis 1 year after the index procedure for treatment of subcutaneous adhesions. CEMR is a viable and safe option for the treatment of chronic complete proximal hamstring tears, with good to excellent short-term functional outcome. Level of evidence: IV.
Prognostic and Predictive Impact of Primary Tumor Sidedness for Previously Untreated Advanced Colorectal Cancer
Authors: Yin Jun , Cohen Romain , Jin Zhaohui , Liu Heshan , Pederson Levi , Adams Richard , Grothey Axel , Maughan Timothy S , Venook Alan , Van Cutsem Eric , Punt Cornelis , Koopman Miriam , Falcone Alfredo , Tebbutt Niall C , Seymour Matthew T , Bokemeyer Carsten , Rubio Eduardo Diaz , Kaplan Richard , Heinemann Volker , Chibaudel Benoist , Yoshino Takayuki , Zalcberg John , Andre Thierry , De Gramont Aimery , Shi Qian , Lenz Heinz-Josef 
Published: May 2021

Abstract

Background
Unplanned subgroup analyses from several studies have suggested primary tumor sidedness (PTS) as a potential prognostic and predictive parameter in metastatic colorectal cancer (mCRC). We aimed to investigate the impact of PTS on outcomes of mCRC patients.

Methods
PTS data of 9277 mCRC patients from 12 first-line randomized trials in the ARCAD database were pooled. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for age, sex, performance status, prior radiation/chemotherapy, and stratified by treatment arm. Predictive value was tested by interaction term between PTS and treatment (cetuximab plus chemotherapy vs chemotherapy alone). All statistical tests were 2-sided.

Results
Compared with right-sided metastatic colorectal cancer patients (n = 2421, 26.1%), left-sided metastatic colorectal cancer patients (n = 6856, 73.9%) had better OS (median = 21.6 vs 15.9 months; adjusted hazard ratio [HRadj] = 0.71, 95% confidence interval [CI] = 0.67 to 0.76; P &lt; .001) and PFS (median = 8.6 vs 7.5 months; HRadj = 0.80, 95% CI = 0.75 to 0.84; P &lt; .001). Interaction between PTS and KRAS mutation was statistically significant (Pinteraction &lt; .001); left-sidedness was associated with better prognosis among KRAS wild-type (WT) (OS HRadj = 0.59, 95% CI = 0.53 to 0.66; PFS HRadj =0.68, 95% CI = 0.61 to 0.75) but not among KRAS mutated tumors. Among KRAS-WT tumors, survival benefit from anti-EGFR was confirmed for left-sidedness (OS HRadj = 0.85, 95% CI = 0.75 to 0.97; P = .01; PFS HRadj = 0.77, 95% CI = 0.67 to 0.88; P &lt; .001) but not for right-sidedness.

Conclusions
The prognostic value of PTS is restricted to the KRAS-WT population. PTS is predictive of anti-EGFR efficacy, with a statistically significant improvement of survival for left-sidedness mCRC patients. These results suggest treatment choice in mCRC should be based on both PTS and KRAS status.