bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequential ruptures of penetrating atherosclerotic ulcers of ascending aorta, aortic arch and descending thoracic aorta
Authors: Kaul Pankaj , Paniagua Rodolfo , Petsa Afroditi , Singh Raj 
Published: October 2020

Abstract
Background
Penetrating ulcers of aorta, aortic dissections and intramural hematomas all come under acute aortic syndromes and have important similarities and differences.

Case report
We report a 67 year old man with rupture of a large penetrating ulcer of the distal ascending aorta with hemopericardium and left hemothorax. He underwent interposition graft replacement of ascending aorta and hemi-arch with a 30 mm Gelweave Vascutek graft but represented 6 months later with development of a penetrating ulcer which ruptured into a huge 14 cm pseudoaneurysm. This was repaired with a 28 mm Vascutek Gelseal graft replacement of arch and interposition graft reconstruction of innominate and left common carotid arteries. 6 weeks later, however, he ruptured his proximal descending aorta and underwent TEVAR satisfactorily. Unfortunately, 2 days later, he developed a pathological fracture of left proximal tibia with metastasis from a primary renal cell carcinoma. He died 3 weeks later from respiratory failure.
We shall briefly outline the similarities and differences in presentation and management of penetrating aortic ulcers, aortic dissections and intramural haematomas. We shall discuss, in greater detail, penetrating ulcers of thoracic aorta, their natural history, location, complications and management.

Conclusion
This case report is unique on account of initial successful surgical redressal following rupture of penetrating ulcer of distal ascending aorta into left pleural and pericardial cavities, normally associated with instant death. The haemodynamic effects of the rupture were staggered due to initial contained rupture into a smaller pseudoaneurysm, followed by a further rupture into a false aneurysmal sac followed eventually by generalised rupture into the pleural and pericardial cavities - a unique way of aortic rupture. Further development of another penetrating ulcer and a small pseudoaneurysm in the distal arch 6 months later which further ruptured into a larger 14 cm false aneurysmal sac, which again did not result in exsanguination, is again extraordinarily rare. Thereafter he underwent emergency thoracic endovascular aortic repair (TEVAR) for a further rupture of descending thoracic aorta. All three ruptures were managed successfully and would usually be associated with near-certain death, only for the patient to succumb eventually to the complications of metastatic renal cell carcinoma.
Loop electrosurgical excision procedure combined with cold coagulation for cervical intraepithelial neoplasia and adenocarcinoma in-situ: a feasible treatment with a low risk of residual/recurrent disease
Authors: Yang Eun Jung , Kim Nae Ry , Choi Ji Yeon , Kim Wook Youn , Lee Sun Joo 
Published: October 2020

Abstract
Objective
This study was performed to evaluate the significance of positive resection margins (RMs) with the loop electrosurgical excision procedure combined with cold coagulation (LEEP with CC) as a definitive treatment for patients with cervical intraepithelial neoplasia (CIN) and adenocarcinoma in-situ.

Methods
We retrospectively reviewed 467 patients who underwent LEEP with CC. A right-angled triangular loop in a single pass followed by a CC (120 °C) to the cone bed for 10 to 20 s was used. Pathology reports and clinical data were obtained and evaluated.

Results
Histopathology evaluation of LEEP tissue samples revealed the presence of CIN 1 in 69, CIN 2/3 in 366, AIS in 5 and invasive carcinoma in 16 (microinvasive squamous cell carcinoma (SCC) and invasive SCC, 13 and 3) patients. Margins were positive in 66 (14.5%) cases: 0 in CIN 1, 54 in CIN 2/3 (12.4%), 1 in AIS (20.0%) and 11 in microinvasive/invasive SCC (68.8%). Although 54 CIN2/3 patients with positive RMs did not undergo additional treatment, 1 of these (1.9%) was confirmed to have residual CIN3 at the first follow-up. Two of 8 (25.0%) microinvasive SCC patients with positive RMs were confirmed to have residual diseases (1 microinvasive SCC and 1 invasive SCC) after hysterectomy. Four out of 360 (1 positive RM, 3 negative RM) CIN cases recurred during the study period.

Conclusions
These results suggest that CIN patients with positive RMs after LEEP with CC may be followed up without additional treatment.
Artificial intelligence algorithm for predicting cardiac arrest using electrocardiography
Authors: Kwon Joon-myoung , Kim Kyung-Hee , Jeon Ki-Hyun , Lee Soo Youn , Park Jinsik , Oh Byung-Hee 
Published: October 2020

Abstract
Background
In-hospital cardiac arrest is a major burden in health care. Although several track-and-trigger systems are used to predict cardiac arrest, they often have unsatisfactory performances. We hypothesized that a deep-learning-based artificial intelligence algorithm (DLA) could effectively predict cardiac arrest using electrocardiography (ECG). We developed and validated a DLA for predicting cardiac arrest using ECG.

Methods
We conducted a retrospective study that included 47,505 ECGs of 25,672 adult patients admitted to two hospitals, who underwent at least one ECG from October 2016 to September 2019. The endpoint was occurrence of cardiac arrest within 24 h from ECG. Using subgroup analyses in patients who were initially classified as non-event, we confirmed the delayed occurrence of cardiac arrest and unexpected intensive care unit transfer over 14 days.

Results
We used 32,294 ECGs of 10,461 patients and 4483 ECGs of 4483 patients from a hospital were used as development and internal validation data, respectively. Additionally, 10,728 ECGs of 10,728 patients from another hospital were used as external validation data, which confirmed the robustness of the developed DLA. During internal and external validation, the areas under the receiver operating characteristic curves of the DLA in predicting cardiac arrest within 24 h were 0.913 and 0.948, respectively. The high risk group of the DLA showed a significantly higher hazard for delayed cardiac arrest (5.74% vs. 0.33%, P < 0.001) and unexpected intensive care unit transfer (4.23% vs. 0.82%, P < 0.001). A sensitivity map of the DLA displayed the ECG regions used to predict cardiac arrest, with the DLA focused most on the QRS complex.

Conclusions
Our DLA successfully predicted cardiac arrest using diverse formats of ECG. The results indicate that cardiac arrest could be screened and predicted not only with a conventional 12-lead ECG, but also with a single-lead ECG using a wearable device that employs our DLA.
Does cystic fibrosis constitute an advantage in COVID-19 infection?
Authors: Bezzerri Valentino , Lucca Francesca , Volpi Sonia , Cipolli Marco 
Published: October 2020

AbstractThe Veneto region is one of the most affected Italian regions by COVID-19. Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), may constitute a risk factor in COVID-19. Moreover, respiratory viruses were generally associated with severe pulmonary impairment in cystic fibrosis (CF). We would have therefore expected numerous cases of severe COVID-19 among the CF population. Surprisingly, we found that CF patients were significantly protected against infection by SARS-CoV-2. We discussed this aspect formulating some reasonable theories.
Candida thrombophlebitis in children: a systematic review of the literature
Authors: Colomba Claudia , Campa Luigi , Siracusa Lucia , Giordano Salvatore , Vella Maria C. , Corsello Giovanni , Giuffrè Mario , Cascio Antonio 
Published: October 2020

Abstract
Objective
To describe a case of thrombophlebitis associated with Candida infection and to analyze other published reports to define clinical characteristics, prognostic data, diagnostic and therapeutic strategies.

Study design
A computerized search was performed without language restriction using PubMed and Scopus databases. An article was considered eligible for inclusion if it reported cases with Candida thrombophlebitis. Our case was also included in the analysis.

Results
A total of 16 articles reporting 27 cases of Candida thrombophlebitis were included in our review. The median age of patients was 4 years. In 10 cases there was a thrombophlebitis of peripheral veins; in the remaining cases the deep venous circle was interested. Candida albicans was the most frequently involved fungal species. The most recurrent risk factors were central venous catheter (19/28), broad spectrum antibiotics (17/28), intensive care unit (8/28), surgery (3/28), mechanical assisted ventilation (5/28), total parenteral nutrition (8/28), cancer (2/28), premature birth (6/28), cystic fibrosis (2/28). Fever was the most frequent clinical feature. All children with peripheral and deep thrombophlebitis were given antifungal therapy: amphotericin B was the most used, alone or in combination with other antifungal drugs. Heparin was most frequently used as anticoagulant therapy. Illness was fatal in two cases.

Conclusion
Candida thrombophlebitis is a rare but likely underdiagnosed infectious complication in pediatric critically ill patients. It is closely connected to risk factors such as central venous catheter, hospitalization in intensive care unit, prematurity, assisted ventilation, chronic inflammatory diseases. Antifungal therapy and anticoagulant drugs should be optimized for each patient and surgical resection is considered in the persistence of illness.
Chlorhexidine bathing of the exposed circuits in extracorporeal membrane oxygenation: an uncontrolled before-and-after study
Authors: Yeo Hye Ju , Kim Dohyung , Ha Mihyang , Je Hyung Gon , Kim Jeong Soo , Cho Woo Hyun 
Published: October 2020

Abstract
Background
Although the prevention of extracorporeal membrane oxygenation (ECMO) catheter-related infection is crucial, scientific evidence regarding best practices are still lacking.

Methods
We conducted an uncontrolled before-and-after study to test whether the introduction of disinfection with 2% chlorhexidine gluconate (CHG) and 70% isopropyl alcohol (IPA) of the exposed circuits and hub in patients treated with ECMO would affect the rate of blood stream infection (BSI) and microbial colonization of the ECMO catheter. We compared the microbiological and clinical data before and after the intervention.

Results
A total of 1740 ECMO catheter days in 192 patients were studied. These were divided into 855 ECMO catheter days in 96 patients before and 885 ECMO catheter days in 96 patients during the intervention. The rates of BSI were significantly decreased during the intervention period at 11.7/1000 ECMO catheter days before vs. 2.3/1000 ECMO catheter days during (difference 9.4, 95% confidence interval (CI) 1.5–17.3, p = 0.019). Furthermore, the colonization of the ECMO catheter was similarly significantly reduced during the intervention period at 10.5/1000 ECMO catheter days before vs. 2.3/1000 ECMO catheter days during intervention (difference 8.3, 95% CI 0.7–15.8, p = 0.032). Hospital mortality (41.7% vs. 24%, p = 0.009) and sepsis-related death (17.7% vs. 6.3%, p = 0.014) were also significantly decreased during intervention.

Conclusion
Extensive disinfection of exposed ECMO circuits and hub with 2% CHG/IPA was associated with a reduction in both BSI and microbial colonization of ECMO catheters. A further randomized controlled study is required to verify these results.

Trial registration
KCT 0004431
Trastuzumab-induced upregulation of a protein set in extracellular vesicles emitted by ErbB2-positive breast cancer cells correlates with their trastuzumab sensitivity
Authors: Drucker Arik , Yoo Byong Hoon , Khan Iman Aftab , Choi Dongsic , Montermini Laura , Liu Xiaoyang , Jovanovic Sanja , Younis Tallal , Rosen Kirill V. 
Published: October 2020

AbstractBackgroundErbB2/HER2 oncoprotein often drives breast cancers (BCs) which are treated with the anti-ErbB2 antibody trastuzumab. The efficacy of trastuzumab-based metastatic BC therapies is routinely assessed by imaging studies. Trastuzumab typically becomes ineffective in the case of this disease and is then replaced by other drugs. Biomarkers of BC trastuzumab response could allow imaging studies and the switch to other drugs to occur earlier than is now possible. Moreover, bone-only BC metastases can be hard to measure, and biomarkers of their trastuzumab response could facilitate further treatment decisions. Such biomarkers are presently unavailable. In this study, we searched for proteins whose levels in BC cell-emitted extracellular vesicles (EVs) potentially correlate with BC trastuzumab sensitivity.MethodsWe isolated EVs from cultured trastuzumab-sensitive and trastuzumab-resistant human BC cells before and after trastuzumab treatment and characterized these EVs by nanoparticle tracking analysis and electron microscopy. We found previously that ErbB2 drives BC by downregulating a pro-apoptotic protein PERP. We now tested whether trastuzumab-induced PERP upregulation in EVs emitted by cultured human BC cells correlates with their trastuzumab sensitivity. We also used mass spectrometry to search for additional proteins whose levels in such EVs reflect BC cell trastuzumab sensitivity. Once we identified proteins whose EV levels correlate with this sensitivity in culture, we explored the feasibility of testing whether their levels in the blood EVs of trastuzumab-treated metastatic BC patients correlate with patients’ response to trastuzumab-based treatments.ResultsWe found that neither trastuzumab nor acquisition of trastuzumab resistance by BC cells affects the size or morphology of EVs emitted by cultured BC cells. We established that EV levels of proteins PERP, GNAS2, GNA13, ITB1, and RAB10 correlate with BC cell trastuzumab response. Moreover, these proteins were upregulated during trastuzumab-based therapies in the blood EVs of a pilot cohort of metastatic BC patients that benefited from these therapies but not in those derived from patients that failed such treatments.ConclusionsUpregulation of a protein set in EVs derived from cultured breast tumor cells correlates with tumor cell trastuzumab sensitivity. It is feasible to further evaluate these proteins as biomarkers of metastatic BC trastuzumab response.
A genome assembly and the somatic genetic and epigenetic mutation rate in a wild long-lived perennial Populus trichocarpa
Authors: Hofmeister Brigitte T. , Denkena Johanna , Colomé-Tatché Maria , Shahryary Yadollah , Hazarika Rashmi , Grimwood Jane , Mamidi Sujan , Jenkins Jerry , Grabowski Paul P. , Sreedasyam Avinash , Shu Shengqiang , Barry Kerrie , Lail Kathleen , Adam Catherine , Lipzen Anna , Sorek Rotem , Kudrna Dave , Talag Jayson , Wing Rod , Hall David W. , Jacobsen Daniel , Tuskan Gerald A. , Schmutz Jeremy , Johannes Frank , Schmitz Robert J. 
Published: October 2020

AbstractBackgroundPlants can transmit somatic mutations and epimutations to offspring, which in turn can affect fitness. Knowledge of the rate at which these variations arise is necessary to understand how plant development contributes to local adaption in an ecoevolutionary context, particularly in long-lived perennials.ResultsHere, we generate a new high-quality reference genome from the oldest branch of a wildPopulus trichocarpatree with two dominant stems which have been evolving independently for 330 years. By sampling multiple, age-estimated branches of this tree, we use a multi-omics approach to quantify age-related somatic changes at the genetic, epigenetic, and transcriptional level. We show that the per-year somatic mutation and epimutation rates are lower than in annuals and that transcriptional variation is mainly independent of age divergence and cytosine methylation. Furthermore, a detailed analysis of the somatic epimutation spectrum indicates that transgenerationally heritable epimutations originate mainly from DNA methylation maintenance errors during mitotic rather than during meiotic cell divisions.ConclusionTaken together, our study provides unprecedented insights into the origin of nucleotide and functional variation in a long-lived perennial plant.
On the definition of a self-sustaining chemical reaction system and its role in heredity
Authors: Liu Yu 
Published: October 2020

Abstract
Background
The ability to self-sustain is one of the essential properties of life. However, a consistent and satisfying definition of self-sustainability is still missing. Currently, self-sustainability refers to either “no-intervention by a higher entity” or “regeneration of all the system’s components”. How to connect self-sustainability with heredity, another essential of life, is another problem, as they are often considered to be independent of each other. Last but not least, current definitions of self-sustainability failed to provide a practical method to empirically discern whether a chemical system is self-sustaining or not.

Results
Here I propose a definition of self-sustainability. It takes into account the chemical reaction network itself and the external environment which is simplified as a continuous-flow stirred tank reactor. One distinct property of self-sustaining systems is that the system can only proceed if molecular triggers (or called, seeds) are present initially. The molecular triggers are able to establish the whole system, indicating that they carry the preliminary heredity of the system. Consequently, life and a large group of fires (and other dissipative systems) can be distinguished. Besides, the general properties and various real-life examples of self-sustaining systems discussed here together indicate that self-sustaining systems are not uncommon.

Conclusions
The definition I proposed here naturally connects self-sustainability with heredity. As this definition involves the continuous-flow stirred tank reactor, it gives a simple way to empirically test whether a system is self-sustaining or not. Moreover, the general properties and various real-life examples of self-sustaining systems discussed here provide practical guidance on how to construct and detect such systems in real biology and chemistry.

Reviewers
This article was reviewed by Wentao Ma and David Baum.
The murine Microenvironment Cell Population counter method to estimate abundance of tissue-infiltrating immune and stromal cell populations in murine samples using gene expression
Authors: Petitprez Florent , Levy Sacha , Sun Cheng-Ming , Meylan Maxime , Linhard Christophe , Becht Etienne , Elarouci Nabila , Tavel David , Roumenina Lubka T. , Ayadi Mira , Sautès-Fridman Catherine , Fridman Wolf H. , de Reyniès Aurélien 
Published: October 2020

AbstractQuantifying tissue-infiltrating immune and stromal cells provides clinically relevant information for various diseases. While numerous methods can quantify immune or stromal cells in human tissue samples from transcriptomic data, few are available for mouse studies. We introduce murine Microenvironment Cell Population counter (mMCP-counter), a method based on highly specific transcriptomic markers that accurately quantify 16 immune and stromal murine cell populations. We validated mMCP-counter with flow cytometry data and showed that mMCP-counter outperforms existing methods. We showed that mMCP-counter scores are predictive of response to immune checkpoint blockade in cancer mouse models and identify early immune impacts of Alzheimer’s disease.
Radiographic remission in rheumatoid arthritis quantified by computer-aided joint space analysis (CASJA): a post hoc analysis of the RAPID 1 trial
Authors: Pfeil Alexander , Nussbaum Anica , Renz Diane M. , Hoffmann Tobias , Malich Ansgar , Franz Marcus , Oelzner Peter , Wolf Gunter , Böttcher Joachim 
Published: October 2020

Abstract
Background
The reduction of finger joint space width (JSW) in patients with rheumatoid arthritis (RA) is strongly associated with joint destruction. Treatment with certolizumab pegol (CZP), a PEGylated anti-TNF, has been proven to be effective in RA patients. The computer-aided joint space analysis (CAJSA) provides the semiautomated measurement of joint space width at the metacarpal-phalangeal joints (MCP) based on hand radiographs. The aim of this post hoc analysis of the RAPID 1 trial was to quantify MCP joint space distance (JSD-MCP) measured by CAJSA between baseline and week 52 in RA patients treated with certolizumab pegol (CZP) plus methotrexate (MTX) compared with MTX/placebo.

Methods
Three hundred twenty-eight patients were included in the post hoc analysis and received placebo plus MTX, CZP 200 mg plus MTX and CZP 400 mg plus MTX. All patients underwent X-rays of the hand at baseline and week 52 as well as assessment of finger joint space narrowing of the MCP using CAJSA (Version 1.3.6; Sectra; Sweden). The joint space width (JSW) was expressed as mean joint space distance of the MCP joints I to V (JSD-MCPtotal).

Results
The MTX group showed a significant reduction of joint space of − 4.8% (JSD-MCPtotal), whereas in patients treated with CZP 200 mg/MTX and CZP 400 mg/MTX a non-significant change (JSD-MCPtotal + 0.6%) was observed. Over 52 weeks, participants with DAS28 remission (DAS28 ≤ 2.6) exhibited a significant joint space increase of + 3.3% (CZP 200 mg plus MTX) and + 3.9% (CZP pegol 400 mg plus MTX).

Conclusion
CZP plus MTX did not reduce JSD-MCPtotal estimated by CAJSA compared with MTX/placebo. Furthermore, clinical remission (DAS28 ≤ 2.6) in patients treated with CZP plus MTX was associated with an increasing JSD, indicating radiographic remission in RA.
Mycophenolate mofetil for systemic sclerosis: drug exposure exhibits considerable inter-individual variation—a prospective, observational study
Authors: Andréasson Kristofer , Neringer Karl , Wuttge Dirk M. , Henrohn Dan , Marsal Jan , Hesselstrand Roger 
Published: October 2020

AbstractObjectiveMycophenolate mofetil (MMF) is an established therapy for systemic sclerosis (SSc), but its pharmacokinetics in this disease remains unexplored. We have investigated drug exposure in MMF-treated patients with SSc in relation to clinical features of the disease and common concomitant drugs.MethodsThis study was predefined to include 35 MMF-treated SSc patients who were using MMF at a fixed dose of 0.5, 1.0 or 1.5 g twice daily since at least 3 months. The 12-h drug exposure of the active MMF metabolite mycophenolic acid (MPA) was estimated by repeated analysis of plasma MPA over a 6-h period. This 12-h drug exposure was dose normalised to a daily intake of 3 g MMF (MPA_AUC3g) in order to compare subjects using MMF at different doses. Drug exposure was analysed in reference to the clinical characteristics including body weight, renal function, autoantibodies, intestinal dysbiosis, intestinal inflammation assessed by faecal (F)-calprotectin, intestinal symptoms assessed by the University of California Los Angeles Scleroderma Trial Consortium Gastrointestinal Tract Instrument 2.0 and concomitant drug usage including proton-pump inhibitors (PPI).ResultsThirty-four out of 35 study participants completed the study. The mean daily MMF dose was 2.1 g. Drug exposure expressed as MPA_AUC3gvaried up to 8-fold between patients (median 115, range 27–226 mg h/L).MPA_AUC3gwas inversely related to body weight (rs = − 0.58,p < 0.001) and renal function (rs = − 0.34,p = 0.054). Anti-topoisomerase-1 antibodies and male sex were associated with lower MPA_AUC3g(87 vs 123 and 71 vs 141;p = 0.008 andp = 0.015, respectively). MPA_AUC3gwas inversely related to the intestinal abundance of lactobacilli and to F-calprotectin (rs = − 0.54,p = 0.004;rs = − 0.36,p = 0.034), but not to gastrointestinal symptoms. MPA_AUC3gwas inversely related to PPI usage (rs = − 0.45,p = 0.007). We found no association between MPA_AUC3gand disease subtype, disease duration or disease activity.ConclusionMMF-treated SSc patients exhibit considerable inter-individual variation in drug exposure, and lower MPA levels were primarily found in PPI users with poor prognostic factors. Body weight, renal function, sex, serology, gastrointestinal manifestations and/or measuring individual MPA exposure should be considered when using MMF for SSc.