bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular risk assessment in multiple myeloma patients undergoing carfilzomib therapy: a new risk prediction model for cardiovascular adverse events
Authors: Astarita A , Mingrone G , Airale L , Vallelonga F , Catarinella C , Cesareo M , Leone D , Bruno G , Maffei I , Veglio F , Milan A 
Published: February 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Cardiovascular adverse events (CVAEs) are closely related to Carfilzomib (CFZ) therapy in multiple myeloma (MM), but validated management protocols are lacking. Moreover, the incidence, nature and risk factors for each type of CVAEs are incompletely characterized.

Purpose
To assess if the European Myeloma Network Guidelines (EMN) protocol is effective on cardiovascular risk assessment before CFZ starting. A prediction model for estimating the probability of CVAEs was developed and validated. Major and hypertensive-related CVAEs were investigated.

Methods
A perspective study on 116 MM patients scheduled for CFZ therapy was conducted from 2015 to 2020. Before CFZ starting, a baseline evaluation, according to the EMN protocol, was performed; during the follow-up, the incidence of CVAEs was detected. The potential risk factors for CVAEs were identified and a risk score was developed.

Results
The rate of all-grade CVAEs was 44.8% (24.1% CTCAE≥3): 14.7% experienced major CVEAs (41.2% arrhythmias, 23.5% acute ischemic cardiopathy as most represented) and 30.2% hypertensive-related CVAEs. At baseline, five independent predictors for all-CVAEs were identified: office systolic blood pressure (p = 0.003), 24-hours blood pressure variability (p = 0.004), left ventricular mass (p = 0.015), pulse wave velocity (p = 0.002) and global longitudinal strain (p = 0.033). The resulting CVAEs risk score allows to define the low- and high-risk groups, obtaining a sensibility of 94% in predicting CVAEs (AUC 0.76).

Conclusions
The comprehensive evaluation of EMN Guidelines is effective in CVAEs prediction. The use of CVAEs risk score will identify the higher risk patients, targeting appropriate follow-ups and organizing effective risk mitigation strategies.
Instrumental determinants with CVAEs Parameters No CVAEs N = 64 [N (%)] CVAEs N = 52[N (%)] P value LV mass/BSA 85.30 ± 19.72 95.14 ± 21.75 0.013 LV hypertrophy [&gt; = 95 g/m2 F &gt; = 115 g/m2 M] 8 (12.7) 16 (30.8) 0.018 LV dilation 5 (9.3) 4 (8.9) 0.949 LV EF % 63.03 ± 6.56 61.96 ± 7.13 0.414 GLS % -22.37 ± 2.56 -21.3 ± 2.46 0.029 LV Diastolic dysfunction 1 (1.6) 0(0) 0.362 PWV 7.41 ± 1.63 8.55 ± 1.855 0.002 PWV &sup3; 8.75 m/s 10 (17.5) 24 (54.2) 0.000 SBP Systolic Blood Pressure; ABPM Ambulatory Blood Pressure Monitoring; BPV Blood Pressure Variability; BSA Body Surface Area; SD Standard Deviation; EF Ejection Fraction; GLS Global Longitudinal Strain; LV Left Ventricle; PWV Pulse Wave Velocity Abstract Figure. CVAEs risk score
Machine learning: principles and applications for thoracic surgery
Authors: Ostberg Nicolai P , Zafar Mohammad A , Elefteriades John A 
Published: February 2021

Abstract

OBJECTIVES
Machine learning (ML) has experienced a revolutionary decade with advances across many disciplines. We seek to understand how recent advances in ML are going to specifically influence the practice of surgery in the future with a particular focus on thoracic surgery.

METHODS
Review of relevant literature in both technical and clinical domains.

RESULTS
ML is a revolutionary technology that promises to change the way that surgery is practiced in the near future. Spurred by an advance in computing power and the volume of data produced in healthcare, ML has shown remarkable ability to master tasks that had once been reserved for physicians. Supervised learning, unsupervised learning and reinforcement learning are all important techniques that can be leveraged to improve care. Five key applications of ML to cardiac surgery include diagnostics, surgical skill assessment, postoperative prognostication, augmenting intraoperative performance and accelerating translational research. Some key limitations of ML include lack of interpretability, low quality and volumes of relevant clinical data, ethical limitations and difficulties with clinical implementation.

CONCLUSIONS
In the future, the practice of cardiac surgery will be greatly augmented by ML technologies, ultimately leading to improved surgical performance and better patient outcomes.
Diameter change in completely remodelled proximal descending aorta after acute type I dissection repair: implications for estimating the pre-dissection size
Authors: Jung Joon Chul , Sohn Bongyeon , Chang Hyoung Woo , Lee Jae Hang , Kim Dong Jung , Kim Jun Sung , Lim Cheong , Park Kay-Hyun 
Published: February 2021

Abstract

OBJECTIVES
Pre-dissection diameter of the proximal descending thoracic aorta (p-DTA), if available, would be the reference for determining the size of the stent graft or elephant trunk. Acute type B dissection is known to increase p-DTA diameter by 23% (Rylski factor). This study aimed to investigate the accuracy of estimating post-remodelling diameter of the p-DTA based on the Rylski factor and other post-dissection morphological parameters in acute type I dissection, based on the assumption that the post-remodelling diameter is similar to the pre-dissection diameter.

METHODS
In 60 patients with acute type I dissection showing complete remodelling of the p-DTA false lumen after surgical repair, preoperative and post-remodelling computed tomography scans were reviewed. Parameters, including maximal true lumen diameter (TLDmax) and aortic area-derived diameter divided by the Rylski factor (AoDRylski), were measured at the p-DTA.

RESULTS
After complete remodelling, p-DTA diameter decreased by 4.1 mm (P &lt; 0.001). The equivalent to the Rylski factor was 15%. Both TLDmax and AoDRylski frequently showed ≥2 mm discrepancy from post-remodelling aortic diameter (36.7% and 48.3%, respectively, P = 0.30). When 2 parameters coincided within 2 mm, two-third of their estimations were accurate. AoDRylski was more accurate than TLDmax in patients with a large extent of circumferential dissection, and vice versa with less circumferential dissection (P = 0.027).

CONCLUSIONS
Prediction of post-remodelling aortic diameter relying on a single morphologic parameter carries a substantial risk of overestimation and underestimation. Evaluation based on the extent of circumferential dissection together with the 2 parameters may provide a more reliable estimation.
Near-Chromosome-Level Genome Assembly of the Dark Septate Endophyte Laburnicola rhizohalophila: A Model for Investigating Root-Fungus Symbiosis
Authors: He Xinghua , Yuan Zhilin 
Published: February 2021

Abstract
The novel DSE Laburnicola rhizohalophila (Pleosporales, Ascomycota) is frequently found in the halophytic seepweed (Suaeda salsa). In this article, we report a near-chromosome-level hybrid assembly of this fungus using a combination of short-read Illumina data to polish assemblies generated from long-read Nanopore data. The reference genome for L. rhizohalophila was assembled into 26 scaffolds with a total length of 64.0 Mb and a N50 length of 3.15 Mb. Of them, 17 scaffolds approached the length of intact chromosomes, and 5 had telomeres at one end only. A total of 10,891 gene models were predicted. Intriguingly, 27.5 Mb of repeat sequences that accounted for 42.97% of the genome was identified, and long terminal repeat retrotransposons were the most frequent known transposable elements, indicating that transposable element proliferation contributes to its increased genome size. BUSCO analyses using the Fungi_odb10 data set showed that 95.0% of genes were complete. In addition, 292 carbohydrate active enzymes, 33 secondary metabolite clusters, and 84 putative effectors were identified in silico. The resulting high-quality assembly and genome features are not only an important resource for further research on understanding the mechanism of root-fungi symbiotic interactions but will also contribute to comparative analyses of genome biology and evolution within Pleosporalean species.
Extreme diversification driven by parallel events of massive loss of heterozygosity in the hybrid lineage of Candida albicans
Authors: Mixão Verónica , Saus Ester , Boekhout Teun , Gabaldón Toni 
Published: February 2021

Abstract
Candida albicans is the most commonly reported species causing candidiasis. The taxonomic classification of C. albicans and related lineages is controversial, with Candida africana (syn. C. albicans var. africana) and Candida stellatoidea (syn. C. albicans var. stellatoidea) being considered different species or C. albicans varieties depending on the authors. Moreover, recent genomic analyses have suggested a shared hybrid origin of C. albicans and C. africana, but the potential parental lineages remain unidentified. Although the genomes of C. albicans and C. africana have been extensively studied, the genome of C. stellatoidea has not been sequenced so far. In order to get a better understanding of the evolution of the C. albicans clade, and to assess whether C. stellatoidea could represent one of the unknown C. albicans parental lineages, we sequenced C. stellatoidea type strain (CBS 1905). This genome was compared to that of C. albicans and of the closely related lineage C. africana. Our results show that, similarly to C. africana, C. stellatoidea descends from the same hybrid ancestor as other C. albicans strains and that it has undergone a parallel massive loss of heterozygosity.
What Can Serology Tell Us About the Burden of Infertility in Women Caused by Chlamydia?
Authors: Horner Patrick J , Anyalechi Gloria E , Geisler William M 
Published: February 2021

Abstract
Chlamydia trachomatis (CT) causes pelvic inflammatory disease, which may result in tubal factor infertility (TFI) in women. Serologic assays may be used to determine the proportion of women with and without TFI who have had previous CT infection and to generate estimates of infertility attributable to chlamydia. Unfortunately, most existing CT serologic assays are challenged by low sensitivity and, sometimes, specificity for prior CT infection; however, they are currently the only available tests available to detect prior CT infection. Modeling methods such as finite mixture modeling may be a useful adjunct to quantitative serologic data to obtain better estimates of CT-related infertility. In this article, we review CT serological assays, including the use of antigens preferentially expressed during upper genital tract infection, and suggest future research directions. These methodologic improvements, coupled with creation of new biomarkers for previous CT infection, should improve our understanding of chlamydia’s contribution to female infertility.
Oral Immunotherapy With Human Secretory Immunoglobulin A Improves Survival in the Hamster Model of Clostridioides difficile Infection
Authors: Chiari Estelle F , Weiss William , Simon Michael R , Kiessig Stephan T , Pulse Mark , Brown Stephen C , Gerding Hanne R , Mandago Maurice , Gisch Karina , von Eichel-Streiber Christoph 
Published: February 2021

Abstract
Coadministration of human secretory IgA (sIgA) together with subtherapeutic vancomycin enhanced survival in the Clostridioides difficile infection (CDI) hamster model. Vancomycin (5 or 10 mg/kg × 5 days) plus healthy donor plasma sIgA/monomeric IgA (TID × 21 days) or hyperimmune sIgA/monomeric IgA (BID × 13 days) enhanced survival. Survival was improved compared to vancomycin alone, P = .018 and .039 by log-rank Mantel-Cox, for healthy and hyperimmune sIgA, respectively. Passive immunization with sIgA (recombinant human secretory component plus IgA dimer/polymer from pooled human plasma) can be administered orally and prevents death in a partially treated CDI hamster model.
Settling Interstate Trade Disputes: Lessons from the EFTA Complaints Procedure
Authors: Fahner Johannes Hendrik 
Published: February 2021

ABSTRACT
When the European Free Trade Association (EFTA) was founded 60 years ago, the contracting parties established a dispute settlement procedure that sought to strike a balance between the need to supervise compliance with the EFTA Convention and the need to respect the sovereignty of the member states. The procedure of Article 31 empowered the EFTA Council to hear interstate complaints, establish examining committees, issue recommendations, and authorize retaliation. This article investigates the successes and failures of this mechanism on the basis of historical documents from the EFTA archives. It provides an overview of the complaints that were brought under Article 31 and analyses how the Council exercised its functions in dealing with these cases. The article evaluates why the complaints procedure quickly fell into disuse, finding that it failed to provide a real alternative to ordinary discussions in the Council. The article argues that lessons can be drawn from this understudied chapter of European integration, concluding that systems of dispute settlement in international economic law should avoid fusing diplomatic and judicial elements if this might preclude an independent evaluation of the legal questions raised in the context of a concrete dispute.
Off-pump external pericardial patch repair for post-infarct left ventricular free wall rupture: a case series
Authors: Mohamed S , Mazhar K , Patel A J , Jeeji R , Ridley P , Balacumaraswami L 
Published: February 2021

Abstract
We describe an off-pump surgical approach to this challenging condition supported by our results from a case series, which would add to existing literature in the management of this life-threatening complication. We identified seven patients who underwent surgical intervention for left ventricular (LV) free wall rupture at our institution. They were all diagnosed to have cardiac tamponade secondary to free wall rupture of the LV in the presence of acute myocardial infarction. The surgical technique comprised of utilizing an external pericardial patch which was secured using surgical biological glues (fibrin-based sealants or gelatin hydrogels). The 30-day mortality, 1-year survival and 2-year survival were 57, 42 and 42%, respectively. Advanced age, female gender and use of cardiopulmonary bypass were characteristics that were not significantly associated with survival. We advocate the use of an off-pump external pericardial patch repair strategy as a ‘bridge to recovery’ in this extremely high-risk group of patients.
Ultra high-risk PFA ependymoma is characterized by loss of chromosome 6q
Authors: Baroni Lorena V , Sundaresan Lakshmikirupa , Heled Ayala , Coltin Hallie , Pajtler Kristian W , Lin Tong , Merchant Thomas E , McLendon Roger , Faria Claudia , Buntine Molly , White Christine L , Pfister Stefan M , Gilbert Mark R , Armstrong Terri S , Bouffet Eric , Kumar Sachin , Taylor Michael D , Aldape Kenneth D , Ellison David W , Gottardo Nicholas G , Kool Marcel , Korshunov Andrey , Hansford Jordan R , Ramaswamy Vijay 
Published: February 2021

Abstract

Background
Within PF-EPN-A, 1q gain is a marker of poor prognosis, however, it is unclear if within PF-EPN-A additional cytogenetic events exist which can refine risk stratification.

Methods
Five independent non-overlapping cohorts of PF-EPN-A were analyzed applying genome-wide methylation arrays for chromosomal and clinical variables predictive of survival.

Results
Across all cohorts, 663 PF-EPN-A were identified. The most common broad copy number event was 1q gain (18.9%), followed by 6q loss (8.6%), 9p gain (6.5%), and 22q loss (6.8%). Within 1q gain tumors, there was significant enrichment for 6q loss (17.7%), 10q loss (16.9%), and 16q loss (15.3%). The 5-year progression-free survival (PFS) was strikingly worse in those patients with 6q loss, with a 5-year PFS of 50% (95% CI 45%-55%) for balanced tumors, compared with 32% (95% CI 24%-44%) for 1q gain only, 7.3% (95% CI 2.0%-27%) for 6q loss only and 0 for both 1q gain and 6q loss (P = 1.65 × 10−13). After accounting for treatment, 6q loss remained the most significant independent predictor of survival in PF-EPN-A but is not in PF-EPN-B. Distant relapses were more common in 1q gain irrespective of 6q loss. RNA sequencing comparing 6q loss to 6q balanced PF-EPN-A suggests that 6q loss forms a biologically distinct group.

Conclusions
We have identified an ultra high-risk PF-EPN-A ependymoma subgroup, which can be reliably ascertained using cytogenetic markers in routine clinical use. A change in treatment paradigm is urgently needed for this particular subset of PF-EPN-A where novel therapies should be prioritized for upfront therapy.
Baseline Frailty Status Influences Recovery Patterns and Outcomes Following Alignment Correction of Cervical Deformity
Authors: Pierce Katherine E , Passias Peter G , Daniels Alan H , Lafage Renaud , Ahmad Waleed , Naessig Sara , Lafage Virginie , Protopsaltis Themistocles , Eastlack Robert , Hart Robert , Burton Douglas , Bess Shay , Schwab Frank , Shaffrey Christopher , Smith Justin S , Ames Christopher ,   on behalf of the International Spine Study Group (ISSG)
Published: February 2021

Abstract

BACKGROUND
Frailty severity may be an important determinant for impaired recovery after cervical spine deformity (CD) corrective surgery.

OBJECTIVE
To evaluate postop clinical recovery among CD patients between frailty states undergoing primary procedures.

METHODS
Patients >18 yr old undergoing surgery for CD with health-related quality of life (HRQL) data at baseline, 3-mo, and 1-yr postoperative were identified. Patients were stratified by the modified CD frailty index scale from 0 to 1 (no frailty [NF] <0.3, mild/severe fraily [F] >0.3). Patients in NF and F groups were propensity score matched for TS-CL (T1 slope [TS] minus angle between the C2 inferior end plate and the C7 inferior end plate [CL]) to control for baseline deformity. Area under the curve was calculated for follow-up time intervals determining overall normalized, time-adjusted HRQL outcomes; Integrated Health State (IHS) was compared between NF and F groups.

RESULTS
A total of 106 CD patients were included (61.7 yr, 66% F, 27.7 kg/m2)—by frailty group: 52.8% NF, 47.2% F. After propensity score matching for TS-CL (mean: 38.1°), 38 patients remained in each of the NF and F groups. IHS-adjusted HRQL outcomes from baseline to 1 yr showed a significant difference in Euro-Qol 5 Dimension scores (NF: 1.02, F: 1.07, P = .016). No significant differences were found in the IHS Neck Disability Index (NDI) and modified Japanese Orthopedic Association between frailty groups (P > .05). F patients had more postop major complications (31.3%) compared to the NF (8.9%), P = .004, though DJK occurrence and reoperation between the groups was not significant.

CONCLUSION
While all groups exhibited improved postop disability and pain scores, frail patients experienced greater amount of improvement in overall health state compared to baseline disability. This signifies that with frailty severity, patients have more room for improvement postop compared to baseline quality of life.
Specific decorations of 17-hydroxygeranyllinalool diterpene glycosides solve the autotoxicity problem of chemical defense inNicotiana attenuata
Authors: Heiling Sven , Llorca Lucas Cortes , Li Jiancai , Gase Klaus , Schmidt Axel , Schäfer Martin , Schneider Bernd , Halitschke Rayko , Gaquerel Emmanuel , Baldwin Ian Thomas 
Published: February 2021

AbstractThe native diploid tobacco Nicotiana attenuata produces abundant, potent anti-herbivore defense metabolites known as 17-hydroxygeranyllinalool diterpene glycosides (HGL-DTGs) whose glycosylation and malonylation biosynthetic steps are regulated by jasmonate signaling. To characterize the biosynthetic pathway of HGL-DTGs, we conducted a genome-wide analysis of uridine diphosphate glycosyltransferases (UGTs) and identified 107 family-1 UGT members. The transcript levels of three UGTs were highly correlated with the transcript levels two key HGL-DTG biosynthetic genes: geranylgeranyl diphosphate synthase (NaGGPPS) and geranyllinalool synthase (NaGLS). NaGLS’s role in HGL-DTG biosynthesis was confirmed by virus-induced gene silencing. Silencing the Uridine diphosphate (UDP)-rhamnosyltransferase gene UGT91T1 demonstrated its role in the rhamnosylation of HGL-DTGs. In vitro enzyme assays revealed that UGT74P3 and UGT74P4 use UDP-glucose for the glucosylation of 17-hydroxygeranyllinalool (17-HGL) to lyciumoside I. Plants with stable silencing of UGT74P3 and UGT74P5 were severely developmentally deformed, pointing to a phytotoxic effect of the aglycone. The application of synthetic 17-HGL and silencing of the UGTs in HGL-DTG-free plants confirmed this phytotoxic effect. Feeding assays with tobacco hornworm (Manduca sexta) larvae revealed the defensive functions of the glucosylation and rhamnosylation steps in HGL-DTG biosynthesis. Glucosylation of 17-HGL is therefore a critical step that contributes to the resulting metabolites’ defensive function and solves the autotoxicity problem of this potent chemical defense.
Ammonium application mitigates the effects of elevated carbon dioxide on the carbon/nitrogen balance ofPhoebe bourneiseedlings
Authors: Wang Xiao , Wei Xiaoli , Wu Gaoyin , Chen Shengqun 
Published: February 2021

AbstractThe study of plant responses to increases in atmospheric carbon dioxide (CO2) concentration is crucial to understand and to predict the effect of future global climate change on plant adaptation and evolution. Increasing amount of nitrogen (N) can promote the positive effect of CO2, while how N forms would modify the degree of CO2 effect is rarely studied. The aim of this study was to determine whether the amount and form of nitrogen (N) could mitigate the effects of elevated CO2 (eCO2) on enzyme activities related to carbon (C) and N metabolism, the C/N ratio, and growth of Phoebe bournei (Hemsl.) Y.C. Yang. One-year-old P. bournei seedlings were grown in an open-top air chamber under either an ambient CO2 (aCO2) (350 ± 70 μmol•mol−1) or an eCO2 (700 ± 10 μmol•mol−1) concentration and cultivated in soil treated with either moderate (0.8 g per seedling) or high applications (1.2 g per seedling) of nitrate or ammonium. In seedlings treated with a moderate level of nitrate, the activities of key enzymes involved in C and N metabolism (i.e., Rubisco, Rubisco activase and glutamine synthetase) were lower under eCO2 than under aCO2. By contrast, key enzyme activities (except GS) in seedlings treated with high nitrate or ammonium were not significantly different between aCO2 and eCO2 or higher under eCO2 than under aCO2. The C/N ratio of seedlings treated with moderate or high nitrate under eCO2was significantly changed compared with the seedlings grown under aCO2, whereas the C/N ratio of seedlings treated with ammonium was not significantly different between aCO2 and eCO2. Therefore, under eCO2, application of ammonium can be beneficial C and N metabolism and mitigate effects on the C/N ratio.