bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep MRD profiling defines outcome and unveils different modes of treatment resistance in standard- and high-risk myeloma
Authors: Goicoechea Ibai , Puig Noemi , Cedena Maria-Teresa , Burgos Leire , Cordón Lourdes , Vidriales María-Belén , Flores-Montero Juan , Gutierrez Norma C. , Calasanz Maria-Jose , Ramos Maria-Luisa Martin , Lara-Astiaso David , Vilas-Zornoza Amaia , Alignani Diego , Rodriguez Idoia , Sarvide Sarai , Alameda Daniel , Garcés Juan José , Rodriguez Sara , Fresquet Vicente , Celay Jon , Garcia-Sanz Ramón , Martinez-Lopez Joaquin , Oriol Albert , Rios Rafael , Martin-Sanchez Jesus , Martinez-Martinez Rafael , Sarra Josep , Hernandez Miguel-Teodoro , de la Rubia Javier , Krsnik Isabel , Moraleda Jose-Maria , Palomera Luis , Bargay Joan , Martinez-Climent Jose-Angel , Orfao Alberto , Rosiñol Laura , Mateos Maria-Victoria , Lahuerta Juan-José , Blade Joan , San Miguel Jesús , Paiva Bruno 
Published: July 2020

Abstract
Patients with multiple myeloma (MM) carrying standard- or high-risk cytogenetic abnormalities (CAs) achieve similar complete response (CR) rates, but the later have inferior progression-free survival (PFS). This questions the legitimacy of CR as a treatment endpoint and represents a biological conundrum regarding the nature of tumor reservoirs that persist after therapy in high-risk MM. We used next-generation flow (NGF) cytometry to evaluate measurable residual disease (MRD) in MM patients with standard- vs high-risk CAs (n = 300 and 90, respectively) enrolled in the PETHEMA/GEM2012MENOS65 trial, and to identify mechanisms that determine MRD resistance in both patient subgroups (n = 40). The 36-month PFS rates were higher than 90% in patients with standard- or high-risk CAs achieving undetectable MRD. Persistent MRD resulted in a median PFS of ∼3 and 2 years in patients with standard- and high-risk CAs, respectively. Further use of NGF to isolate MRD, followed by whole-exome sequencing of paired diagnostic and MRD tumor cells, revealed greater clonal selection in patients with standard-risk CAs, higher genomic instability with acquisition of new mutations in high-risk MM, and no unifying genetic event driving MRD resistance. Conversely, RNA sequencing of diagnostic and MRD tumor cells uncovered the selection of MRD clones with singular transcriptional programs and reactive oxygen species–mediated MRD resistance in high-risk MM. Our study supports undetectable MRD as a treatment endpoint for patients with MM who have high-risk CAs and proposes characterizing MRD clones to understand and overcome MRD resistance. This trial is registered at www.clinicaltrials.gov as #NCT01916252.
A robust nonlinear low-dimensional manifold for single cell RNA-seq data
Authors: Verma Archit , Engelhardt Barbara E. 
Published: July 2020

AbstractBackgroundModern developments in single-cell sequencing technologies enable broad insights into cellular state. Single-cell RNA sequencing (scRNA-seq) can be used to explore cell types, states, and developmental trajectories to broaden our understanding of cellular heterogeneity in tissues and organs. Analysis of these sparse, high-dimensional experimental results requires dimension reduction. Several methods have been developed to estimate low-dimensional embeddings for filtered and normalized single-cell data. However, methods have yet to be developed for unfiltered and unnormalized count data that estimate uncertainty in the low-dimensional space. We present a nonlinear latent variable model with robust, heavy-tailed error and adaptive kernel learning to estimate low-dimensional nonlinear structure in scRNA-seq data.ResultsGene expression in a single cell is modeled as a noisy draw from a Gaussian process in high dimensions from low-dimensional latent positions. This model is called the Gaussian process latent variable model (GPLVM). We model residual errors with a heavy-tailed Student’s t-distribution to estimate a manifold that is robust to technical and biological noise found in normalized scRNA-seq data. We compare our approach to common dimension reduction tools across a diverse set of scRNA-seq data sets to highlight our model’s ability to enable important downstream tasks such as clustering, inferring cell developmental trajectories, and visualizing high throughput experiments on available experimental data.ConclusionWe show that our adaptive robust statistical approach to estimate a nonlinear manifold is well suited for raw, unfiltered gene counts from high-throughput sequencing technologies for visualization, exploration, and uncertainty estimation of cell states.
The oilseed rape developmental expression resource: a resource for the investigation of gene expression dynamics during the floral transition in oilseed rape
Authors: Jones D. Marc , Olson Tjelvar S. G. , Pullen Nick , Wells Rachel , Irwin Judith A. , Morris Richard J. 
Published: July 2020

Abstract
Background
Transcriptome time series can be used to track the expression of genes during development, allowing the timing, intensity, and dynamics of genetic programmes to be determined. Furthermore, time series analysis can reveal causal relationships between genes, leading to an understanding of how the regulatory networks are rewired during development. Due to its impact on yield, a developmental transition of agricultural interest in crops is the switch from vegetative to floral growth. We previously reported the collection of genome-wide gene expression data during the floral transition in the allopolyploid crop Brassica napus (oilseed rape, OSR). To provide the OSR research community with easy access to this dataset, we have developed the Oilseed Rape Developmental Expression Resource (ORDER; http://order.jic.ac.uk).

Results
ORDER enables users to search for genes of interest and plot expression patterns during the floral transition in both a winter and a spring variety of OSR. We illustrate the utility of ORDER using two case studies: the first investigating the interaction between transcription factors, the second comparing genes that mediate the vernalisation response between OSR and radish (Raphanus sativus L.). All the data is downloadable and the generic website platform underlying ORDER, called AionPlot, is made freely and openly available to facilitate the dissemination of other time series datasets.

Conclusions
ORDER provides the OSR research community with access to a dataset focused on a period of OSR development important for yield. AionPlot, the platform on which ORDER is built, will allow researchers from all fields to share similar time series datasets.
Comparison of the effects of sugammadex and neostigmine on hospital stay in robot-assisted laparoscopic prostatectomy: a retrospective study
Authors: Min Byung-Hun , Oh Tak Kyu , Song In-Ae , Jeon Young-Tae 
Published: July 2020

Abstract
Background
Sugammadex reduces postoperative complications. We sought to determine whether it could reduce the length of hospital stay, post-anesthetic recovery time, unplanned readmission, and charges for patients who underwent robot-assisted laparoscopic prostatectomy (RALP) when compared to neostigmine.

Methods
This was a retrospective observational study of patients who underwent RALP between July 2012 and July 2017, in whom rocuronium was used as a neuromuscular blocker. The primary outcome was the length of hospital stay after surgery in patients who underwent reversal with sugammadex when compared to those who underwent reversal with neostigmine. The secondary outcomes were post-anesthetic recovery time, hospital charges, and unplanned readmission within 30 days after RALP.

Results
In total, 1430 patients were enrolled. Using a generalized linear model in a propensity score-matched cohort, sugammadex use was associated with a 6% decrease in the length of hospital stay (mean: sugammadex 7.7 days vs. neostigmine 8.2 days; odds ratio [OR] 0.94, 95% confidence interval [CI] [0.89, 0.98], P = 0.008) and an 8% decrease in post-anesthetic recovery time (mean: sugammadex 36.7 min vs. neostigmine 40.2 min; OR 0.92, 95% CI [0.90, 0.94], P < 0.001) as compared to neostigmine use; however, it did not reduce the 30-day unplanned readmission rate (P = 0.288). The anesthesia charges were higher in the sugammadex group than in the neostigmine group (P < 0.001); however, there were no significant differences between the groups in terms of postoperative net charges (P = 0.061) and total charges (P = 0.100).

Conclusions
Compared to the reversal of rocuronium effects with neostigmine, reversal with sugammadex after RALP was associated with a shorter hospital stay and post-anesthetic recovery time, and was not associated with 30-day unplanned readmission rates and net charges.
Privacy-preserving semi-parallel logistic regression training with fully homomorphic encryption
Authors: Carpov Sergiu , Gama Nicolas , Georgieva Mariya , Troncoso-Pastoriza Juan Ramon 
Published: July 2020

AbstractBackgroundPrivacy-preserving computations on genomic data, and more generally on medical data, is a critical path technology for innovative, life-saving research to positively and equally impact the global population. It enables medical research algorithms to be securely deployed in the cloud because operations on encrypted genomic databases are conducted without revealing any individual genomes. Methods for secure computation have shown significant performance improvements over the last several years. However, it is still challenging to apply them on large biomedical datasets.MethodsThe HE Track of iDash 2018 competition focused on solving an important problem in practical machine learning scenarios, where a data analyst that has trained a regression model (both linear and logistic) with a certain set of features, attempts to find all features in an encrypted database that will improve the quality of the model. Our solution is based on the hybrid framework Chimera that allows for switching between different families of fully homomorphic schemes, namelyTFHEandHEAAN.ResultsOur solution is one of the finalist of Track 2 of iDash 2018 competition. Among the submitted solutions, ours is the only bootstrapped approach that can be applied for different sets of parameters without re-encrypting the genomic database, making it practical for real-world applications.ConclusionsThis is the first step towards the more general feature selection problem across large encrypted databases.
Identification of the fatty acid synthase interaction network via iTRAQ-based proteomics indicates the potential molecular mechanisms of liver cancer metastasis
Authors: Huang Juan , Tang Yao , Zou Xiaoqin , Lu Yi , She Sha , Zhang Wenyue , Ren Hong , Yang Yixuan , Hu Huaidong 
Published: July 2020

Abstract
Background
Fatty acid synthase (FASN) is highly expressed in various types of cancer and has an important role in carcinogenesis and metastasis. To clarify the mechanisms of FASN in liver cancer invasion and metastasis, the FASN protein interaction network in liver cancer was identified by targeted proteomic analysis.

Methods
Wound healing and Transwell assays was performed to observe the effect of FASN during migration and invasion in liver cancer. Isobaric tags for relative and absolute quantitation (iTRAQ)-based mass spectrometry were used to identify proteins interacting with FASN in HepG2 cells. Differential expressed proteins were validated by co-immunoprecipitation, western blot analyses and confocal microscopy. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to demonstrate the mechanism of FASN regulating metastasis.

Results
FASN knockdown inhibited migration and invasion of HepG2 and SMMC7721 cells. A total of, 79 proteins interacting with FASN were identified. Additionally, gene ontology term enrichment analysis indicated that the majority of biological regulation and cellular processes that the FASN-interacting proteins were associated with. Co-precipitation and co-localization of FASN with fascin actin-bundling protein 1 (FSCN1), signal-induced proliferation-associated 1 (SIPA1), spectrin β, non-erythrocytic 1 (SPTBN1) and CD59 were evaluated. Knockdown of FASN in liver cancer reduced the expression of FSCN1, SIPA1, SPTBN1 and CD59. Furthermore, inhibition of FASN, FSCN1 or SPTBN1 expression in liver cancer resulted in alterations of epithelial–mesenchymal transition (EMT)-associated markers E-cadherin, N-cadherin, vimentin and transcription factors, Snail and Twist, at the mRNA level, and changes in matrix metallopeptidase (MMP)-2 and MMP-9 protein expression.

Conclusion
The results suggested that the FASN-interacting protein network produced by iTRAQ-based proteomic analyses may be involved in regulating invasion and metastasis in liver cancer by influencing EMT and the function of MMPs.
Serious takotsubo cardiomyopathy: an autopsy case presenting severe irreversible myocardial damage after frequent episodes of recurrence
Authors: Mizutani Kenichi , Shioya Akihiro , Hirose Yasuyo , Saito Ryuhei , Yamada Sohsuke 
Published: July 2020

Abstract
Background
Takotsubo cardiomyopathy is characterized by transient dysfunction of the medial to apical segment of the left ventricle. Recurrence within a few months or years has been reported and serious complications, including arrhythmia, acute cardiac shock and cardiac rupture, can arise; however, recurrence is rare and takotsubo cardiomyopathy is typically a reversible functional disorder.

Case presentation
A 91-year-old Japanese woman with a past medical history of angina pectoris, hypertension and uterine carcinoma noted bilateral axillary pain and presented herself to an emergency room. Although the pain improved and she went home, there were several subsequent episodes of recurrent chest pain. At approximately 1 week after the onset, she was hospitalized as her symptom worsened. Electrocardiography showed low voltage in limb and chest leads, and ST-segment elevation in leads II, III, aVF and V3 to V6. Echocardiography revealed medial to apical dyskinesia and basal hypercontractility of the left ventricle, and cardiac tamponade. Pericardiocentesis improved the symptom, but not her cardiac dysfunction. At 3 days after her admission, cardiopulmonary resuscitation was performed due to ventricular fibrillation. She died on the 5th day of admission (2 weeks after the onset). At autopsy, the left ventricle was dilatated and the apical ventricular wall was thin. On microscopy, remarkable wavy change and thinning of myocardium were diffusely observed, especially at the apex and the anterior to lateral wall of the left ventricle, interventricular septum and right ventricle, intermingled with interstitial fibrosis, hemorrhage and neutrophil infiltration. Contraction band necrosis was mainly observed on the posterior to inferior wall of the left ventricle.

Conclusion
Our case showed severe morphological myocardial change after several chest pain episodes that were considered to be takotsubo cardiomyopathy. This notable case suggests that the frequent recurrence of serious takotsubo cardiomyopathy is life threatening and can lead to irreversible serious myocardial degeneration.
Wound closure in epidermolysis bullosa: data from the vehicle arm of the phase 3 ESSENCE Study
Authors: Murrell Dedee F. , Paller Amy S. , Bodemer Christine , Browning John , Nikolic Milos , Barth Jay A. , Lagast Hjalmar , Krusinska Eva , Reha Allen ,   on behalf of the ESSENCE Study Group
Published: July 2020

Abstract
Background
Chronic wounds are a fundamental issue for patients with epidermolysis bullosa (EB). Herein, we assess the natural history of wound closure in patients with EB who were randomly assigned to the vehicle-control arm of the multicenter, randomized, double-blind, phase 3 ESSENCE (NCT02384460) trial.

Methods
ESSENCE was designed to assess the efficacy and safety of a topical cream formulation of 6% allantoin (SD-101 6%) vs vehicle (SD-101 0%) in patients ≥1 month old who had a diagnosis of EB (simplex, recessive dystrophic, or intermediate junctional) and a target wound 10–50 cm2 present for ≥21 days. Time to complete target wound closure and the proportion of patients with target wound closure over time were analyzed overall and by parameters including patient age and baseline body surface area index (BSAi) of total wound burden (< 5% and ≥ 5%). Changes in BSAi of lesional skin, pain, and itching were also assessed.

Results
The vehicle-control arm included 87 patients. Mean (standard deviation [SD]) time to target wound closure within 3 months was 53.6 (28.6) days, with a range of 14 to 142 days. The proportion of patients with target wound closure increased over time from 7.1% at day 14 to 53.6% at month 3. Mean (SD) changes from baseline in BSAi of total wound burden and BSAi of lesional skin at month 3 were −2.3% (6.3) and −5.0% (13.5) of total body coverage, respectively. Reductions in pain and itching were observed at day 7 and maintained for 3 months. Faster healing times and a greater proportion of patients with wound closure were observed in patients aged 1 month to < 2 years; those with wounds < 30 days old, and in those with BSAi of total body wound burden < 5%.

Conclusions
Treatment response observed in the vehicle-control arm of the ESSENCE study was unexpectedly high and may have been due to unforeseen benefits of vehicle or enhanced wound care provided by the clinical trial staff. These observations will help inform the study design of future trials in patients with EB.

Trial registration
ClinicalTrials.gov, NCT02384460; Date of registration: February 13, 2015; First participant enrollment: March 11, 2015.
Anti-proliferative activities of Byrsocarpus coccineus Schum. and Thonn. (Connaraceae) using ovarian cancer cell lines
Authors: Ukwade Caroline E. , Ebuehi Osaretin A. T. , Adisa Rahmat A. , Singh Santosh K. , Singh Rajesh 
Published: July 2020

Abstract
Background
Ovarian cancer (OvCa) is one of the most lethal tumors of gynecologic malignancies, due to lack of early detection, and a high rate of metastasis. The standard treatment for OvCa is surgery and cytotoxic chemotherapy. However, to overcome the high cost and side effects of these treatments, medicinal plants are widely used in developing countries to treat OvCa. Byrsocarpus coccineus plant preparation has been administered to patients traditionally in the management of tumors in Nigeria. In this study, we investigated the anti-proliferative effects of B. coccineus ethanol leaf extract against OVCAR-3 and SW 626 OvCa cell lines. After the treatment of the two cell lines with the extracts, analyses were carried out to determine inhibition of proliferation and expression of cell cycle markers, pro-apoptotic, and anti-apoptotic markers.

Results
Results showed that B. coccineus ethanol leaf extract, significantly inhibited cell migration and colony formation in OVCAR-3 and SW 626 treated cells in a dose-dependent manner. Results also show that B. coccineus ethanol leaf extract modulated the expression of tumor suppressor gene (p53), cell cycle progression, pro- and anti-apoptotic gene, and the pro-inflammatory cytokines.

Conclusions
These results suggest that B. coccineus have anti-proliferative properties and could induce apoptosis. Further investigation will be carried out to isolate bioactive compounds for the treatment of ovarian cancer.
Reflections on the design of corporate headquarters
Authors: Campbell Andrew 
Published: July 2020

AbstractThe design of corporate headquarters (CHQ) is a specialist and important area of organization design. It is important because of the influence that a CHQ has over the portfolio of businesses it owns. A good CHQ can improve the performance of its businesses. A bad CHQ causes its businesses to perform less well. This article describes the lessons learned from a 30-year career researching, advising, and governing corporate leaders. It covers the reasons why CHQ design is so important, why CHQ design work often also involves strategy work, what activities are needed at the CHQ level, and the problem of subtracted value. The ambition is to help practitioners design better CHQ and help researchers design more relevant research.
Prevalence and seroconversion of hepatitis C among hemodialysis patients in Assiut governorate, Egypt
Authors: Kerollos Kerollos Motwade N. , El-Ameen Hussein Ahmed , El Wahed Lobna Abd , Azoz Nashwa Mostafa A. 
Published: July 2020

Abstract
Background
The prevalence of hepatitis C (HCV) infection among the patients on hemodialysis (HD) varies from country to country and from one center to another in the same country. Despite the existence of guidelines for the infection control program, Egypt is one of the countries with high HCV prevalence. In Egypt, the prevalence of HCV among hemodialysis patients in 2015 survey was 50.7%. This study aimed to evaluate the prevalence and seroconversion rate of hepatitis C infection and the risk factors for seroconversion in our community hemodialysis units.

Results
The prevalence of HCV was 34.8% among hemodialysis patients. The seroconversion rate was 13.2%. The positive history of blood transfusion and the frequency of blood transfusion, in addition to the handling by medical staff to equipment and blood products and the number of inserted temporary dialysis catheters, were found to be significant risk factors for seroconversion.

Conclusion
We concluded that there is a high prevalence of HCV infection in the dialysis units of our community and a relatively high seroconversion rate among hemodialysis patients.
Separating Information About Cash Flows from Information About Risk in Losses
Authors: Li Bin 
Published: July 2020

Prior literature interprets the weak earnings response coefficient (ERC) of accounting losses as a manifestation either of lack of forward-looking information in losses or of market mispricing of losses. Based on return decomposition theory, I predict that losses contain information not only about future cash flows (i.e., cash flow news) but also, about risk (i.e., expected returns and discount rate news). However, these informational components have offsetting valuation effects, resulting in a muted ERC. Consistent with the prediction, I show that, after controlling for information about risk (mainly expected returns), the ERC of losses becomes statistically significant with more negative returns for larger losses when returns are measured either annually or around earnings announcements. Moreover, loss firms will continue to have poor future earnings and operating cash flows, and larger losses are associated with more negative analyst forecast revisions in the loss-reporting year. I also document that losses provide more negative cash flow information when they are not because of research and development expensing, when they trigger operational curtailments, and when they are less likely to reverse to profits. Further tests confirm the robustness of my findings to considering future return drifts/reversals, alternative proxies for expected returns and discount rate news, alternative test portfolios, and alternative model specifications. Overall, my paper provides new insights into the information content of losses. This paper was accepted by Suraj Srinivasan, accounting.