bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adequacy of early-stage breast cancer systemic adjuvant treatment to Saint Gallen-2013 statement: the MCC-Spain study
Authors: Gómez-Acebo Inés , Dierssen-Sotos Trinidad , Mirones Mónica , Pérez-Gómez Beatriz , Guevara Marcela , Amiano Pilar , Sala Maria , Molina Antonio J. , Alonso-Molero Jéssica , Moreno Victor , Suarez-Calleja Claudia , Molina-Barceló Ana , Alguacil Juan , Marcos-Gragera Rafael , Fernández-Ortiz María , Sanz-Guadarrama Oscar , Castaño-Vinyals Gemma , Gil-Majuelo Leire , Moreno-Iribas Conchi , Aragonés Nuria , Kogevinas Manolis , Pollán Marina , Llorca Javier 
Published: March 2021

AbstractThe St Gallen Conference endorsed in 2013 a series of recommendations on early breast cancer treatment. The main purpose of this article is to ascertain the clinical factors associated with St Gallen-2013 recommendations accomplishment. A cohort of 1152 breast cancer cases diagnosed with pathological stage < 3 in Spain between 2008 and 2013 was begun and then followed-up until 2017/2018. Data on patient and tumour characteristics were obtained from medical records, as well as their first line treatment. First line treatments were classified in three categories, according on whether they included the main St Gallen-2013 recommendations, more than those recommended or less than those recommended. Multinomial logistic regression models were carried out to identify factors associated with this classification and Weibull regression models were used to find out the relationship between this classification and survival. About half of the patients were treated according to St Gallen recommendations; 21% were treated over what was recommended and 33% received less treatment than recommended. Factors associated with treatment over the recommendations were stage II (relative risk ratio [RRR] = 4.2, 2.9–5.9), cancer positive to either progesterone (RRR = 8.1, 4.4–14.9) or oestrogen receptors (RRR = 5.7, 3.0–11.0). Instead, factors associated with lower probability of treatment over the recommendations were age (RRR = 0.7 each 10 years, 0.6–0.8), poor differentiation (RRR = 0.09, 0.04–0.19), HER2 positive (RRR = 0.46, 0.26–0.81) and triple negative cancer (RRR = 0.03, 0.01–0.11). Patients treated less than what was recommended in St Gallen had cancers in stage 0 (RRR = 21.6, 7.2–64.5), poorly differentiated (RRR = 1.9, 1.2–2.9), HER2 positive (RRR = 3.4, 2.4–4.9) and luminal B-like subtype (RRR = 3.6, 2.6–5.1). Women over 65 years old had a higher probability of being treated less than what was recommended if they had luminal B-like, HER2 or triple negative cancer. Treatment over St Gallen was associated with younger women and less severe cancers, while treatment under St Gallen was associated with older women, more severe cancers and cancers expressing HER2 receptors.
Dynamic roles of inflammasomes in inflammatory tumor microenvironment
Authors: Jang Jeong-Hoon , Kim Do-Hee , Surh Young-Joon 
Published: March 2021

AbstractThe inflammatory tumor microenvironment has been known to be closely connected to all stages of cancer development, including initiation, promotion, and progression. Systemic inflammation in the tumor microenvironment is increasingly being recognized as an important prognostic marker in cancer patients. Inflammasomes are master regulators in the first line of host defense for the initiation of innate immune responses. Inflammasomes sense pathogen-associated molecular patterns and damage-associated molecular patterns, following recruitment of immune cells into infection sites. Therefore, dysregulated expression/activation of inflammasomes is implicated in pathogenesis of diverse inflammatory disorders. Recent studies have demonstrated that inflammasomes play a vital role in regulating the development and progression of cancer. This review focuses on fate-determining roles of the inflammasomes and the principal downstream effector cytokine, IL-1β, in the tumor microenvironment.
A multiscale view of the Phanerozoic fossil record reveals the three major biotic transitions
Authors: Rojas Alexis , Calatayud Joaquin , Kowalewski Michał , Neuman Magnus , Rosvall Martin 
Published: March 2021

AbstractThe hypothesis of the Great Evolutionary Faunas is a foundational concept of macroevolutionary research postulating that three global mega-assemblages have dominated Phanerozoic oceans following abrupt biotic transitions. Empirical estimates of this large-scale pattern depend on several methodological decisions and are based on approaches unable to capture multiscale dynamics of the underlying Earth-Life System. Combining a multilayer network representation of fossil data with a multilevel clustering that eliminates the subjectivity inherent to distance-based approaches, we demonstrate that Phanerozoic oceans sequentially harbored four global benthic mega-assemblages. Shifts in dominance patterns among these global marine mega-assemblages were abrupt (end-Cambrian 494 Ma; end-Permian 252 Ma) or protracted (mid-Cretaceous 129 Ma), and represent the three major biotic transitions in Earth’s history. Our findings suggest that gradual ecological changes associated with the Mesozoic Marine Revolution triggered a protracted biotic transition comparable in magnitude to the end-Permian transition initiated by the most severe biotic crisis of the past 500 million years. Overall, our study supports the notion that both long-term ecological changes and major geological events have played crucial roles in shaping the mega-assemblages that dominated Phanerozoic oceans.
A Neural Marker of Speech Intention: Evidence From Contingent Negative Variation
Authors: Kidwai Juhi , Brumberg Jonathan S. , Marsh Brianna M. 
Published: March 2021

PurposeThis study investigated whether changes in brain activity preceding spoken words can be used as a neural marker of speech intention. Specifically, changes in the contingent negative variation (CNV) were examined prior to speech production in three different study designs to determine a method that maximizes signal detection in a speaking task.MethodElectroencephalography data were collected in three different protocols to elicit the CNV in a spoken word task that varied the timing and type of linguistic information. The first protocol provided participants with the word to be spoken before the instruction of whether or not to speak, the second provided both the word and the instruction to speak, and the third provided the instruction to speak before the word. Participants (N= 18) were split into three groups (one for each protocol) and were instructed to either speak (Go) or refrain from speaking (NoGo) each word according to task instructions. The CNV was measured by analyzing the difference in slope between Go and NoGo trials.ResultsStatistically significant effects of hemispheric laterality on the CNV slope confirm the third protocol where the participants know they will speak in advance of the word, as the paradigm that reliably elicits a CNV response related to speech intention.ConclusionsThe maximal CNV response when the instruction is known before the word indicates the neural processing measured in this protocol may reflect a generalized speech intention process in which the speech-language systems become prepared to speak and then execute production once the word information is provided. Further analysis of the optimal protocol identified in this study requires additional experimental investigation to confirm its role in eliciting an objective marker of speech intention.Supplemental Materialhttps://doi.org/10.23641/asha.14111468
Laparoscopically assisted Adenomyomectomy Using the Double/Multiple-Flap Method with Temporary Occlusion of the Bilateral Uterine Artery and Utero-Ovarian Vessels in Comparison with the Double/Multiple-Flap Only Method
Authors: Ji Limei , Jin Lanying , Zheng Shunjie , Shao Mingjun , Cui Dawei , Hu Min 
Published: March 2021

Abstract
Introduction Adenomyomectomy is the most conservative surgical treatment for adenomyosis. However, the surgical efficacy of this treatment and the best approach to use are still debated. We aimed to evaluate the efficacy of laparoscopic adenomyomectomy using the double/multiple-flap method combined with temporary occlusion of the bilateral uterine artery and the utero-ovarian vessels to treat symptomatic adenomyosis.
Patients We recruited 155 patients with symptomatic adenomyosis and divided them into group A (n = 76) and group B (n = 79), with each group treated using a different surgical approach. All eligible women were informed of the potential complications, benefits, and alternatives of each approach before they were assigned into one of the two groups. In group A, we performed laparoscopic adenomyomectomy with the double/multiple-flap method while in group B, we performed a double/multiple-flap adenomyomectomy combined with temporary occlusion of the bilateral uterine artery and utero-ovarian vessels. Over a 24-month follow-up period, we evaluated operating time, intraoperative blood loss, visual analog scale (VAS) scores, anti-Mullerian hormone levels, uterine volume, and relief of menorrhagia.
Results There were no significant differences between groups A and B with respect to VAS scores, relief of menorrhagia and uterine volume at 3 months, 6 months, 12 months and 24 months after surgery (p > 0.05). Both groups showed significant improvement of these parameters after surgery compared with preoperative values (p < 0.05). Blood loss in group B was significantly lower than in group A (p < 0.001) while there was no significant difference in operating times (p > 0.05). Levels of AMH did not differ significantly between the groups throughout the follow-up period (p > 0.05).
Conclusion Laparoscopic adenomyomectomy with temporary occlusion of the bilateral uterine artery and the utero-ovarian vessels offers a feasible surgical option to treat symptomatic adenomyoma.
Time-resolved turbulent dynamo in a laser plasma
Authors: Bott Archie F. A. , Tzeferacos Petros , Chen Laura , Palmer Charlotte A. J. , Rigby Alexandra , Bell Anthony R. , Bingham Robert , Birkel Andrew , Graziani Carlo , Froula Dustin H. , Katz Joseph , Koenig Michel , Kunz Matthew W. , Li Chikang , Meinecke Jena , Miniati Francesco , Petrasso Richard , Park Hye-Sook , Remington Bruce A. , Reville Brian , Ross J. Steven , Ryu Dongsu , Ryutov Dmitri , Séguin Fredrick H. , White Thomas G. , Schekochihin Alexander A. , Lamb Donald Q. , Gregori Gianluca 
Published: March 2021

Significance
Our laser-plasma experiment has reproduced the physical process thought to be responsible for generating and sustaining magnetic fields in turbulent plasmas (the “fluctuation dynamo”), and has accessed the viscosity-dominated regime of relevance to most of the plasma in the universe. These measurements are also time resolved, which provides evolutionary information about the fluctuation dynamo (including the field’s growth rate) previously available only from simulations. The efficient amplification of large-scale magnetic fields seen in our experiment could explain the origin of large-scale fields that are observed in turbulent astrophysical plasmas, but are not predicted by current analytical calculations or idealized simulations of the fluctuation dynamo.
Gradient descent dynamics in the mixed p-spin spherical model: finite-size simulations and comparison with mean-field integration
Authors: Folena Giampaolo , Franz Silvio , Ricci-Tersenghi Federico 
Published: March 2021

Abstract
We perform numerical simulations of a long-range spherical spin glass with two and three body interaction terms. We study the gradient descent dynamics and the inherent structures found after a quench from initial conditions well thermalized at temperature T
in. In very large systems, the dynamics perfectly agrees with the integration of the mean-field dynamical equations. In particular, we confirm the existence of an onset initial temperature, within the liquid phase, below which the energy of the inherent structures undoubtedly depends on T
in. This behavior is in contrast with that of pure models, where there is a ‘threshold energy’ that attracts all the initial configurations in the liquid. Our results strengthen the analogy between mean-field spin glass models and supercooled liquids.
Precision Verification: Effect of Experiment Design on False Acceptance and False Rejection Rates
Authors: Lim Chun Yee , Markus Corey , Loh Tze Ping 
Published: March 2021

Abstract

Objectives
We examined the false acceptance rate (FAR) and false rejection rate (FRR) of varying precision verification experimental designs.

Methods
Analysis of variance was applied to derive the subcomponents of imprecision (ie, repeatability, between-run, between-day imprecision) for complex matrix experimental designs (day × run × replicate; day × run). For simple nonmatrix designs (1 day × multiple replicates or multiday × 1 replicate), ordinary standard deviations were calculated. The FAR and FRR in these different scenarios were estimated.

Results
The FRR increased as more samples were included in the precision experiment. The application of an upper verification limit, which seeks to cap FRR at 5% for multiple experiments, significantly increased the FAR. The FRR decreases as the observed imprecision increases relative to the claimed imprecision and when a greater number of days, runs, or replicates are included in the verification design. Increasing the number or days, runs, or replicates also reduces the FAR for between-day imprecision and repeatability.

Conclusions
Design of verification experiments should incorporate the local availability of resources and analytical expertise. The largest imprecision component should be targeted with a greater number of measurements. Consideration of both FAR and FRR should be given when committing a platform into service.
sepal: identifying transcript profiles with spatial patterns by diffusion-based modeling
Authors: Andersson Alma , Lundeberg Joakim 
Published: March 2021

Abstract

Motivation
Collection of spatial signals in large numbers has become a routine task in multiple omics-fields, but parsing of these rich datasets still pose certain challenges. In whole or near-full transcriptome spatial techniques, spurious expression profiles are intermixed with those exhibiting an organized structure. To distinguish profiles with spatial patterns from the background noise, a metric that enables quantification of spatial structure is desirable. Current methods designed for similar purposes tend to be built around a framework of statistical hypothesis testing, hence we were compelled to explore a fundamentally different strategy.

Results
We propose an unexplored approach to analyze spatial transcriptomics data, simulating diffusion of individual transcripts to extract genes with spatial patterns. The method performed as expected when presented with synthetic data. When applied to real data, it identified genes with distinct spatial profiles, involved in key biological processes or characteristic for certain cell types. Compared to existing methods, ours seemed to be less informed by the genes’ expression levels and showed better time performance when run with multiple cores.

Availabilityand implementation
Open-source Python package with a command line interface (CLI), freely available at https://github.com/almaan/sepal under an MIT licence. A mirror of the GitHub repository can be found at Zenodo, doi: 10.5281/zenodo.4573237.

Supplementary information
Supplementary data are available at Bioinformatics online.
A novel remitting leukodystrophy associated with a variant in FBP2
Authors: Gizak Agnieszka , Diegmann Susann , Dreha-Kulaczewski Steffi , Wiśniewski Janusz , Duda Przemysław , Ohlenbusch Andreas , Huppke Brenda , Henneke Marco , Höhne Wolfgang , Altmüller Janine , Thiele Holger , Nürnberg Peter , Rakus Dariusz , Gärtner Jutta , Huppke Peter 
Published: March 2021

Abstract
Leukodystrophies are genetic disorders of cerebral white matter that almost exclusively have a progressive disease course. We became aware of three members of a family with a disorder characterized by a sudden loss of all previously acquired abilities around 1 year of age followed by almost complete recovery within 2 years. Cerebral MRI and myelin sensitive imaging showed a pronounced demyelination that progressed for several months despite signs of clinical improvement and was followed by remyelination. Exome sequencing did not-identify any mutations in known leukodystrophy genes but revealed a heterozygous variant in the FBP2 gene, c.343G&gt;A, p. Val115Met, shared by the affected family members. Cerebral MRI of other family members demonstrated similar white matter abnormalities in all carriers of the variant in FBP2. The FBP2 gene codes for muscle fructose 1,6-bisphosphatase, an enzyme involved in gluconeogenesis that is highly expressed in brain tissue. Biochemical analysis showed that the variant has a dominant negative effect on enzymatic activity, substrate affinity, cooperativity and thermal stability. Moreover, it also affects the non-canonical functions of muscle fructose 1,6-bisphosphatase involved in mitochondrial protection and regulation of several nuclear processes. In patients’ fibroblasts, muscle fructose 1,6-bisphosphatase shows no colocalization with mitochondria and nuclei leading to increased reactive oxygen species production and a disturbed mitochondrial network. In conclusion, the results of this study indicate that the variant in FBP2 disturbs cerebral energy metabolism and is associated with a novel remitting leukodystrophy.
Case report of Takotsubo syndrome following seizures in a patient with pyruvate carboxylase deficiency
Authors: Sahdev Nikhil , Oji Onyedikachi , Babu Aswin , Dutta Roy Smita 
Published: March 2021

Abstract

Background
Takotsubo syndrome (TS) is defined as transient left ventricular dysfunction, which is often related to an emotional or physically stressful event. We describe a case of TS in a lady with pyruvate carboxylase deficiency (PCD). Pyruvate carboxylase deficiency is rare condition with the majority of those affected demonstrating signs of failure to thrive, recurrent seizures, and metabolic acidosis. To our knowledge, this is the first documented case of TS in an individual with PCD.

Case summary
This 28-year-old female presented to the emergency department after a tonic-clonic seizure. For 4 days prior to the presentation, she had been suffering from cough and pyrexia. On Day 2, she developed abdominal pain associated with tachycardia and hypotension, and an elevated troponin (791 ng/L). The echocardiogram showed a severely impaired left ventricular systolic function, regional wall motion abnormalities (RWMAs), and a visually estimated left ventricular ejection fraction of 25–30%. Eight days following admission her clinical state significantly improved, with a reduction troponin to 60 ng/L. A repeat echocardiogram on Day 9 showed complete resolution of cardiac function with no RWMAs. Following this, she was discharged from hospital the next day with a diagnosis of TS.

Discussion
This is the first case report of TS in a patient with PCD. In this case, multiple aetiologies of TS such as emotional and physical stress, seizures, and acute infection were considered. This case also highlights that TS should be an important differential diagnosis in patients presenting with cardiac symptoms.
A case report of a symptomatic right anomalous coronary artery with concomitant atherosclerotic disease: the benefit of a sequential comprehensive non-invasive and invasive diagnostic approach
Authors: Bigler Marius Reto , Huber Adrian Thomas , Räber Lorenz , Gräni Christoph 
Published: March 2021

Abstract

Background
Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital disease associated with an increased risk of myocardial ischaemia, ventricular arrhythmias, and heart failure.

Case summary
A 75-year-old Caucasian man was referred for invasive coronary angiography (ICA) due to atypical chest pain. Invasive coronary angiography demonstrated non-significant atherosclerotic disease of the left coronary artery and an anomalous origin of the right coronary artery (RCA); without selective intubation. Coronary computed tomography angiography (CCTA) revealed a right-AAOCA with interarterial and intramural course, and a soft plaque in the distal RCA. Subsequent physical-stress single-photon emissions computed tomography (SPECT) showed exercise-induced inferoapical myocardial ischaemia, giving a Class IC level of evidence for surgical correction of the AAOCA. Repeated ICA with selective R-AAOCA intubation confirmed an 80% distal atherosclerotic stenosis, which was treated with direct stenting. Subsequent invasive physiologic evaluation under maximal dobutamine-volume challenge (gradually increasing dose of dobutamine max. 40 μg/kg per body weight/min, 3000 mL ringer lactate and 1 mg atropine was given until the patient reached a maximum of 145 b.p.m.), revealed a haemodynamically non-relevant anomalous segment with a fractional flow reserve (FFR) of 0.91. A follow-up SPECT was normal, and the patient was completely symptom-free at 1 month.

Discussion
We present the sequential diagnostic approach in a symptomatic patient with a right anomalous coronary artery and concomitant atherosclerotic disease. Using this approach, the patient could be deferred from guideline recommended open-heart surgery of the AAOCA, as direct invasive dobutamine/volume FFR revealed haemodynamic non-relevance of the anomalous segment after stenting the concomitant atherosclerotic stenosis in the distal segment within the same coronary artery.
Between Participation and Capture in International Rule-Making: The WHO Framework of Engagement with Non-State Actors
Authors: Berman Ayelet 
Published: March 2021

Abstract
There has been a tremendous rise in the participation of non-state actors – notably business – in international rule-making. While such participation has many benefits, the risk that rule-making gets captured – that is, that rules are made in line with business’ profit-driven interest rather than in the public interest – has increased too. This article, first, explores the growing problem of capture in international rule-making and identifies three modes of capture that have become particularly prevalent in international policy-making: information capture, representational capture and resource capture. The article then explores the World Health Organization’s (WHO) 2016 Framework of Engagement with Non-State Actors (FENSA) and how effectively it manages these risks. FENSA is interesting because it is the first policy by an international organization seeking to comprehensively and systematically regulate non-state actor engagement and to prevent related risks. In assessing FENSA, the article focuses on the WHO’s engagement of two main actors: the Big Food industry and voluntary donors. Finally, the article seeks to draw more general lessons as to the capacity of FENSA-like reforms to prevent capture in international rule-making.