bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperthyroidism in pregnancy: design and methodology of a Danish multicenter study
Authors: Torp Nanna Maria Uldall , Pedersen Inge Bülow , Carlé Allan , Karmisholt Jesper Scott , Ebbehøj Eva , Grove-Laugesen Diana , Brix Thomas Heiberg , Bonnema Steen Joop , Schrijvers Bieke F. , Nygaard Birte , Sigurd Lena Bjergved , Feldt-Rasmussen Ulla , Klose Marianne , Rasmussen Åse Krogh , Andersen Stig , Andersen Stine Linding 
Published: April 2023

Abstract
Background
Graves’ disease (GD) is the main cause of hyperthyroidism in women of the fertile age. In pregnant women, the disease should be carefully managed and controlled to prevent maternal and fetal complications. Observational studies provide evidence of the adverse effects of untreated hyperthyroidism in pregnancy and have in more recent years substantiated a risk of teratogenic side effects with the use of antithyroid drugs (ATDs). These findings have challenged the clinical recommendations regarding the choice of treatment when patients become pregnant. To extend observational findings and support future clinical practice, a systematic collection of detailed clinical data in and around pregnancy is needed.

Methods
With the aim of collecting clinical and biochemical data, a Danish multicenter study entitled ‘Pregnancy Investigations on Thyroid Disease’ (PRETHYR) was initiated in 2021. We here describe the design and methodology of the first study part of PRETHYR. This part focuses on maternal hyperthyroidism and recruits female patients in Denmark with a past or present diagnosis of GD, who become pregnant, as well as women who are treated with ATDs in the pregnancy, irrespective of the underlying etiology. The women are included during clinical management from endocrine hospital departments in Denmark, and study participation includes patient questionnaires in pregnancy and postpartum as well as review of medical records from the mother and the child.

Results
Data collection was initiated on November 1, 2021 and covered all five Danish Regions from March 1, 2022. Consecutive study inclusion will continue, and we here report the first status of inclusion. As of November 1, 2022, a total of 62 women have been included in median pregnancy week 19 (interquartile range (IQR): 10–27) with a median maternal age of 31.4 years (IQR: 28.5–35.1). At inclusion, 26 women (41.9%) reported current use of thyroid medication; ATDs (n = 14), Levothyroxine (n = 12).

Conclusion
This report describes a newly established systematic and nationwide collection of detailed clinical data on pregnant women with hyperthyroidism and their offspring. Considering the course and relatively low prevalence of GD in pregnant women, such nationwide design is essential to establish a sufficiently large cohort.
Insights into high-grade serous carcinoma pathobiology using three-dimensional culture model systems
Authors: Tomas Emily , Shepherd Trevor G. 
Published: April 2023

AbstractEpithelial ovarian cancer (EOC) research has become more complex as researchers try to fully understand the metastatic process. Especially as we delve into the concept of tumour dormancy, where cells transition between proliferative and dormant states to survive during disease progression. Thus, the in vitro models used to conduct this research need to reflect this vast biological complexity. The innovation behind the many three-dimensional (3D) spheroid models has been refined to easily generate reproducible spheroids so that we may understand the various molecular signaling changes of cells during metastasis and determine therapeutic efficacy of treatments. This ingenuity was then used to develop the 3D ex vivo patient-derived organoid model, as well as multiple co-culture model systems for EOC research. Although, researchers need to continue to push the boundaries of these current models for in vitro and even in vivo work in the future. In this review, we describe the 3D models already in use, where these models can be developed further and how we can use these models to gain the most knowledge on EOC pathogenesis and discover new targeted therapies.
Clinical risk factors for increased respiratory drive in intubated hypoxemic patients
Authors: Spinelli Elena , Pesenti Antonio , Slobod Douglas , Fornari Carla , Fumagalli Roberto , Grasselli Giacomo , Volta Carlo Alberto , Foti Giuseppe , Navalesi Paolo , Knafelj Rihard , Pelosi Paolo , Mancebo Jordi , Brochard Laurent , Mauri Tommaso 
Published: April 2023

Abstract
Background
There is very limited evidence identifying factors that increase respiratory drive in hypoxemic intubated patients. Most physiological determinants of respiratory drive cannot be directly assessed at the bedside (e.g., neural inputs from chemo- or mechano-receptors), but clinical risk factors commonly measured in intubated patients could be correlated with increased drive. We aimed to identify clinical risk factors independently associated with increased respiratory drive in intubated hypoxemic patients.

Methods
We analyzed the physiological dataset from a multicenter trial on intubated hypoxemic patients on pressure support (PS). Patients with simultaneous assessment of the inspiratory drop in airway pressure at 0.1-s during an occlusion (P0.1) and risk factors for increased respiratory drive on day 1 were included. We evaluated the independent correlation of the following clinical risk factors for increased drive with P0.1: severity of lung injury (unilateral vs. bilateral pulmonary infiltrates, PaO2/FiO2, ventilatory ratio); arterial blood gases (PaO2, PaCO2 and pHa); sedation (RASS score and drug type); SOFA score; arterial lactate; ventilation settings (PEEP, level of PS, addition of sigh breaths).

Results
Two-hundred seventeen patients were included. Clinical risk factors independently correlated with higher P0.1 were bilateral infiltrates (increase ratio [IR] 1.233, 95%CI 1.047–1.451, p = 0.012); lower PaO2/FiO2 (IR 0.998, 95%CI 0.997–0.999, p = 0.004); higher ventilatory ratio (IR 1.538, 95%CI 1.267–1.867, p < 0.001); lower pHa (IR 0.104, 95%CI 0.024–0.464, p = 0.003). Higher PEEP was correlated with lower P0.1 (IR 0.951, 95%CI 0.921–0.982, p = 0.002), while sedation depth and drugs were not associated with P0.1.

Conclusions
Independent clinical risk factors for higher respiratory drive in intubated hypoxemic patients include the extent of lung edema and of ventilation-perfusion mismatch, lower pHa, and lower PEEP, while sedation strategy does not affect drive. These data underline the multifactorial nature of increased respiratory drive.
Comprehensive benchmark and architectural analysis of deep learning models for nanopore sequencing basecalling
Authors: Pagès-Gallego Marc , de Ridder Jeroen 
Published: April 2023

Abstract
Background
Nanopore-based DNA sequencing relies on basecalling the electric current signal. Basecalling requires neural networks to achieve competitive accuracies. To improve sequencing accuracy further, new models are continuously proposed with new architectures. However, benchmarking is currently not standardized, and evaluation metrics and datasets used are defined on a per publication basis, impeding progress in the field. This makes it impossible to distinguish data from model driven improvements.

Results
To standardize the process of benchmarking, we unified existing benchmarking datasets and defined a rigorous set of evaluation metrics. We benchmarked the latest seven basecaller models by recreating and analyzing their neural network architectures. Our results show that overall Bonito’s architecture is the best for basecalling. We find, however, that species bias in training can have a large impact on performance. Our comprehensive evaluation of 90 novel architectures demonstrates that different models excel at reducing different types of errors and using recurrent neural networks (long short-term memory) and a conditional random field decoder are the main drivers of high performing models.

Conclusions
We believe that our work can facilitate the benchmarking of new basecaller tools and that the community can further expand on this work.
Effects of advanced glycation end products (AGEs) on the differentiation potential of primary stem cells: a systematic review
Authors: Xu Kuishuai , Zhang Liang , Yu Ning , Ren Zhongkai , Wang Tianrui , Zhang Yingze , Zhao Xia , Yu Tengbo 
Published: April 2023

AbstractThe formation and accumulation of advanced glycation end products (AGEs) have been associated with aging and the development, or worsening, of many degenerative diseases, such as atherosclerosis, chronic kidney disease, and diabetes. AGEs can accumulate in a variety of cells and tissues, and organs in the body, which in turn induces oxidative stress and inflammatory responses and adversely affects human health. In addition, under abnormal pathological conditions, AGEs create conditions that are not conducive to stem cell differentiation. Moreover, an accumulation of AGEs can affect the differentiation of stem cells. This, in turn, leads to impaired tissue repair and further aggravation of diabetic complications. Therefore, this systematic review clearly outlines the effects of AGEs on cell differentiation of various types of primary isolated stem cells and summarizes the possible regulatory mechanisms and interventions. Our study is expected to reveal the mechanism of tissue damage caused by the diabetic microenvironment from a cellular and molecular point of view and provide new ideas for treating complications caused by diabetes.
Exploring expert perceptions about microplastics: from sources to potential solutions
Authors: Grünzner Maja , Pahl Sabine , White Mathew P. , Thompson Richard C. 
Published: April 2023

AbstractConcern about plastic pollution, including microplastics, is high amongst European citizens, and effective actions are needed to reduce microplastic pollution. However, there is still uncertainty and debate about the major sources, impacts, and in particular the solutions. The aim of the current study was to gather expert perceptions about the risks of different microplastic sources to the natural environment and human health (measured as the likelihood and severity of negative impacts resulting from exposure), as well as the feasibility and effectiveness of different solutions. Experts were identified as scientists working on plastic. Usable responses were received from 73 experts with an average of 5 years’ experience in plastic research. Experts thought that there was currently stronger evidence for microplastic impacts on the natural environment than on human health, that, accordingly, the risks were higher, and they were more worried about impacts on the natural environment than on human health. Experts perceived tyre particles and textile fibres to be the main sources of microplastics presenting risk for both natural environment and human health. Various solutions were rated as relatively effective and feasible overall. Solutions that were rated as above-average in terms of effectiveness and feasibility included education and awareness programmes, washing machine filters, bans of plastic items, simplified design of products, and circular economy approaches. However, experts were uncertain about the effectiveness and feasibility of recovery and clean-up solutions, with overall ratings for these being below-average in comparison to other solutions earlier in the plastic life cycle. An improved understanding of expert views on these matters could inform the distribution of limited research resources and help prioritise research questions, especially with regard to potential solutions and interventions which will be critical for the success of the UN Plastics Treaty.
The heterogeneity of depressions: A phenomenological viewpoint
Authors: Stanghellini Giovanni 
Published: April 2023

Abstract
What is commonly referred to as “depression” indicates a heterogeneous complex disorder that includes distinct psychopathological forms. A more accurate classification can be achieved by assessing the individual experiences of depression and tracing back each of these forms to the specific vulnerable structure from which they emerge. Each of these vulnerable forms of existence can be characterized by focusing on their values. I identify four main prototypes. Homo melancholicus is impressive for their over-normality, extreme social adjustment, and conformism; their depressive decomposition is characterized by the experience of loss. The values of homo œconomicus are utility (every action must be directed toward production) and optimization (what costs more than it produces is a dead branch to be cut); their depressive decomposition is marked by insolvency. Homo dissipans’ values are excess (feeling animated by an inexhaustible drive to “pour out” of oneself, especially outside the limits of composure and reasonableness) and expenditure (an ethical attitude that gives its approval to excess and to its metamorphic and destructive power); their depressive decomposition is epitomized by inner incoherence and emptiness. The style of homo nevroticus form of existence is subjugated by the condemnation to limitation and the diktat of prohibition; their depressive decomposition is characterized by frustration and demoralization.
Electron-doping Ruddlesden-Popper nickelate
Authors: Chen X. , Jiang P. , Zhong Z. 
Published: April 2023

Abstract
The discovery of cuprate and iron-based superconductors in the last three decades has stimulated a great enthusiasm in researching high T

C
superconductors. For cuprate, a lot of superconducting compounds were discovered and the superconducting behavior can be tuned by changing the number of the

layer. Currently, a cuprate-like superconductor, i.e., nickelate, is reported, which opens a new era in the field of superconductivity. However, the superconducting behavior is only limited in quite a few nickelate compounds. Here, based on first-principles calculations, we investigate the electronic band structure of Ruddlesden Popper (RP) phase and reduced RP (rRP) phase nickelates, and the electron doping influences on these phases. Our results further indicate that the most effective electron-doping selection for these RP/rRP phases is the fluorine replacing the oxygen sites (FO) of LaO or

layer to control the

electron state. This

doping not only introduces electrons to system but also keeps the effective single

band. Our theoretical predictions would contribute to the discovering of more possible nickelate superconductors.
Intravenous Thrombolysis for Acute Ischemic Stroke
Authors: Grotta James C. 
Published: April 2023

ABSTRACT

OBJECTIVE
This article reviews the history of IV thrombolysis, its current indications and implementation, the duality of the “time is brain” versus “tissue clock” approaches, the impact of endovascular thrombectomy on IV thrombolysis, the emergence of tenecteplase, and future research directions.

LATEST DEVELOPMENTS
The growing use of factor Xa inhibitors has increasingly caused patients with stroke to be excluded from treatment with IV thrombolysis. Important geographic, socioeconomic, sex, race, and ethnic disparities have been identified in the implementation of IV thrombolysis and need to be overcome. IV thrombolysis substantially improves outcomes when provided within the first golden hour after stroke onset in patients treated in mobile stroke units, supporting the “time is brain” concept and encouraging the possible value of more widespread implementation of the mobile stroke unit approach. At the same time, other studies have shown that IV thrombolysis can be successful in patients whose “tissue clock” is still ticking up to 9 hours after stroke onset or in patients who awaken with their stroke, as demonstrated by favorable imaging profiles. These considerations, along with the emergence of endovascular thrombectomy, have fostered examination of our care systems, including the “drip and ship” versus direct to comprehensive or endovascular thrombectomy stroke center approaches, as well as the possibility of skipping IV thrombolysis in certain patients treated with endovascular thrombectomy. Data suggesting that tenecteplase is at least noninferior to alteplase, as well as its more convenient dosing, has led to its increased use. Ongoing studies are evaluating newer thrombolytics and adding antithrombotic therapy to IV thrombolysis.

ESSENTIAL POINTS
IV thrombolysis remains the most common acute stroke treatment. Advances in acting faster to treat stroke have increased its efficacy, and advances in imaging have expanded its use. However, implementing these advances and overcoming disparities in IV thrombolysis use remain major challenges.
Diagnosis and Management of Large Artery Atherosclerosis
Authors: Chaturvedi Seemant 
Published: April 2023

ABSTRACT

OBJECTIVE
Ischemic stroke due to large vessel atherosclerosis is a significant cause of stroke globally. With the aging population, the number of people with atherosclerotic stroke will increase in the coming decades. This article reviews the recent developments in the assessment and treatment of extracranial and intracranial atherosclerotic disease.

LATEST DEVELOPMENTS
More intensive dual antiplatelet therapy can now be recommended for patients with transient ischemic attack or stroke. More stringent blood pressure and lipid control is also advised. The need for carotid revascularization will likely decrease in the coming decades because of advances in multimodal medical therapy; in particular, the role of revascularization for treating asymptomatic carotid stenosis is controversial. Patients with symptomatic intracranial stenosis should receive intensive medical therapy. Interest in high-resolution carotid plaque imaging is growing.

ESSENTIAL POINTS
The prevention of stroke due to large vessel atherosclerosis has improved owing to advances in medical therapies. The role of carotid revascularization is unclear for many patient subgroups.
Pediatric Ischemic Stroke
Authors: Fox Christine 
Published: April 2023

ABSTRACT

OBJECTIVE
Pediatric cerebrovascular disease is one of the leading causes of death and disability in children. Survivors of childhood stroke and their families are often left to cope with long-lasting sequelae, such as barriers to school reentry and long-term challenges in attaining independence as adults. Because childhood stroke is rare and providers may not be familiar with the disorder, this article reviews the risk factors, acute management, and sequelae of ischemic stroke in children.

LATEST DEVELOPMENTS
High-quality evidence has resulted in an organized approach to emergent treatment of ischemic stroke in adults, but most front-line providers are less prepared for emergent stroke management in children. The level of evidence for reperfusion therapies in children remains low but is growing. Thrombolysis and thrombectomy are sometimes considered for hyperacute treatment of stroke in children. Readiness for pediatric stroke at regional centers should include an organized approach to pediatric stroke triage and management based on extrapolation from adult stroke trials, expert consensus, and emerging pediatric studies.

ESSENTIAL POINTS
This review provides up-to-date information about ischemic stroke risk factors and management in children. Preparation for rapid stroke diagnosis and management in children may improve outcomes.
Management of Unruptured Intracranial Aneurysms and Brain Arteriovenous Malformations
Authors: Nguyen Thanh Ngoc 
Published: April 2023

ABSTRACT

OBJECTIVE
Managing a patient with an unruptured brain aneurysm or brain arteriovenous malformation (AVM) can lead to uncertainty about preventive treatment. While the bleeding risks are low, the morbidity or mortality associated with a hemorrhagic event is not insignificant. The objective of this article is to review the natural history of these vascular entities, the risk factors for hemorrhage, preventive treatment options, and the risks of treatment.

LATEST DEVELOPMENTS
Randomized trials to inform preventive treatment strategies for unruptured intracranial aneurysms and brain AVMs are ongoing. Higher angiographic obliteration rates of unruptured intracranial aneurysms have been reported with the flow-diversion technique compared with alternative standard techniques. One randomized trial for unruptured brain AVMs showed a higher rate of morbidity and mortality in patients who underwent interventional treatment compared with observation.

ESSENTIAL POINTS
The decision to treat a patient with a brain aneurysm should consider patient factors, the patient’s life expectancy, aneurysm anatomical factors, and treatment risks. Patients with unruptured brain AVMs should be observed in light of recent clinical trial data or enrolled in an ongoing clinical trial.
Hemato-vascular specification requires arnt1 and arnt2 genes in zebrafish embryos
Authors: Edwards Hailey E. , Elizalde Mary Jane , Souder Jaclyn P. , Gorelick Daniel A. 
Published: April 2023

ABSTRACT
During embryonic development, a subset of cells in the mesoderm germ layer are specified as hemato-vascular progenitor cells, which then differentiate into endothelial cells and hematopoietic stem and progenitor cells. In zebrafish, the transcription factor npas4l (cloche) is required for the specification of hemato-vascular progenitor cells. However, it is unclear whether npas4l is the sole factor at the top of the hemato-vascular specification cascade. Here, we show that arnt1 and arnt2 genes are required for hemato-vascular specification. We found that arnt1;arnt2 double mutant zebrafish embryos, but not arnt1 or arnt2 single mutants, lack blood cells and most endothelial cells. arnt1/2 mutants have reduced or absent expression of etsrp and tal1, the earliest known endothelial and hematopoietic transcription factor genes. We found that Npas4l binds both Arnt1 and Arnt2 proteins in vitro, consistent with the idea that PAS domain-containing bHLH transcription factors act in a multimeric complex to regulate gene expression. Our results demonstrate that npas4l, arnt1 and arnt2 act together to regulate endothelial and hematopoietic cell fate, where each gene is necessary, but not sufficient, to drive hemato-vascular specification.
The non-canonical Wnt receptor Ror2 is required for cartilage cell polarity and morphogenesis of the craniofacial skeleton in zebrafish
Authors: Dranow Daniel B. , Le Pabic Pierre , Schilling Thomas F. 
Published: April 2023

ABSTRACT
Non-canonical/β-catenin-independent Wnt signaling plays crucial roles in tissue/cell polarity in epithelia, but its functions have been less well studied in mesenchymal tissues, such as the skeleton. Mutations in non-canonical Wnt signaling pathway genes cause human skeletal diseases such as Robinow syndrome and Brachydactyly Type B1, which disrupt bone growth throughout the endochondral skeleton. Ror2 is one of several non-canonical Wnt receptor/co-receptors. Here, we show that ror2−/− mutant zebrafish have craniofacial skeletal defects, including disruptions of chondrocyte polarity. ror1−/− mutants appear to be phenotypically wild type, but loss of both ror1 and ror2 leads to more severe cartilage defects, indicating partial redundancy. Skeletal defects in ror1/2 double mutants resemble those of wnt5b−/− mutants, suggesting that Wnt5b is the primary Ror ligand in zebrafish. Surprisingly, the proline-rich domain of Ror2, but not its kinase domain, is required to rescue its function in mosaic transgenic experiments in ror2−/− mutants. These results suggest that endochondral bone defects in ROR-related human syndromes reflect defects in cartilage polarity and morphogenesis.