bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective, observational study on medication for opioid use disorder during pregnancy and risk for neonatal abstinence syndrome
Authors: Sujan Ayesha , Cleary Emma , Douglas Edie , Aujla Rubin , Boyars Lisa , Smith Claire , Guille Constance 
Published: September 2021

Abstract

Objectives
The prevalence of opioid use disorder (OUD) among pregnant women is increasing. Research consistently demonstrates the efficacy of medications for OUD (MOUD); however, researchers have called for additional studies evaluating the safety of MOUD during pregnancy, particularly the relative safety of two commonly used MOUD medications—methadone and buprenorphine. This study aimed to evaluate the consequences of MOUD exposure during pregnancy on risk for neonatal abstinence syndrome (NAS).

Methods
In a clinical sample of infants born to women with OUD, we evaluated the risk of NAS among those exposed to (i) methadone and (ii) buprenorphine compared with those unexposed to MOUD, as well as the risk of NAS among those exposed to (i) methadone compared with those exposed to (ii) buprenorphine.

Results
Compared with buprenorphine-exposed infants (n = 37), methadone-exposed infants (n = 27) were at increased risk for NAS (odds ratio [OR] = 4.67, 95% confidence interval [CI]: 1.03, 21.17). Compared with unexposed infants (n = 43), buprenorphine-exposed infants were at decreased risk for NAS (OR = 0.45, 95% CI: 0.14, 1.39) and methadone-exposed infants were at increased risk for NAS (OR = 2.64, 95% CI: 0.79, 8.76), though these associations were not statistically significant.

Conclusions
Our study suggests that when methadone and buprenorphine are equally appropriate options for the treatment of OUD in pregnant women, buprenorphine may add the additional benefit of reduced risk of newborn NAS.
The teacher, the institution and the war: primary schooling in France, 1913–1924
Authors: Saint-Fuscien Emmanuel 
Published: September 2021

Abstract
What if not only the new pedagogy emerging in Europe during the interwar years, but the institutional development of the school in the twentieth century owed something to educational experience in the era of the First World War? This is the question posed by this article, which aims to address the way in which the school represented the war, asking in turn how the war transformed the school. It aims to interrogate changes in pedagogical practice and interaction within the school during wartime, but also to examine the changes brought about after the return of peace.
Sharp Increase of Problematic Mitogenomes of Birds: Causes, Consequences, and Remedies
Authors: Sangster George , Luksenburg Jolanda A 
Published: September 2021

Abstract
Authentic DNA sequences are crucial for reliable evolutionary inference. Concerns about the identification of DNA sequences have been voiced several times in the past but few quantitative studies exist. Mitogenomes play important roles in phylogenetics, phylogeography, population genetics, and DNA identification. However, the large number of mitogenomes being published routinely, often in brief data papers, has raised questions about their authenticity. In this study, we quantify problematic mitogenomes of birds and their reusage in other papers. Of 1,876 complete or partial mitogenomes of birds published until January 1, 2020, the authenticity of 1,559 could be assessed with sequences of conspecifics. Of these, 78 (5.0%) were found to be problematic, including 45 curated reference sequences. Problems were due to misidentification (33), chimeras of two or three species (23), sequencing errors/numts (18), incorrect sequence assembly (1), mislabeling at GenBank but not in the final paper (2), or vice versa (1). The number of problematic mitogenomes has increased sharply since 2012. Worryingly, these problematic sequences have been reused 436 times in other papers, including 385 times in phylogenies. No less than 53% of all mitogenomic phylogenies/networks published until January 1, 2020 included at least one problematic mitogenome. Problematic mitogenomes have resulted in incorrect phylogenetic hypotheses and proposals for unwarranted taxonomic revision, and may have compromised comparative analyses and measurements of divergence times. Our results indicate that a major upgrade of quality control measures is warranted. We propose a comprehensive set of measures that may serve as a new standard for publishing mitogenome sequences.
VC@Scale: Scalable and high-performance variant calling on cluster environments
Authors: Ahmad Tanveer , Al Ars Zaid , Hofstee H Peter 
Published: September 2021

Abstract

Background
Recently many new deep learning–based variant-calling methods like DeepVariant have emerged as more accurate compared with conventional variant-calling algorithms such as GATK HaplotypeCaller, Sterlka2, and Freebayes albeit at higher computational costs. Therefore, there is a need for more scalable and higher performance workflows of these deep learning methods. Almost all existing cluster-scaled variant-calling workflows that use Apache Spark/Hadoop as big data frameworks loosely integrate existing single-node pre-processing and variant-calling applications. Using Apache Spark just for distributing/scheduling data among loosely coupled applications or using I/O-based storage for storing the output of intermediate applications does not exploit the full benefit of Apache Spark in-memory processing. To achieve this, we propose a native Spark-based workflow that uses Python and Apache Arrow to enable efficient transfer of data between different workflow stages. This benefits from the ease of programmability of Python and the high efficiency of Arrow’s columnar in-memory data transformations.

Results
Here we present a scalable, parallel, and efficient implementation of next-generation sequencing data pre-processing and variant-calling workflows. Our design tightly integrates most pre-processing workflow stages, using Spark built-in functions to sort reads by coordinates and mark duplicates efficiently. Our approach outperforms state-of-the-art implementations by &gt;2 times for the pre-processing stages, creating a scalable and high-performance solution for DeepVariant for both CPU-only and CPU + GPU clusters.

Conclusions
We show the feasibility and easy scalability of our approach to achieve high performance and efficient resource utilization for variant-calling analysis on high-performance computing clusters using the standardized Apache Arrow data representations. All codes, scripts, and configurations used to run our implementations are publicly available and open sourced; see https://github.com/abs-tudelft/variant-calling-at-scale.
Magmatic fluid pathways in the upper crust: insights from dense magnetotelluric observations around the Kuju Volcanoes, Japan
Authors: Aizawa Koki , Utsugi Mitsuru , Kitamura Keigo , Koyama Takao , Uyeshima Makoto , Matsushima Nobuo , Takakura Shinichi , Inagaki Haruhiro , Saito Hiroki , Fujimitsu Yasuhiro 
Published: September 2021

SUMMARYMagnetotelluric (MT) observations have revealed subvertical electrical conductors that extend from shallow depths into the mid-crust at various geothermal zones, active volcanoes and active faults worldwide. These deeply rooted subvertical conductors have typically been interpreted to represent entire zones of dedicated fluid transport through the crust. We estimate the high-resolution 3-D crustal resistivity structure below the Kuju Volcanoes, Japan, using dense observations from 153 broad-band MT measurement sites and 40 telluric measurement sites. The resistivity structure highlights subvertical conductors that merge into a deep conductor to the north of the volcanoes, with deep low-frequency earthquakes occurring near the southeastern edge of this subvertical conductor at 10–30 km depth. This deep conductor branches into several subvertical conductors at 2–10 km depth, coinciding with a shallow zone where tectonic earthquakes rarely occur. The surface expressions of active geothermal areas and past volcanic eruptions are all located above the edges of the conductors at 2–6 km depth. Widespread conductive layers exist around the volcanoes above 2 km depth, and their distribution approximately corresponds to a low-gravity-anomaly zone. We discuss the nature of these subvertical conductors, the potential causes of their complex structure and their relationship to local magmatic fluid transport. These subvertical conductors, a shallow clay-rich layer, developed fracture systems and high-strength solidified magma may all contribute to magmatic fluid transport to the surface at the Kuju Volcanoes. In this study, we add the possibility that the edges of these subvertical conductors act as important magmatic fluid pathways.
Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing
Authors: Yang Bin , Borgeaud Alicia C , Buřičová Marcela , Aeschbach Lorène , Rodríguez-Lima Oscar , Ruiz Buendía Gustavo A , Cinesi Cinzia , Taylor Alysha S , Baubec Tuncay , Dion Vincent 
Published: September 2021

Abstract
Expanded CAG/CTG repeat disorders affect over 1 in 2500 individuals worldwide. Potential therapeutic avenues include gene silencing and modulation of repeat instability. However, there are major mechanistic gaps in our understanding of these processes, which prevent the rational design of an efficient treatment. To address this, we developed a novel system, ParB/ANCHOR-mediated Inducible Targeting (PInT), in which any protein can be recruited at will to a GFP reporter containing an expanded CAG/CTG repeat. Previous studies have implicated the histone deacetylase HDAC5 and the DNA methyltransferase DNMT1 as modulators of repeat instability via mechanisms that are not fully understood. Using PInT, we found no evidence that HDAC5 or DNMT1 modulate repeat instability upon targeting to the expanded repeat, suggesting that their effect is independent of local chromatin structure. Unexpectedly, we found that expanded CAG/CTG repeats reduce the effectiveness of gene silencing mediated by targeting HDAC5 and DNMT1. The repeat-length effect in gene silencing by HDAC5 was abolished by a small molecule inhibitor of HDAC3. Our results have important implications on the design of epigenome editing approaches for expanded CAG/CTG repeat disorders. PInT is a versatile synthetic system to study the effect of any sequence of interest on epigenome editing.
Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease
Authors: Zheng Wen-Qiang , Pedersen Signe Vandal , Thompson Kyle , Bellacchio Emanuele , French Courtney E , Munro Benjamin , Pearson Toni S , Vogt Julie , Diodato Daria , Diemer Tue , Ernst Anja , Horvath Rita , Chitre Manali , Ek Jakob , Wibrand Flemming , Grange Dorothy K , Raymond Lucy , Zhou Xiao-Long , Taylor Robert W , Ostergaard Elsebet 
Published: September 2021

Abstract
TARS2 encodes human mitochondrial threonyl tRNA-synthetase that is responsible for generating mitochondrial Thr-tRNAThr and clearing mischarged Ser-tRNAThr during mitochondrial translation. Pathogenic variants in TARS2 have hitherto been reported in a pair of siblings and an unrelated patient with an early onset mitochondrial encephalomyopathy and a combined respiratory chain enzyme deficiency in muscle. We here report five additional unrelated patients with TARS2-related mitochondrial diseases, expanding the clinical phenotype to also include epilepsy, dystonia, hyperhidrosis and severe hearing impairment. In addition, we document seven novel TARS2 variants—one nonsense variant and six missense variants—that we demonstrate are pathogenic and causal of the disease presentation based on population frequency, homology modeling and functional studies that show the effects of the pathogenic variants on TARS2 stability and/or function.
A data harmonization pipeline to leverage external controls and boost power in GWAS
Authors: Chen Danfeng , Tashman Katherine , Palmer Duncan S , Neale Benjamin , Roeder Kathryn , Bloemendal Alex , Churchhouse Claire , Ke Zheng Tracy 
Published: September 2021

Abstract
The use of external controls in genome-wide association study (GWAS) can significantly increase the size and diversity of the control sample, enabling high-resolution ancestry matching and enhancing the power to detect association signals. However, the aggregation of controls from multiple sources is challenging due to batch effects, difficulty in identifying genotyping errors and the use of different genotyping platforms. These obstacles have impeded the use of external controls in GWAS and can lead to spurious results if not carefully addressed. We propose a unified data harmonization pipeline that includes an iterative approach to quality control and imputation, implemented before and after merging cohorts and arrays. We apply this harmonization pipeline to aggregate 27 517 European control samples from 16 collections within dbGaP. We leverage these harmonized controls to conduct a GWAS of Crohn’s disease. We demonstrate a boost in power over using the cohort samples alone, and that our procedure results in summary statistics free of any significant batch effects. This harmonization pipeline for aggregating genotype data from multiple sources can also serve other applications where individual level genotypes, rather than summary statistics, are required.
Hyperactive HRAS dysregulates energetic metabolism in fibroblasts from patients with Costello syndrome via enhanced production of reactive oxidizing species
Authors: Carpentieri Giovanna , Leoni Chiara , Pietraforte Donatella , Cecchetti Serena , Iorio Egidio , Belardo Antonio , Pietrucci Daniele , Di Nottia Michela , Pajalunga Deborah , Megiorni Francesca , Mercurio Laura , Tatti Massimo , Camero Simona , Marchese Cinzia , Rizza Teresa , Tirelli Valentina , Onesimo Roberta , Carrozzo Rosalba , Rinalducci Sara , Chillemi Giovanni , Zampino Giuseppe , Tartaglia Marco , Flex Elisabetta 
Published: September 2021

Abstract
Germline-activating mutations in HRAS cause Costello syndrome (CS), a cancer prone multisystem disorder characterized by reduced postnatal growth. In CS, poor weight gain and growth are not caused by low caloric intake. Here, we show that constitutive plasma membrane translocation and activation of the GLUT4 glucose transporter, via reactive oxygen species-dependent AMP-activated protein kinase α and p38 hyperactivation, occurs in primary fibroblasts of CS patients, resulting in accelerated glycolysis and increased fatty acid synthesis and storage as lipid droplets. An accelerated autophagic flux was also identified as contributing to the increased energetic expenditure in CS. Concomitant inhibition of p38 and PI3K signaling by wortmannin was able to rescue both the dysregulated glucose intake and accelerated autophagic flux. Our findings provide a mechanistic link between upregulated HRAS function, defective growth and increased resting energetic expenditure in CS, and document that targeting p38 and PI3K signaling is able to revert this metabolic dysfunction.
Family Identity and Roles in the Context of Li-Fraumeni Syndrome: “No One’s Like Us Mutants”
Authors: Wilsnack Catherine , Young Jennifer L. , Merrill Shana L. , Groner Victoria , Loud Jennifer T. , Bremer Renee C. , Greene Mark H. , Khincha Payal P. , Werner-Lin Allison 
Published: September 2021

Abstract
Li-Fraumeni syndrome (LFS) is a rare hereditary cancer syndrome in which individuals have a significantly increased risk of developing multiple cancers throughout the life span. An LFS diagnosis may shift the individual’s sense of self and tolerance of cancer risk as they engage in cancer screening and cancer prevention activities. This study examined the impact of family identity on health decision making, communication, and role function. Forty-five families completed one or more interviews during an annual, protocol-specific cancer screening study. An interdisciplinary team analyzed 66 interviews using interpretive description and modified grounding theory. Thematically, identity emerged as an evolving construct regarding self and/or family, embedded in historical and ongoing experiences with LFS. Notions of individual and shared family identities guided decision making related to healthcare and influenced interpersonal communication and role function between supportive networks and families. Alignment between individual, family, and generational identities may shape engagement in genetic testing, risk management, and family life. Medical teams that are unequipped to address the psychosocial challenges that LFS populations face may include mental health professionals on interprofessional care teams to navigate risk management and consequential familial conflict.
Blastocyst formation is similar in obese and normal weight women: a morphokinetic study
Authors: Bellver José , Brandão Pedro , Alegre Lucía , Meseguer Marcos 
Published: September 2021

Abstract

STUDY QUESTION
Does the embryo cleavage pattern and rate of blastocyst formation differ between normal weight and obese women undergoing IVF?

SUMMARY ANSWER
Embryo morphokinetic development, final blastocyst formation rate and blastocyst morphology do not differ between obese and normal weight women.

WHAT IS KNOWN ALREADY
Female obesity has been related to impaired IVF outcomes. Although the mechanisms responsible for this detrimental effect are thought to include impaired oocyte and embryo quality and reduced endometrial receptivity, they are yet to be confirmed. Embryo quality has been commonly assessed using static morphological criteria. Only three studies have analysed the progress of embryos up to the blastocyst stage in women with elevated BMI, but they have used small samples of patients or have obtained contradictory results.

STUDY DESIGN, SIZE, DURATION
This retrospective, cohort study, was performed from January 2016 to May 2020. A total of 3316 ICSI cycles from 2822 women were included, of which 1251 cycles were part of a preimplantation genetic testing programme. In total, 17 848 embryos were analysed.

PARTICIPANTS/MATERIALS, SETTING, METHODS
This study reports on the IVF cycles of infertile women, with a known BMI, who underwent ICSI and whose embryos were grown until the fifth/sixth day of development in a time-lapse system. Patients were grouped as follows. Underweight was defined as a BMI &lt;18.5 kg/m2; normal weight was a BMI of 18.5–24.9 kg/m2; overweight was a BMI of 25–29.9 kg/m2; and obesity was a BMI of ≥30 kg/m2. Embryo development was assessed on an external computer with analysis software.

MAIN RESULTS AND THE ROLE OF CHANCE
Despite an initial slower pattern of embryo development, the blastocyst formation rate on day 5 or on day 5 plus day 6 did not differ in obese women with respect to the other three BMI groups. Moreover, based on the evaluation of inner cell mass and the trophectoderm on both days of blastocyst development, embryo quality was similar across the BMI groups, as were the pattern of development and arrest up to blastocyst formation and the distribution of the categories of full, expanded and hatching blastocysts.

LIMITATIONS, REASONS FOR CAUTION
Limitations include the retrospective analysis of data, the use of BMI as the only parameter to define normal/abnormal female body weight, and the lack of complete information about clinical outcomes.

WIDER IMPLICATIONS OF THE FINDINGS
Blastocyst formation and embryo morphokinetics are not affected by female obesity, and the poorer IVF outcomes described for such women are probably due to deficient endometrial receptivity. The role of endometrial progesterone exposure on the day of embryo transfer should be analysed in future studies as a possible determining factor.

STUDY FUNDING/COMPETING INTEREST(S)
No external funding was used and there are no competing interests.

TRIAL REGISTRATION NUMBER
N/A.
Off the beaten path: what drives scientists’ entry into new fields?
Authors: Kelchtermans Stijn , Neicu Daniel , Veugelers Reinhilde 
Published: September 2021

AbstractGiven that venturing into unknown territory carries substantial risk, scientists do not take the decision to enter a new field lightly. This paper analyzes a broad set of factors associated with the risks and rewards from entry into new-to-the-researcher scientific fields, including individual capacities and preferences as well as incentives stemming from career progression and access to funding. Using a panel of researchers in biomedical sciences and science and engineering from a large European research university, we find that productivity affects new field entry as such but is not associated with entry into fields that are very distant to one’s current expertise. Scientists in more senior ranks, with larger co-author networks and collaborating with PhD students, are more likely to enter new fields, but these factors do not represent an additional push to enter very remote fields. Such “long jumps” are more likely to be made by above-average talented rather than merely productive researchers. Finally, accounting for its endogeneity, we find that funding does not make new field entry more likely.
Corporate governance and R&D investment: the role of debt financing
Authors: Muhammad Hussain , Migliori Stefania , Mohsni Sana 
Published: September 2021

AbstractThis paper examines the role of debt financing in the relationship between corporate governance and research and development (R&D) investment using a sample of publicly traded U.S. pharmaceutical firms from 2009 to 2018. The results show a positive and significant association between corporate governance mechanisms (such as board size, board independence, board gender diversity, and ownership concentration) and R&D investment and a negative and significant association between debt financing and R&D investment. In addition, we show that debt financing plays a moderating role and a partial mediating role in the relationship between corporate governance mechanisms and R&D investment. Specifically, debt financing attenuates the negative effect of board size on R&D investment and accentuates the positive effect of ownership concentration on R&D investment. Our study helps to shed light on a close and complex relationship existing between the firm’s choices of corporate governance, debt financing, and R&D investments, which the previous literature has so far examined in a partial and fragmented way. To ensure effective R&D investment, firms need to consider the effect of debt financing on corporate governance decisions.
Research, innovation, and bankruptcy: evidence from European manufacturing firms
Authors: Agostino Mariarosaria , Scalera Domenico , Succurro Marianna , Trivieri Francesco 
Published: September 2021

Abstract
This paper investigates the effects of R&D and innovation activities of firms on the risk of bankruptcy. The analysis is carried out on data drawn from the EU-EFIGE Survey and Amadeus Database (Bureau Van Dijk) on European manufacturing firms over the years 2009–2014. The empirical evidence shows that default probability is increasing in R&D investments and decreasing in innovation and productivity of research, measured by the ratio of innovation revenues to R&D outlays. In addition, to disentangle the influence of different innovation strategies (product, process, and patenting), 16 different firm profiles are compared. Firms carrying out R&D, adopting process innovation, and filing for patents are found to show the lowest probability of default. Sensitivity checks indicate that research and innovation do not affect the risk of financial distress events short of default (such as reorganization or application for insolvency procedure). Our findings are robust to potential endogeneity and hence allow for causal inference about the relationship between research and innovation and corporate bankruptcy.