bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Quality Arabidopsis Thaliana Genome Assembly with Nanopore and HiFi Long Reads
Authors: Wang Bo , Yang Xiaofei , Jia Yanyan , Xu Yu , Jia Peng , Dang Ningxin , Wang Songbo , Xu Tun , Zhao Xixi , Gao Shenghan , Dong Quanbin , Ye Kai 
Published: September 2021

Abstract
Arabidopsis thaliana is an important and long-established model species for plant molecular biology, genetics, epigenetics, and genomics. However, the latest version of reference genome still contains a significant number of missing segments. Here, we reported a high-quality and almost complete Col-0 genome assembly with two gaps (named Col-XJTU) by combining the Oxford Nanopore Technologies ultra-long reads, Pacific Biosciences high-fidelity long reads, and Hi-C data. The total genome assembly size is 133,725,193 bp, introducing 14.6 Mb of novel sequences compared to the TAIR10.1 reference genome. All five chromosomes of the Col-XJTU assembly are highly accurate with consensus quality (QV) scores &gt; 60 (ranging from 62 to 68), which are higher than those of the TAIR10.1 reference (ranging from 45 to 52). We completely resolved chromosome (Chr) 3 and Chr5 in a telomere-to-telomere manner. Chr4 was completely resolved except the nucleolar organizing regions, which comprise long repetitive DNA fragments. The Chr1 centromere (CEN1), reportedly around 9 Mb in length, is particularly challenging to assemble due to the presence of tens of thousands of CEN180 satellite repeats. Using the cutting-edge sequencing data and novel computational approaches, we assembled a 3.8-Mb-long CEN1 and a 3.5-Mb-long CEN2. We also investigated the structure and epigenetics of centromeres. Four clusters of CEN180 monomers were detected, and the centromere-specific histone H3-like protein (CENH3) exhibited a strong preference for CEN180 Cluster 3. Moreover, we observed hypomethylation patterns in CENH3-enriched regions. We believe that this high-quality genome assembly, Col-XJTU, would serve as a valuable reference to better understand the global pattern of centromeric polymorphisms, as well as the genetic and epigenetic features in plants.
How Joseph Smith Encountered Printing Plates and Founded Mormonism
Authors: Hazard Sonia 
Published: September 2021

ABSTRACTDid Joseph Smith, the founder of Mormonism, really find gold plates? This article considers that basic question from a new materialist perspective. Drawing on textual and material-bibliographical evidence, it argues that Smith, and possibly also a group of witnesses, may have had a formative physical encounter with a set of plates and that this encounter was partly responsible for provoking the events and interpretations that followed. These plates could have been either stereotype plates or copper plates, both commonly used for industrial printing in the nineteenth-century United States. This article also takes the empirical investigation into what Smith may have encountered as an occasion to reflect, methodologically and theoretically, on the role of ordinary material objects in processes of religious and historical change.
Labeling Poststorm Coastal Imagery for Machine Learning: Measurement of Interrater Agreement
Authors: Goldstein Evan B. , Buscombe Daniel , Lazarus Eli D. , Mohanty Somya D. , Rafique Shah Nafis , Anarde Katherine A. , Ashton Andrew D. , Beuzen Tomas , Castagno Katherine A. , Cohn Nicholas , Conlin Matthew P. , Ellenson Ashley , Gillen Megan , Hovenga Paige A. , Over Jin‐Si R. , Palermo Rose V. , Ratliff Katherine M. , Reeves Ian R. B. , Sanborn Lily H. , Straub Jessamin A. , Taylor Luke A. , Wallace Elizabeth J. , Warrick Jonathan , Wernette Phillipe , Williams Hannah E. 
Published: September 2021

AbstractClassifying images using supervised machine learning (ML) relies on labeled training data—classes or text descriptions, for example, associated with each image. Data‐driven models are only as good as the data used for training, and this points to the importance of high‐quality labeled data for developing a ML model that has predictive skill. Labeling data is typically a time‐consuming, manual process. Here, we investigate the process of labeling data, with a specific focus on coastal aerial imagery captured in the wake of hurricanes that affected the Atlantic and Gulf Coasts of the United States. The imagery data set is a rich observational record of storm impacts and coastal change, but the imagery requires labeling to render that information accessible. We created an online interface that served labelers a stream of images and a fixed set of questions. A total of 1,600 images were labeled by at least two or as many as seven coastal scientists. We used the resulting data set to investigate interrater agreement: the extent to which labelers labeled each image similarly. Interrater agreement scores, assessed with percent agreement and Krippendorff's alpha, are higher when the questions posed to labelers are relatively simple, when the labelers are provided with a user manual, and when images are smaller. Experiments in interrater agreement point toward the benefit of multiple labelers for understanding the uncertainty in labeling data for machine learning research.
An Observational Based Modeling of the Surface Layer Particulate Nitrate in the North China Plain During Summertime
Authors: Tan Zhaofeng , Wang Haichao , Lu Keding , Dong Huabin , Liu Yuhan , Zeng Limin , Hu Min , Zhang Yuanhang 
Published: September 2021

AbstractParticulate nitrate (pNO3−) is an important component in atmospheric fine particulate matter. Here, we present a case study investigating the production and loss processes of pNO3− in surface‐layer based on the observation at a regional site Wangdu in North China Plain (NCP) during summer. The averaged diurnal of nitric acid (HNO3) production reached a maximum of 1.5 μg m−3 h−1 determined from the observed OH and NO2, indicating a fast HNO3 production in the surface layer during the daytime. The chemical processes affecting surface nitrate concentration and daily variation were simulated by a box model based on the Regional Atmospheric Chemical Mechanism version 2 and coupled with the ISORROPIA‐II thermodynamic equilibrium model. The chemical formation of total soluble nitrate (TNO3) at the surface layer cannot explain the fast increase of pNO3− in the morning and overshoot pNO3− in the afternoon, suggesting missing processes in the model. The pNO3− budget analysis suggests the importance of entrainment from residual layer air into the surface layer as an important process for surface pNO3− concentration enhancement in the early morning. In the afternoon, the partition to pNO3− was limited due to the high temperature near the ground. Nevertheless, the observed fast nitrate production still significantly overshot pNO3− in the afternoon. This difference indicates HNO3 production was less efficient throughout the boundary layer than what was observed in the surface layer. Our results highlight the importance of vertical measurements to understand the formation mechanism of nitrate pollution in summer.
Dual targeting of JAK2 and ERK interferes with the myeloproliferative neoplasm clone and enhances therapeutic efficacy
Authors: Brkic Sime , Stivala Simona , Santopolo Alice , Szybinski Jakub , Jungius Sarah , Passweg Jakob R. , Tsakiris Dimitrios , Dirnhofer Stefan , Hutter Gregor , Leonards Katharina , Lischer Heidi E. L. , Dettmer Matthias S. , Neel Benjamin G. , Levine Ross L. , Meyer Sara C. 
Published: September 2021

AbstractMyeloproliferative neoplasms (MPN) show dysregulated JAK2 signaling. JAK2 inhibitors provide clinical benefits, but compensatory activation of MAPK pathway signaling impedes efficacy. We hypothesized that dual targeting of JAK2 and ERK1/2 could enhance clone control and therapeutic efficacy. We employed genetic and pharmacologic targeting of ERK1/2 in Jak2V617F MPN mice, cells and patient clinical isolates. Competitive transplantations of Jak2V617F vs. wild-type bone marrow (BM) showed that ERK1/2 deficiency in hematopoiesis mitigated MPN features and reduced the Jak2V617F clone in blood and hematopoietic progenitor compartments. ERK1/2 ablation combined with JAK2 inhibition suppressed MAPK transcriptional programs, normalized cytoses and promoted clone control suggesting dual JAK2/ERK1/2 targeting as enhanced corrective approach. Combined pharmacologic JAK2/ERK1/2 inhibition with ruxolitinib and ERK inhibitors reduced proliferation of Jak2V617F cells and corrected erythrocytosis and splenomegaly of Jak2V617F MPN mice. Longer-term treatment was able to induce clone reductions. BM fibrosis was significantly decreased in MPLW515L-driven MPN to an extent not seen with JAK2 inhibitor monotherapy. Colony formation from JAK2V617F patients’ CD34+ blood and BM was dose-dependently inhibited by combined JAK2/ERK1/2 inhibition in PV, ET, and MF subsets. Overall, we observed that dual targeting of JAK2 and ERK1/2 was able to enhance therapeutic efficacy suggesting a novel treatment approach for MPN.
High-resolution two-photon polymerization: the most versatile technique for the fabrication of microneedle arrays
Authors: Faraji Rad Zahra , Prewett Philip D. , Davies Graham J. 
Published: September 2021

AbstractMicroneedle patches have received much interest in the last two decades as drug/vaccine delivery or fluid sampling systems for diagnostic and monitoring purposes. Microneedles are manufactured using a variety of additive and subtractive micromanufacturing techniques. In the last decade, much attention has been paid to using additive manufacturing techniques in both research and industry, such as 3D printing, fused deposition modeling, inkjet printing, and two-photon polymerization (2PP), with 2PP being the most flexible method for the fabrication of microneedle arrays. 2PP is one of the most versatile and precise additive manufacturing processes, which enables the fabrication of arbitrary three-dimensional (3D) prototypes directly from computer-aided-design (CAD) models with a resolution down to 100 nm. Due to its unprecedented flexibility and high spatial resolution, the use of this technology has been widespread for the fabrication of bio-microdevices and bio-nanodevices such as microneedles and microfluidic devices. This is a pioneering transformative technology that facilitates the fabrication of complex miniaturized structures that cannot be fabricated with established multistep manufacturing methods such as injection molding, photolithography, and etching. Thus, microstructures are designed according to structural and fluid dynamics considerations rather than the manufacturing constraints imposed by methods such as machining or etching processes. This article presents the fundamentals of 2PP and the recent development of microneedle array fabrication through 2PP as a precise and unique method for the manufacture of microstructures, which may overcome the shortcomings of conventional manufacturing processes.
Nanomedicine and graphene-based materials: advanced technologies for potential treatments of diseases in the developing nervous system
Authors: Cellot Giada , Franceschi Biagioni Audrey , Ballerini Laura 
Published: September 2021

Abstract
The interest in graphene-based nanomaterials (GBNs) application in nanomedicine, in particular in neurology, steadily increased in the last decades. GBNs peculiar physical–chemical properties allow the design of innovative therapeutic tools able to manipulate biological structures with subcellular resolution. In this review, we report GBNs applications to the central nervous system (CNS) when these nanomaterials are engineered as potential therapeutics to treat brain pathologies, with a focus on those of the pediatric age. We revise the state-of-the art studies addressing the impact of GBNs in the CNS, showing that the design of GBNs with different dimensions and chemical compositions or the use of specific administration routes and doses can limit unwanted side effects, exploiting GBNs efficacy in therapeutic approaches. These features favor the development of GBNs-based multifunctional devices that may find applications in the field of precision medicine for the treatment of disorders in the developing CNS. In this framework, we address the suitability of GBNs to become successful therapeutic tools, such as drug nano-delivery vectors when being chemically decorated with pharmaceutical agents and/or other molecules to obtain a high specific targeting of the diseased area and to achieve a controlled release of active molecules.

Impact

The translational potential of graphene-based nanomaterials (GBNs) can be used for the design of novel therapeutic approaches to treat pathologies affecting the brain with a focus on the pediatric age.

GBNs can be chemically decorated with pharmaceutical agents and molecules to obtain a highly specific targeting of the diseased site and a controlled drug release.

The type of GBNs, the selected functionalization, the dose, and the way of administration are factors that should be considered to potentiate the therapeutic efficacy of GBNs, limiting possible side effects.

GBNs-based multifunctional devices might find applications in the precision medicine and theranostics fields.
Consolidation/reconsolidation therapies for the prevention and treatment of PTSD and re-experiencing: a systematic review and meta-analysis
Authors: Astill Wright Laurence , Horstmann Louise , Holmes Emily A. , Bisson Jonathan I. 
Published: September 2021

AbstractTranslational research highlights the potential of novel 'memory consolidation/reconsolidation therapies' to treat re-experiencing symptoms and post-traumatic stress disorder (PTSD). This systematic review and meta-analysis assessed the efficacy of so-called memory consolidation/reconsolidation therapies in randomised controlled trials (RCTs) for prevention and treatment of PTSD and symptoms of re-experiencing in children and adults (PROSPERO: CRD42020171167). RCTs were identified and rated for risk of bias. Available data was pooled to calculate risk ratios (RR) for PTSD prevalence and standardised mean differences (SMD) for PTSD/re-experiencing severity. Twenty-five RCTs met inclusion criteria (16 prevention and nine treatment trials). The methodology of most studies had a significant risk of bias. We found a large effect of reconsolidation interventions in the treatment of PTSD (11 studies, n = 372, SMD: −1.42 (−2.25 to −0.58), and a smaller positive effect of consolidation interventions in the prevention of PTSD (12 studies, n = 2821, RR: 0.67 (0.50 to 0.90). Only three protocols (hydrocortisone for PTSD prevention, Reconsolidation of Traumatic Memories (RTM) for treatment of PTSD symptoms and cognitive task memory interference procedure with memory reactivation (MR) for intrusive memories) were superior to control. There is some emerging evidence of consolidation and reconsolidation therapies in the prevention and treatment of PTSD and intrusive memories specifically. Translational research should strictly adhere to protocols/procedures describing precise reconsolidation conditions (e.g. MR) to both increase the likelihood of positive findings and more confidently interpret negative findings of putative reconsolidation agents.
Genome-wide association study of frontotemporal dementia identifies a C9ORF72 haplotype with a median of 12-G4C2 repeats that predisposes to pathological repeat expansions
Authors: Reus Lianne M. , Jansen Iris E. , Mol Merel O. , van Ruissen Fred , van Rooij Jeroen , van Schoor Natasja M. , Tesi Niccolò , Reinders Marcel J. T. , Huisman Martijn A. , Holstege Henne , Visser Pieter Jelle , de Boer Sterre C. M. , Hulsman Marc , Ahmad Shahzad , Amin Najaf , Uitterlinden Andre G. , Ikram Arfan , van Duijn Cornelia M. , Seelaar Harro , Ramakers Inez H. G. B. , Verhey Frans R. J. , van der Lugt Aad , Claassen Jurgen A. H. R. , Jan Biessels Geert , De Deyn Peter Paul , Scheltens Philip , van der Flier Wiesje M. , van Swieten John C. , Pijnenburg Yolande A. L. , van der Lee Sven J. 
Published: September 2021

AbstractGenetic factors play a major role in frontotemporal dementia (FTD). The majority of FTD cannot be genetically explained yet and it is likely that there are still FTD risk loci to be discovered. Common variants have been identified with genome-wide association studies (GWAS), but these studies have not systematically searched for rare variants. To identify rare and new common variant FTD risk loci and provide more insight into the heritability of C9ORF72-related FTD, we performed a GWAS consisting of 354 FTD patients (including and excluding N = 28 pathological repeat carriers) and 4209 control subjects. The Haplotype Reference Consortium was used as reference panel, allowing for the imputation of rare genetic variants. Two rare genetic variants nearby C9ORF72 were strongly associated with FTD in the discovery (rs147211831: OR = 4.8, P = 9.2 × 10−9, rs117204439: OR = 4.9, P = 6.0 × 10−9) and replication analysis (P < 1.1 × 10−3). These variants also significantly associated with amyotrophic lateral sclerosis in a publicly available dataset. Using haplotype analyses in 1200 individuals, we showed that these variants tag a sub-haplotype of the founder haplotype of the repeat expansion that was previously found to be present in virtually all pathological C9ORF72 G4C2 repeat lengths. This new risk haplotype was 10 times more likely to contain a C9ORF72 pathological repeat length compared to founder haplotypes without one of the two risk variants (~22% versus ~2%; P = 7.70 × 10−58). In haplotypes without a pathologic expansion, the founder risk haplotype had a higher number of repeats (median = 12 repeats) compared to the founder haplotype without the risk variants (median = 8 repeats) (P = 2.05 × 10−260). In conclusion, the identified risk haplotype, which is carried by ~4% of all individuals, is a major risk factor for pathological repeat lengths of C9ORF72 G4C2. These findings strongly indicate that longer C9ORF72 repeats are unstable and more likely to convert to germline pathological C9ORF72 repeat expansions.
Neural correlates of emotional reactivity and regulation in traumatized North Korean refugees
Authors: Lee Kyung Hwa , Lee Ha Young , Park Inkyung , Lee Yu Jin , Kim Nambeom , Jeon Sehyun , Kim Soohyun , Jeon Jeong Eun , Kim Seog Ju 
Published: September 2021

AbstractRefugees often report heightened emotional reactivity and emotion regulation difficulties and are at high risk for mental health problems. Given that refugees are repeatedly exposed to traumatic events that may cause changes in the brain, the present study examined neural correlates of emotional reactivity and regulation and their associations with refugee features (e.g., cumulative trauma) and the severity of psychiatric symptoms (e.g., post-traumatic stress disorder [PTSD]) in North Korean (NK) refugees. Forty NK refugees with trauma exposure and varying levels of psychopathology and 41 healthy South Korean (SK) controls without trauma exposure participated in this study. They performed an emotion regulation task during a functional magnetic resonance imaging (fMRI) assessment. Region of interest (ROI), whole brain, and generalized psychophysiological interaction (gPPI) analyses were conducted. NK refugees with trauma exposure and varying levels of psychopathology showed increased activation in response to negative socio-affective pictures in regions involved in affective processing, including the amygdala and hippocampus, relative to healthy SK controls without trauma exposure. They also exhibited greater prefrontal cortex (PFC) activation, amygdala–PFC functional connectivity (FC), and hippocampal–PFC FC during emotion regulation. More severe PTSD symptoms were associated with greater hippocampal response to negative pictures (vs. neutral pictures) in NK refugees. This study provides neuroscientific evidence for neural alterations in association with emotional reactivity and regulation in traumatized refugees. These findings may contribute to a better mechanistic understanding of emotional reactivity and regulation in refugees and suggest potential ways to address the emotional and mental problems of traumatized refugees.
Predictive values of tumor necrosis factor-α for depression treatment outcomes: effect modification by hazardous alcohol consumption
Authors: Choi Wonsuk , Kang Hee-Ju , Kim Ju-Wan , Kim Hee Kyung , Kang Ho-Cheol , Lee Ju-Yeon , Kim Sung-Wan , Stewart Robert , Kim Jae-Min 
Published: September 2021

AbstractInflammation is potentially associated with poor antidepressant treatment outcomes. Pro-inflammatory cytokines are influenced by hazardous alcohol consumption. The aim of the present study was to investigate the effects of the serum tumor necrosis factor-α (sTNF-α) level on antidepressant treatment outcomes in terms of the 12-week and 12-month remission rates and 24-month relapse rate, and to investigate the potential modifying effects of alcohol consumption on these associations in patients with depressive disorders. At baseline, sTNF-α was measured and alcohol-related data from the Alcohol Use Disorders Identification Test (AUDIT) and consumption history were collected from 1094 patients. Patients received stepwise antidepressant treatment. Remission at 12 weeks and 12 months was defined as a Hamilton Depression Rating Scale (HAMD) score ≤ 7. Relapse (HAMD score ≥ 14) was identified until 24 months for those who had initially responded (HAMD score <14) at 12 weeks. Higher sTNF-α levels were found to have significant effects on the 12-week and 12-month non-remission and 24-month relapse rates. These effects were more prominent in those with low levels of alcohol consumption (AUDIT score ≤ 8 or no current alcohol consumption); the effects were not significant in those exhibiting hazardous alcohol consumption (AUDIT score > 8 or current drinking). Significant interactions were found for the 12-month non-remission and relapse rates, although the interaction was not statistically significant for 12-week remission. In conclusion, baseline sTNF-α levels may be a useful predictor for both short- and long-term antidepressant treatment outcomes, and the consideration of alcohol consumption status may increase predictability, in particular for long-term outcomes.