bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward Better Reproducibility in Experimental Research on New Agents for Pulmonary Hypertension. An Analysis of Data from Four Hundred Animal Studies
Authors: Jasińska-Stroschein Magdalena 
Published: December 2020

Abstract
Purpose
Pre-clinical data can provide a rationale for subsequent clinical trials and they are the first step in drug development; however, the therapeutic effect observed during animal studies does not necessarily translate to similar results in humans.

Methods
Taking the example of pulmonary hypertension, the present study explores whether the methodological aspects of preclinical experiments can determine the final result.

Results
The present paper describes a systematic analysis of 409 studies conducted on a variety of animal models to identify potential drug candidates for PH treatment; it explores the influence of various aspects of study design on the final outcome, e.g. type of animal model of PH, dosage schedules of tested agents, type of anesthesia, measurement of exercise intolerance or animal survival.

Conclusions
The animal models of PH used for pre-clinical studies are diverse and there are several methodological items within the established protocols that can determine the obtained result.
Tracing anthropogenic sources of Tantalum and Niobium in Bothnian Bay sediments, Sweden
Authors: Sutliff-Johansson S , Pontér S , Engström E , Rodushkin I , Peltola P , Widerlund A 
Published: December 2020

Abstract
Purpose
This study aims to evaluate temporal trends of Tantalum (Ta) and Niobium (Nb) concentrations in northern Baltic Sea sediments with focus on the potential impact from the Rönnskär sulfide ore smelter, located 15 km east of Skellefteå in northern Sweden. The potential of Ta or Nb to serve as tracers for environmental pollution caused by the electronic waste is compared. Lastly, correlations between Ta and Nb concentrations and those of major redox elements are investigated.

Methods
A 35-cm-deep core was collected in the harbor bay (Kallholmsfjärden) outside of the smelter. A secondary 6-m-deep sediment core was collected in the deep Bothnian Bay for comparative purposes. Element screening analysis was conducted the using ICP-SFMS for the Kallhomsfjärden core and a combination of ICP-SFMS and ICP-OES for the Bothnian Bay core. In the final analysis, a 5-step sequential extraction technique was preformed to allow for better prediction of the fate and mobility of Ta and Nb.

Results and discussion
In the vicinity of the smelter, Ta concentration increases from 0.42 to 3.8 ppm from the time coinciding with the beginning of electronic waste processing. Conversely, Nb concentration remained stable at background levels throughout the core at 6.33 ± 0.78 ppm. The Nb/Ta ratio thus changed from 14.5 to 1.7, reflecting an increase of anthropogenic input of Ta into the bay sediments. In the pre-industrial part of the sediment, concentrations of both elements follow concentration of aluminosilicates in the core. In recent sediments, however, the anthropogenic Ta exhibits an association with hydrous ferric oxides (HFOs) and organic matter.

Conclusions
Notable increases in Ta concentrations began following the beginning of scrap metal and electronic waste processing at the Rönnskär smelter. Anthropogenic Ta introduced in the upper portion of the sediment and are more associated with HFOs and organic material than natural Ta seen in the deeper parts of the core where detrital Ta is most common. Niobium was not affected by the Rönnskär smelter and displayed no notable change to the preindustrial background.
Language-responsive support for multiplicative thinking as unitizing: results of an intervention study in the second grade
Authors: Götze Daniela , Baiker Annica 
Published: December 2020

AbstractMultiplicative thinking involves the ability to coordinate bundled units on a more abstract level than additive thinking and implies the identification of the different meanings of the multiplier and the multiplicand. The transition from additive to multiplicative thinking, however, constitutes an obstacle for many children. Specific formulations that are typically used in classroom discourse for talking about multiplicative tasks and situations (e.g., ‘3 times 4’ or ‘3 lots of 4’) might inhibit meaning-making processes because they do not address the idea of unitizing. A language-responsive introduction to multiplication that addresses the core idea of unitizing and that uses phrases such as ‘3 times 4 means you have 3 fours’ may help to overcome these problems. In the study presented in this paper, three second grade primary school teachers joined a teacher program to introduce multiplication in their classes (n = 66) by addressing meaning-making phrases. Another 58 second graders taught by teachers without this teacher program served as the control group. A specially developed multiplication test gave insight into the children’s understanding of multiplication as unitizing immediately after the intervention (posttest) and nearly three months later (follow-up test). We found significant differences between the intervention and control groups in the multiplication posttest. These differences could be underlined in the follow-up test. Our results indicate that a language-responsive teaching intervention that focuses on meaning-making processes can lead to long-term insights and help to develop multiplicative thinking as unitizing.
Force feedback-based quality monitoring of the friction stir welding process utilizing an analytic algorithm
Authors: Rabe P. , Schiebahn A. , Reisgen U. 
Published: December 2020

AbstractThe friction stir welding (FSW) process is known as a solid-state welding process, comparatively stable against external influences. Therefore, the process is commonly used with fixed welding parameters, utilizing axial force control or position control strategies. External and internal process disturbances introduced by workpiece, gap tolerance, tool wear, or machine/tool inadequacies are rarely monitored, and conclusions about the weld seam quality, based on the recorded process data, are not drawn. This paper describes an advancement, improving on research into the correlation of process force feedback events or gradual force changes and the resulting weld seam characteristics. Analyzing the correlation between examined weld sections and high-resolution rate force data, a quality monitoring system based on an analytic algorithm is described. The monitoring system is able to accurately distinguish sound welds from such with internal (void) and external (flash) defects.
Mental health outcomes among patients from Fangcang shelter hospitals exposed to coronavirus disease 2019: An observational cross‐sectional study
Authors: Zhang Guang‐Yin , Liu Qi , Lin Jing‐Yu , Yan Lin , Shen Li , Si Tian‐Mei 
Published: December 2020

AbstractBackgroundThe coronavirus disease 2019 (COVID‐19) is not only attacking physical health, but it is also increasing psychological suffering. This study aimed to observe the impact of the COVID‐19 pandemic on mental health outcomes among patients with mild to moderate illness in Fangcang shelter hospitals.MethodsWe conducted an observational, cross‐sectional study of 129 patients with mild to moderate illness from Jiangxia Fangcang shelter hospitals in Wuhan, China. The participants were assessed by quantifying their symptoms of depression, anxiety, insomnia, and stressful life events and analyzing potential risk factors associated with these symptoms. Using correlation analysis, we examined associations between exposure to COVID‐19 and subsequent psychological distress in response to the outbreak.ResultsIn total, 49.6% of participants had depressive or anxiety symptoms. The depressive and anxiety symptoms were highly related to sleep disturbances and hypochondriasis (all r > 0.50, P < 0.01). The impact of the event was positively related to depressive symptoms, anxiety symptoms, sleep disturbances, hypochondriasis and life events (all r > 0.35, P < 0.01) but was negatively related to psychological resilience (r = −0.41, P < 0.01). The presence of the COVID‐19 infection in this setting was associated with increased anxiety, depression and stress levels, and decreased sleep quality, and seriously affected patients’ quality of life as well as adversely affecting the course and prognosis of physical diseases.ConclusionThe sleep quality, anxiety, and depression of COVID‐19 patients in Fangcang shelter hospitals were significantly related to the impact of the epidemic.
Dog bite injuries to the face: A narrative review of the literature
Authors: Ali Shirwa Sheik , Ali Sharaf Sheik 
Published: December 2020

AbstractObjectiveDog bite injuries remain a public health concern for two key reasons: the physical threat to health following attack and the infective sequelae a canine bite can incur. Facial bite injuries can result in significant emotional, psychological and physical trauma to victims involved. This narrative review elucidates the current presentation and management of dog bite injuries to the face.Data Sources and MethodsA literature search was conducted electronically using the search terms “dog bite” and “face” and “management” using the National Library of Medicine (Pubmed) and the Cochrane Library. There were no time nor language restrictions. A total of 79 studies were initially retrieved using the search algorithm. After screening of the titles and abstracts, 9 full texts were retrieved, and a total of 7 studies included.ResultsThe number of patients included in each study following a dog bite ranged from 40 to 223. The percentage of children included in each study (aged <18 years old) ranged from 27.5% to 100%. The majority of dog bite injuries to the face were managed by primary repair, ranging from 56.3% to 100%. Prophylactic antibiotics were used in most studies for dog bite injuries, ranging from 81% to 100%. The secondary infection rate following a dog bite ranged from 0 to 35%.ConclusionThis review highlights that children are disproportionately affected by canine bite injuries to the face relative to adults. The dog involved in the attack is typically known to the victim, with the lips, the cheek and the nose representing the most common sites of facial injury. More units are managing such injuries with primary repair and prophylactic antibiotics. Reconstructive procedures most commonly involve a local or advancement flap, a full thickness skin graft or a split skin graft. These are typically performed by Plastic Surgery and Maxillofacial Surgery specialists.
Informing Seasonal Proxy‐Based Flow Reconstructions Using Baseflow Separation: An Example From the Potomac River, United States
Authors: Torbenson M. C. A. , Stagge J. H. 
Published: December 2020

AbstractPaleoclimatic perspectives on hydrological variability can offer valuable information on the frequency and magnitude of extreme events. Tree‐ring records are a common proxy used to reconstruct past streamflow due to their interannual resolution and often strong correlation with hydroclimate variability. The separation of streamflow into theoretical baseflow and stormflow constituents is regularly utilized to differentiate between flow‐generating processes; however, it has yet to see use in paleoclimate reconstructions. We compare three approaches which use log‐linear, gamma‐distributed, and baseflow‐separated regression, respectively, to reconstructing flow at a well‐studied gage—the Potomac River at Point of Rock, Maryland. Preinstrumental baseflow and streamflow for summer were estimated for the past 350 years using a regional network of tree‐ring chronologies. Additionally, estimates of winter flow were produced for the same period using a nonoverlapping set of tree‐ring data. Tree growth appears to have a stronger relationship with baseflow than with streamflow for both seasons, supporting the use of baseflow as predictand. The number of chronologies subsequently chosen as predictors for streamflow was also lower than for baseflow and represents an additional source of reconstruction bias/uncertainty when total streamflow is the predictand. Historical records support the validity of both summer and winter reconstructions. The winter reconstruction indicates that several years of consecutive below‐mean flows, on par with the 1960s drought, occurred with higher frequency prior to the instrumental era. Our results suggest that baseflow separation can improve reconstruction skill and provide additional information to water resource management on the long‐term variability of hydrological extremes.
Hepatocyte cannabinoid 1 receptor nullification alleviates toxin-induced liver damage via NF-κB signaling
Authors: Kim Yoo , Gautam Sudeep , Aseer Kanikkai Raja , Kim Jaekwan , Chandrasekaran Prabha , Mazucanti Caio Henrique , Ghosh Paritosh , O’Connell Jennifer F. , Doyle Máire E. , Appleton Ashley , Lehrmann Elin , Liu Qing-Rong , Egan Josephine M. 
Published: December 2020

AbstractCannabinoid 1 receptor (CB1R) expression is upregulated in the liver with viral hepatitis, cirrhosis, and both alcoholic and non-alcoholic fatty liver disease (FLD), whereas its expression is muted under usual physiological conditions. Inhibiting CB1R has been shown to be beneficial in preserving hepatic function in FLD but it is unclear if inhibiting CB1R during an inflammatory response to an acute hepatic injury, such as toxin-induced injury, would also be beneficial. We found that intrinsic CB1R in hepatocytes regulated liver inflammation-related gene transcription. We tested if nullification of hepatocyte-specific CB1R (hCNR1−/−) in mice protects against concanavalin A (Con A)-induced liver injury. We looked for evidence of liver damage and markers of inflammation in response to Con A by measuring liver enzyme levels and proinflammatory cytokines (e.g., TNF-α, IL-1β, IL-6, IL-17) in serum collected from hCNR1−/− and control mice. We observed a shift to the right in the dose-response curve for liver injury and inflammation in hCNR1−/− mice. We also found less inflammatory cell infiltration and focal necrosis in livers of hCNR1−/− mice compared to controls, resulting from downregulated apoptotic markers. This anti-apoptotic mechanism results from increased activation of nuclear factor kappa B (NF-κB), especially cAMP-dependent cannabinoid signaling and membrane-bound TNF-α, via downregulated TNF-α receptor 2 (TNFR2) transcription levels. Collectively, these findings provide insight into involvement of CB1R in the pathogenesis of acute liver injury.
LncRNA kcnq1ot1 promotes lipid accumulation and accelerates atherosclerosis via functioning as a ceRNA through the miR-452-3p/HDAC3/ABCA1 axis
Authors: Yu Xiao-Hua , Deng Wen-Yi , Chen Jiao-Jiao , Xu Xiao-Dan , Liu Xian-Xia , Chen Lei , Shi Meng-Wen , Liu Qi-Xian , Tao Min , Ren Kun 
Published: December 2020

AbstractKcnq1 overlapping transcript 1 (kcnq1ot1), an imprinted antisense lncRNA in the kcnq1 locus, acts as a potential contributor to cardiovascular disease, but its role in atherosclerosis remains unknown. The aim of this study was to explore the effects of kcnq1ot1 on atherogenesis and the underlying mechanism. Our results showed that kcnq1ot1 expression was significantly increased in mouse aorta with atherosclerosis and lipid-loaded macrophages. Lentivirus-mediated kcnq1ot1 overexpression markedly increased atherosclerotic plaque area and decreased plasma HDL-C levels and RCT efficiency in apoE−/− mice fed a Western diet. Upregulation of kcnq1ot1 also reduced the expression of miR-452-3p and ABCA1 but increased HDAC3 levels in mouse aorta and THP-1 macrophages. Accordingly, kcnq1ot1 overexpression inhibited cholesterol efflux and promoted lipid accumulation in THP-1 macrophages. In contrast, kcnq1ot1 knockdown protected against atherosclerosis in apoE−/− mice and suppressed lipid accumulation in THP-1 macrophages. Mechanistically, kcnq1ot1 enhanced HDAC3 expression by competitively binding to miR-452-3p, thereby inhibiting ABCA1 expression and subsequent cholesterol efflux. Taken together, these findings suggest that kcnq1ot1 promotes macrophage lipid accumulation and accelerates the development of atherosclerosis through the miR-452-3p/HDAC3/ABCA1 pathway.
Nature-inspired remodeling of (aza)indoles to meta-aminoaryl nicotinates for late-stage conjugation of vitamin B3 to (hetero)arylamines
Authors: Varun Begur Vasanthkumar , Vaithegi Kannan , Yi Sihyeong , Park Seung Bum 
Published: December 2020

AbstractDespite the availability of numerous routes to substituted nicotinates based on the Bohlmann–Rahtz pyridine synthesis, the existing methods have several limitations, such as the inevitable ortho-substitutions and the inability to conjugate vitamin B3 to other pharmaceutical agents. Inspired by the biosynthesis of nicotinic acid (a form of vitamin B3) from tryptophan, we herein report the development of a strategy for the synthesis of meta-aminoaryl nicotinates from 3-formyl(aza)indoles. Our strategy is mechanistically different from the reported routes and involves the transformation of (aza)indole scaffolds into substituted meta-aminobiaryl scaffolds via Aldol-type addition and intramolecular cyclization followed by C–N bond cleavage and re-aromatization. Unlike previous synthetic routes, this biomimetic method utilizes propiolates as enamine precursors and thus allows access to ortho-unsubstituted nicotinates. In addition, the synthetic feasibility toward the halo-/boronic ester-substituted aminobiaryls clearly differentiates the present strategy from other cross-coupling strategies. Most importantly, our method enables the late-stage conjugation of bioactive (hetero)arylamines with nicotinates and nicotinamides and allows access to the previously unexplored chemical space for biomedical research.
High-speed atomic force microscopy highlights new molecular mechanism of daptomycin action
Authors: Zuttion Francesca , Colom Adai , Matile Stefan , Farago Denes , Pompeo Frédérique , Kokavecz Janos , Galinier Anne , Sturgis James , Casuso Ignacio 
Published: December 2020

AbstractThe increase in speed of the high-speed atomic force microscopy (HS-AFM) compared to that of the conventional AFM made possible the first-ever visualisation at the molecular-level of the activity of an antimicrobial peptide on a membrane. We investigated the medically prescribed but poorly understood lipopeptide Daptomycin under infection-like conditions (37 °C, bacterial lipid composition and antibiotic concentrations). We confirmed so far hypothetical models: Dap oligomerization and the existence of half pores. Moreover, we detected unknown molecular mechanisms: new mechanisms to form toroidal pores or to resist Dap action, and to unprecedently quantify the energy profile of interacting oligomers. Finally, the biological and medical relevance of the findings was ensured by a multi-scale multi-nativeness—from the molecule to the cell—correlation of molecular-level information from living bacteria (Bacillus subtilis strains) to liquid-suspended vesicles and supported-membranes using electron and optical microscopies and the lipid tension probe FliptR, where we found that the cells with a healthier state of their cell wall show smaller membrane deformations.
Analytical validity of nanopore sequencing for rapid SARS-CoV-2 genome analysis
Authors: Bull Rowena A. , Adikari Thiruni N. , Ferguson James M. , Hammond Jillian M. , Stevanovski Igor , Beukers Alicia G. , Naing Zin , Yeang Malinna , Verich Andrey , Gamaarachchi Hasindu , Kim Ki Wook , Luciani Fabio , Stelzer-Braid Sacha , Eden John-Sebastian , Rawlinson William D. , van Hal Sebastiaan J. , Deveson Ira W. 
Published: December 2020

AbstractViral whole-genome sequencing (WGS) provides critical insight into the transmission and evolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Long-read sequencing devices from Oxford Nanopore Technologies (ONT) promise significant improvements in turnaround time, portability and cost, compared to established short-read sequencing platforms for viral WGS (e.g., Illumina). However, adoption of ONT sequencing for SARS-CoV-2 surveillance has been limited due to common concerns around sequencing accuracy. To address this, here we perform viral WGS with ONT and Illumina platforms on 157 matched SARS-CoV-2-positive patient specimens and synthetic RNA controls, enabling rigorous evaluation of analytical performance. We report that, despite the elevated error rates observed in ONT sequencing reads, highly accurate consensus-level sequence determination was achieved, with single nucleotide variants (SNVs) detected at >99% sensitivity and >99% precision above a minimum ~60-fold coverage depth, thereby ensuring suitability for SARS-CoV-2 genome analysis. ONT sequencing also identified a surprising diversity of structural variation within SARS-CoV-2 specimens that were supported by evidence from short-read sequencing on matched samples. However, ONT sequencing failed to accurately detect short indels and variants at low read-count frequencies. This systematic evaluation of analytical performance for SARS-CoV-2 WGS will facilitate widespread adoption of ONT sequencing within local, national and international COVID-19 public health initiatives.
Primary effusion lymphoma enhancer connectome links super-enhancers to dependency factors
Authors: Wang Chong , Zhang Luyao , Ke Liangru , Ding Weiyue , Jiang Sizun , Li Difei , Narita Yohei , Hou Isabella , Liang Jun , Li Shijun , Xiao Haipeng , Gottwein Eva , Kaye Kenneth M. , Teng Mingxiang , Zhao Bo 
Published: December 2020

AbstractPrimary effusion lymphoma (PEL) has a very poor prognosis. To evaluate the contributions of enhancers/promoters interactions to PEL cell growth and survival, here we produce H3K27ac HiChIP datasets in PEL cells. This allows us to generate the PEL enhancer connectome, which links enhancers and promoters in PEL genome-wide. We identify more than 8000 genomic interactions in each PEL cell line. By incorporating HiChIP data with H3K27ac ChIP-seq data, we identify interactions between enhancers/enhancers, enhancers/promoters, and promoters/promoters. HiChIP further links PEL super-enhancers to PEL dependency factors MYC, IRF4, MCL1, CCND2, MDM2, and CFLAR. CRISPR knock out of MEF2C and IRF4 significantly reduces MYC and IRF4 super-enhancer H3K27ac signal. Knock out also reduces MYC and IRF4 expression. CRISPRi perturbation of these super-enhancers by tethering transcription repressors to enhancers significantly reduces target gene expression and reduces PEL cell growth. These data provide insights into PEL molecular pathogenesis.
Blood and lymphatic systems are segregated by the FLCN tumor suppressor
Authors: Tai-Nagara Ikue , Hasumi Yukiko , Kusumoto Dai , Hasumi Hisashi , Okabe Keisuke , Ando Tomofumi , Matsuzaki Fumio , Itoh Fumiko , Saya Hideyuki , Liu Chang , Li Wenling , Mukouyama Yoh-suke , Marston Linehan W. , Liu Xinyi , Hirashima Masanori , Suzuki Yutaka , Funasaki Shintaro , Satou Yorifumi , Furuya Mitsuko , Baba Masaya , Kubota Yoshiaki 
Published: December 2020

AbstractBlood and lymphatic vessels structurally bear a strong resemblance but never share a lumen, thus maintaining their distinct functions. Although lymphatic vessels initially arise from embryonic veins, the molecular mechanism that maintains separation of these two systems has not been elucidated. Here, we show that genetic deficiency of Folliculin, a tumor suppressor, leads to misconnection of blood and lymphatic vessels in mice and humans. Absence of Folliculin results in the appearance of lymphatic-biased venous endothelial cells caused by ectopic expression of Prox1, a master transcription factor for lymphatic specification. Mechanistically, this phenotype is ascribed to nuclear translocation of the basic helix-loop-helix transcription factor Transcription Factor E3 (TFE3), binding to a regulatory element of Prox1, thereby enhancing its venous expression. Overall, these data demonstrate that Folliculin acts as a gatekeeper that maintains separation of blood and lymphatic vessels by limiting the plasticity of committed endothelial cells.