bluuebunny/crossref_metadata_2025_split huggingface dataset:
Random rotation for identifying differentially expressed genes with linear models following batch effect correction
Authors: Hettegger Peter , Vierlinger Klemens , Weinhaeusel Andreas 
Published: January 2021

AbstractMotivationData generated from high-throughput technologies such as sequencing, microarray and bead-chip technologies are unavoidably affected by batch effects (BEs). Large effort has been put into developing methods for correcting these effects. Often, BE correction and hypothesis testing cannot be done with one single model, but are done successively with separate models in data analysis pipelines. This potentially leads to biased P-values or false discovery rates due to the influence of BE correction on the data.ResultsWe present a novel approach for estimating null distributions of test statistics in data analysis pipelines where BE correction is followed by linear model analysis. The approach is based on generating simulated datasets by random rotation and thereby retains the dependence structure of genes adequately. This allows estimating null distributions of dependent test statistics, and thus the calculation of resampling-based P-values and false-discovery rates following BE correction while maintaining the alpha level.AvailabilityThe described methods are implemented as randRotation package on Bioconductor: https://bioconductor.org/packages/randRotation/Contactp.hettegger@gmail.comSupplementary informationSupplementary data are available at Bioinformatics online.
Memory Suppression Ability can be Robustly Predicted by the Internetwork Communication of Frontoparietal Control Network
Authors: Yang Wenjing , Zhuang Kaixiang , Liu Peiduo , Guo Yuhua , Chen Qunlin , Wei Dongtao , Qiu Jiang 
Published: January 2021

Abstract
Memory suppression (MS) is essential for mental well-being. However, no studies have explored how intrinsic resting-state functional connectivity (rs-FC) predicts this ability. Here, we adopted the connectome-based predictive modeling (CPM) based on the resting-state fMRI data to investigate whether and how rs-FC profiles in predefined brain networks (the frontoparietal control networks or FPCN) can predict MS in healthy individuals with 497 participants. The MS ability was assessed by MS-induced forgetting during the think/no-think paradigm. The results showed that FPCN network was especially informative for generating the prediction model for MS. Some regions of FPCN, such as middle frontal gyrus, superior frontal gyrus and inferior parietal lobe were critical in predicting MS. Moreover, functional interplay between FPCN and multiple networks, such as dorsal attention network (DAN), ventral attention network (VAN), default mode network (DMN), the limbic system and subcortical regions, enabled prediction of MS. Crucially, the predictive FPCN networks were stable and specific to MS. These results indicated that FPCN flexibility interacts with other networks to underpin the ability of MS. These would also be beneficial for understanding how compromises in these functional networks may have led to the intrusive thoughts and memories characterized in some mental disorders.
Task-Dependent Functional and Effective Connectivity during Conceptual Processing
Authors: Kuhnke Philipp , Kiefer Markus , Hartwigsen Gesa 
Published: January 2021

AbstractConceptual knowledge is central to cognition. Previous neuroimaging research indicates that conceptual processing involves both modality-specific perceptual-motor areas and multimodal convergence zones. For example, our previous functional magnetic resonance imaging (fMRI) study revealed that both modality-specific and multimodal regions respond to sound and action features of concepts in a task-dependent fashion (Kuhnke P, Kiefer M, Hartwigsen G. 2020b. Task-dependent recruitment of modality-specific and multimodal regions during conceptual processing. Cereb Cortex. 30:3938–3959.). However, it remains unknown whether and how modality-specific and multimodal areas interact during conceptual tasks. Here, we asked 1) whether multimodal and modality-specific areas are functionally coupled during conceptual processing, 2) whether their coupling depends on the task, 3) whether information flows top-down, bottom-up or both, and 4) whether their coupling is behaviorally relevant. We combined psychophysiological interaction analyses with dynamic causal modeling on the fMRI data of our previous study. We found that functional coupling between multimodal and modality-specific areas strongly depended on the task, involved both top-down and bottom-up information flow, and predicted conceptually guided behavior. Notably, we also found coupling between different modality-specific areas and between different multimodal areas. These results suggest that functional coupling in the conceptual system is extensive, reciprocal, task-dependent, and behaviorally relevant. We propose a new model of the conceptual system that incorporates task-dependent functional interactions between modality-specific and multimodal areas.
Dynamin-related protein 1 inhibition reduces hepatic PCSK9 secretion
Authors: Rogers Maximillian A , Hutcheson Joshua D , Okui Takehito , Goettsch Claudia , Singh Sasha A , Halu Arda , Schlotter Florian , Higashi Hideyuki , Wang Lixiang , Whelan Mary C , Mlynarchik Andrew K , Daugherty Alan , Nomura Masatoshi , Aikawa Masanori , Aikawa Elena 
Published: January 2021

Abstract

Aims
Proteostasis maintains protein homeostasis and participates in regulating critical cardiometabolic disease risk factors including proprotein convertase subtilisin/kexin type 9 (PCSK9). Endoplasmic reticulum (ER) remodeling through release and incorporation of trafficking vesicles mediates protein secretion and degradation. We hypothesized that ER remodeling that drives mitochondrial fission participates in cardiometabolic proteostasis.

Methods and results
We used in vitro and in vivo hepatocyte inhibition of a protein involved in mitochondrial fission, dynamin-related protein 1 (DRP1). Here, we show that DRP1 promotes remodeling of select ER microdomains by tethering vesicles at ER. A DRP1 inhibitor, mitochondrial division inhibitor 1 (mdivi-1) reduced ER localization of a DRP1 receptor, mitochondrial fission factor, suppressing ER remodeling-driven mitochondrial fission, autophagy, and increased mitochondrial calcium buffering and PCSK9 proteasomal degradation. DRP1 inhibition by CRISPR/Cas9 deletion or mdivi-1 alone or in combination with statin incubation in human hepatocytes and hepatocyte-specific Drp1-deficiency in mice reduced PCSK9 secretion (−78.5%). In HepG2 cells, mdivi-1 increased low-density lipoprotein receptor via c-Jun transcription and reduced PCSK9 mRNA levels via suppressed sterol regulatory binding protein-1c. Additionally, mdivi-1 reduced macrophage burden, oxidative stress, and advanced calcified atherosclerotic plaque in aortic roots of diabetic Apoe-deficient mice and inflammatory cytokine production in human macrophages.

Conclusions
We propose a novel tethering function of DRP1 beyond its established fission function, with DRP1-mediated ER remodeling likely contributing to ER constriction of mitochondria that drives mitochondrial fission. We report that DRP1-driven remodeling of select ER micro-domains may critically regulate hepatic proteostasis and identify mdivi-1 as a novel small molecule PCSK9 inhibitor.
Habitat Associations of Carrion Beetles (Coleoptera: Silphidae) Across a Full Annual Cycle
Authors: Engasser Emmy L , Stone Rachel L , Jameson Mary Liz 
Published: January 2021

AbstractNecrophagous insects play an important role in decomposition and nutrient recycling of decomposing vertebrates. Ecological studies of carrion-associated beetles enhance forensic investigations by providing information about community assemblages and predictable patterns of succession. However, lack of standardized protocols that include replication, spatial scale, and phenology reduce detection of patterns and predictions. To address these gaps and examine the influence of habitat (woodlands vs grasslands) and abiotic factors on carrion beetle (Coleoptera: Silphidae) communities, we developed an experimental approach from broad to finer scale located within the Kansas Flint Hills across a full annual cycle (12 contiguous months). In total, 3,333 adult carrion beetles in nine species were collected from pitfall traps baited with rat carrion over thirteen 4-wk collecting periods. PERMANOVA and NMDS demonstrate that the silphid beetle community was significantly different in species composition between grassland and woodland habitats, but communities did not differ significantly in overall mean abundance, mean species richness, or mean species diversity. Two species exhibited strong habitat associations; one associated with grassland habitat (Nicrophorus marginatus F.) and one with woodland habitat (Nicrophorus orbicollis Say). Our results reveal that habitat associations of silphid beetles can be useful in forensic investigations by determining corpse relocation and in ecological studies that explore niche filtering.
Preoperative prognostic nutritional index level is associated with tumour-infiltrating lymphocyte status in patients with surgically resected lung squamous cell carcinoma
Authors: Kitahara Hirokazu , Shoji Fumihiro , Akamine Takaki , Kinoshita Fumihiko , Haratake Naoki , Takenaka Tomoyoshi , Tagawa Tetsuzo , Sonoda Takashi , Shimokawa Mototsugu , Maehara Yoshihiko , Mori Masaki 
Published: January 2021

Abstract

OBJECTIVES
The prognostic nutritional index (PNI) is an indicator of systemic immune-nutritional condition and is a well-known prognostic biomarker in lung cancer patients. Tumour-infiltrating lymphocytes (TILs) is a specific histological feature of cancers, influencing an individual’s immunological tumour responses. However, whether PNI can reflect lung cancer patients’ prognosis through local immunity such as TIL is unclear.

METHODS
We selected 64 lung squamous cell carcinoma patients who underwent curative operations. We investigated the significance of preoperative PNI level and evaluated the relationship between PNI and immune cells surrounding the lung cancer tissue using immunohistochemical analysis of a cluster of differentiation (CD)3, CD4, CD8 and CD68.

RESULTS
A low-PNI level was significantly associated with a worse postoperative prognosis (P = 0.042). The PNI (hazard ratio 2.768, 95% confidence interval 1.320–5.957; P = 0.007) was an independent prognostic factor. The low-PNI group had a significantly shorter recurrence-free survival and overall survival (P = 0.013 and P = 0.002, log-rank test) compared with the high-PNI group. A significant positive correlation between PNI components including preoperative peripheral blood lymphocyte count and serum albumin concentration, and TILs, was observed. Absolute numbers of TILs in the preoperative high-PNI group were significantly increased compared with those in the preoperative low-PNI group (CD3+ cells; P = 0.002, CD4+ cells; P = 0.049 and CD8+ cells; P = 0.024).

CONCLUSIONS
The preoperative PNI level was strongly associated with the postoperative outcome in lung cancer patients. Considering the positive relationship between preoperative PNI level and TIL status, preoperative immune-nutritional condition may influence lung cancer patients’ postoperative prognosis through local immunity as well as systemic immune response.
Heart-team hybrid approach to persistent atrial fibrillation with dilated atria: the added value of continuous rhythm monitoring
Authors: Lapenna Elisabetta , Cireddu Manuela , Nisi Teodora , Ruggeri Stefania , Del Forno Benedetto , Monaco Fabrizio , Bargagna Marta , D’Angelo Giuseppe , Bisceglia Caterina , Gulletta Simone , Agricola Eustachio , Castiglioni Alessandro , Alfieri Ottavio , De Bonis Michele , Della Bella Paolo 
Published: January 2021

Abstract

OBJECTIVES
To assess by a continuous implantable rhythm monitoring (ILR) the mid-term outcomes of a staged-hybrid approach for patients with persistent/long-standing persistent atrial fibrillation (AF) and dilated atria.

METHODS
Fifty patients [age 57 (standard deviation, SD: 8.3), previous catheter ablation 66%, AF history 6.5 (2–12) years, left ventricular ejection fraction 56 (SD: 7.9)%, left atrial volume index 44 (38–56) ml/m2] with persistent (44%) or long-standing persistent (56%) AF, underwent a 2-staged hybrid ablation (thoracoscopic epicardial procedure with Cobra-Fusion system and transcatheter Rhythmia mapping with endocardial touch-up of gaps). All patients received an ILR.

RESULTS
No hospital deaths and no stroke occurred. Follow-up was 98% complete [median 22 (11–34) months]. The 2-year arrhythmia-free survival off class I–III antiarrhythmic drugs/electrical cardioversion/redo catheter ablation and the arrhythmia control (maintenance of sinus rhythm with or without antiarrhythmic drugs/electrical cardioversion) were 65 (SD: 7.1)% and 82 (SD: 5.8)%, respectively. The occurrence of AF in the blanking period was identified as an independent predictor of AF recurrence (odds ratio 26.6, 95% confidence interval 5.3, 132.3; P &lt; 0.001). At longitudinal analysis, the predicted prevalence of sinus rhythm and sinus rhythm off class I–III antiarrhythmic drugs/electrical cardioversion/redo catheter ablation was 82% and 69% at 2 years, respectively. Among patients with recurrence, 50% had short-lasting asymptomatic episodes, identified only by ILR monitoring. The proportion of patients with AF burden ≤1% was 82% and 91% at 1 and 2 years, respectively, and in these cases, left atrial volume index decreased from 46 (SD: 12) ml/m2 to 41 (SD: 11) ml/m2 (P = 0.026).

CONCLUSIONS
A staged hybrid approach yields promising results in selected patients with persistent/long-standing persistent AF and dilated left atrium who are at very high risk of AF recurrence. The use of ILR in this setting should become a standard to optimize patient management.
Anoxygenic photo- and chemo-synthesis of phototrophic sulfur bacteria from an alpine meromictic lake
Authors: Di Nezio Francesco , Beney Clarisse , Roman Samuele , Danza Francesco , Buetti-Dinh Antoine , Tonolla Mauro , Storelli Nicola 
Published: January 2021

ABSTRACT
Meromictic lakes are interesting ecosystems to study anaerobic microorganisms due their permanent stratification allowing the formation of a stable anoxic environment. The crenogenic meromictic Lake Cadagno harbors an important community of anoxygenic phototrophic sulfur bacteria responsible for almost half of its total productivity. Besides their ability to fix CO2 through photosynthesis, these microorganisms also showed high rates of dark carbon fixation via chemosyntesis. Here, we grew in pure cultures three populations of anoxygenic phototrophic sulfur bacteria previously isolated from the lake, accounting for 72.8% of the total microbial community and exibiting different phenotypes: (1) the motile, large-celled purple sulfur bacterium (PSB) Chromatium okenii, (2) the small-celled PSB Thiodictyon syntrophicum and (3) the green sulfur bacterium (GSB) Chlorobium phaeobacteroides. We measured their ability to fix CO2 through photo- and chemo-synthesis, both in situ in the lake and in laboratory under different incubation conditions. We also evaluated the efficiency and velocity of H2S photo-oxidation, an important reaction in the anoxygenic photosynthesis process. Our results confirm that phototrophic sulfur bacteria strongly fix CO2 in the presence of light and that oxygen increases chemosynthesis at night, in laboratory conditions. Moreover, substancial differences were displayed between the three selected populations in terms of activity and abundance.
Identifying virulence determinants of multidrug-resistant Klebsiella pneumoniae in Galleria mellonella
Authors: Bruchmann Sebastian , Feltwell Theresa , Parkhill Julian , Short Francesca L 
Published: January 2021

ABSTRACT
Infections caused by Klebsiella pneumoniae are a major public health threat. Extensively drug-resistant and even pan-resistant strains have been reported. Understanding K. pneumoniae pathogenesis is hampered by the fact that murine models of infection offer limited resolution for non-hypervirulent strains which cause the majority of infections. The insect Galleria mellonella larva is a widely used alternative model organism for bacterial pathogens. We have performed genome-scale fitness profiling of a multidrug-resistant K. pneumoniae ST258 strain during infection of G. mellonella, to determine if this model is suitable for large-scale virulence factor discovery in this pathogen. Our results demonstrated a dominant role for surface polysaccharides in infection, with contributions from siderophores, cell envelope proteins, purine biosynthesis genes and additional genes of unknown function. Comparison with a hypervirulent strain, ATCC 43816, revealed substantial overlap in important infection-related genes, as well as additional putative virulence factors specific to ST258, reflecting strain-dependent fitness effects. Our analysis also identified a role for the metalloregulatory protein NfeR (YqjI) in virulence. Overall, this study offers new insight into the infection fitness landscape of K. pneumoniae, and provides a framework for using the highly flexible and easily scalable G. mellonella infection model to dissect molecular virulence mechanisms of bacterial pathogens.
Biobank for multidrug-resistant tuberculosis research: importance of sequential samples
Authors: Hwang Yoohyun , Kim Jiyeon , Park Seungkyu , Ryoo Sungweon 
Published: January 2021

ABSTRACT
Since 2013, Masan National Tuberculosis Hospital has collected standardized specimens from its tuberculosis patients, which include a large number of multidrug-resistant strains. The repository collects matched participants and their bacilli samples, compiling sequential samples from the beginning of treatment. The repository aims to provide resources for in-depth international research.
Overstory Retention and Stock Type Impact Survival and Growth of Underplanted Shortleaf Pine Beneath a Hardwood Canopy
Authors: Schnake David K , Roberts Scott D , Willis John L , Kushla John D , Munn Ian A 
Published: January 2021

AbstractThis study was established to evaluate underplanting as a method of reestablishing a shortleaf pine (Pinus echinata Mill.) component to a dry upland hardwood stand in the Piedmont region of the southeastern United States. Replicated treatment plots were harvested to retain four levels (approximately 0, 3, 7, and 10 m2 of basal area per hectare) of residual overstory density. One-year-old containerized seedlings with both smaller (93.4 cm3) and larger (113.1 cm3) plugs and bareroot seedlings were underplanted beneath the residual overstory treatments. After five growing seasons, seedling survival averaged 61% and was not meaningfully affected by residual overstory density. Seedling height growth ranged from 1.42 m to 2.61 m and was inversely related to residual overstory density. Containerized seedlings with larger plugs had the highest survival (77.4%) and best height growth (2.11 m), followed by containerized seedlings with smaller plugs (64.3%, 1.76 m) and bareroot seedlings (40.2%, 1.85 m). The results of this study indicated that underplanting containerized seedlings, particularly those with higher plug volume and greater plug depth, was a suitable option for reestablishing shortleaf pine on drier, hardwood dominated upland sites in the Piedmont. However, even low levels of overstory retention suppressed seedling height growth after a few years.
Mitochondrial Genome Evolution in Pelagophyte Algae
Authors: Sibbald Shannon J , Lawton Maggie , Archibald John M 
Published: January 2021

Abstract
The Pelagophyceae are marine stramenopile algae that include Aureoumbra lagunensis and Aureococcus anophagefferens, two microbial species notorious for causing harmful algal blooms. Despite their ecological significance, relatively few genomic studies of pelagophytes have been carried out. To improve understanding of the biology and evolution of pelagophyte algae, we sequenced complete mitochondrial genomes for A. lagunensis (CCMP1510), Pelagomonas calceolata (CCMP1756), and five strains of Aureoc. anophagefferens (CCMP1707, CCMP1708, CCMP1850, CCMP1984, and CCMP3368) using Nanopore long-read sequencing. All pelagophyte mitochondrial genomes assembled into single, circular mapping contigs between 39,376 bp (P. calceolata) and 55,968 bp (A. lagunensis) in size. Mitochondrial genomes for the five Aureoc. anophagefferens strains varied slightly in length (42,401–42,621 bp) and were 99.4–100.0% identical. Gene content and order were highly conserved between the Aureoc. anophagefferens and P. calceolata genomes, with the only major difference being a unique region in Aureoc. anophagefferens containingDNA adenine and cytosine methyltransferase (dam/dcm) genes that appear to be the product of lateral gene transfer from a prokaryotic or viral donor. Although the A. lagunensis mitochondrial genome shares seven distinct syntenic blocks with the other pelagophyte genomes, it has a tandem repeat expansion comprising ∼40% of its length, and lacks identifiable rps19 and glycine tRNA genes. Laterally acquired self-splicing introns were also found in the 23S rRNA (rnl) gene of P. calceolata and the coxI gene of the five Aureoc. anophagefferens genomes. Overall, these data provide baseline knowledge about the genetic diversity of bloom-forming pelagophytes relative to nonbloom-forming species.
Use of Korean dramas to facilitate precision mental health understanding and discussion for Asian Americans
Authors: Ta Park Van My , Park Cate Jongkyung , Kim Charles , Nguyen Nhi Cristina Y , Tran Anh T , Chiang Anna , Rho Si-inn J , Olaisen R Henry , Vuong Quyen , Rosas Lisa G , Cho Mildred K 
Published: January 2021

Summary
Precision mental health holds great potential for revolutionizing care and reducing the burden of mental illness. All races and ethnicities such as Asian Americans, the fastest growing racial group in the United States (U.S.), need to be engaged in precision mental health research. Owing to its global popularity, Korean drama (‘K-drama’) television shows may be an effective educational tool to increase precision mental health knowledge, attitudes and behaviors among Asian Americans. This qualitative study examined the participants’ perspectives about and acceptance of using K-dramas to educate and engage Asian Americans about precision mental health. Twelve workshops were conducted in English, Vietnamese and Korean with a convenience sample in the San Francisco Bay Area in the U.S. (n = 122). Discussions were coded for themes. Findings revealed that all language groups reported positive reactions to using K-dramas to learn about precision health, genetics and mental health. Overall, participants shared that they learned about topics that are not generally talked about (e.g. precision health; genetic testing; mental health), from other people’s perspectives, and the importance of mental health. Participants expressed how much they enjoyed the workshop, how they felt relieved due to the workshop, thought the workshop was interesting, and had an opportunity for self-reflection/healing. This pilot test demonstrated that K-dramas has promise to be used as a health educational tool in a workshop format focused on mental health among a diverse group of Asian Americans. Given the widespread access to K-dramas, they present a scalable opportunity for increasing awareness about specific health topics.