bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse Histopathologic Characteristics in Small Papillary Renal Cell Carcinomas Have Minimal Impact on Prognosis
Authors: Yang Chen , Shuch Brian , Kluger Harriet M , Serrano Maria , Kibel Adam S , Humphrey Peter A , Adeniran Adebowale J
Published: January 2021

Objectives

Tumor size has long been used in the management decision-making of patients with renal masses. Active surveillance had recently gained traction in selected patients with tumor size of 4 cm or less. Adverse histopathologic characteristics in papillary renal cell carcinoma (PRCC) have been shown to correlate with worse prognosis. We aimed to study whether such features in small PRCCs provide additional prognostic information.

Methods

Nephrectomies from our institution were collected and reviewed to evaluate for adverse histopathologic features. Clinical follow-up information was collected for all cases. Relationships between the variables were examined by Wilcoxon test and logistic regression.

Results

We identified 291 consecutive cases of PRCC. Adverse tumor histopathologic characteristics were significantly related to size. In PRCCs with size greater than 4 cm, there were more cases with high World Health Organization/International Society of Urological Pathology grade and necrosis. Adverse histologic features are less commonly seen in small PRCC and are not associated with lower disease-free survival or disease-specific survival.

Conclusions

Identification of these features in small PRCCs (≤4 cm) through needle core biopsy examination would not provide additional prognostic information in patients for whom active surveillance is considered. Clinical and radiologic follow-up in patients with small renal masses that have a known histologic diagnosis of PRCC should be sufficient.
M2R: a Python add-on to cobrapy for modifying human genome-scale metabolic reconstruction using the gut microbiota models
Authors: Weglarz-Tomczak Ewelina , Tomczak Jakub M. , Brul Stanley
Published: January 2021

Motivation

The gut microbiota is the human body’s largest population of microorganisms that interact with human intestinal cells. They use ingested nutrients for fundamental biological processes and have important impacts on human physiology, immunity and metabolome in the gastrointestinal tract.

Results

Here, we present M2R, a Python add-on to cobrapy that allows incorporating information about the gut microbiota metabolism models to human genome-scale metabolic models (GEMs) like RECON3D. The idea behind the software is to modify the lower bounds of the exchange reactions in the model using aggregated in- and out-fluxes from selected microbes. M2R enables users to quickly and easily modify the pool of the metabolites that enter and leave the GEM, which is particularly important for those looking into an analysis of the metabolic interaction between the gut microbiota and human cells and its dysregulation.

Availability and implementation

M2R is freely available under an MIT License at https://github.com/e-weglarz-tomczak/m2r.

Supplementary information

Supplementary data are available at Bioinformatics online.
Random rotation for identifying differentially expressed genes with linear models following batch effect correction
Authors: Hettegger Peter , Vierlinger Klemens , Weinhaeusel Andreas
Published: January 2021

Motivation

Data 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.

Results

We 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.

Availability

The described methods are implemented as randRotation package on Bioconductor: https://bioconductor.org/packages/randRotation/

Contact

p.hettegger@gmail.com

Supplementary information

Supplementary 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

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

Conceptual 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

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

Necrophagous 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

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

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 < 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

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

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

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

This 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

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

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.
Photoreceptor cilia, in contrast to primary cilia, grant entry to a partially assembled BBSome
Authors: Hsu Ying , Seo Seongjin , Sheffield Val C
Published: January 2021

The BBSome is a protein complex consisting of BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, BBS9 and BBS18 that associates with intraflagellar transport complexes and specializes in ciliary trafficking. In primary cilia, ciliary entry requires the fully assembled BBSome as well as the small GTPase, ARL6 (BBS3). Retinal photoreceptors possess specialized cilia. In light of key structural and functional differences between primary and specialized cilia, we examined the principles of BBSome recruitment to photoreceptor cilia. We performed sucrose gradient fractionation using retinal lysates of Bbs2−/−, Bbs7−/−, Bbs8−/− and Bbs3−/− mice to determine the status of BBSome assembly, then determined localization of BBSome components using immunohistochemistry. Surprisingly, we found that a subcomplex of the BBSome containing at least BBS1, BBS5, BBS8 and BBS9 is recruited to cilia in the absence of BBS2 or BBS7. In contrast, a BBSome subcomplex consisting of BBS1, BBS2, BBS5, BBS7 and BBS9 is found in Bbs8−/− retinas and is denied ciliary entry in photoreceptor cells. In addition, the BBSome remains fully assembled in Bbs3−/− retinas and can be recruited to photoreceptor cilia in the absence of BBS3. We compared phenotypic severity of their retinal degeneration phenotypes. These findings demonstrate that unlike primary cilia, photoreceptor cilia admit a partially assembled BBSome meeting specific requirements. In addition, the recruitment of the BBSome to photoreceptor cilia does not require BBS3. These findings indicate that the ciliary entry of the BBSome is subjected to cell-specific regulation, particularly in cells with highly adapted forms of cilia such as photoreceptors.
Neisseria gonorrhoeae antimicrobial resistance in Spain: a prospective multicentre study
Authors: Salmerón Paula , Viñado Belén , Arando Maider , Alcoceba Eva , Romero Beatriz , Menéndez Blanca , Bernal Samuel , Idigoras Pedro , Colomina Javier , Martin-Saco Gloria , Leal-Negredo Álvaro , Torreblanca Aurora , Martínez Olalla , Serra-Pladevall Judit
Published: January 2021

Objectives

Gonococcal infection is one of the most reported sexually transmitted infections and antimicrobial resistance in Neisseria gonorrhoeae (NG) is challenging for the treatment of this infection. This observational study aimed to describe antimicrobial resistance of NG and epidemiological data from patients with gonococcal infection in eight regions of Spain, for updating the local therapeutic guidelines.

Methods

MICs of penicillin, cefixime, ceftriaxone, azithromycin, ciprofloxacin, fosfomycin and gentamicin were determined by Etest for all NG isolates recovered from 1 April 2018 to 30 September 2019 from 10 hospitals in Spain. Resistance determinants were identified using logistic regression analysis. Differences with a P value <0.05 were considered statistically significant.

Results

Antimicrobial susceptibility testing was performed for 2571 gonococci isolated from 2429 patients. 44.5% (945/2124) of patients were MSM. The resistance rate to extended-spectrum cephalosporins was low, with 0.2% (6/2561) of isolates resistant to ceftriaxone and 1.7% (44/2517) of isolates resistant to cefixime. The overall azithromycin resistance rate was 12.1% (310/2560), but differed greatly depending on the area. 56.2% (1366/2429) of the strains studied were ciprofloxacin resistant. MIC50 and MIC90 values of gentamicin and fosfomycin were 4 and 8 mg/L and 24 and 48 mg/L, respectively.

Conclusions

Our study shows that NG susceptibility to extended-spectrum cephalosporins remains high in Spain. The azithromycin resistance rate questions the suitability of dual therapy. This study provides data of interest for updating the national treatment guidelines and highlights the need to develop and implement a national sentinel gonococcal antimicrobial susceptibility programme.
Using machine learning to improve the accuracy of patient deterioration predictions: Mayo Clinic Early Warning Score (MC-EWS)
Authors: Romero-Brufau Santiago , Whitford Daniel , Johnson Matthew G , Hickman Joel , Morlan Bruce W , Therneau Terry , Naessens James , Huddleston Jeanne M
Published: January 2021

Objective

We aimed to develop a model for accurate prediction of general care inpatient deterioration.

Materials and Methods

Training and internal validation datasets were built using 2-year data from a quaternary hospital in the Midwest. Model training used gradient boosting and feature engineering (clinically relevant interactions, time-series information) to predict general care inpatient deterioration (resuscitation call, intensive care unit transfer, or rapid response team call) in 24 hours. Data from a tertiary care hospital in the Southwest were used for external validation. C-statistic, sensitivity, positive predictive value, and alert rate were calculated for different cutoffs and compared with the National Early Warning Score. Sensitivity analysis evaluated prediction of intensive care unit transfer or resuscitation call.

Results

Training, internal validation, and external validation datasets included 24 500, 25 784 and 53 956 hospitalizations, respectively. The Mayo Clinic Early Warning Score (MC-EWS) demonstrated excellent discrimination in both the internal and external validation datasets (C-statistic = 0.913, 0.937, respectively), and results were consistent in the sensitivity analysis (C-statistic = 0.932 in external validation). At a sensitivity of 73%, MC-EWS would generate 0.7 alerts per day per 10 patients, 45% less than the National Early Warning Score.

Discussion

Low alert rates are important for implementation of an alert system. Other early warning scores developed for the general care ward have achieved lower discrimination overall compared with MC-EWS, likely because MC-EWS includes both nursing assessments and extensive feature engineering.

Conclusions

MC-EWS achieved superior prediction of general care inpatient deterioration using sophisticated feature engineering and a machine learning approach, reducing alert rate.
The Production and Use of the Film It Stays With You: Use of Force by UN Peacekeepers in Haiti to Challenge the Exclusion of Survivors’ Experiences from Peacekeeping Success Stories
Authors: Wills Siobhán , McLaughlin Cahal
Published: January 2021

During its operations against gangs in the period 2004–2007 the UN Stabilization Mission in Haiti (MINUSTAH) killed and injured many people who were not posing a threat to anyone and were not involved in criminal activity. In Operations Iron Fist (2005) and New Forest (2006) an estimated 60 people were killed, some by bullets fired from helicopters penetrating the roofs of their corrugated metal shacks. Survivors claim that no one from the UN or from any state agency has ever visited their neighbourhood to speak to them—‘it’s as though you’re worthless’. This article discusses the making of the film It Stays With You: Use of Force by UN Peacekeepers in Haiti—which was produced using participatory practices—and the project team’s use of the film to raise awareness of the need for reform of UN rules of engagement and for an investigation into excessive use of force by MINUSTAH. The article also discusses the use of the film to challenge the exclusion from the MINUSTAH success narrative of the stories of the people who live in the targeted community, and to provide a platform that might enable the experiences of survivors to be publicly acknowledged internationally. Funded by the Arts and Humanities Research Council, It Stays With You forms part of an interdisciplinary law and film studies research project, which explores the role of film as a method of addressing trauma and as a means of highlighting the need for a human rights-oriented approach to accountability in the conduct of UN law enforcement operations.
Landowner Concern about Wildfires and Implementation of Fuel Reduction Treatments
Authors: Shrestha Anusha , Grala Robert K , Grado Stephen C , Roberts Scott D , Gordon Jason S
Published: January 2021

Fuel reduction treatments implemented by nonindustrial private forest (NIPF) landowners affect wildfire hazard potential on both their tracts and surrounding lands. However, it is not clear how concerned they are about wildfire damages and what actions they are willing to take to lower wildfire hazard. This study determined the landowner concern level about wildfire damages and identified factors affecting their concern and fuel treatment implementation using seemingly unrelated and binary probit models, respectively. Approximately, 68% of landowners were concerned about property damage due to wildfires, and 45% implemented some fuel reduction treatments. The most common and least costly fuel treatment was prescribed burning ($18/acre) followed by chemical ($59/acre) and mechanical ($127/acre) treatments. Raising awareness about potential monetary losses due to wildfires, assisting landowners in preparing written forest management plans, and prioritizing areas with predominant pine cover will encourage landowner participation in hazardous fuel reduction programs and facilitate more effective wildfire mitigation.
Species abundance is jointly determined by functional traits and negative density dependence in a subtropical forest in southern China
Authors: Wang Weitao , Jiang Yun , Li Buhang , Xi Nianxun , Chen Yongfa , He Dong , Feng Jiayi , Chu Chengjin
Published: January 2021

Aims

The factors affecting species abundance are a subject of ongoing debates in community ecology. Empirical studies have demonstrated that tree abundance is affected by plant functional traits and negative density dependence (NDD). However, few studies have focused on the combined effects of NDD and plant functional traits on species abundance.

Methods

In this study, we used tree functional traits and two census data from a 50-ha forest dynamic plot in the Heishiding (HSD) Nature Reserve to explore the combined effects of functional traits and NDD on species abundance. Using hierarchical Bayesian models, we analyzed how neighbor densities affected the survival of saplings from 130 species and extracted posterior means of the coefficients to represent NDD. The structural equation modeling (SEM) analysis was then applied to investigate the causal relationships among species functional traits, NDD and species abundance.

Important Findings

SEM showed that tree functional traits, including specific leaf area (SLA), leaf area (LA), leaf dry matter content (LDMC), leaf N content (LNC), maximum electron transport rate (ETRmax) and conspecific adult negative density dependence (CNDDadult), together explained 20% of the total variation in tree abundance. Specifically, SLA affected tree abundance both directly and indirectly via CNDDadult, with a totally negative influence on abundance. LDMC and LNC had only indirect effects mediated by CNDDadult on tree abundance. ETRmax and LA had directly negative effects on abundance, but their direct connections with CNDDadult were not observed. In addition, CNDDadult was negatively correlated with species abundance, indicating that abundant species are under stronger NDD. Among these investigated traits, SLA contributed the most to the variation in CNDDadult and abundance. We argued that our findings of trait–CNDDadult–abundance relationships can improve our understanding of the determinants of species commonness and rarity in forests.
Psychosocial Moderators and Outcomes of a Randomized Effectiveness Trial for Child Asthma
Authors: Weinstein Sally M , Pugach Oksana , Rosales Genesis , Mosnaim Giselle S , Orozco Kimberly , Pappalardo Andrea A , Martin Molly A
Published: January 2021

Objective

Psychosocial factors play a role in child asthma morbidity and disparities, but their impact on asthma intervention effectiveness is less understood. This study examined how child, parent, and family psychosocial factors moderated asthma response to, and changed in response to, 2 community asthma interventions among urban minority youth.

Methods

Asthma Action at Erie was a randomized comparative effectiveness trial examining a community health worker (CHW) home intervention versus certified asthma educator (AE-C) services for children aged 5–16 with uncontrolled asthma (N = 223; mean age = 9.37, SD = 3.02; 85.2% Hispanic). Asthma control was assessed via the Asthma Control Test (ACT)/childhood ACT and activity limitation. Baseline child/parent depression and posttraumatic stress disorder (PTSD) symptoms, family chaos, and social support were examined as treatment moderators. We also tested intervention effects on psychosocial outcomes.

Results

For parents with higher baseline depression symptoms, youth in the CHW group had greater ACT improvement by 24 months (7.49 points) versus AE-C (4.76 points) and 51% reduction in days of limitation by 6 months versus AE-C (ß = −0.118; p = .0145). For higher parent PTSD symptoms, youth in CHW had 68% fewer days of limitation at 24 months versus AE-C (ß = −0.091; p = .0102). Psychosocial outcomes did not vary by group, but parent depression, parent and child PTSD symptoms, and social support improved for all.

Conclusions

CHW intervention was associated with improved asthma control among families with higher parent strain. Findings have implications for utilizing tailored CHW home interventions to optimize asthma outcomes in at-risk families.
Lymphocyte Aggregation in Low-Grade B-Cell Lymphoma
Authors: Walradth Eric A
Published: January 2021

Platelet and erythrocyte agglutination is known to happen in vitro due to EDTA or temperature-induced cold antibodies. Leukocyte agglutination is far less common, and its etiology is not always known. The 2 cases presented herein are of low-grade B-cell lymphomas consistent with splenic marginal-zone lymphoma that presented with lymphocyte agglutination. In Case A, the lymphocyte aggregates were not resolved by warming the sample or by non-EDTA anticoagulation. In Case B, the lymphocyte aggregates were largely resolved by warming the specimen at 37°C for 15 minutes. The 2 cases presented herein further show that the etiology of lymphocyte aggregation can have multiple causes, even within the same disease process.
Implications of recoil kicks for black hole mergers from LIGO/Virgo catalogs
Authors: Fragione Giacomo , Loeb Abraham
Published: January 2021

The first and second Gravitational Wave Transient Catalogs by the LIGO/Virgo Collaboration include 50 confirmed merger events from the first, second, and first half of the third observational runs. We compute the distribution of recoil kicks imparted to the merger remnants and estimate their retention probability within various astrophysical environments as a function of the maximum progenitor spin (χmax), assuming that the LIGO/Virgo binary black hole (BBH) mergers were catalyzed by dynamical assembly in a dense star cluster. We find that the distributions of average recoil kicks are peaked at about $150\, \rm km\, s^{-1}$, $250\, \rm km\, s^{-1}$, $350\, \rm km\, s^{-1}$, $600\, \rm km\, s^{-1}$, for maximum progenitor spins of 0.1, 0.3, 0.5, 0.8, respectively. Only environments with escape speed ${\gtrsim}100\, \rm km\, s^{-1}$, as found in galactic nuclear star clusters as well as in the most massive globular clusters and super star clusters, could efficiently retain the merger remnants of the LIGO/Virgo BBH population even for low progenitor spins (χmax = 0.1). In the case of high progenitor spins (χmax ≳ 0.5), only the most massive nuclear star clusters can retain the merger products. We also show that the estimated values of the effective spin and of the remnant spin of GW170729, GW190412, GW190519_153544, and GW190620_030421 can be reproduced if their progenitors were moderately spinning (χmax ≳ 0.3), while for GW190517_055101 if the progenitors were rapidly spinning (χmax ≳ 0.8). Alternatively, some of these events could be explained if at least one of the progenitors is already a second-generation BH, originated from a previous merger.
The SR-protein Npl3 is an essential component of the meiotic splicing regulatory network in Saccharomyces cerevisiae
Authors: Sandhu Rima , Sinha Aniketa , Montpetit Ben
Published: January 2021

The meiotic gene expression program in Saccharomyces cerevisiae involves regulated splicing of meiosis-specific genes via multiple splicing activators (e.g. Mer1, Nam8, Tgs1). Here, we show that the SR protein Npl3 is required for meiotic splicing regulation and is essential for proper execution of the meiotic cell cycle. The loss of Npl3, though not required for viability in mitosis, caused intron retention in meiosis-specific transcripts, inefficient meiotic double strand break processing and an arrest of the meiotic cell cycle. The targets of Npl3 overlapped in some cases with other splicing regulators, while also having unique target transcripts that were not shared. In the absence of Npl3, splicing defects for three transcripts (MER2, HOP2 and SAE3) were rescued by conversion of non-consensus splice sites to the consensus sequence. Methylation of Npl3 was further found to be required for splicing Mer1-dependent transcripts, indicating transcript-specific mechanisms by which Npl3 supports splicing. Together these data identify an essential function for the budding yeast SR protein Npl3 in meiosis as part of the meiotic splicing regulatory network.
Accelerator design for 1.3-MW beam power operation of the J-PARC Main Ring
Authors: Igarashi Susumu , Satou Kenichirou , Ohmori Chihiro , Arakaki Yoshitugu , Furusawa Masashi , Hara Keigo , Hasegawa Katsushi , Hashimoto Yoshinori , Hori Yoichiro , Hotchi Hideaki , Ishii Koji , Kadowaki Kotomi , Kamikubota Norihiko , Kimura Takuro , Kobayashi Aine , Koseki Tadashi , Kubota Chikashi , Kurimoto Yoshinori , Matsumoto Noriyuki , Miura Kazuki , Morita Yuichi , Murasugi Shigeru , Muto Ryotaro , Naito Fujio , Nakamura Takeshi , Niki Kazuaki , Nomura Masahiro , Ohmi Kazuhito , Okada Masashi , Okamura Katsuya , Oogoe Takao , Orii Asato , Sato Kenichi , Sato Yoichi , Sato Yoshihiro , Shibata Tatsunobu , Shimada Taihei , Shimamoto Masayuki , Shimogawa Tetsushi , Shirakata Masashi , Sugimoto Takuya , Sugiyama Yasuyuki , Takano Jumpei , Takiyama Yoichi , Tamura Fumihiko , Tejima Masaki , Tomizawa Masahito , Toyama Takeshi , Uota Masahiko , Yamada Shuei , Yamamoto Masanobu , Yamamoto Noboru , Yanaoka Eiichi , Yoshii Masahito
Published: January 2021

The J-PARC Main Ring (MR) has supplied the high-intensity proton beam for the T2K long-baseline neutrino experiment since 2010. The present beam power is 510 kW and the total number of protons on the target reaches $3.64\times10^{21}$. To observe charge-conjugation and parity-transformation (CP) violation in the lepton sector with high accuracy, more protons need to be delivered to the T2K target. The project to upgrade the beam power to 1.3 MW started as a mid-term plan of the MR. In parallel to preparing a full technical design report, the technical designs of hardware upgrades using new technologies and all accelerator components that are necessary to deliver the 1.3-MW beam power are summarized and consolidated in this short paper. Further, this paper includes beam dynamics studies and simulation results for handling $3.3\times 10^{14}$ protons per pulse (ppp) without significant beam loss in the ring and transport lines. The Hyper-Kamiokande (HK) project has recently been approved, and construction has started; the MR upgrade and HK project will work together efficiently to study the CP violation.