bluuebunny/crossref_metadata_2025 huggingface dataset:
Conditioning intensity and peritransplant flow cytometric MRD dynamics in adult AML
Authors: Paras Gabrielle , Morsink Linde M. , Othus Megan , Milano Filippo , Sandmaier Brenda M. , Zarling Lucas C. , Palmieri Raffaele , Schoch Gary , Davis Chris , Bleakley Marie , Flowers Mary E. D. , Deeg H. Joachim , Appelbaum Frederick R. , Storb Rainer , Walter Roland B.
Published: January 2022

In acute myeloid leukemia (AML), measurable residual disease (MRD) before or after allogeneic hematopoietic cell transplantation (HCT) is an established independent indicator of poor outcome. To address how peri-HCT MRD dynamics could refine risk assessment across different conditioning intensities, we analyzed 810 adults transplanted in first or second remission after myeloablative conditioning (MAC; n = 515) or non-MAC (n = 295) who underwent multiparameter flow cytometry–based MRD testing before as well as 20 to 40 days after allografting. Patients without pre- and post-HCT MRD (MRDneg/MRDneg) had the lowest risks of relapse and highest relapse-free survival (RFS) and overall survival (OS). Relative to those patients, outcomes for MRDpos/MRDpos and MRDneg/MRDpos patients were poor regardless of conditioning intensity. Outcomes for MRDpos/MRDneg patients were intermediate. Among 161 patients with MRD before HCT, MRD was cleared more commonly with a MAC (85 of 104; 81.7%) than non-MAC (33 of 57; 57.9%) regimen (P = .002). Although non-MAC regimens were less likely to clear MRD, if they did, the impact on outcome was greater. Thus, there was a significant interaction between conditioning intensity and “MRD conversion” for relapse (P = .020), RFS (P = .002), and OS (P = .001). Similar findings were obtained in the subset of 590 patients receiving HLA-matched allografts. C-statistic values were higher (indicating higher predictive accuracy) for peri-HCT MRD dynamics compared with the isolated use of pre-HCT MRD status or post-HCT MRD status for prediction of relapse, RFS, and OS. Across conditioning intensities, peri-HCT MRD dynamics improve risk assessment over isolated pre- or post-HCT MRD assessments in patients with AML.
The association of lung function and pulmonary vasculature volume with cardiorespiratory fitness in the community
Authors: McNeill Jenna , Chernofsky Ariel , Nayor Matthew , Rahaghi Farbod N. , San Jose Estepar Raul , Washko George , Synn Andrew , Vasan Ramachandran S. , O'Connor George , Larson Martin G. , Ho Jennifer E. , Lewis Gregory D.
Published: January 2022

Background

Cardiorespiratory fitness is not limited by pulmonary mechanical reasons in the majority of adults. However, the degree to which lung function contributes to exercise response patterns among ostensibly healthy individuals remains unclear.

Methods

We examined 2314 Framingham Heart Study participants who underwent cardiopulmonary exercise testing (CPET) and pulmonary function testing. We investigated the association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and diffusing capacity of the lung for carbon monoxide (DLCO) with the primary outcome of peak oxygen uptake (V′O2) along with other CPET parameters using multivariable linear regression. Finally, we investigated the association of total and peripheral pulmonary blood vessel volume with peakV′O2.

Results

We found lower FEV1, FVC andDLCOwere associated with lower peakV′O2. For example, a 1 L lower FEV1and FVC was associated with a 7.1% (95% CI 5.1–9.1%) and 6.0% (95% CI 4.3–7.7%) lower peakV′O2, respectively. By contrast, FEV1/FVC was not associated with peakV′O2. Lower lung function was associated with lower oxygen uptake efficiency slope, oxygen pulse slope,V′O2at anaerobic threshold (AT), minute ventilation (V′E) at AT and breathing reserve. In addition, lower total and peripheral pulmonary blood vessel volume were associated with lower peakV′O2.

Conclusions

In a large, community-based cohort of adults, we found lower FEV1, FVC andDLCOwere associated with lower exercise capacity, as well as oxygen uptake efficiency slope and ventilatory efficiency. In addition, lower total and peripheral pulmonary blood vessel volume were associated with lower peakV′O2. These findings underscore the importance of lung function and blood vessel volume as contributors to overall exercise capacity.
CFTRvariants are associated with chronic bronchitis in smokers
Authors: Saferali Aabida , Qiao Dandi , Kim Wonji , Raraigh Karen , Levy Hara , Diaz Alejandro A. , Cutting Garry R. , Cho Michael H. , Hersh Craig P.
Published: January 2022

Introduction

Loss-of-function variants in both copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF); however, there is evidence that reduction in CFTR function due to the presence of one deleterious variant can have clinical consequences. Here, we hypothesise thatCFTRvariants in individuals with a history of smoking are associated with chronic obstructive pulmonary disease (COPD) and related phenotypes.

Methods

Whole-genome sequencing was performed through the National Heart, Lung, and Blood Institute TOPMed (TransOmics in Precision Medicine) programme in 8597 subjects from the COPDGene (Genetic Epidemiology of COPD) study, an observational study of current and former smokers. We extracted clinically annotatedCFTRvariants and performed single-variant and variant-set testing for COPD and related phenotypes. Replication was performed in 2118 subjects from the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study.

Results

We identified 301 coding variants within theCFTRgene boundary: 147 of these have been reported in individuals with CF, including 36 CF-causing variants. We found that CF-causing variants were associated with chronic bronchitis in variant-set testing in COPDGene (one-sided p=0.0025; OR 1.53) and in meta-analysis of COPDGene and ECLIPSE (one-sided p=0.0060; OR 1.52). Single-variant testing revealed that the F508del variant was associated with chronic bronchitis in COPDGene (one-sided p=0.015; OR 1.47). In addition, we identified 32 subjects with two or moreCFTRvariants on separate alleles and these subjects were enriched for COPD cases (p=0.010).

Conclusions

Cigarette smokers who carry one deleteriousCFTRvariant have higher rates of chronic bronchitis, while presence of twoCFTRvariants may be associated with COPD. These results indicate that genetically mediated reduction in CFTR function contributes to COPD related phenotypes, in particular chronic bronchitis.
Lysyl oxidase like 2 is increased in asthma and contributes to asthmatic airway remodelling
Authors: Ramis Jopeth , Middlewick Robert , Pappalardo Francesco , Cairns Jennifer T. , Stewart Iain D. , John Alison E. , Naveed Shams-Un-Nisa , Krishnan Ramaswamy , Miller Suzanne , Shaw Dominick E. , Brightling Christopher E. , Buttery Lee , Rose Felicity , Jenkins Gisli , Johnson Simon R. , Tatler Amanda L.
Published: January 2022

Background

Airway smooth muscle (ASM) cells are fundamental to asthma pathogenesis, influencing bronchoconstriction, airway hyperresponsiveness and airway remodelling. The extracellular matrix (ECM) can influence tissue remodelling pathways; however, to date no study has investigated the effect of ASM ECM stiffness and cross-linking on the development of asthmatic airway remodelling. We hypothesised that transforming growth factor-β (TGF-β) activation by ASM cells is influenced by ECM in asthma and sought to investigate the mechanisms involved.

Methods

This study combinesin vitroandin vivoapproaches: human ASM cells were usedin vitroto investigate basal TGF-β activation and expression of ECM cross-linking enzymes. Human bronchial biopsies from asthmatic and nonasthmatic donors were used to confirm lysyl oxidase like 2 (LOXL2) expression in ASM. A chronic ovalbumin (OVA) model of asthma was used to study the effect of LOXL2 inhibition on airway remodelling.

Results

We found that asthmatic ASM cells activated more TGF-β basally than nonasthmatic controls and that diseased cell-derived ECM influences levels of TGF-β activated. Our data demonstrate that the ECM cross-linking enzyme LOXL2 is increased in asthmatic ASM cells and in bronchial biopsies. Crucially, we show that LOXL2 inhibition reduces ECM stiffness and TGF-β activationin vitro, and can reduce subepithelial collagen deposition and ASM thickness, two features of airway remodelling, in an OVA mouse model of asthma.

Conclusion

These data are the first to highlight a role for LOXL2 in the development of asthmatic airway remodelling and suggest that LOXL2 inhibition warrants further investigation as a potential therapy to reduce remodelling of the airways in severe asthma.
The role of electrical stimulation for rehabilitation and regeneration after spinal cord injury
Authors: Karamian Brian A. , Siegel Nicholas , Nourie Blake , Serruya Mijail D. , Heary Robert F. , Harrop James S. , Vaccaro Alexander R.
Published: January 2022

Electrical stimulation is used to elicit muscle contraction and can be utilized for neurorehabilitation following spinal cord injury when paired with voluntary motor training. This technology is now an important therapeutic intervention that results in improvement in motor function in patients with spinal cord injuries. The purpose of this review is to summarize the various forms of electrical stimulation technology that exist and their applications. Furthermore, this paper addresses the potential future of the technology.
Is reverse total shoulder arthroplasty (rTSA) more advantageous than anatomic TSA (aTSA) for osteoarthritis with intact cuff tendon? A systematic review and meta-analysis
Authors: Kim Hyojune , Kim Chul-Ho , Kim Minsoo , Lee Wonsun , Jeon In-Ho , Lee Kwang Won , Koh Kyoung Hwan
Published: January 2022

Purpose

We aimed to compare the outcomes and complications of anatomical shoulder arthroplasty (aTSA) and reverse total shoulder arthroplasty (rTSA) for primary glenohumeral osteoarthritis with intact cuff tissue.

Materials and methods

The MEDLINE, Embase, and Cochrane Library databases were systematically searched for studies published before March 2, 2021 using the PRISMA guidelines. Studies were included if they directly compared aTSA and rTSA for treating primary glenohumeral arthritis. A meta-analysis was performed using six studies that compared radiologic outcomes, functional scores, and range of motion (ROM). All the data were pooled using a random-effects model. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated as dichotomous data, while continuous data were analyzed using mean differences with 95% CIs.

Results

Two independent researchers reviewed 1,061 studies. Six studies met the inclusion criteria. The range of motion, especially external rotation, was better for aTSA than for rTSA (MD = − 10.28, 95% CI: − 16.69 to − 3.88, P = 0.002). Functional scores showed no difference between aTSA and rTSA. Glenoid loosening (OR = 0.17, 95% CI: 0.06–0.50, P = 0.001) was more common with aTSA, and scapula notching (OR = 10.63, 95% CI: 1.73–65.27, P = 0.01) with rTSA. In the mid-term follow-up, the overall revision rate showed no difference between aTSA and rTSA, with a pooled OR of 0.33 (95% CI: 0.07–1.57, P = 0.16).

Conclusion

A better ROM was achieved after aTSA than after rTSA. There was no difference in the revision rate at mid-term follow-up between aTSA and rTSA. Glenoid loosening was more common with aTSA, and scapula notching with rTSA.

Level of evidence: Level IV, Meta-analysis.
Non-parametric synergy modeling of chemical compounds with Gaussian processes
Authors: Shapovalova Yuliya , Heskes Tom , Dijkstra Tjeerd
Published: January 2022

Background

Understanding the synergetic and antagonistic effects of combinations of drugs and toxins is vital for many applications, including treatment of multifactorial diseases and ecotoxicological monitoring. Synergy is usually assessed by comparing the response of drug combinations to a predicted non-interactive response from reference (null) models. Possible choices of null models are Loewe additivity, Bliss independence and the recently rediscovered Hand model. A different approach is taken by the MuSyC model, which directly fits a generalization of the Hill model to the data. All of these models, however, fit the dose–response relationship with a parametric model.

Results

We propose the Hand-GP model, a non-parametric model based on the combination of the Hand model with Gaussian processes. We introduce a new logarithmic squared exponential kernel for the Gaussian process which captures the logarithmic dependence of response on dose. From the monotherapeutic response and the Hand principle, we construct a null reference response and synergy is assessed from the difference between this null reference and the Gaussian process fitted response. Statistical significance of the difference is assessed from the confidence intervals of the Gaussian process fits. We evaluate performance of our model on a simulated data set from Greco, two simulated data sets of our own design and two benchmark data sets from Chou and Talalay. We compare the Hand-GP model to standard synergy models and show that our model performs better on these data sets. We also compare our model to the MuSyC model as an example of a recent method on these five data sets and on two-drug combination screens: Mott et al. anti-malarial screen and O’Neil et al. anti-cancer screen. We identify cases in which the HandGP model is preferred and cases in which the MuSyC model is preferred.

Conclusion

The Hand-GP model is a flexible model to capture synergy. Its non-parametric and probabilistic nature allows it to model a wide variety of response patterns.
LaRA 2: parallel and vectorized program for sequence–structure alignment of RNA sequences
Authors: Winkler Jörg , Urgese Gianvito , Ficarra Elisa , Reinert Knut
Published: January 2022

Background

The function of non-coding RNA sequences is largely determined by their spatial conformation, namely the secondary structure of the molecule, formed by Watson–Crick interactions between nucleotides. Hence, modern RNA alignment algorithms routinely take structural information into account. In order to discover yet unknown RNA families and infer their possible functions, the structural alignment of RNAs is an essential task. This task demands a lot of computational resources, especially for aligning many long sequences, and it therefore requires efficient algorithms that utilize modern hardware when available. A subset of the secondary structures contains overlapping interactions (called pseudoknots), which add additional complexity to the problem and are often ignored in available software.

Results

We present the SeqAn-based software LaRA 2 that is significantly faster than comparable software for accurate pairwise and multiple alignments of structured RNA sequences. In contrast to other programs our approach can handle arbitrary pseudoknots. As an improved re-implementation of the LaRA tool for structural alignments, LaRA 2 uses multi-threading and vectorization for parallel execution and a new heuristic for computing a lower boundary of the solution. Our algorithmic improvements yield a program that is up to 130 times faster than the previous version.

Conclusions

With LaRA 2 we provide a tool to analyse large sets of RNA secondary structures in relatively short time, based on structural alignment. The produced alignments can be used to derive structural motifs for the search in genomic databases.
HESML: a real-time semantic measures library for the biomedical domain with a reproducible survey
Authors: Lastra-Díaz Juan J. , Lara-Clares Alicia , Garcia-Serrano Ana
Published: January 2022

Background

Ontology-based semantic similarity measures based on SNOMED-CT, MeSH, and Gene Ontology are being extensively used in many applications in biomedical text mining and genomics respectively, which has encouraged the development of semantic measures libraries based on the aforementioned ontologies. However, current state-of-the-art semantic measures libraries have some performance and scalability drawbacks derived from their ontology representations based on relational databases, or naive in-memory graph representations. Likewise, a recent reproducible survey on word similarity shows that one hybrid IC-based measure which integrates a shortest-path computation sets the state of the art in the family of ontology-based semantic measures. However, the lack of an efficient shortest-path algorithm for their real-time computation prevents both their practical use in any application and the use of any other path-based semantic similarity measure.

Results

To bridge the two aforementioned gaps, this work introduces for the first time an updated version of the HESML Java software library especially designed for the biomedical domain, which implements the most efficient and scalable ontology representation reported in the literature, together with a new method for the approximation of the Dijkstra’s algorithm for taxonomies, called Ancestors-based Shortest-Path Length (AncSPL), which allows the real-time computation of any path-based semantic similarity measure.

Conclusions

We introduce a set of reproducible benchmarks showing that HESML outperforms by several orders of magnitude the current state-of-the-art libraries in the three aforementioned biomedical ontologies, as well as the real-time performance and approximation quality of the new AncSPL shortest-path algorithm. Likewise, we show that AncSPL linearly scales regarding the dimension of the common ancestor subgraph regardless of the ontology size. Path-based measures based on the new AncSPL algorithm are up to six orders of magnitude faster than their exact implementation in large ontologies like SNOMED-CT and GO. Finally, we provide a detailed reproducibility protocol and dataset as supplementary material to allow the exact replication of all our experiments and results.
Protein complexes detection based on node local properties and gene expression in PPI weighted networks
Authors: Yu Yang , Kong Dezhou
Published: January 2022

Background

Identifying protein complexes from protein–protein interaction (PPI) networks is a crucial task, and many related algorithms have been developed. Most algorithms usually employ direct neighbors of nodes and ignore resource allocation and second-order neighbors. The effective use of such information is crucial to protein complex detection.

Result

Based on this observation, we propose a new way by combining node resource allocation and gene expression information to weight protein network (NRAGE-WPN), in which protein complexes are detected based on core-attachment and second-order neighbors.

Conclusions

Through comparison with eleven methods in Yeast and Human PPI network, the experimental results demonstrate that this algorithm not only performs better than other methods on 75% in terms of f-measure+, but also can achieve an ideal overall performance in terms of a composite score consisting of five performance measures. This identification method is simple and can accurately identify more complexes.
Comparative genomics and phylogenetic relationships of two endemic and endangered species (Handeliodendron bodinieri and Eurycorymbus cavaleriei) of two monotypic genera within Sapindales
Authors: Yang Jiaxin , Hu Guoxiong , Hu Guangwan
Published: January 2022

Background

Handeliodendron Rehder and Eurycorymbus Hand.-Mazz. are the monotypic genera in the Sapindaceae family. The phylogenetic relationship of these endangered species Handeliodendron bodinieri (Lévl.) Rehd. and Eurycorymbus cavaleriei (Lévl.) Rehd. et Hand.-Mazz. with other members of Sapindaceae s.l. is not well resolved. A previous study concluded that the genus Aesculus might be paraphyletic because Handeliodendron was nested within it based on small DNA fragments. Thus, their chloroplast genomic information and comparative genomic analysis with other Sapindaceae species are necessary and crucial to understand the circumscription and plastome evolution of this family.

Results

The chloroplast genome sizes of Handeliodendron bodinieri and Eurycorymbus cavaleriei are 151,271 and 158,690 bp, respectively. Results showed that a total of 114 unique genes were annotated in H. bodinieri and E. cavaleriei, and the ycf1 gene contained abundant SSRs in both genomes. Comparative analysis revealed that gene content, PCGs, and total GC content were remarkably similar or identical within 13 genera from Sapindaceae, and the chloroplast genome size of four genera was generally smaller within the family, including Acer, Dipteronia, Aesculus, and Handeliodendron. IR boundaries of the H. bodinieri showed a significant contraction, whereas it presented a notable expansion in E. cavaleriei cp genome. Ycf1, ndhC-trnV-UAC, and rpl32-trnL-UAG-ccsA were remarkably divergent regions in the Sapindaceae species. Analysis of selection pressure showed that there are a few positively selected genes. Phylogenetic analysis based on different datasets, including whole chloroplast genome sequences, coding sequences, large single-copy, small single-copy, and inverted repeat regions, consistently demonstrated that H. bodinieri was sister to the clade consisting of Aesculus chinensis and A. wangii and strongly support Eurycorymbus cavaleriei as sister to Dodonaea viscosa.

Conclusion

This study revealed that the cp genome size of the Hippocastanoideae was generally smaller compared to the other subfamilies within Sapindaceae, and three highly divergent regions could be used as the specific DNA barcodes within Sapindaceae. Phylogenetic results strongly support that the subdivision of four subfamilies within Sapindaceae, and Handeliodendron is not nested within the genus Aesculus.
Long range PCR-based deep sequencing for haplotype determination in mixed HCMV infections
Authors: Brait Nadja , Külekçi Büşra , Goerzer Irene
Published: January 2022

Background

Short read sequencing has been used extensively to decipher the genome diversity of human cytomegalovirus (HCMV) strains, but falls short to reveal individual genomes in mixed HCMV strain populations. Novel third-generation sequencing platforms offer an extended read length and promise to resolve how distant polymorphic sites along individual genomes are linked. In the present study, we established a long amplicon PacBio sequencing workflow to identify the absolute and relative quantities of unique HCMV haplotypes spanning over multiple hypervariable sites in mixtures. Initial validation of this approach was performed with defined HCMV DNA templates derived from cell-culture enriched viruses and was further tested for its suitability on patient samples carrying mixed HCMV infections.

Results

Total substitution and indel error rate of mapped reads ranged from 0.17 to 0.43% depending on the stringency of quality trimming. Artificial HCMV DNA mixtures were correctly determined down to 1% abundance of the minor DNA source when the total HCMV DNA input was 4 × 104 copies/ml. PCR products of up to 7.7 kb and a GC content < 55% were efficiently generated when DNA was directly isolated from patient samples. In a single sample, up to three distinct haplotypes were identified showing varying relative frequencies. Alignments of distinct haplotype sequences within patient samples showed uneven distribution of sequence diversity, interspersed by long identical stretches. Moreover, diversity estimation at single polymorphic regions as assessed by short amplicon sequencing may markedly underestimate the overall diversity of mixed haplotype populations.

Conclusions

Quantitative haplotype determination by long amplicon sequencing provides a novel approach for HCMV strain characterisation in mixed infected samples which can be scaled up to cover the majority of the genome by multi-amplicon panels. This will substantially improve our understanding of intra-host HCMV strain diversity and its dynamic behaviour.
Maize/peanut intercropping improves nutrient uptake of side-row maize and system microbial community diversity
Authors: Zhao Xinhua , Dong Qiqi , Han Yi , Zhang Kezhao , Shi Xiaolong , Yang Xu , Yuan Yang , Zhou Dongying , Wang Kai , Wang Xiaoguang , Jiang Chunji , Liu Xibo , Zhang He , Zhang Zhimeng , Yu Haiqiu
Published: January 2022

Background

Intercropping, a diversified planting pattern, increases land use efficiency and farmland ecological diversity. We explored the changes in soil physicochemical properties, nutrient uptake and utilization, and microbial community composition in wide-strip intercropping of maize and peanut.

Results

The results from three treatments, sole maize, sole peanut and intercropping of maize and peanut, showed that intercropped maize had a marginal advantage and that the nutrient content of roots, stems and grains in side-row maize was better than that in the middle row of intercropped maize and sole maize. The yield of intercropped maize was higher than that of sole cropping. The interaction between crops significantly increased soil peroxidase activity, and significantly decreased protease and dehydrogenase activities in intercropped maize and intercropped peanut. The diversity and richness of bacteria and fungi decreased in intercropped maize rhizosphere soil, whereas the richness of fungi increased intercropped peanut. RB41, Candidatus-udaeobacter, Stropharia, Fusarium and Penicillium were positively correlated with soil peroxidase activity, and negatively correlated with soil protease and dehydrogenase activities. In addition, intercropping enriched the functional diversity of the bacterial community and reduced pathogenic fungi.

Conclusion

Intercropping changed the composition and diversity of the bacterial and fungal communities in rhizosphere soil, enriched beneficial microbes, increased the nitrogen content of intercropped maize and provided a scientific basis for promoting intercropping in northeastern China.
Microbiome analyses of 12 psyllid species of the family Psyllidae identified various bacteria including Fukatsuia and Serratia symbiotica, known as secondary symbionts of aphids
Authors: Nakabachi Atsushi , Inoue Hiromitsu , Hirose Yuu
Published: January 2022

Background

Psyllids (Hemiptera: Psylloidea) comprise a group of plant sap-sucking insects that includes important agricultural pests. They have close associations not only with plant pathogens, but also with various microbes, including obligate mutualists and facultative symbionts. Recent studies are revealing that interactions among such bacterial populations are important for psyllid biology and host plant pathology. In the present study, to obtain further insight into the ecological and evolutionary behaviors of bacteria in Psylloidea, we analyzed the microbiomes of 12 psyllid species belonging to the family Psyllidae (11 from Psyllinae and one from Macrocorsinae), using high-throughput amplicon sequencing of the 16S rRNA gene.

Results

The analysis showed that all 12 psyllids have the primary symbiont, Candidatus Carsonella ruddii (Gammaproteobacteria: Oceanospirillales), and at least one secondary symbiont. The majority of the secondary symbionts were gammaproteobacteria, especially those of the family Enterobacteriaceae (order: Enterobacteriales). Among them, symbionts belonging to “endosymbionts3”, which is a genus-level monophyletic group assigned by the SILVA rRNA database, were the most prevalent and were found in 9 of 11 Psyllinae species. Ca. Fukatsuia symbiotica and Serratia symbiotica, which were recognized only as secondary symbionts of aphids, were also identified. In addition to other Enterobacteriaceae bacteria, including Arsenophonus, Sodalis, and “endosymbionts2”, which is another genus-level clade, Pseudomonas (Pseudomonadales: Pseudomonadaceae) and Diplorickettsia (Diplorickettsiales: Diplorickettsiaceae) were identified. Regarding Alphaproteobacteria, the potential plant pathogen Ca. Liberibacter europaeus (Rhizobiales: Rhizobiaceae) was detected for the first time in Anomoneura mori (Psyllinae), a mulberry pest. Wolbachia (Rickettsiales: Anaplasmataceae) and Rickettsia (Rickettsiales: Rickettsiaceae), plausible host reproduction manipulators that are potential tools to control pest insects, were also detected.

Conclusions

The present study identified various bacterial symbionts including previously unexpected lineages in psyllids, suggesting considerable interspecific transfer of arthropod symbionts. The findings provide deeper insights into the evolution of interactions among insects, bacteria, and plants, which may be exploited to facilitate the control of pest psyllids in the future.
Rhizosphere analysis of field-grown Panax ginseng with different degrees of red skin provides the basis for preventing red skin syndrome
Authors: Dong Ling , Bian Xingbo , Zhao Yan , Yang He , Xu Yonghua , Han Yongzhong , Zhang Lianxue
Published: January 2022

Background

Ginseng red skin root syndrome (GRS) is one of the most common ginseng (Panax ginseng Meyer) diseases. It leads to a severe decline in P. ginseng quality and seriously affects the P. ginseng industry in China. However, as a root disease, the characteristics of the GRS rhizosphere microbiome are still unclear.

Methods

The amplicon bacterial 16 S rRNA genes and fungal ITS (Internal Transcribed Spacer) regions Illumina sequencing technology, combined with microbial diversity and composition analysis based on R software, was used to explore the relationship between soil ecological environment and GRS.

Results

There were significant differences in the diversity and richness of soil microorganisms between the rhizosphere with different degrees of disease, especially between healthy P. ginseng (HG) and heavily diseased groups. The variation characteristics of microbial abundance in different taxa levels were analyzed. The interaction network of rhizosphere microorganisms of P. ginseng under GRS background was established. We also found that different P. ginseng rhizosphere microbial communities have multiple changes in stability and complexity through the established interaction network. Microbes closely related to potential pathogenic fungi were also identified according to the interaction network, which provided clues for looking for biological control agents. Finally, the Distance-based redundancy analysis (dbRDA) results indicated that total phosphorus (TP), available potassium (AK), available phosphorus (AP), catalase (CAT), invertase (INV) are the key factors that influence the microbial communities. Moreover, the content of these key factors in the rhizosphere was negatively correlated with disease degrees.

Conclusions

In this study, we comprehensively analyzed the rhizosphere characteristics of P. ginseng with different levels of disease, and explored the interaction relationship among microorganisms. These results provide a basis for soil improvement and biological control of field-grown in the future.
Chlorosis seedling lethality 1 encoding a MAP3K protein is essential for chloroplast development in rice
Authors: Liang Jiayan , Zhang Qiuxin , Liu Yiran , Zhang Jingjing , Wang Wenyi , Zhang Zemin
Published: January 2022

Background

Mitogen-activated protein kinase (MAPK) cascades are conserved signaling modules in eukaryotic organisms and play essential roles in immunity and stress responses. However, the role of MAPKs in chloroplast development remains to be evidently established.

Results

In this study, a rice chlorosis seedling lethality 1 (csl1) mutant with a Zhonghua11 (ZH11, japonica) background was isolated. Seedlings of the mutant were characterized by chlorotic leaves and death after the trefoil stage, and chloroplasts were observed to contain accumulated starch granules. Molecular cloning revealed that OsCSL1 encoded a MAPK kinase kinase22 (MKKK22) targeted to the endoplasmic reticulum (ER), and functional complementation of OsCSL1 was found to restore the normal phenotype in csl1 plants. The CRISPR/Cas9 technology was used for targeted disruption of OsCSL1, and the OsCSL1-Cas9 lines obtained therein exhibited yellow seedlings which phenocopied the csl1 mutant. CSL1/MKKK22 was observed to establish direct interaction with MKK4, and altered expression of MKK1 and MKK4 was detected in the csl1 mutant. Additionally, disruption of OsCSL1 led to reduced expression of chloroplast-associated genes, including chlorophyll biosynthetic genes, plastid-encoded RNA polymerases, nuclear-encoded RNA polymerase, and nuclear-encoded chloroplast genes.

Conclusions

The findings of this study revealed that OsCSL1 played roles in regulating the expression of multiple chloroplast synthesis-related genes, thereby affecting their functions, and leading to wide-ranging defects, including chlorotic seedlings and severely disrupted chloroplasts containing accumulated starch granules.
Non-parametric estimation of reference adjusted, standardised probabilities of all-cause death and death due to cancer for population group comparisons
Authors: Rutherford Mark J. , Andersson Therese M.-L. , Myklebust Tor Åge , Møller Bjørn , Lambert Paul C.
Published: January 2022

Background

Ensuring fair comparisons of cancer survival statistics across population groups requires careful consideration of differential competing mortality due to other causes, and adjusting for imbalances over groups in other prognostic covariates (e.g. age). This has typically been achieved using comparisons of age-standardised net survival, with age standardisation addressing covariate imbalance, and the net estimates removing differences in competing mortality from other causes. However, these estimates lack ease of interpretability. In this paper, we motivate an alternative non-parametric approach that uses a common rate of other cause mortality across groups to give reference-adjusted estimates of the all-cause and cause-specific crude probability of death in contrast to solely reporting net survival estimates.

Methods

We develop the methodology for a non-parametric equivalent of standardised and reference adjusted crude probabilities of death, building on the estimation of non-parametric crude probabilities of death. We illustrate the approach using regional comparisons of survival following a diagnosis of rectal cancer for men in England. We standardise to the covariate distribution and other cause mortality of England as a whole to offer comparability, but with close approximation to the observed all-cause region-specific mortality.

Results

The approach gives comparable estimates to observed crude probabilities of death, but allows direct comparison across population groups with different covariate profiles and competing mortality patterns. In our illustrative example, we show that regional variations in survival following a diagnosis of rectal cancer persist even after accounting for the variation in deprivation, age at diagnosis and other cause mortality.

Conclusions

The methodological approach of using standardised and reference adjusted metrics offers an appealing approach for future cancer survival comparison studies and routinely published cancer statistics. Our non-parametric estimation approach through the use of weighting offers the ability to estimate comparable survival estimates without the need for statistical modelling.
Stacked survival models for residual lifetime data
Authors: McVittie James H. , Wolfson David B. , Addona Vittorio , Li Zhaoheng
Published: January 2022

When modelling the survival distribution of a disease for which the symptomatic progression of the associated condition is insidious, it is not always clear how to measure the failure/censoring times from some true date of disease onset. In a prevalent cohort study with follow-up, one approach for removing any potential influence from the uncertainty in the measurement of the true onset dates is through the utilization of only the residual lifetimes. As the residual lifetimes are measured from a well-defined screening date (prevalence day) to failure/censoring, these observed time durations are essentially error free. Using residual lifetime data, the nonparametric maximum likelihood estimator (NPMLE) may be used to estimate the underlying survival function. However, the resulting estimator can yield exceptionally wide confidence intervals. Alternatively, while parametric maximum likelihood estimation can yield narrower confidence intervals, it may not be robust to model misspecification. Using only right-censored residual lifetime data, we propose a stacking procedure to overcome the non-robustness of model misspecification; our proposed estimator comprises a linear combination of individual nonparametric/parametric survival function estimators, with optimal stacking weights obtained by minimizing a Brier Score loss function.
Effect of Helicobacter pylori infection on malignancy of undifferentiated-type gastric cancer
Authors: Tanaka Masami , Hoteya Shu , Kikuchi Daisuke , Nomura Kosuke , Ochiai Yorinari , Okamura Takayuki , Hayasaka Junnosuke , Suzuki Yugo , Mitsunaga Yutaka , Dan Nobuhiro , Odagiri Hiroyuki , Yamashita Satoshi , Matsui Akira
Published: January 2022

Background

Although almost all cases of gastric cancer are caused by Helicobacter pylori (HP) infection, there are some rare exceptions. Furthermore, the clinicopathological characteristics of gastric cancer may differ depending on HP infection status. This study aimed to determine the clinicopathological characteristics of undifferentiated-type gastric cancer (UD-GC) according to HP status.

Methods

The study involved 83 patients with UD-GC who were selected from 1559 patients with gastric cancer who underwent endoscopic resection at our hospital and whose HP infection status was confirmed. Clinicopathological characteristics were evaluated according to HP status (eradicated, n = 28; infected, n = 32; not infected, n = 23).

Results

In patients without HP infection, UD-GCs were < 20 mm and intramucosal with no vascular invasion. In patients with eradicated HP, there was no correlation between development of UD-GC and time since eradication. Nine of twelve patients with a tumor detected ≥ 5 years after eradication had undergone yearly endoscopy. Submucosal invasion was observed in two of four patients and lymphovascular invasion in three of four patients whose UD-GC was detected ≥ 10 years after eradication. There was no significant between-group difference in the frequency of lesions with invasion into the submucosal layer or deeper (14.3%, 10.5%, and 0% in the UD-E, UD-I, and UD-U groups, respectively).

Conclusion

The clinicopathological characteristics of UD-GC were similar between HP-infected patients and HP-eradicated patients. Three of four patients with eradicated HP whose UD-GC developed ≥ 10 years after eradication were not eligible for endoscopic treatment and required additional surgery resection. In contrast, UD-GC was curable by endoscopic resection in all patients without HP infection.
Comparison of the innovative endoscopic oropharyngeal airway and the conventional mouthpiece in elderly outpatients undergoing esophagogastroduodenoscopy under sedation: a prospective and randomized study
Authors: Zhang Wei , Zhu Chun , Chen Xu , Tao Lei , He Keqiang , Wu Hao , Chai Xiaoqing , Wang Sheng , Xia Min
Published: January 2022

Background

Undesirable outcomes may appear for elderly patients undergoing esophagogastroduodenoscopy (EGD) under sedation, such as hypoxia and hypotension. The aim of our study was to investigate the ability of the innovative endoscopic oropharyngeal airway to reduce the frequency of hypoxia during EGD under sedation in elderly patients.

Methods

In this trial, aged patients undergoing EGD were randomized into airway group and mouthpiece group. The primary outcome was the incidence of the minimum pulse oxygen saturation < 90% and minimum pulse oxygen saturation. In addition, sedation dose, recovery time, emergency management and adverse reactions were recorded.

Results

360 patients completed the study (180 in each groups). The minimum pulse oxygen saturation during EGD was significantly higher in airway group (97.66 ± 2.96%) than in mouthpiece group (95.52 ± 3.84%, P < 0.001). The incidence of pulse oxygen saturation of 85–89% of airway group (5.0%, 9/180) was lower than mouthpiece group (10.6%, 19/180, P = 0.049). The endoscopy entry time in airway group was 3 (2, 4) seconds and in mouthpiece group was 5 (4, 6) (P < 0.001). Propofol total dose and awakening time were significantly lower in the airway group than in the mouthpiece group (P = 0.020 and P = 0.012, respectively). Furthermore, the incidence rate of hypotension was significantly higher in mouthpiece group (12.2%) than in airway group (5.0%) (P = 0.015). By comparison with the mouthpiece group, the satisfaction of endoscopists was higher in airway group (P = 0.012).

Conclusion

Elderly patients undergoing EGD, Endoscopy Protector was associated with a significantly lower incidence of hypoxia, shortened endoscopy entry time and more stable hemodynamics.

Trial registration: ChiCTR, ChiCTR2000031998, 17/04/2020. http://www.chictr.org.cn/index.aspx
Individual Pharmacotherapy Management (IPM) - I: a group-matched retrospective controlled clinical study on prevention of complicating delirium in the elderly trauma patients and identification of associated factors
Authors: Drewas Luise , Ghadir Hassan , Neef Rüdiger , Delank Karl-Stefan , Wolf Ursula
Published: January 2022

Background

Delirium is one of the most frequent complications in hospitalized elderly patients with additional costs such as prolongation of hospital stays and institutionalization, with risk of reduced functional recovery, long-term cognitive impairment, and increased morbidity and mortality. We analyzed the effect of individual pharmacotherapy management (IPM) in the University Hospital Halle in geriatric trauma patients on complicating delirium and aimed to identify associated factors.

Methods

In a retrospective controlled clinical study of 404 hospitalized trauma patients ≥70 years we compared the IPM intervention group (IG) with a control group (CG) before IPM implementation. Delirium was recorded from the hospital discharge letter. The medication review and data records included baseline data, all medications, diagnoses, electrocardiogram (ECG), laboratory and vital parameters during hospitalization. The IPM internist and the senior trauma physician guaranteed personnel and structural continuity in the implementation of the interdisciplinary patient rounds.

Results

There was a highly matched congruence between CG and IG in terms of age, gender, residency, BMI, most diagnoses, and injury patterns to compare the two groups. The total number of medications per patient was 11.1 ± 4.9 (CG) versus 10.4 ± 3.6 (IG). Our targeted IPM focus on 6 frontline aspects with reduction of antipsychotics, anticholinergic burden, benzodiazepines, serotonergic opioids, elimination of pharmacokinetic and pharmacodynamic drug interactions and overdosage reduced complicating delirium from 5% to almost zero at 0.5%. The association of IPM with a significant 10-fold reduction, OR = 0.09 [95% CI 0.01–0.7], in univariable regression, maintained of clinical relevance in multivariable regression OR = 0.1 [95% CI 0.01–1.1]. Factors most strongly associated with complicating delirium in univariable regression were cognitive dysfunction, nursing home residency, muscle relaxants, antiparkinsonian agents, xanthines, transient disorientation documented in the fall risk scale, antibiotic-requiring infections, antifungals, antipsychotics, and intensive care stay, the two latter maintaining significance in multivariable regression.

Conclusions

IPM is associated with a highly effective prevention of complicating delirium in the elderly trauma patients. For patient safety it should be integrated as an essential preventative contribution. The associated factors help identify patients at risk.
Factors associated with 90-day acute ischemic stroke in patients ≥70 years old with total hip arthroplasty for hip fracture
Authors: He Rui , Wang Guoyou , Li Ting , Shen Huarui , LijuanZhang
Published: January 2022

Background

Postoperative ischemic stroke is a devastating complication following total hip arthroplasty (THA). The purpose of the current study was to investigate the incidence of postoperative acute ischemic stroke (AIS) in patients ≥70 years old with THA for hip fracture after 90 days and independent risk factors associated with 90-day AIS.

Methods

A multicenter retrospective study was conducted, patients ≥70 years old with THA for hip fracture under general anesthesia were included from February 2017 to March 2020. Patients with AIS within 90 days after THA were identified as AIS group; patients with no AIS were identified as no AIS group. The baseline characteristics and risk factors were collected, multivariable logistic regression was used to identify independent risk factors of 90-dayAIS.

Results: 2517 patients (mean age 76.18 ± 6.01) were eligible for inclusion in the study. 2.50% (63/2517) of patients had 90-day AIS. Compared with no AIS, older age, diabetes, hyperlipidemia, atrial fibrillation (AF) and higher D-dimer value were more likely in patients with AIS (P < 0.05), and anticoagulant use was fewer in patients with AIS. ROC curve analysis showed that the optimal cut point of D-dimer for AIS was D-dimer≥4.12 μg/ml. Multivariate logistic regression analysis showed that D-dimer≥4.12 μg/ml [adjusted odds ratio (aOR), 4.44; confidence interval (CI), 2.50–7.72; P < 0.001], older age (aOR, 1.08; 95%CI, 1.03–1.12; P < 0.001), hyperlipidemia (aOR, 2.28; 95%CI, 1.25–4.16; P = 0.007), atrial fibrillation (aOR, 5.84; 95% CI, 1.08–15.68; P = 0.001), and diabetes (aOR, 2.60; 95% CI, 1.56–4.39; P < 0.001) were associated with increased risk of 90-day AIS after THA.

Conclusions

In conclusion, we found that the incidence of 90-day AIS in patients≥70 years old with THA for hip fracture was 2.5%. Older age, diabetes, hyperlipidemia, AF and higher D-dimer value were independent risk factors for 90-day AIS in patients≥70 years old with THA for hip fracture.