bluuebunny/crossref_metadata_2025 huggingface dataset:
Nominalizations in the Romance Languages
Authors: Fábregas Antonio , Marín Rafael
Published: April 2022

The term nominalization refers to a specific type of category-changing morphological operation that produces nouns from other lexical categories, most productively verbs and adjectives. By extension, it is also used to refer to the resulting derived nouns. In Romance languages, nominalization generally involves addition of a suffix to the base (cf. Italian generoso ‘generous’ > generos-ità ‘generosity’), and such suffixes are called nominalizers. However there are also cases of nouns built from other categories without any overt nominalizer (cf. Spanish inútil ‘useless’ > inútil ‘useless person’); descriptively, this process is called conversion, and it is debatable whether it should also be treated as a nominalization or whether another different kind of morphological operation is involved here.

Nominalizations can be divided in several classes depending on a variety of semantic and syntactic factors, such as the type of entities that they denote or the ability to introduce arguments. The main nominalization classes are (a) complex event nominalizations, which come from verbs, can combine with some temporal and aspectual modifiers, and have the ability to introduce at least an internal argument; (b) state nominalizations, which denote states associated to the verbs that serve as their bases; (c) participant nominalizations, which denote different types of arguments of the base, such as agents, resulting objects, locations or recipients; and (d) quality nominalizations, coming from adjectives and more restrictively from verbs, which denote a set of properties related to their base. Different classes of predicates select for different nominalization types, and there is a debate surrounding which tests capture in a more complete way the nuances of this taxonomy.

Nominalizers impose different types of restrictions to their bases: aspectual restrictions (individual-level vs. stage-level, (a) telicity, dynamicity, etc.), argument structure restrictions (agent vs. nonagent, different types of internal arguments), morphological restrictions (for instance, selecting only verbs that belong to a particular conjugation class), and finally conceptual restrictions (for instance, showing a strong preference for bases belonging to a particular conceptual domain).

In Romance languages, nominalizations sometimes alternate with other word classes, most significantly infinitives (see article on “Infinitival Clauses in the Romance Languages” in this encyclopedia). Infinitival constructions in Romance can display a mixture of verbal and nominal properties, or be totally recategorized as nouns, and in both cases they can compete with prototypical nominalizations. Less generally, participles (see article on “Participial Relative Clauses” in this encyclopedia), gerunds and supines can also display nominalization properties in some Romance varieties.
Catalan
Authors: Ordóñez Francisco
Published: April 2022

Catalan is a “medium-sized” Romance language spoken by over 10 million speakers, spread over four nation states: Northeastern Spain, Andorra, Southern France, and the city of L’Alguer (Alghero) in Sardinia, Italy. Catalan is divided into two primary dialectal divisions, each with further subvarieties: Western Catalan (Western Catalonia, Eastern Aragon, and Valencian Community) and Eastern Catalan (center and east of Catalonia, Balearic Islands, Rosselló, and l’Alguer).

Catalan descends from Vulgar Latin. Catalan expanded during medieval times as one of the primary vernacular languages of the Kingdom of Aragon. It largely retained its role in government and society until the War of Spanish Succession in 1714, and since it has been minoritized. Catalan was finally standardized during the beginning of the 20th century, although later during the Franco dictatorship it was banned in public spaces. The situation changed with the new Spanish Constitution promulgated in 1978, when Catalan was declared co-official with Spanish in Catalonia, the Valencian Community, and the Balearic Islands.

The Latin vowel system evolved in Catalan into a system of seven stressed vowels. As in most other Iberian Romance languages, there is a general process of spirantization or lenition of voiced stops. Catalan has a two-gender grammatical system and, as in other Western Romance languages, plurals end in -s; Catalan has a personal article and Balearic Catalan has a two-determiner system for common nouns. Finally, past perfective actions are indicated by a compound tense consisting of the auxiliary verb anar ‘to go’ in present tense plus the infinitive.

Catalan is a minoritized language everywhere it is spoken, except in the microstate of Andorra, and it is endangered in France and l’Alguer. The revival of Catalan in the post-dictatorship era is connected with a movement called linguistic normalization. The idea of normalization refers to the aim to return Catalan to a “normal” use at an official level and everyday level as any official language.
A Neuropsychological Approach to Mild Cognitive Impairment
Authors: Alfano Dennis P , Grummisch Julia A , Gordon Jennifer L , Hadjistavropoulos Thomas
Published: April 2022

Objective

A neuropsychological approach to the detection and classification of mild cognitive impairment (MCI) using “gold standard” clinical ratings (CRs) was examined in a sample of independently functioning community dwelling seniors. The relationship between CRs and life satisfaction, concurrent validity of cognitive screening measures, and agreement between CRs and existing criteria for MCI were also determined.

Method

One hundred and forty-two participants, aged 75 years and older, were administered a comprehensive battery of neuropsychological tests, along with self-report measures of psychological and psychosocial functioning, and functional independence. CRs were based on demographically corrected neuropsychological variables.

Results

The prevalence of MCI identified using CRs in this sample was 26.1%. Single and multiple domain subtypes of MCI were readily identified with subtypes reflecting Amnestic and Executive Function impairment predominating. Executive Function was a significant predictor of Life Satisfaction. The MoCA and MMSE both showed weak performance in detecting MCI based on CRs. There was substantial agreement between CRs and the classification criteria for MCI defined by Petersen/Winblad and Jak/Bondi. A global deficit score had near perfect performance as a proxy for CRs in detecting MCI in this sample.

Conclusions

The results provide strong support for the utility of neuropsychological CRs as a “gold standard” operational definition in the detection and classification of MCI in older adults.
A parameter-free deep embedded clustering method for single-cell RNA-seq data
Authors: Zeng Yuansong , Wei Zhuoyi , Zhong Fengqi , Pan Zixiang , Lu Yutong , Yang Yuedong
Published: April 2022

Clustering analysis is widely used in single-cell ribonucleic acid (RNA)-sequencing (scRNA-seq) data to discover cell heterogeneity and cell states. While many clustering methods have been developed for scRNA-seq analysis, most of these methods require to provide the number of clusters. However, it is not easy to know the exact number of cell types in advance, and experienced determination is not always reliable. Here, we have developed ADClust, an automatic deep embedding clustering method for scRNA-seq data, which can accurately cluster cells without requiring a predefined number of clusters. Specifically, ADClust first obtains low-dimensional representation through pre-trained autoencoder and uses the representations to cluster cells into initial micro-clusters. The clusters are then compared in between by a statistical test, and similar micro-clusters are merged into larger clusters. According to the clustering, cell representations are updated so that each cell will be pulled toward centers of its assigned cluster and similar clusters, while cells are separated to keep distances between clusters. This is accomplished through jointly optimizing the carefully designed clustering and autoencoder loss functions. This merging process continues until convergence. ADClust was tested on 11 real scRNA-seq datasets and was shown to outperform existing methods in terms of both clustering performance and the accuracy on the number of the determined clusters. More importantly, our model provides high speed and scalability for large datasets.
HLAB: learning the BiLSTM features from the ProtBert-encoded proteins for the class I HLA-peptide binding prediction
Authors: Zhang Yaqi , Zhu Gancheng , Li Kewei , Li Fei , Huang Lan , Duan Meiyu , Zhou Fengfeng
Published: April 2022

Human Leukocyte Antigen (HLA) is a type of molecule residing on the surfaces of most human cells and exerts an essential role in the immune system responding to the invasive items. The T cell antigen receptors may recognize the HLA-peptide complexes on the surfaces of cancer cells and destroy these cancer cells through toxic T lymphocytes. The computational determination of HLA-binding peptides will facilitate the rapid development of cancer immunotherapies. This study hypothesized that the natural language processing-encoded peptide features may be further enriched by another deep neural network. The hypothesis was tested with the Bi-directional Long Short-Term Memory-extracted features from the pretrained Protein Bidirectional Encoder Representations from Transformers-encoded features of the class I HLA (HLA-I)-binding peptides. The experimental data showed that our proposed HLAB feature engineering algorithm outperformed the existing ones in detecting the HLA-I-binding peptides. The extensive evaluation data show that the proposed HLAB algorithm outperforms all the seven existing studies on predicting the peptides binding to the HLA-A*01:01 allele in AUC and achieves the best average AUC values on the six out of the seven k-mers (k=8,9,...,14, respectively represent the prediction task of a polypeptide consisting of k amino acids) except for the 9-mer prediction tasks. The source code and the fine-tuned feature extraction models are available at http://www.healthinformaticslab.org/supp/resources.php.
One among many: the enigmatic case of the Miocene mammal, Kolponomos newportensis
Authors: Modafferi Maria , Melchionna Marina , Castiglione Silvia , Tamagnini Davide , Maiorano Luigi , Sansalone Gabriele , Profico Antonio , Girardi Giorgia , Raia Pasquale
Published: April 2022

Kolponomos newportensis is an enigmatic Miocene mammal allied to stem Pinnipedimorpha. It has been suggested that Kolponomos fed on hard-shelled benthic marine invertebrates by using its mandible as a wedge to dislodge its prey from the sea bottom by means of strong pull and torque forces. This unique feeding style was thought to originate from a singular case of mosaic convergence in mandible biomechanics between Kolponomos and the sabretoothed cat Smilodon, which complied with similarly strong torque forces when grappling with prey. As such forces must have reflected on the cranium as well, we hypothesize that the convergence between Kolponomos and the sabretoothed cats could have affected its shape. To test this hypothesis, we looked for patterns of morphological convergence in cranial shape between Kolponomos and sabretoothed cats. We found that Kolponomos is not distinctly closer to Smilodon than a number of other pinnipeds. Yet, local areas of shape convergence with Smilodon are observed in the canine area and the posterior part of the cranium, that is where the bite applies and the temporalis muscle is located, respectively. These results indicate that the mosaic convergence present between the mandibles of Kolponomos and Smilodon is partially reflected in the cranium as well.
Terrestrialization in gastropods: lineages, ecological constraints and comparisons with other animals
Authors: Vermeij Geerat J , Watson-Zink Victoria M
Published: April 2022

Evolutionary transitions from water to land are infrequent. The physical contrasts between these media are amplified by biological differences in the patterns of selection. A new compilation, based on published phylogenetic and fossil evidence, identifies 30 separate instances of terrestrial colonization by gastropods, at least 12 from the sea and 14 from freshwater. Pre-Cenozoic transitions, mainly from freshwater and all tropical, resulted in high terrestrial diversity. Most Cenozoic colonizations were local, especially on oceanic islands, and yielded few terrestrial species. An increasingly predator-rich terrestrial environment after the Cretaceous made colonization on land unlikely except in cryptic habitats and on islands. Colonization from the sea became possible only in the Cenozoic, when marine lineages became specialized for life on the upper seashore. The results are compared with terrestrial colonizations by other groups of plants and animals.
Training allows switching from limited-capacity manipulations to large-capacity perceptual processing
Authors: Malinovitch Tamar , Albouy Philippe , Zatorre Robert J , Ahissar Merav
Published: April 2022

In contrast to perceptual tasks, which enable concurrent processing of many stimuli, working memory (WM) tasks have a very small capacity, limiting cognitive skills. Training on WM tasks often yields substantial improvement, suggesting that training might increase the general WM capacity. To understand the underlying processes, we trained a test group with a newly designed tone manipulation WM task and a control group with a challenging perceptual task of pitch pattern discrimination. Functional magnetic resonance imaging (fMRI) scans confirmed that pretraining, manipulation was associated with a dorsal fronto-parietal WM network, while pitch comparison was associated with activation of ventral auditory regions. Training induced improvement in each group, which was limited to the trained task. Analyzing the behavior of the group trained with tone manipulation revealed that participants learned to replace active manipulation with a perceptual verification of the position of a single salient tone in the sequence presented as a tentative reply. Posttraining fMRI scans revealed modifications in ventral activation of both groups. Successful WMtrained participants learned to utilize auditory regions for the trained task. These observations suggest that the huge task-specific enhancement of WM capacity stems from a task-specific switch to perceptual routines, implemented in perceptual regions.
Catabolism of sialic acids in an environmental microbial community
Authors: Tomás-Martínez Sergio , Chen Le Min , Neu Thomas R , Weissbrodt David G , van Loosdrecht Mark C M , Lin Yuemei
Published: April 2022

Sialic acids are a family of nine-carbon negatively charged carbohydrates. In animals, they are abundant on mucosa surfaces as terminal carbohydrates of mucin glycoproteins. Some commensal and pathogenic bacteria are able to release, take up and catabolize sialic acids. Recently, sialic acids have been discovered to be widespread among most microorganisms. Although the catabolism of sialic acids has been intensively investigated in the field of host–microbe interactions, very limited information is available on microbial degradation of sialic acids produced by environmental microorganisms. In this study, the catabolic pathways of sialic acids within a microbial community dominated by ‘Candidatus Accumulibacter’ were evaluated. Protein alignment tools were used to detect the presence of the different proteins involved in the utilization of sialic acids in the flanking populations detected by 16S rRNA gene amplicon sequencing. The results showed the ability of Clostridium to release sialic acids from the glycan chains by the action of a sialidase. Clostridium and Chryseobacterium can take up free sialic acids and utilize them as nutrient. Interestingly, these results display similarities with the catabolism of sialic acids by the gut microbiota. This study points at the importance of sialic acids in environmental communities in the absence of eukaryotic hosts.
Theory-based implementation of physical activity programs in worksite health promotion settings: a systematic review
Authors: Grønningsæter Hilde , Kiland Charlotte
Published: April 2022

Worksites are important settings for implementing health promotion programs. Evidence for sustainable upscaling of physical activity (PA) programs and critical evaluation of the implementation process are scarce. In this article, we address the following research questions: (i) To what extent is the implementation process of PA programs theoretically informed? (ii) What characterizes the implementation process of PA programs in theory driven studies? (iii) Which facilitators and barriers are identified in the implementation process and at what level? We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The databases Medline (Ovid) and Sportdiscuss (Ebsco) were searched for peer-reviewed original articles published in English (2000–2020), from a European, North American, New Zealand and Australian context. Reported implementation components and facilitators/barriers (F/Bs) were detected, interpreted and analyzed according to implementation theory. Appraisal of methodological quality on included studies was executed. Of 767 eligible studies, 17 studies were included, 11 of which conducted a theory-based process evaluation of the implementation. They implemented composite PA programs, at two or more levels with internal or mixed implementation teams. F/Bs were most frequently related to the implementation component ‘fidelity’, corresponding to organizational and implementer level, and the component ‘reach’ corresponding to program and participant level. Notably, only one study reported F/Bs on the socio-political level. Despite more frequent use in recent years of theory-based implementation, few studies reported implementation effectiveness. Major challenges regarding incoherent use of theoretical concepts and scarcity of empirically tested frameworks are discussed.
Evaluating ecosystem impacts of gear regulations in a data-limited fishery—comparing approaches to estimate predator–prey interactions in Ecopath with Ecosim
Authors: Rehren Jennifer , Coll Marta , Jiddawi Narriman , Kluger Lotta Clara , Omar Omar , Christensen Villy , Pennino Maria Grazia , Wolff Matthias
Published: April 2022

Ecosystem models, such as Ecopath with Ecosim (EwE), are useful tools for developing ecosystem-based management strategies. Model development, however, requires data for the estimation of input parameters including time series for calibration. Most small-scale fisheries lack such information, making it difficult to reliably use ecosystem models for management strategy exploration. This is the case for the Chwaka Bay fishery (Zanzibar), where an increase in dragnets has led to concerns for unsustainable development. While EwE could help to explore the impacts of gear regulations in the bay, this is hampered by the lack of time series to estimate the predator–prey interactions (vulnerabilities) in the model. Here, we explore available approaches for estimating the vulnerabilities to simulate the effects of a dragnet prohibition with and without reallocation of fishing effort. Simulations suggest that banning dragnets would be beneficial for the fishing community judged by the increase in biomass of functional groups and fishers’ profits, but not if dragnet fishers were to continue fishing in the bay by reallocating to other gears, indicated by the reduced fish biomass and fishers’ profits. The overall trend (decreasing or increasing) in the changes of functional groups, ecosystem indicators, and profits were relatively consistent across vulnerability settings, illustrating that an unfitted EwE model can be used for qualitative management strategy exploration.
High prevalence of straying in a wild brown trout (Salmo trutta) population in a fjord system
Authors: Källo Kristi , Baktoft Henrik , Kristensen Martin Lykke , Birnie-Gauvin Kim , Aarestrup Kim
Published: April 2022

Natal homing is a prevalent life-history strategy among salmonids. However, not all individuals return to their natal river, a behaviour known as straying. In this study, we investigated the prevalence of straying and its connection to different life-history characteristics in an anadromous brown trout (Salmo trutta) population. In total, 21 538 juvenile out-migrating brown trout were tagged with Passive Integrated Transponder (PIT) tags in two years. Individuals were grouped according to their developmental status (parr, pre-smolt, and smolt) at the time of out-migration to investigate the effect of such life-history characteristic on the likelihood of straying. High number of anadromous brown trout (36%) were detected in non-natal rivers. Individuals spending longer time at sea were less likely to stray. Additionally, the likelihood of straying was dependent on the developmental status during out-migration, with parr having lower likelihood to stray compared to pre-smolt and smolt. However, the latter is further dependent on length and timing of juvenile out-migration. These results indicate that straying is an inherent part of this anadromous brown trout population and it is influenced by several life-history characteristics at different life stages. This may have significant implications to genetic structure within and between populations and to population dynamics.
The fabrication and testing of a self-sensing MWCNT nanocomposite sensor for oil leak detection
Authors: Al-Bahrani Mohammed , Bouaissi Aissa , Cree Alistair
Published: April 2022

Oil spillage, due to either direct or indirect accidents, can cause major environmental and economic issues if not detected and remedied immediately. In this study, the unique properties of carbon nanotubes have shown a substantial sensing capability for such a purpose when incorporated into a nanostructured composite material. A high-efficiency self-sensing nanocomposite sensor was fabricated by inserting highly conductive multi-walled carbon nanotubes (MWCNTs) into an elastomeric polymer substrate. The microstructure of the nanocomposite sensor was studied using scanning electronic microscopy and Raman spectroscopy. The response rate of the sensor was evaluated against different MWCNT concentrations, geometrical thickness and applied strains (causing by stretching). The results indicated that the response rate of the sensor (β) decreased with increasing MWCNT concentration and showed the strongest response when the sensor contained a 1.0 wt % concentration of MWCNTs. Additionally, it was found that the response time of the self-sensing nanocomposite sensors decreased in keeping with decreases in the sensor thickness. Moreover, when the sensor was subjected to strain, while immersed in an oil bath, it was found that the response rate (β) of the unstretched self-sensing nanocomposite sensor was significantly lower than that of the stretched one. The sensors given a 3% applied strain presented a response rate (β) ≈ 7.91 times higher than of the unstretched one. The self-sensing nanocomposite sensor described here shows good potential to be employed for oil leakage detection purposes due to its effective self-damage sensing capability and high sensing efficiency and low power consumption.
Pancreatic Ductal Carcinoma Risk Associated With Hereditary Cancer-Risk Genes
Authors: Gardiner Anna , Kidd John , Elias Maria C , Young Kayla , Mabey Brent , Taherian Nassim , Cummings Shelly , Malafa Mokenge , Rosenthal Eric , Permuth Jennifer B
Published: April 2022

Background

Although several hereditary cancer predisposition genes have been implicated in pancreatic ductal adenocarcinoma (PDAC) susceptibility, gene-specific risks are not well defined and are potentially biased because of the design of previous studies. More precise and unbiased risk estimates can result in screening and prevention better tailored to genetic findings.

Methods

This is a retrospective analysis of 676 667 individuals, 2445 of whom had a personal diagnosis of PDAC, who received multigene panel testing between 2013 and 2020 from a single laboratory. Clinical data were obtained from test requisition forms. Multivariable logistic regression models determined the increased risk of PDAC because of pathogenic variants (PVs) in various genes as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Multivariable odds ratios were adjusted for age, personal and/or family cancer history, and ancestry.

Results

Overall, 11.1% of patients with PDAC had a PV. Statistically significantly elevated PDAC risk (2-sided P < .05) was observed for CDK2NA (p16INK4a) (OR = 8.69, 95% CI = 4.69 to 16.12), ATM (OR = 3.44, 95% CI = 2.58 to 4.60), MSH2 (OR = 3.17, 95% CI = 1.70 to 5.91), PALB2 (OR = 3.09, 95% CI = 2.02 to 4.74), BRCA2 (OR = 2.55, 95% CI = 1.99 to 3.27), and BRCA1 (OR = 1.62, 95% CI = 1.07 to 2.43).

Conclusions

This study provides PDAC risk estimates for 6 genes commonly included in multigene panel testing for hereditary cancer risk. These estimates are lower than those from previous studies, possibly because of adjustment for family history, and support current recommendations for germline testing in all PDAC patients, regardless of a personal or family history of cancer.
Circular RNA hsa_circ_0026344 suppresses gastric cancer cell proliferation, migration and invasion via the miR-590-5p/PDCD4 axis
Authors: Lv Long , Du Jinghu , Wang Daorong , Yan Zeqiang
Published: April 2022

Objectives

Circular RNA (CircRNA) is a class of non-coding RNA transcripts, with multiple pathophysiological functions. Instead, the mechanism and function of circRNA in gastric cancer (GC) are not fully deciphered.

Methods

CircRNA_0026344 (circ_0026344), microRNA (miR)-590-5p and programmed cell death 4 (PDCD4) mRNA expression levels in GC tissues and cells were probed by quantitative real-time PCR. Cell viability, migration and aggressiveness were examined by cell counting kit-8 and transwell assays. Additionally, the interplay among circ_0026344, miR-590-5p and PDCD4 was verified with bioinformatics and dual-luciferase reporter gene assay. Western blot was conducted to probe PDCD4 protein expression.

Key findings

Circ_0026344 expression was underexpressed in GC tissues and cells, which was associated with clinicopathological characteristics such as tumour size, tumor-node-metastasis stage and lymph node metastasis. Circ_0026344 overexpression restrained the malignant biological behaviours of GC cells, while circ_0026344 knockdown functioned oppositely. Circ_0026344 could act as a competing endogenous RNA of miR-590-5p to negatively modulate its expression, and this miRNA could mitigate the impact of circ_0026344 on GC cells. In addition, PDCD4 was identified as the downstream target of miR-590-5p, and PDCD4 expression was positively modulated by circ_0026344.

Conclusions

Circ_0026344 up-regulates PDCD4 expression via sponging miR-590-5p, thus inhibiting the progression of GC. This study further expounds the underlying molecular mechanism in the GC progression.
Clinical outcomes of extended intralesional curettage with cementation without implant augmentation in non-fracture giant cell tumor of bone around the knee
Authors: Sukpanichyingyong Sermsak , Salang Krits , Sangkomkamhang Thananit
Published: April 2022

There remains a lack of consensus regarding the necessity of implant augmentation or fixation after intralesional curettage in giant cell tumor of bone (GCTB) around the knee. This study assessed whether cementation alone is effective and safe in GCTB with a non-fracture around the knee. We retrospectively examined clinical data from 14 GCTB patients treated from 2012 to 2022. Outcome parameters were Musculoskeletal Tumor Society (MSTS) score, postoperative fracture, metastases, recurrence and complications. Of the 14 GCTB cases examined, 10 were at the distal femur and four were at the proximal tibia. Mean patient age was 32 years, and follow-up time was 61 months. Mean tumor size was 61 × 79 × 50 mm, and MSTS score was 89.2%. There were no cases of postoperative fracture. Defect reconstruction with cementation alone may be strong enough to provide immediate stability and prevent postoperative fracture in GCTB around the knee.
Laparoscopic cholecystectomy for acalculous, gangrenous cholecystitis on an outpatient COVID-19 adult: a case report
Authors: Liapis Stavros Chrysovalantis , Stavrou Alexios , Perivoliotis Konstantinos , Christodoulou Prokopis , Kalodimos Georgios , Kitsakis Georgios , Kapatou Kassiani , Ziamas Dimitrios , Lytras Dimitrios
Published: April 2022

We report the rare case of an acalculous, gangrenous cholecystitis on a, previously healthy, outpatient COVID-19 adult. The 53-year-old patient presented to the emergency department due to epigastric pain and fever and was admitted to the COVID-19 department. Due to clinical and laboratory deterioration, a computed tomography scan was performed that confirmed the diagnosis of acalculous cholecystitis. The patient was submitted to laparoscopic cholecystectomy. Intraoperatively, a gangrenous gallbladder was identified. Immunohistology validated the presence of specimen wall vasculitis and vessel thrombosis.
The aberrant levels of decorin induce damages of human salivary gland epithelial cells and polarization of macrophages
Authors: Gao Rongfen , Tang Jungen , Dong Yuanji , Ming Bingxia , Yu Zhihua , Zhong Jixin , Dong Lingli
Published: April 2022

Objectives

This study aimed to preliminarily address the levels of decorin (DCN, a critical component of extracellular matrix) and its potential roles in primary Sjögren’s syndrome (pSS).

Methods

DCN levels were determined in the salivary glands of experimental SS (ESS) mice and pSS patients by RNA sequencing, bioinformatics analysis, or immunohistochemical staining. Its correlation with interested genes and co-localization with a putative receptor was studied in pSS patients. In addition, its potential roles on salivary gland epithelium and macrophages were tested by exogenous administration to corresponding cell lines, followed by the evaluation of apoptosis using flow cytometry or cytokine expression using quantitative real-time polymerase chain reaction.

Results

Our data revealed a significant elevation of DCN in the salivary glands of the ESS mice model and pSS patients. In addition, the bioinformatics analysis of DCN in the GSE40611 (RNA-seq, parotid glands) dataset displayed an elevation of the DCN level in the parotid glands of pSS patients that positively correlated with several chemokines (CXCL13, CXCL9, and CCL20), Interleukin -1 β (IL1 -β), and caspase3 but negatively correlated with the proliferation relative gene MKI67. The stimulatory effects of DCN on the salivary gland epithelial cells (A253 cell line) and macrophages have been determined as they are considered active participants in the progression of SS. The data showed that DCN induced the apoptosis of A253 cells and polarization of macrophages towards the M1 phenotype, characterized by the expression of pro-inflammatory cytokines.

Conclusions

Our study provided preliminary evidence to understand the clinical significance of DCN in pSS and broadened our horizons in understanding the mechanism of pSS.
A systematic comparison of FOSL1, FOSL2 and BATF-mediated transcriptional regulation during early human Th17 differentiation
Authors: Shetty Ankitha , Tripathi Subhash Kumar , Junttila Sini , Buchacher Tanja , Biradar Rahul , Bhosale Santosh D , Envall Tapio , Laiho Asta , Moulder Robert , Rasool Omid , Galande Sanjeev , Elo Laura L , Lahesmaa Riitta
Published: April 2022

Th17 cells are essential for protection against extracellular pathogens, but their aberrant activity can cause autoimmunity. Molecular mechanisms that dictate Th17 cell-differentiation have been extensively studied using mouse models. However, species-specific differences underscore the need to validate these findings in human. Here, we characterized the human-specific roles of three AP-1 transcription factors, FOSL1, FOSL2 and BATF, during early stages of Th17 differentiation. Our results demonstrate that FOSL1 and FOSL2 co-repress Th17 fate-specification, whereas BATF promotes the Th17 lineage. Strikingly, FOSL1 was found to play different roles in human and mouse. Genome-wide binding analysis indicated that FOSL1, FOSL2 and BATF share occupancy over regulatory regions of genes involved in Th17 lineage commitment. These AP-1 factors also share their protein interacting partners, which suggests mechanisms for their functional interplay. Our study further reveals that the genomic binding sites of FOSL1, FOSL2 and BATF harbour hundreds of autoimmune disease-linked SNPs. We show that many of these SNPs alter the ability of these transcription factors to bind DNA. Our findings thus provide critical insights into AP-1-mediated regulation of human Th17-fate and associated pathologies.
The Collapse of Infectious Disease Diagnoses Commonly Due to Communicable Respiratory Pathogens During the Coronavirus Disease 2019 Pandemic: A Time Series and Hierarchical Clustering Analysis
Authors: Zhang Ali , Surette Matthew D , Schwartz Kevin L , Brooks James I , Bowdish Dawn M E , Mahdavi Roshanak , Manuel Douglas G , Talarico Robert , Daneman Nick , Shurgold Jayson , MacFadden Derek
Published: April 2022

Background

Nonpharmaceutical interventions such as physical distancing and mandatory masking were adopted in many jurisdictions during the coronavirus disease 2019 pandemic to decrease spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We determined the effects of these interventions on incidence of healthcare utilization for other infectious diseases.

Methods

Using a healthcare administrative dataset, we employed an interrupted time series analysis to measure changes in healthcare visits for various infectious diseases across the province of Ontario, Canada, from January 2017 to December 2020. We used a hierarchical clustering algorithm to group diagnoses that demonstrated similar patterns of change through the pandemic months.

Results

We found that visits for infectious diseases commonly caused by communicable respiratory pathogens (eg, acute bronchitis, acute sinusitis) formed distinct clusters from diagnoses that often originate from pathogens derived from the patient’s own flora (eg, urinary tract infection, cellulitis). Moreover, infectious diagnoses commonly arising from communicable respiratory pathogens (hierarchical cluster 1: highly impacted diagnoses) were significantly decreased, with a rate ratio (RR) of 0.35 (95% confidence interval [CI], .30–.40; P < .001) after the introduction of public health interventions in April–December 2020, whereas infections typically arising from the patient’s own flora (hierarchical cluster 3: minimally impacted diagnoses) did not demonstrate a sustained change in incidence (RR, 0.95 [95% CI, .90–1.01]; P = .085).

Conclusions

Public health measures to curtail the incidence of SARS-CoV-2 were widely effective against other communicable respiratory infectious diseases with similar modes of transmission but had little effect on infectious diseases not strongly dependent on person-to-person transmission.
Survival Outcomes of Adjuvant Chemotherapy in Elderly Patients with Stage III Colon Cancer
Authors: Khalil Lana , Gao Xingyu , Switchenko Jeffrey M , Alese Olatunji B , Akce Mehmet , Wu Christina , Diab Maria , El-Rayes Bassel F , Shaib Walid L
Published: April 2022

Background

The survival impact of multi-agent (MAC) compared with single-agent (SAC) adjuvant chemotherapy (AC) in elderly patients with stage III colon cancer (CC) remains controversial. The aim of this study was to compare survival outcomes of MAC and SAC in this population utilizing the National Cancer Database (NCDB).

Patients and Methods

Patients aged ≥70 years with pathological stage III CC diagnosed in 2004-2015 were identified in the NCDB. Univariate and multivariable analyses were conducted, and Kaplan-Meier analysis and Cox proportional hazard models were used to identify associations between MAC vs. SAC and overall survival (OS).

Results

Among 41 707 elderly patients (≥70 years old) with stage III CC, about half (n = 20 257; 48.5%) received AC; the majority (n = 12 923, 63.8%) received MAC. The median age was 79 (range 70-90). The majority were female (n = 11 201, 55.3%), Caucasians (88%) and had moderately differentiated tumor grade (n = 12 619, 62.3%), tumor size >4 cm (11 785, 58.2%), and negative surgical margins (18 496, 91.3%). Low-risk stage III CC constituted 50.6% (n = 10 264) of the study population. High-risk stage III CC was associated with worse OS compared with low-risk disease (HR 0.35, 0.34-0.36, P < .001). Multi-agent chemotherapy was associated with a better 5-year OS compared with SAC (P < .001). High-risk stage III patients who received MAC vs. SAC had an OS of 4.2 vs. 3.4 years, respectively (P < .001). Low-risk stage III patients who received MAC vs. SAC had a median OS of 8.5 vs. 7 years (P < .001). In univariate and multivariable analyses, male sex, positive surgical margin, insurance and facility types, age, year of diagnosis, tumor size, and Charlson-Deyo score of >2 were associated with worse OS (P < .05).

Conclusions

Any adjuvant chemotherapy has a trend of survival benefits. Multi-agent chemotherapy seems to have an enhanced benefit in the 70-75 age group. Multi-agent chemotherapy seemed to have similar efficacy as SAC in those aged >76 years.
A kaleidoscope of photosynthetic antenna proteins and their emerging roles
Authors: Arshad Rameez , Saccon Francesco , Bag Pushan , Biswas Avratanu , Calvaruso Claudio , Bhatti Ahmad Farhan , Grebe Steffen , Mascoli Vincenzo , Mahbub Moontaha , Muzzopappa Fernando , Polyzois Alexandros , Schiphorst Christo , Sorrentino Mirella , Streckaité Simona , van Amerongen Herbert , Aro Eva-Mari , Bassi Roberto , Boekema Egbert J , Croce Roberta , Dekker Jan , van Grondelle Rienk , Jansson Stefan , Kirilovsky Diana , Kouřil Roman , Michel Sylvie , Mullineaux Conrad W , Panzarová Klára , Robert Bruno , Ruban Alexander V , van Stokkum Ivo , Wientjes Emilie , Büchel Claudia
Published: April 2022

Photosynthetic light-harvesting antennae are pigment-binding proteins that perform one of the most fundamental tasks on Earth, capturing light and transferring energy that enables life in our biosphere. Adaptation to different light environments led to the evolution of an astonishing diversity of light-harvesting systems. At the same time, several strategies have been developed to optimize the light energy input into photosynthetic membranes in response to fluctuating conditions. The basic feature of these prompt responses is the dynamic nature of antenna complexes, whose function readily adapts to the light available. High-resolution microscopy and spectroscopic studies on membrane dynamics demonstrate the crosstalk between antennae and other thylakoid membrane components. With the increased understanding of light-harvesting mechanisms and their regulation, efforts are focusing on the development of sustainable processes for effective conversion of sunlight into functional bio-products. The major challenge in this approach lies in the application of fundamental discoveries in light-harvesting systems for the improvement of plant or algal photosynthesis. Here, we underline some of the latest fundamental discoveries on the molecular mechanisms and regulation of light harvesting that can potentially be exploited for the optimization of photosynthesis.
Update on the Role and Utility of Extracellular Vesicles in Hematological Malignancies
Authors: Bazzoni Riccardo , Tanasi Ilaria , Turazzi Nice , Krampera Mauro
Published: April 2022

Extracellular vesicles (EVs) are membrane-surrounded cellular particles released by virtually any cell type, containing numerous bioactive molecules, including lipids, proteins, and nucleic acids. EVs act as a very efficient intercellular communication system by releasing their content into target cells, thus affecting their fate and influencing several biological processes. EVs are released both in physiological and pathological conditions, including several types of cancers. In hematological malignancies (HM), EVs have emerged as new critical players, contributing to tumor-to-stroma, stroma-to-tumor, and tumor-to-tumor cell communication. Therefore, EVs have been shown to play a crucial role in the pathogenesis and clinical course of several HM, contributing to tumor development, progression, and drug resistance. Furthermore, tumor EVs can reprogram the bone marrow (BM) microenvironment and turn it into a sanctuary, in which cancer cells suppress both the normal hematopoiesis and the immunological antitumor activity, conferring a therapy-resistant phenotype. Due to their physicochemical characteristics and pro-tumor properties, EVs have been suggested as new diagnostic biomarkers, therapeutic targets, and pharmacological nanocarriers. This review aims to provide an update on the pathogenetic contribution and the putative therapeutic utility of EVs in hematological diseases.
Timescales modulate optimal lysis–lysogeny decision switches and near-term phage reproduction
Authors: Shivam Shashwat , Li Guanlin , Lucia-Sanz Adriana , Weitz Joshua S
Published: April 2022

Temperate phage can initiate lysis or lysogeny after infecting a bacterial host. The genetic switch between lysis and lysogeny is mediated by phage regulatory genes as well as host and environmental factors. Recently, a new class of decision switches was identified in phage of the SPbeta group, mediated by the extracellular release of small, phage-encoded peptides termed arbitrium. Arbitrium peptides can be taken up by bacteria prior to infection, modulating the decision switch in the event of a subsequent phage infection. Increasing the concentration of arbitrium increases the chance that a phage infection will lead to lysogeny, rather than lysis. Although prior work has centered on the molecular mechanisms of arbitrium-induced switching, here we focus on how selective pressures impact the benefits of plasticity in switching responses. In this work, we examine the possible advantages of near-term adaptation of communication-based decision switches used by the SPbeta-like group. We combine a nonlinear population model with a control-theoretic approach to evaluate the relationship between a putative phage reaction norm (i.e. the probability of lysogeny as a function of arbitrium) and the extent of phage reproduction at a near-term time horizon. We measure phage reproduction in terms of a cellular-level metric previously shown to enable comparisons of near-term phage fitness across a continuum from lysis to latency. We show the adaptive potential of communication-based lysis–lysogeny responses and find that optimal switching between lysis and lysogeny increases the near-term phage reproduction compared to fixed responses, further supporting both molecular- and model-based analyses of the putative benefits of this class of decision switches. We further find that plastic responses are robust to the inclusion of cellular-level stochasticity, variation in life history traits, and variation in resource availability. These findings provide further support to explore the long-term evolution of plastic decision systems mediated by extracellular decision-signaling molecules and the feedback between phage reaction norms and ecological context.
Identification of Quinone Outside Inhibitor Fungicide-Resistant Isolates of Zymoseptoria tritici from Kentucky Wheat Fields
Authors: White Nathaniel H. , Bradley Carl A.
Published: April 2022

Soft red winter wheat (Triticum aestivum) production in Kentucky often utilizes no-till farming, a practice that can be favorable for fungal plant pathogens that overwinter in crop residue. One such pathogen, Zymoseptoria tritici, is the causal agent of Septoria tritici blotch and a prominent pathogen of wheat in Kentucky. The limitations of inoculum management and lack of fully resistant wheat cultivars increase the importance of foliar fungicide applications as a tool for management of Septoria tritici blotch. Quinone outside inhibitor (QoI) fungicides (Fungicide Resistance Action Committee, FRAC, Group 11) are one of the main classes of foliar fungicides used in wheat. A single mutation in the fungal cytochrome b gene can confer resistance to this class of fungicides. In this study, 79 Z. tritici isolates collected from 11 Kentucky counties during 2020 were screened for QoI resistance. Amplifying and sequencing a section of the cytochrome b gene spanning a section where mutations can occur that confer QoI resistance, revealed that 19 out of the 79 isolates tested (24.1%) had the G143A mutation. In vitro assays conducted on a small selection of isolates confirmed that isolates with the G143A mutation were resistant to QoI-fungicides. This study is the first to identify isolates of Z. tritici with the G143A mutation in Kentucky. Wheat producers in Kentucky and the surrounding areas should implement management practices that include rotating to nonhost crops, planting wheat cultivars with moderate resistance to Septoria tritici blotch and applying fungicides that contain active ingredients from other FRAC groups.
Opposite Beet Cyst Nematode Infection Phenotypes of Transgenic Arabidopsis Between Overexpressing GmSNAP18 and AtSNAP2 and Between Overexpressing GmSHMT08 and AtSHMT4
Authors: Zhao Jie , Duan Yukai , Kong Lingan , Huang Wenkun , Peng Deliang , Liu Shiming
Published: April 2022

The rhg1-a GmSNAP18 (an α-SNAP) and Rhg4 GmSHMT08 are two major cloned genes conferring soybean cyst nematode resistance in Peking-type soybeans, but the application of α-SNAPs and SHMTs in cyst nematode management remains elusive. In this study, GmSNAP18 and GmSHMT08, together with their orthologs in Arabidopsis, AtSNAP2 (an α-SNAP) and AtSHMT4, were individually transformed into Arabidopsis Col-0 to generate the transgenic lines, and the growth of transgenic plants, beet cyst nematode (BCN) infection phenotypes, and AtSNAP2, AtSHMT4, and AtPR1 expression patterns were analyzed using Arabidopsis−BCN compatible interaction system, in addition with protein−protein interaction assay. Pulldown and BiFC assays revealed that GmSNAP18 and GmSHMT08 interacted with AtSHMT4 and AtSNAP2, respectively. Plant root growth was not impacted by overexpression of GmSNAP18 and AtSNAP2. However, overexpression of GmSHMT08 and AtSHMT4 both increased plant height, additionally, overexpression of GmSHMT08 decreased rosette leaf size. Overexpression of GmSNAP18 and GmSHMT08 both suppressed AtPR1 expression and significantly enhanced BCN susceptibility, while overexpression of AtSNAP2 and AtSHMT4 both substantially boosted AtPR1 expression and remarkably enhanced BCN resistance, in transgenic Arabidopsis. Overexpression of GmSNAP18 reduced, while overexpression of AtSNAP2 unaltered AtSHMT4 expression. Overexpression of GmSHMT08 and AtSHMT4 both suppressed AtSNAP2 expression in transgenic Arabidopsis. Thus, different expression patterns of AtPR1 and AtSHMT4 are likely associated with opposite BCN infection phenotypes of Arabidopsis between overexpressing GmSNAP18 and AtSNAP2, and between overexpressing GmSHMT08 and AtSHMT4; and boosted AtPR1 expression are required for enhanced BCN resistance in Arabidopsis. All these results establish a basis for extension of α-SNAPs and SHMTs in cyst nematode management.
Technology-Enhanced CPD: Sailing Safely Through the COVID-19 Storm and Building a Better New Normal
Authors: Hlede Vjekoslav
Published: April 2022

COVID-19 has shocked our CME/CPD world and the broader educational system. It has activated existing semi-dormant forces, creating a perfect storm of changes. While the crisis will hopefully be over soon, other forces are here to stay. This paper discusses (1) the interaction between the newly emboldened forces, (2) strategies we can use to navigate through the COVID storm safely, and (3) how we can utilize all available forces to create long-lasting positive change in CME/CPD.