Previous Lists Research Articles

High-throughput untargeted metabolomics reveals metabolites and metabolic pathways that differentiate two divergent pig breeds

Metabolomics can describe the molecular phenome and may contribute to dissecting the biological processes linked to economically relevant traits in livestock species. Comparative analyses of metabolomic profiles in purebred pigs can provide insights into the basic biological mechanisms that may explain differences in production performances. Following this concept, this study was designed to compare, on a large scale, the plasma metabolomic profiles of two Italian heavy pig breeds (Italian Duroc, IDU, and Italian Large White, ILW) to indirectly evaluate the impact of their different genetic backgrounds on the breed metabolomes. We utilised a high-throughput untargeted metabolomics approach in a total of 962 pigs that allowed us to detect and relatively quantify 722 metabolites from various biological classes. The molecular data were analysed using a bioinformatics pipeline specifically designed for identifying differentially abundant metabolites between the two breeds in a robust and statistically significant manner, including the Boruta algorithm, which is a Random Forest wrapper, and sparse Partial Least Squares Discriminant Analysis (sPLS-DA) for feature selection. After thoroughly evaluating the impact of random components on missing value imputation, 100 discriminant metabolites were selected by Boruta and 17 discriminant metabolites (all included within the previous list) were identified with sPLS-DA. About half of the 100 discriminant metabolites had a higher concentration in one or the other breed (48 in Italian Large White pigs, with a prevalence of amino acids and peptides; 52 in Italian Duroc pigs, with a prevalence of lipids). These metabolites were from seven distinct super pathways and had an absolute mean value of percentage difference between the two breeds (|Δ|%) of 39.2±32.4. Six of these metabolites had |Δ|%>100. A general correlation network analysis based on Boruta identified metabolites consisted of 31 singletons and 69 metabolites connected by 141 edges, with two large clusters (>15 nodes), three medium clusters (3-6 nodes) and 8 additional pairs, with most metabolites belonging to the same super pathway. The major cluster representing the lipids super-pathway included 24 metabolites, primarily sphingomyelins. Overall, this study identified metabolomic differences between Italian Duroc and Italian Large White pigs explained by the specific genetic background of the two breeds. These biomarkers can explain the biological differences between these two breeds and can have potential practical applications in pig breeding and husbandry.

Kimboza, a Small Lowland Forest With an Outstanding Herpetofauna Diversity in East Africa.

The Eastern Arc Mountains (EAM) and Coastal forests of Tanzania are renowned for harboring large number of threatened and endemic vertebrate species, yet most of these areas have been partially studied. The Kimboza Nature Forest Reserve (KNFR) is a small forest which is in transition between the EAM and Coastal forests, and among the poorly surveyed areas for amphibians and reptiles. We conducted systematic surveys across the KNFR in 2012 and between 2020 and 2023 using a range of approaches with the aim of establishing a comprehensive and updated list of reptile and amphibian species and assess the contribution of EAM and Coastal forests to the KNFR's herpetofauna. We identified 77 species, 29 amphibians and 48 reptiles, substantially updating previous species lists. Three of these species (Kinyongia magomberae, Trachylepis boulengeri and Philothamnus macrops) represent range extensions from previously known ranges. Fourteen species are endemic to East Africa, 11 of them being restricted to Tanzania. These results make the KNFR the richest forest reserve for herpetofauna per square km in Tanzania, and most similar in its composition to the Coastal, rather than Eastern Arc forests. With the caveats concerning taxonomic uncertainties and the inequalities of sampling intensity across the region, this study shows that the KNFR is an important area that deserves conservation attention. The KNFR, like other Coastal forests, is under significant pressure from anthropogenic activities which call for an urgent action to protect this small but rich forest.

Frequency of Hebrew word usage by children with intellectual and developmental disabilities: implications for AAC core vocabulary

Appropriate vocabulary selection for augmentative and alternative communication (AAC) intervention is crucial to support communication and language development in children with intellectual and developmental disabilities (IDD). Core vocabulary lists are commonly used to guide this process, and there is a need for language-specific consideration. This paper aimed to develop a wordlist for selecting the core vocabulary for AAC intervention for young Hebrew-speaking children with IDD. Five children (age 3;5–8;4) were audio-recorded in naturalistic interactions with an interviewer and family members. Using Levy’s clinical corpus in the Child Language Data Exchange System (CHILDES) and Child Phonology Analyzer (CPA) tools and preestablished codes, wordlists with usage frequencies were extracted and coded for lexeme, lexical categories and functions or content. The percentages of the 20, 50, 100, and 200 most frequent lexemes were calculated for each child and for the five children combined. The top 200 most frequently used lexemes constituted 85% of the composite lexicon. A comparison was made between this study list and a previous list derived from language samples of typically developing (TD). Lexemes representing function words dominated, albeit with a slight preference for content words in children with IDD. Among the content words, children with IDD used more adverbs, while children with TD used more verbs. Implications for AAC core vocabulary are discussed.

Improving dictionary-based named entity recognition with deep learning.

Dictionary-based named entity recognition (NER) allows terms to be detected in a corpus and normalized to biomedical databases and ontologies. However, adaptation to different entity types requires new high-quality dictionaries and associated lists of blocked names for each type. The latter are so far created by identifying cases that cause many false positives through manual inspection of individual names, a process that scales poorly. In this work, we aim to improve block list s by automatically identifying names to block, based on the context in which they appear. By comparing results of three well-established biomedical NER methods, we generated a dataset of over 12.5 million text spans where the methods agree on the boundaries and type of entity tagged. These were used to generate positive and negative examples of contexts for four entity types (genes, diseases, species, and chemicals), which were used to train a Transformer-based model (BioBERT) to perform entity type classification. Application of the best model (F1-score = 96.7%) allowed us to generate a list of problematic names that should be blocked. Introducing this into our system doubled the size of the previous list of corpus-wide blocked names. In addition, we generated a document-specific list that allows ambiguous names to be blocked in specific documents. These changes boosted text mining precision by ∼5.5% on average, and over 8.5% for chemical and 7.5% for gene names, positively affecting several biological databases utilizing this NER system, like the STRING database, with only a minor drop in recall (0.6%). All resources are available through Zenodo https://doi.org/10.5281/zenodo.11243139 and GitHub https://doi.org/10.5281/zenodo.10289360.

Conceptualizing Barriers to Individual Recycling: A Qualitative Study with Multiple Stakeholders in Türkiye

ABSTRACT Increasing individual recycling rates is critical to achieving expected recycling targets. According to the social marketing approach promoting individual recycling behavior requires exploring, measuring, and managing the barriers that may deter individuals from recycling in a specific region. Although previous studies list some barriers, these barriers are likely to vary across studies, and clear conceptualizations are mostly missing. This study aims to explore and conceptualize the barriers to set a basis for future operationalization and systematic measurement. For this purpose, in-depth interviews were conducted with municipality authorities, representatives of leading environmental NGOs, and consumers in Türkiye. A total of 54 different first-level barriers were identified, and then first-level barriers were grouped thematically, revealing 20 second-level barriers, which are considered as personal, structural, social, or mediating barriers. Conceptual definitions for 20 second-level barriers are provided. The study also includes basic statistics regarding prominent barriers for different target groups.

Educational Assessment Knowledge and Skills for Teachers Revisited

In this article, I provide an update to a previous list of Educational Assessment Knowledge and Skills for Teachers. I argue that recent work in classroom assessment suggests expanding the list in several ways, adding additional statements about formative assessment’s connection to student learning and statements about assessment practices in their various contexts. This view of educational assessment knowledge and skills for teachers as contextual and situated was absent from the original 2011 list.

Distributed neighbor discovery with mobility adaptive probing for beyond 5G D2D communications

Representing a paradigm shift in cellular communication, Device-to-Device (D2D) Communication is an emerging technology that enables direct communication between two User Equipments(UEs) without going through the Base Station. It enables decentralization of cellular networks, enhances network capacity, increases spectral efficiency, and offloads network traffic. In order to proceed with direct D2D communication, the devices must have knowledge of the proximal devices and should work in all coverage scenarios such as in-coverage, partial-coverage and out-of-coverage. Most of the existing works on Device Discovery are based on 3GPP Model A and Model B. However, these schemes suffer from overhead of discovery message exchanges with the increase in the number of devices in a mobile environment. To address these issues, we propose a distributed and adaptive device discovery mechanism that can discover the proximal UEs in all possible scenarios. To achieve this, we propose a Hybrid Discovery Model ‘H’, which uses the concept of ‘Who are there?’. In Model ‘H’, the discoverer sends a single request message to discover all proximal devices. The responses of the proximal UEs are staggered based on the estimated number of neighbors to avoid collisions. In addition to that, we adapt the discovery mechanism to the relative mobility of the neighborhood using our proposed Adaptive Probing Algorithm named ‘ReMAP’. The relative mobility is determined based on the current and previous neighbor lists of each UE. The key advantage of our proposed mechanism is that we do not require the knowledge of position and mobility pattern of the UEs. We implement and evaluate our proposed work in D2D Module of the NS3 simulator. From the simulation results, we observe that our proposed model shows better performance in terms of the number of UEs discovered and reduced number of discovery message exchanges compared to the state-of-the-art. We also compare the performance of ReMAP with a constant probing mechanism and show the improvement in terms of adaptability to the mobility of the neighborhood.

In the Footsteps of Wolfgang Franke: Revisiting Chinese Temples in Bangkok

In the 19th and early 20th centuries, Chinese immigrants constituted up to 50% of the population in Bangkok. Beyond their religious role, Chinese temples served as community centers, fostering social connections, news exchange, and providing entertainment for newcomers in the Thai capital. With archival records scarce, the preserved epigraphy within these temples emerges as a crucial historical source. This article revisits Wolfgang Franke’s documented sites from the 1970s and 1980s, finding that the inscribed objects generally remain intact, and indicating stability in Bangkok’s Chinese temple culture over the last fifty years. Addressing the lack of a comprehensive listing of Chinese temples and their locations, the article presents a geo-referenced survey, significantly expanding previous lists. The survey data are available online as supplemental material, contributing to the documentation of Chinese religious sites in Southeast Asia. The article concludes by reflecting on the historical evolution of temple construction in Bangkok.

Inversion and Arabic Language DNA (LDNA) Theory: A Negative Dimensional (D-) Word-from-Word Approach

In this paper, the "Inter-Inversion and Language DNA (LDNA) Theory" is presented. Each Arabic letter has its symmetric letter in a DNA-like combination. The theory is very important in philology, the words' meanings, and development of a new language and/or dialect. It is a negative dimensional (D-) word-from-word approach (given a new term: lexical topology). The Language DNA (LDNA) process can be added, as the eighth process, to the previous list of the basic processes by which new words are created, and consequently, it is the compromising eighth source of the language. The inverted word gives the similar meaning of the original word. Some of the meanings are well-known, whereas the others were either used in the past and lost because of the natural selection law or were never known but might be used in the future. Additionally, it enriches the meaning of the word and may give extended negative dimensional meaning of the interpreted text.

An updated checklist of the amphibians and reptiles of Nayarit, Mexico with conservation status and comparison with adjoining States

Herein, we present an updated list of the species of amphibians and reptiles that inhabit Nayarit, Mexico. In the years since the publication of a previous list in 2016, threats to amphibians and reptiles in Nayarit have continued unabated and efforts to more fully catalogue the richness of Nayarit’s herpetofauna have continued. Nayarit harbours 162 native species of amphibians and reptiles, representing 35 families and 85 genera. These include 37 species of amphibians (35 anurans and two salamanders) and 125 species of reptiles (one crocodile, 44 lizards, 69 snakes and 11 turtles). Of the amphibian and reptile species in Nayarit, 102 are endemic to Mexico and two endemic to Nayarit. The ecoregion with the highest richness of amphibians and reptiles in Nayarit is the Trans-Mexican Volcanic Belt followed closely by the Sierra Madre Occidental and then the Sierra Madre del Sur, the Pacific Lowlands and the Nayarit Islands. Just 5.8% of the species of amphibians and reptiles in Nayarit is IUCN-listed as Vulnerable, Endangered or Critically Endangered, 11.1% are placed in a protected category by SEMARNAT and nearly a third are categorised as high risk by the Environmental Vulnerability Score. The herpetofauna of Nayarit overlaps the most with Jalisco (88.9%). One of the main conclusions of our updated list of the amphibian and reptile species of Nayarit is that our understanding of the full complement of species is not complete, especially the reptiles.

Pengembangan Bigbook Berbasis Metode Eja Pada Pelajaran Bahasa Indonesia Untuk Meningkatkan Minat Belajar Siswa Di Sekolah Dasar

The development of the Big Book based on the spelling method in Indonesian language lessons to increase students' interest in learning in elementary schools is based on the understanding that high interest in learning plays a crucial role in achieving learning. The aim of this research is to test the effectiveness of bigbook media based on the spelling method based on learning interest in elementary school students. The method used in this study uses a library research method or approach. Library research (library research) is research in which data collection is carried out by collecting data from various literature. This method is based on the previous page list which is often used initially, but this is also available, but the Ledger is available on both sides of the screen and visually which means it is in the right place. Just the same, a lot of people who have nothing to do with anyone else want to know what to do, but what's going on here.

Ants of Kamchatka: checklist, DNA-barcoding and key (Hymenoptera, Formicidae)

Kamchatka is a remote volcanic peninsula in the sub-arctic Far East of Russia. Its myrmecofauna has been scientifically addressed several times. However, previous species lists are contradictory in part and a modern study seems to be lacking. Based on literature review, I conclude that 12 species and 4 genera (Camponotus, Formica, Leptothorax and Myrmica) of ants may be native to Kamchatka. Of those, 9 were found in the field, 3 having a Holarctic, 3 a trans-Palearctic and 3 an East Palearctic distribution. Most species diversity was found at mid-elevations, in pine shrubs and mixed forests, while deciduous forests and open habitats at lower altitudes were surprisingly species poor. DNA-barcoding was performed for 57 specimens/9 species. Genetic diversity (COI) was low for 8/9 species, with the exception of Leptothorax acervorum, for which all samples were of a different haplotype and 2 haplogroups were identified. For the encountered Holarctic and trans-Palearctic species, closely related haplotypes (<0.7% raw distance) occur in Europe and/or North America. Some Formica ants were morphologically atypical, with workers partially resembling those of F. fusca, while gynes identified as F. lemani. Morphometric analysis and DNA-barcoding suggested that all these specimens belong to a single species, F. lemani. Standard images for all specimens and an illustrated key to the worker caste are provided.

Half of Atlantic reef-building corals at elevated risk of extinction due to climate change and other threats.

Atlantic reef-building corals and coral reefs continue to experience extensive decline due to increased stressors related to climate change, disease, pollution, and numerous anthropogenic threats. To understand the impact of ocean warming and reef loss on the estimated extinction risk of shallow water Atlantic reef-building scleractinians and milleporids, all 85 valid species were reassessed under the IUCN Red List Categories and Criteria, updating the previous Red List assessment of Atlantic corals published in 2008. For the present assessment, individual species declines were estimated based on the modeled coral cover loss (1989-2019) and projected onset of annual severe bleaching events (2020-2050) across the Atlantic. Species traits were used to scale species' relative vulnerability to the modeled cover declines and forecasted bleaching events. The updated assessments place 45.88%-54.12% of Atlantic shallow water corals at an elevated extinction risk compared to the previous assessments conducted in 2008 (15.19%-40.51%). However, coral cover loss estimates indicate an improvement in reef coverage compared to the historic time-series used for the 2008 assessments. Based on this, we infer that, although remaining dangerously high, the rate of Atlantic reef coral cover decline has surprisingly slowed in recent decades. However, based on modeled projections of sea-surface temperature that predict the onset of annual severe bleaching events within the next 30 years, we listed 26 (out of 85) species as Critically Endangered in the IUCN Red List. Each of these species had previously been listed under a lower threatened category and this result alone highlights the severe threat future bleaching events pose to coral survival and the reef ecosystems they support.

Challenges for Future Robotic Sorters of Mixed Industrial Waste: A Survey

To achieve recycling of mixed industrial waste toward an advanced sustainable society, waste sorting automation through robots is crucial and urgent. For this purpose, a robot is required to recognize the category, shape, pose, and condition of different waste items and manipulate them according to the category to be sorted. This survey considers three potential difficulties in the sorting automation: 1) End-effector: to robustly grasp and manipulate different waste items with dirt and deformations; 2) Sensor: to recognize the category, shape, and pose of existing objects to be manipulated and the wet and dirty conditions of their surfaces; and 3) Planner: to generate feasible and efficient sequences and trajectories. This survey includes 76 references to studies related to automatic waste sorting and 159 references to worldwide waste recycling attempts. This pioneering investigation reveals the possibility and limitations of conventional systems; thus, providing insights on open issues and potential technologies to achieve a robot-incorporated sorter for the chaotic mixed waste is one of its contributions. This paper further presents a system design policy for readers and discusses future advanced sorters, thereby contributing to the field of robotics and automation. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Note to Practitioners</i> —Most automated sorting systems operate for limited target waste items. This study is motivated by the automation of mixed industrial waste treatment facilities using advanced robotic sorters. Emerging advances and increasing functionalities of robot system components will widen system applicability and increase use cases in the chaotic mixed industrial waste domain. This paper surveys the research conducted to date, discusses open issues and potential approaches, and presents user guides that provide practitioners with a system design policy. The user guides created according to the strengths and weaknesses of each system configuration provide future researchers and developers with a useful a priori design policy that has been thus far validated on efficiency, quality, productivity, and reliability. A question-and-answer style guide and a sorting-target-aware previous study reference list allows users to find the desired system configuration, including the investigated components according to their purpose.

Autologous fat grafting and adipose-derived stem cells therapy for acute burns and burn-related scar: A systematic review.

The objective of this study was to analyze all available research on the application of autologous fat grafting (AFG) and adipose-derived stem cells (ADSC) to present evidence-based recommendations, particularly in the clinical treatment of acute burns and burn-related scars. We conducted a systematic search of PubMed, COCHRANE, and EMBASE, as well as a manual search of previous reviews' reference lists up. The risk of bias (RoB) was assessed using RoB 2.0 and ROBINS-I, where appropriate. Six eligible studies were selected (2 randomized clinical trials [RCT], 1 retrospective cohort, and 3 experimental studies) with subjects ranging from 3 to 100. Only one study evaluated the use of AFG for acute burns. Improvements in wound healing, vascularization, scar characteristics, and tissue architecture were generally observed in some studies, supported by molecular markers, while one study reported nonsignificant results. Subjective patient satisfaction was reported to have improved. Functional outcomes improvement in the treated regions was minimal. However, study heterogeneity arose mainly from treatment protocols. Cautious results interpretation due to potential bias, especially in selection and confounding domains, and limited clinical trials are important to note. More studies are needed to evaluate. AFG and ADSC hold potential as valuable treatment options for burn-related scars, supported by a body of evidence, but further well-designed RCT are needed. The efficacy of acute burn settings is yet to be further evaluated since evidence is limited.

An Updated Prioritization of Geroscience- Guided FDA-Approved Drugs Repurposed to Target Aging

The biological mechanisms of aging drive the development of chronic diseases such as cardiovascular disease, diabetes, dementia, and cancer that dominate our current medical system. Geroscience-guided approaches seek to mitigate these pathological consequences of aging by targeting the fundamental hallmarks of aging. Using modalities that modulate these aging mechanisms to reinforce longevity we can prevent the onset of these diseases as well as target many of them at once. In this way, geroscience-guided approaches hope to extend both lifespan and healthspan in the near future. This article builds upon a previous paper which proposed a standardized process for evaluating FDA-approved medications for their geroscience potential and prioritized them to reflect preclinical and clinical evidence. In this article, we provide an update of the previous list of candidate gerotherapeutics to reflect the new and rapidly evolving evidence. We include the geroscience-guided evidence for three new FDA-approved drugs which did not have strong arguments for inclusion before: bisphosphonates, GLP-1 receptor agonists, beta blockers. This updated prioritization should help guide the efforts and financial investments for translating geroscience and allow immediate progress involving such candidate gerotherapeutics, especially the top 4 drugs: SGLT2 inhibitors, metformin, bisphosphonates, and GLP-1 receptor agonists. Since all of these drugs have been approved for safety and used extensively, repurposing them as gerotherapeutics should be considered in older adults.

Assessing the conservation status of mangroves in Rakhine, Myanmar

Abstract Ecosystem degradation is a key challenge that human society faces, as ecosystems provide services that are tied to human well‐being. Particularly, mangrove ecosystems provide important services to communities but are suffering heavy degradation, loss and potential collapse due to anthropogenic activities. The IUCN Red List of Ecosystems is a transparent and consistent framework for assessing ecosystems' risk of collapse and is increasingly used to inform legislation and ecosystem management globally. Satellite data have become increasingly common in environmental monitoring due to their extensive spatial and temporal coverage. Here, recent advances in analyses using satellite‐derived data were implemented to reassess the conservation status of the ‘Rakhine mangrove forest on mud’, an important intertidal ecosystem in Myanmar, extending a previous national Red List assessment that assessed the ecosystem as Critically Endangered. By incorporating additional data sources and analyses, the extended assessment produced more robust results and reduced the uncertainty in the previous assessment. Overall, the ecosystem was assessed as Critically Endangered (range: Vulnerable to Critically Endangered) as a result of historical mangrove extent loss. Recent losses and biotic disruptions were also observed, which would have led to the ecosystem being assessed as Vulnerable. While the final outcome of the Red List assessment remained at Critically Endangered due to the historical state of the mangroves pre‐dating the temporal coverage from satellite data, the uncertainty of the ecosystem's status was reduced, and the reassessment highlighted the recent areal changes and mangrove degradation that has occurred. The importance of conducting reassessments when new data become available is discussed, and a template for future mangrove Red List assessments that use satellite data as their primary source of information to improve the robustness of their results is presented.

Continental fishes of Nicaragua: diversity, distribution and conservation status; with an annotated and illustrated checklist of species and an identification guide to families.

Based on a combination of intensive literature review, electronic database searches, re-identification of museum specimens, and fieldwork, we provide an updated checklist of the continental fishes of Nicaragua. This checklist, systematically arranged at the ordinal and familial level, includes nomenclatural revisions, distributional information, conservation status, and when appropriate, cross-references to previous lists and revisionary works on the fish fauna of the country and region (Central America); illustrations and descriptions to the family level and color photographs of some representative species are also included. According to our results, the native Nicaraguan continental fish fauna is composed of 244 species, divided into 111 genera, 45 families, 24 orders, and two classes; increasing by 60 (i.e., 32.6%) the number of species originally reported by Villa (1982; i.e., the most comprehensive work published to date). The majority of the Nicaraguan native continental fish species, according to their supposed tolerance to salinity, are peripheral (68.9%), followed by secondary freshwater fishes (23.8%), and primary freshwater fishes (only 7.4%). Fish diversity in the 19 major river basins ranged between 21 and 90 species (mean = 58 species, median = 60); the Escondido (Es; 87 species), in the Atlantic, and the Pacfico de Nicaragua (PN; 90), in the Pacific, presented the highest species richness. Most species (188) are restricted to elevations between 0 and 100 meters above sea level (masl); only a few species (18), in contrast, were found at elevations greater than 500 masl (up to 780 masl). Fourteen species in this revision are listed as endemic to Nicaragua. Regarding their conservation status, 22 species (9.0%) are categorized, according to the International Union for Conservation of Nature (IUCN), as Data Deficient, 186 (76.2%) as Least Concern, and seven (2.9%) as Near Threatened; while 24 species (9.8%) are listed as Threatened, thirteen (5.3%) as Vulnerable, two (0.8%) as Endangered, and nine (3.7%) as Critically Endangered. Five species (2.0%) have not yet been evaluated. Six exotic species are also reported. Our results provide a framework for future taxonomic and biogeographic works on fishes from this country and region (Central America), particularly by providing up-to-date knowledge on nomenclature and distributions. In addition, the data provided in this revision will help to monitor fish distributional changes in the future due to human introductions and global change and will aid in conservation decisions concerning Nicaraguan continental fishes.

Conditional versus non-conditional incentives to maximise return of participant completed questionnaires in clinical trials: a cluster randomised study within a trial

BackgroundHigh participant retention enhances the validity of clinical trials. A monetary incentive can increase retention, but it is not known if when it is provided and if it is conditional matters. We aimed to determine whether there was a difference in the number of follow-up trial questionnaires returned when a monetary (gift voucher) incentive was given to participants at recruitment (non-conditional), compared to informing participants at recruitment that the incentive would be given only once their 14-day daily diary (questionnaire) had been returned (conditional).MethodA cluster randomised study within a trial embedded within the Antivirals for influenza-Like Illness, An rCt of Clinical and Cost effectiveness in primary CarE (ALIC4E) Trial. Matched site pairs (GP practices) were randomised using computer-generated random numbers, to either a non-conditional or conditional monetary voucher incentive (only once their 14-day daily diary (questionnaire) had been returned. Sites were matched on previous recruitment levels and practice list size. Analyses were conducted according to randomised groups irrespective of compliance with a two-sided 5% level statistical significance level. The main analysis of the primary outcome (site proportion of diaries returned) was linear regression accounting for site pair (using cluster-robust variance). Additional weighted, paired and non-parametric sensitivity analyses were conducted. Secondary outcomes were the site average number of completed pages, time to return diary, and cost related to the incentive (administration and postage).ResultsOf the 42 randomised sites (21 for each intervention), only 28 recruited at least one participant with only 10 practice pairs recruiting participants at both constituent sites. Raw diaries return proportions were 0.58 (127/220) and 0.73 (91/125) for non-conditional and conditional incentive groups. Regression analysis adjusted for site pair showed no significant difference in returns, − 0.09, (95% CI, − 0.29, 0.10, p = 0.34); when weighted, there was still no clear difference: 0.15 (95% CI, − 0.02, 0.31, p = 0.07). There was no clear statistical evidence of a difference in time taken to return questionnaires, nor the proportion of pages completed, by the intervention group in the main analyses (all p > 0.05). The conditional incentive was approximately £23 cheaper per diary returned based upon observed data.ConclusionThere was no clear evidence of a statistically significant difference in the proportion of participant-completed diaries returned between conditional or non-conditional incentive groups. The time to questionnaire return and completeness of the returned questionnaires were similar in both groups. There was substantial statistical uncertainty in the findings. Some of the sensitivity analyses suggested that a meaningful benefit of a conditional incentive of a magnitude that would be meaningful was plausible. The conditional approach costs less in cash terms.

RNA-binding protein 14 promotes phase separation to sustain prostate specific antigen expression under androgen deprivation in human prostate cancer

Castration-resistant prostate cancer (CRPC) is a big challenge in managing prostate cancer patients. The androgen receptor (AR) pathway is a major driver even in CRPC under androgen deprivation. The mechanism in maintaining of the AR pathway under androgen deprivation remains elusive. The recent discovery of biomolecular condensate, a membrane-less intracellular construct formed by liquid-liquid phase separation (LLPS), that facilitate molecular assembly, encouraged the re-screening of our previous microarray data list. We selected Rbm14 as a target molecule for further analysis because it works as a coactivator of nuclear receptors as well as it facilitates formation of biomolecular condensates via its intrinsically disordered region. GFP-tagged Rbm14 transfected into HEK293T cells formed droplet-like puncta, which diminished following treatment with 1,6-hexanediol. Droplet-like structures were also observed in immunofluorescence for endogenous RBM14 of PC-3 and DU145 cells. Luciferase assay revealed that Rbm14 enhanced androgen-responsive element (ARE)-mediated reporter activity in all conditions with or without testosterone and AR. Co-immunoprecipitation confirmed the Rbm14–AR interaction. Long non-coding RNAs, including NEAT1, SRA1, and HOTAIR, were also interacted with Rbm14. Small interfering RNAs of NEAT1 reduced ARE-mediated reporter activity, while transfection of SRA1 and HOTAIR enhance the reporter activity. Treatment with 1,6-hexanediol as well as transfection with a dominant-negative splice variant of Rbm14 reduced expression of prostate specific antigen (PSA), a prototype of androgen-regulated gene, in LNCaP, PC-3, and DU145 cells under androgen deprivation. Immunohistochemically, RBM14 expression was substantially upregulated in prostate cancer tissues after androgen deprivation therapy than in untreated tumors. In conclusion, RBM14 is a novel factor involved in maintenance of PSA expression via phase separation under androgen deprivation in prostate cancer.