bluuebunny/crossref_metadata_2025 huggingface dataset:
Clustered transposon insertion via formation of chromatin loops
Authors: Prizak Roshan , Hilbert Lennart
Published: February 2022

Transposons, which are DNA sequences that can move to new positions in the genome, make up a large fraction of eukaryotic genomes and occur in clusters. The insertion of transposons into the genome is hindered by compact folding of chromatin, supposedly preventing aberrant or even pathogenic insertion. Chromatin can, however, be decompacted as a consequence of transposon insertion, leading to increased accessibility and, in consequence, further insertions. While these observations suggest a positive feedback between chromatin unfolding and transposon insertion, how such a feedback might contribute to clustered transposon insertion remains poorly understood. In this study, we analyze polymer models of a self-interacting chromatin domain that unfolds as increasing numbers of transposons are inserted and block the self-interaction. On the one hand, we find that, if additional transposons are inserted adjacently to already inserted transposons, the unfolding of the chromatin domain changes from a sharp globule-coil transition to a more gradual extension of loops from a core that remains folded. On the other hand, we find that adjacent transposon insertion emerges either when transposases are excluded from densely packed chromatin, or when transposon insertion proceeds very quickly in relation to the thermal equilibration of polymer configurations. We thus derive from our model physical conditions for clustered transposon insertion and the resulting spatial compartmentalization of chromatin. An according role was recently suggested for LINE-1 and Alu repeats, which occur in clusters and drive the mesoscopic compartmentalization of the mammalian genome.

Significance Statement

A large part of the genome is composed of repetitive sequences, so-called transposons. Transposons are involved in important processes, such as early embryonic development or control over which genes are used by the cell. Transposons frequently occur in clusters, where many similar sequence motifs are grouped together. Recent studies suggest that the insertion of transposons can result in local unfolding of the genome, favoring insertion of yet more transposons. Our work simulates a simplified region of the genome and transposases, which are the molecules that insert transposons into the genome. Surprisingly, large and fast-acting transposases favor the formation of distinct loops that contain most of the inserted transposons, providing a potential explanation for the clustered insertion of transposons.
ProBioQuest: a database and semantic analysis engine for literature, clinical trials, and patents related to probiotics
Authors: Chan Po Lam , Lauw Susana , Ma Ka Lee , Kei Nelson , Ma Ka Leong , Wong Yiu On , Lam Ho Yan , Ting Rina , Yau Tsz Kwan , Nong Wenyan , Huang Dandan , Xie Yichun , Keung Cheung Peter Chi , Kwan Hoi Shan
Published: February 2022

The use of probiotics to improve health via the modulation of gut microbiota has gained wide attention. The growing volume of investigations of probiotic microorganisms and commercialized probiotic products has created the need for a database to organize the health-promoting functions driven by probiotics reported in academic articles, clinical trials, and patents. Currently, no such database is available. We constructed ProBioQuest to collect up-to-date literature related to probiotics from PubMed.gov, ClinicalTrials.gov, and Patents View. More than 2.8 million articles were collected by the end of 2021: PubMed.gov: 2 656 818; Clinical Trials.gov: 205 349; Patents View: 32 536. Automated information technology-assisted procedures enabled us to collect the data continuously, providing the most up-to-date information. Statistical functions and semantic analyses are provided on the website as an advanced search engine, which contributes to the semantic tool of this database for information search and analyses. The semantic analytical output provides categorised search results and functions to enhance further analysis. A keyword bank is included which can display multiple tables of contents. Users can select keywords from different displayed categories to achieve easy filtered searches. Additional information on the searched items can be browsed via the link-out function. ProBioQuest is not only useful to scientists and health professionals, but also to dietary supplement manufacturers and the general public. In this paper, the method we used to build this database-web system is described. Applications of ProBioQuest for several literature-based analyses of probiotics are included as examples of the various uses to which this search engine can be put. ProBioQuest can be accessed free of charge at http://kwanlab.bio.cuhk.edu.hk/PBQ/.

Database URL

http://kwanlab.bio.cuhk.edu.hk/PBQ/
Biomechanical dependence of SARS-CoV-2 infections
Authors: Paul Alexandra , Kumar Sachin , Kaoud Tamer S. , Pickett Madison , Bohanon Amanda L. , Zoldan Janet , Dalby Kevin N. , Parekh Sapun H.
Published: February 2022

Older people have been disproportionately vulnerable to the current SARS-CoV-2 pandemic, with an increased risk of severe complications and death compared to other age groups. A mix of underlying factors has been speculated to give rise to this differential infection outcome, including changes in lung physiology, weakened immunity, and severe immune response. Our study focuses on the impact of biomechanical changes in lungs that occur as individuals age, i.e., the stiffening of the lung parenchyma and increased matrix fiber density. We used hydrogels with an elastic modulus of 0.2 and 50 kPa and conventional tissue culture surfaces to investigate how infection rate changes with parenchymal tissue stiffness in lung epithelial cells challenged with SARS-CoV-2 Spike (S) protein pseudotyped lentiviruses. Further, we employed electrospun fiber matrices to isolate the effect of matrix density. Given the recent data highlighting the importance of alternative virulent strains, we included both the native strain identified in early 2020 and an early S protein variant (D614G) that was shown to increase the viral infectivity markedly. Our results show that cells on softer and sparser scaffolds, closer resembling younger lungs, exhibit higher infection rates by the WT and D614G variant. This suggests that natural changes in lung biomechanics do not increase the propensity for SARS-CoV-2 infection and that other factors, such as a weaker immune system, may contribute to increased disease burden in the elderly.
Functional connectivity of the inferior frontal gyrus: A meta-analytic connectivity modeling study
Authors: Bulut Talat
Published: February 2022

Background

Neurocognitive models of language processing highlight the role of the left inferior frontal gyrus (IFG) in the functional network underlying language. Furthermore, neuroscience research has shown that IFG is not a uniform region anatomically, cytoarchitectonically or functionally. However, no previous study explored the language-related functional connectivity patterns of different IFG subdivisions using a meta-analytic connectivity approach.

Purpose

The present meta-analytic connectivity modeling (MACM) study aimed to identify language-related coactivation patterns of the left and right IFG subdivisions.

Method

Six regions of interest (ROIs) were defined using a probabilistic brain atlas corresponding to pars opercularis (BA44), pars triangularis (BA45) and pars orbitalis (Fo6&7) of IFG in both hemispheres. The ROIs were used to search the BrainMap functional database to identify neuroimaging experiments with healthy, right-handed participants reporting language-related activations in each ROI. Activation likelihood estimation analyses were then performed on the foci extracted from the identified studies to compute functional convergence for each ROI, which was also contrasted with the other ROIs within the same hemisphere. In addition, a behavioral analysis was conducted to determine functional specificity for language subdomains within each ROI.

Results

A primarily left-lateralized functional network was revealed for the left and right IFG subdivisions. The left IFG ROIs exhibited a more robust coactivation pattern than the right IFG ROIs. In particular, the left posterior-dorsal IFG (BA44) was associated with the most extensive coactivation pattern involving bilateral frontal, bilateral parietal, left temporal, left subcortical (thalamus and putamen), and right cerebellar regions, while the left anterior-ventral IFG (BA45 and Fo6&7) revealed a predominantly left-lateralized involvement of frontotemporal regions.

Conclusion

The findings align with the neurocognitive models of language processing that propose a division of labor among the left IFG subdivisions and their respective functional networks. Also, the opercular part of left IFG (BA44) stands out as a major hub in the language network with connections to diverse cortical, subcortical and cerebellar structures.
Reconstitution of 3′ end processing of mammalian pre-mRNA reveals a central role of RBBP6
Authors: Schmidt Moritz , Kluge Florian , Sandmeir Felix , Kühn Uwe , Schäfer Peter , Tüting Christian , Ihling Christian , Conti Elena , Wahle Elmar
Published: February 2022

The 3′ ends of almost all eukaryotic mRNAs are generated in an essential two-step processing reaction: endonucleolytic cleavage of an extended precursor followed by the addition of a poly(A) tail. By reconstituting the reaction from overproduced and purified proteins, we provide a minimal list of 14 polypeptides that are essential and two that are stimulatory for RNA processing. In a reaction depending on the polyadenylation signal AAUAAA, the reconstituted system cleaves pre-mRNA at a single preferred site corresponding to the one used in vivo. Among the proteins, cleavage factor I stimulates cleavage but is not essential, consistent with its prominent role in alternative polyadenylation. RBBP6 is required, with structural data showing it to contact and presumably activate the endonuclease CPSF73 through its DWNN domain. The C-terminal domain of RNA polymerase II is dispensable. ATP, but not its hydrolysis, supports RNA cleavage by binding to the hClp1 subunit of cleavage factor II with submicromolar affinity.
Development of assessment framework for environmental sustainability in higher education institutions
Authors: Menon Shalini , Suresh M.
Published: February 2022

Purpose

Unsustainable actions have resulted in the deterioration of the environment. Higher education institutions are social entities responsible for developing future leaders who have the skills and abilities to solve societal challenges. This study aims to develop a conceptual assessment model of environmental sustainability in higher education and apply the model to test the environmental sustainability level of a higher education institution.

Design/methodology/approach

The fuzzy logic method is used to develop the conceptual model, and a higher education institution in India was selected for evaluating the environmental sustainability level.

Findings

The fuzzy environmental sustainability index for the higher education institution selected for the study was computed as (3.58, 4.95, 6.33). The computed value identifies the institution as “environmentally sustainable”. The calculation of the fuzzy performance importance index further helped in identifying weak attributes that need improvement.

Research limitations/implications

The result of this study would help the management understand their current environmental sustainability level and take corrective measures to improve the weak attributes. It would also assist the institution in reworking its processes and practices.

Originality/value

This study has contributed to the literature of environmental sustainability assessment by creating a conceptual model for evaluating environmental sustainability in higher education. This model can be applied to any higher education institution.
Title: Intergenerational gaps in women’s grassroots peacebuilding in Ghana: a critique of “inclusive peacebuilding”
Authors: Paalo Sebastian Angzoorokuu
Published: February 2022

Purpose

The purpose of this paper is to examine the idea of inclusion in women’s bottom-up peacebuilding in Ghana. Inspired by the growing importance of “inclusion” and “local empowerment” in the discourse and practice of local ownership in peacebuilding, this paper seeks to investigate the scope and degree of inclusion of key actors such as women and youth, and how that affects peacebuilding and sustainable peace in some conflict-affected zones.

Design/methodology/approach

This study adopts a cross-sectional case study design and qualitative strategy. It is based on semi-structured interviews and focus group discussions conducted with actors who have been engaged in grassroots peacebuilding in Ghana and West Africa. The analysis was largely inductive, identifying emerging themes and patterns in the research data.

Findings

The findings indicate that young women are usually absent or not engaged meaningfully in the mobilization of women and youth in the “inclusive” grassroots peacebuilding in Ghana. This is due to the prevalence of deep-seated cultural and political prejudices or stereotypes about women in the areas studied. As these local constructs and thus practices are difficult to change or challenge, peacebuilding non-governmental organizations (NGOs) usually deploy innovative ways by mobilizing socially constructed women’s positionalities – as “whistleblowers,” “cross-ethnic/cross-cultural actors” and “socially networked actors” – in ways that promote women in contemporary peacebuilding discourses and practices. Through mobilizing these stereotypes (to forestall possible provocation, especially from dominant actors or gatekeepers), peacebuilding NGOs have subtly positioned women centrally within a vibrant peace infrastructure in Ghana. Yet, due to the dominance of some patriarchal sociopolitical structures, only older women and young men occupy the spaces for women and youth’s peacebuilding.

Originality/value

To the best of the author’s knowledge, this is one of the first research papers to question not only the scope but also the degree of inclusion and participation of women in peacebuilding in sub-Sahara Africa. This has nuanced scholarly debates on the subject and encouraged the development of innovative programmes targeted at a more comprehensive gendered and youth-ed inclusion to address the inequality gap in peacebuilding discourses and practices.
Lean R&D practices and its impact on organizational performance: evidence from R&D-based manufacturers in Malaysia
Authors: Tan Owee Kowang , Mohd Hamel Nabila , Ong Choon Hee , Goh Chin Fei , Rasli Amran
Published: February 2022

Purpose

The study aims to explore how lean research and development (R&D) tools and techniques (T&T: i.e. R&D hard practices) affect the relationship between lean R&D soft practices and organization performance within R&D-based manufacturing firms in Malaysia.

Design/methodology/approach

The current study is a quantitative study that utilized an online survey questionnaire for data collection. Data were collected based on a cross-sectional survey of R&D managers from 102 R&D-based manufacturing firms in Malaysia. Structural equation modeling (SEM) was used to test the impact of lean R&D soft and hard practices on firms' performance.

Findings

As per the study findings, it was determined that T&T of lean R&D was significant mediator in the relationship between lean R&D soft practices (i.e. managerial practices, transformational leadership, financial capability and supplier involvement) and R&D firms' performance.

Practical implications

The study delivers an important message to R&D companies that lean practices could be applied in R&D environments to drive organization performance.

Originality/value

The study extends the knowledge regarding lean principles and framework beyond the domains of production and services. The study offers new conceptual contribution in term of lean principles and framework in R&D environments by introducing the role of lean R&D tools and technique to enhance the effects of lean R&D practices on organization performance.
The TRISEC framework for optimizing conversational agent design across search, experience and credence service contexts
Authors: Blazevic Vera , Sidaoui Karim
Published: February 2022

Purpose

Service providers increasingly use conversational agents (CAs), such as chatbots, to effectively communicate with customers while managing interaction costs and providing round-the-clock customer service. Yet, the adoption and implementation of such agents in service contexts remains a hit-and-miss, and firms often struggle to balance their CAs implementation complexities and costs with relation to their service objectives, technology design and customer experiences. The purpose of this paper is to provide guidance on optimizing CA design, therefore, the authors develop a conceptual framework, TRISEC, that integrates service logic, technology design and customer experience to examine the implementation of CA solutions in search, experience and credence (SEC) contexts.

Design/methodology/approach

The paper draws on service marketing and communications research, combining the service context classification scheme of search, experience and credence and the technology infused service marketing triangle foci (service, technology and customer) in its conceptual development.

Findings

The authors find that an opportunity exists in recognizing the importance of context when designing CAs and aiming to achieve a balance between service objectives, technology design and customer experiences.

Originality/value

This study contributes to service management and communications research literature by providing interactive service marketing researchers with the highly generalizable TRISEC framework to aid in optimizing CA design and implementation in interactive customer communication technologies. Furthermore, the study provides an array of future research avenues. From a practical perspective, this study aims at providing managers with a means to optimize CA technology design while maintaining a balance between customer centricity and implementation complexity and costs in different service contexts.
Renewing models for change
Authors: Pregmark Johanna E.
Published: February 2022

Purpose

This paper aims to contribute to discussion around the need for improved models for change in a rapidly changing world. It also aims to provide insights for further discussion around how a Nordic management approach can relate to the need for new change ideas. Since Lewin proposed that change requires unfreezing, moving and refreezing, several changes in models have been introduced. Many models include similar factors such as the need for a vision, a clear process and to motivate change. These change factors are investigated in this paper and related to a fast-paced, uncertain and volatile environment

Design/methodology/approach

Based on a collaborative research approach, engaging with leaders in five organizations, all headquartered in the Nordic countries, this paper examines problems with traditional change models in a contemporary context as well as how these challenges could be handled.

Findings

This paper concludes that leaders still find value in traditional models but see that these models need to be adapted to include elements of more recent research. This paper suggests tweaks in traditional change factors and ends with a proposition with a renewed model for change.

Originality/value

The ideas in this paper could be seen as a bridge between traditional and modern models – a bridge that seems to be needed in practice. It draws on action research and close relationships with top management, as they are working with change – potentially giving the study a unique angle on a practical, widespread problem: succeeding with change
Parasite dynamics in North American monarchs predicted by host density and seasonal migratory culling
Authors: Majewska Ania A. , Davis Andrew K. , Altizer Sonia , de Roode Jacobus C.
Published: February 2022

Insect–pathogen dynamics can show seasonal and inter‐annual variations that covary with fluctuations in insect abundance and climate. Long‐term analyses are especially needed to track parasite dynamics in migratory insects, in part because their vast habitat ranges and high mobility might dampen local effects of density and climate on infection prevalence.

Monarch butterfliesDanaus plexippusare commonly infected with the protozoanOphryocystis elektroscirrha(OE). Because this parasite lowers monarch survival and flight performance, and because migratory monarchs have experienced declines in recent decades, it is important to understand the patterns and drivers of infection.

Here we compiled data onOEinfection spanning 50 years, from wild monarchs sampled in the United States, Canada and Mexico during summer breeding, fall migrating and overwintering periods. We examined eastern versus western North American monarchs separately, to ask how abundance estimates, resource availability, climate and breeding season length impact infection trends. We further assessed the intensity of migratory culling, which occurs when infected individuals are removed from the population during migration.

Average infection prevalence was four times higher in western compared to eastern subpopulations. In eastern North America, the proportion of infected monarchs increased threefold since the mid‐2000s. In the western region, the proportion of infected monarchs declined sharply from 2000 to 2015, and increased thereafter. For both eastern and western subpopulations, years with greater summer adult abundance predicted greater infection prevalence, indicating that transmission increases with host breeding density. Environmental variables (temperature and NDVI) were not associated with changes in the proportion of infected adults. We found evidence for migratory culling of infected butterflies, based on declines in parasitism during fall migration. We estimated that tens of millions fewer monarchs reach overwintering sites in Mexico as a result ofOE, highlighting the need to consider the parasite as a potential threat to the monarch population.

Increases in infection among eastern North American monarchs post‐2002 suggest that changes to the host’s ecology or environment have intensified parasite transmission. Further work is needed to examine the degree to which human practices, such as mass caterpillar rearing and the widespread planting of exotic milkweed, have contributed to this trend.
Vaccine hesitancy and emerging parental norms: A qualitative study in Taiwan
Authors: Kuan Chen‐I
Published: February 2022

This article reports a qualitative study on vaccine hesitancy in Taiwan. Based on its findings, this research illuminates the close relationships between expanding vaccine hesitancy and current parental norms. It answers the following questions: how do parents understand their roles and responsibilities regarding childhood vaccination under new parental norms? How do new parental norms interweave with other social contexts to shape parental practices of childhood vaccination? This research collected data from March 2018 to July 2020. This research observed lectures and activities concerning childhood vaccination organised by parental groups and interviewed 24 parents and three CDC professionals. Results show that ‘uniqueness of every child’, ‘informed decision‐making’ and ‘intensive parenthood’ are three essential elements in contemporary parental norms that significantly influence parents’ experiences regarding childhood vaccination. Under the norms, parents perceive their responsibility to inform themselves and make decisions most suitable for their children. Results also highlight the tension when health authorities failed to recognise new parental roles in childhood vaccination. The current lack of communication on childhood vaccination causes parents’ anxiety even among those who comply with vaccination policy. Health authorities and professionals should pay attention to new parental norms affecting people's childhood vaccination practices and develop suitable communication strategies.
Lay perceptions of modern prejudice toward “White” and “Asian” people: It matters who said it, whom it's about, and who's judging
Authors: Platow Michael J. , Van Rooy Dirk , Wang Chris , Ollis Lara , Knight Clinton G. , Blakey Parker , Calaby Pablo , Cho Haejung , Kim Jeongin , Naar Hayden , Oh Jordan Veng Thang , Stoney Corinne , Wilson‐Woolley Kate , Augoustinos Martha , Tal Daniel Bar , Spears Russell
Published: February 2022

We propose that part of the problem in combatting prejudice lies in people's dynamic understandings of what prejudice is. To examine this, we asked participants to rate the degree to which they perceived specific group‐relevant attitudes as prejudice. In Study 1, White participants perceived the attitudes as more prejudiced when the attitudes were targeted at Asian people than at White people and when expressed by an Anglo‐European speaker than by an Asian speaker. Study 2 was a direct replication but expanded the sample to include Asian participants. The Study 1 results were partially replicated in Study 2, although the target main effect was stronger among White than Asian participants. Together, the data suggest a normative legitimacy process in which injunctive norms dictate appropriate and inappropriate speakers and targets of specific group‐relevant attitudes. The data also confirm the original proposition of dynamic understandings of prejudice. Prejudice is understood by people not only by what is said but also by who is saying it and whom it is about. To the degree that these latter two variables are dynamic, then prejudice judgements themselves will remain so. We conclude by considering the implications of our data for both psychological theory and applications in prejudice‐reduction efforts.
Epithelial and sensory mechanisms of nasal hyperreactivity
Authors: Velasco Enrique , Delicado‐Miralles Miguel , Hellings Peter W. , Gallar Juana , Van Gerven Laura , Talavera Karel
Published: February 2022

“Nasal hyperreactivity” is a key feature in various phenotypes of upper airway diseases, whereby reactions of the nasal epithelium to diverse chemical and physical stimuli are exacerbated. In this review, we illustrate how nasal hyperreactivity can result from at least three types of mechanisms: (1) impaired barrier function, (2) hypersensitivity to external and endogenous stimuli, and (3) potentiation of efferent systems. We describe the known molecular basis of hyperreactivity related to the functional impairment of epithelial cells and somatosensory innervation, and indicate that the thermal, chemical, and mechanical sensors determining hyperreactivity in humans remain to be identified. We delineate research directions that may provide new insights into nasal hyperreactivity associated with rhinitis/rhinosinusitis pathophysiology and therapeutics. The elucidation of the molecular mechanisms underlying nasal hyperreactivity is essential for the treatment of rhinitis according to the precepts of precision medicine.
Bruton's tyrosine kinase inhibition—An emerging therapeutic strategy in immune‐mediated dermatological conditions
Authors: Mendes‐Bastos Pedro , Brasileiro Ana , Kolkhir Pavel , Frischbutter Stefan , Scheffel Jörg , Moñino‐Romero Sherezade , Maurer Marcus
Published: February 2022

Bruton's tyrosine kinase (BTK), a member of the Tec kinase family, is critically involved in a range of immunological pathways. The clinical application of BTK inhibitors for B‐cell malignancies has proven successful, and there is strong rationale for the potential benefits of BTK inhibitors in some autoimmune and allergic conditions, including immune‐mediated dermatological diseases. However, the established risk‐to‐benefit profile of “first‐generation” BTK inhibitors cannot be extrapolated to these emerging, non‐oncological, indications. “Next‐generation” BTK inhibitors such as remibrutinib and fenebrutinib entered clinical development for chronic spontaneous urticaria (CSU); rilzabrutinib and tirabrutinib are being studied as potential treatments for pemphigus. Promising data from early‐phase clinical trials in CSU suggest potential for these agents to achieve strong pathway inhibition, which may translate into measurable clinical benefits, as well as other effects such as the disruption of autoantibody production. BTK inhibitors may help to overcome some of the shortcomings of monoclonal antibody treatments for immune‐mediated dermatological conditions such as CSU, pemphigus, and systemic lupus erythematosus. In addition, the use of BTK inhibitors may improve understanding of the pathophysiological roles of mast cells, basophils, and B cells in such conditions.
ECG method for positioning the tip of peripherally inserted central catheters in patients with atrial fibrillation
Authors: Zhao Conghui , Zhu Yuxin , Yin Xinxin , Zhang Congcong , He Yingxia , Gao Jingfang
Published: February 2022

Objective

To observe the changes of F waves on electrocardiograms (ECGs) in patients with persistent atrial fibrillation during the insertion of a peripherally inserted central catheter (PICC), and to analyze the application effect of the ECG method (through F wave changes) for guiding PICC tip positioning.

Methods

Seventy‐two patients who met the inclusion criteria and needed a PICC catheter were selected as the research subjects. We observed waveforms in the ECGs when the tip of the catheter reached a predetermined position. The chest X‐ray results were used as the gold standard to calculate the sensitivity and specificity, and judge the safety and accuracy of ECG‐guided PICC tip positioning in patients with atrial fibrillation.

Results

Of the 72 patients, there was no significant difference between the ECG method and chest X‐ray results (χ2 = 0.2, p > 0.05). Sixty‐one patients had F wave changes on ECG and 10 had no obvious changes (X‐ray results confirmed that five patients had a tip position that was too shallow, two had ectopic tip positions, and three were located in the correct place). The sensitivity of the method was 95.7% and the specificity was 80%.

Conclusion

As the ECG baselines of patients with persistent atrial fibrillation were difficult to judge and the F wave was irregular, we found that the F wave was significantly higher than before catheter insertion and fell back while withdrawing the catheter, so the catheter should be fed until the F wave significantly increased as the correct position of the catheter tip.
Effects of pharmacist interventions on cardiovascular risk factors and outcomes: An umbrella review of meta‐analysis of randomized controlled trials
Authors: Rattanavipanon Wipharak , Chaiyasothi Thanaputt , Puchsaka Punyawee , Mungkornkaew Rachata , Nathisuwan Surakit , Veettil Sajesh K. , Chaiyakunapruk Nathorn
Published: February 2022

Aims

To grade the evidence from published meta‐analyses of randomized controlled trials (RCTs) that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes.

Methods

MEDLINE, Embase, and the Cochrane Library were searched from database inception to July 2021. Meta‐analyses of RCTs were eligible. Quality of evidence were assessed by GRADE approach.

Results

From 9308 publications, 149 full‐text articles were evaluated for eligibility, and 24 studies with 85 unique meta‐analyses that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes were selected. Overall, 71.7% (61/85) of unique meta‐analyses showed significant impacts of pharmacist intervention. For the quality of evidence, 63.4% of meta‐analyses had large heterogeneity (I2 > 50%) while 1.2, 16.5, 32.9 and 49.4% of meta‐analyses were graded as high, moderate, low and very low quality based on GRADE approach, respectively. Among meta‐analyses with moderate quality, pharmacist interventions significantly mitigated risk factors (including 6/3 mmHg reduction of blood pressure, increased the rate of lipid control, glucose control and smoking cessation (pooled odds ratio, [95% confidence interval] 1.91 [1.55, 2.35], 3.11 [2.3, 4.3] and 2.3 [1.33, 3.97], respectively) and improved medication adherence (1.67 [1.38, 2.02]). Furthermore, pharmacist interventions significantly reduced all‐cause mortality (0.72 [0.58, 0.89]) and improved quality of life in patients suffering from chronic heart failure.

Conclusion

This umbrella review found convincing evidence that pharmacist intervention can provide a wide range of benefits in cardiovascular disease management, ranging from risk factor control, improvement in medication adherence and, in some settings, reduction in morbidity and mortality.
An e‐Delphi study to obtain expert consensus on the level of risk associated with preventable e‐prescribing events
Authors: Heed Jude , Klein Stephanie , Slee Ann , Watson Neil , Husband Andy , Slight Sarah Patricia
Published: February 2022

Aims

We aim to seek expert opinion and gain consensus on the risks associated with a range of prescribing scenarios, preventable using e‐prescribing systems, to inform the development of a simulation tool to evaluate the risk and safety of e‐prescribing systems (ePRaSE).

Methods

We conducted a two‐round e‐Delphi survey where expert participants were asked to score pre‐designed prescribing scenarios using a five‐point Likert scale to ascertain the likelihood of occurrence of the prescribing event, likelihood of occurrence of harm and the severity of the harm.

Results

Twenty‐four experts consented to participate with 15 pand 13 participants completing rounds 1 and 2, respectively. Experts agreed on the level of risk associated with 136 out of 178 clinical scenarios with 131 scenarios categorised as high or extreme risk.

Conclusion

We identified 131 extreme or high‐risk prescribing scenarios that may be prevented using e‐prescribing clinical decision support. The prescribing scenarios represent a variety of categories, with drug–disease contraindications being the most frequent, representing 37 (27%) scenarios, and antimicrobial agents being the most common drug class, representing 28 (21%) of the scenarios. Our e‐Delphi study has achieved expert consensus on the risk associated with a range of clinical scenarios with most of the scenarios categorised as extreme or high risk. These prescribing scenarios represent the breadth of preventable prescribing error categories involving both basic and advanced clinical decision support. We will use the findings of this study to inform the development of the e‐prescribing risk and safety evaluation tool.
Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: A systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force
Authors: Miskowiak Kamilla W. , Seeberg Ida , Jensen Mette B. , Balanzá‐Martínez Vicent , del Mar Bonnin Caterina , Bowie Christopher R. , Carvalho Andre F. , Dols Annemieke , Douglas Katie , Gallagher Peter , Hasler Gregor , Lafer Beny , Lewandowski Kathryn E. , López‐Jaramillo Carlos , Martinez‐Aran Anabel , McIntyre Roger S. , Porter Richard J. , Purdon Scot E. , Schaffer Ayal , Stokes Paul , Sumiyoshi Tomiki , Torres Ivan J. , Van Rheenen Tamsyn E. , Yatham Lakshmi N. , Young Allan H. , Kessing Lars V. , Burdick Katherine E. , Vieta Eduard
Published: February 2022

Background

Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence‐based pro‐cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations.

Methods

The review included RCTs of candidate pro‐cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta‐Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials.

Results

We identified 16 RCTs (N = 859) investigating cognitive remediation (CR; k = 6; N = 311), direct current or repetitive magnetic stimulation (k = 3; N = 127), or pharmacological interventions (k = 7; N = 421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre‐screening for objective cognitive impairment, no primary outcome and no information on allocation sequence masking.

Conclusions

Evidence for pro‐cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre‐screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real‐world functioning, investigate multimodal interventions and include neuroimaging.
Characterisation of infections in patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent
Authors: On Sandy , Rath Carolyn G. , Lan Michelle , Wu Bobby , Lau Kimberly M. , Cheung Edna , Alegria William , Young Rebecca , Tan Marisela , Kim Carrie , Phun Jennifer , Patel Nimish , Mannis Gabriel , Logan Aaron C. , Kennedy Vanessa , Goodman Aaron , Taplitz Randy A. , Young Patricia A. , Wen Raymond , Saunders Ila M.
Published: February 2022

We investigated the incidence of invasive fungal infections (IFIs) and other infectious complications in patients receiving venetoclax and hypomethylating agent therapy for acute myeloid leukaemia (AML). This retrospective, multicentre cohort study included adult patients with AML who received at least one cycle of venetoclax and either azacitidine or decitabine between January 2016 and August 2020. The primary outcome was the incidence of probable or confirmed IFI. Secondary outcomes included antifungal prophylaxis prescribing patterns, incidence of bacterial infections, and incidence of neutropenic fever hospital admissions. Among 235 patients, the incidence of probable or confirmed IFI was 5.1%. IFI incidence did not differ significantly according to age, antifungal prophylaxis use, or disease status. In the subgroup of patients with probable or confirmed IFIs, six (50%) were receiving antifungal prophylaxis at the time of infection. The overall incidence of developing at least one bacterial infection was 33.6% and 127 (54%) patients had at least one hospital admission for febrile neutropenia. This study demonstrated an overall low risk of developing probable or confirmed IFI as well as a notable percentage of documented bacterial infections and hospital admissions due to neutropenic fever.
Unveiling the complexity and ecological function of aquatic macrophyte–animal networks in coastal ecosystems
Authors: Manca Federica , Mulà Clelia , Gustafsson Camilla , Mauri Achille , Roslin Tomas , Thomas David N. , Benedetti‐Cecchi Lisandro , Norkko Alf , Strona Giovanni
Published: February 2022

Network theory offers innovative tools to explore the complex ecological mechanisms regulating species associations and interactions. Although interest in ecological networks has grown steadily during the last two decades, the application of network approaches has been unequally distributed across different study systems: while some kinds of interactions (e.g. plant–pollinator and host–parasite) have been extensively investigated, others remain relatively unexplored. Among the latter, aquatic macrophyte–animal associations in coastal environments have been largely neglected, despite their major role in littoral ecosystems. The ubiquity of macrophyte systems, their accessibility and multi‐faceted ecological, economical and societal importance make macrophyte–animal systems an ideal subject for ecological network science. In fact, macrophyte–animal networks offer an aquatic counterpart to terrestrial plant–animal networks. In this review, we show how the application of network analysis to aquatic macrophyte–animal associations has the potential to broaden our understanding of how coastal ecosystems function. Network analysis can also provide a key to understanding how such ecosystems will respond to on‐going and future threats from anthropogenic disturbance and environmental change. For this, we: (i) identify key issues that have limited the application of network theory and modelling to aquatic animal–macrophyte associations; (ii) illustrate through examples based on empirical data how network analysis can offer new insights on the complexity and functioning of coastal ecosystems; and (iii) provide suggestions for how to design future studies and establish this new research line into network ecology.
Critical thermal limits in ants and their implications under climate change
Authors: Nascimento Geraldo , Câmara Talita , Arnan Xavier
Published: February 2022

Critical thermal limits (CTLs) constrain the performance of organisms, shaping their abundance, current distributions, and future distributions. Consequently, CTLs may also determine the quality of ecosystem services as well as organismal and ecosystem vulnerability to climate change. As some of the most ubiquitous animals in terrestrial ecosystems, ants are important members of ecological communities. In recent years, an increasing body of research has explored ant physiological thermal limits. However, these CTL data tend to centre on a few species and biogeographical regions. To encourage an expansion of perspectives, we herein review the factors that determine ant CTLs and examine their effects on present and future species distributions and ecosystem processes. Special emphasis is placed on the implications of CTLs for safeguarding ant diversity and ant‐mediated ecosystem services in the future. First, we compile, quantify, and categorise studies on ant CTLs based on study taxon, biogeographical region, methodology, and study question. Second, we use this comprehensive database to analyse the abiotic and biotic factors shaping ant CTLs. Our results highlight how CTLs may affect future distribution patterns and ecological performance in ants. Additionally, we identify the greatest remaining gaps in knowledge and create a research roadmap to promote rapid advances in this field of study.
Real‐world efficacy of treatment with benralizumab, dupilumab, mepolizumab and reslizumab for severe asthma: A systematic review and meta‐analysis
Authors: Charles David , Shanley Jemma , Temple Sasha‐Nicole , Rattu Anna , Khaleva Ekaterina , Roberts Graham
Published: February 2022

Background

Severe asthma is a major cause of morbidity. Some patients may benefit from biological therapies. Most evaluations of these treatments are derived from randomized controlled trials (RCTs), but few patients are eligible for these trials. Studies involving more diverse groups of participants exist, but there is a lack of precise pooled estimates.

Objective

This systematic review aims to evaluate the real‐world efficacy of recently and nearly licensed biological therapies for severe asthma to assess the generalizability of the RCT data.

Methods

Clinical outcomes including exacerbation rate, oral corticosteroid usage, forced expiratory volume in 1 second (FEV1) and fractional exhaled nitric oxide (FeNO) were examined. Studies were assessed for risk of bias using the Critical Appraisal Skills Programme checklist tool. The certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE).

Results

A total of 21 studies examining biologicals in real‐world settings were identified; they mostly focused on benralizumab and mepolizumab. The introduction of biologicals reduced the annualized exacerbation rate significantly by −3.79 (95% confidence interval [CI] −4.53, −3.04), −3.17 (95% CI −3.74, −2.59) and −6.72 (95% CI −8.47, −4.97) with benralizumab, mepolizumab and reslizumab, respectively. Likewise, improvements were observed in FEV1 (0.17 L 95% CI 0.11, 0.24) and FeNO (−14.23 ppb 95% CI −19.71, −8.75) following the treatment with mepolizumab. After treatment with benralizumab, there was an increase in FEV1 (0.21 L 95% CI 0.08, 0.34).

Conclusions

These data demonstrate that anti‐IL5 biologicals may improve the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs. The data were mainly retrospective and unadjusted, so estimated effect sizes may not be reliable. More data are needed to acquire accurate effect estimates in different subpopulations of patients.
Bone‐density testing interval and transition to osteoporosis in differentiated thyroid carcinoma patients on TSH suppression therapy
Authors: Park Hyunju , Park Jun , Yoo Heejin , Kim Seonwoo , Koh Jang Hyun , Jee Jae Hwan , Min Yong‐Ki , Chung Jae Hoon , Kim Tae Hyuk , Kang Mira , Kim Sun Wook
Published: February 2022

Objective

Thyrotropin (TSH) suppression therapy is a standard treatment after surgery for differentiated thyroid carcinoma (DTC). It may be associated with osteoporosis in postmenopausal women. However, there are no guidelines for bone mineral density (BMD) testing intervals to screen for osteoporosis in these patients. Therefore, we evaluated the timing of repeated BMD testing in DTC patients with TSH suppression according to baseline T‐scores.

Design, Patients, and Measurement

We retrospectively evaluated 658 DTC patients who underwent BMD testing more than twice between January 2007 and January 2020. A 1:3 propensity score matching was conducted to compare the timing of repeated BMD tests between the DTC and non‐DTC groups. We stratified the participants into four groups based on their baseline T‐scores: normal (−1.00 or higher), mild osteopenia (−1.01 to −1.49), moderate osteopenia (−1.50 to −1.99), and severe osteopenia (−2.00 to −2.49). Additionally, the 10% of patients in each group that transitioned to osteoporosis were analysed.

Results

The estimated BMD testing interval for 10% of patients who developed osteoporosis was 85 months for patients with initially mild osteopenia, 65 months for those with moderate osteopenia, and 15 months for those with severe osteopenia in the DTC group. In the non‐DTC group, the testing intervals for mild, moderate, and severe osteopenia were 98, 57, and 13 months, respectively. On multivariate analysis, baseline T‐score (mild osteopenia: hazard ratio [HR] 5.91, p = .105; moderate osteopenia: HR, 25.27, p = .02; and severe osteopenia: HR, 134.82, p < .001) and duration of TSH suppression (tertile 2: HR, 2.25, p = .005; Tertile 3: 1.78, p = .033) were independent risk factors for osteoporosis in the DTC group.

Conclusion

This study provides guidance for the timing of repeated BMD tests in women over 50 years of age with TSH suppression. The rescreening interval for BMD testing can be modified based on the baseline T‐score. The appropriate BMD testing intervals in female DTC patients were similar to those in non‐DTC females.