bluuebunny/crossref_metadata_2025 huggingface dataset:
Incorporating belowground traits: avenues towards a whole‐tree perspective on performance
Authors: Weemstra Monique , Kuyper Thomas W. , Sterck Frank J. , Umaña María Natalia
Published: June 2022

Tree performance depends on the coordinated functioning of interdependent leaves, stems and (mycorrhizal) roots. Integrating plant organs and their traits, therefore, provides a more complete understanding of tree performance than studying organs in isolation. Until recently, our limited understanding of root traits impeded such a whole‐tree perspective on performance, but recent developments in root ecology provide new impetuses for integrating the below‐ and aboveground. Here, we identify two key avenues to further develop a whole‐tree perspective on performance and highlight the conceptual and practical challenges and opportunities involved in including the belowground. First, traits of individual roots need to be scaled up to the root system as a whole to determine belowground functioning, e.g. total soil water and nutrient uptake, and hence performance. Second, above‐ and belowground plant organs need to be mechanistically connected to account for how they functionally interact and to investigate their combined impacts on tree performance. We further identify mycorrhizal symbiosis as the next frontier and emphasize several courses of actions to incorporate these symbionts in whole‐tree frameworks. By scaling up and mechanistically integrating (mycorrhizal) roots as argued here, the belowground can be better represented in whole‐tree conceptual and mechanistic models; ultimately, this will improve our estimates of not only the functioning and performance of individual trees, but also the processes and responses to environmental change of the communities and ecosystems they are part of.
Sarcopenia and cardiovascular risk indices: Its impact on cardiovascular events and mortality in dialysis patients
Authors: Baltacı Mehmet Akif , Atmis Volkan , Metin Yavuz , Aktar Merve , Eren Sayeste Akkan , Sengul Sule , Ates Kenan , Kutlay Sim
Published: June 2022

Background: Sarcopenia is a common complication in end‐stage renal disease. Low muscle strength and muscle mass are risk factors for cardiovascular disease and mortality in patients undergoing dialysis. We studied the relation between sarcopenia and pre‐atherosclerotic markers and its effect on cardiovascular events and death in dialysis patients. Methods: We measured muscle strength, muscle mass, carotid intima‐media thickness, and pulse wave velocity in 106 patients. Sarcopenia was diagnosed according to the EWGSOP‐2 suggestions. Patients with low muscle strength and low muscle mass were considered sarcopenic. The follow‐up period for cardiovascular events and mortality was 24 months. Results: The mean age and dialysis duration were 57.4 ± 16.6 and 6.5 ± 4.9 years, respectively. Of all patients, 53 (50%) were male and 70 (66%) were on hemodialysis treatment. Sarcopenia and low muscle strength were seen in 47.1% and 88.7%, respectively. Hemodialysis patients were more likely to be sarcopenic than peritoneal dialysis patients (p = 0.001). Ferritin and Kt/V levels were higher, and body mass index was lower significantly in sarcopenic patients (p < 0.001). There was no significant difference in carotid intima‐media thickness and pulse wave velocity measurements between the groups (p = 0.62 and p = 0.68, respectively). There was no statistically significant difference in cardiovascular events and mortality in cases with and without sarcopenia (p = 0.43 and p = 0.17, respectively). Conclusion: There was no association between sarcopenia and pre‐atherosclerotic markers, cardiovascular events, and all‐cause mortality in dialysis patients. Techniques to detect low muscle strength and muscle mass need standardization, and new specific cut‐off levels must be defined for dialysis patients.
Learning from Stoke‐on‐Trent: Multiple ontologies, ontological alterity and the city
Authors: Pile Steve
Published: June 2022

This paper seeks to learn from Stoke‐on‐Trent by asking questions about the ontologies of cities. It does so by counterposing two accounts of Stoke‐on‐Trent: one grounded in a critique of neoliberal urban development (or rather post‐industrial decline), and the other grounded in the experiences of Spiritualists. Placed side‐by‐side, Stoke‐on‐Trent demonstrates that cities accommodate more than one lived reality or mode of existence (ontology). The coexistence of multiple ontologies has been observed elsewhere, as a discussion of the work of Tariq Jazeel and Eduardo Viveiros de Castro shows. The important point, then, is that Stoke‐on‐Trent highlights the ontological heterogeneity of a city that seems to have only one story to tell: post‐industrial decline. This raises further questions: in part, about ontological alterity; in part, about the production of new ontologies; but, significantly, about the politics of coexisting ontologies – which ontologies count, and which do not.
Digital displacement: The spatialities of contentious politics in China's digital territory
Authors: Morris Carwyn
Published: June 2022

This paper conceptualises digital displacement as both a way through which the digital, dynamic and fragile spatialities of contentious politics can be examined and as a geographic critique of censorship. Digital displacement, understood here as the act of removing users from the digital places and spaces they wish to remain in and use, often through the act of deletion, is conceptualised through the digital displacement of two contentious political groups that attempted to contest the forced eviction of migrants from Beijing in 2017; hashtag focused #BeijingSurgery# and instant messaging group using BeijingTogether. Explored through participant observation, interviews and playful digital exploration, this paper examines the spatialities that made multiple digital displacements possible and the activist spatialities that emerged during and post‐displacement. In exploring this, I develop a flexible vocabulary around digital place, space, scale, territory and mobility to analyse the practices of digital displacement, to understand the socio‐spatial positionality of activists involved in digitally centred contentious politics and to contextualise their territorial positionality within Chinese digital territory and global digital territories. Through the examination of #BeijingSurgery# and BeijingTogether, the article highlights: the importance of digital territorial positionality for both activists and the digital places and spaces used for contentious politics; that within systems of digital spatial governance, deletion and displacement can be effective strategies of repressive governance with wide‐ranging displacement effects; and that while digital displacement is not necessarily the ending point of contentious politics, the re‐production of activist spatialities is more difficult when the authority being protested against governs the digital territory used for protest.
Critical Metaphor Analysis: A Systematic Step-by-step Guideline
Authors: Imani Aliakbar
Published: June 2022

Metaphor analysis is a growing field of research and has particularly gained popularity in discourse and critical discourse studies over the last two decades. This has led to various analytical frameworks proposed for metaphor analysis. However, the inherent subjectivity and complexity of metaphor analysis leaves space for a systematic and step-by-step guideline. Hence, this paper proposes a guideline composed of four levels, 16 main questions, and 29 sub-questions, adapted from the existing frameworks, particularly Charteris-Black’s (2004) Critical Metaphor Analysis. This guideline is by no means claimed to meet all requirements for an in-depth metaphor analysis; however, it can still be beneficial and valuable from many aspects such as providing a series of simplified easy-to-follow steps which can always be used as part of a more in-depth metaphor analysis.
Needs Analysis of English Language Use in Tourism Industry in Selangor, Malaysia
Authors: Kholidi Muh Azhar , Azhan Nurin Auni Syauqina , Ariawan Soni
Published: June 2022

English proficiency is required in all professional areas, but it has become essential in the tourist industry because of its specific characteristics. Needs analysis plays a vital role in developing the curriculum in English for specific purposes. This studyidentifies the needs and the problems of English language usage among the tourism industry employees in Selangor, Malaysia. The questionnaire was used as the primary data focusing on speaking, listening, reading, and writing skills. Utilising a descriptive research design, a total of 50 respondents were randomly selected for the study. The findings showed that in general, the respondents’ overall needs of English language skills were rated at a high level. Meanwhile, regarding the employees’ problems in using English at work were found at a moderate level. The problems encountered were less high compared to their English language needs. The necessities resonated what English skills are essentials for them to use in their job and to know the elements of each skill to be improved when they learn English. The implication of the findings will be helpful to develop and expand existing English for Tourism curriculum or ESP courses, particularly in Malaysia and Indonesia, to create a more effective English for tourism course based on the needs of the tourism industry employees in the future.
Investigating the Benefits of Video-making Projects in Developing English Communication Skills
Authors: Oleiwi Raghad , Bunari Ghazali
Published: June 2022

Project-based learning (PBL) is a learning method that is tested in many stages of education. Notably, video-making projects are frequently used to help English as Second Language (ESL) students actively apply the target language learned in the classroom to real-world situations.  However, only a few studies have discussed the use of video-making projects by undergraduate students as active learning assignments and their benefits in developing communication skills. Therefore, the objective of this study is to investigate students’ perceptions of the effects of video-making projects, a form of PBL on their English writing and speaking skills. A qualitative research design was conducted by interviewing students about their experiences with video-making projects. The participants of this study were 7 undergraduate students from the school of computer engineering at a Malaysian public university taking the required course titled English Communication Skills. The students were asked by their teacher to produce one video project as a requirement of the course. The data from the interviews were analyzed qualitatively. The findings of the study revealed that the students' attitudes towards the benefits and the use of video-making projects were overwhelmingly positive. They perceived that there were improvements in their English communication skills by gaining many new words, practicing better pronunciations, and using correct grammar. Consequently, it is strongly recommended to apply the video-making project in writing and speaking classes as an alternative way to enhance students’ writing and speaking abilities.
A Numerical Study of the Flow Field Driven by a Submerged, High-Speed, Gaseous Jet
Authors: Jana Amartya , Hoskoti Lokanna , Sucheendran Mahesh M.
Published: June 2022

The analysis of the numerical study of underwater high-speed gas jets is presented in this study. This work aims to understand the development of the flow structure of the gas jets submerged in water and assess the performance of the jet in terms of the thrust under varying operating conditions. The behavior of the submerged gas jet is studied under two operating parameters, namely, the pressure ratio (ratio of the pressure of the gas jet at the nozzle exit to ambient pressure) and the depth of water at which the propulsion takes place. The effort utilizes computational fluid dynamics using the finite volume method to solve the unsteady Reynolds-averaged Navier–Stokes equations in a two-dimensional axisymmetric domain combined with the mixture model for the multiphase flow. The unsteady behavior of different flow variables under varying operating parameters is discussed in detail. Further, the flow physics of a submerged supersonic gas jet is compared with a supersonic gas jet expanded in the air under a similar set of operating parameters. The effects of density difference between the gas and water have been studied from the comparative analysis.
Glacial ice supports a distinct and undocumented polar bear subpopulation persisting in late 21st-century sea-ice conditions
Authors: Laidre Kristin L. , Supple Megan A. , Born Erik W. , Regehr Eric V. , Wiig Øystein , Ugarte Fernando , Aars Jon , Dietz Rune , Sonne Christian , Hegelund Peter , Isaksen Carl , Akse Geir B. , Cohen Benjamin , Stern Harry L. , Moon Twila , Vollmers Christopher , Corbett-Detig Russ , Paetkau David , Shapiro Beth
Published: June 2022

Polar bears are susceptible to climate warming because of their dependence on sea ice, which is declining rapidly. We present the first evidence for a genetically distinct and functionally isolated group of polar bears in Southeast Greenland. These bears occupy sea-ice conditions resembling those projected for the High Arctic in the late 21st century, with an annual ice-free period that is >100 days longer than the estimated fasting threshold for the species. Whereas polar bears in most of the Arctic depend on annual sea ice to catch seals, Southeast Greenland bears have a year-round hunting platform in the form of freshwater glacial mélange. This suggests that marine-terminating glaciers, although of limited availability, may serve as previously unrecognized climate refugia. Conservation of Southeast Greenland polar bears, which meet criteria for recognition as the world’s 20th polar bear subpopulation, is necessary to preserve the genetic diversity and evolutionary potential of the species.
Design and printing of proprioceptive three-dimensional architected robotic metamaterials
Authors: Cui Huachen , Yao Desheng , Hensleigh Ryan , Lu Haotian , Calderon Ariel , Xu Zhenpeng , Davaria Sheyda , Wang Zhen , Mercier Patrick , Tarazaga Pablo , Zheng Xiaoyu (Rayne)
Published: June 2022

Advances in additive manufacturing techniques have enabled the creation of stimuli-responsive materials with designed three-dimensional (3D) architectures. Unlike biological systems in which functions such as sensing, actuation, and control are closely integrated, few architected materials have comparable system complexity. We report a design and manufacturing route to create a class of robotic metamaterials capable of motion with multiple degrees of freedom, amplification of strain in a prescribed direction in response to an electric field (and vice versa), and thus, programmed motions with self-sensing and feedback control. These robotic metamaterials consist of networks of piezoelectric, conductive, and structural elements interwoven into a designed 3D lattice. The resulting architected materials function as proprioceptive microrobots that actively sense and move.
A chemoenzymatic strategy for site-selective functionalization of native peptides and proteins
Authors: Fryszkowska Anna , An Chihui , Alvizo Oscar , Banerjee Goutami , Canada Keith A. , Cao Yang , DeMong Duane , Devine Paul N. , Duan Da , Elgart David M. , Farasat Iman , Gauthier Donald R. , Guidry Erin N. , Jia Xiujuan , Kong Jongrock , Kruse Nikki , Lexa Katrina W. , Makarov Alexey A. , Mann Benjamin F. , Milczek Erika M. , Mitchell Vesna , Nazor Jovana , Neri Claudia , Orr Robert K. , Orth Peter , Phillips Eric M. , Riggins James N. , Schafer Wes A. , Silverman Steven M. , Strulson Christopher A. , Subramanian Nandhitha , Voladri Rama , Yang Hao , Yang Jie , Yi Xiang , Zhang Xiyun , Zhong Wendy
Published: June 2022

The emergence of new therapeutic modalities requires complementary tools for their efficient syntheses. Availability of methodologies for site-selective modification of biomolecules remains a long-standing challenge, given the inherent complexity and the presence of repeating residues that bear functional groups with similar reactivity profiles. We describe a bioconjugation strategy for modification of native peptides relying on high site selectivity conveyed by enzymes. We engineered penicillin G acylases to distinguish among free amino moieties of insulin (two at amino termini and an internal lysine) and manipulate cleavable phenylacetamide groups in a programmable manner to form protected insulin derivatives. This enables selective and specific chemical ligation to synthesize homogeneous bioconjugates, improving yield and purity compared to the existing methods, and generally opens avenues in the functionalization of native proteins to access biological probes or drugs.
Structural basis of nucleosome retention during transcription elongation
Authors: Filipovski Martin , Soffers Jelly H. M. , Vos Seychelle M. , Farnung Lucas
Published: June 2022

In eukaryotes, RNA polymerase (Pol) II transcribes chromatin and must move past nucleosomes, often resulting in nucleosome displacement. How Pol II unwraps the DNA from nucleosomes to allow transcription and how DNA rewraps to retain nucleosomes has been unclear. Here, we report the 3.0-angstrom cryo–electron microscopy structure of a mammalian Pol II-DSIF-SPT6-PAF1c-TFIIS-nucleosome complex stalled 54 base pairs within the nucleosome. The structure provides a mechanistic basis for nucleosome retention during transcription elongation where upstream DNA emerging from the Pol II cleft has rewrapped the proximal side of the nucleosome. The structure uncovers a direct role for Pol II and transcription elongation factors in nucleosome retention and explains how nucleosomes are retained to prevent the disruption of chromatin structure across actively transcribed genes.
Upstart DNA sequencers could be a ‘game changer’
Authors: Pennisi Elizabeth
Published: June 2022

Increasing potential for fast, cheap genomes may break open biology’s bottleneck and broaden clinical uses
Mutant Prevention Concentrations of Ciprofloxacin and Levofloxacin and Target Gene Mutations of Fluoroquinolones in Elizabethkingia anophelis
Authors: Lin I-Fan , Lai Chung-Hsu , Lin Shang-Yi , Lee Ching-Chi , Lee Nan-Yao , Liu Po-Yu , Yang Chih-Hui , Huang Yi-Han , Lin Jiun-Nong
Published: June 2022

Fluoroquinolones are potentially effective against
Elizabethkingia anophelis
. We investigated the MIC, mutant prevention concentration (MPC), and target gene mutations of fluoroquinolones in
E. anophelis
.
S. cerevisiae Cells Can Grow without the Pds5 Cohesin Subunit
Authors: Choudhary Karan , Itzkovich Ziv , Alonso-Perez Elisa , Bishara Hend , Dunn Barbara , Sherlock Gavin , Kupiec Martin
Published: June 2022

Sister chromatid cohesion is vital for faithful chromosome segregation, chromosome folding into loops, and gene expression. A multisubunit protein complex known as cohesin holds the sister chromatids from S phase until the anaphase stage.
DNA Damage-Inducible Pyocin Expression Is Independent of RecA in
xerC
-Deleted Pseudomonas aeruginosa
Authors: Bronson Adam S. , Baggett Nina S. , Cabeen Matthew T.
Published: June 2022

The opportunistic pathogen
Pseudomonas aeruginosa
produces pyocins—intraspecific, interbacterial killing complexes. The canonical pathway for pyocin production involves DNA damage and RecA activation.
Formation of Iron Oxide Nanoparticles in the Internal Cavity of Ferritin-Like Dps Protein: Studies by Anomalous X-Ray Scattering
Authors: Shtykova Eleonora V. , Petoukhov Maxim V. , Mozhaev Andrey A.
Published: June 2022

DNA-binding protein from starved cells (Dps) takes a special place among dodecamer mini-ferritins. Its most important function is protection of bacterial genome from various types of destructive external factors viain celluloDps–DNA co-crystallization. This protective response results in the emergence of bacterial resistance to antibiotics and other drugs. The protective properties of Dps have attracted a significant attention of researchers. However, Dps has another equally important functional role. Being a ferritin-like protein, Dps acts as an iron depot and protects bacterial cells from the oxidative damage initiated by the excess of iron. Here we investigated formation of iron oxide nanoparticles in the internal cavity of the Dps dodecamer. We used anomalous small-angle X-ray scattering as the main research technique, which allows to examine the structure of metal-containing biological macromolecules and to analyze the size distribution of metal nanoparticles formed in them. The contributions of protein and metal components to total scattering were distinguished by varying the energy of the incident X-ray radiation near the edge of the metal atom absorption band (the K-band for iron). We examined Dps specimens containing 50, 500, and 2000 iron atoms per protein dodecamer. Analysis of the particle size distribution showed that, depending on the iron content in the solution, the size of the nanoparticles formed inside the protein molecule was 2 to 4 nm and the growth of metal nanoparticles was limited by the size of the protein inner cavity. We also found some amount of iron ions in the Dps surface layer. This layer is very important for the protein to perform its protective functions, since the surface-located N-terminal domains determine the nature of interactions between Dps and DNA. In general, the results obtained in this work can be useful for the next step in studying the Dps phenomenon, as well as in creating biocompatible and solution-stabilized metal nanoparticles.
Design and development of a clinical decision support system for community health workers to support early detection and management of non-communicable disease
Authors: Zaman Sojib Bin , Silva Nisal De , Goh Tian Yu , Evans Roger G , Singh Rajkumari , Singh Rajesh , Singh Akash , Singh Parul , Thrift Amanda G
Published: June 2022

Background

Numerous groups have developed software applications (apps) for use by community health workers (CHWs) in hard-to-reach settings. However, these have either not been based on clinical guidelines or are not freely available. Our objectives were to (1) design and develop an app for use by CHWs; and (2) conduct preliminary testing of the app to identify potential obstacles.

Methods

We used the principle of human-centred design to develop an app programmed to an Android operating system. We used a mixed-methods approach which included site observations, meetings with stakeholders and the app development team, and laboratory simulation to fine tune the design. The ‘Mobile Application Rating Scale’ (MARS) was used for testing reliability and quality. We also assessed the validity of the app by matching the uploaded data with ‘gold standard’ preset answers.

Results

Depending on human–computer interactions, the app has reminder, advisor, critic and guide functions which can facilitate CHWs to make clinical decisions. We found the app is usable based on the final score of the MARS tool, and that the entered data were accurate. We present the simple procedures that were followed to develop this Android app. The app, including all of its code, is freely available.

Conclusion

The app shows promise as a tool for the management of non-communicable disease in a rural setting in India. The next step will be to refine the app in a field setting and then to evaluate its efficacy in a large-scale clinical trial.
Protocol for a prospective quasi-experimental study on SARS-CoV-2 transmission during outdoor sports events in France: the COVID-ESO project
Authors: Elias Christelle , Nail-Billaud Sandrine , Basset Patrick , Laurent Frédéric , Dantony Emmanuelle , Fauvernier Mathieu , Roy Pascal , Vanhems Philippe
Published: June 2022

Introduction

The spread of SARS-CoV-2 and its variants in the community remains a major concern despite the application of control measures including the banning of mass sporting events. The circulation of SARS-CoV-2 within the general population, and potentially within the population practicing outdoor sports activities, suggests contexts conducive to the transmission of the virus. We hypothesise that outdoor sports events (OSEs) do not present a higher risk of SARS-CoV-2 contamination. The objective of the COVID-ESO project is to measure if individuals participating in OSE present a similar risk of SARS-CoV-2 transmission compared with individuals not participating in OSE, in France.

Methods and analysis

The COVID-ESO project is a prospective, quasi-experimental study to be conducted in volunteer individuals likely to participate in OSE. Six events are targeted across France to be included. Three sport trials will be eligible for the study: running, cycling and triathlon. Each individual participating in the OSE will choose one of his or her usual training partner to be eligible for the unexposed control group. Individuals will be matched (1:1) on age, sex and the district of residence. Individuals assigned to the exposed group will participate in the OSE, whereas individuals assigned to the unexposed group will not participate in the OSE. All individuals will be asked to perform saliva tests on the day of the event and 7 days after the event. A questionnaire including sociodemographic, clinical and exposure data to SARS-CoV-2 will be sent by email for both groups on the day before the event and 7 days after the event. Differences in SARS-CoV-2 infection rates between the exposed versus the unexposed group will be analysed by fitting a conditional logistic regression model, adjusted for potential confounders. As the sport events unfold, data will be analyzed by performing sequential meta-analyses.

Ethics and dissemination

This protocol has been approved by the ethical committee. Ethical approval has been obtained for the Clinical research and committee of South West of France, 10 June 2021. COMITE DE PROTECTION DES PERSONNES DU SUD-OUEST ET OUTRE-MER 4 under the reference number 21.03.23.71737/CPP2021-04-045 a COVID/2021-A00845-36. Findings generated from this study will be shared to national health and sport authorities.
Sharing information about domestic violence and abuse in healthcare: an analysis of English guidance and recommendations for good practice
Authors: Dheensa Sandi , Feder Gene
Published: June 2022

Background

Over two million adults experience domestic violence and abuse (DVA) in England and Wales each year. Domestic homicide reviews often show that health services have frequent contact with victims and perpetrators, but healthcare professionals (HCPs) do not share information related to DVA across healthcare settings and with other agencies or services.

Aim

We aimed to analyse and highlight the commonalities, inconsistencies, gaps and ambiguities in English guidance for HCPs around medical confidentiality, information sharing or DVA specifically.

Setting

The English National Health Service.

Design and method

We conducted a desk-based review, adopting the READ approach to document analysis. This approach is a method of qualitative health policy research and involves four steps for gathering, and extracting information from, documents. Its four steps are: (1) Ready your materials, (2) Extract data, (3) Analyse data and (4) Distill your findings. Documents were identified by searching websites of national bodies in England that guide and regulate clinical practice and by backwards citation-searching documents we identified initially.

Results

We found 13 documents that guide practice. The documents provided guidance on (1) sharing information without consent, (2) sharing with or for multiagency risk assessment conferences (MARACs), (3) sharing for formal safeguarding and (4) sharing within the health service. Key findings were that guidance documents for HCPs emphasise that sharing information without consent can happen in only exceptional circumstances; documents are inconsistent, contradictory and ambiguous; and none of the documents, except one safeguarding guide, mention how coercive control can influence patients’ free decisions.

Conclusions

Guidance for HCPs on sharing information about DVA is numerous, inconsistent, ambiguous and lacking in detail, highlighting a need for coherent recommendations for cross-speciality clinical practice. Recommendations should reflect an understanding of the manifestations, dynamics and effects of DVA, particularly coercive control.
Coprescribing of opioids and high-risk medications in the USA: a cross-sectional study with data from national ambulatory and emergency department settings
Authors: Suvada Kara , Zimmer Anna , Soodalter Jesse , Malik Jimi S , Kavalieratos Dio , Ali Mohammed K
Published: June 2022

Objective

Describe trends in opioid plus high-risk medication coprescribing in the USA.

Design

Analyses of serial, cross-sectional, nationally representative data of the National Ambulatory Medical Care Survey (NAMCS) over 2007–2016 and the National Hospital Ambulatory Medical Care Survey (NHAMCS) over 2007–2018.

Setting

US ambulatory (NAMCS) and emergency department (ED, NHAMCS) settings.

Participants

Patient visits in which the patient was 18 years and older with an opioid prescription in the NAMCS or NHAMCS databases.

Primary and secondary outcome measures

Frequency of opioid plus high-risk medication coprescribing.

Results

From a combined sample of 700 499 visits over 2007–2018, there were 105 720 visits (15.1%) where opioids were prescribed. n=31 825 were from NAMCS and n=73 895 were from NHAMCS. The mean prevalence of coprescription of opioids and high-risk medications for the combined NAMCS and NHAMCS sample was 18.4% in 2007, peaked at 33.2% in 2014 and declined to 23.8% in 2016. Compared with adults receiving opioid prescriptions alone, those coprescribed opioids and high-risk medications were older, more likely female, white and using private or Medicare insurance (p<0.0001).

Conclusions

Coprescribing is more common in ambulatory than ED settings and has been declining, yet one in four patient visits where opioids were prescribed resulted in coprescribed, high-risk medications in 2016. Efforts and research to help lower the rates of high-risk prescribing are needed.
Patient-reported outcome measures following surgeries in implant dentistry and associated factors: a cross-sectional study
Authors: Wu Xinyu , Ye Mengjie , Sun Jiahui , Yan Qi , Shi Bin , Xia Haibin
Published: June 2022

Objectives

We aimed to evaluate the patient-reported outcome measures (PROMs) of dental implant surgeries and analyse the associated indicators.

Design

A cross-sectional study design was used.

Setting

Department of Oral Implantology, Hospital of Stomatology, Wuhan University (May 2020–April 2021).

Participants

Participants with missing teeth in need of implant-supported rehabilitation.

Interventions

Dental implant placement and/or bone augmentation procedures.

Primary and secondary outcome measures

The primary outcome was discomfort on postoperative day 1, measured using a numerical rating scale (NRS). Secondary outcomes included pain and anxiety during surgery; discomfort on postoperative days 3, 7 and 14; and post-surgical complications.

Results

A total of 366 participants were included, of which 288 (78.7%) and 328 (89.7%) reported no to mild pain and anxiety (NRS 0–3) during surgery, respectively. The proportion of patients reporting discomfort decreased from postoperative day 1 (57.7%) to day 3 (36.1%) and day 7 (17.5%). The most frequent postoperative adverse events were pain and swelling. Patient-related factors (age, sex, smoking, alcohol consumption, history of periodontitis, and pain and anxiety during surgery) and surgery-related factors (type and extent of surgical procedure) were analysed. The factors associated with the severity of discomfort after surgery included alcohol consumption, pain perception during surgery, bone augmentation procedures and age (p<0.05). Similarly, the factors associated with the duration of discomfort included alcohol consumption, pain perception during surgery and age (p<0.05).

Conclusions

PROMs related to dental implant surgeries can be predicted using certain risk indicators. Alcohol consumption, pain during surgery and age were associated with discomfort following dental implant surgery.
Safety and tumour-specific immunological responses of combined dendritic cell vaccination and anti-CD40 agonistic antibody treatment for patients with metastatic pancreatic cancer: protocol for a phase I, open-label, single-arm, dose-escalation study (REACtiVe-2 trial)
Authors: Lau Sai Ping , van ’t Land Freek R , van der Burg Sjoerd H , Homs Marjolein Y V , Lolkema Martijn P , Aerts Joachim G J V , van Eijck Casper H J
Published: June 2022

Introduction

The prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) is dismal and conventional chemotherapy treatment delivers limited survival improvement. Immunotherapy may complement our current treatment strategies. We previously demonstrated that the combination of an allogeneic tumour-lysate dendritic cell (DC) vaccine with an anti-CD40 agonistic antibody resulted in robust antitumour responses with survival benefit in a murine PDAC model. In the Rotterdam PancrEAtic Cancer Vaccination-2 trial, we aim to translate our findings into patients. This study will determine the safety of DC/anti-CD40 agonistic antibody combination treatment, and treatment-induced tumour-specific immunological responses.

Methods and analysis

In this open-label, single-centre (Erasmus Univsersity Medical Center, Rotterdam, Netherlands), single-arm, phase I dose finding study, adult patients with metastatic pancreatic cancer with progressive disease after FOLFIRINOX chemotherapy will receive monocyte-derived DCs loaded with an allogeneic tumour lysate in conjunction with a CD40 agonistic antibody. This combination-immunotherapy regimen will be administered three times every 2 weeks, and booster treatments will be given after 3 and 6 months following the third injection. A minimum of 12 and a maximum of 18 patients will be included. The primary endpoint is safety and tolerability of the combination immunotherapy. To determine the maximum tolerated dose, DCs will be given at a fixed dosage and anti-CD40 agonist in a traditional 3+3 dose-escalation design. Secondary endpoints include radiographic response according to the RECIST (V.1.1) and iRECIST criteria, and the detection of antitumour specific immune responses.

Ethics and dissemination

The Central Committee on Research Involving Human Subjects (CCMO; NL76592.000.21) and the Medical Ethics Committee (METC; MEC-2021-0566) of the Erasmus M.C. University Medical Center Rotterdam approved the conduct of the trial. Written informed consent will be required for all participants. The results of the trial will be submitted for publication in a peer-reviewed scientific journal.

Trial registration number

NL9723.
Factors influencing participation in physical activity for persons living with dementia in rural and northern communities in Canada: a qualitative study
Authors: Freeman Shannon , Pelletier Chelsea , Ward Kirsten , Bechard Lauren , Regan Kayla , Somani Salima , Middleton Laura Elizabeth
Published: June 2022

Objective

In recognition that engagement in physical activities for persons living with dementia can be challenging in rural and northern communities, the objective of this study was to explore the factors influencing physical activity participation among persons living with dementia in rural/northern communities and to identify the locally-driven mitigation strategies participants used to address barriers to physical activity.

Setting

Interviews and focus groups were conducted in two locations in northern British Columbia, Canada including a rural community (<10 000 persons) and a medium-sized geographically isolated city (<80 000 persons). Both communities are located at substantial distances (>700 km) from larger urban centres.

Participants

Twenty-nine individuals participated including healthcare providers (n=8), community exercise professionals (n=12), persons living with dementia (n=4) and care partners (n=5).

Results

Rural and northern contextual factors including aspects of the built and natural environment were the main drivers of physical activity for persons living with dementia. Limited capacity in the health system to support physical activity due to a lack of referrals, poor communication mechanisms and limited resources for programming created challenges for physical activity participation. At the community level, local champions filled gaps in physical activity programming by leveraging informal networks to organise opportunities. Programme-level factors included a lack of consistency in staff, and challenges defining programme scope given limited population size and the fear of stigma for persons living with dementia.

Conclusions

Environmental context and limited access to specialised programming affect the opportunities for persons living with dementia to engage in physical activities. Rural and northern communities showed resiliency in providing physical activity opportunities yet remained fragile due to human resource challenges. Without reliable resources and sustained support from the health system, local champions remain vulnerable to burnout. Enhancing support for local champions may provide greater stability and support to physical activity promotion in rural and northern communities.
Understanding the development and function of the gut microbiota in health and inflammation
Authors: Selvakumar Deepak , Evans Dolan , Coyte Katharine Z , McLaughlin John , Brass Andy , Hancock Laura , Cruickshank Sheena
Published: June 2022

The gut microbiota is known to play an important role in maintaining gut health through a symbiotic relationship with the host. Altered gut microbiota is a common feature of several diseases of the gastrointestinal tract; however, the causal relationship between microbiota and disease pathogenesis is poorly understood. Necrotising enterocolitis (NEC) and inflammatory bowel disease (IBD) are both severe inflammatory diseases affecting the gastrointestinal tract. Although they affect very different patient populations, with NEC primarily being a disease of prematurity and IBD predominantly affecting adults although children can be affected, they both demonstrate common features of gut microbial dysbiosis and a dysregulated host immune response. By comparing and contrasting the changes in gut microbiota, host immune response and function, we aim to highlight common features in diseases that may seem clinically unrelated. Key areas of interest are the role of pattern recognition receptors in altered recognition and responses to the gut microbiota by the host immune system and the associated dysfunctional gut epithelial barrier. The challenge of identifying causal relationships between microbiota and disease is ever-present; however, considering a disease-agnostic approach may help to identify mechanistic pathways shared across several clinical diseases.
Characteristics and renal survival of patients with lupus nephritis with glomerular immunoglobulin G4deposition: a single-centre retrospective analysis
Authors: Jiang Xue , Lan Lan , Zhou Qin , Wang Huijing , Wang Huiping , Chen Jianghua , Han Fei
Published: June 2022

Objective

Renal injury is common in SLE. Immune complex deposition plays an important role in the development of lupus nephritis (LN), while little is known about glomerular IgG4deposition in patients with LN. This study aimed to investigate the characteristics and renal outcome of patients with LN with glomerular IgG4deposition.

Methods

This is a single-centre retrospective study enrolling 89 patients with biopsy-proven LN. Clinicopathological features, treatment responses and renal outcomes were collected and compared between patients with and without glomerular IgG4deposition. Renal outcome events include progression of renal dysfunction and end-stage renal disease.

Results

Thirty (33.7%) patients had glomerular IgG4deposition. Patients with glomerular IgG4deposition had lower serum albumin level (25.06±8.61 g/L vs 28.29±6.31 g/L, p=0.05), more class V LN (60.0% vs 35.6%, p=0.03), more positive phospholipase A2 receptor (PLA2R) staining (43.3% vs 18.6%, p=0.01), more IgG1deposits (96.7% vs 64.4%, p=0.01) and less C3 deposits (46.7% vs 72.9%, p=0.02) than those without glomerular IgG4deposition. They also had better renal survival than those without glomerular IgG4deposition (96.7% vs 79.7%, p=0.03). Multivariate Cox regression showed that high serum creatinine level (relative risk (RR)=1.005, 95% CI 1.002 to 1.008, p=0.01) and high Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores (RR=1.078, 95% CI 1.004 to 1.157, p=0.04) independently correlated with poor renal outcome, while glomerular IgG4deposition tended to correlate with good renal outcome (RR=5.95, 95% CI 0.759 to 45.97, p=0.09). Further, patients with both glomerular IgG4and PLA2R positivity (n=13) had higher levels of serum C3 and C4 and less glomerular C3 deposits compared with those with positive IgG4but negative PLA2R in the glomerulus (n=17), and had a tendency of low SLEDAI score (p=0.07).

Conclusions

Patients with LN with glomerular IgG4deposits may have better renal survival, and patients with LN with simultaneous glomerular IgG4and PLA2R deposits may have low disease activity.
Disease monitoring using lung function trajectory in lymphangioleiomyomatosis: assessment in two national cohorts
Authors: Johnson Jan , Stewart Iain , Johnson Simon R
Published: June 2022

Study question

In lymphangioleiomyomatosis, airflow obstruction and impairment of gas transfer progress at variable rates and serial lung function is recommended for disease monitoring. As these measurements are variable, recognising subjects needing treatment can be difficult. We used two prospective national cohorts to study change over time and variation in FEV1to inform clinical decision making.

Patients and methods

Clinical and lung function data for 141 UK and 148 American subjects were studied. Multilevel mixed effects modelling, route mean square analysis of errors and Bland-Altman analysis were used to analyse variability in lung function over time.

Results

At baseline assessment, DLCOwas reduced to a greater degree than FEV1. In untreated patients, FEV1and DLCOdeclined at proportionately similar rates independent of initial lung function. In mechanistic target of rapamycin (mTOR) inhibitor treated patients, FEV1stabilised but DLCOcontinued to decline. FEV1/DLCOper cent predicted ratio was 1.37 (0.43) at baseline and increased to 1.41 (0.50) after 42 (24) months (p=0.0002). At least five measurements were required before >70% of individuals had estimates of rate of FEV1loss within 50 mL/year and DLCOloss within 0.1 mmol/min/kPa/year of the final values.

Conclusions

While FEV1and DLCOfall proportionately in most, in early disease and during mTOR inhibitor treatment, DLCOshould also be monitored as it may fall independent of FEV1. Since at least five observations over many months are required to make confident estimates of FEV1and DLCOtrajectories, new strategies are needed to measure disease activity and target early treatment appropriately.
Environmental risks and sphingolipid signatures in adult asthma and its phenotypic clusters: a multicentre study
Authors: Wu Chao-Chien , Wang Chin-Chou , Chung Wen-Yu , Sheu Chau-Chyun , Yang Yi-Hsin , Cheng Ming-Yen , Lai Ruay-Sheng , Leung Sum-Yee , Lin Chi-Cheng , Wei Yu-Feng , Lin Ching-Hsiung , Lin Sheng-Hao , Hsu Jeng-Yuan , Huang Wei-Chang , Tseng Chia-Cheng , Lai Yung-Fa , Cheng Meng-Hsuan , Chen Huang-Chi , Yang Chih-Jen , Hsu Shih-Chang , Su Chian-Heng , Wang Chien-Jen , Liu Huei-Ju , Chen Hua-Ling , Hsu Yuan-Ting , Hung Chih-Hsing , Lee Chon-Lin , Huang Ming-Shyan , Huang Shau-Ku
Published: June 2022

Background

Adult asthma is phenotypically heterogeneous with unclear aetiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity.

Methods

Environmental risk was evaluated by assessing the records of National Health Insurance Research Database (NHIRD) and residence-based air pollution (particulate matter with diameter less than 2.5 micrometers (PM2.5) and PM2.5-bound polycyclic aromatic hydrocarbons (PAHs)), integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case–control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-distributed stochastic neighbor embedding (t-SNE) integrating 18 clinical and demographic variables.

Findings

In the NHIRD dataset, modest increase in the relative risk with time-lag effect for emergency (N=209 837) and outpatient visits (N=638 538) was observed with increasing levels of PM2.5and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH, posing a significant risk for current asthma (ORs=1.28–3.48) and its severity, correlating with the level of oxidative stress markers, notably Nε-(hexanoyl)-lysine (r=0.108–0.311, p<0.05), but not with the accumulated levels of PM2.5exposure. Further, levels of circulating sphingosine-1-phosphate and ceramide-1-phosphate were found to discriminate asthma (p<0.001 and p<0.05, respectively), correlating with the levels of PAH (r=0.196, p<0.01) and metal exposure (r=0.202–0.323, p<0.05), respectively, and both correlating with circulating inflammatory markers (r=0.186–0.427, p<0.01). Analysis of six phenotypic clusters and those cases with comorbid type 2 diabetes mellitus (T2DM) revealed cluster-selective environmental risks and biosignatures.

Interpretation

These results suggest the potential contribution of environmental factors from multiple sources, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity.
Effect of hydrogenated fat-embedded calcium gluconate on lactation performance in dairy cows
Authors: Seymour D.J. , McKnight L.L. , Carson M. , Sanz-Fernandez M.V. , Daniel J.B. , Metcalf J.A. , Martín-Tereso J. , Doelman J.
Published: June 2022

Hydrogenated fat-embedded calcium gluconate (HFCG), a prebiotic mixture designed to target the hindgut, has improved milk and component yields when supplemented in mid-lactation cows, likely due to improved hindgut health. The objective of this study was to evaluate production responses to HFCG when fed to dairy cattle over a full lactation. Seventy-four Holstein cows (21 primiparous, 53 multiparous) were used in a randomized complete block design comparing supplementation with HFCG (approximately 16 g/day supplement delivering approximately 6.4 g active ingredient) to a negative control from approximately 21 days prior to calving until end of lactation. In multiparous cattle supplemented with HFCG, average daily milk protein yield ( P = 0.037) was increased during the first 8 weeks of lactation, while average daily yields of milk fat, and fat- and energy-corrected milk tended ( P ≤ 0.075) to increase over the same period of time. Increased yields were likely supported by the concurrent increase in dry matter intake ( P = 0.036). Future work is needed to characterize the mode of action of this product within both the hindgut lumen and host, as well as investigate the potential differential responses between primiparous and multiparous animals over the course of lactation.