bluuebunny/crossref_metadata_2025 huggingface dataset:
It is worth taking a closer look: A field experiment on intergroup contact between Austrian pupils and refugees
Authors: Nägele Sophie , Corcoran Katja , Klocke Ulrich
Published: July 2023

Intergroup contact is an effective way to improve intergroup relations, but appropriate evaluative and field research is lacking. We assessed the short- and long-term effectiveness of intergroup contact between refugees and pupils with the workshop “Taking a Closer Look.” A total of 388 pupils from 11 Austrian schools were divided into two groups: the contact group attended the workshop including intergroup contact; and the no-contact group, without it. Intergroup contact predicted changes from 1 week before to immediately after the workshop: The pupils’ attitudes toward refugees improved in the contact group, whereas they remained unchanged in the no-contact group. Empathy, support for refugee-friendly policies, and willingness to engage in intergroup contact increased in both groups, but significantly stronger in the contact group. Intergroup anxiety decreased and knowledge about refugees increased equally in both groups. One month after the workshop, this knowledge gain remained stable in both groups, but the other effects disappeared.
Do people believe in misleading information disseminated via memes? The role of identity and anger
Authors: Molina Maria D.
Published: July 2023

Do people believe in misleading information disseminated via contemporary Internet memes? Do they believe in it more compared with information provided via text? This research explores these questions via a 3 (modality: contemporary internet meme vs text-only vs text-with-explanation) × 2 (identity-congruence: congruent vs incongruent) between-subject online experiment, using two contexts of investigation (crime and taxes). Findings indicate that identity-congruent posts (vs incongruent), regardless of modality, were perceived as more credible. These effects occurred due to the invocation of the self-identity heuristic (if content is similar to my identity, then it is automatically credible) and the other-identity heuristic (if content is similar to the identity of others in my network, then it is automatically credible). However, the effects of identity-congruent posts were diminished when the content was presented as a contemporary Internet meme (vs text). This occurred because identity-congruent posts in meme modality evoke anger.
Investigation of a GDI injector with an innovative flowmeter for high-pressure transient flows
Authors: Ferrari Alessandro , Pizzo Pietro , Vento Oscar
Published: July 2023

A new flowmeter for high pressure flows, characterized by intense dynamic events, is presented. The flowmeter algorithm is based on the measurement of two pressure signals along the investigated pipe, and the flowrate is obtained through an ordinary differential equation given by the combination of the continuity and the momentum partial differential equations. This flowmeter has been applied to a GDI injector to monitor the flowrate that enters the injector during an injection event. A 1D numerical model of the GDI injector has been set up and validated, and the numerical outcomes have been used to confirm the consistency of the experimental results obtained from the new flowmeter, for both single and pilot-main injections. The internal dynamics of the injector has also been investigated, using both the 1D numerical tool and the innovative flowmeter. A possible feedback-control strategy has been set up to compensate for any inaccuracy of the injected mass by applying the flowmeter to the hydraulic high-pressure circuit.
Skills and Competencies Gained From a Psychology Bachelor's Degree: European Graduates’ Perspectives
Authors: Papageorgi Ioulia , Falzon Nicola , Sokolova Lenka , Stuchlikova Iva , Salvatore Sergio , Williamson Morag , Foster Juliet , Pavlin-Bernardic Nina , Beara Mirjana , Bakker Helen , Dutke Stephan
Published: July 2023

Results from a survey conducted by the European Federation of Psychologists’ Associations Board of Educational Affairs are reported. A total of 227 psychology graduates from across Europe responded to an online survey. Participants were presented with a set of psychology subject-specific competencies and a set of general competencies and asked to rate the extent to which (a) their Bachelor studies supported the development of these competencies and (b) these competencies were relevant for employment as well as to comment on the value of a Psychology Bachelor degree. Findings suggest that an education in psychology develops psychological skills, but also graduates with more general competencies. Overall, psychological competencies appear to develop to a high level through the Bachelor in Psychology, with the exception of specific practical skills. On the contrary, general competencies appear to not develop to an adequate degree. Practical skills focusing on the administration of psychological tools, psychometric instruments and specialist software, as well as general competencies relating to computer literacy skills, communication skills and team-working skills should be further developed to prepare graduates adequately for employment. The study highlights the value of an education in psychology particularly for those individuals who do not wish to enter the applied psychology professions or academia.
Sleeping Healthy, Living Healthy: Using Iterative, Participatory Processes to Develop and Adapt an Integrated Sleep Hygiene/Mind-Body Integrative Health Intervention for Urban Adolescents
Authors: Garbers Samantha , Ancheta April J. , Gold Melanie A. , Maier Malia , Bruzzese Jean-Marie
Published: July 2023

Racial and ethnic minority adolescents living in urban settings experience sleep disparities. Few interventions have been developed to address these disparities. Guided by principles of participatory design and inclusion, our team developed a novel intervention that combined sleep hygiene education with mind-body integrative health (MBIH) practices to improve sleep quality among adolescents in New York City. The goal of this article is to describe our iterative development and design process, the final product, and future directions. Our participatory approach incorporated information from formative work with adolescents having lived experience, practitioners, and syntheses of published literature. The final intervention—Sleeping Healthy, Living Healthy—consists of six, 40-minute group sessions and one 20-minute individual session designed for high school students. Each session has a set of learning objectives, combining instruction, group activities, and discussions on sleep hygiene and MBIH topics. Our manualized intervention includes handouts created by a graphic design team that served as a review and reminder for home practice. We describe intervention implementation to two unique cohorts and detail our methods used to fine-tune the intervention between cohorts. Our partnership with and insights from both adolescents and practitioners serve as a guide for researchers aiming to use participatory methods to develop interventions to decrease health disparities in specific populations.
Metamodern Nature of Hideo Kojima's Death Stranding Synopsis and Gameplay
Authors: Radchenko Simon
Published: July 2023

Games are valuable cultural phenomena — they might indicate social, cultural, and even political trends and agendas. Moreover, they might bare an accurate representation of a common structure of a feeling. Conversely, video games might be studied and understood based on up-to-date cultural trends, one of which is metamodernism. This paper contributes to determining what metamodern games in terms of synopsis and gameplay are. After considering the methodological features of studying video games from a metamodern perspective, it presents a metamodern study case of Hideo Kojima's Death Stranding. Examining oscillation, empathy, constructionism, and object-oriented relations in Kojima's game, the paper proves it to be a shining example of metamodern gaming. Furthermore, analyzing Death Stranding gameplay features from a metamodern perspective determines metamodern-related gameplay elements and strategies.
Evaluation of a pharmacist-led interprofessional chronic pain clinic in Canada
Authors: Jorgenson Derek , Halpape Katelyn
Published: July 2023

Background:

Chronic noncancer pain (CNCP) is a common condition that affects individuals at a biopsychosocial level and can significantly impair function and quality of life. Referral to an interprofessional CNCP program is recommended for most patients; however, these clinics are limited in number and capacity. Expanding access by testing new service delivery models would be of value. The purpose of this study was to measure the impact of a new pharmacist-led, interprofessional model of care developed at the University of Saskatchewan Chronic Pain Clinic.

Methods:

A retrospective chart audit was conducted using data that included adult patients referred for CNCP management between May 2020 and December 2021. Medication use, overall health status (using the Clinical Global Impression of Change–Improvement [CGI-I] scale) and patient readiness to change (using the Transtheoretical Model) were measured 6 months after the initial appointment.

Results:

The study included 138 patients. Of the 80 patients taking an opioid, 22.5% were switched to buprenorphine/naloxone and the remainder had their mean morphine-equivalent dose reduced by a mean of 41.7 mg/d. Overall patient health status was minimally improved and many patients moved into the Action stage of change.

Discussion:

Changes in opioid use demonstrate a clinically important shift toward safer medication regimens that are less likely to lead to toxicity and unintended overdose. CGI-I data suggest that these patients, whose health status is typically very difficult to change, did not deteriorate but slightly improved after attending the clinic.

Conclusion:

The unique pharmacist-led, interprofessional model of care used by the University of Saskatchewan Chronic Pain Clinic may offer a viable alternative to traditional physician-led models.
Memory and time in early Quakerism
Authors: Hinds Hilary
Published: July 2023

This article explores the ambiguous place of memory – its absences and presences, its strategic mobilisation and theological redundancy – in the practices and writings of the early Quaker movement. Quakers’ commitment to unprogrammed, largely silent, worship and to spontaneous speech meant that memory had no place in their Meetings for Worship. Nevertheless, the movement was actively intent on conserving the memory of its early years, ensuring that its writings, published and unpublished, were preserved, by developing systems of copying and archiving key documents. Memory is thus central to the ambitions and practices of the early movement and yet also rendered redundant by aspects of its theology. The article investigates traces of memory in the composition of the Journal of George Fox, the movement’s first leader, and finds its strategic rhetorical mobilisation of memory to be rooted in Quakers’ distinctive understandings of human and divine time.
Treatment of and Attitudes Towards ‘Other’ Languages in Modern Russia: Evidence from Metalinguistic Discourse
Authors: Hye Hyun Nam , Kapitolina Fedorova
Published: July 2023

Russian Federation, being de jure and de facto linguistically diverse multilingual country, can be described, at the same time, as being under a strong influence of monolingual language ideology, with Russian totally domineering in most public spheres. Minority languages and especially languages of migrants lack official recognition and support, and their speakers often have to face prejudices and negative stereotypes. The paper aims at revealing language ideology prevailing in modern Russia through analysis of attitudes to languages other than Russian as they are expressed in discourse about language, i.e. metadiscourse. When approaching it, it is important to distinguish state discourse (manifestation of official language policy) and public discourse (collective attitudes towards certain sublanguages and their users expressed more or less directly). The analysis shows that over the past two decades, official language ideology in Russia has shifted from guaranteeing linguistic equality and diversity to having an emphasis on unity and purity and giving support to the Russian language. This reorientation is realized through status planning, corpus planning, and acquisition planning. At the level of public discourse, analysis of collective attitudes towards the languages used by non-native speakers demonstrates that a significant part of the Russian-speaking population express negative attitudes towards non-native speakers and their poor Russian language skills, which once again confirms that there is dominant monolingualism and purism in public discourse. However, language practices in Russia are gradually becoming more diverse which can become a challenge for monolingualism and purism in future.
Numbers in News Articles: Effects of Presence, Errors, and (False) Recall
Authors: Appelman Alyssa
Published: July 2023

This experiment ( N = 300) tests the effects of numbers and math errors in online news articles. Several readers struggled to recall and recognize the numbers and math errors in the articles, but there were significant effects of thinking they saw them—Regardless of experimental condition, readers who noticed (or imagined) numbers reported higher content quality, and readers who noticed (or imagined) errors reported lower content and source quality. Findings are discussed through the Heuristic-Systematic Processing Model, and implications for media trust are explored.
Influence of Emotional Branding on Consumers’ Purchase Intention: A Study on Scale Development and Mediating Role of Celebrity Endorsement
Authors: Niharika  , Yadav Rajan
Published: July 2023

Emotional branding is a powerful branding strategy that has a significant influence on consumers final purchasing decisions, and marketers have used it extensively. The purpose of this research is to create a multifactor instrument for measuring emotional branding, to show that it can predict consumer behaviour and to investigate the mediating role of celebrity endorsement (CE) in this relationship. The study is divided into three sections. A multistage scale development and validation process was the initial step. Exploratory factor analysis determines the emotional branding scale’s (EBS’s) components in the second stage. Third, confirmatory factor analysis (CFA) validated the scale. Study 1 shows scale development and zero- and first-order CFA. Study 2 shows how does CE mediate the relationship between emotional branding and purchase intention (PI). The findings indicate that each of the four structures contains 32 elements from the EBS. The study reveals that the EBS has four components (i.e., sensory appeal, brand attachment appeal, communication appeal and patriotism appeal). Emotional branding affects PI directly and statistically. CE partially mediates emotional branding and purchase intention.
Changes in Physiological Indices Before and After Nursing Care of Postoperative Patients With Esophageal Cancer in the ICU
Authors: Kawano Takanori , Ono Hiroshi , Abe Masaki , Umeshita Koji
Published: July 2023

Introduction

Various stressors have been identified in patients in the intensive care unit (ICU), including postoperative pain, ventilatory management, and nursing care. However, sedated patients are less responsive, and nurses have difficulty capturing their stressors.

Objective

To investigate patient stress caused by nursing care performed in the ICU on sedated patients based on changes in physiological indices.

Methods

We observed nursing care performed on patients with postoperative esophageal cancer under sedation in the ICU. This included endotracheal suctioning and turning, the time required for the care, and the patients’ behavioral responses. Information on arousal levels, autonomic nervous system indices, and vital signs were also obtained. The changes in indicators before and after care were then compared and analyzed.

Results

There were 14 patients in the study. The mean age of the patients was 68 years. Ninety-nine scenes of nursing care were observed, and in six of these, additional bolus sedation was administered because of the patient's significant body movements. In endotracheal suctioning, no significant changes were observed in all indicators. In turning, vital signs changed significantly, and when both were continued, all indicators changed significantly.

Conclusion

Our study found that different types and combinations of nursing care may cause different stresses to the patients. Moreover, the autonomic nervous system indices may be more likely to react to stresses in a variety of nursing care, while arousal levels may be more likely to react to burdensome stresses. If the characteristics of these physiological indicators can be understood and effectively utilized during care, it may be possible to better identify and reduce patient stress during sedation management.
Effectiveness of Economic Value Added (EVA) and Conventional Performance Measures - Evidences from India
Authors: Sharma Anil K.
Published: July 2023

In this paper we have tried to find out the effectiveness of EVA in selected Indian companies. During last decade, value added measures like EVA has gained popularity and companies around the world have started disclosing EVA figures in their financial statements, as a part of corporate social responsibility agenda. This is because of shifting corporate objective from profit maximization to value or wealth maximization. The paper examines whether selected companies are able to create value for their shareholders or not. For this, performance of selected companies has been analyzed using traditional performance measures such as ROCE, ROE and EPS alongwith value added measures called EVA. With the help of various statistical techniques like Regression, Trend analysis, Chi square and ANOVA, the present study tests the various hypotheses and reveals that except for few, majorities of the sample companies are able to continuously create value for their shareholders during the study period. Study provide that EVA is gaining popularity in India as important measures of firm performance and more companies should disclose EVA figures in their financial report so as to reveal correct financial position to the various stakeholders.
Hand-Over Process Improvement in Large Construction Projects
Authors: Hassan M.K. , Kandeil A.R. , Nady A.E.
Published: July 2023

Unlike any other industry, construction industry has not fully implemented TQM philosophy. This can be attributed to the complex nature of construction projects, which has numerous and overlapping activities. The present research is an attempt to solve one of the major problems in large construction projects, manifested in the delay of handing-over apartments to end customer in contracted time. The DMAIC procedures of the Six Sigma, problem-solving methods together with the CPM and PERT project planning techniques have been integrated in this research to achieve the required objective.
An Econometric Study of Trading Behaviour of Institutional Investors in Indian Stock Market: The Vector Auto regression Approach
Authors: Mishra Shekhar , Debasish Sathya Swaroop
Published: July 2023

The present paper endeavours to study the trading behaviour of foreign institutional investors (FIIs) and domestic institutional investors (DIIs) in Indian stock market. The study ascertains whether the purchase trade and sale trade behaviour of foreign institutional investors is different from their domestic counterparts and whether their trading pattern remains persistent over time. The paper adopts multivariate Vector Auto Regression (VAR) approach to analyse these issues. As compared to earlier studies, the present paper uses a wider definition of domestic institutional investors (DIIs) that includes not only mutual funds (MFs) but also banks, insurance companies and other domestic financial institutions. The outcome of the analysis indicate that the foreign institutional investors (FIIs) appear to be very short term momentum buyers in their purchase trade and appear to be neither momentum nor contrarian sellers in their sale trade. Additionally the trading behaviour of both foreign and domestic institutional investors also shows the evidence of contemporaneous trade and intra group herding in Indian stock market. The Variance Decomposition Analysis also indicates that trading behaviour of institutional investors and market index returns have impact on each other in Indian stock market.
Mutations associated with progression in follicular lymphoma predict inferior outcomes at diagnosis: Alliance A151303
Authors: Russler-Germain David A. , Krysiak Kilannin , Ramirez Cody , Mosior Matthew , Watkins Marcus P. , Gomez Felicia , Skidmore Zachary L. , Trani Lee , Gao Feng , Geyer Susan , Cashen Amanda F. , Mehta-Shah Neha , Kahl Brad S. , Bartlett Nancy L. , Alderuccio Juan P. , Lossos Izidore S. , Ondrejka Sarah L. , Hsi Eric D. , Martin Peter , Leonard John P. , Griffith Malachi , Griffith Obi L. , Fehniger Todd A.
Published: July 2023

Follicular lymphoma (FL) is clinically heterogeneous, with select patients tolerating extended watch-and-wait, whereas others require prompt treatment, suffer progression of disease within 24 months of treatment (POD24), and/or experience aggressive histologic transformation (t-FL). Because our understanding of the relationship between genetic alterations in FL and patient outcomes remains limited, we conducted a clinicogenomic analysis of 370 patients with FL or t-FL (from Cancer and Leukemia Group B/Alliance trials 50402/50701/50803, or real-world cohorts from Washington University School of Medicine, Cleveland Clinic, or University of Miami). FL subsets by grade, stage, watch-and-wait, or POD24 status did not differ by mutation burden, whereas mutation burden was significantly higher in relapsed/refractory (rel/ref) FL and t-FL than in newly diagnosed (dx) FL. Nonetheless, mutation burden in dx FL was not associated with frontline progression-free survival (PFS). CREBBP was the only gene more commonly mutated in FL than in t-FL yet mutated CREBBP was associated with shorter frontline PFS in FL. Mutations in 20 genes were more common in rel/ref FL or t-FL than in dx FL, including 6 significantly mutated genes (SMGs): STAT6, TP53, IGLL5, B2M, SOCS1, and MYD88. We defined a mutations associated with progression (MAP) signature as ≥2 mutations in these 7 genes (6 rel/ref FL or t-FL SMGs plus CREBBP). Patients with dx FL possessing a MAP signature had shorter frontline PFS, revealing a 7-gene set offering insight into FL progression risk potentially more generalizable than the m7–Follicular Lymphoma International Prognostic Index (m7-FLIPI), which had modest prognostic value in our cohort. Future studies are warranted to validate the poor prognosis associated with a MAP signature in dx FL, potentially facilitating novel trials specifically in this high-risk subset of patients.
Plasmodium falciparum infection of human erythroblasts induces transcriptional changes associated with dyserythropoiesis
Authors: Feldman Tamar P. , Ryan Yana , Egan Elizabeth S.
Published: July 2023

During development down the erythroid lineage, hematopoietic stem cells undergo dramatic changes to cellular morphology and function in response to a complex and tightly regulated program of gene expression. In malaria infection, Plasmodium spp parasites accumulate in the bone marrow parenchyma, and emerging evidence suggests erythroblastic islands are a protective site for parasite development into gametocytes. Although it has been observed that Plasmodium falciparum infection in late-stage erythroblasts can delay terminal erythroid differentiation and enucleation, the mechanism(s) underlying this phenomenon are unknown. Here, we apply RNA sequencing after fluorescence-activated cell sorting of infected erythroblasts to identify transcriptional responses to direct and indirect interaction with P falciparum. Four developmental stages of erythroid cells were analyzed: proerythroblast, basophilic erythroblast, polychromatic erythroblast, and orthochromatic erythroblast. We found extensive transcriptional changes in infected erythroblasts compared with that in uninfected cells in the same culture, including dysregulation of genes involved in erythroid proliferation and developmental processes. Although some indicators of cellular oxidative and proteotoxic stress were common across all stages of erythropoiesis, many responses were specific to cellular processes associated with developmental stage. Together, our results evidence multiple possible avenues by which parasite infection can induce dyserythropoiesis at specific points along the erythroid continuum, advancing our understanding of the molecular determinants of malaria anemia.
A critical interpretive synthesis of the lived experiences and health and patient-reported outcomes of people living with COPD who isolated during the COVID-19 pandemic
Authors: Swain Rose , Forsyth Faye , Bowers Ben , Early Frances , Kuhn Isla , Shrivastva Sagar , Tufnell Rachel , Fuld Jonathan
Published: July 2023

Aims:

To determine the lived experiences of people with COPD who isolated at home during the coronavirus disease 2019 (COVID-19) pandemic, and explore how these experiences affected health and patient-reported outcomes.

Methods:

Keyword searches were performed in five bibliographic databases. Critical interpretative synthesis (CIS) methods were used to interrogate and understand patterns across studies.

Results:

23 studies were identified; three employed qualitative methods and 20 quantitative methods. Application of CIS methods highlighted a core synthetic concept that appeared to underpin experiences and outcomes, that of a heightened perception of risk. Using the Risk Perception Model as a framework, we found that cognitive factors such as knowledge of underlying health status and the transmissibility of COVID-19; experiential factors including previous episodes of breathlessness and hospitalisation; and sociocultural factors such as access to trusted sources of information, influenced perceptions of risk. In turn, this influenced behaviour, which translated to outcomes such as reduced hospitalisations, deconditioning and social isolation as people avoided “high-risk” situations and settings.

Conclusions:

Patients with COPD who isolated at home during the COVID-19 pandemic had a heightened perception of risk which was influenced by cognitive, experiential and sociocultural factors. The consequences of this were varied and included both positive (reduced exacerbations and hospitalisations) and negative (social isolation, deconditioning, diminished capacity for self-care) outcomes. Understanding risk and the impacts it can have could help clinicians to support people with COPD return to their pre-pandemic way of living and enable better communication of ongoing risk from respiratory viral illness.
RGA1 Negatively Regulates Thermo-tolerance by Affecting Carbohydrate Metabolism and the Energy Supply in Rice
Authors: Feng Baohua , Xu Yongqiang , Fu Weimeng , Li Hubo , Li Gengmi , Li Juncai , Wang Wenting , Tao Longxing , Chen Tingting , Fu Guanfu
Published: July 2023

Background

Signal transduction mediated by heterotrimeric G proteins, which comprise the α, β, and γ subunits, is one of the most important signaling pathways in rice plants.RGA1, which encodes the Gα subunit of the G protein, plays an important role in the response to various types of abiotic stress, including salt, drought, and cold stress. However, the role ofRGA1in the response to heat stress remains unclear.

Results

The heat-resistant mutantett1(enhanced thermo-tolerance 1) with a new allele of theRGA1gene was derived from an ethane methyl sulfonate-induced Zhonghua11 mutant. After 45 °C heat stress treatment for 36 h and recovery for 7 d, the survival rate of theett1mutants was significantly higher than that of wild-type (WT) plants. The malondialdehyde content was lower, and the maximum fluorescence quantum yield of photosystem II, peroxidase activity, andhspexpression were higher inett1mutants than in WT plants after 12 h of exposure to 45 °C. The RNA-sequencing results revealed that the expression of genes involved in the metabolism of carbohydrate, nicotinamide adenine dinucleotide, and energy was up-regulated inett1under heat stress. The carbohydrate content and the relative expression of genes involved in sucrose metabolism indicated that carbohydrate metabolism was accelerated inett1under heat stress. Energy parameters, including the adenosine triphosphate (ATP) content and the energy charge, were significantly higher in theett1mutants than in WT plants under heat stress. Importantly, exogenous glucose can alleviate the damages on rice seedling plants caused by heat stress.

Conclusion

RGA1negatively regulates the thermo-tolerance in rice seedling plants through affecting carbohydrate and energy metabolism.
A high-throughput screening system for SARS-CoV-2 entry inhibition, syncytia formation and cell toxicity
Authors: Jancy Shine Varghese , Lupitha Santhik Subhasingh , Chandrasekharan Aneesh , Varadarajan Shankara Narayanan , Nelson-Sathi Shijulal , Prasad Roshny , Jones Sara , Easwaran Sreekumar , Darvin Pramod , Sivasailam Aswathy , Santhoshkumar Thankayyan Retnabai
Published: July 2023

Background

The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell is mediated through the binding of the SARS-CoV-2 Spike protein via the receptor binding domain (RBD) to human angiotensin-converting enzyme 2 (hACE2). Identifying compounds that inhibit Spike-ACE2 binding would be a promising and safe antiviral approach against COVID-19.

Methods

In this study, we used a BSL-2 compatible replication-competent vesicular stomatitis virus (VSV) expressing Spike protein of SARS-CoV-2 with eGFP reporter system (VSV-eGFP-SARS-CoV-2) in a recombinant permissive cell system for high-throughput screening of viral entry blockers. The SARS-CoV-2 permissive reporter system encompasses cells that stably express hACE2-tagged cerulean and H2B tagged with mCherry, as a marker of nuclear condensation, which also enables imaging of fused cells among infected EGFP positive cells and could provide real-time information on syncytia formation.

Results

A limited high-throughput screening identified six natural products that markedly inhibited VSV-eGFP-SARS-CoV-2 with minimum toxicity. Further studies of Spike-S1 binding using the permissive cells showed Scillaren A and 17-Aminodemethoxygeldanamycin could inhibit S1 binding to ACE2 among the six leads. A real-time imaging revealed delayed inhibition of syncytia by Scillaren A, Proscillaridin, Acetoxycycloheximide and complete inhibition by Didemnin B indicating that the assay is a reliable platform for any image-based drug screening.

Conclusion

A BSL-2 compatible assay system that is equivalent to the infectious SARS-CoV-2 is a promising tool for high-throughput screening of large compound libraries for viral entry inhibitors against SARS-CoV-2 along with toxicity and effects on syncytia. Studies using clinical isolates of SARS-CoV-2 are warranted to confirm the antiviral potency of the leads and the utility of the screening system.
OGRE: calculate, visualize, and analyze overlap between genomic input regions and public annotations
Authors: Berres Sven , Gromoll Jörg , Wöste Marius , Sandmann Sarah , Laurentino Sandra
Published: July 2023

Background

Modern genome sequencing leads to an ever-growing collection of genomic annotations. Combining these elements with a set of input regions (e.g. genes) would yield new insights in genomic associations, such as those involved in gene regulation. The required data are scattered across different databases making a manual approach tiresome, unpractical, and prone to error. Semi-automatic approaches require programming skills in data parsing, processing, overlap calculation, and visualization, which most biomedical researchers lack. Our aim was to develop an automated tool providing all necessary algorithms, benefiting both bioinformaticians and researchers without bioinformatic training.

Results

We developed overlapping annotated genomic regions (OGRE) as a comprehensive tool to associate and visualize input regions with genomic annotations. It does so by parsing regions of interest, mining publicly available annotations, and calculating possible overlaps between them. The user can thus identify location, type, and number of associated regulatory elements. Results are presented as easy to understand visualizations and result tables. We applied OGRE to recent studies and could show high reproducibility and potential new insights. To demonstrate OGRE’s performance in terms of running time and output, we have conducted a benchmark and compared its features with similar tools.

Conclusions

OGRE’s functions and built-in annotations can be applied as a downstream overlap association step, which is compatible with most genomic sequencing outputs, and can thus enrich pre-existing analyses pipelines. Compared to similar tools, OGRE shows competitive performance, offers additional features, and has been successfully applied to two recent studies. Overall, OGRE addresses the lack of tools for automatic analysis, local genomic overlap calculation, and visualization by providing an easy to use, end-to-end solution for both biologists and computational scientists.
Multiple refractory intracellular pathogen infections in a human immunodeficiency virus-negative patient with anti-interferon-γ autoantibodies: a case report
Authors: Wang Hongxia , Lei Rong , Ji Yang , Xu Wei , Zhang Keke , Guo Xiang
Published: July 2023

Background

The clinical presentation of adult-onset immunodeficiency with anti-interferon (IFN)-γ autoantibodies with intracellular pathogens can be highly variable, which can lead to misdiagnosis during the early stage of disease.

Case presentation

We report a complex case of a 54-year-old Chinese male who was human immunodeficiency virus-negative. He had a presence of anti-IFN-γ autoantibodies and suffered from various intracellular pathogenic infections. The patient was admitted to our hospital for the first time in July 2016 with severe pneumonia, and he experienced multiple pneumonia infections between 2017 and 2019. In March 2019, the patient was hospitalized due to pulmonary lesions and multiple-bone destruction. During hospitalization, the patient was confirmed to have disseminated Talaromyces marneffei infection and was successfully treated with antifungal therapy for 1 year. In June 2021, Mycobacterium kansasii infection was detected by positive culture and progressive bone destruction. A high concentration of anti-IFN-γ antibodies was observed in the patient’s serum. In addition, Listeria monocytogenes was isolated by blood culture, and the presence of L. monocytogenes in cerebrospinal fluid was confirmed by next-generation sequencing. Following anti-non-tuberculous mycobacteria (NTM) therapy and anti-bacterial therapy, the patient’s symptoms, pulmonary lesions, and bone destruction gradually improved.

Conclusions

Although the clinical presentation of adult-onset immunodeficiency with anti-IFN-γ autoantibodies can be highly variable, the diagnosis should be considered if patients suffer from unexplained repeated bacterial or opportunistic infections.

Conventional and advanced molecular testing should be used, as needed, for microbiological diagnoses among this special immunodeficient population.
The joint effect of gestational diabetes mellitus and hypertension contribute to higher risk of diabetes mellitus after delivery: a nationwide population-based study
Authors: Kek Ho-Poh , Su Yu-Tsun , Tey Shu-Jiin , Yang Ming-Chun , Chang Li-Ching , Hung Yun-Hsiang , Tsai Ching-Chung
Published: July 2023

Background

Gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) are known risk factors for postpartum diabetes mellitus (DM) and hypertension, respectively. This study aimed to examine the association between the co-occurrence of GDM and PIH and the subsequent development of diabetes mellitus (DM), hypertension, and metabolic syndrome.

Methods

A cohort study was conducted using data from the Taiwan National Health Insurance Research Database (TNHIRD). The study population included 2,297,613 pregnant women with no history of certain medical conditions who gave birth between 2004 and 2015. The women were classified into four cohorts based on their medical history: GDM cohort, PIH cohort, both GDM and PIH cohort, and normal cohort (without GDM and PIH).

Results

The GDM cohort had a higher risk of developing DM, hypertension, and metabolic syndrome than the normal cohort, with hazard ratios of 7.07, 1.54, and 2.51, respectively. The PIH cohort also had an increased risk for these conditions compared with the normal cohort, with hazard ratios of 3.41, 7.26, and 2.68, respectively. The cohort with both GDM and PIH had the highest risk of developing postpartum DM, hypertension, and metabolic syndrome, with hazard ratios of 21.47, 8.02, and 5.04, respectively, compared with the normal cohort.

Conclusion

The cohort of patients with both GDM and PIH had the highest impact on developing postpartum DM compared with either condition alone cohort. Furthermore, the co-occurrence of both conditions increases the risk, with a higher likelihood of developing postpartum DM than hypertension or metabolic syndrome.
Impact of COVID-19 control on lung, breast, and colorectal pathological cancer diagnoses. A comparison between the Netherlands, Aotearoa New Zealand, and Northern Ireland
Authors: Mitchell Helen , Mclean Jennifer , Gavin Anna T , Visser Otto , Millar Elinor , Luff Tessa , Bennett Damien
Published: July 2023

Background

The COVID-19 pandemic was managed in Aotearoa New Zealand (NZ) by a COVID-19 elimination policy, involving border closure and an initial national lockdown. This was different to most other countries including Northern Ireland (NI) and the Netherlands (NED). We quantify the effect of these policies on the diagnosis of three major cancers, comparing NZ with these two European countries.

Method

Data from NED, NZ and NI population-based cancer registries were used to assess trends in all pathologically diagnosed (PD) lung, breast, and colorectal cancers from March to December 2020 (pandemic period) and compared to the similar pre-pandemic period (2017–2019). Trend data were also collated on COVID-19 cases and deaths per 100,000 in each population.

Results

Comparing the pre-pandemic period to the pandemic period there were statistically significant reductions in numbers of lung (↓23%) and colorectal (↓15%) PD cancers in NI and numbers of breast (↓18%) and colorectal cancer (↓18.5%) diagnosed in the NED. In NZ there was no significant change in the number of lung (↑10%) or breast cancers (↑0.2%) but a statistically significant increase in numbers of colorectal cancer diagnosed (↑5%).

Conclusion

The impact of COVID-19 on cancer services was mitigated in NZ as services continued as usual reflecting minimal healthcare disruption and protected cancer services linked with the elimination approach adopted. The reduction in PD cases diagnosed in NED and NI were linked with higher COVID-19 rates and reflect societal restrictions which resulted in delayed patient presentation to primary and secondary care, disruption to screening and healthcare services as a result of COVID-19 infections on staff and the need to shift intensive care to COVID-19 patients. Reductions in PD cancers in NI and the NED and in particularly lung cancers in NI, highlight the need for targeted public health campaigns to identify and treat ‘missing’ patients. Protecting cancer services should be a priority in any future pandemic or systemic healthcare system disruption.
Sociocultural and structural influences on HIV Pre-Exposure Prophylaxis (PrEP) Engagement and Uptake among African American Young adults
Authors: Ayangeakaa Suur D. , Kerr Jelani , Combs Ryan M. , Harris Lesley M. , Sears Jeanelle S. , Parker Kimberly , Sterrett-Hong Emma
Published: July 2023

Background

Pre-exposure prophylaxis (PrEP) demonstrates effectiveness in decreasing new cases of HIV. However, few African Americans use PrEP, despite being disproportionately impacted by HIV. Understanding the influence of sociocultural and structural factors on PrEP use among multiple priority groups of African Americans, including but not limited to men who have sex with men, may improve PrEP engagement and uptake. The social ecological model (SEM) as a framework guided the understanding of how these factors operate on multiple levels to influence PrEP use among this population.

Methods

This study derived data from the Afya PrEP study consisting of eleven focus groups (N = 63) with 18-29-year-old African American sexual and gender minority and heterosexual individuals at heightened behavioral vulnerability to HIV. We employed constructivist grounded theory processes to inductively analyze the data. A pooled kappa score of 0.90 indicated excellent inter-rater agreement.

Results

Factors impacting PrEP engagement among African American young adults included: (1) Community/social network influences; (2) medical mistrust; (3) stigma; (4) PrEP availability and accessibility, which had two sub-categories: (a) cost and (b) where to obtain PrEP; and (5) PrEP engagement strategies, which had two sub-categories: (a) current AIDS service organizations’ PrEP engagement practices and (b) recommended future PrEP engagement strategies. Categories one through three represent sociocultural factors, and categories four and five represent structural factors that influence perceptions and attitudes of African American young adults regarding PrEP.

Conclusion

Our study highlights sociocultural and structural factors that act as barriers and facilitators to PrEP engagement. The SEM guided the understanding of how these factors operated on multiple levels. One of the sociocultural factors, community/social network influences operated at the interpersonal level of the SEM; the other two, stigma and medical mistrust, operated at the community level. The structural factors (PrEP availability, accessibility, and engagement strategies) operated at the institutional/organizational level. Thus, multi-level interventions are warranted to improve PrEP engagement among various African American young adult priority groups.
The underlying molecular mechanisms and biomarkers between periodontitis and COVID-19
Authors: Qin Danlei , Yu Feiyan , Wu Dongchao , Han Chong , Yao Xuemin , Yang Lulu , Yang Xi , Wang Qianqian , He Dongning , Zhao Bin
Published: July 2023

Objective

Emerging evidence shows the clinical consequences of patient with COVID-19 and periodontitis are not promising, and periodontitis is a risk factor. Periodontitis and COVID-19 probably have a relationship. Hence, this study aimed to identify the common molecular mechanism that may help to devise potential therapeutic strategies in the future.

Material and methods

We analyzed two RNA-seq datasets for differential expressed genes, enrichment of biological processes, transcription factors (TFs) and deconvolution-based immune cell types in periodontitis, COVID-19 and healthy controls. Relationships between TFs and mRNA were established by Pearson correlation analysis, and the common TFs-mRNA regulatory network and nine co-upregulated TFs of the two diseases was obtained. The RT-PCR detected the TFs.

Results

A total of 1616 and 10201 differentially expressed gene (DEGs) from periodontitis and COVID-19 are found. Moreover, nine shared TFs and common biological processes associated with lymphocyte activation involved in immune response were identified across periodontitis and COVID-19. The cell type enrichment revealed elevated plasma cells among two diseases. The RT-PCR further confirmed the nine TFs up-regulation in periodontitis.

Conclusion

The pathogenesis of periodontitis and COVID-19 is closely related to the expression of TFs and lymphocyte activation, which can provide potential targets for treatment.
Using Palliative Leaders in Facilities to Transform Care for People with Alzheimer’s Disease (UPLIFT-AD): protocol of a palliative care clinical trial in nursing homes
Authors: Unroe Kathleen T. , Ersek Mary , Tu Wanzhu , Floyd Alexander , Becker Todd , Trimmer Jessica , Lamie Jodi , Cagle John
Published: July 2023

Background

Palliative care is an effective model of care focused on maximizing quality of life and relieving the suffering of people with serious illnesses, including dementia. Evidence shows that many people receiving care in nursing homes are eligible for and would benefit from palliative care services. Yet, palliative care is not consistently available in nursing home settings. There is a need to test pragmatic strategies to implement palliative care programs in nursing homes.

Methods/design

The UPLIFT-AD (Utilizing Palliative Leaders in Facilities to Transform care for people with Alzheimer’s Disease) study is a pragmatic stepped wedge trial in 16 nursing homes in Maryland and Indiana, testing the effectiveness of the intervention while assessing its implementation. The proposed intervention is a palliative care program, including 1) training at least two facility staff as Palliative Care Leads, 2) training for all staff in general principles of palliative care, 3) structured screening for palliative care needs, and 4) on-site specialty palliative care consultations for a one-year intervention period. All residents with at least moderate cognitive impairment, present in the facility for at least 30 days, and not on hospice at baseline are considered eligible. Opt-out consent is obtained from legal decision-makers. Outcome assessments measuring symptoms and quality of care are obtained from staff and family proxy respondents at four time points: pre-implementation (baseline), six months after implementation, at 12 months (conclusion of implementation), and six months after the end of implementation. Palliative care attitudes and practices are assessed through surveys of frontline nursing home staff both pre- and post-implementation. Qualitative and quantitative implementation data, including fidelity assessments and interviews with Palliative Care Leads, are also collected. The study will follow the Declaration of Helsinki.

Discussion

This trial assesses the implementation and effectiveness of a robust palliative care intervention for residents with moderate-to-advanced cognitive impairment in 16 diverse nursing homes. The intervention represents an innovative, pragmatic approach that includes both internal capacity-building of frontline nursing home staff, and support from external palliative care specialty consultants.

Trial registration

The project is registered on ClinicalTrials.gov: NCT04520698.