bluuebunny/crossref_metadata_2025 huggingface dataset:
Trust matters: The Addressing Vaccine Hesitancy in Europe Study
Authors: Vuolanto Pia , Almeida Ana Nunes , Anderson Alistair , Auvinen Petra , Beja André , Bracke Piet , Cardano Mario , Ceuterick Melissa , Correia Tiago , De Vito Elisabetta , Delaruelle Katrijn , Delicado Ana , Esposito Maurizio , Ferrara Maria , Gariglio Luigi , Guerreiro Cátia , Marhánková Jaroslava Hasmanová , Hilário Ana Patrícia , Hobson-West Pru , Iorio Juliana , Järvinen Katri-Maria , Koivu Annariina , Kotherová Zuzana , Kuusipalo Aapo , Lermytte Esther , Mendonça Joana , Morais Rita , Numerato Dino , Polak Paulina , Rudek Tadeusz , Sbaragli Sara , Scavarda Alice , Silva Katielle , da Silva Pedro Alcantâra , Sivelä Jonas , Moura Eva Soares , Świątkiewicz-mośny Maria , Tipaldo Giuseppe , Wagner Aleksandra
Published: February 2024

This article presents the design of a seven-country study focusing on childhood vaccines, Addressing Vaccine Hesitancy in Europe (VAX-TRUST), developed during the COVID-19 pandemic. The study consists of (a) situation analysis of vaccine hesitancy (examination of individual, socio-demographic and macro-level factors of vaccine hesitancy and analysis of media coverage on vaccines and vaccination and (b) participant observation and in-depth interviews of healthcare professionals and vaccine-hesitant parents. These analyses were used to design interventions aimed at increasing awareness on the complexity of vaccine hesitancy among healthcare professionals involved in discussing childhood vaccines with parents. We present the selection of countries and regions, the conceptual basis of the study, details of the data collection and the process of designing and evaluating the interventions, as well as the potential impact of the study. Laying out our research design serves as an example of how to translate complex public health issues into social scientific study and methods.
Radiographic sarcopenic obesity measurements in elderly trauma patients do not predict adverse discharge disposition over injury severity score
Authors: Oh John S. , Peterson Christine M. , Alvarez Carolina , Layng Stephen C. , Pradhan Sandeep , Shen Chan , Lee Jungeun Jasmine , Osevala Nicole M. , Armen Scott B.
Published: February 2024

Introduction

There is a need for a predictive tool for adverse discharge disposition in the injured elderly patient population. However, many measurements of frailty are not practical and radiographic measurements of muscle and adipose tissue have yet to be correlated with adverse discharge disposition in this population.

Methods

A retrospective review of a prospectively gathered trauma database at a level one trauma center was performed, studying all adult trauma patients aged 55 years or older with an inpatient stay of greater than 2 days. Patients with a non-survivable head trauma (head Abbreviated Injury Score of 6) or serious central nervous system injury, history of cirrhosis or solid organ transplantation, those actively being treated with immunosuppressive medications, and those without an abdominal computerized tomography (CT) scan within the first 48 h of admission were excluded. Sarcopenia, sarcopenic obesity (SO), and five-item frailty index (5-iFI) score were obtained and analyzed against adverse discharge disposition.

Results

The study evaluated 444 patients, of which 48.9% were male with a median age of 78 years (range 55–99 years). All patients sustained blunt trauma, shock index was positive in 13.7%, and median ISS was 10 (range 1–43). SO was not independently predictive of adverse discharge disposition. Additionally, neither sarcopenia nor 5-iFI scores were found to be independently predictive. Lower ISS and age were found to be protective against adverse discharge disposition.

Conclusion

CT-based measurements of muscle and adipose tissue may not add value over traditional injury scores in older trauma patients.
Book review: Amdani, Y., World of Opportunity: Bringing Sustainable Business to Fragile Economies
Authors: Christie John P.
Published: February 2024

Amdani, Y., World of Opportunity: Bringing Sustainable Business to Fragile Economies (ForbesBooks, 2023), 208pp. £7.79 and eBook $9.99. ISBN: 9798887501222.
From Interpretation to Interruption: Embracing disruptive analysis
Authors: Clark Timothy
Published: February 2024

Qualitative analysis is, inherently, a complex, messy and nuanced process. In the context of contested notions of validity, for novice researchers there is therefore an attraction in adopting established, systematic and formulaic approaches. Yet, in prioritising methodical processes, over critical engagement and methodologically coherent quality criteria, these approaches can risk limiting research to a process of cataloguing and reporting face value readings. This research note reflects on an attempt to address and examine this risk in a doctoral research project by progressing from an initial thematic interpretative approach to data analysis to a secondary stage informed by ideas of interruptive analysis. The paper introduces a conceptualisation of interruption as prioritising interrogation of aspects of presentation, over a focus on the interpretation of content or a shift from analysing what is said, to how it is said. Empirical data from research exploring doctoral students’ methodological decision-making is utilised to illustrate the approach and to provoke consideration of the value of embracing disruption. Analysis of two narrative accounts from the study is presented, providing a snapshot of the different understandings and an insight into the learning it generated. The learning in this research note is intended to act as an illustration and provocation for thinking rather than any form of procedural guide.
Monstrous Pedagogy at the Intersections of White Privilege, Visible Disability
Authors: Mulderink Carrie Elizabeth
Published: February 2024

This autoethnographic article centers my White, disabled, and female body as a site of knowledge and struggle within the context of teaching an introductory communication course. I chronicle through key experiences I have had as an official instructor. I draw from various scholars whose work explicates the official teacher’s body as consequential. As a White woman with a visible disability, I use Calafell’s articulation of monstrosity to process through how I perform my White, disabled, female identities in the classroom.
An Examination of the Use of Large Language Models to Aid Analysis of Textual Data
Authors: Tai Robert H. , Bentley Lillian R. , Xia Xin , Sitt Jason M. , Fankhauser Sarah C. , Chicas-Mosier Ana M. , Monteith Barnas G.
Published: February 2024

The increasing use of machine learning and Large Language Models (LLMs) opens up opportunities to use these artificially intelligent algorithms in novel ways. This article proposes a methodology using LLMs to support traditional deductive coding in qualitative research. We began our analysis with three different sample texts taken from existing interviews. Next, we created a codebook and inputted the sample text and codebook into an LLM. We asked the LLM to determine if the codes were present in a sample text provided and requested evidence to support the coding. The sample texts were inputted 160 times to record changes between iterations of the LLM response. Each iteration was analogous to a new coder deductively analyzing the text with the codebook information. In our results, we present the outputs for these recursive analyses, along with a comparison of the LLM coding to evaluations made by human coders using traditional coding methods. We argue that LLM analysis can aid qualitative researchers by deductively coding transcripts, providing a systematic and reliable platform for code identification, and offering a means of avoiding analysis misalignment. Implications of using LLM in research praxis are discussed, along with current limitations.
Pioneering the Use of Tracker Data to Evaluate Lean-Led Hospital Design
Authors: Schouten Hannelore , Heusinkveld Stefan , Benders Jos
Published: February 2024

Objective:

This study aims to examine how we can effectively and affordably evaluate the impact of design concepts such as Lean-Led Hospital Design (LLHD) on the allocation of nurses’ time spent at different locations. Particularly in patient rooms, as this can be seen as value-adding time.

Background:

LLHD aims to create a hospital environment that supports value creation for patients and reduces waste. However, only a few studies measure its’ effects. One of the reasons for this absence is the lack of an adequate and affordable way to evaluate.

Method:

Nurses’ time spent in patient rooms was used as a proxy for value-adding time. Through studying a pioneering case of LLHD, and drawing on a pre-/postoccupancy evaluation approach, this study used an innovative methodology utilizing mobile tracking devices to adequately provide reliable data about the time nurses spend at specific locations.

Results:

Our analysis reveals that the answer to the question concerning the impact of LLHD, as advocated by its proponents, on nurses’ allocation of time for value-adding activities versus waste time remains inconclusive. Our findings indicate no discernible difference in the amount of value-adding time nurses spent in the old facility compared to the new one.

Conclusion:

Our experience suggests that mobile tracking devices offer an affordable, efficient means of collecting data that produces objective measurements. Nevertheless, the interpretation of this time-based data necessitates the inclusion of supplementary qualitative information.
The Association of Self-Esteem With Health and Well-Being: A Quantitative Synthesis of 40 Meta-Analyses
Authors: Zell Ethan , Johansson Julia S.
Published: February 2024

Prior meta-analyses have examined the association between self-esteem and a variety of specific outcomes. Here we aggregated data across 40 unique meta-analyses, which collectively included more than 2,000 studies and 1 million participants to examine the cross-sectional association between self-esteem and overall health/well-being. Results indicated that self-esteem has a robust overall association with health/well-being ( r = .31). Moderator analyses indicated that self-esteem associations are consistent across regions, self-esteem scales, and research designs (correlational, case/control), robust across objective and subjective outcomes, and similar to the associations of other established predictors (locus of control, neuroticism, social support). However, self-esteem associations were smaller in child/adolescent samples ( r = .23) and in studies examining physical health ( r = .15) as opposed to mental health ( r = .42) or psychological adjustment ( r = .29). As the first to estimate its overall association with health/well-being, this report should stimulate theoretical integration on the potential benefits of self-esteem.
Proton Pump Inhibitors Use in Kidney Transplant Recipients: A Population-Based Study
Authors: Kiberd James , Quinn Robert R. , Ravani Pietro , Lentine Krista L. , Clarke Alix , Jeong Rachel , Faruque Labib , Lam Ngan N.
Published: February 2024

Background:

Kidney transplant recipients are commonly prescribed proton-pump inhibitors (PPIs), but due to concern for polypharmacy, chronic use should be limited.

Objective:

The objective was to describe PPI use in kidney transplant recipients beyond their first year of transplant to better inform and support deprescribing initiatives.

Design:

We conducted a retrospective, population-based cohort study using linked health care databases.

Setting:

This study was conducted in Alberta, Canada.

Patients:

We included all prevalent adult, kidney-only transplant recipients between April 2008 and December 2017 who received their transplant between May 2002 and December 2017.

Measurements:

The primary outcome was ongoing or new PPI use and patterns of use, including frequency and duration of therapy, and assessment of indication for PPI use.

Methods:

We ascertained baseline characteristics, covariate information, and outcome data from the Alberta Kidney Disease Network (AKDN). We compared recipients with evidence of a PPI prescription in the 3 months prior to study entry to those with a histamine-2-receptor antagonist (H2Ra) fill and those with neither.

Results:

We identified 1823 kidney transplant recipients, of whom 868 (48%) were on a PPI, 215 (12%) were on an H2Ra, and 740 (41%) were on neither at baseline. Over a median follow-up of 5.4 years (interquartile range [IQR] = 2.6-9.3), there were almost 45 000 unique PPI prescriptions dispensed, the majority (80%) of which were filled by initial PPI users. Recipients who were on a PPI at baseline would spend 91% (IQR = 70-98) of their graft survival time on a PPI in follow-up, and nephrologists were the main prescribers. We identified an indication for ongoing PPI use in 54% of recipients with the most common indication being concurrent antiplatelet use (26%).

Limitations:

Our kidney transplant recipients have access to universal health care coverage which may limit generalizability. We identified common gastrointestinal indications for PPI use but did not include rare conditions due to concerns about the validity of diagnostic codes. In addition, symptoms suggestive of reflux may not be well coded as the focus of follow-up visits is more likely to focus on kidney transplant.

Conclusions:

Many kidney transplant recipients are prescribed a PPI at, or beyond, the 1-year post-transplant date and are likely to stay on a PPI in follow-up. Almost half of the recipients in our study did not have an identifiable indication for ongoing PPI use. Nephrologists frequently prescribe PPIs to kidney transplant recipients and should be involved in deprescribing initiatives to reduce polypharmacy.
Cognition, willingness, and behavior towards human papillomavirus vaccination in Chinese university students: Planned behavior, health beliefs, and media influence
Authors: Zhou Xinyuan , Whyke Thomas William , Wang Aiqing
Published: February 2024

This study assessed Human papillomavirus (HPV) vaccination knowledge, willingness, and status among University of Nottingham Ningbo undergraduate students, utilizing the Theory of Planned Behaviour (TPB) and Health Belief Model (HBM). Self-administered questionnaires covered demographics, sexual behavior, and factors influencing vaccination intentions. Quantitative and qualitative analyses included t-tests, ANOVA, Pearson correlation, logistic regression, and linear regression. Of 373 surveyed students, the HPV vaccination rate was notably higher than in previous studies (45.84%). While participants demonstrated good HPV knowledge, male students were less aware. Intentions to vaccinate were high, influenced by gender, profession, parental education, family/friend cancer history, and health status. The study confirmed TPB and HBM’s efficacy in predicting vaccination intentions, enhancing media-related aspects and perceived barriers. Gender differences in HPV information exposure, media use, and representations were identified, offering insights for optimized health communication strategies.
Bibliometric Study of Scientific Output Between 2011 and 2020 Regarding Teaching-Learning of the Sciences Through Comic Books
Authors: Gemelli Emanuela , Olmedo-Moreno Eva , Úbeda-Sánchez Álvaro Manuel , Rodríguez-Sabiote Clemente
Published: February 2024

The main aims of the present research were to: (1) describe the scientific outputs indexed in the Scopus and Web of Science databases, from now on WoS, regarding the use of comic books as didactic resources in the teaching-learning of the sciences, and; (2) establish the conceptual structure of scientific output regarding the use of comic books as didactic resources in the teaching-learning of science. A quantitative-bibliometric methodology was followed on a sample of 60 scientific documents recovered using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses strategy, from now on PRISMA. Findings suggest that the topic is still emerging given the novelty of the discipline and that published studies tend to be low impact in terms of the number of citations they receive. With regards to the conceptual structure, the most relevant themes and trends to emerge pertained to medical education, comic books and illustrations, and the use of mobile devices. Finally, analysis of the keywords used by the top 20 most relevant authors, it was possible to infer a degree of correspondence between sources, keywords and the continents responsible for the greatest scientific output on the topic.
Influence of Board Governance Characteristics on Sustainability Accounting and Reporting in a Developing Country: Evidence From Nigeria Large Businesses
Authors: Ikpor Isaac Monday , Akanu Otu Otu , Ugwu Joy , Udu Gabriel Obasi Chidozie , Ulo Fabian Udum , Achilike Nicholas , Adama Linus , Oganezi Bethel
Published: February 2024

Even though the determinants of sustainability reporting have been highly studied, the influence of Board Governance characteristics on sustainability reporting has mainly remained understudied in Africa, especially Nigeria, despite the overwhelming Business opportunities in the country. This study, therefore, investigates the influence of Board Governance on sustainability accounting and reporting, drawing insights from large businesses listed in Nigerian stock exchanges. Using a sample of 167 reports drawn from three sources—annual reports, sustainability reports, and website over the period 2015 to 2020, this study employs content analysis to quantify three layers of sustainability disclosure and fixed effects regression estimation model to predict the influence of Board governance variables on sustainability reporting quality. Our results indicate that Board governance characteristics such as Board capacity, board independence and Board Incentives are significant factors that affect sustainability reporting quality. The results further suggest that although the number of directors on the board is positively associated with the quality of sustainability reporting, CEO duality is insignificant and has a negative association with the quality of sustainability reporting. This study provides evidence that setting up long-term incentive-based compensation affects sustainability reporting positively in developing countries, such as Nigeria.
Sinistral Portal Hypertension Due to a Pancreatic Pseudocyst: A Rare Cause of Upper Gastrointestinal Bleeding
Authors: Bathobakae Lefika , Ozgur Sacide S. , Aiken Arielle , Mahmoud Anas , Escobar Jessica , Melki Gabriel , Cavanagh Yana , Baddoura Walid
Published: February 2024

Sinistral portal hypertension (SPH), also known as segmental portal hypertension, is a complication of pancreatic disorders and an extremely rare cause of upper gastrointestinal (GI) bleeding. SPH is observed in patients without cirrhosis and arises from splenic vein thrombosis. Unmitigated backflow of blood may cause gastric venous congestion and ultimately GI hemorrhage. Herein, we report a rare case of massive hematemesis due to SPH in a male patient with a history of chronic pancreatitis and pancreatic pseudocyst. Our patient was successfully treated with endoscopic necrosectomy followed by open splenectomy, distal pancreatectomy, and partial gastric resection.
Effect of Oral Prednisone on the Prevention and Management of Proliferative Vitreoretinopathy After Open-Globe Injury
Authors: Yao Tianyuan , Chauhan Muhammad Z. , Uwaydat Sami H.
Published: February 2024

Purpose: To determine the impact of oral prednisone on the final visual acuity (VA) and prevention of proliferative vitreoretinopathy (PVR) in patients having pars plana vitrectomy (PPV) for globe injuries. Methods: A retrospective chart review was performed of all globe injuries with an initial repair and subsequent PPV between 2009 and 2018. Data included the initial VA, zones of injury, initial closure date, time to secondary intervention (PPV), oral prednisone (1 mg/kg/day) use, the final VA, and enucleation rate. Multivariable regression models were used to assess the impact of oral prednisone use on anatomic and functional outcomes. Results: The mean (±SD) patient age was 46.25 ±18.56 years (range, 13-92); 131 (83.9%) were men. Oral prednisone intake was recorded in 81 patients (52.3%). The prednisone group had significantly more zone 3 involvement ( P = .001), worse initial VA (2.28 vs 1.92 logMAR; P = .003), and a greater mean number of surgeries ( P = .020) than the no-steroids (control) group but an equivalent final logMAR VA (1.57 vs 1.52; P = .881). The prednisone group had significant VA improvement ( P = .025); however, oral prednisone use did not predict the development of PVR (29.23% vs 12.90%; odds ratio [OR], 2.81; 95% CI, 0.89-8.85) or retinal detachment (27.27% vs 29.58%; OR, 0.59; 95% CI, 0.23-1.56). Conclusions: Despite a worse initial clinical presentation, patients who received oral prednisone had significant visual improvement compared with the control group. However, oral prednisone (1 mg/kg/day) use at the time of injury did not decrease the PVR rate.
Surgical Approach to Acute Osteochondral Fracture With Patellar Instability in Skeletally Immature Patients
Authors: Coladonato Carlo , Wilson Sean M. , Freedman Kevin B.
Published: February 2024

Background:

Patellar instability is a common condition that affects many young, active patients and can lead to long-term disability. This video aims to provide insights in the treatment of acute osteochondral fractures in skeletally immature patients after acute patellar dislocation.

Indications:

Patients who present with acute patellar dislocation and evidence of osteochondral fracture or osteochondral fracture with a loose body are potential candidates for medial patellofemoral ligament reconstruction (MPFLR) with osteochondral fragment fixation.

Technique Description:

In case 1, arthroscopy revealed a medial patellar facet defect. A medial patellar incision was made with dissection down to the vastus medialis oblique fascia and medial retinaculum. Before continuing to capsulotomy, the dissection for the MPFLR is completed by dissecting down to create a plane between layers 2 and 3. Capsulotomy is then performed with retrieval of the loose body, preparation of the patellar defect, and fixation of the osteochondral fragment. The MPFLR is then performed. An allograft is fixed to the patella with 2 pushlock anchors, and to a distally directed femoral tunnel using a 7-mm pitchfork SwiveLock tenodesis anchor, with care to avoid the medial femoral physis. The capsulotomy is then closed underneath the graft, with layer 2 closed above it. In case 2, a large osteochondral fracture of the lateral femoral condyle with loose cartilage flaps was arthroscopically identified. An anterior incision was made and a lateral lengthening was completed to perform a laterally based arthrotomy to expose the defect on the lateral femoral condyle. The defect site was prepared and the loose body was secured and fixated into the donor site lesion using bioabsorbable screws. The MPFLR was completed as in case 1, and the wound was closed in standard fashion.

Results:

Acute patellar dislocation with osteochondral fracture has been shown to lower both subjective and functional patient outcome measures. A recent study suggests that in large osteochondral fractures after patella dislocation, internal fixation improves mid- and long-term outcomes when compared with debridement alone.

Conclusion:

The MPFLR with concurrent osteochondral fracture fixation in patients with open physes is a reliable option for improving patellar stability and protecting articular cartilage from further injury.

Patient Consent Disclosure Statement:

The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form.
An Interdisciplinary Approach to Supporting the Personal Development of College Students With an Intellectual Disability
Authors: Smith Hill Rebecca B. , Stinnett Chelsea VanHorn , Plotner Anthony J. , Fields Alexander M. , Lewis Olivia J. , Castle Madeline
Published: February 2024

High-quality inclusive postsecondary education programs strive for authentic inclusion of students with intellectual and developmental disabilities. Typicality for students and enhanced integration into the larger institution of higher education are guiding principles outlined in recently developed, national model standards. With these novel and inclusive opportunities, students often need support to navigate and troubleshoot the myriad situations that may arise as a result of this level of inclusion on a college campus. Inclusive college programs typically provide support in academic, employment, and independent living domains but often neglect building skills encapsulated under “personal development.” This paper describes a unique personal development model of support with aligned theoretical underpinnings and interdisciplinary practices derived from social work, counselor education, and education fields.
Learning From Self-Advocates: Changing Perspectives About Disability
Authors: Snider Julia E. , Oosting Alexis A. , Andersen Amy J. , DeWaard Jennifer
Published: February 2024

Many educators learn about people with disabilities without learning from them. This article describes the value of inviting people with disabilities, including individuals with extensive support needs (ESN), to share their experiences and knowledge with others. In this article, we describe how to create a Self-Advocate Guest Presenter Series to provide opportunities for individuals with disabilities to tell their stories. In addition, this article includes ideas to support educators in using what they learned from the presenters within their classrooms and advocacy.
Folic acid-functionalized PEGylated niosomes co-encapsulated cisplatin and doxoribicin exhibit enhanced anticancer efficacy
Authors: Safari Sharafshadeh Mona , Tafvizi Farzaneh , Khodarahmi Parvin , Ehtesham Somayeh
Published: February 2024

The medical field is faced with the difficult task of developing a new approach to curing cancer, which is prevalent in organs such as the breast and ovaries and has a high mortality rate. Since chemotherapy is the conventional method of treatment, efforts are being made to improve it to help patients function better. Fortunately, with the use of nanocarriers and their remarkable ability to manage and direct drug delivery, progress is being made in cancer treatment. In addition, folic acid-coated nanocarriers offer several advantages in drug delivery, including improved stability, bioavailability, targeted delivery and drug solubility. These properties make them promising tools for improving cancer treatment efficacy. This research focused on investigating the stability of a specific niosomal formulation (consisting of Span 60 and cholesterol) under different temperature conditions (4 and 25 ℃) for 2 months. In addition, the drug release rate of the formulation was evaluated. The results showed that the size and polydispersity index increased significantly in the stability studies, but the entrapment efficiency% decreased dramatically over time. In addition, encapsulation of drugs in niosomal formulations resulted in stable and slow drug release. The cytotoxicity evaluation results of formulations containing doxorubicin and cisplatin show their significant inhibitory effect on both breast and ovarian cancer cell lines (IC50 for DOX–CIS–Nio@PEG–FA formulation was 6.11 and 17.87 µg/mL for A2780 and MCF-7, respectively). Niosomes loaded with a combination of two drugs were found to affect gene expression in the cancer cell lines tested. They decreased the expression of BCl2, VEGF, CCND1, and HER2 genes while increasing the expression of BAX gene. Flow cytometry results indicated that niosomes loaded with doxorubicin and cisplatin increased the rate of apoptosis in both cell lines compared to a drug mixture. ROS and cell cycle arrest, confirm the significant inhibition of cancer cells and their destruction in the presence of the synthesized noisome formulation in comparison to free drugs and the combination of two drugs. The potential of this novel approach for delivering drugs to cancer cells lies in the ability to combine treatments and target multiple cancers simultaneously. Such formulations allow co-delivery of drugs to different cancer cells, thereby improving the efficacy of chemotherapy through synergistic effects between drugs.

Graphical Abstract
Transcriptomic analysis of intestinal organoids, derived from pigs divergent in feed efficiency, and their response to Escherichia coli
Authors: Madsen Ole , Rikkers Roxann S.C. , Wells Jerry M. , Bergsma Rob , Kar Soumya K. , Taverne Nico , Taverne-Thiele Anja J. , Ellen Esther D. , Woelders Henri
Published: February 2024

Background

There is increasing interest in using intestinal organoids to study complex traits like feed efficiency (FE) and host-microbe interactions. The aim of this study was to investigate differences in the molecular phenotype of organoids derived from pigs divergent for FE as well as their responses to challenge with adherent and invasiveEscherichia coli(E. coli).

Results

Colon and ileum tissue from low and high FE pigs was used to generate 3D organoids and two dimensional (2D) monolayers of organoid cells forE. colichallenge. Genome-wide gene expression was used to investigate molecular differences between pigs that were phenotypically divergent for FE and to study the difference in gene expression after challenge withE. coli. We showed, (1) minor differences in gene expression of colon organoids from pigs with low and high FE phenotypes, (2) that anE. colichallenge results in a strong innate immune gene response in both colon and ileum organoids, (3) that the immune response seems to be less pronounced in the colon organoids of high FE pigs and (4) a slightly stronger immune response was observed in ileum than in colon organoids.

Conclusions

These findings demonstrate the potential for using organoids to gain insights into complex biological mechanisms such as FE.
Effects of circadian clock disruption on gene expression and biological processes in Aedes aegypti
Authors: Shetty Vinaya , Adelman Zach N. , Slotman Michel A.
Published: February 2024

Background

This study explores the impact of disrupting the circadian clock through a Cycle gene knockout (KO) on the transcriptome of Aedes aegypti mosquitoes. The investigation aims to uncover the resulting alterations in gene expression patterns and physiological processes.

Results

Transcriptome analysis was conducted on Cyc knockout (AeCyc-/-) and wild-type mosquitoes at four time points in a light-dark cycle. The study identified system-driven genes that exhibit rhythmic expression independently of the core clock machinery. Cyc disruption led to altered expression of essential clock genes, affecting metabolic processes, signaling pathways, stimulus responses and immune responses. Notably, gene ontology enrichment of odorant binding proteins, indicating the clock's role in sensory perception. The absence of Cyc also impacted various regulation of metabolic and cell cycle processes was observed in all time points.

Conclusions

The intricate circadian regulation in Ae. aegypti encompasses both core clock-driven and system-driven genes. The KO of Cyc gene instigated extensive gene expression changes, impacting various processes, thereby potentially affecting cellular and metabolic functions, immune responses, and sensory perception. The circadian clock's multifaceted involvement in diverse biological processes, along with its role in the mosquito's daily rhythms, forms a nexus that influences the vector's capacity to transmit diseases. These insights shed light on the circadian clock's role in shaping mosquito biology and behavior, opening new avenues for innovative disease control strategies.
Association between C10X polymorphism in the CARD8 gene and inflammatory markers in young healthy individuals in the LBA study
Authors: Fransén Karin , Hiyoshi Ayako , Paramel Geena V. , Hurtig-Wennlöf Anita
Published: February 2024

Background

The Caspase activation and recruitment domain 8 (CARD8) protein is a component of innate immunity as a negative regulator of NF- ĸB, and has been associated with regulation of proteins involved in inflammation. Expression ofCARD8mRNA and protein has been identified in human atherosclerotic lesions, and the truncated T30A variant (rs2043211) ofCARD8has been associated with lower C-reactive (CRP) and MCP-1 levels in myocardial infarction patients. The present study examines the role of a genetic variation in theCARD8gene in relation to a selection of markers of inflammation.

Methods

In a cross-sectional study of young healthy individuals (18.0–25.9 yrs,n = 744) the association between the rs2043211 variant in theCARD8gene and protein markers of inflammation was assessed. Genotyping of theCARD8C10X (rs2043211) polymorphism was performed with TaqMan real time PCR on DNA from blood samples. Protein levels were studied via Olink inflammation panel (https://olink.com/). Using linear models, we analyzed men and two groups of women with and without estrogen containing contraceptives separately, due to previous findings indicating differences between estrogen users and non-estrogen using women. Genotypes were analyzed by additive, recessive and dominant models.

Results

The minor (A) allele of the rs2043211 polymorphism in theCARD8gene was associated with lower levels of CCL20 and IL-6 in men (CCL20, Additive model:p = 0.023; Dominant model:p = 0.016. IL-6, Additive model:p = 0.042; Dominant model:p = 0.039). The associations remained significant also after adjustment for age and potential intermediate variables.

Conclusions

Our data indicate that CARD8 may be involved in the regulation of CCL20 and IL-6 in men. No such association was observed in women.

These findings strengthen and support previous in vitro data on IL-6 and CCL20 and highlight the importance ofCARD8as a factor in the regulation of inflammatory proteins. The reason to the difference between sexes is however not clear, and the influence of estrogen as a possible factor important for the inflammatory response needs to be further explored.
Contextual effects: how to, and how not to, quantify them
Authors: Saueressig Tobias , Pedder Hugo , Owen Patrick J , Belavy Daniel L
Published: February 2024

The importance of contextual effects and their roles in clinical care controversial. A Cochrane review published in 2010 concluded that placebo interventions lack important clinical effects overall, but that placebo interventions can influence patient-reported outcomes such as pain and nausea. However, systematic reviews published after 2010 estimated greater contextual effects than the Cochrane review, which stems from the inappropriate methods employed to quantify contextual effects. The effects of medical interventions (i.e., the total treatment effect) can be divided into three components: specific, contextual, and non-specific. We propose that the most effective method for quantifying the magnitude of contextual effects is to calculate the difference in outcome measures between a group treated with placebo and a non-treated control group. Here, we show that other methods, such as solely using the placebo control arm or calculation of a ‘proportional contextual effect,’ are limited and should not be applied. The aim of this study is to provide clear guidance on best practices for estimating contextual effects in clinical research.
Sex steroid and cognitive function among community-dwelling older men with or without vascular risk factors: a cross-sectional study
Authors: Tang Shuning , Huang Limei , Lin Fangting , Chen Xiuqin , Wang Yunhui , Xu Jixiang , Wang Yujie , Gao Junling , Xiao Qianyi
Published: February 2024

Background

The relationship of testosterone and estradiol concentrations with cognitive function among community-dwelling older men was inconclusive. To examine the association of serum testosterone and estradiol concentrations with cognitive function in older men with or without vascular risk factors (VRFs).

Methods

This cross-sectional study consisted of 224 community-dwelling men aged 65–90 years in the Songjiang District of Shanghai, China. Serum testosterone and estradiol were measured by electrochemiluminescence immunoassay. The following five factors were defined as VRFs in this study: obesity, history of hypertension, diabetes, stroke, and coronary heart disease. Multivariable linear regression was used to examine the association of testosterone and estradiol with the Mini-Mental State Examination (MMSE) in participants with or without VRF. Restricted cubic spline (RCS) regression was performed to account for the nonlinearity of these associations.

Results

An inverted “U” shaped non-linear relationship was found between testosterone concentration and MMSE score in men with one VRF (P overall =.003, non-linear P =.002). Estradiol showed an inverted “U” shaped non-linear relationship with MMSE score independent of VRFs (men without VRF, P overall =.049, non-linear P =.015; men with one VRF, overall P =.007, non-linear P =.003; men with two or more VRFs, overall P =.009, non-linear P =.005).

Conclusion

In older men, an optimal level of sex steroid concentration may be beneficial to cognitive function and the VRFs should be considered when interpreting the relationship between sex steroid and cognitive function.
Dexamethasone versus methylprednisolone for multiple organ dysfunction in COVID-19 critically ill patients: a multicenter propensity score matching study
Authors: Aljuhani Ohoud , Korayem Ghazwa B. , Altebainawi Ali F. , AlMohammady Daniah , Alfahed Amjaad , Altebainawi Elaf F. , Aldhaeefi Mohammed , Badreldin Hisham A. , Vishwakarma Ramesh , Almutairi Faisal E. , Alenazi Abeer A. , Alsulaiman Thamer , Alqahtani Rahaf Ali , Al Dhahri Fahad , Aldardeer Namareq , Alenazi Ahmed O. , Al Harbi Shmeylan , Kensara Raed , Alalawi Mai , Al Sulaiman Khalid
Published: February 2024

Background

Dexamethasone usually recommended for patients with severe coronavirus disease 2019 (COVID-19) to reduce short-term mortality. However, it is uncertain if another corticosteroid, such as methylprednisolone, may be utilized to obtain better clinical outcome. This study assessed dexamethasone’s clinical and safety outcomes compared to methylprednisolone.

Methods

A multicenter, retrospective cohort study was conducted between March 01, 2020, and July 31, 2021. It included adult COVID-19 patients who were initiated on either dexamethasone or methylprednisolone therapy within 24 h of intensive care unit (ICU) admission. The primary outcome was the progression of multiple organ dysfunction score (MODS) on day three of ICU admission. Propensity score (PS) matching was used (1:3 ratio) based on the patient’s age and MODS within 24 h of ICU admission.

Results

After Propensity Score (PS) matching, 264 patients were included; 198 received dexamethasone, while 66 patients received methylprednisolone within 24 h of ICU admission. In regression analysis, patients who received methylprednisolone had a higher MODS on day three of ICU admission than those who received dexamethasone (beta coefficient: 0.17 (95% CI 0.02, 0.32), P = 0.03). Moreover, hospital-acquired infection was higher in the methylprednisolone group (OR 2.17, 95% CI 1.01, 4.66; p = 0.04). On the other hand, the 30-day and the in-hospital mortality were not statistically significant different between the two groups.

Conclusion

Dexamethasone showed a lower MODS on day three of ICU admission compared to methylprednisolone, with no statistically significant difference in mortality.
Performance evaluation of Truenat MTB and Truenat MTB-RIF DX assays in comparison to gene XPERT MTB/RIF ultra for the diagnosis of pulmonary tuberculosis in Uganda
Authors: Ssengooba Willy , Katamba Achilles , Sserubiri James , Semugenze Derrick , Nyombi Abdunoor , Byaruhanga Raymond , Turyahabwe Stavia , Joloba Moses L.
Published: February 2024

Background

The World Health Organization endorsed Truenat MTB rapid molecular assay in 2020 and recommended additional in-country evaluation studies before uptake. We evaluated the accuracy and operational feasibility of Truenat MTB assay (Truenat) in comparison with GeneXpert Ultra and culture.

Methods

In a cross-sectional study of 250 presumptive TB patients, participants were requested to provide a sputum sample on the day of their visit to the clinic. The sputum sample was homogenized and a portion was tested using GeneXpert Ultra as per the routine standard procedure and the other portion was tested using Truenat assay at the clinic laboratory. The second sample portion was processed for Concentrated Fluorescent smear Microscopy (CFM), LJ, and MGIT cultures. Truenat sensitivity and specificity were compared to GeneXpert Ultra and culture. Test performance characteristics and operational feasibility assessment data through interview of the study laboratory staff were also collected and summarized as proportions and percentages.

Results

Of the 250 participants recruited in the study, the sensitivity and specificity of Truenat was n/N (%, 95%CI); 66/82 (80.5, 70.2–88.4) and 156/159 (98.1, 94.5–99.6) when compared with Ultra, 50/64 (89.3, 66.0-87.4) and 166/180 (92.2, 87.2–95.6) when compared with LJ, 58/71 (81.7,70.7–89.8) and 131/138 (94.9, 89.8–97.9) when compared to MGIT culture and 59/73 (80.8, 69.9–89.1) and 159/169 (94.1,89.3–97.1) when compared to LJ and/or MGIT culture. The sensitivity of Truenat was lower, 14/23 (60.9, 40.6–82.8) among smear-negative compared to 45/50 (90.0, 78.1–96.6) among smear-positive participants but not different by HIV status. There were no special training needs especially among laboratory personnel with previous GeneXpert /molecular test experience, 19/242 (7.8%) error/invalid, and 12 (17,4%) uninterpretable/indeterminate results mainly for rifampicin resistance determination. However, there were 3 (3.5%) of GeneXpert Ultra indeterminate results.

Conclusion

Among presumptive TB patients in Uganda, the Truenat assay has high sensitivity and specificity. The Truenat assay has acceptable operational feasibility attributes when compared with the GeneXpert Assay.
Ultrasound characteristics of normal parathyroid glands and analysis of the factors affecting their display
Authors: Wu Cuiping , Zhu Binyang , Kang Song , Wang Shiyu , Liu Yingying , Mei Xue , Zhang He , Jiang Shuangquan
Published: February 2024

Background

Parathyroid glands are important endocrine glands, and the identification of normal parathyroid glands is crucial for their protection. The aim of this study is to explore the sonographic characteristics of normal parathyroid glands and analyze the factors affecting their display.

Methods

Seven hundred three subjects who underwent physical examination at our hospital were included. The number, location, size, morphology, echogenicity and blood flow distribution of parathyroid glands were recorded. The ultrasound characteristics and display rate were also summarized. Meanwhile, shear wave elastography was performed in 50 cases to provide the stiffness measurements, and 26 cases received contrast-enhanced ultrasonography for the assessment of microcirculatory perfusion. Furthermore, we analyzed the factors affecting parathyroid display, including basic information of the subjects and ultrasound features of the thyroid.

Results

① A total of 1038 parathyroid glands were detected, among which, 79.29% were hyperechoic, 20.71% were isoechoic, 88.15% were oval-shaped, and 86.71% had blood flow of grade 0-I. ② 81.79% of the subjects had at least one parathyroid gland detected. ③ The Emean, Emax, PI and AUC of the parathyroid glands were significantly lower than those of the adjacent thyroid tissue (P < 0.05). ④ The display of normal parathyroid glands was related to BMI, thyroid echogenicity and thyroid volume of the subjects (P < 0.05).

Conclusions

Normal parathyroid glands tend to appear as oval-shaped hyperechoic nodules with blood flow of grade 0-I. BMI, thyroid echogenicity and thyroid volume are independent factors affecting the display of parathyroid glands.
Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
Authors: Boccacino Jacqueline Marcia , dos Santos Peixoto Rafael , Fernandes Camila Felix de Lima , Cangiano Giovanni , Sola Paula Rodrigues , Coelho Bárbara Paranhos , Prado Mariana Brandão , Melo-Escobar Maria Isabel , de Sousa Breno Pereira , Ayyadhury Shamini , Bader Gary D. , Shinjo Sueli Mieko Oba , Marie Suely Kazue Nagahashi , da Rocha Edroaldo Lummertz , Lopes Marilene Hohmuth
Published: February 2024

Background

Glioblastoma (GBM) is an aggressive brain tumor that exhibits resistance to current treatment, making the identification of novel therapeutic targets essential. In this context, cellular prion protein (PrPC) stands out as a potential candidate for new therapies. Encoded by the PRNP gene, PrPC can present increased expression levels in GBM, impacting cell proliferation, growth, migration, invasion and stemness. Nevertheless, the exact molecular mechanisms through which PRNP/PrPC modulates key aspects of GBM biology remain elusive.

Methods

To elucidate the implications of PRNP/PrPC in the biology of this cancer, we analyzed publicly available RNA sequencing (RNA-seq) data of patient-derived GBMs from four independent studies. First, we ranked samples profiled by bulk RNA-seq as PRNPhigh and PRNPlow and compared their transcriptomic landscape. Then, we analyzed PRNP+ and PRNP- GBM cells profiled by single-cell RNA-seq to further understand the molecular context within which PRNP/PrPC might function in this tumor. We explored an additional proteomics dataset, applying similar comparative approaches, to corroborate our findings.

Results

Functional profiling revealed that vesicular dynamics signatures are strongly correlated with PRNP/PrPC levels in GBM. We found a panel of 73 genes, enriched in vesicle-related pathways, whose expression levels are increased in PRNPhigh/PRNP+ cells across all RNA-seq datasets. Vesicle-associated genes, ANXA1, RAB31, DSTN and SYPL1, were found to be upregulated in vitro in an in-house collection of patient-derived GBM. Moreover, proteome analysis of patient-derived samples reinforces the findings of enhanced vesicle biogenesis, processing and trafficking in PRNPhigh/PRNP+ GBM cells.

Conclusions

Together, our findings shed light on a novel role for PrPC as a potential modulator of vesicle biology in GBM, which is pivotal for intercellular communication and cancer maintenance. We also introduce GBMdiscovery, a novel user-friendly tool that allows the investigation of specific genes in GBM biology.