bluuebunny/crossref_metadata_2025 huggingface dataset:
Collaboratively Designing an App for a More Personalized, Community-Endorsed Continuous Glucose Monitoring Onboarding Experience: An Early Study
Authors: Chao Edward C. , Zhang Mingjin , Houle Mary A. , Rataj Heidi
Published: November 2023

Background:

Acclimating to a new technology device, such as a continuous glucose monitor (CGM), can be challenging. Current resources may not sufficiently answer questions patients living with diabetes (PWD) may have. We asked how we might improve the process to onboard a PWD to CGM. Our specific aims were (1) to develop, employing a co-designing approach, a prototype of an app for facilitating onboarding to CGM and (2) to obtain early feedback on its usability.

Methods:

We applied a human-centered design (HCD) approach; this process first seeks to deeply understand the unmet needs and frustrations users face. After wearing a demonstration CGM; observing PWD onboarding with health care professionals (HCPs) in clinic; and interviewing 8 PWD and 2 HCP, we developed, tested, and refined a low-fidelity prototype of a clickable app. With insights from this initial round of feedback, we then created a high-fidelity prototype with 3 key features: (1) individual entry of goals and questions; (2) a daily progress tracker for these goals; and (3) a community portal that facilitates exchange of questions and answers. We used the validated System Usability Scale (SUS) to quantify user feedback.

Results:

Focus group participants found our early app to be usable and acceptable. Measurement of usability by the SUS yielded a score of 74, which is above average (68) reported for all applications tested, per usability.gov.

Conclusions:

Our early prototype app is a more personalized, additional tool that could bridge an information and support gap for patients who are new to CGM. This app could also help PWD on an ongoing basis, by evolving with them to enhance ease and engagement with diabetes self-management.
Analysis of Molecular Changes and Features in Rat Knee Osteoarthritis Cartilage: Progress From Cellular Changes to Structural Damage
Authors: Zhao Zixi , Ito Akira , Kuroki Hiroshi , Aoyama Tomoki
Published: November 2023

Objective

Although knee osteoarthritis (KOA) is a common disease, there is a lack of specific prevention and early treatment methods. Hence, this study aimed to examine the molecular changes occurring at different stages of KOA to elucidate the dynamic nature of the disease.

Design

Using a low-force compression model and analyzing RNA sequencing data, we identified molecular changes in the transcriptome of knee joint cartilage, including gene expression and molecular pathways, between the cellular changes and structural damage stages of KOA progression. In addition, we validated hub genes using an external dataset.

Results

Gene set enrichment analysis (GSEA) identified the following pathways to be associated with KOA: “B-cell receptor signaling pathway,” “cytokine-cytokine receptor interaction,” and “hematopoietic cell lineage.” Expression analysis revealed 585 differentially expressed genes, with 579 downregulated and 6 upregulated genes. Enrichment and clustering analyses revealed that the main molecular clusters were involved in cell cycle regulation and immune responses. Furthermore, the hub genes Csf1r, Cxcr4, Cxcl12, and Ptprc were related to immune responses.

Conclusions

Our study provides insights into the dynamic nature of early-stage KOA and offers valuable information to support the development of effective intervention strategies to prevent the irreversible damage associated with KOA, thereby addressing a major clinical challenge.
Designing digital solutions for sustainability: Navigating conflicting stakeholder requirements with dignity in mind
Authors: Tona Olgerta , Asatiani Aleksandre
Published: November 2023

This teaching case examines the challenges of designing a digital solution to address complex sustainability problems. The case follows the vice president for innovation of a mid-sized European digital agency involved in a project dedicated to designing a digital application that connects climate-conscious investors, banks, and homeowners in need of loans for green house renovations. In this case, students need to navigate stakeholders’ conflicting needs and consider broader aspects of environmental, social, and economic sustainability in the design of digital applications. At the same time, this digital solution should seek to promote stakeholders’ dignity.
Exposing the Care Conundrum of Low-Energy Pelvic Ring Fractures in Older Adults: A Review of 322 Patients
Authors: Abernathy Bailey R. , Huyke-Hernández Fernando A. , Rivard Rachael L. , Schroder Lisa K. , Switzer Julie A.
Published: November 2023

Introduction

A care conundrum for low-energy pelvic ring fracture patients in which they face financial burden after not qualifying for an inpatient stay of 3 days or more has been noted in the literature. The purpose of this study was to identify factors that lead to inpatient length of stay (IP LOS) ≥3 days in older adults with nonoperative pelvic ring fragility fractures and to highlight the challenging financial decision-making of those with IP LOS <3 days in the context of the Medicare 3-day rule.

Methods

This was a retrospective review of 322 patients aged ≥65 presenting from March 2016 and February 2019 to either of 2 emergency departments (EDs) after a ground-level fall resulting in a pelvic ring fracture. Patient demographic, IP LOS, and mortality data were extracted. Case management notes were analyzed to summarize financial decision-making for patients with IP LOS <3 days. Multivariate logistic regression analysis was conducted to identify factors that predicted IP LOS ≥3 days and mortality.

Results

IP LOS ≥3 days was associated with presentation to level I hospital (OR .30 [.19, 0.50]) and being single (OR 2.50 [1.10, 5.68]). 70.3% required a post-acute skilled nursing facility (SNF) stay. Of patients with LOS <3 days, 25.0% were financially responsible for their SNF stay, while 7.9% elected home care due to financial reasons. Overall 30-day, 90-day, and 1-year mortality were 2.5%, 8.1%, and 20.8%, respectively. For patients with LOS <3 days, returning to assisted living compared to discharging to a SNF increased 90-day mortality risk (HR 8.529, P = .0451). Having Medicare trended towards increased 90-day mortality risk compared to commercial insurance (HR 4.556, P = .0544).

Conclusion

The current system is failing older adult patients who sustain nonoperative low-energy pelvic ring fractures in terms of financial coverage of necessary post-acute treatment. This care conundrum has yet to be solved.
Bone Health Management in Elective Orthopaedic Surgery: A Claims-Based Observational Study
Authors: Jeray Kyle J. , Williams Setareh A. , Wang Yamei , Pearman Leny , Pyrih Nick , Singla Karun , Han Benjamin H. , Bukata Susan V.
Published: November 2023

Introduction

There are limited data on the management of bone health, including bone mineral density (BMD) evaluation and osteoporosis (OP) treatment, in patients undergoing elective orthopaedic surgeries.

Methods

This was a retrospective cohort study using administrative claims data from Symphony Health, PatientSource for patients aged ≥50 years with documented kyphoplasty/vertebroplasty (KP/VP), total knee arthroplasty (TKA), and total hip arthroplasty (THA). Risk stratification to identify patients at very high risk for fracture (VHRFx) was based on clinical practice guideline recommendations to the extent information on variables of interest were available from the claims database.

Results

A total of 251 919 patients met inclusion criteria: KP/VP (31 018), TKA (149 849), and THA (71 052). The majority were female (80.3%) with a mean (SD) age of 68.5 (7.5) years. Patients undergoing KP/VP were older and had a greater comorbidity burden associated with risk for falls, mobility issues, muscle weakness, and respiratory and cardiovascular diseases. In the 6 months before surgery, 11.8% of patients were tested and/or received treatment for OP. Patients undergoing KP/VP were more likely to be tested and/or treated (17.5%) than patients undergoing TKA (11.0%) or THA (10.9%). Overall, men had a lower rate of testing and/or treatment than women (4.6% vs 13.5%). In the 12 months before surgery, patients with an OP diagnosis and at VHRFx (30.8%) had a higher rate of treatment and/or testing than those without OP (11.5%), or those without OP but with a fracture in the year preceding surgery (10.2%).

Conclusions

Bone health management is suboptimal in patients undergoing elective orthopaedic surgeries and is worse in men than in women. Proper management of OP before and after surgery may improve outcomes.
Functional Somatic Syndromes Are Associated With Varied Postoperative Outcomes and Increased Opioid Use After Spine Surgery: A Systematic Review
Authors: Masood Raisa , LeRoy Taryn E. , Moverman Michael A. , Feldman Matthew W. , Rogerson Ashley , Salzler Matthew J.
Published: November 2023

Study Design

Systematic Review

Objective

To perform a systematic review assessing the relationship between functional somatic syndromes (FSSs) and clinical outcomes after spine surgery.

Methods

A systematic review of online databases (PubMed and Web of Science) through December 2021 was conducted via PRISMA guidelines to identify all studies investigating the impact of at least one FSS (fibromyalgia, irritable bowel syndrome (IBS), chronic headaches/migraines, interstitial cystitis, chronic fatigue syndrome, multiple chemical sensitivity) on outcomes after spine surgery. Outcomes of interest included patient reported outcome measures (PROMs), postoperative opioid use, cost of care, complications, and readmission rates.

Results

A total of 207 records were identified. Seven studies (n = 40,011 patients) met inclusion criteria with a mean MINORS score of 16.6 out of 24. Four studies (n = 21,086) reported postoperative opioid use; fibromyalgia was a strong risk factor for long-term opioid use after surgery whereas the association with chronic migraines remains unclear. Two studies (n = 233) reported postoperative patient reported outcome measures (PROMs) with mixed results suggesting a possible association between fibromyalgia and less favorable PROMs. One study (n = 18,692) reported higher postoperative complications in patients with fibromyalgia.

Conclusion

Patients with fibromyalgia and possibly migraines are at higher risk for prolonged postoperative opioid use and less favorable PROMs after spine surgery. There is limited research on the relationship between other Functional somatic syndromes (FSSs) and outcomes following spine surgery. Growing evidence suggests the variation in outcomes after spine procedures may be attributed to non-identifiable organic patient factors such as FSSs.
WALANT Scaphoid Fixation Under Field Sterility: A Case Report and Description of Technique
Authors: Ponich Brett , Turk Madison , Ramji Maleka , Knox Aaron
Published: November 2023

Wide Awake Local Anesthesia No Tourniquet (WALANT) technique has become an increasingly popular method of treating common hand pathologies. We present its application in the treatment of an acute minimally displaced scaphoid fracture. In addition, we demonstrate this can be achieved with field sterility using minimal surgical PPE and draping in a minor surgery setting, outside the main operating room theatre.
The Effectiveness of Online Learning in The Emerging Academic Environment: A Structural Equation Modelling (SEM) Approach
Authors: Chaudhary Manoj Kumar , Mahato Surendra , Adhikari Madhav
Published: November 2023

This study investigates the mediating influence of perceived ease of use on the relationship among faculty perspective, students’ perspective, technology perspective and the effectiveness of online learning. Employing a causal-comparative research design, data were collected from 390 respondents using a five-point Likert scale. Structural equation modelling through AMOS was employed as the data analysis tool. The research findings reveal that perceived ease of use plays a crucial mediating role in the association among faculty perspective, students’ perspective, technology perspective and the effectiveness of online learning. The results underscore the significance of user experience and the ease with which individuals interact with online learning platforms in influencing the overall effectiveness of online education. These findings offer valuable insights into enhancing the design and implementation of online learning systems, with the aim of improving user satisfaction and maximizing the educational outcomes of online learning environments. As technology continues to play an integral role in modern education, understanding the role of perceived ease of use becomes paramount in creating engaging and effective online learning experiences. Future research avenues may delve deeper into specific factors that contribute to perceived ease of use, further enriching our understanding of the intricate dynamics between user perspectives and online learning effectiveness.
“My People Wouldn’t Stand For This”: Ethnic Studies as Critical Civic Education
Authors: Gibbs Brian
Published: November 2023

Using testimonio method and methodology, this paper provides the stories and narratives of three Chicanx teachers who developed and taught an Ethnic Studies course to Latinx students in a large urban high school. Long celebrated as a way to fill in missing history, art, literature, resistance, and knowledge of communities of color, this paper argues that Ethnic Studies is also a vehicle to grow and embolden student sense of critical civic literacy. Through the narratives that emerge from these three teachers, the curriculum and pedagogy offered by these teachers positively impacts and propels students to advocate for themselves and their communities through civic and political action. The purpose of this article is to highlight the curricular and pedagogical choices of three teachers teaching Ethnic Studies and how Ethnic Studies can be used as a tool to increase Critical Civic Literacy.
ESCAPE the Boring Lecture: Tips and Tricks on Building Puzzles for Medical Education Escape Rooms
Authors: Shah Ashish S , Pitt Michael , Norton Laura
Published: November 2023

Escape rooms in medical education are a novel, game-based learning approach for teaching medical topics. In these escape rooms, learners complete a sequential series of medical-themed puzzles leading them to “escape” a specific story. Designing puzzles can be anxiety-provoking and may be the gatekeeper for educators in medicine to create their own escape rooms. Though there have been publications on the importance and methods of building a healthcare-themed-escape room, there is a gap in the literature on designing puzzles to teach specific learning objectives successfully. In this Scholarly Perspective, the authors share puzzle ideas and support tools and use Bloom's taxonomy as the framework to teach educators how to design challenging and engaging escape room puzzles.
The Impact of COVID-19 on the Training of Anesthesiologists in Hong Kong: Overcoming the Challenge
Authors: Chan Kevin Kai Wai , Yang Timothy Xianyi , Chan Albert Kam Ming
Published: November 2023

Objectives

This study aimed to investigate the impact of COVID-19 on the training of anesthesiologists in Hong Kong.

Introduction

COVID-19 has caused a substantial impact on anesthesiology training in multiple domains. The challenges faced by both trainees and educators remain a significant concern and adaptations in clinical teaching are warranted. We conducted this study to quantify the impact and identify learning areas in recurring pandemics.

Methods

Electronic surveys were distributed to anesthesiology trainees and fellows in Hospital Authority in Hong Kong. Data from respondents were collated and analyzed. Reliability analysis and exploratory factor analysis (EFA) were performed.

Results

A total of 97 responses were collected and analyzed. Majority (59% of trainees and 79% of fellows) agreed that the COVID-19 pandemic negatively impacted anesthesia training overall. Bag-mask ventilation and direct laryngoscopy were the 2 most affected areas in airway training; 47% of fellows observed a technical skill decline among trainees. Most respondents (64% of trainees and 71% of fellows) agreed that simulation sessions could help with residents’ training. Exploratory factor analysis indicated the following subscales: loss of educational opportunities, loss of caseload and formal training, loss of technical skills (regional and procedural), loss of technical skills (airway management), the hampering of ICU rotations, and difficulty teaching residents.

Conclusion

The COVID-19 pandemic has caused disruptions in caseload, technical skills training, work-based assessment, and continued medical education, hampering both trainees’ and fellows’ education. Measures to counter the effect of the pandemic were discussed. Our findings will help educators better understand the challenges, marshal resources, and plan to enhance trainees’ educational experience.
Book review: Amiya Kumar Das, Grassroots Democracy and Governance in India: Understanding Power, Sociality and Trust
Authors: Pathan Shofiul Alom
Published: November 2023

Amiya Kumar Das, Grassroots Democracy and Governance in India: Understanding Power, Sociality and Trust (Singapore: Springer Nature, 2022), 178 pp., €109.99, ISBN: 978-981-19-5109-1 (Hardcover).
“The Worker's Party sold out the street vendors”: Revanchist populism and the crisis of labor in Belo Horizonte, Brazil
Authors: Nogueira Mara
Published: November 2023

In this paper, I examine the links between revanchist populism and the labor crisis in Brazil, a country with a stratified labor market where informality is prevalent among low-income, racialized groups. I analyze the struggles of street vendors for accessing urban space in Belo Horizonte, Brazil, where the Worker’s Party (PT) played a key role in evicting vendors from public spaces and criminalizing their activity in the early 2000s. I focus on the connections between this initiative and a more recent “revitalization” policy that displaced street vendors from public spaces in the city center. In this context, I explore the political discourses of displaced workers during the 2018 elections that brought Bolsonaro to power. I show how the eviction stimulated antipetismo (anti-PT sentiment) among street vendors by triggering collective memories and rage against the party that “sold them out.” I argue that street vendors strongly identify as workers but are excluded from the unionized waged workingmen notion central to unions and Latin American left-wing parties. By discussing how street vendors reiterate their position as workers and not criminals, I highlight their identification with a moral notion of worker aligned with Bolsonaro’s conservative anti-crime agenda. I thus argue that support for Bolsonaro among street vendors was stimulated by the shortcomings of Brazil’s urban reform as well as the lack of appropriate policy responses to an increasingly heterogeneous and informalized workforce. I conclude by emphasizing the importance of supporting the collective struggles of non-waged workers as a path beyond revanchist populism.
A critical appraisal of professional competency frameworks: What guidance is provided for stroke rehabilitation clinicians managing ‘complexity’?
Authors: Indar Alyssa , Nelson Michelle , Berta Whitney , Mylopoulos Maria
Published: November 2023

Background

Given current health system trends, clinicians increasingly care for patients with complex care needs. There is a recognized lack of evidence to support clinician decision-making in these situations, as complex or multimorbid patients have been historically excluded from the types of research that inform clinical practice guidelines. However, expert clinicians at sites of excellence (e.g., Stroke Distinction sites) provide measurably excellent care. We sought to review profession-specific competency frameworks to locate information that may be supporting the development of clinician expertise when managing the care of patients with complex care needs.

Methods

We conducted a review of the professional competency frameworks for core members of the inpatient stroke rehabilitation team, to determine the degree of guidance and/or preparation for the management of patients with complex care needs. We developed and applied an assessment rubric to locate references to patient complexity, multimorbidity and complexity theory.

Results

Across the professional competency frameworks, there are some references to complexity at patient- and team-levels; there are fewer references to system-level complexity. We noted a lack of clear guidance for clinicians regarding the management of patients with complex care needs.

Conclusion

Further research is needed to explore how clinicians develop expertise in the management of patients with complex care needs, as we noted minimal guidance in the professional competency frameworks. However, we suggest that integrating complexity-related language into professional competency frameworks could better prime novice clinicians for new learning in the workplace and ease their transition into working in a complex context.
Renal Amyloidosis Secondary to Monoclonal Gammopathy of Renal Significance in a Young Patient: A Case Report
Authors: Ghosh Shreya , Gulati Yuvraj , Kala Chayanika , Garg Akansha , Thakur Ashwani Kumar
Published: November 2023

Monoclonal gammopathy of renal significance (MGRS), a subtype of plasma cell disorder, usually occurs in individuals >50 years. Amyloid light chain (AL)-associated primary amyloidosis can occur in both young and elderly individuals. However, the progression of AL amyloidosis is usually reported in aged MGRS patients several years after its onset. Herein, we report the case of a young patient with persistent proteinuria and bilateral edema. Histopathological examination confirmed a differential diagnosis of MGRS. Further, Congo red and immunohistochemical staining of the renal biopsy confirmed the presence of lambda-light-chain-derived amyloid deposits in the affected kidney. We report the predominance of MGRS-associated renal amyloidosis in a young patient, conflicting with the age criteria. This case report highlights age as an independent risk factor, signifying the need to diagnose amyloidosis in young people.
Image-centric compression of protein structures improves space savings
Authors: Staniscia Luke , Yu Yun William
Published: November 2023

Background

Because of the rapid generation of data, the study of compression algorithms to reduce storage and transmission costs is important to bioinformaticians. Much of the focus has been on sequence data, including both genomes and protein amino acid sequences stored in FASTA files. Current standard practice is to use an ordinary lossless compressor such as gzip on a sequential list of atomic coordinates, but this approach expends bits on saving an arbitrary ordering of atoms, and it also prevents reordering the atoms for compressibility. The standard MMTF and BCIF file formats extend this approach with custom encoding of the coordinates. However, the brand new Foldcomp tool introduces a new paradigm of compressing local angles, to great effect. In this article, we explore a different paradigm, showing for the first time that image-based compression using global angles can also significantly improve compression ratios. To this end, we implement a prototype compressor ‘PIC’, specialized for point clouds of atom coordinates contained in PDB and mmCIF files. PIC maps the 3D data to a 2D 8-bit greyscale image and leverages the well developed PNG image compressor to minimize the size of the resulting image, forming the compressed file.

Results

PIC outperforms gzip in terms of compression ratio on proteins over 20,000 atoms in size, with a savings over gzip of up to 37.4% on the proteins compressed. In addition, PIC’s compression ratio increases with protein size.

Conclusion

Image-centric compression as demonstrated by our prototype PIC provides a potential means of constructing 3D structure-aware protein compression software, though future work would be necessary to make this practical.
Alterations in gut microbiota and metabolite profiles in patients with infantile cholestasis
Authors: Jin Meng , Cui Jinghua , Ning Huijuan , Wang Meijuan , Liu Wenwen , Yao Kunyu , Yuan Jing , Zhong Xuemei
Published: November 2023

Background

Infantile cholestasis (IC) is the most common hepatobiliary disease in infants, resulting in elevated direct bilirubin levels. Indeed, hepatointestinal circulation impacts bile acid and bilirubin metabolism. This study evaluates changes in the gut microbiota composition in children with IC and identifies abnormal metabolite profiles associated with microbial alterations.

Results

The gut microbiota in the IC group exhibits the higher abundance of Veillonella, Streptococcus and Clostridium spp. (P < 0.05), compared to healthy infants (CON) group. Moreover, the abundance of Ruminococcus, Vibrio butyricum, Eubacterium coprostanogenes group, Intestinibacter, and Faecalibacterium were lower (P < 0.05). In terms of microbiota-derived metabolites, the levels of fatty acids (palmitoleic, α-linolenic, arachidonic, and linoleic) (P < 0.05) increased and the levels of amino acids decreased in IC group. Furthermore, the abundances of Ruminococcus, Eubacterium coprostanoligenes group, Intestinibacter and Butyrivibrio are positively correlated with proline, asparagine and aspartic acid, but negatively correlated with the α-linolenic acid, linoleic acid, palmitoleic acid and arachidonic acid. For analysis of the relationship between the microbiota and clinical index, it was found that the abundance of Veillonella and Streptococcus was positively correlated with serum bile acid content (P < 0.05), while APTT, PT and INR were negatively correlated with Faecalibalum and Ruminococcus (P < 0.05).

Conclusion

Microbiota dysbiosis happened in IC children, which also can lead to the abnormal metabolism, thus obstructing the absorption of enteral nutrition and aggravating liver cell damage. Veillonella, Ruminococcus and Butyrivibrio may be important microbiome related with IC and need further research.
Blood-nerve barrier enhances chronic postsurgical pain via the HIF-1α/ aquaporin-1 signaling axis
Authors: Wu Pei-zhi , Yao Ju , Meng Bei , Qin Yi-Bin , Cao Su
Published: November 2023

Background

Blood nerve barrier (BNB) participates in the development of neuropathic pain. AQP1 is involved in peripheral pain perception and is negatively correlated with HIF-1α phenotype, which regulates endothelial permeability. However, the role of HIF-1α-AQP1-mediated BNB dysfunction in Chronic Postsurgical Pain (CPSP) has not been reported.

Methods

Male Sprague-Dawley rats were randomized into 5 groups: (i) Naive group; (ii) Sham group; (iii) SMIR group: skin/muscle incision and retraction for one hour. Behavioral tests were performed for the three groups, BNB vascular permeability and western blotting were conducted to determine HIF-1α and AQP1 protein expression. (iv) The SMIR + HIF-1α inhibitor group; (v) SMIR + DMSO group. Rats in the two groups were administered with HIF-1α inhibitor (2ME2) or DMSO intraperitoneally on the third day post-SMIR surgery followed by performance of behavioral tests, BNB permeability assessment, and determination of HIF-1α, AQP1 and NF200 protein levels.

Results

The permeability of BNB was significantly increased and the expression of AQP1 was downregulated on the 3rd and 7th days post-operation. AQP1 is mainly located in neurons and NF200, CGRP-positive nerve fibers. HIF-1α was highly expressed on the third day post-operation. HIF-1α inhibitor reversed the decrease in AQP1 expression and increase in NF200 expression, barrier permeability and hyperalgesia induced by SMIR on the 3rd day post-surgery.

Conclusions

Early dysfunction of BNB mediated by HIF-1α/AQP1 activated by SMIR may be an important mechanism to promote acute postoperative painful transformation of CPSP. Preadaptive protection of endothelial cells around nerve substructures may be an important countermeasure to inhibit CPSP transformation. Early impairment of BNB function mediated by HIF-1α/AQP1 activated by SMIR may be an important mechanism for promoting acute postoperative pain transformation of CPSP.
PAC1 deficiency reduces chondrogenesis in atherosclerotic lesions of hypercholesterolemic ApoE-deficient mice
Authors: Blümm C. , Bonaterra G. A. , Schwarzbach H. , Eiden L. E. , Weihe E. , Kinscherf R.
Published: November 2023

Background

Induction of chondrogenesis is associated with progressive atherosclerosis. Deficiency of the ADCYAP1 gene encoding pituitary adenylate cyclase-activating peptide (PACAP) aggravates atherosclerosis in ApoE deficient (ApoE−/−) mice. PACAP signaling regulates chondrogenesis and osteogenesis during cartilage and bone development. Therefore, this study aimed to decipher whether PACAP signaling is related to atherogenesis-related chondrogenesis in the ApoE−/− mouse model of atherosclerosis and under the influence of a high-fat diet.

Methods

For this purpose, PACAP−/−/ApoE−/−, PAC1−/−/ApoE−/−, and ApoE−/− mice, as well as wildtype (WT) mice, were studied under standard chow (SC) or cholesterol-enriched diet (CED) for 20 weeks. The amount of cartilage matrix in atherosclerotic lesions of the brachiocephalic trunk (BT) with maximal lumen stenosis was monitored by alcian blue and collagen II staining on deparaffinized cross sections. The chondrogenic RUNX family transcription factor 2 (RUNX2), macrophages [(MΦ), Iba1+], and smooth muscle cells (SMC, sm-α-actin) were immunohistochemically analyzed and quantified.

Results

ApoE−/− mice fed either SC or CED revealed an increase of alcian blue-positive areas within the media compared to WT mice. PAC1−/−/ApoE−/− mice under CED showed a reduction in the alcian blue-positive plaque area in the BT compared to ApoE−/− mice. In contrast, PACAP deficiency in ApoE−/− mice did not affect the chondrogenic signature under either diet.

Conclusions

Our data show that PAC1 deficiency reduces chondrogenesis in atherosclerotic plaques exclusively under conditions of CED-induced hypercholesterolemia. We conclude that CED-related chondrogenesis occurs in atherosclerotic plaques via transdifferentiation of SMCs and MΦ, partly depending on PACAP signaling through PAC1. Thus, PAC1 antagonists or PACAP agonists may offer therapeutic potential against pathological chondrogenesis in atherosclerotic lesions generated under hypercholesterolemic conditions, especially in familial hypercholesterolemia. This discovery opens therapeutic perspectives to be used in the treatment against the progression of atherosclerosis.
Adjunctive tonic motor activation enables opioid reduction for refractory restless legs syndrome: a prospective, open-label, single-arm clinical trial
Authors: Buchfuhrer Mark J. , Roy Asim , Rodriguez Stephanye , Charlesworth Jonathan D.
Published: November 2023

Background

There is a large population of restless legs syndrome (RLS) patients who are refractory to medication. Whereas experts recommend off-label opioids as an effective long-term treatment for refractory RLS, reducing opioid dose could substantially reduce side effects and risks. Tonic motor activation (TOMAC) is a nonpharmacological therapeutic device indicated for refractory RLS. Here, we investigated if TOMAC could enable opioid dose reduction for refractory RLS.

Methods

This prospective, open-label, single-arm clinical trial [NCT04698343] enrolled 20 adults taking ≤ 60 morphine milligram equivalents (MMEs) per day for refractory RLS. Participants self-administered 30-min TOMAC sessions bilaterally over the peroneal nerve when RLS symptoms presented. During TOMAC treatment, opioid dose was reduced iteratively every 2–3 weeks until Clinician Global Impression of Improvement (CGI-I) score relative to baseline exceeded 5. Primary endpoint was percent of participants who successfully reduced opioid dose ≥ 20% with CGI-I ≤ 5. Secondary endpoints included mean successful percent opioid dose reduction with CGI-I ≤ 5.

Results

On average, participants were refractory to 3.2 medications (SD 1.6) and were taking a stable dose of opioids for 5.3 years (SD 3.9). Seventy percent of participants (70%, 14 of 20) successfully reduced opioid dose ≥ 20% with CGI-I ≤ 5. Mean percent opioid dose reduction with CGI-I ≤ 5 was 29.9% (SD 23.7%, n = 20) from 39.0 to 26.8 MME per day. Mean CGI-I score at the reduced dose was 4.0 (SD 1.4), indicating no change to RLS severity.

Conclusions

For refractory RLS, TOMAC enabled substantial opioid dose reduction without increased RLS symptoms. These results suggest that TOMAC has the potential to reduce the risk profile associated with opioid therapy for refractory RLS.

Trial registration

ClinicalTrials.gov trial number NCT04698343 registered on January 6, 2021.
Immunological characteristics of immunogenic cell death genes and malignant progression driving roles of TLR4 in anaplastic thyroid carcinoma
Authors: Xu Tong , Zhu Chaozhuang , Song Feifeng , Zhang Wanli , Yuan Mengnan , Pan Zongfu , Huang Ping
Published: November 2023

Anaplastic thyroid carcinoma (ATC) was a rare malignancy featured with the weak immunotherapeutic response. So far, disorders of immunogenic cell death genes (ICDGs) were identified as the driving factors in cancer progression, while their roles in ATC remained poorly clear. Datasets analysis identified that most ICDGs were high expressed in ATC, while DE-ICDGs were located in module c1_112, which was mainly enriched in Toll-like receptor signalings. Subsequently, the ICD score was established to classify ATC samples into the high and low ICD score groups, and function analysis indicated that high ICD score was associated with the immune characteristics. The high ICD score group had higher proportions of specific immune and stromal cells, as well as increased expression of immune checkpoints. Additionally, TLR4, ENTPD1, LY96, CASP1 and PDIA3 were identified as the dynamic signature in the malignant progression of ATC. Notably, TLR4 was significantly upregulated in ATC tissues, associated with poor prognosis. Silence of TLR4 inhibited the proliferation, metastasis and clone formation of ATC cells. Eventually, silence of TLR4 synergistically enhanced paclitaxel-induced proliferation inhibition, apoptosis, CALR exposure and release of ATP. Our findings highlighted that the aberrant expression of TLR4 drove the malignant progression of ATC, which contributed to our understanding of the roles of ICDGs in ATC.
The combined effects of overweight/obesity and dietary antioxidant quality score on hypertension in children and adolescents
Authors: Zhong Ying , Zhang Zhiqun , Hu Youfang
Published: November 2023

Background

This study was to evaluate the combined effects of overweight/obesity and DAQS on the risk of hypertension in children and adolescents.

Methods

In this cross-sectional study, the data of 14,316 subjects were extracted from the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression analysis was used to explore the associations of obesity and DAQS with the risk of hypertension. The combined effect of overweight/obesity and DAQS on the risk of hypertension was evaluated.

Results

Body mass index (BMI)-for-age < 85th percentile was associated with reduced risk of hypertension in children and adolescents [odds ratio (OR) = 0.48, 95% confidence interval (CI): 0.41–0.62]. No significant association between DAQS ≥ 3 and the risk of hypertension before and after the adjustment of confounders (P > 0.05). Subjects with BMI-for-age of < 85th percentile and DAQS < 3 was associated with decreased risk of hypertension (OR = 0.53, 95%CI: 0.35–0.79). People with BMI-for-age of < 85th percentile and DAQS ≥ 3 was correlated with decreased risk of hypertension (OR = 0.52, 95%CI: 0.36–0.74). Subgroup analysis revealed that in subjects aged ≥ 12 years, decreased risk of hypertension was observed in BMI-for-age < 85th percentile and DAQS < 3 group (OR = 0.48, 95%CI: 0.31–0.73) as well as BMI-for-age < 85th percentile and DAQS ≥ 3 group (OR = 0.47, 95%CI: 0.32–0.67). In boys, BMI-for-age < 85th percentile and DAQS < 3 group (OR = 0.45, 95%CI: 0.25–0.81) as well as BMI-for-age < 85th percentile and DAQS ≥ 3 group (OR = 0.40, 95%CI: 0.25–0.65) were correlated with decreased risk of hypertension.

Conclusion

Overweight/obesity and DAQS had combined effects on the risk of hypertension in children and adolescents, which implied that for children and adolescents with normal weight, to keep normal weight combined with high quality of diet might be recommended.
ARFID Genes and Environment (ARFID-GEN): study protocol
Authors: Bulik Cynthia M. , Micali Nadia , MacDermod Casey M. , Qi Baiyu , Munn-Chernoff Melissa A. , Thornton Laura M. , White Jennifer , Dinkler Lisa , Pisetsky Emily M. , Johnson Jessica , Devine Katelin R. , Ortiz Shelby N. , Silverman Ava E. , Berthold Natasha , Dumain Alexis , Guintivano Jerry , Halvorsen Matthew , Crowley James J.
Published: November 2023

Background

The Avoidant Restrictive Food Intake Disorder – Genes and Environment (ARFID-GEN) study is a study of genetic and environmental factors that contribute to risk for developing ARFID in children and adults.

Methods

A total of 3,000 children and adults with ARFID from the United States will be included. Parents/guardians and their children with ARFID (ages 7 to 17) and adults with ARFID (ages 18 +) will complete comprehensive online consent, parent verification of child assent (when applicable), and phenotyping. Enrolled participants with ARFID will submit a saliva sample for genotyping. A genome-wide association study of ARFID will be conducted.

Discussion

ARFID-GEN, a large-scale genetic study of ARFID, is designed to rapidly advance the study of the genetics of eating disorders. We will explicate the genetic architecture of ARFID relative to other eating disorders and to other psychiatric, neurodevelopmental, and metabolic disorders and traits. Our goal is for ARFID to deliver “actionable” findings that can be transformed into clinically meaningful insights.

Trial registration

ARFID-GEN is a registered clinical trial: clinicaltrials.gov NCT05605067.
Clustering of lifestyle behaviours and analysis of their associations with MAFLD: a cross-sectional study of 196,515 individuals in China
Authors: Zhou Bingqian , Gong Ni , He Qingnan , Huang Xinjuan , Zhu Jingchi , Zhang Lijun , Huang Yanyan , Tan Xinyun , Xia Yuanqin , Zheng Yu , Shi Qiuling , Qin Chunxiang
Published: November 2023

Background

The aggregation of lifestyle behaviours and their association with metabolic-associated fatty liver disease (MAFLD) remain unclear. We identified lifestyle patterns and investigated their association with the risk of developing MAFLD in a sample of Chinese adults who underwent annual physical examinations.

Methods

Annual physical examination data of Chinese adults from January 2016 to December 2020 were used in this study. We created a scoring system for lifestyle items combining a statistical method (multivariate analysis of variance) and clinical expertise (Delphi method). Subsequently, principal component analysis and two-step cluster analysis were implemented to derive the lifestyle patterns of men and women. Binary logistic regression analysis was used to explore the prevalence risk of MAFLD among lifestyle patterns stratified by sex.

Results

A total of 196,515 subjects were included in the analysis. Based on the defined lifestyle scoring system, nine and four lifestyle patterns were identified for men and women, respectively, which included “healthy or unhealthy” patterns and mixed patterns containing a combination of healthy and risky lifestyle behaviours. This study showed that subjects with an unhealthy or mixed pattern had a significantly higher risk of developing MAFLD than subjects with a relatively healthy pattern, especially among men.

Conclusions

Clusters of unfavourable behaviours are more prominent in men than in women. Lifestyle patterns, as important factors influencing the development of MAFLD, show significant sex differences in the risk of MAFLD. There is a strong need for future research to develop targeted MAFLD interventions based on the identified behavioural clusters by sex stratification.
Mediation of the association between social environmental characteristics of family childcare home and weight status in children by diet quality
Authors: Jiang Qianxia , Risica Patricia Markham , Tovar Alison , Cooksey Stowers Kristen , Schwartz Marlene B. , Lombardi Caitlin , Gans Kim M.
Published: November 2023

Background

The food and beverages served in family childcare homes (FCCHs) may play an important role in the development of childhood overweight and obesity. This analysis examines whether children’s diet quality mediates the relationship between foods and beverages served in FCCHs and preschool-aged children’s weight status.

Methods

Trained and certified staff conducted observations for two days in each FCCH, using the Environment and Policy Assessment and Observation (EPAO) measure to determine the foods and beverages served to children (N = 370) in FCCHs (N = 120). They also used the Dietary Observation in Child Care (DOCC) protocol to assess children’s food and beverage intake during childcare, from which we calculated the Healthy Eating Index-2015 (HEI), a measure of diet quality. Height and weight were measured for each child with parent consent from which the child’s body mass index (BMI) z-scores were calculated. A multilevel mediation analysis was conducted to indicate whether children’s diet quality mediates the relations between food and beverage served in FCCHs and preschool-aged children’s weight status.

Results

Children’s total HEI scores significantly mediated the relationship between the EPAO subscale Food Provided and children’s BMI z-scores (B=-0.01, p < .05, 95% CI = [-0.03, − 0.002]). Further, the EPAO subscale Food Provided was positively associated with the total HEI score (B = 0.75, p < .01, 95% CI = [0.32, 1.18]). Total HEI scores were negatively associated with BMI z-score (B=-0.01, p < .05, 95% CI = [-0.02, − 0.001]).

Conclusion

Children’s diet quality did significantly mediate the relationship between the food served in FCCHs and children’s weight status. More longitudinal studies with longer follow-up periods need to be conducted to confirm these relationships. Further, future studies need to examine the relationships between a broader spectrum of FCCH environmental characteristics and home environment with children’s weight status, as well as other mediators including physical activity.
Do patients attempt and succeed in quitting smoking during tuberculosis treatment? A prospective cohort study
Authors: Lee Jiwon , Chung Chaeuk , Jung Sung Soo , Park Hye Kyeong , Lee Sung-Soon , Lee Ki Man , Min Jinsoo
Published: November 2023

Background

Despite a well-known relation between smoking tobacco and the tuberculosis epidemic, the factors associated with smoking cessation in tuberculosis patients are unclear. This study aims to examine the cascade of smoking cessation and the factors associated with persistent smoking among tuberculosis patients.

Methods

We conducted a prospective cohort study enrolling adult patients with pulmonary tuberculosis between 2016 and 2019 in the Republic of Korea. We examined the smoking status at baseline, followed the current smokers, re-examined their smoking status after 6 months of anti-tuberculosis treatment, and identified the factors associated with persistent smoking.

Results

Of the 419 enrolled patients, 109 (26.0%) were current smokers at baseline. Of the 79 current smokers who completed the 6-month survey, 24 (30.4%) succeeded in quitting smoking after 6 months of treatment. The adjusted odds ratio for persistent smoking was 6.57 (95% confidence interval [CI], 1.76–27.83) for drinking and 0.15 (95% CI, 0.03–0.68) for diabetes comorbidity.

Conclusion

Drinking alcohol and diabetes comorbidity were important factors in smoking cessation. Only one third of the tuberculosis patients in our study cohort succeeded in quitting smoking during the 6-month treatment period. More aggressive interventions for smoking cessation should be adopted within the national anti-tuberculosis program.
Current cough and sputum assessed by the cough and sputum assessment-questionnaire (CASA-Q) is associated with quality of life impairment in cystic fibrosis
Authors: Charon Lucie , Launois Claire , Perotin Jeanne-Marie , Ravoninjatovo Bruno , Mulette Pauline , Ancel Julien , Guillard Thomas , Muggeo Anaëlle , Dormoy Valérian , Griffon Muriel , Carré Sophie , Lebargy François , Deslée Gaëtan , Dury Sandra
Published: November 2023

Background

Cough and sputum are major symptoms in cystic fibrosis (CF) that contribute to the impairment of quality of life.

Methods

This prospective single centre cross-sectional pilot study aimed to evaluate the results of a self-administered questionnaire assessing cough and sputum symptoms (2 domains), and their impact (2 domains) on daily activities in the previous week, named the Cough and Sputum Assessment Questionnaire (CASA-Q) in CF adult patients at stable state, and to analyse associations with clinical, functional, microbiological, radiological data, and two quality of life scales: the Cystic Fibrosis Questionnaire Revised (CFQ-R) and the Saint George Respiratory Questionnaire (SGRQ).

Results

Forty-eight patients were included in this analysis (69% men; median age of 27.8 ± 8.1 years; median body mass index of 21.8 + 3.3 kg/m²; mean FEV1 of 64 ± 30% of the predicted value). The mean values of the CASA-Q domains were 58 ± 23 for cough symptoms, 77 ± 24 for cough impact, 62 ± 25 for sputum symptoms and 84 ± 21 for sputum impact. Impairment in CASA-Q cough and sputum domains was associated with dyspnea mMRC scale (p < 0.005 for all 4 domains of CASA-Q) and exacerbations in the previous year (p < 0.05 for CASA-Q symptoms domains). We also found correlations between all domains of the CASA-Q and quality of life questionnaires including SGRQ (p < 0.001) and to a lesser extend CFQ-R. We identified a clinical phenotype (female gender, ΔF508 heterozygous mutation, dyspnea mMRC scale) associated with an impairment of CASA-Q score and quality of life using a 2-step cluster analysis.

Conclusions

CASA-Q allows the assessment of cough and sputum in CF adult patients and is associated with quality of life impairment. This simple easy-to-use tool could be used in routine clinical practice and in clinical studies to assess cough and sputum in CF patients.

Trial Registration

The study was registered on ClinicalTrials.gov (NCT02924818, first posted on 5th October 2016).