bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding frictions in patient-reported outcome-based community healthcare – An institutional logics perspective
Authors: Mejdahl Caroline Trillingsgaard , Nielsen Berit Kjærside , Nielsen Camilla Palmhøj , Nielsen Lise Arnth , Terkildsen Morten Deleuran
Published: December 2024

Objective

Patient-reported outcome (PRO) measures in community-based healthcare play a significant role in the emerging field of digital health. This qualitative study explored healthcare professionals’ (HCPs’) experiences of integrating ‘MyPROfile’ as a dialogue tool in consultations in community healthcare.

Methods

Adopting a qualitative approach with a social constructivist perspective, the study utilised qualitative interviews, participant observations, and focus group interviews. Data were analysed using reflective thematic analysis, guided by theories on institutional logics.

Results

In the analysis, we identified two distinct institutional logics related to HCPs’ experiences integrating PRO measures into their existing practice. Frictions emerged as HCPs integrated the PRO-based dialogue tool, highlighting frictions between an existing Care logic rooted in a holistic health promotion paradigm and the introduced PRO logic. According to the HCPs, the PRO-based practice was perceived as divergent from holistic, narrative-based care, emphasising a shift towards a more reductionist and evaluative model of care.

Conclusions

The study underscores the importance of understanding institutional logics in integrating technologies like PRO measures in healthcare settings. The identified frictions necessitate reflexive venues and collaborative relationships to align differing logics for successful integration. Additionally, incorporating citizens’ perspectives is vital for developing effective rehabilitation and prevention programmes. Moving forward, stakeholder engagement in reflective discussions and workshops is crucial to bridge the gap between the introduced technology and the existing health promotion paradigm, ensuring a seamless and meaningful integration of PRO measures in community healthcare settings.
(Re)Platforming subcultures: Sinosphere board game geeks
Authors: Harrington Johnathan
Published: December 2024

In this paper, I argue that while regional platformisation often takes a utilitarian role, replacing services which are not offered as readily outside of global platforms’ strong reach, there is also an underemphasised performative role as these same online websites become integral to platform-dependent subcultures and their identity formation. I look at board game geeks, who share a culture as much about playing games as it is about performing an identity through collecting games, discussing new releases, and sharing knowledge and enthusiasm with other geeks. Through this I argue that as geek culture becomes increasingly platformed and offline-first communities transfer increasingly online, regional efforts to participate in board game geek culture often require replatformisation for reasons ranging from solving pragmatic issues to replicating global board game geeks’ platformed experience. Through data collection efforts on Modian, China’s largest crowdfunding website, as well as an interdisciplinary literature analysis, I argue that as platformisation assumes a non-existing globality, Sinosphere board game geeks find themselves excluded from this increasingly online-first interconnected subculture, and they ultimately have had to find different ways to renegotiate their identities as geeks. They do this through ill-fitting platformisation, constantly enduring structural friction from online platforms made for western audiences; as well as replatformisation, where I show how regional users find new means to perform the online-first board game geek.
A Mixed-Methods Exploration of the Admissions Process and Criteria for Inclusive Postsecondary Education Programs
Authors: Gilson Carly B. , Prahl Alison , Morissette Luis , Kwon Dongjin , Walker Paige
Published: December 2024

The exponential growth of inclusive postsecondary education (IPSE) programs in the United States has reshaped transition pathways for many young adults with intellectual and developmental disabilities (IDD). However, limited research pertains to the admissions process and eligibility criteria of IPSE programs, leading to a lack of knowledge of how to best equip students for successful entry into college. We conducted a survey ( n = 89) and interviews ( n = 14) with IPSE staff members to explore the admissions process and eligibility criteria of IPSE programs and the extent to which staff views align with the criteria of their programs. Our sample represented 62 programs across 32 states. Findings indicated that, although admissions criteria vary widely, most IPSE programs evaluate applicants based on their functional skills and social behaviors rather than academic skills. We share implications for research and practice in transition planning, secondary instruction, and college preparation for students with IDD.
Analysis of spinal muscular atrophy patients from the spinal muscular atrophy and muscular dystrophy registry of Pakistan
Authors: Aziz Bisma , Arif Ahmed A , Kazi Kulsum , Kirmani Salman , Ansar Zeeshan , Nasir Asghar , Ibrahim Shahnaz Hamid , Ahmed Khairunnisa Mukhtiar , Hasan Zahra , Khan Sara
Published: December 2024

Background

Spinal Muscular Atrophy (SMA) leads to motor neuron loss, with progressive muscle weakness and wasting. Nationwide registries for neuromuscular diseases are pivotal for assessing epidemiology, preparing for clinical trials, and for adopting standardized management guidelines.

Objectives

This paper aims to present data gathered during the establishment of Pakistan's inaugural registry for genetically confirmed SMA cases.

Methods

In this retrospective study, 215 participants with genetically confirmed SMA were recruited. Telephonic interviews were conducted to collect data for the Muscular Disease Registry of Pakistan that was analyzed using STATA version 17.0.

Results

SMA type 1 was the most common type (71.2%, n = 153). Amongst patients who were tested for survival motor neuron ( SMN2) copies, the majority (84.4%, n = 168) had two SMN2 copies. SMA types were significantly associated with the ability to sit (p < 0.001) and walk (p < 0.001), and usage of a wheelchair (p = 0.0054). SMN2 copy numbers were significantly associated with the ability to sit (p = 0.020) and walk (p = 0.031).

Conclusions

This study highlights the high prevalence of SMA genotypes and phenotypes associated with severe disease in our population. Our findings reiterate the challenging prognosis for Pakistani children with SMA and underscore the necessity of the development of nationwide newborn screening programs and making treatments available.
Plasma-derived protein and imaging biomarkers distinguish disease severity in oculopharyngeal muscular dystrophy
Authors: Smith Ian C , Sampaio Marcos L , Melkus Gerd , Meier-Ross Kaitlynn , Chakraborty Shaoni , Stotts Cameron , Bourque Pierre R , Lochmuller Hanns , Brais Bernard , Ayoub Othmane , Perkins Theodore J , Khacho Mireille , Warman-Chardon Jodi
Published: December 2024

Background:

Oculopharyngeal muscular dystrophy (OPMD) is a rare, late-onset, slowly progressive neuromuscular disorder characterized by ptosis, dysphagia, and proximal limb weakness. Emerging clinical trials require rapidly accessible and sensitive biomarkers to evaluate OPMD disease progression and potential response to future treatments.

Objective:

This cross-sectional study was designed to identify candidate circulating protein and imaging biomarkers of OPMD severity for future use in clinical trials.

Methods:

Twenty-five individuals with OPMD (age 63.3 ± 10.5 years; GCN copy number of 13 in PABPN1) were assessed using the 7k SOMAScan assay to profile the plasma proteome, and MRI to quantify replacement of muscle by fat. OPMD severity was first categorized using the clinical presence/absence of limb weakness, and protein signals were considered distinguishing if they differed by more than 30% between subgroups and had statistically significant P-values after correcting for multiple comparisons. Distinguishing proteins were contrasted with age-matched controls ( n = 10). OPMD severity was also treated as a continuous variable using fat fraction of the soleus muscle, and proteins were considered distinguishing if the slope of relationship between protein signal and soleus fat fraction differed significantly from zero after correcting for multiple comparisons. Pathway analyses were conducted using Metascape and the Database for Annotation, Visualization, and Integrated Discovery webtools.

Results:

Eighteen plasma proteins distinguished OPMD on both indicators of severity. Pathway analyses identified skeletal muscle tissue, phagocytosis/engulfment, and extracellular matrix organization as enriched ontology clusters in OPMD with limb weakness. The most distinguishing plasma protein signals (ACTN2, MYOM2, CA3, APOBEC2, MYL3, and PDLIM3) were over 200% higher in OPMD with limb weakness than OPMD without limb weakness as well as controls, and correlated strongly with percent of fatty replacement of soleus ( r = 0.89 ± 0.04).

Conclusions:

The candidate biomarkers identified contribute to the ongoing search for sensitive and accessible biomarkers of OPMD progression, prognosis, and monitoring.
Creating an augmented possession framework to evaluate phases of play and application in international football
Authors: Deb Bikash , Fernandez-Navarro Javier , Jarman Ian , McRobert Allistair P
Published: December 2024

Performance analysts routinely perform game plan evaluations of their in possession play, breaking it down into phases: 1st Phase, 2nd Phase, Final Phase and Transition Defence to Attack. To evaluate a team's performance in relation to their game plan, this study showcases a framework to allow the measurement of tactical strategies in different phases of the game. This framework augments possession sequence data, a series of on-ball events until a stoppage or turnover, with notational analysis data (phases of play and phase outcomes) to evaluate team style and performance across 82 international football matches from 2018 to 2022. From this enhanced possession framework, we assessed the impact of specific events, i.e., progressive passes on phase outcomes, by conducting a series of mixed effects multivariable logistic regression models. Progressive passing showed increased odds of positive phase outcomes when attempting to enter the Final Phase including successful phase progressions (aOR 2.57 [2.19–3.02]), dangerous possession (aOR 1.79 [1.56–2.04]), shot (aOR 1.70 [1.44–2.01]), critical chance (aOR 1.91 [1.27–2.86]), and goal (aOR 2.05 [1.34–3.12]). This framework has allowed the development of novel metrics and visualisations, such as how teams create dangerous possessions, which aids the post-match review process.
The Impact of Humble Leadership on Knowledge-Sharing and Creativity in Nursing Setting: A Cross-Sectional Study
Authors: Al-Rjoub Saleem , Mrayyan Majd T.
Published: December 2024

Introduction

Leadership styles are pivotal in encouraging employee engagement, influencing team dynamics, and enhancing patient outcomes. Humble leadership is characterized by self-awareness, openness, and appreciation for others. This leadership style is underexplored in healthcare.

Objective

This study investigated whether humble leadership impacts knowledge-sharing and employees’ creativity.

Methods

A descriptive cross-sectional design was used. Data were collected from nursing educators, nurses, and nursing leaders from various universities and hospitals in Jordan. Descriptive analysis was applied to display the general characteristics of the study participants. The general linear model was conducted to analyze the impact of humble leadership on knowledge-sharing and employees’ creativity.

Results

This study revealed that humble leadership significantly impacted knowledge-sharing and employees’ creativity. These findings highlight the critical role of humble leadership in promoting and fostering knowledge-sharing and creativity within educational institutions and healthcare settings.

Conclusion

Leaders’ humble leadership impacted knowledge-sharing among employees and the creativity of nursing educators, nurses, and nursing leaders. Training programs are needed to develop humble nurses’ and leaders’ leadership because they contribute to nursing educators’, nurses’, and nursing leaders’ creativity while maintaining employee knowledge-sharing.
2024 IFFAS Award for Excellence Winner: Minimally Invasive Chevron Akin for Hallux Valgus Surgery: A Prospective Observational Study with Mean 6.7 year Follow Up
Authors: Townsend Oliver , Hill Niall , Reaney Adam , Koç Togay , Lewis Thomas L. , Gordon David
Published: December 2024

Category:

Bunion

Introduction/Purpose:

Minimally invasive chevron and Akin (MICA) osteotomy surgery has become an established technique for correction of hallux valgus deformities. As a relatively new technique, however, long-term follow-up data is limited in the literature to 2-3 years. The purpose of this study is to assess a large cohort of patients undergoing MICA with minimum 5 year follow up, to evaluate the longer-term results of this procedure, using validated patient reported outcome measures (PROMs).

Methods:

5-year PROM data was prospectively collected from 101 patients who underwent 147 primary MICA osteotomies between July 2014 and April 2018, performed by a single surgeon. Primary clinical outcome measures collected included visual analogue scale for pain (VAS-pain), Manchester-Oxford Foot Questionnaire (MOXFQ) and EuroQol-5 Dimensions (EQ-5D). Data were collected pre-operatively, at 2 years and after minimum 5 years. Statistical significance was set at p< 0.05.

Results:

147 MICA osteotomies were performed on the feet of 101 patients (96 females, 5 males). Mean follow-up was 6.5 years (standard deviation [SD] 0.9 years), with all patients completing at least 5 years follow-up. The MOXFQ scores (mean ± SD) for all 147 feet improved for all domains: from 45.8 ± 21.9 preoperatively to 10.3 ± 16.8 postoperatively for Pain (p < 0.001), from 40.0 ± 23.8 to 9.1 ± 18.2 for Walking and Standing (p < 0.001), and from 48.5 ± 23.1 to 8.9 ± 18.5 for Social Interaction (p < 0.001). VAS-pain improved from 31.3 ± 22.6 preoperatively to 12.0 ± 20.6 postoperatively (p < 0.001). EQ-5D-5L Index improved from 0.739 ± 0.144 preoperatively to 0.900 ± 0.120 postoperatively (p < 0.001).

Conclusion:

This is the largest study reporting the patient reported outcomes following MICA with minimum five year follow up. This study demonstrates significant improvement in patient reported clinical outcome measures at mean 6.5 year follow up. MICA can be considered as an effective and long-lasting option for the correction of hallux valgus deformity.
Atelocollagen Injection Enhances the Healing of Nonoperatively Treated Achilles Tendon Tears
Authors: Song Jaehwang , Kang Chan , Jo Seongkyeong
Published: December 2024

Category:

Basic Sciences/Biologics; Sports

Introduction/Purpose:

There is growing interest in nonoperative treatment for the management of Achilles tendon ruptures (ATRs). However, nonoperative treatment is limited by the risk of tendon reruptures and low satisfaction rates. Recently, atelocollagen injections have been reported to have beneficial effects on tendon healing. The purpose of this study is to evaluate the beneficial effects of injected atelocollagen on Achilles tendon healing and investigate the mechanism of atelocollagen on tendon healing.

Methods:

Percutaneous tenotomy of the right Achilles tendon in 66 rats was performed. The animals were equally divided into the noninjection group (NG) and the collagen injection group (CG). At 1, 3, and 6 weeks, the Achilles functional index (AFI), cross-sectional area, load to failure, stiffness, stress, and the modified Bonar score were assessed. Transmission electron microscopy (TEM), western blotting, and immunohistochemistry were also performed.

Results:

The AFI (–6.8 vs 243.0, respectively; P = .040), load to failure (42.1 vs 27.0 N, respectively; P = .049), and stiffness (18.8 vs 10.3 N/mm, respectively; P = .049) were higher in the CG than those in NG at 3 weeks. There were no significant differences in histological scores. TEM analysis showed that the mean diameter of collagen fibrils in the CG was greater than that in the NG at 3 weeks (117.2 vs 72.6 nm, respectively; P < .001) and 6 weeks (202.1 vs 144.0 nm, respectively; P < .001). Western blot analysis showed that the expression of collagen type I in the CG was higher than that in the NG at 1 week (P = .005) and 6 weeks (P = .001).

Conclusion:

An atelocollagen injection had beneficial effects on the healing of nonoperatively treated Achilles tendon injuries. The Achilles tendon of CG rats exhibited better functional, biomechanical, and morphological outcomes compared with NG rats. The molecular data indicated that the mechanism of atelocollagen injections may be associated with an increased amount of collagen type I. The scheme and the outcomes of the present study 1. The flowchart of the experiment groups and surgical procedures involved in this study. 2. Functional analysis. 3. Biomechanical testing. 4. Histological analysis. 5. Transmission electron microscopy (TEM) analysis. 6. Western blot analysis.
Arthroscopic Repair of the Anterior Talofibular Ligament Produces Good Clinical Outcome Scores Both with and without Inferior Extensor Retinaculum Reinforcement: A Meta-Analysis
Authors: Murray Benjamin , Mirghasemi Ali , Shaffer Gene , Raphael James
Published: December 2024

Category:

Arthroscopy; Ankle

Introduction/Purpose:

Arthroscopic techniques for lateral ankle instability generally involve either direct repair solely of the anterior talofibular ligament (ATFL) remnant or repair of the ATFL with inferior extensor retinaculum (IER) reinforcement. Both techniques produce strong clinical outcomes, which questions the necessity of IER reinforcement. Studies comparing arthroscopic lateral ankle ligament stabilization techniques are limited, especially those directly comparing pure ATFL repair to ATFL repair with IER reinforcement. The purpose of this study is to compare clinical outcomes of arthroscopic repair of the ATFL without IER reinforcement to arthroscopic ATFL repair procedures involving IER reinforcement

Methods:

A meta-analysis per PRISMA guidelines was conducted. Search keywords included arthroscopic, all-inside, ankle stabilization, lateral ankle sprain, anterior talofibular ligament, and lateral ankle instability. To assess the relationship of type of surgical procedure (ATFL repair with versus without IER reinforcement) to reported clinical outcomes based on the American Orthopaedic Foot and Ankle Society (AOFAS) score, the Karlsson and Peterson Scoring System for Ankle Function (KAFS), and the Visual Analogue Score (VAS), we used the standardized mean difference (SMD) with a 95% confidence interval of preoperative to postoperative scores as an effect size. The method of random-effects model was used to calculate the overall summary estimates.

Results:

638 studies met the initial search criteria. 34 studies met final inclusion criteria and were included in the meta-analysis. Patients receiving arthroscopic ATFL repair both with and without IER reinforcement had significantly improved pre-operative to post-operative clinical outcome scores. Arthroscopic ATFL repair with IER reinforcement resulted in a significantly higher pre-operative to post-operative SMD for KAFS (p=0.091) and VAS (p=0.065) scores compared to arthroscopic ATFL repair without IER reinforcement. There was no significant difference in the pre-operative to post-operative SMD of AOFAS (p=0.453) scores when comparing surgical procedures.

Conclusion:

Arthroscopic ATFL repair produces strong clinical outcome scores both with and without IER reinforcement.
Frosted Branch Angiitis–Like Retinal Vasculitis Developing After Scleral Buckle Surgery
Authors: Desai Arjun , Tyagi Mudit , Narula Ritesh
Published: December 2024

Purpose: To describe a case of frosted branch angiitis–like retinal vasculitis that developed after scleral buckle surgery. Methods: A single case was evaluated. Results: Five days after nondrainage scleral buckle surgery with a segmental buckle and encircling band, an otherwise healthy 39-year-old man presented with frosted branch angiitis. Treatment initially involved oral corticosteroids. After 5 days of treatment, there was a decrease in the subretinal exudation; however, the break appeared to be lifting with persistent subretinal fluid. Pars plana vitrectomy (PPV) with silicone oil (SO) injection was performed. A vitreous biopsy was taken during the PPV that was negative for bacterial, fungal, and viral markers. The patient’s blood and urine culture showed no microbial growth, ruling out an infectious cause. Ultimately, the SO was removed, with a good visual outcome. Conclusions: Although the cause is unknown, retinal vasculitis may occur after scleral buckle surgery, albeit rarely.
Brazilian jeitinho: Historical development, current research, and its impact on personality assessment
Authors: Zanon Cristian , Luz Jéssica Vargas da , da Silva Taís Bopp , Lima Marlos A. de
Published: December 2024

Brazilian jeitinho constitutes an emic hierarchical personality trait related to problem-solving strategies, including creativity, breaking rules, and corruption. This manuscript provides a historical perspective of the Brazilian culture, describing how colonization might have impacted how many Brazilians deal with adversities and everyday situations. Additionally, we present research on Brazilian jeitinho and indicate how widely known conceptions of malandragem, or crafty jeitinho, possibly affect the validity of self-reported big-five personality tests. Finally, we advocate for the integration of anchoring vignettes and self-enhancement measures within personality assessments to mitigate the bias introduced by the Brazilian jeitinho on personality item responses.
Capabilities for the paramedic preceptor role: A scoping review
Authors: Van Noordenburg Andrew , Jacob Elisabeth , Devenish Scott
Published: December 2024

Paramedic preceptors play a critical role in supporting a learner's transition to practice. However, many paramedics have received limited training or education on how to be a preceptor. Providing access to a targeted preceptor education programme may further enhance paramedics’ capacity in this role. To help inform preceptor education, this research answers the question ‘What capabilities are required for the paramedic preceptor role?’ Capabilities are a combination of knowledge, skills and attributes used to work effectively and take appropriate action in various and novel settings. MEDLINE, CINAHL, ERIC, Web of Science and Scopus databases were searched using the Joanna Briggs Institute (JBI) methodology. Manual searches of Google Scholar, Trove and relevant paramedic-specific journals were also undertaken. Eligible for inclusion were peer-reviewed publications and grey literature from 2004 onwards written in English which discuss paramedic preceptor capabilities. Thirty-six articles were included in the review utilising this search strategy. Four overarching capabilities were identified for the paramedic preceptor role. First, the learning and teaching capability included having knowledge of feedback, assessment, adult learning theory and how to guide critical thinking and be a coach. Second, the interpersonal capability included having the skills to build positive relationships, act as a counsellor, provide psychological safety, communicate effectively and support socialisation. Third, the professional capability comprised of preceptors being clinically competent and critical thinkers. Finally, the personal capability included having the attributes of a role model and possessing an intrinsic desire to be a preceptor. Paramedics require opportunities to develop the knowledge, skills and attributes identified in this review to be capable preceptors. These findings can also inform the design of a paramedic preceptor education programme.
The pleiotropic effects of statins: a comprehensive exploration of neurovascular unit modulation and blood–brain barrier protection
Authors: Liu Jia-Cheng , Lei Shuang-Yin , Zhang Dian-Hui , He Qian-Yan , Sun Ying-Ying , Zhu Hong-Jing , Qu Yang , Zhou Sheng-Yu , Yang Yi , Li Chao , Guo Zhen-Ni
Published: December 2024

The blood–brain barrier (BBB) is the most central component of the neurovascular unit (NVU) and is crucial for the maintenance of the internal environment of the central nervous system and the regulation of homeostasis. A multitude of neuroprotective agents have been developed to exert neuroprotective effects and improve the prognosis of patients with ischemic stroke. These agents have been designed to maintain integrity and promote BBB repair. Statins are widely used as pharmacological agents for the treatment and prevention of ischemic stroke, making them a cornerstone in the pharmacological armamentarium for this condition. The primary mechanism of action is the reduction of serum cholesterol through the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which results in a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in cholesterol clearance. Nevertheless, basic and clinical research has indicated that statins may exert additional pleiotropic effects beyond LDL-C reduction. Previous studies on ischemic stroke have demonstrated that statins can enhance neurological function, reduce inflammation, and promote angiogenic and synaptic processes following ischemic stroke. The BBB has been increasingly recognized for its role in the development and progression of ischemic stroke. Statins have also been found to play a potential BBB protective role by affecting members of the NVU. This review aimed to provide a comprehensive theoretical basis for the clinical application of statins by systematically detailing how statins influence the BBB, particularly focusing on the regulation of the function of each member of the NVU.

Graphical Abstract
GLUT1 exacerbates trophoblast ferroptosis by modulating AMPK/ACC mediated lipid metabolism and promotes gestational diabetes mellitus associated fetal growth restriction
Authors: Zhang Qin , Yuan Xi , Luan Xiaojin , Lei Ting , Li Yiran , Chu Wei , Yao Qi , Baker Philip N. , Qi Hongbo , Li Hui
Published: December 2024

Background

Gestational diabetes mellitus (GDM) has been associated with several fetal complications, such as macrosomia and fetal growth restriction (FGR). Infants from GDM associated FGR are at increased risk for adult-onset obesity and associated metabolic disorders. However, the underlying mechanisms of GDM associated FGR remain to be explored.

Methods

We analyzed placentas from GDM patients with FGR for ferroptosis markers and GLUT1 expression. High glucose conditions were established by adding different concentrations of D-Glucose to the 1640 cell culture medium. RSL3 were used to test ferroptosis sensitivity in trophoblast cells. GLUT1 was inhibited using siRNA or its inhibitor WZB117 to assess its impact on ferroptosis inhibition in HTR8/SVneo cell line. Mechanistic studies explored the effects of GLUT1 on AMPK and ACC phosphorylation, which in turn impacted lipid metabolism and ferroptosis. In mouse models, streptozotocin (STZ)-induced GDM was treated with WZB117 and the ferroptosis inhibitor liproxstatin-1 (Lip-1). Finally, AMPK and ACC phosphorylation levels were evaluated in GDM patient samples.

Results

In this study, placentas from GDM patients with FGR showed signs of ferroptosis and upregulation of GLUT1. In cell models, high glucose conditions sensitized trophoblast cells to ferroptosis and induced GLUT1 expression. Interestingly, GLUT1 inhibition significantly suppressed ferroptosis in trophoblast cells under high glucose conditions. Mechanistically, elevated GLUT1 inhibited AMPK phosphorylation and reduced ACC phosphorylation, thereby promoting lipid synthesis and facilitating ferroptosis. In pregnant mice, STZ-induced hyperglycemia led to FGR, and treatment with either the GLUT1 inhibitor WZB117 or the ferroptosis inhibitor Lip-1 alleviated the FGR phenotype. Moreover, in vivo elevation of GLUT1 increased ferroptosis markers, decreased AMPK/ACC phosphorylation, and resulted in altered lipid metabolism, which likely contributed to the observed phenotype. Finally, placental samples from GDM patients showed reduced AMPK and ACC phosphorylation.

Conclusions

Our findings suggest a potential role of ferroptosis in GDM associated FGR and indicate that the dysregulated GLUT1-AMPK-ACC axis may be involved in the pathogenesis of GDM associated FGR in clinicals.
Crosstalk between CD180-overexpression macrophages and glioma cells worsens patient survival through malignant phenotype promotion and immunosuppressive regulation
Authors: Wang Wen , Li Junsheng , He Qiheng , Liu Chenglong , Zheng Zhiyao , Zhang Bojian , Mou Siqi , Sun Wei , Zhao Jizong
Published: December 2024

Background

Understanding the molecular mechanisms in immunosuppressive regulation is crucial for improving immunotherapeutic strategies. Macrophages, the major immune cells in tumor microenvironment (TME), play a dual role in tumor progression. CD180, primarily expressed in macrophages, remains unclear and requires further investigation.

Methods

RNA-seq data were obtained to analyze CD180 expression in gliomas and assess its prognostic value. The comprehensive immune infiltration analysis was performed. Single-cell RNA-seq (scRNA-seq) data were used to examine CD180 expression distribution at the cellular level. CD180-overexpression macrophages were co-cultured with three glioma cell lines. The effects on glioma cell behavior were evaluated through qRT-PCR, Western blot, CCK-8 assay, EdU assay, Transwell assay, TUNEL assay, and flow cytometry. Differentially expressed genes (DEGs) and their potential biological functions were analyzed between different CD180 expression groups. Consensus clustering was used to identify CD180-related glioma subtypes.

Results

CD180 was significantly upregulated in glioma samples and associated with poor prognosis. High CD180 expression was correlated with increased immune cell infiltration, particularly macrophages, and elevated levels of immune checkpoints. Analysis of scRNA-seq data revealed the predominant expression of CD180 in macrophages within the glioma TME. In vitro experiments demonstrated that CD180-overexpression macrophages promoted glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while decreasing apoptosis. Mutations in TP53 and PTEN were significantly more prevalent in the high CD180 expression group. We identified nine chemotherapeutic agents that were more effective in glioma patients with high CD180 expression. Additionally, two CD180-related glioma subtypes with distinct prognosis were identified.

Conclusions

This study confirmed the prognostic role of CD180 in glioma and its involvement in immunosuppressive regulation and malignant phenotype promotion. Therefore, CD180 was considered as a promising target for immunotherapeutic strategies in glioma treatment.
Elucidating the role of gut microbiota metabolites in diabetes by employing network pharmacology
Authors: Yao Weiguo , Huo Jinlin , Ji Jing , liu Kun , Tao Pengyu
Published: December 2024

Background

Extensive research has underscored the criticality of preserving diversity and equilibrium within the gut microbiota for optimal human health. However, the precise mechanisms by which the metabolites and targets of the gut microbiota exert their effects remain largely unexplored. This study utilizes a network pharmacology methodology to elucidate the intricate interplay between the microbiota, metabolites, and targets in the context of DM, thereby facilitating a more comprehensive comprehension of this multifaceted disease.

Methods

In this study, we initially extracted metabolite information of gut microbiota metabolites from the gutMGene database. Subsequently, we employed the SEA and STP databases to discern targets that are intricately associated with these metabolites. Furthermore, we leveraged prominent databases such as Genecard, DisGeNET, and OMIM to identify targets related to diabetes. A protein-protein interaction (PPI) network was established to screen core targets. Additionally, we conducted comprehensive GO and KEGG enrichment analyses utilizing the DAVID database. Moreover, a network illustrating the relationship among microbiota-substrate-metabolite-target was established.

Results

We identified a total of 48 overlapping targets between gut microbiota metabolites and diabetes. Subsequently, we selected IL6, AKT1 and PPARG as core targets for the treatment of diabetes. Through the construction of the MSMT comprehensive network, we discovered that the three core targets exert therapeutic effects on diabetes through interactions with 8 metabolites, 3 substrates, and 5 gut microbiota. Additionally, GO analysis revealed that gut microbiota metabolites primarily regulate oxidative stress, inflammation and cell proliferation. KEGG analysis results indicated that IL-17, PI3K/AKT, HIF-1, and VEGF are the main signaling pathways involved in DM.

Conclusion

Gut microbiota metabolites primarily exert their therapeutic effects on diabetes through the IL6, AKT1, and PPARG targets. The mechanisms of gut microbiota metabolites regulating DM might involve signaling pathways such as IL-17 pathways, HIF-1 pathways and VEGF pathways.
Influence of liberal versus conservative oxygen therapies on the hemodynamic parameters of mechanically ventilated patients with sepsis: a randomized clinical trial
Authors: Ghazaly Huda F. , Aly Ahmed Alsaied A. , Tammam Ahmed S. , Hassan Mahmoud M. , Hammad Soudy S. , Mahmoud Naggeh M. , Hemaida Tarek S.
Published: December 2024

Background

There is no significant evidence verifying the efficacy of liberal versus conservative oxygen therapy on hemodynamics in patients with sepsis. We investigated how liberal and conservative oxygen therapy influenced stroke volume, cardiac output, and vasopressor needs in patients with sepsis undergoing mechanical ventilation.

Methods

This randomized clinical trial included 106 patients with an admission diagnosis of infection, a Sequential Organ Failure Assessment (SOFA) score of two points or higher and required invasive mechanical ventilation for at least 72 h. Patients were randomly assigned to one of two oxygenation strategies: liberal (n = 53) with a target SpO2 of ≥ 96% or conservative (n = 53) with a target SpO2 of 88–92%. Transthoracic Doppler echocardiography was done twice to measure stroke volume and cardiac output, initially upon enrollment in the trial and then 72 h later. The primary outcome was stroke volume. Secondary outcomes were cardiac output, vasopressor use, mechanical ventilation duration, ICU stay length, and adverse events.

Results

Stroke volume and cardiac output measurements did not differ significantly between research groups after 72 h of oxygenation treatment (p = 0.459 and 0.637, respectively). Forty-five patients (84.9%) in the conservative oxygen therapy group needed vasopressors to maintain their mean arterial pressure above 65 mmHg, whereas 35 patients (66.0%) in the liberal group did (p = 0.024). A multivariate logistic regression analysis of the independent variables for vasopressor requirements revealed that patients in the conservative oxygen group were 3.83 times more likely to require vasopressors (AOR = 3.83, 95% CI: 1.31–11.18, p = 0.014) than those in the liberal group. Older patients (AOR = 1.03, 95% CI: 1.01–1.07, p = 0.038) and those with higher SOFA scores (AOR = 1.36, CI: 1.09–1.68, P = 0.005) were significantly more likely to need vasopressors.

Conclusions

Liberal or conservative oxygen therapy did not influence stroke volume or cardiac output measurements in mechanically ventilated patients with sepsis. Patients in the conservative oxygen group were more likely to require vasopressors than those in the liberal group.

Trial registration

This study was approved by the Ethics Committee of Aswan University Hospital (approval number: Aswu/460/5/20) (registration date: 05/05/2020) and registered on ClinicalTrials.gov (NCT04824703) (03/30/2021).
Strain echocardiography predictors in patients with concomitant cardiac amyloidosis and aortic stenosis: a cross-sectional study
Authors: Jafarisis Samira , Masoumi Shahab , Khezerlouy-Aghdam Naser , Toutounchi Kia Seyed , Sarmadian Amirreza Jabbaripour , Hamzehzadeh Sina , Shariati Akram , Parizad Razieh , Rabori Venus Shahabi
Published: December 2024

Background

Concomitant cardiac amyloidosis (CA) and aortic stenosis (AS) may be mistaken for isolated AS, potentially impacting the treatment strategy and patient’s prognosis. Therefore, it is crucial to distinguish between these conditions, as failure to promptly diagnose CA may lead to considerable complications. The aim of this study is to investigate the diagnostic value of strain predictors in patients with concomitant CA and AS compared to isolated AS.

Methods

Forty-two patients with severe AS suspected of concomitant CA based on a comprehensive clinical evaluation were selected to undergo 99mTc-DPD scintigraphy. Those showing Perugini grade 2 or 3 tracer uptakes without evidence of monoclonal gammopathy were diagnosed with CA and underwent speckle-tracking echocardiography. Furthermore, strain analysis was performed to evaluate myocardial deformation, with a focus on detecting apical sparing and reduction in bull’s eye mapping, resulting in the characteristic “cherry on top” sign.

Results

Eight patients were diagnosed with CA, representing 19.0% of those suspected of concomitant CA and 7.8% of the overall cohort with severe AS. AF arrhythmia was significantly more frequent in these patients compared to those with isolated AS. Echocardiography findings revealed that E/E’ ratio and RALS were significantly higher in patients with concomitant CA, while GLS and mean basal LS were significantly lower in this group. The “cherry on top” sign was detected in 19 patients (45.2%), present in 100% of those with concomitant CA and AS, versus 32.4% in isolated AS cases (P = 0.04). This sign demonstrated a sensitivity of 100% and a specificity of 67.6% for predicting concomitant CA and AS.

Conclusions

In conclusion, the “cherry on top” sign was significantly more prevalent in patients with concomitant CA and AS, compared to those with isolated AS, demonstrating a sensitivity of 100% and a specificity of 67.6% for predicting concomitant CA. Moreover, RALS and E/E’ ratios were significantly higher in patients with concomitant CA, whereas GLS and mean basal LS were significantly lower in this group.
Addressing treatment switching in the ALTA-1L trial with g-methods: exploring the impact of model specification
Authors: Al Tawil Amani , McGrath Sean , Ristl Robin , Mansmann Ulrich
Published: December 2024

Background

Treatment switching in randomized clinical trials introduces challenges in performing causal inference. Intention To Treat (ITT) analyses often fail to fully capture the causal effect of treatment in the presence of treatment switching. Consequently, decision makers may instead be interested in causal effects of hypothetical treatment strategies that do not allow for treatment switching. For example, the phase 3 ALTA-1L trial showed that brigatinib may have improved Overall Survival (OS) compared to crizotinib if treatment switching had not occurred. Their sensitivity analysis using Inverse Probability of Censoring Weights (IPCW), reported a Hazard Ratio (HR) of 0.50 (95% CI, 0.28-0.87), while their initial ITT analysis estimated an HR of 0.81 (0.53-1.22).

Methods

We used a directed acyclic graph to depict the clinical setting of the ALTA-1L trial in the presence of treatment switching, illustrating the concept of treatment-confounder feedback and highlighting the need for g-methods. In a re-analysis of the ALTA-1L trial data, we used IPCW and the parametric g-formula to adjust for baseline and time-varying covariates to estimate the effect of two hypothetical treatment strategies on OS: “always treat with brigatinib” versus “always treat with crizotinib”. We conducted various sensitivity analyses using different model specifications and weight truncation approaches.

Results

Applying the IPCW approach in a series of sensitivity analyses yielded Cumulative HRs (cHRs) ranging between 0.38 (0.12, 0.98) and 0.73 (0.45,1.22) and Risk Ratios (RRs) ranging between 0.52 (0.32, 0.98) and 0.79 (0.54,1.17). Applying the parametric g-formula resulted in cHRs ranging between 0.61 (0.38,0.91) and 0.72 (0.43,1.07) and RRs ranging between 0.71 (0.48,0.94) and 0.79 (0.54,1.05).

Conclusion

Our results consistently indicated that our estimated ITT effect estimate (cHR: 0.82 (0.51,1.22) may have underestimated brigatinib’s benefit by around 10-45 percentage points (using IPCW) and 10-20 percentage points (using the parametric g-formula) across a wide range of model choices. Our analyses underscore the importance of performing sensitivity analyses, as the result from a single analysis could potentially stand as an outlier in a whole range of sensitivity analyses.

Trial registration

Clinicaltrials.gov Identifier: NCT02737501 on April 14, 2016.
Historical and future heat-related mortality in Portugal’s Alentejo region
Authors: Neto Dora , Araújo Miguel Bastos
Published: December 2024

Background

The increased severity of extreme weather and anticipated climate change has intensified heat stress-related mortality worldwide. This study examines the historical short-term effects of heat on mortality in Alentejo, Portugal’s warmest region, and projects it up to the end of the century.

Methods

Using data from 1980 to 2015 during warm seasons (May-September), the association between daily mortality by all-causes and mean temperature was examined following a case time series design, applied at both regional and subregional scales. Projections for daily temperatures were obtained from regional climate models and greenhouse gas emission scenarios (RCP4.5, RCP8.5). We also examined temporal shifts in mortality considering potential long-term and seasonal adaptative responses to heat. We then quantified the yearly effects of heat by calculating absolute and relative excess mortality from 1980 to 2015, specifically during the heatwave of 2003 (July 27 to August 15), and in future projections at 20-year intervals through 2100.

Results

The analysis revealed a significant rise in mortality risk at temperatures exceeding a minimum mortality temperature (MMT) of 19.0 °C, with an exponential trend and delayed effects lasting up to 5 days. The risk increased by 413% at the maximum extreme temperature of 36.6 °C. From 1980 to 2015, 2.32% of total deaths, equating to over 5,296 deaths, were heat-associated. No significant shifts over time were noted in the population’s response to heat. Future projections, without adaptation and demographic changes, show a potential increase in mortality by 15.88% under a “no mitigation policy” scenario by 2100, while mitigation measures could limit the rise to 6.61%.

Conclusion

Results underscore the urgent need for protective health policies to reduce regional population vulnerability and prevent premature heat-related deaths across the century.
An overview of patients with intertrochanteric femoral fractures treated with proximal femoral nail fixation using important criteria
Authors: Aygün Ümit , Şenocak Eyüp , Aksay Mehmet Fatih , Çiçek Ali Can , Halaç Orkun , Toy Serdar
Published: December 2024

Background

This study aimed to assess important criteria, including osteoporosis, fracture type, implant position within the bone, fracture reduction, and radiographic union, in patients with intertrochanteric femoral fractures treated with proximal femoral nail (PFN) fixation and to show their effect on clinical outcomes.

Methods

PFN fixation was applied in 73 patients (41 females, 32 males; mean age: 64.5 ± 6.2). The T score, fracture type according to the AO Foundation and Orthopedic Trauma Association (AO/OTA), implant-related complications (IRCs), Harris hip score (HHS), Jensen social function (JSF) score, and Parker-Palmer mobility score (PPMS), postoperative reduction classification, screw position according to the Cleveland zone, Radiographic Union Scale for the Hip (RUSH) score, and tip-apex distance (TAD) were recorded.

Results

Most screws were in central-central (n = 42) and inferior-central (n = 11) positions. IRCs were seen mostly in cases of screws placed in peripheral zones (n = 10) and were not observed in almost any patient with a TAD ≤ 25 mm (n = 52) (p < 0.001). Most of the patients with acceptable or good fracture reduction did not have IRCs (n = 11 and 50, respectively) (p < 0.001). Half of type 3A1 (n = 13) and most type 3A2 (n = 20) fractures showed radiographic union at 3 months, and most type 3A3 (n = 9) fractures showed radiographic union at 5 months (p < 0.05). At 12 months, type 3A2 fractures had the highest HHS (79.2 ± 5.3) and PPMS (3.9 ± 1.5), while type 3A3 fractures had the lowest HHS (70.3 ± 4.6) and PPMS (0.6 ± 2.8) (p < 0.05). At 12 and 24 months, type 3A3 fractures had higher JSF scores (2.8 ± 0.4 and 3.5 ± 0.5, respectively); at 3 months, type 3A1 fractures had higher JSF scores (3.1 ± 0.3) (p < 0.05). The radiographic bone union time was prolonged in patients with a T score ≤ -2.5 standard deviation (SD) (p < 0.05). The HHS and PPMS increased while the RUSH score, considered as the radiographic union, was going towards the 4th month and decreased after the 4th month (p < 0.05).

Conclusions

Considering the criteria (osteoporosis, fracture type, implant position within the bone, fracture reduction, and radiographic union) examined in this study, satisfactory results can be obtained with PFN fixation in the treatment of patients with intertrochanteric femoral fractures.
The biomechanical effects of clear aligner trimline designs and extensions on orthodontic tooth movement: a systematic review
Authors: Nakornnoi Theerasak , Srirodjanakul Watcharee , Chintavalakorn Rochaya , Santiwong Peerapong , Sipiyaruk Kawin
Published: December 2024

Background

Clear aligner treatment (CAT) has emerged as an effective alternative to conventional multibracket systems in orthodontics. The trimline design and extension of aligners may significantly influence their biomechanical performance and tooth movement efficacy.

Aim

To systematically review the biomechanical effects of different aligner trimline designs and extensions on orthodontic tooth movement.

Methods

A systematic search was conducted across PubMed, Scopus, Embase, ProQuest Dissertations & Theses Global, and Google Scholar for studies published between January 2000 and August 2024. The review included any types of empirical research focusing on the influence of trimline of orthodontic aligners on tooth movement efficacy conducted between January 2000 and August 2024. The Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool was used for quality assessment.

Results

Twelve studies met the inclusion criteria, all assessed as having low to moderate risk of bias. Aligner trimline design significantly influenced orthodontic tooth movement efficacy through two primary mechanisms: enhanced force delivery and increased aligner retention. Aligners with straight and extended margins generally exerted higher forces and moments compared to scalloped or shorter designs. This resulted in greater tooth displacement for certain movements, particularly intrusion, translation, tipping, and root torquing. Extended trimlines also demonstrated superior retention. However, the effects varied depending on the type of tooth movement.

Conclusion

Aligner trimline designs and extensions can significantly influence biomechanical performance and tooth movement efficacy in CAT. Straight extended trimlines generally demonstrate superior force delivery and retention, leading to more predictable clinical outcomes. This could reduce the need for revisions, thereby decreasing overall treatment time and increasing patient satisfaction. However, further research is needed to investigate the interactions between aligner trimline designs and other factors to develop evidence-based guidelines for their optimal combination in various clinical scenarios.