bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of high-pressure compression stockings and compression bandages for ulcer treatment in venous ulcer patients
Authors: Toz Hasan , Kuserli Yusuf , Türkyılmaz Gülsüm , Türkyılmaz Saygın , Kavala Ali Aycan
Published: December 2024

Objectives

This study aims to compare the effectiveness of compression bandages and compression stockings in the treatment of venous ulcers following venous ulcer surgery.

Method

A total of 170 patients who underwent venous ulcer surgery were included in this retrospective study. Patients were divided into two groups: the first group used compression bandages, and the second group used compression stockings. In all patients, a sterile cotton dressing from the venous ulcer care kit was first applied directly over the open ulcer to protect the wound bed. Both groups were followed for 3 months. Demographic and clinical characteristics such as age, gender, smoking status, hypertension, peripheral arterial disease (PAD), and diabetes mellitus (DM) were recorded. Primary endpoints included changes in ulcer size, calf circumference, NPRS pain scores, and VCSS scores. Measurements were taken before treatment, at 1 week, at 1 month, and at 3 months. The data were statistically analyzed using appropriate methods.

Results

The results showed that the compression bandage group had a more significant reduction in ulcer size compared to the compression stocking group. The ulcer size in the bandage group decreased from 16.5 ± 2.2 cm2 to 7.9 ± 5.1 cm2 after 3 months, while in the stocking group, it reduced from 16.1 ± 1.8 cm2 to 9.6 ± 3.1 cm2 ( p < .001). Additionally, the calf circumference showed a greater reduction in the bandage group, from 41.3 ± 1.9 cm to 35.3 ± 2.9 cm, compared to the stocking group, which showed a reduction from 40.7 ± 1.8 cm to 38.1 ± 2.4 cm ( p < .001). NPRS pain scores also decreased more significantly in the bandage group, with scores dropping from 8.0 ± 1.1 to 2.9 ± 2.8, while the stocking group saw a decrease from 7.9 ± 1.2 to 5.4 ± 2.4 ( p < .001). VCSS scores improved in both groups, but the bandage group showed a more marked improvement from 19.6 ± 5.1 to 5.2 ± 8.3 compared to the stocking group, which improved from 18.0 ± 5.1 to 7.1 ± 4.7 ( p < .001).

Conclusion

The findings suggest that compression bandages may be more effective than compression stockings in the post-surgical treatment of venous ulcers, particularly in terms of reducing ulcer size, calf circumference, and pain, as well as improving VCSS scores. These results support the continued use of compression bandages as a primary treatment modality for venous ulcers following surgery.
Exploring the network leadership practice of Master Principal Studio hosts in China
Authors: Zheng Yulian , Qian Haiyan , Song Jingyan , Chen Shuangye
Published: December 2024

The Master Principal Studio (MPS) in China is a key component of the Leading Program for Excellent Principals ( ming xiaozhang gongcheng). In this initiative, outstanding principals are selected and endorsed by official authorities to establish studios, where they serve as hosts. Junior principals and middle leaders join these studios as members, participating in collaborative learning experiences. MPS fosters a network of schools, connecting principals at different stages of their professional growth. This research explores the network leadership practices of MPS hosts. Data were collected through semi-structured interview with 13 hosts, 19 members, 10 student principals (as extended members), and 4 studio assistants in 13 different levels of MPSs in China. The findings show that the MPSs’ hosts employed various network leadership strategies to create an empowering and supportive learning ecosystem within the studio. This sheds light on the importance of nurturing and leveraging diverse relationships within professional learning networks to achieve collective success and drive educational advancement.
Reflecting on flexibility in the probation system: Learning from Catalonia and England and Wales
Authors: Vasilescu Cristina , Dominey Jane
Published: December 2024

The criminological literature affirms that the flexibility of probation officers is a very important aspect and highly valued by the community users' population and, in fact, is an important element that stands out in good-quality supervision in the community. However, flexibility remains an abstract concept and varies according to different jurisdictions. Moreover, there is little literature on what it means in theory and in practice to be flexible, how it is understood by professionals and how it is understood by users. This article reviews the literature on flexibility and discretion by differentiating between two frequently related concepts. It takes the example of Catalonia and England and Wales and the respective research in which the authors have been involved to examine what is meant by flexibility, conceptually and in practice. To do so, they analyse the experiences of both professionals and the user population in both jurisdictions through an intersectional perspective focused mainly on gender. Finally, evidence-based implications are presented.
Severe malnutrition predicts early postoperative complications in aseptic revision total shoulder arthroplasty
Authors: Liu Steven H , Mahboubi Ardakani Rustin , Loyst Rachel A , Cerri-Droz Patricia , Komatsu David E , Wang Edward D
Published: December 2024

Background

This study investigates the association between the Geriatric Nutritional Risk Index (GNRI), a simple readily available measure of malnutrition risk, and 30-day postoperative complications following revision total shoulder arthroplasty (TSA).

Methods

The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients who underwent TSA between 2015 and 2022. The study population was divided into three groups based on preoperative GNRI: normal/reference (GNRI > 98), moderate malnutrition (92 ≤ GNRI ≤ 98), and severe malnutrition (GNRI < 92). Logistic regression analysis was conducted to investigate the connection between preoperative GNRI and postoperative complications.

Results

Compared to normal nutrition, moderate malnutrition was not independently associated with postoperative complications. Compared to normal nutrition, severe malnutrition was independently associated with a greater likelihood of experiencing any complication (odds ratio (OR) 3.08, 95% confidence interval (CI) 1.80–5.27; P < 0.001), blood transfusions (OR 3.68, 95% CI 1.40–9.66; P = 0.008), non-home discharge (OR 2.99, 95% CI 1.50–5.98; P = 0.002), and length of stay >2 days (OR 3.10, 95% CI 1.77–5.42; P < 0.001).

Discussion

Severe malnutrition based on GNRI is a predictor of early complications following revision TSA, however moderate malnutrition is not.
Through their eyes: A retrospective mixed-methods study on the experiences and support needs of children growing up with a parent with Huntington’s disease
Authors: Daemen Maud MJ , Duits Annelien A , van der Meer Lucienne B , Andriessen Ruben L , Veenhuizen Ruth B , Wassenberg Renske , Peeters Tanja , de Jager Lia , Oosterloo Mayke
Published: December 2024

Background

Growing up with a parent with Huntington's disease (HD) profoundly impacts children. However, this impact and children's needs are often misunderstood, even by professional services. Even when resources are available, children often feel that their needs are unmet, raising concerns about the adequacy of available guidance and support.

Objective

This study aims to offer an in-depth understanding of the multifaceted impact of growing up with a parent with HD, examining the needs for professional guidance on emotional and social aspects, and identifying specific areas where support can be improved to better aid them.

Methods

This retrospective study utilized an exploratory sequential mixed methods design, combining qualitative focus groups ( n = 13) and a quantitative survey ( n = 23). Qualitative data were analyzed using an inductive thematic analysis with a descriptive phenomenological approach. Quantitative data were analyzed using descriptive statistics.

Results

The impact of HD on children extends across various domains, affecting self-development, social interactions, and family dynamics. Support received at home varied, with limited access to professional help. Support needs primarily revolved around emotional support and access to comprehensive information. Key support providers, such as parents, peers, mentors, healthcare providers and coaches with expertise in HD, play crucial roles in addressing these needs.

Conclusions

The study underscores challenges faced by children in HD families. By centering our efforts on the emotional well-being of these children, offering tailored information, involving their social network, providing community-based support, and strengthening parental support systems, we can improve the support required by children in these families.
Comparing Headlines During Conflict: War and Peace Journalism in the Coverage of the 2023 Israel-Gaza War in the Associated Press and Qatar News Agency
Authors: Kozman Claudia , Cozma Raluca
Published: December 2024

This study is a comparative content analysis of the Associated Press (AP) and Qatar News Agency (QNA) in their coverage of the 2023–2024 Israel-Gaza war. Focusing on the news headlines of AP and QNA in the first 4 months of the war, the study analyzed their use of war versus peace journalism indicators. Overall, the results revealed approximately equal levels of war and peace journalism, with significant differences in indicators between the two agencies. AP's focus on elites, the here-and-now, partisanship, and good and bad actors, indicated more war journalism levels than QNA that leaned toward peace journalism. However, the latter demonized Israel while victimizing and advocating for Gaza, whereas AP was less demonizing of either side, reported the invisible effects of the war, and mostly stayed away from labeling any side as good or bad.
An integrated subacute stroke ward within a community hospital increases rehabilitation efficiency and reduces healthcare expenditure
Authors: Tay San San , Goh Teck Kheng Edward , Tun Mon Hnin , Neo Edmund Jin Rui , Lee Onn Kei Angel
Published: December 2024

Background

Stroke is a leading cause of hospitalisation, disability, and death in Singapore. The healthcare system’s rehabilitative care model has seen ongoing evolution in response to changing patient needs and healthcare financing demands. Changi General Hospital (CGH) and St Andrew’s Community Hospital (SACH) collaborated on an integrated subacute stroke ward (SSW) in 2019 to optimise the transfer of stroke patients to the subacute rehabilitation setting.

Objective

To evaluate the outcomes of the integrated SSW.

Methods

This was a retrospective study. Anonymised data was used to evaluate functional, financial, and length-of-stay (LOS) outcomes.

Results

There were 71 patients in the control group (historical cohort) and 226 patients in the SSW cohort. Both groups were demographically, medically, and functionally similar except for a higher proportion of lacunar infarcts (LACI) in the SSW group. Although functional scores by Modified Barthel Index (MBI) were similar on discharge, the total LOS fell significantly (20 days) for the SSW group, with significant improvements in median rehabilitation efficiency (19.6 vs 10.9) but not median rehabilitation effectiveness (35.3 vs 31.0). Subgroup analysis revealed no impact from the disproportionate number of LACIs. Gross bill size, when corrected for inflation, was significantly lower across the combined hospitalisation ($31,270 vs $40,005).

Conclusions

This collaboration achieved savings in healthcare expenditure and LOS without compromising functional outcomes. The community hospital is a potent bridge for care transition and integrated services such as the SSW can optimise the rehabilitation journey for patients with stroke. Innovation in care provision can help to address the ever-changing challenges of healthcare.
Cutaneous involvement of light chain deposition disease: A case report
Authors: Vafaei-Nodeh Saba , Masoudi Hamid
Published: December 2024

Light chain deposition disease is a rare condition associated with plasma cell dyscrasia and other lymphoproliferative disorders in which there is overproduction and deposition of non-amyloid light chains in various organs, leading to organ dysfunction. It is well-established that the majority of patients with light chain deposition disease exhibit renal involvement. Although awareness of extrarenal manifestations is increasing, cutaneous involvement has rarely been reported. Herein, we present a case of light chain deposition disease with cutaneous manifestations in the absence of any renal disease. A biopsy of the skin revealed amorphous eosinophilic material within the superficial dermis. Using special stains, immunohistochemistry, and direct immunofluorescence, the deposits were confirmed to be kappa light chains.
Factors Influencing Patient Enrollment in a Community-based Physical Activity Program After Healthcare Provider Referral: A Mixed Methods Study
Authors: Schumacher Leah M. , Trilk Jennifer L. , McNulty Lia K. , Ylitalo Kelly R. , Eskuri Stephanie , Brooks John M. , Estabrooks Paul A. , Jindal Meenu , Stoutenberg Mark
Published: December 2024

Introduction and Objectives:

Structured physical activity (PA) programs help to prevent and manage chronic diseases, yet systematic approaches to identify and enroll patients in these programs are lacking. Exercise is Medicine Greenville (EIMG) is a novel clinic-to-community model that identifies patients with chronic diseases in primary care settings and connects them to a structured, evidence-informed, community-based PA program. This study assessed influences on PA program enrollment using a mixed methods design.

Methods:

Data were collected from 12 clinics over 18 months. Electronic health record data were used to quantitively compare the characteristics of referred patients who did versus did not enroll. Semi-structured interviews were conducted with a subset of non-enrollees to elucidate barriers and facilitators to enrollment.

Results:

Of the 217 referred patients who were eligible, 84 (38.7%) enrolled in the PA program. A greater percentage of enrollees had a history of high cholesterol (73.8%) relative to non-enrollees (57.9%, χ2 (1, N = 217) = 5.66, P = .02). Twenty-six patients completed qualitative interviews. Three themes emerged from interviews: (1) positive referral experiences with opportunity for enhanced information sharing and improved flow; (2) strong patient motivation, perceived capability, and social support; and (3) external barriers, such as cost and time, that prevented enrollment.

Conclusions:

Findings can guide improvements to the EIMG model, thus increasing its positive impact on individual- and community-level health. Findings can also inform efforts to build similar clinic-to-community PA models at other health systems.
Editorial Board Representation in Criminology: A Call to Address Racial Disparities
Authors: Breetzke G. D.
Published: December 2024

There is increased awareness of the structural exclusionary practices that permeate throughout almost all sectors of society, including higher education. One small but meaningful way in which this marginalization manifests itself throughout academia more generally, and within the knowledge production process more specifically, is through editorial board representation. This study investigates the racial breakdown of scholars listed as editorial board members for all journals under the “Criminology and Penology” category of the Clarivate Analytics’ Web of Science database. The study also examines the extent to which the racial representation of editorial board members is associated with journal quality. Almost 90% of all editorial board members across all criminology journals are White. The findings of this study highlight not only the glaring lack of racial diversity in editorial board compositions within criminology but is indicative of a broader systematic marginalization of certain groups that continues to perpetuate throughout academia in general. A number of potential strategies that can be used to increase the racial representativeness of editorial boards are outlined.
Location Preferences for Accessing Long-Acting Injectable Pre-Exposure Prophylaxis (LA-PrEP) Among Men Who Have Sex With Men (MSM) Currently on Daily Oral PrEP
Authors: Glick Jennifer L. , Nestadt Danielle F. , Sanchez Travis , Li Kevin , Hannah Marissa , Rawlings M Keith , Rinehart Alex R. , Sarkar Supriya , Vannappagari Vani
Published: December 2024

We investigated men who have sex with men's (MSM) location preferences for long-acting injectable pre-exposure prophylaxis (LA-PrEP). MSM ( n = 1076) who completed the 2021 American Men's Internet Survey, were currently prescribed oral PrEP, and expressed LA-PrEP interest reported location preferences for receiving LA-PrEP: healthcare provider (HCP) setting, pharmacy, or at-home. HCP settings were preferred by 60% of participants; 26% preferred home and 14% preferred pharmacy. In adjusted models, high healthcare stigma was associated with preferring pharmacy and at-home versus HCP, while high friends/family stigma was associated with preferring HCP settings versus pharmacy. Healthcare access history was associated with preference for HCP setting versus home. Being 25 to 29 or 30 to 29 years old versus 40+ was associated with preferring HCP versus home. Private insurance was associated with location preferences. Findings support the need for multiple LA-PrEP service locations to best reach MSM and highlight multiple complex factors that influence such preferences.
Return to Sports After Surgical Treatment of Rotator Cuff Tear in Young Athletes: A Systematic Review and Meta-analysis
Authors: Li Haoyue , Song Qingfa , Wu Xingyuan , Shi Chengxi , Shao Zhenxing , Cui Guoqing
Published: December 2024

Background:

Young athletes who undergo surgery for a rotator cuff tear (RCT) are expected to return to sports (RTS) at the preinjury level.

Purpose:

To determine the rate and level of RTS and associated factors after RCT surgery in young athletes.

Study Design:

Systematic review; Level of evidence, 4.

Methods:

A literature search was performed in PubMed, Embase, and Cochrane Library the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The inclusion criteria were studies in English evaluating RTS after surgical treatment of RCTs in athletes <40 years. Study quality was evaluated according to the Methodological Index for Nonrandomized Studies scores. Fixed-effects and random-effects meta-analyses were conducted to investigate the overall RTS rate and the ability to RTS at the preinjury level and explore the heterogeneity of the studies.

Results:

Of 168 studies initially identified, 13 studies (332 athletes; 270 competitive and 62 recreational) were included. The mean age of the athletes was 26.1 years (range, 13.2-39 years). Eleven studies (289 athletes) reported the type of sports; the most common sports were baseball (n = 195), football (n = 47), and tennis (n = 13). A total of 25 athletes were lost to follow-up, leaving 307 athletes with postoperative RTS data for meta-analysis. The combined rate of RTS according to the fixed-effects model was 84% (95% CI, 80%-88%). The level of RTS was evaluated in 11 studies (251 athletes), and according to the random-effects models, the combined rate of RTS at the preinjury level was 63% (95% CI, 49%-77%). In a subgroup analysis, the rate of RTS at the preinjury level was significantly different between competitive athletes (61% [95% CI, 46%-76%]) and recreational athletes (89% [95% CI, 78%-99%]) ( P = .004).

Conclusion:

Results of this review indicated that most young athletes were able to RTS after RCT surgery, and more than half were able to RTS at the preinjury level. Compared with competitive athletes, a higher proportion of recreational athletes were able to RTS at the preinjury level after surgery.
A systematic study of molecular targets of cannabidiol in Alzheimer's disease
Authors: Patil Nil , Patil Khushalika , Jain Mukul , Mohammed Arifullah , Yadav Alpa , Dhanda Parmdeep Singh , Kole Chittaranjan , Dave Kirtan , Kaushik Prashant , Azhar Abdul Razab Mohammad Khairul , Hamzah Zulhazman , Nawi Norazlina Mat
Published: December 2024

Background

Alzheimer's disease (AD) is a prevalent, incurable, and chronic neurodegenerative condition characterized by the accumulation of amyloid-β protein (Aβ), disrupting various bodily systems. Despite the lack of a cure, phenolic compounds like cannabidiol (CBD), a non-psychoactive component of cannabis, have emerged as potential therapeutic agents for AD.

Objective

This systematic review explores the impact of different types of cannabidiol on AD, unveiling their neuroprotective mechanisms.

Methods

The research used PubMed, Scopus, and Web of Science databases with keywords like “Alzheimer's disease” and “Cannabidiol.” Studies were evaluated based on title, abstract, and relevance to treating AD with CBD. No restrictions on research type or publication year. Excluded were hypothesis papers, reviews, books, unavailable articles, etc.

Results

Microsoft Excel identified 551 articles, with 92 included in the study, but only 22 were thoroughly evaluated. In-vivo and in-silico studies indicate that CBD may disrupt Aβ42, reduce pro-inflammatory molecule release, prevent reactive oxygen species formation, inhibit lipid oxidation, and counteract Aβ-induced increases in intracellular calcium, thereby protecting neurons from apoptosis.

Conclusions

In summary, the study indicates that CBD and its analogs reduce the production of Aβ42. Overall, these findings support the potential of CBD in alleviating the underlying pathology and symptoms associated with AD, underscoring the crucial need for further rigorous scientific investigation to elucidate the therapeutic applications and mechanisms of CBD in AD.
Chlamydia trachomatis infections in Kenya – sexually transmitted and ocular infections: a scoping review
Authors: Sohaili Aarman , Morre Servaas A. , Thomas Pierre P. M.
Published: December 2024

Background:

Chlamydia trachomatis (CT), a Gram-negative intracellular bacterium, is differentiated into three biovars associated with distinct clinical syndromes, ranging from trachoma, the world’s cause of preventable blindness, to the most common sexually transmitted infection. This variability underscores CT’s significant impact on public health, particularly in low-resource settings. In Kenya, where the demographic is predominantly younger, the burden of CT remains poorly understood and potentially underestimated.

Objectives:

This study aimed to assess the prevalence of both sexually transmitted and ocular CT across various regions and populations within Kenya.

Eligibility criteria:

Articles on CT population testing and laboratory detection, from 2014 to date, in English or Swahili only.

Sources of evidence:

Electronic databases of PubMed and Google Scholar were used.

Design:

A scoping review.

Charting methods:

This study conducted a systematic scoping review, following Arksey and O’Malley’s framework and adhering to PRISMA guidelines for scoping reviews (PRISMA-ScR).

Results:

This study incorporates findings from 19 original studies on sexually transmitted CT and seven on ocular CT. CT prevalence for four identified populations: sexually active females 2%–13%, men who have sex with men 1.3%–51%, pregnant women 2.5%–14.9% and other population groups 2.8%–16.4%. By contrast, studies on ocular CT, all performed in rural settings, found prevalence surpassing the WHO’s 10% threshold primarily amongst children and mothers.

Conclusion:

The variability in CT prevalence across different demographics and geographical regions emphasizes the impact of socio-economic, environmental and diagnostic factors on disease transmission and detection. The insights gained here can serve as a foundation for evidence-based health policies and interventions aimed at mitigating the burden of CT in Kenya.
Every Speech and Language Therapist Can Be an Ethical Leader: Revisiting the Language of Ethics (Part 1 of 2)
Authors: McAllister Lindy , Kenny Belinda , Kelly Áine , Kellaghan Sinead , Carroll Clare , Lyons Rena
Published: December 2024

Speech and language therapists (SLTs) are generally aware of and skilled in managing ethical issues in providing services to individual clients and families. However they may struggle with ethical concerns as they strive to deliver the best possible services in the context of increasing caseload volume and complexity, changing models of service delivery, service restructures and changes in support and professional development. This paper overviews the language of ethics, approaches to ethics and ethical decision-making, as tools for SLTs to analyse, articulate and manage ethical concerns associated with changing services and professional supervision contexts, in order to advocate for their clients and services and demonstrate ethical leadership in their workplaces.
Single-cell RNA sequencing reveals the contribution of smooth muscle cells and endothelial cells to fibrosis in human atrial tissue with atrial fibrillation
Authors: An Na , Yang Fan , Zhang Guoxia , Jiang Yuchen , Liu Haoqi , Gao Yonghong , Li Yingjian , Ji Peifeng , Shang Hongcai , Xing Yanwei
Published: December 2024

Aims

Atrial fibrillation (AF) has high mortality and morbidity rates. However, the intracellular molecular complexity of the atrial tissue of patients with AF has not been adequately assessed.

Methods and results

We investigated the cellular heterogeneity of human atrial tissue and changes in differentially expressed genes between cells using single-cell RNA sequencing, fluorescence in situ hybridization, intercellular communication, and cell trajectory analysis. Using genome-wide association studies (GWAS) and proteomics, we discovered cell types enriched for AF susceptibility genes. We discovered eight different cell types, which were further subdivided into 23 subpopulations. In AF, the communication strength between smooth muscle cells (SMCs) and fibroblast (FB) 3 cells increased and the relevant signaling pathways were quite similar. Subpopulations of endothelial cells (ECs) are mainly involved in fibrosis through TXNDC5 and POSTN. AF susceptibility genes revealed by GWAS were especially enriched in neuronal and epicardial cells, FB3, and lymphoid (Lys) cells, whereas proteomic sequencing differential proteins were concentrated in FB3 cells and SMCs.

Conclusions

This study provides a cellular landscape based on the atrial tissue of patients with AF and highlights intercellular changes and differentially expressed genes that occur during the disease process. A thorough description of the cellular populations involved in AF will facilitate the identification of new cell-based interventional targets with direct functional significance for the treatment of human disease.
Effects of psychedelics on neurogenesis and broader neuroplasticity: a systematic review
Authors: Lima da Cruz Rafael V. , Leão Richardson N. , Moulin Thiago C.
Published: December 2024

In the mammalian brain, new neurons continue to be generated throughout life in a process known as adult neurogenesis. The role of adult-generated neurons has been broadly studied across laboratories, and mounting evidence suggests a strong link to the HPA axis and concomitant dysregulations in patients diagnosed with mood disorders. Psychedelic compounds, such as phenethylamines, tryptamines, cannabinoids, and a variety of ever-growing chemical categories, have emerged as therapeutic options for neuropsychiatric disorders, while numerous reports link their effects to increased adult neurogenesis. In this systematic review, we examine studies assessing neurogenesis or other neurogenesis-associated brain plasticity after psychedelic interventions and aim to provide a comprehensive picture of how this vast category of compounds regulates the generation of new neurons. We conducted a literature search on PubMed and Science Direct databases, considering all articles published until January 31, 2023, and selected articles containing both the words “neurogenesis” and “psychedelics”. We analyzed experimental studies using either in vivo or in vitro models, employing classical or atypical psychedelics at all ontogenetic windows, as well as human studies referring to neurogenesis-associated plasticity. Our findings were divided into five main categories of psychedelics: CB1 agonists, NMDA antagonists, harmala alkaloids, tryptamines, and entactogens. We described the outcomes of neurogenesis assessments and investigated related results on the effects of psychedelics on brain plasticity and behavior within our sample. In summary, this review presents an extensive study into how different psychedelics may affect the birth of new neurons and other brain-related processes. Such knowledge may be valuable for future research on novel therapeutic strategies for neuropsychiatric disorders.
Extinguishing the flames of inflammation: retardant effect of chlorquinaldol on NLRP3-driven diseases
Authors: Wang Zhilei , Liu Jingwen , Mou Yu , Li Yuchen , Liao Wenhao , Yao Menglin , Wang Ting , Shen Hongping , Sun Qin , Tang Jianyuan
Published: December 2024

Background

NLRP3 inflammasome immoderate activation results in the occurrence of various inflammatory diseases, but the clinic medications targeting NLRP3 inflammasome are still not available currently. The strategy of drug repurposing can reorient the direction of therapy, which is an indispensable method of drug research. In this study, an antimicrobial agent chlorquinaldol (CQ) was conducted to assess the effect on NLRP3 inflammasome and novel clinical value on NLRP3-driven diseases.

Methods

The effect of CQ on NLRP3 inflammasome activation and pyroptosis was studied in mouse and human macrophages. ASC oligomerization, intracellular potassium, reactive oxygen species production, and NLRP3-ASC interaction were used to evaluate the suppression mechanism of CQ on inflammasome activation. Finally, the ameliorative effects of CQ in the model of LPS-induced peritonitis, dextran sodium sulfate (DSS)-induced colitis, and monosodium urate (MSU)-induced gouty arthritis were evaluated in vivo.

Results

CQ is a highly powerful NLRP3 inhibitor that has feeble impact on the NLRC4 or AIM2 inflammasome activation in mouse and human macrophages. Further study indicated that CQ exhibits its suppression effect on NLRP3 inflammasome by blocking NLRP3-ASC interaction and hydroxyl on the benzene ring is vital for the assembly and activation of NLRP3 inflammasome. Furthermore, in vivo experiments demonstrated that administration of CQ has outstanding therapeutic action on LPS-induced peritonitis, DSS-induced colitis, and MSU-induced gouty inflammation in mice.

Conclusions

Collectively, the current study discoveries the antimicrobial agent CQ as a potentially specific NLRP3 inhibitor, and its use provides a feasible therapeutic approach for the treatment of NLRP3-driven diseases.
Depressed TFAM promotes acetaminophen-induced hepatotoxicity regulated by DDX3X–PGC1α–NRF2 signaling pathway
Authors: Chen Sisi , Cao Yaling , Fan Zihao , Xu Ling , Pan Zhenzhen , Gao Yao , Wei Linlin , Wei Qiaoxin , Tian Yuan , Zhang Xiangying , Liu Mei , Ren Feng
Published: December 2024

Background

Acetaminophen (APAP)-induced acute liver injury (AILI) is the most prevalent cause of acute liver failure and mitochondrial dysfunction plays a dominant role in the pathogenesis of AILI. Mitochondrial transcription factor A (TFAM) is an important marker for maintaining mitochondrial functional homeostasis, but its functions in AILI are unclear. This study aimed to investigate the function of TFAM and its regulatory molecular mechanism in the progression of AILI.

Methods

The roles of TFAM and DEAD (Asp-Glu-Ala-Asp) box polypeptide 3 X-linked (DDX3X) in AILI were determined with TFAM overexpression and DDX3X knockdown, respectively.

Results

TFAM expression was suppressed in AILI patients. TFAM overexpression alleviated liver necrosis and mitochondrial dysfunction. Treatment of the AILI mice model with N-acetylcysteine (NAC), a drug used to treat APAP overdose, resulted in significant TFAM activation. In vivo experiments confirmed that TFAM expression was negatively regulated by DDX3X. Mechanistic studies showed that nuclear respiratory factor 2 (NRF-2), a key regulator of TFAM, was selectively activated after DDX3X knockdown via activated peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1α), in vivo and in vitro.

Conclusions

This study demonstrates that depressed hepatic TFAM plays a key role in the pathogenesis of AILI, which is regulated by the DDX3X–PGC1α–NRF2 signaling pathway.
Identification and validation of differentially expressed disulfidptosis-related genes in hypertrophic cardiomyopathy
Authors: Fan Huimin , Tan Xin , Xu Shuai , Zeng Yiyao , Zhang Hailong , Shao Tong , Zhao Runze , Zhou Peng , Bo Xiaohong , Fan Jili , Fu Yangjun , Ding Xulong , Zhou Yafeng
Published: December 2024

Hypertrophic cardiomyopathy (HCM) is one of the most common cardiovascular diseases with no effective treatment due to its complex pathogenesis. A novel cell death, disulfidptosis, has been extensively studied in the cancer field but rarely in cardiovascular diseases. This study revealed the potential relationship between disulfidptosis and hypertrophic cardiomyopathy and put forward a predictive model containing disulfidptosis-associated genes (DRGs) of GYS1, MYH10, PDMIL1, SLC3A2, CAPZB, showing excellent performance by SVM machine learning model. The results were further validated by western blot, RNA sequencing and immunohistochemistry in a TAC mice model. In addition, resveratrol was selected as a therapeutic drug targeting core genes using the CTD database. In summary, this study provides new perspectives for exploring disulfidptosis-related biomarkers and potential therapeutic targets for hypertrophic cardiomyopathy.
Cerebral blood flow and arterial responses in migraine: history and future perspectives
Authors: Olesen Jes
Published: December 2024

Introduction

It is largely accepted that migraine with aura (MA) is caused by cortical spreading depression (CSD) and that migraine without aura (MO) is not. This is mostly based on old studies of regional cerebral blood flow (rCBF) and studies of vascular responses. These studies are partly forgotten today and may, therefore, be worthwhile reviewing.

Methods

The review is based on the authors life-long involvement in these issues and his knowledge of the relevant literature plus scrutiny of reference lists of these papers.

Results

The strongest evidence for CSD in MA came from studies using intraarterial injection of 133-Xenon and recording from 254 areas of the relevant hemisphere. Measurements could be taken before and during development of an attack because the procedure triggered MA. The findings were identical to many features of CSD. They were confirmed using 133-Xenon Single Photon Emission Computerized Tomography (SPECT).It was shown that the generally accepted vasospastic theory of migraine was incorrect. Headache started while rCBF was decreased and did not change during later hyperperfusion. rCBF remained normal in MO but later studies have shown increase in areas also activated by other pain. Flow Was focally increased in the brain stem also after treatment of the pain. Dilatation of large cerebral arteries during MO attack was first shown with ultrasound and later confirmed by MR angiography which also showed a lack of dilatation of extracerebral arteries.

Discussion

Much has in later years been done using modern PET and MR techniques. These studies have confirmed the old studies and have added many new aspects which are not reviewed here. The final proof of CSD during MA and its absence during MO still awaits the definitive study.

Conclusion

Studies from the 1980ies and 1990ies caused a fundamental shift in our understanding of the vascular and cortical mechanisms of migraine. They remain a solid base for our current understanding and inspire further study.
Perspectives on managing innovation readiness in long-term care: a Q-methodology study
Authors: van den Hoed Monique W. , Daniëls Ramon , Beaulen Audrey , Hamers Jan P. H. , van Exel Job , Backhaus Ramona
Published: December 2024

Background

The scarcity of resources in long-term care demands more than ever that organizations in this sector are prepared for innovation to ensure affordable access to care for older adults. Organizations that are innovation ready are more capable of implementing innovations. Therefore, a better understanding of how stakeholders view innovation readiness in long-term care can provide actionable strategies to enhance their innovative capacities. ‘Innovation readiness’ indicates the level of maturity of an organization to succeed in any type of innovation. Our study explored perspectives among stakeholders on what they consider important for organizations in long-term care for older adults to be innovation ready.

Methods

Q-methodology, a mixed-methods approach, was used to investigate the perspectives of 30 stakeholders connected to long-term care for older adults in the Netherlands: academics, (top)management, innovation managers, client representatives, staff, and consultants. Stakeholders were asked to rank 36 statements on innovation readiness on importance. Statements were extracted from literature research and qualitative interviews. Thereafter in the post-interviews stakeholders explained their ranking and reflected on the statements. By-person factor analysis was used to identify clusters in the ranking data. Together with the qualitative data from follow-up interviews, these clusters were interpreted and described as perspectives of the stakeholders.

Results

Four distinct perspectives were identified on what they consider important for innovation readiness in long-term care: (1) ‘supportive role of management’ (2) ‘participation of the client (system) and employees’ (3) ‘setting the course and creating conditions’ and (4) ‘structuring decision-making, roles and responsibilities’. The 36 statements represented a complete overview of innovation readiness factors. No additional innovation factors to those previously identified in the literature emerged from the interviews.

Conclusions

Stakeholders agree that all factors contributing to innovation readiness of long-term care organizations for older adults are accounted for. The variety of perspectives on what is most important shows there is no agreement among stakeholders about a fixed route toward innovation readiness. However, stakeholders suggested a temporal order of the innovation readiness factors, preferably starting with formulating the innovation ambition. This study’s results could contribute to developing an assessment tool to deliver a structured approach for managers to assess the innovation readiness of their organization.

Registration

The study received ethical approval on April 13, 2022 from the Medical Ethics Board of Zuyderland Medical Center in the Netherlands with the number METCZ20220036.
Longitudinal anemia status and risk for adverse outcomes in former smokers with COPD
Authors: Kunitomo Yukiko , Woo Han , Balasubramanian Aparna , Fawzy Ashraf , Lin Cheng Ting , Raju Sarath , Belz Daniel C , McCormack Meredith C , Koehler Kirsten , Hansel Nadia N , Putcha Nirupama
Published: December 2024

Background

Anemia is a prevalent comorbidity in COPD associated with increased morbidity. However, the significance of longitudinal anemia status and variation in anemia status trends over time in COPD are not known. Furthermore, individuals with COPD and smoking history often have multiple comorbidities, in particular cardiovascular disease. The objective of this study was to evaluate the association between longitudinal anemia status and COPD outcomes, accounting for comorbid cardiovascular disease.

Methods

Serial hemoglobin measures and clinical outcomes were obtained in former smokers with moderate to severe COPD from two clinical studies over a 6-to-9-month period. In the first analysis, the association between repeated measures of time-varying anemia status and outcomes was assessed by generalized estimating equations adjusted for covariates including cardiovascular disease. In the second analysis, each participant’s anemia risk profile during the study period was characterized as high versus low anemia risk-growth rate. Mean differences in the progression of COPD outcomes over time between the two groups were assessed using a generalized linear mixed model. Effect modification by baseline coronary artery calcium (CAC) burden was explored.

Results

There were 159 individuals with mean age of 66.5 years (± 8.3) and mean FEV1% predicted of 51.4% (± 17.0), of which 41% were ever-anemic during the study period. Repeated measures of anemia status were associated with higher St. George’s Respiratory Questionnaire (SGRQ) scores (β 2.5, 95% CI: 0.1,4.8, p = 0.04), lower 6-minute walk distance (6MWD) (β -38.6, 95% CI: -67.7,-7.4, p = 0.02), and higher rate of moderate-to-severe exacerbations over the prospective follow-up period (IRR 1.8, 95% CI: 1.1,2.8, p = 0.02). There was effect modification by CAC burden such that with higher burden the mean difference in COPD outcome by anemia status was greater for a subset of symptom scores. Participants with profiles of increasing anemia risk had higher estimated rates of decline in the FEV1% predicted and 6MWD and increase in SGRQ scores compared to those with stable or decreasing anemia risk.

Conclusions

Longitudinal anemia status trends may be predictive of COPD disease trajectory. Anemia status by repeated measures analysis is associated with COPD morbidity with potentially stronger associations in the setting of high CAC burden.
Enhancing knee osteoarthritis diagnosis with DMS: a novel dense multi-scale convolutional neural network approach
Authors: Zhang Di , Dong Yuting , Xu Yao , Qian Junhui , Ye Miaoyu , Yuan Qiang , Luo Jian
Published: December 2024

Background

Osteoarthritis (OA) of the knee is a prevalent chronic degenerative joint condition that is having a growing impact on a global scale., posing a challenge in diagnosis which is often reliant on time-consuming and error-prone visual analysis by physicians. There is a critical need for an automated, efficient, and accurate diagnostic method to improve early detection and treatment.

Methods

We developed a novel Convolutional Neural Network (CNN) module, Dense Multi-Scale (DMS), an advancement over Multi-Scale Convolution (MSC). This module utilizes dense connections in convolutions of varying sizes (1 × 1, 3 × 3, 5 × 5) and across layers, enhancing feature reuse and complexity recognition, thereby improving recognition capabilities. Dense connections also facilitate deeper network architecture and mitigate gradient vanishing problems. We compared our model with a standard baseline model and validated it using an unseen-data test set.

Results

The DMS model exhibited exceptional performance in unseen-data tests, achieving 73.00% average accuracy (ACC) and 92.73% area under the curve (AUC), surpassing the baseline model’s (DenseNet) 63.52% ACC and 88.76% AUC. This highlights the DMS model’s superior predictive capability for knee OA.

Conclusion

The DMS model presents a significant advancement in predicting and grading knee OA, holding substantial clinical importance. It promises to aid radiologists in accurate diagnosis and grading, and in choosing appropriate treatments, thereby reducing misdiagnosis and patient burden.
Zhishi Xiebai Guizhi Decoction modulates hypoxia and lipid toxicity to alleviate pulmonary vascular remodeling of pulmonary hypertension in rats
Authors: Fu Min , Li Yuan , Liu Jingjing , Liu Junjie , Wei Jiaoxia , Qiao Yuxin , Zhong Hanxin , Han Dongyang , Lu Haitao , Yao Li
Published: December 2024

Background

Pulmonary hypertension (PH) is a severe cardio-pulmonary vascular disease, involves complex molecular mechanism especially during the pathological process of pulmonary vascular remodeling, brings a significant challenge to clinical treatment and thus resulting in high mortality rates. Classic Traditional Chinese medicine formula, Zhishi Xiebai Guizhi Decoction (ZXGD), holds therapeutic potential for PH. In present study, we sought to explore therapeutic potential of ZXGD against PH in rats.

Methods

We employed a combination methods of chemical profiling, echocardiographic, morphologic measurements, molecular biology, rats models and cultured pulmonary artery smooth muscle cells (PASMCs) to achieve this.

Results

Eighteen compounds were precisely identified in ZXGD using UHPLC-QTOF-MS/MS. Our data demonstrated ZXGD could alleviate PH by reducing pulmonary artery pressure and alleviating pulmonary vascular remodeling in rats. Specifically, ZXGD was found to intervene in abnormal expansion of PASMCs, thereby attenuating pulmonary vascular remodeling. ZXGD was also observed to modulate expressions of HIF-1α, ROS, and Nrf2 to alleviate hypoxia and oxidative stress. Additionally, ZXGD significantly regulated disorders in pro-inflammatory cytokines, thus mitigating inflammation. Furthermore, ZXGD decreased levels of decadienyl-l-carnitine and LDL-C, while elevating HDL-C and lipid droplet counts, thereby reducing cholesterol and lipid toxicity and preserving mitochondrial function. Importantly, inhibition of HIF-1α reversed expression of key pathological triggers for pulmonary vascular remodeling. Neohesperidin and naringin in ZXGD extract were identified as the primary contributors to its pharmacological effects against PH.

Conclusion

Altogether, our study empirically explored therapeutic potential and pharmacological mechanisms of ZXGD in treating PH, offering a groundwork for the development of novel anti-PH drugs.

Graphical Abstract
Crafting inclusive parenting programs– considerations for deaf families: a qualitative study
Authors: Ikwara Asher Emmanuel , Nabagesera Rebecca , Isiko Isaac
Published: December 2024

Background

The parenting of children by deaf parents has many challenges that require a barrier-breaking approach to ensure inclusivity and accessibility. Therefore, this study explored pathways for crafting inclusive parenting programs, fostering a future where every family thrives, regardless of hearing ability.

Methods

This was a qualitative study that employed in-depth interviews with 20 deaf parents and utilized thematic content analysis. This study was carried out at events organized by the Uganda National Association of the Deaf (UNAD) at Makerere College School. Deaf parents were purposively selected from attendees at events organised by the Uganda National Association of the Deaf (UNAD) during the specified celebrations.

Results

An analysis of interviews with deaf parents identified six crucial themes for inclusive parenting programs. Language education was highlighted for strengthening family bonds. Communication and relationship building emphasized equal treatment and love for deaf children. Cultural sensitivity and education were deemed essential, as visual tools and district associations were used. Tailoring content for deaf children emphasized playful and educational materials, such as sign language videos. The utilization of technology for accessible programs and the promotion of community involvement are recognized as critical components.

Conclusion

This study emphasized the unique experiences of deaf parents, highlighting the need for sign language education, cultural sensitivity, and technology while addressing challenges like limited resources, stigma, and advocacy gaps in parenting programs.