bluuebunny/crossref_metadata_2025 huggingface dataset:
Productive infection of the retinal pigment epithelium by SARS-CoV-2: Initial effects and consideration of long-term consequences
Authors: Hultgren Nan W , Petcherski Anton , Torriano Simona , Komirisetty Ravikiran , Sharma Madhav , Zhou Tianli , Burgess Barry L , Ngo Jennifer , Osto Corey , Shabane Byourak , Shirihai Orian S , Kelesidis Theodoros , Williams David S
Published: December 2024

As the SARS-CoV-2 coronavirus continues to evolve and infect the global population, many individuals are likely to suffer from post-acute sequelae of SARS-CoV-2 infection (PASC). Manifestations of PASC include vision symptoms, but little is known about the ability of SARS-CoV-2 to infect and impact the retinal cells. Here, we demonstrate that SARS-CoV-2 can infect and perturb the retinal pigment epithelium (RPE) in vivo, after intranasal inoculation of a transgenic mouse model of SARS-CoV-2 infection, and in cell culture. Separate lentiviral studies showed that SARS-CoV-2 Spike protein mediates viral entry and replication in RPE cells, while the Envelope and ORF3a proteins induce morphological changes. Infection with major variants of SARS-CoV-2 compromised the RPE barrier function and phagocytic capacity. It also caused complement activation and production of cytokines and chemokines, resulting in an inflammatory response that spread across the RPE layer. This inflammatory signature has similarities to that associated with the onset of age-related macular degeneration (AMD), a major cause of human blindness, resulting from RPE pathology that eventually leads to photoreceptor cell loss. Thus, our findings suggest that post-acute sequelae of SARS-CoV-2 infection of the RPE may have long-term implications for vision, perhaps comparable to the increased occurrence of AMD found among individuals infected by HIV, but with greater public health consequences due to the much larger number of SARS-CoV-2 infections.
Improving debriefing practices for participants in social science experiments
Authors: Clayton Katherine , Porter Ethan , Velez Yamil , Wood Thomas J
Published: December 2024

Social science experiments often expose participants to false, deceptive, or otherwise harmful content. In an effort to mitigate the effects of such content and to comply with regulatory standards, these studies usually conclude by “debriefing” participants about the content they encountered, on the assumption that doing so will eliminate the effects of exposure. We present evidence showing that this assumption is not always correct. After standard debriefs, participants who have seen political misinformation often remain worse-informed than if they had never been exposed to misinformation in the first place. We then design and test a new approach to debriefing, which entails (i) debriefing as soon after exposure to harmful content as possible; (ii) providing an informative correction; and (iii) requiring participants to affirm that they have been exposed to false information. Across multiple experiments, we show that this approach is far superior to standard debriefs at reducing the effects of false or harmful content on political attitudes and beliefs. Our approach makes it possible to study the effects of false or harmful content on attitudes and beliefs without posing significant risks to participants.
ZHX3 interacts with CEBPB to repress hepatic gluconeogenic gene expression and uric acid secretion
Authors: Tan Wei Xuan , Lim Lillian Yuxian , Afsha Nesha , Chan Gloria Mei En , Ching Carmen , Oguz Gokce , Neo Suat Peng , Mohamed Ali Safiah , Ramasamy Adaikalavan , Gunaratne Jayantha , Hunziker Walter , Khoo Chin Meng , Teo Adrian Kee Keong
Published: December 2024

ZHX3, which encodes for a transcriptional repressor, is associated with fasting blood glucose (FBG) levels and increased type 2 diabetes (T2D) risk but its role in cell types involved in glucose metabolism is not well understood. Here, we show that the deletion of ZHX3 in the human pancreatic β-cell line EndoC-βH1 did not impair glucose-stimulated insulin secretion (GSIS) nor perturb its transcriptome. On the other hand, we found that ZHX3 represses the expression of gluconeogenic genes PCK1 and G6PC1 in the human hepatoma line HepG2. Transcriptomic analysis of ZHX3-deficient HepG2 cells revealed that the uric acid transporter gene SLC17A1 was up-regulated, which consequentially led to increased uric acid secretion. High levels of uric acid could then impair GSIS in EndoC-βH1 cells. Subsequently, in-depth co-immunoprecipitation followed by mass spectrometry analysis of ZHX3 in HepG2 cells identified transcription factor CEBPB as its binding partner, required to repress the transcription of PCK1, G6PC1, and partially SLC17A1 in HepG2 cells. Overall, our study uncovered the role of ZHX3 in regulating glucose metabolism in hepatocytes, thereby influencing FBG levels and their association with T2D risk.
The comparison of the efficacy of intramuscular tetracosactide and subacromial triamcinolone injection in rotator cuff tendinitis: a randomized trial
Authors: Orandi Amir Hossein , Mansour Amirpasha , Bagheri Nima , Majedi Hossein , Emami Meibodi Seyed Ali , Pestehei Seyed Khalil , Saberian Peyman
Published: December 2024

Objectives

Rotator cuff tendinitis (RCT) is a tendon inflammation often following subacromial impingement syndrome. One of the non-surgical management modalities for RCT is subacromial injection of corticosteroids. Some studies have claimed a correlation between ACTH (Adrenocorticotropic Hormone) deficiency and rotator cuff lesions; hence, intramuscular ACTH analogue injection has been recommended as an option. This research aimed to compare the effectiveness of these two treatment methods.

Methods

We conducted a study with 86 patients suffering from RCT. The patients were randomly divided into two groups of 43; one group received a subacromial injection of 40 mg of triamcinolone acetonide, while the other group received 1 mg of intramuscular tetracosactide injection. We recorded the Constant–Murley (CM) and visual analogue scale (VAS) scores for each patient before and 4 weeks after injections to measure pain acuity and joint functionality. Later, we compared and analysed the two scores in each group.

Results

Based on the statistical analysis, the mean ages of the participants in the triamcinolone and tetracosactide groups were 53.21 ± 11.37 and 54.56 ± 11.98, respectively. Both groups demonstrated an improvement in VAS for pain and CM scores (P < 0.05). However, the VAS for pain score decreased, and the CM score increased more significantly in the triamcinolone group than in the tetracosactide group (P < 0.05).

Conclusion

Although both treatment methods exhibit promise for pain relief, subacromial injection of triamcinolone appears more efficacious than intramuscular injection of tetracosactide in patients with RCT, based on a 4-week follow-up.

Trial registration

Iranian Registry of Clinical Trials, https://irct.behdasht.gov.ir, IRCT20240110060673N1.
Analysis of risk factors for abnormal renal function in patients with gout in Southwest China: a cross-sectional study
Authors: Zhang Ting , Zeng Ziqian , Xu Dan , Dang Wantai
Published: December 2024

Objective

To analyse the associations between renal function and clinical laboratory indicators and explore the renal function abnormality risk factors for gout patients in Southwest China.

Methods

Outpatient and hospitalized gout patients (n = 4384) at the First Affiliated Hospital of Chengdu Medical College between January 2017 and December 2020 were divided into normal (n = 2393) and abnormal (n = 1991) renal function groups according to their eGFR. The relationships between clinical laboratory indicators and the eGFR were analysed, and a logistic regression model was fit to identify significant risk factors.

Results

Sex, age, absolute lymphocyte count (ALC), cystatin C (CysC), homocysteine (Hcy) and thyroid stimulating hormone (TSH) were associated with renal function abnormalities (P < 0.05), whereas age [odds ratio (95% CI) = 1.06 (1.05–1.08), P < 0.001], Hcy [1.02 (1.00–1.04), P = 0.028], CysC [1.72 (1.54–1.92), P < 0.001], ALC [0.71 (0.52–0.97), P = 0.03] and TSH [1.08 (1.00–1.17), P = 0.049] were abnormal renal function risk factors for gout patients. After stratification by UA, binary logistic regression analysis identified the following risk factors: Q1 age [1.06 (1.02–1.11), P = 0.003], CysC [1.67 (1.30–2.16), P < 0.001]; Q2 age [1.09 (1.06–1.12), P < 0.001], CysC [1.55 (1.28–1.88), P < 0.001], FT3 [0.66 (0.46–0.96), P = 0.029]; Q3 age [1.06 (1.03–1.09), P < 0.001], CysC [1.75 (1.41–2.18), P < 0.001], Hcy [1.04 (1.00–1.08), P = 0.047], ALC [0.35 (0.18–0.69), P = 0.002]; Q4 age [1.05 (1.02–1.09), P = 0.004], CysC [1.79 (1.40–2.30), P < 0.001].

Conclusion

ALC and levels of TSH and serum Cys could be used for monitoring for abnormal renal function in patients with gout.
A Scleroderma and Raynaud’s UK (SRUK) national survey to explore rheumatologists’ awareness, approaches to diagnosis and management and training needs within systemic sclerosis
Authors: Blamont Emma , Farrington Sue , Glover-Southworth Nina , Cornwell Gemma , Gibson Laura , Sloan Melanie , Hughes Michael
Published: December 2024

Objectives

Patients’ outcomes and experiences can be affected by rheumatologist knowledge and awareness of systemic sclerosis (SSc). Our survey, directed at UK-based rheumatologists, aimed to expand our understanding of the above points along with their ability to keep up to date with guidelines defining best practice.

Methods

Rheumatologists were invited to participate in an online survey, with the results analysed and presented descriptively and graphically by SRUK.

Results

Of the 150 UK rheumatologists surveyed, 2% reported that they had not heard of SSC and 18.7% reported having a limited understanding of the condition. A total of 44% of respondents reported that they were fully versed in the signs and symptoms of SSc. The majority of those surveyed shared the broad view that all aspects of SSc, including services (63.4%), specialist positions (64.7%), research (73.1%) and training and education (70%), are either completely or somewhat underfunded. Most respondents (87.4%) reported that their workload allowed them to ‘somewhat’ (48.74%) or ‘completely’ (38.66%) keep up to date with official guidelines. Scleroderma and Raynaud’s UK (SRUK) (47.9%), followed by NICE (43.7%), were the most highly used sources of information utilized among those surveyed.

Conclusion

Our survey reveals a serious gap in the awareness and the signs and symptoms of SSc among some UK rheumatologists, in addition to a perception that services, training and education in this area are underfunded. Our findings indicate that there is a role for the provision of further education and training as part of continued professional development.
Psoriatic Arthritis Priority Setting Partnership: patient- and clinician-informed considerations for future UK health service delivery
Authors: James Lija , Hailey Louise , Bundy Christine , Burstow Helen , Chandler David , Cowper Russ , Helliwell Philip , Joannes Lucille , Kelly Andy , Kennedy Bronagh , Kinsella Suzannah , McAteer Helen , Mukherjee Sandeep , Packham Jon , Wise Elspeth , Young Helen , Dures Emma , Coates Laura C
Published: December 2024

Objectives

Little is known about the ideal service delivery model and shortcomings in patient experiences in the NHS for patients with psoriatic arthritis (PsA). The objective of this work was to identify unmet needs perceived within the current health service delivery model for PsA from the UK Psoriatic Arthritis Priority Setting Partnership (PsA-PSP).

Methods

An online survey was conducted in 2020 and distributed to people with PsA, their carers and clinicians to identify research priorities in PsA. The participants were asked to submit three questions unanswered in PsA research. A proportion of submissions related to health service delivery were identified, which were deemed as out of scope for the main PsA-PSP but nevertheless important to report. Content analysis was used to analyse these submissions separately.

Results

We reviewed 138 submissions that were not related to the James Lind PSP and research priorities in PsA. Among these, 118 (85.5%) were focused on health service delivery and were classified into five main themes: rheumatology service, primary care navigation, education, holistic care, and ethnicity, diversity and inclusion. Further analysis within the rheumatology service theme revealed additional sub-themes that emphasized integrating multidisciplinary services, improving access to advice lines and ensuring fair access to treatments.

Conclusion

The five key themes provide valuable insights into the important areas of interest within health service delivery in the UK. By understanding these themes, policymakers, healthcare providers and researchers can better prioritize their efforts and address the specific care needs of people with PsA, their care providers and clinicians.
Ultrasonography for the assessment of enthesitis in psoriatic arthritis: systematic review with meta-analysis
Authors: Bibas Noémie , Pignon Caroline , Lopez-Medina Clementina , Gandjbakhch Frédérique , Fautrel Bruno , Gossec Laure
Published: December 2024

Objectives

The specificity of US for enthesitis in PsA is unclear. The objective was to analyse the specificity of US enthesitis in Mode B and using power Doppler for the diagnosis of PsA through a systematic review with meta-analysis.

Methods

Systematic review in PubMed 2010 to June 2023 of studies of adult patients with confirmed PsA with or without a control group of non-PsA patients, reporting information on US enthesitis. Data were analysed on (i) the prevalence of US enthesitis (presence of at least one enthesitis) in PsA patients and non-PsA patients, (ii) specificity and sensitivity of US enthesitis and then specifically power Doppler for PsA diagnosis and (iii) most specific localizations of enthesitis in PsA patients. Pooled percentages and means were evaluated using univariate random effects meta-analysis.

Results

In 76 articles, 5927 patients with PsA were compared with 3423 controls (59.0% of whom had psoriasis). The prevalence of US enthesitis was 73.7% (95% CI 56.6–90.9%) in PsA patients vs 12.6% (2.6–22.3%) in controls. The pooled specificity and sensitivity of Mode B US were 73.2% (59.3–87.0%) and 62.1% (47.9–76.4%); and of power Doppler, were 97.9% (96.5–99.5%) and 14.7% (8.2–21.2%), respectively. The site most frequently involved in PsA but not in controls was the Achilles tendon, in which erosions and power Doppler activity were most discriminant.

Conclusion

In this systematic review, US enthesitis was highly prevalent in PsA patients. Evidencing enthesitis by US was found to be reasonably specific and could contribute to the diagnosis of PsA; power Doppler was highly specific, however it was rarely present.
Predictors of rituximab efficacy in systemic sclerosis-associated interstitial lung disease: machine-learning analysis of the DESIRES trial
Authors: Kuzumi Ai , Oba Koji , Ebata Satoshi , Kashiwabara Kosuke , Ueda Keiko , Uemura Yukari , Watadani Takeyuki , Fukasawa Takemichi , Miura Shunsuke , Yoshizaki-Ogawa Asako , Kage Hidenori , Sato Shinichi , Yoshizaki Ayumi
Published: December 2024

Objectives

Rituximab is emerging as a promising therapeutic option for systemic sclerosis-associated interstitial lung disease (SSc-ILD). However, little is known about factors that predict the efficacy of rituximab in SSc-ILD.

Methods

A post-hoc analysis was performed on prospective data from 48 patients with SSc-ILD in the double-blind, randomized, placebo-controlled DESIRES trial. A total of 28 baseline factors were selected as candidates to predict the efficacy of rituximab on the percentage of predicted forced vital capacity (ppFVC) at 24 weeks. A machine learning causal tree algorithm was used to explore the combination of predictors to identify subpopulations with a good response to rituximab.

Results

Serum levels of C-reactive protein (CRP) and Krebs von den Lungen-6 (KL-6) were selected as branches of the decision tree to stratify patients into three subpopulations. In the subpopulation with serum CRP levels ≥0.055 mg/dl, ΔppFVC was significantly higher in the rituximab group than in the placebo group [difference 8.01% (95% CI: 4.40%, 11.62%)]. In the subpopulation with serum CRP levels <0.055 mg/dl and serum KL-6 levels ≥364 U/ml, ΔppFVC was comparable between the two groups [difference 2.47% (95% CI: −1.99%, 6.92%)]. In the subpopulation with serum CRP levels <0.055 mg/dl and serum KL-6 levels <364 U/ml, ΔppFVC was significantly lower in rituximab than in placebo [difference −6.85% (95% CI: −10.80%, −2.91%)].

Conclusion

Even slight elevations in serum CRP levels are associated with the improvement in ppFVC and may serve as predictors of rituximab efficacy in SSc-ILD.
Migrating arts with (out) migrating artists: Decentering the global art world
Authors: Lee Kangsan , Levitt Peggy , Valdivia-Moreno Chantal
Published: December 2024

Most models of cultural globalization describe circulation to and around conventional cultural centers. The art world becomes more inclusive, but its fundamental hierarchies remain in place. In this paper, we describe another form of cultural globalization called “decentering”, which involves the circulation and increased interconnectedness between peripheries, either with or without their integration to cultural centers. Using a mixed methods approach, we examined the global circulation of artists from Argentina, Lebanon, and South Korea in the past 20 years (2000–2019). The results show their works circulated to a broader range of destinations, more rapidly than their early artistic cohorts, without necessarily passing through traditional art centers. This trend was particularly true for younger artists. We attribute the increasing prominence of decentering to three factors: (1) The mobility of early artists that enables later artists to gain recognition without physically migrating, (2) the role of vernacularizers, and (3) labeling as categorization. Our research contributes to understandings of cultural globalization by demonstrating how these factors broaden the geographies of the global contemporary art world and encourage more vibrant artistic circulation within and between peripheries.
Critical roles of extracellular vesicles in periodontal disease and regeneration
Authors: Jing Lin , Wang Hong-Yu , Zhang Ning , Zhang Wen-Jie , Chen Yuzhe , Deng Dao-Kun , Li Xuan , Chen Fa-Ming , He Xiao-Tao
Published: December 2024

Extracellular vesicles (EVs) are evolutionarily conserved communication mediators that play key roles in the development of periodontal disease as well as in regeneration processes. This concise review first outlines the pathogenic mechanisms through which EVs derived from bacteria lead to the progression of periodontitis, with a focus on the enrichment of virulence factors, the amplification of immune responses, and the induction of bone destruction as key aspects influenced by bacterial EVs. This review aims to elucidate the positive effects of EVs derived from mesenchymal stem cells (MSC-EVs) on periodontal tissue regeneration. In particular, the anti-inflammatory properties of MSC-EVs and their impact on the intricate interplay between MSCs and various immune cells, including macrophages, dendritic cells, and T cells, are described. Moreover, recent advancements regarding the repair-promoting functions of MSC-EVs are detailed, highlighting the mechanisms underlying their ability to promote osteogenesis, cementogenesis, angiogenesis, and the homing of stem cells, thus contributing significantly to periodontal tissue regeneration. Furthermore, this review provides insights into the therapeutic efficacy of MSC-EVs in treating periodontitis within a clinical context. By summarizing the current knowledge, this review aims to provide a comprehensive understanding of how MSC-EVs can be harnessed for the treatment of periodontal diseases. Finally, a discussion is presented on the challenges that lie ahead and the potential practical implications for translating EV-based therapies into clinical practices for the treatment of periodontitis.
SMG5, a component of nonsense‐mediated mRNA decay, is essential for the mouse spermatogonial differentiation and maintenance
Authors: Tan Xiao , Chen Chengyan , Gao Xiyao , Wang Hua , Zhang Youming , Li Tangliang
Published: December 2024

Mammalian spermatogenesis is a tightly controlled cellular process including spermatogonial development and differentiation, meiosis of spermatocyte, and the morphological specification of haploid spermatozoa, during which the post‐transcriptional gene regulations are vital but poorly understood. Nonsense‐mediated mRNA decay (NMD), a highly conserved post‐transcriptional regulatory mechanism of gene expression in eukaryotes, recently emerges as a licensing mechanism in cell fate transition, including stem cell differentiation and organogenesis. The function of NMD in spermatogonial development remains elusive. Here we found knockout of SMG5, an important component of the NMD machinery, in embryonic germ cells led to the failure of spermatogenesis and male infertility. SMG5 null resulted in defective differentiation and maintenance of spermatogonia, which affected initiation of meiosis, ultimately caused a “Sertoli cell‐only” phenotype. Transcriptome analysis revealed that SMG5 loss led to serious defects in NMD with targets features including PTC, long 3′ UTR, and 5′ uORFs. Furthermore, SMG5 loss downregulates gene transcripts involved in spermatogonia expansion and differentiation. During the spermatogonial differentiation, the deletion of SMG5 led to hyperactivation of the p38 MAPK signaling pathway, which triggered widespread cell death. These results suggest that SMG5 mediated NMD plays an important role in spermatogenesis by regulating the p38 MAPK signaling pathway.
Integrating Generative Artificial Intelligence Into Medical Education: Curriculum, Policy, and Governance Strategies
Authors: Triola Marc M. , Rodman Adam
Published: December 2024

The rapid advancement of generative artificial intelligence (GAI) is poised to revolutionize medical education, clinical decision-making, and health care workflow. Despite considerable interest and a surfeit of newly available tools, medical educators largely lack both competencies and guidance on how to incorporate the new and rapidly evolving world of GAI into the core medical school curriculum and experiences of undergraduate medical education. This Scholarly Perspective highlights the need for medical schools to adapt to this new paradigm by implementing policies, governance, and curricula that address the ethical, technical, and pedagogical implications of GAI. The authors recommend creating policies for appropriate GAI use, designed to protect institutional and patient data, and provide students with clarity on the appropriate use of AI for education. The authors suggest that implementing GAI governance at institutions is crucial to create guiding principles on ethical and equitable GAI use and involving students as coinventors of local innovation. The authors argue that providing faculty and learners with tools and training for safe experimentation with GAI and defining competencies for students and faculty are essential. Curricula for GAI should focus on implications of clinical uses. The authors propose a set of new competencies for GAI that build on those already established for AI in general. Given how dynamic the world of GAI is and how quickly new innovations are changing longstanding practices of clinical medicine, it is imperative that the medical education community acts together to share best practices, gather data to assess the impact of GAI education, continuously update the expected competencies of medical students, and help students prepare for a career that will be continually changed by GAI.
EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis by regulating endoplasmic reticulum stress in knee osteoarthritis
Authors: Chen Yang , Dong Shanshan , Zeng Xin , Xu Qing , Liang Mingwei , Liao Guangneng , Li Lan , Shen Bin , Lu Yanrong , Si Haibo
Published: December 2024

Background:

Knee osteoarthritis (OA) is still challenging to prevent or treat. Enhanced endoplasmic reticulum (ER) stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration. This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms, which have rarely been reported.

Methods:

The expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2), microRNA-142-3p (miR-142-3p), and high mobility group box 1 (HMGB1) and the levels of ER stress, pyroptosis, and metabolic markers in normal and OA chondrocytes were investigated by western blotting, quantitative polymerase chain reaction, immunohistochemistry, fluorescence in situ hybridization, fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone (FAM-YVAD-FMK)/Hoechst 33342/propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and cell viability assessments. The effects of EZH2, miR-142-3p, and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation, luciferase reporters, gain/loss-of-function assays, and rescue assays in interleukin (IL)-1β-induced OA chondrocytes. The mechanistic contribution of EZH2, miR-142-3p, and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically, histologically, and immunohistochemically in surgically induced OA rats.

Results:

Increased EZH2 and HMGB1, decreased miR-142-3p, enhanced ER stress, and activated pyroptosis in chondrocytes were associated with OA occurrence and progression. EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes. EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation, and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3′-UTR of the HMGB1 gene. Moreover, ER stress mediated the effects of EZH2, miR-142-3p, and HMGB1 on chondrocyte pyroptosis. In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2, miR-142-3p, and HMGB1 and their effects on chondrocyte ER stress and pyroptosis.

Conclusions:

A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA, contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.
Cross-cultural Adaptation and Psychometric Validation of the Chinese Version of the Personal Financial Wellness Scale and Levels of Psychological Financial Hardship in Lung Cancer Patients and Caregivers at Treatment Initiation
Authors: Jia Shumin , Cui Yongchun , Cheung Denise Shuk Ting , Takemura Naomi , Ho Mu-Hsing , Liu Xiaohang , Lin Chia-Chin
Published: December 2024

Background:

The Personal Financial Wellness Scale (PFW) is a potential instrument for screening psychological financial hardship in the Chinese cancer population.

Objective:

To culturally adapt and validate the Chinese version of the PFW (CPFW) and assess the level of psychological financial hardship.

Methods:

One hundred and twenty-eight lung cancer patient-caregiver dyads participated in this cross-sectional study. The CPFW was adapted using the Functional Assessment of Chronic Illness Therapy translation method. Both classical test theory and item response theory analysis were used for validation.

Results:

The CPFW demonstrated good content and face validity. Internal consistency was high (Cronbach's α = .933 for patients, .943 for caregivers). A single-factor structure explained 70.032% and 71.727% of the variance in patients and caregivers, respectively. Mean CPFW scores positively correlated with Comprehensive Score for Financial Toxicity (r = 0.870 in patients, r = 0.849 in caregivers, P < .001), and negatively correlated with National Comprehensive Cancer Network Distress Thermometer (r = −0.484 in patients, r = −0.438 in caregivers, P < .001). Mean scores differed significantly based on insurance schemes and monthly household incomes (P < .001). The most informative and discriminative items were items 8, 4, and 3. Mean CPFW scores were 4.68 ± 2.10 in patients and 5.17 ± 1.98 in caregivers.

Conclusions:

The CPFW is a valid and reliable tool for assessing psychological financial hardship in the Chinese cancer population. Future research should screen and manage financial hardship at treatment initiation.

Implications for Practice:

The CPFW may help clinical professionals gain initiative for alleviating cancer-related financial hardship.

What is Foundational:

The validated and reliable CPFW may help effectively screen and manage financial hardship from a family level along the cancer journey in China.
Physician assistants as primary investigators: options for advancing your career through clinical research
Authors: Arnone Caitlin
Published: December 2024

The majority of physician assistants (PAs) utilize their degrees to provide direct patient care in clinical medicine, but there are many other career options for PAs to consider, including those in clinical research. PAs working in clinical research are most frequently assigned the role of sub-investigator (sub-I). The sub-I functions under the supervision of the principal investigator (PI), who is ultimately responsible for all duties related to the clinical trial at their clinical site. The dynamic between sub-I and PI is similar to the relationship between PA and collaborating physicians in a clinical practice setting. Sub-Is and PIs share similar responsibilities related to the clinical aspects of the trial, and sub-Is can be delegated to perform clinical trial tasks including evaluating and consenting study participants, performing interim visits, ensuring the safety of study participants, and providing concise and timely documentation. Beyond these clinical research tasks, the PI has additional responsibilities, including reviewing all documentation, verifying that protocols are being followed, and ensuring patient safety. The role of the PI is typically reserved for physicians, though no regulations mandate this. Experienced research PAs should consider challenging these norms and seek out opportunities to progress into the PI role as an avenue for career development. This article examines the prerequisites required to hold the role of PI and encourages PAs to consider and advocate for this nontraditional career path.
Loss of RPN1 promotes antitumor immunity via PD-L1 checkpoint blockade in triple-negative breast cancer – experimental studies
Authors: Wang Mengxue , Li Xunjia , Wu Yushen , Wang Long , Zhang Xue , Dai Meng , Long Yang , Zuo Deyu , Li Shengwei , Yin Xuedong
Published: December 2024

Background:

RPN1, also known as ribophorin I (RPN1), is a type I transmembrane protein that plays an important role in glycosylation. However, the effects of RPN1 on cancer progression and immune evasion in breast cancer (BC) have not been identified.

Materials and methods:

The expression of RPN1 was evaluated using RT-qPCR and immunohistochemistry (IHC). The effects of RPN1 on tumor cells were assessed using RT-qPCR, western blotting, flow cytometry, Cell Counting Kit 8 (CCK-8), colony formation assays, and in vivo experiments. The mechanism by which RPN1 modifies programmed death ligand-1 (PD-L1) and the tumor microenvironment was examined by RT-qPCR, western blotting, co-immunoprecipitation (Co-IP), and flow cytometry. The influence of the transcription factor YY1 on RPN1 expression was revealed using bioinformatics analysis, RT-qPCR, and dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays.

Results:

RPN1 is aberrantly expressed in triple-negative breast cancer (TNBC) cells, correlating with increased proliferation and poor prognosis. RPN1 mediates the post-translational modification of PD-L1, enhancing its glycosylation and stability, thus facilitating PD-L1-mediated immune escape and tumor growth. The deletion of RPN1 improves the TNBC microenvironment and enhances the efficacy of anti-PD-1 therapy. Additionally, we uncovered a novel regulatory axis involving YY1/RPN1/YBX1 in PD-L1 regulation, affecting TNBC growth and metastasis.

Conclusions:

Our preliminary study reveals that targeting RPN1 promotes immune suppression, providing a new potential immunotherapy strategy for TNBC. However, further research is necessary to fully elucidate and understand the specific mechanisms of RPN1 in TNBC and its potential for clinical application.
European recommendations from healthcare professionals and people living with obesity on safe practice for bariatric and metabolic surgery medical tourism: a modified Delphi consensus statement from EASO, IFSO-EC, and ECPO
Authors: Dobbie Laurence J , Birney Susie , Breen Cathy , Bryant Sheree , Clare Ken , Ciudin Andreea , Felsenreich Daniel M , Halford Jason C G , Heneghan Helen , Lorenzo Nicola Di , Mooney Vicki , Parmar Chetan , O’Connell Jean , O’Malley Grace , Woodward Euan , Yumuk Volkan D , Peterli Ralph , McGowan Barbara
Published: December 2024

Background:

Bariatric and metabolic surgery tourism (BMT) is becoming an increasingly popular route to treatment for patients living with obesity. Recent reports have highlighted that some patients travelling abroad for bariatric surgery have received inadequate care, fraudulent care, and, tragically, some cases have resulted in death. This study aimed to define consensus in Europe regarding safe practices concerning BMT.

Materials and methods:

IFSO-EC, EASO and ECPO initiated a task force to delineate safe practices in BMT. Two expert European panels were convened, one comprised of healthcare professionals (identified from EASO and IFSO-EC) and the other of patient representatives (identified from ECPO). The study utilized a modified Delphi consensus methodology, and 135 questions were administered. Surveys were conducted anonymously online, and consensus was defined as 70% agreement. Themes analyzed regarding BMT included regulation, pre-operative evaluation, operative care, post-operative care, advertising and online information.

Results:

One hundred and nineteen healthcare professionals and 88 patient representatives participated from 26 countries. The healthcare professional panel included 66 bariatric surgeons, 28 endocrinologists, 18 dietitians, three nurses, two psychologists, one general practitioner and one gastroenterologist. Three questionnaire rounds were conducted for the healthcare professional panel, and two were performed for the patient representative panel. Consensus recommendations were given across all themes relevant to BMT. These included evaluating and managing psychological health, sleep apnea, cardiovascular disease, liver health and dietetic assessment. The recommendations covered the requirements for regulatory standards, including surgeon accreditation and procedural volume. They also included recommendations regarding patient education, standardized operative care, online information provision, and follow-up.

Conclusions:

Through collaboration with healthcare professionals and patients living with obesity, we provide European recommendations regarding safe practices concerning BMT. Further evaluation is required regarding outcomes following BMT. These data, alongside the Delphi consensus recommendations, will inform BMT clinical guideline development.
Nomogram for predicting severe abdominal adhesions prior to definitive surgery in patients with anastomotic fistula post-small intestine resection: a cohort study
Authors: Yao Zheng , Shang Weiwei , Yang Fan , Tian Weiliang , Zhao Guoping , Xu Xin , MD Risheng Zhao , Tian Tao , Li Wuhan , Huang Ming , Zhao Yunzhao , Huang Qian
Published: December 2024

Background:

This study aimed to develop and validate a nomogram for predicting the presence of severe intra-abdominal adhesions before definitive surgery (DS) for anastomotic fistula following small intestine resection (SIR).

Methods:

Patients were enrolled from January 2009 to October 2023 and were randomly divided (2:1) into development and validation cohorts. Predictors of severe adhesion were identified and integrated into a nomogram. The nomogram’s performance was evaluated through calibration, discrimination, and clinical utility. Results: A total of 414 patients were included, with 276 in the development cohort and 138 in the validation cohort. Severe adhesion was diagnosed in 54 (13%) patients, including 37 (13.4%) in the development cohort and 17 (12.3%) in the validation cohort (P = 0.76). Five predictors were identified: Sequential Organ Failure Assessment score, duration of early-stage abdominal infection, preoperative albumin (Alb) <35 g/L, visceral to subcutaneous fat area ratio, and preoperative C-reactive protein >10 mg/L. The nomogram demonstrated robust discrimination, with a concordance index (C-index) of 0.80 (95% CI, 0.76–0.90) in internal validation, and was well-calibrated. In the validation cohort, the model maintained good discrimination (C-index = 0.79; 95% CI, 0.67–0.94) and calibration. Decision curve analysis affirmed the nomogram’s clinical utility.

Conclusion:

This study introduces a practical nomogram for assessing the risk of severe abdominal adhesion prior to DS in patients undergoing surgery for anastomotic fistula after SIR.
Substitution of liposomal bupivacaine for lidocaine reduces incidence of injection-emergent adverse events after intraarticular therapies for knee osteoarthritis: a prospective cohort study
Authors: Lin Junqing , Gao Tao , Zhou Lenian , Liu Tiexin , Wang Qiuke , Lin Zixuan , Zhu Hongyi
Published: December 2024

Background:

Local anesthetics as a part of intraarticular therapies (IATs) are widely used for treating knee osteoarthritis (KOA). Whether the substitution of liposomal bupivacaine (LB) for lidocaine is safe and effective in reducing the incidence of injection-emergent adverse events (AEs) after IATs remains unclear.

Methods:

We recruited outpatients who had a clinical diagnosis of KOA and decided to receive IATs from November 2023 to April 2024. The type of IATs (glucocorticoids, platelet-rich plasma, and hyaluronic acid) for each participant was decided by the preference of patients after consulting with his or her treating physicians. Using lidocaine or LB as local anesthetics was determined by enrollment timing due to considerations of safety. The primary outcome was injection-emergent AEs after IATs. Secondary outcome measures included the Visual Analog Scale (VAS) pain scores and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score.

Results:

In this study, 123 and 103 patients, respectively, received lidocaine and LB according to their enrollment date. Compared with lidocaine, using LB yielded a reduced incidence of AEs in the overall 2 weeks (LB vs. lidocaine, 30.1% vs. 45.5%, P = 0.018) and week 1 (LB vs. lidocaine, 23.3% vs. 39.8%, P = 0.008). After adjusting for sex, baseline body mass index, age, baseline WOMAC pain subscale score, and K–L grade, the substitution of LB for lidocaine was significantly associated with the reduced incidence of AEs in 2 weeks (OR, 0.484; 95% CI, 0.274–0.853; P = 0.012). In the initial 3 days, the LB groups reported better outcomes in terms of VAS pain score (change from baseline of VAS pain, LB vs. lidocaine, day 1 −8.3 ± 8.9 vs. −1.9 ± 9.3, P < 0.001; day 2 −20.6 ± 16.1 vs. −13.7 ± 19.4, P = 0.005; day 3 −22.3 ± 18.5 vs. −16.3 ± 19.3, P = 0.020). The changes from the baseline of the WOMAC pain subscale at day 14 were similar between the two groups (LB vs. lidocaine, −32.2 ± 11.7 vs. −29.4 ± 11.3, P = 0.073).

Conclusion:

With the substitution of LB for lidocaine, patients might have reported reduced incidence of AEs, mainly derived from the superiority in week 1. The substitution of LB for lidocaine was safe in different scenarios of IATs, and future randomized clinical trials were warranted by the current study.
Arthrodesis in the treatment of ankle osteoarthritis due to neglected malleolar fractures in the elderly
Authors: Uluöz Mesut , Gökmen Mehmet Yiğit , Varmiş Hasan Orkun
Published: December 2024

Neglected malleolus fracture cases, among other conditions in which arthrodesis is inevitable, usually present with pseudoarthrosis of the malleolus and impaired ligament balancing. The study aimed to summarize the clinical data results of neglected malleolus fractures accompanied by ankle instability. The retrospective study was conducted at Adana City Training and Research Hospital. The files of the patients diagnosed with nonunion malleolus fractures admitted between January 1, 2018, and July 30, 2023, were analyzed. In addition to the demographics, the type of malleolus fracture, the technique used in arthrodesis surgery, use of graft, union status, presence of early and late complications, visual analog scale (VAS), and Maryland Foot Score (MFS) scores at preoperative, 3-, 6-, and 12-month postoperative visits were recorded. There was a total of 11 files available for analysis. The mean age of the cases was 70.55 ± 5.03, ranging between 65 and 82. The records showed that the patients ignored the need for surgical treatment for an average of 10.64 ± 3.5 months. In terms of the technique, 4 were treated using the Ilizarov only, 3 with the intramedullary nails, 3 with plates and screws, and the remaining Ilizarov and plate. The average duration of the union was 6.27 ± 2.99 months. The mean VAS scores for preoperative, postoperative 3rd, postoperative 6th, and postoperative 12th months were 7.55 ± 0.78, 5.55 ± 2.31, 3.45 ± 2.27, and 2.45 ± 1.44, respectively. The mean Maryland Foot Scores (MFS) for preoperative, postoperative 3rd, postoperative 6th, and postoperative 12th months were 21.82 ± 6.85, 51.27 ± 15.39, 61.18 ± 20.21, and 70.82 ± 5.27, respectively. This study has shown that no matter how difficult the case, if the appropriate implant and basic arthrodesis principles are followed, the union can be achieved, albeit late, in cases with osteoarthritis due to neglected ankle malleolus fracture. Especially in the presence of infection, it should be kept in mind that union may be delayed compared to the regular arthrodesis recovery duration, requiring the team performing the surgery to be familiar with the Ilizarov technique.
Cerebral amyloid angiopathy-related inflammation (CAA-ri): A case report
Authors: Meng Yao , Xiao Yining , Sun Ruohan , Li Lingyu , Dong Yanhong
Published: December 2024

Rationale:

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a treatable condition characterized by an acute or subacute onset, with its primary pathological hallmark being the deposition of amyloid, predominantly β-amyloid (Aβ), within intracranial microvessels. Despite its potential for treatment, CAA-ri is a rare disorder that is frequently underrecognized by clinicians in practice. This article provides a comprehensive overview of the clinical manifestations and therapeutic approaches associated with CAA-ri, aiming to enhance awareness among healthcare professionals.

Patient concerns:

A 67-year-old male patient who suffered from a sudden decline in cognitive functioning, intermittent headache, and dysphoria underwent brain magnetic resonance imaging, susceptibility weighted imaging, and cerebrospinal fluid analysis and was considered probable CAA-ri.

Diagnosis interventions:

During the course of disease development, the patient suffered from a sudden decline in cognitive functioning, mainly in the form of unresponsiveness, decreased comprehension, and increased repetitive language, accompanied by intermittent headaches and dysphoria. Brain magnetic resonance imaging showed numerous white matter in both hemispheres. Susceptibility weighted imaging showed multiple spots of hypointensity in the bilateral cerebral and cerebellar hemispheres, a hypointensity signal in the left occipital lobe, and extensive zones of hypointensity in bilateral sulci. Cerebrospinal fluid analysis was abnormal with elevated levels of protein and low levels of P-tau, Aβ42, and Aβ1-42/Aβ1-40. The use of glucocorticoids greatly reduced his symptoms. This lends credence to the probable CAA-ri diagnosis. The symptoms can be successfully alleviated by administering methylprednisolone sodium succinate.

Outcomes:

During the patient’s hospitalization, immunosuppressive therapy, primarily consisting of methylprednisolone sodium succinate and methylprednisolone, was administered, resulting in a significant improvement in symptoms. Post-discharge, the patient was monitored regularly, revealing a gradual enhancement in cognitive function without recurrence. Consequently, immunosuppressive therapy was discontinued 1 year following the patient’s discharge.

Lessons:

CAA-ri is a rare clinical condition, and timely diagnosis and early treatment are very critical for patient prognosis.
Treatment of sudden sensorineural hearing loss with tinnitus with Fu subcutaneous needling: A case report
Authors: Zhang Jiarui , Lu Jin , Wang Yue , Ding Xinghao
Published: December 2024

Rationale:

Fu’s subcutaneous needling (FSN) is a special acupuncture method that uses FSN to sweep the subcutaneous tissue around or adjacent to the limbs to disperse the pain. Sudden sensorineural hearing loss (SSHL) is a kind of otological emergency with sudden onset within 72 hours, with unilateral hearing loss, and hearing loss of ≥20 dB in 2 connected frequencies, and most of the patients have no obvious triggers. Most patients with SSHL are accompanied by tinnitus, vertigo, and nausea and vomiting.

Patient concerns:

The patient suffered from hearing loss with tinnitus. Although received relevant treatment, the hearing loss and tinnitus did not improve significantly.

Diagnoses:

SSHL with tinnitus.

Interventions:

FSN treatment. A point 5 cm lateral to the point of tension and stiffness of the left trapezius muscle was selected on the affected back as the needle insertion point, and the condition of the neck muscles was improved through the FSN sweeping movement with neck reperfusion activities. The patient received treatment twice a week, and 4 weeks of treatment as a phase. At the end of each phase, a pure tone threshold audiometry, tinnitus evaluation scale Tinnitus Handicap Inventory assessment, and neck muscle palpation were performed.

Outcomes:

The patient’s hearing improved and the Tinnitus Handicap Inventory score decreased.

Lessons:

FSN has a good therapeutic effect on SSHL with tinnitus.
Latest FDA approved drug Elafibranor (Iqirvo): a novel prospect for treatment of primary biliary cholangitis
Authors: Salamat Ali Jawad , Salamat Ali Tooba , Al Hasibuzzaman Md.
Published: December 2024

Elafibranor (Iqirvo) has recently received FDA approval for treating primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA). This novel drug, a dual peroxisome proliferator-activated receptor-α/δ agonist, addresses the unmet need in PBC patients unresponsive to UDCA alone. Clinical trials, particularly the ELATIVE study, have shown significant biochemical improvements, including reduced alkaline phosphatase (ALP) levels and optimized lipid profiles. While common side effects include gastrointestinal discomfort, more severe but rare adverse effects, such as muscle injury and new-onset cholelithiasis, were observed. Elafibranor represents a promising advance in PBC management, offering enhanced efficacy with a tolerable safety profile. However, further research is needed to assess its long-term effectiveness and safety.
Anticoagulation therapy
Authors: Ida Shenaz
Published: December 2024

Anticoagulation therapy is essential for preventing life-threatening events like strokes and deep vein thrombosis. Nurses should understand different anticoagulants, their clinical indications, and key patient education points.
Facilitating the Transition From New Graduate to Practicing Advanced Practice RN
Authors: Kapu April N.
Published: December 2024

The transition from graduate education to clinical practice is a pivotal phase in the career of advanced practice RNs (APRNs). This transition is often marked by a phenomenon known as transition shock, characterized by feelings of anxiety, self-doubt, and inadequacy as new APRNs adjust to the demands of clinical practice.