bluuebunny/crossref_metadata_2025_split huggingface dataset:
The adipokines progranulin and omentin – novel regulators of basic ovarian cell functions
Authors: Sirotkin Alexander V , Fabová Zuzana , Loncová Barbora , Bauerová Maria , Halim Harrath Abdel 
Published: April 2024

AbstractThe present study aimed to examine the effects of progranulin and omentin on basic ovarian cell functions. For this purpose, we investigated the effects of the addition of progranulin and omentin (0, 0.1, 1, or 10 ng/ml) on the viability, proliferation, apoptosis and steroidogenesis of cultured rabbit ovarian granulosa cells. To determine the importance of the interrelationships between granulosa cells and theca cells, we compared the influence of progranulin and omentin on progesterone and estradiol release in cultured granulosa cells and ovarian fragments containing both granulosa cells and theca cells. Cell viability, proliferation, cytoplasmic apoptosis and release of progesterone and estradiol were measured by Cell Counting Kit-8 (CCK-8), BrdU incorporation, cell death detection, and ELISA. Both progranulin and omentin increased granulosa cell viability and proliferation and decreased apoptosis. Progranulin increased progesterone release by granulosa cells but reduced progesterone output by ovarian fragments. Progranulin decreased estradiol release by granulosa cells but increased it in ovarian fragments. Omentin reduced progesterone release in both models. Omentin reduced estradiol release by granulosa cells but promoted this release in ovarian fragments. The present observations are the first to demonstrate that progranulin and omentin can be direct regulators of basic ovarian cell functions. Furthermore, the differences in the effects of these adipokines on steroidogenesis via granulosa and ovarian fragments indicate that these peptides could target both granulosa and theca cells.
Edge-based relative entropy as a sensitive indicator of critical transitions in biological systems
Authors: Hong Renhao , Tong Yuyan , Liu Huisheng , Chen Pei , Liu Rui 
Published: April 2024

Abstract
Background
Disease progression in biosystems is not always a steady process but is occasionally abrupt. It is important but challenging to signal critical transitions in complex biosystems.

Methods
In this study, based on the theoretical framework of dynamic network biomarkers (DNBs), we propose a model-free method, edge-based relative entropy (ERE), to identify temporal key biomolecular associations/networks that may serve as DNBs and detect early-warning signals of the drastic state transition during disease progression in complex biological systems. Specifically, by combining gene‒gene interaction (edge) information with the relative entropy, the ERE method converts gene expression values into network entropy values, quantifying the dynamic change in a biomolecular network and indicating the qualitative shift in the system state.

Results
The proposed method was validated using simulated data and real biological datasets of complex diseases. The applications show that for certain diseases, the ERE method helps to reveal so-called “dark genes” that are non-differentially expressed but with high ERE values and of essential importance in both gene regulation and prognosis.

Conclusions
The proposed method effectively identified the critical transition states of complex diseases at the network level. Our study not only identified the critical transition states of various cancers but also provided two types of new prognostic biomarkers, positive and negative edge biomarkers, for further practical application. The method in this study therefore has great potential in personalized disease diagnosis.
Impact of FAPI-46/dual-tracer PET/CT imaging on radiotherapeutic management in esophageal cancer
Authors: Wegen Simone , Claus Karina , Linde Philipp , Rosenbrock Johannes , Trommer Maike , Zander Thomas , Tuchscherer Armin , Bruns Christiane , Schlößer Hans Anton , Schröder Wolfgang , Eich Marie-Lisa , Fischer Thomas , Schomäcker Klaus , Drzezga Alexander , Kobe Carsten , Roth Katrin Sabine , Weindler Jasmin Josefine 
Published: April 2024

Abstract
Background
Fibroblast activation protein (FAP) is expressed in the tumor microenvironment (TME) of various cancers. In our analysis, we describe the impact of dual-tracer imaging with Gallium-68-radiolabeled inhibitors of FAP (FAPI-46-PET/CT) and fluorodeoxy-D-glucose (FDG-PET/CT) on the radiotherapeutic management of primary esophageal cancer (EC).

Methods
32 patients with EC, who are scheduled for chemoradiation, received FDG and FAPI-46 PET/CT on the same day (dual-tracer protocol, 71%) or on two separate days (29%) We compared functional tumor volumes (FTVs), gross tumor volumes (GTVs) and tumor stages before and after PET-imaging. Changes in treatment were categorized as “minor” (adaption of radiation field) or “major” (change of treatment regimen). Immunohistochemistry (IHC) staining for FAP was performed in all patients with available tissue.

Results
Primary tumor was detected in all FAPI-46/dual-tracer scans and in 30/32 (93%) of FDG scans. Compared to the initial staging CT scan, 12/32 patients (38%) were upstaged in nodal status after the combination of FDG and FAPI-46 PET scans. Two lymph node metastases were only visible in FAPI-46/dual-tracer. New distant metastasis was observed in 2/32 (6%) patients following FAPI-4 -PET/CT. Our findings led to larger RT fields (“minor change”) in 5/32 patients (16%) and changed treatment regimen (“major change”) in 3/32 patients after FAPI-46/dual-tracer PET/CT. GTVs were larger in FAPI-46/dual-tracer scans compared to FDG-PET/CT (mean 99.0 vs. 80.3 ml, respectively (p < 0.001)) with similar results for nuclear medical FTVs. IHC revealed heterogenous FAP-expression in all specimens (mean H-score: 36.3 (SD 24.6)) without correlation between FAP expression in IHC and FAPI tracer uptake in PET/CT.

Conclusion
We report first data on the use of PET with FAPI-46 for patients with EC, who are scheduled to receive RT. Tumor uptake was high and not depending on FAP expression in TME. Further, FAPI-46/dual-tracer PET had relevant impact on management in this setting. Our data calls for prospective evaluation of FAPI-46/dual-tracer PET to improve clinical outcomes of EC.
Clinical and ultrasound features of 46 children with suppurative osteoarthritis: experience from two centers
Authors: Huang Sai-feng , Teng Yue , Hui-Qing Shi  , Chen Wen-Juan , Zhang Xue-Hua 
Published: April 2024

Abstract
Objective
Diagnosing musculoskeletal infections in children is challenging. In recent years, with the advancement of ultrasound technology, high-resolution ultrasound has unique advantages for musculoskeletal children. The aim of this work is to summarize the ultrasonographic and clinical characteristics of children with pyogenic arthritis and osteomyelitis. This study provides a simpler and more effective diagnostic basis for clinical treatment.

Methods
Fifty children with osteomyelitis or arthritis were diagnosed via ultrasound, and the results of the ultrasound diagnosis were compared with those of magnetic resonance imaging and surgery. Clinical and ultrasound characteristics were also analyzed.

Results
Out of 50 patients, 46 were confirmed to have suppurative infection by surgical and microbiological examination. Among these 46 patients, 26 were diagnosed with osteomyelitis and 20 had arthritis. The manifestations of osteomyelitis were subperiosteal abscess (15 patients), bone destruction (17 patients), bone marrow abscess (9 patients), and adjacent joint abscess (13 patients). Osteomyelitis mostly affects the long bones of the limbs, femur and humerus (10 and 9 patients, respectively), followed by the ulna, radius, tibia and fibula (one patient each). The manifestations of arthritis were joint pus (20 patients) and joint capsule thickening (20 patients), and hip dislocation (8 patients). All the patients had arthritis involving the hip joint.

Conclusion
Subperiosteal abscess, bone destruction, and joint abscess with dislocation are ultrasonographic features of pyogenic osteoarthritis. The findings of this work can improve the early diagnosis and differentiation of pyogenic osteoarthritis and provide a reliable basis for treatment.
Associations between hyperuricemia and ultrasound-detected knee synovial abnormalities in middle-aged and older population: a cross-sectional study
Authors: Weng Qianlin , Jiang Ting , Zhang Weiya , Doherty Michael , Yang Zidan , Wei Jie 
Published: April 2024

Abstract
Objectives
Knee synovial abnormalities, potentially treatment targets for knee pain and osteoarthritis, are common in middle-aged and older population, but its etiology remains unclear. We examined the associations between hyperuricemia and knee synovial abnormalities detected by ultrasound in a general population sample.

Methods
Participants aged ≥ 50 years were from a community-based observational study. Hyperuricemia was defined as serum urate (SU) level > 416 µmol/L in men and > 357 µmol/L in women. Ultrasound of both knees was performed to determine the presence of synovial abnormalities, i.e., synovial hypertrophy, effusion, or Power Doppler signal (PDS). We examined the relation of hyperuricemia to prevalence of knee synovial abnormalities and its laterality, and the dose-response relationships between SU levels and the prevalence of knee synovial abnormalities.

Results
In total, 3,405 participants were included in the analysis. Hyperuricemia was associated with higher prevalence of knee synovial abnormality (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI]: 1.02 to 1.43), synovial hypertrophy (aOR = 1.33, 95% CI: 1.05 to 1.68), and effusion (aOR = 1.21, 95% CI: 1.02 to 1.44), respectively. There were dose-response relationships between SU levels and synovial abnormalities. Additionally, the hyperuricemia was more associated with prevalence of bilateral than with that of unilateral knee synovial abnormality, synovial hypertrophy, or effusion; however, no significant association was observed between hyperuricemia and PDS.

Conclusion
In this population-based study we found that hyperuricemia was associated with higher prevalence of knee synovial abnormality, synovial hypertrophy and effusion, suggesting that hyperuricemia may play a role in pathogenesis of knee synovial abnormalities.
Increasing access to mental health supports for 12–17-year-old Indigenous youth with the JoyPop mobile mental health app: study protocol for a randomized controlled trial
Authors: Mushquash Aislin R. , Neufeld Teagan , Malik Ishaq , Toombs Elaine , Olthuis Janine V. , Schmidt Fred , Dunning Crystal , Stasiuk Kristine , Bobinski Tina , Ohinmaa Arto , Newton Amanda , Stewart Sherry H. 
Published: April 2024

Abstract
Background
Indigenous youth in Northwestern Ontario who need mental health supports experience longer waits than non-Indigenous youth within the region and when compared to youth in urban areas. Limited access and extended waits can exacerbate symptoms, prolong distress, and increase risk for adverse outcomes. Innovative approaches are urgently needed to provide support for Indigenous youth in Northwestern Ontario. Using a randomized controlled trial design, the primary objective of this study is to determine the effectiveness of the JoyPop app compared to usual practice (UP; monitoring) in improving emotion regulation among Indigenous youth (12–17 years) who are awaiting mental health services. The secondary objectives are to (1) assess change in mental health difficulties and treatment readiness between youth in each condition to better understand the app’s broader impact as a waitlist tool and (2) conduct an economic analysis to determine whether receiving the app while waiting for mental health services reduces other health service use and associated costs.

Methods
A pragmatic, parallel arm randomized controlled superiority trial will be used. Participants will be randomly allocated in a 1:1 ratio to the control (UP) or intervention (UP + JoyPop) condition. Stratified block randomization will be used to randomly assign participants to each condition. All participants will be monitored through existing waitlist practices, which involve regular phone calls to check in and assess functioning. Participants in the intervention condition will receive access to the JoyPop app for 4 weeks and will be asked to use it at least twice daily. All participants will be asked to complete outcome measures at baseline, after 2 weeks, and after 4 weeks.

Discussion
This trial will evaluate the effectiveness of the JoyPop app as a tool to support Indigenous youth waiting for mental health services. Should findings show that using the JoyPop app is beneficial, there may be support from partners and other organizations to integrate it into usual care pathways.

Trial registration
https://clinicaltrials.gov/study/NCT05898516 [registered on June 1, 2023].
Expression analysis of zinc-metabolizing enzymes in the saliva as a new method of evaluating zinc content in the body: two case reports and a review of the literature
Authors: Sakata Ken-ichiro , Hashimoto Ayako , Kambe Taiho , Sato Jun , Ohga Noritaka , Yamazaki Yutaka , Koyachi Masahide , Tatsuki Itagaki , Okada Mai , Taro Okura , Hikasa Hiroshi , Kitagawa Yoshimasa 
Published: April 2024

Abstract
Background
The activity level of alkaline phosphatase, a zinc-requiring enzyme in the serum, is used to indicate zinc nutritional status; however, it does not correlate with serum zinc levels or subjective symptoms of taste disorder in many cases. Hence, this study focused on the total activity of alkaline phosphatase, a zinc-requiring enzyme. The total alkaline phosphatasa activity level in the saliva was measured before and after zinc supplementation, and the results were compared with serum zinc levels.

Case presentation
This study included patients with hypozincemia, specifically a patient with zinc-deficient taste disorder (patient 1: a 69-year-old Japanese woman) and a patient with glossodynia with zinc deficiency (patient 2: an 82-year-old Japanese woman). Saliva samples were collected, and blood tests were performed before and after zinc supplementation. Subjective symptoms and serum zinc levels were simultaneously evaluated. Zinc supplementation was performed using zinc acetate hydrate or Polaprezinc.

Conclusions
Total alkaline phosphatase activity levels were found to be associated with serum zinc levels and subjective symptoms. A further study with a higher number of patients is necessary to confirm whether total alkaline phosphatase activity levels more accurately reflect the amounts of zinc in the body than serum zinc levels.
Comparison of dysfunctional attitudes, cognitive vulnerability to depression, before and during the COVID-19 pandemic in healthy participants
Authors: Muraosa Haruka , Shirata Toshinori , Saito Yusuke , Noto Keisuke , Suzuki Akihito 
Published: April 2024

Abstract
Background
During the COVID-19 pandemic, depression and suicide rates increased worldwide, and in Japan. Presumably, an increase of neuroticism-related personality traits mediates the relation linking the COVID-19 pandemic with depression and suicide. This study examined COVID-19 pandemic effects on dysfunctional attitudes, cognitive vulnerability to depression, in healthy participants.

Methods
The study used Dysfunctional Attitude Scale (DAS) -24 data of three subscales (i.e., achievement, dependency, and self-control) obtained from 270 Japanese medical students during October 2017 – June 2022. Participants were divided into two groups: those for whom DAS-24 was assessed before the pandemic (phase 1 group, October 2017 – March 2020, n = 178) and those for whom DAS-24 was assessed during the pandemic (phase 2 group, April 2020 – June 2022, n = 92).

Results
Total DAS-24 scores of the phase 2 group were significantly (p = 0.047) lower than those of the phase 1 group. Scores of the dependency subscale for the phase 2 group were significantly (p = 0.002) lower than those for the phase 1 group, but no significant difference was found in the scores of the achievement and self-control subscales.

Conclusions
These findings suggest that a decrease in DAS-24 scores, particularly of the dependency subscale, occurred during the COVID-19 pandemic. Possible mechanisms underlying these results are 1) individuals became less preoccupied with receiving evaluation, 2) individuals realized that self-cognition depending on the approval of others is unimportant, and 3) high levels of dysfunctional attitude were maladaptive for obtaining affective benefits via social interactions during the COVID-19 pandemic.
Assessing the agreement of chronic lung disease of prematurity diagnosis between radiologists and clinical criteria
Authors: Rich Joseph Matthew , Lin Lydia Jing , Le Jonathan Luan , Abe Justin Ryan Ching , Sura Amit 
Published: April 2024

Abstract
Background
Chronic lung disease of prematurity (CLD) is the most prevalent complication of preterm birth and indicates an increased likelihood of long-term pulmonary complications. The accurate diagnosis of this condition is critical for long-term health management. Numerous definitions define CLD with different clinical parameters and radiology findings, making diagnosis of the disease ambiguous and potentially inaccurate.

Methods
95 patients were identified for this study, as determined by the diagnosis or confirmation of CLD in the impression of the radiologist’s report on chest x-ray. Pulmonary function and complications were recorded at multiple benchmark timeframes within each patient’s first few months of life and used for determining eligibility under each definition.

Results
Each clinical definition of CLD had a high sensitivity for patients identified to have CLD by radiologists, correctly fitting over 90% of patients. Most patients included required invasive mechanical ventilation or positive pressure ventilation at 36 weeks postmenstrual age, indicating patients with radiographically confirmed CLD tended to have more severe disease. Radiologists tended to diagnose CLD before 36 weeks postmenstrual age, a timepoint used by multiple standard clinical definitions, with cases called earlier fitting under a larger percentage of definitions than those called later.

Conclusions
Radiologists tend to diagnose CLD in young patients with severe respiratory compromise, and can accurately diagnose the condition before developmental milestones for clinical definitions are met.
Service Evaluation of MyChristie-MyHealth, an Electronic Patient-Reported Outcome Measure Integrated Into Clinical Cancer Care
Authors: Shipman Lee A. , Price James , Abdulwahid Danya , Bayman Neil , Blackhall Fiona , Califano Raffaele , Chan Clara , Coote Joanna , Eaton Marie , Fenemore Jacqueline , Gomes Fabio , Harris Margaret , Halkyard Emma , Lindsay Colin , Neal Hilary , McEntee Delyth , Sheikh Hamid , Summers Yvonne , Taylor Paul , Woolf David , Yorke Janelle , Faivre-Finn Corinne 
Published: April 2024

PURPOSE Electronic patient-reported outcome measures (ePROMs) are digitalized health questionnaires used to gauge patients' subjective experience of health and disease. They are becoming prevalent in cancer care and have been linked to a host of benefits including improved survival. MyChristie-MyHealth is the ePROM established at the Christie NHS Foundation Trust in 2019. We conducted an evaluation of this service to understand user experiences, as well as strategies to improve its functioning. METHODS Data collection: Patients who had opted never to complete MyChristie-MyHealth (n = 87), and those who had completed at least one (n = 87) were identified. Demographic data included age, sex, ethnicity, postcode, diagnosis, treatment intent, and trial status. Semistructured interviews were held with noncompleters (n = 30) and completers (n = 31) of MyChristie-MyHealth, as well as clinician users (n = 6), covering themes such as accessibility, acceptability and usefulness, and open discourse on ways in which the service could be improved. RESULTS Noncompleters of MyChristie-MyHealth were older (median age 72 v 66 years, P = .005), receiving treatment with curative rather than palliative intent (odds ratio [OR], 1.45; P = .045), and less likely to be enrolled on a clinical trial (OR, 0.531; P = .011). They were less likely to own a smartphone (33% v 97%) or have reliable Internet access (45% v 100%). Satisfaction with MyChristie-MyHealth was high in both groups: 93% (n = 29) of completers and 87% (n = 26) noncompleters felt generally happy to complete. Completers of MyChristie-MyHealth wanted their results to be acknowledged by their clinicians. Clinicians wanted results to be displayed in a more user-friendly way. CONCLUSION We have broadly characterized noncompleters of the Christie ePROM to identify those in need of extra support or encouragement in the clinic. An action plan resulting from this review has been compiled and will inform the future development of MyChristie-MyHealth.
Lung Cancer Clinical Trials in Latin America in the Era of Cooperative Groups: A 20-Year Analysis
Authors: Knapp Thomas , Nygaard Joseph , Cassinat Joshua , Galvez Fernando , Gopalan Priya K. 
Published: April 2024

PURPOSE The aim of this study is to characterize lung cancer treatment clinical trials in Latin America before (January 2001-December 2011) and after (January 2012-December 2021) the organization of major Latin American oncology cooperative groups. MATERIALS AND METHODS Interventional clinical trials were identified in ClinicalTrials.gov using the search terms “lung cancer,” country filters for 20 Latin American countries, and study start dates January 1, 2001-December 31, 2011, and January 1, 2012-December 31, 2021. Clinical trials were categorized as either originating in Latin America (LA) or outside Latin America (non-LA) with participation of Latin American countries. Descriptive statistics, two-sided Z-scores, and chi-square analyses with 95% CIs were calculated. RESULTS Overall, 273 clinical trials involving Latin American countries between 2001 and 2021 were identified. Comparing 2001-2011 with 2012-2021, there was an increase in total clinical trials (100 v 173; P < .001). Only 9% (26 of 273) of all trials were LA trials. There was a marked decrease in the proportion of LA trials (14% v 7%, P = .058) and estimated enrollment to LA trials (3,245 v 1,190 patients; P < .001). Recruiting of patients with EGFR (29% v 7%; P < .01) and KRAS (18% v 2%; P < .01) driver mutations also decreased. Trial participation was highest in Brazil, Mexico, Argentina, Chile, and Peru and increased over time: Brazil (61 v 108; 77% increase), Mexico (40 v 88; 120% increase), Argentina (50 v 78; 56% increase), Chile (25 v 57; 128% increase), and Peru (14 v 37; 164% increase). CONCLUSION There was a significant increase in clinical trial participation by Latin American countries, from 2001-2011 to 2012-2021. However, there were few clinical trials which originated in Latin America or focused on patients with driver mutations.
Relativistic generalised uncertainty and the corrected vacuum energy
Authors: Pandey Akshat 
Published: April 2024

Abstract
In this paper we make use of the recent covariant extension of the generalised uncertainty principle to study the corrections to the vacuum energy of the simplest scalar quantum field theory. We then calculate the modifications to the Casimir effect that such a correction to the vacuum energy would bring about. We emphasise that these corrections are indeed physical.