bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure S1 from CD49a Targeting Enhances NK Cell Function and Antitumor Immunity
Authors: Zhang Yu , Li Yangyang , Zhang Zhengfeng , Zheng Xiaodong , Peng Hui , Tian Zhigang , Sun Rui , Sun Haoyu
Published: January 2025

CD49a is upregulated and associated with exhaustion of tumor-infiltrating CD8+ T cells.
Table S3 from Deleting Trim33 in Myeloid Cells Improves the Efficiency of Radiotherapy through an IFNβ-Dependent Antitumor Immune Response
Authors: Assouvie Anaïs , Gerbé-de-Thoré Marine , Torres Claire , Ménard Véronique , Alfaro Alexia , Deutsch Eric , Mondini Michele , Rousselet Germain
Published: January 2025

antibodies used in mass cytometry
Figure S7 from Deleting Trim33 in Myeloid Cells Improves the Efficiency of Radiotherapy through an IFNβ-Dependent Antitumor Immune Response
Authors: Assouvie Anaïs , Gerbé-de-Thoré Marine , Torres Claire , Ménard Véronique , Alfaro Alexia , Deutsch Eric , Mondini Michele , Rousselet Germain
Published: January 2025

Lymphoid populations of tumors grown in LysMcre and Trim33mKO mice
Figure S4 from Deleting Trim33 in Myeloid Cells Improves the Efficiency of Radiotherapy through an IFNβ-Dependent Antitumor Immune Response
Authors: Assouvie Anaïs , Gerbé-de-Thoré Marine , Torres Claire , Ménard Véronique , Alfaro Alexia , Deutsch Eric , Mondini Michele , Rousselet Germain
Published: January 2025

radiotherapy in Ifnar1KO mice, with or without Trim33mKO
Supplementary Figure 6 from Preclinical Development of T Cells Engineered to Express a T-Cell Antigen Coupler Targeting Claudin 18.2–Positive Solid Tumors
Authors: Xu Stacey X. , Wang Ling , Ip Philbert , Randhawa Ritu R. , Benatar Tania , Prosser Suzanna L. , Lal Prabha , Khan Alima Naim , Nitya-Nootan Thanyashanthi , Thakor Gargi , MacGregor Heather , Hayes Danielle L , Vucicevic Andrea , Mathew Princy , Sengupta Sadhak , Helsen Christopher W. , Bader Andreas G.
Published: January 2025

Supplementary Figure 6: TAC01-CLDN18.2 biodistribution in NSG mice carrying OE19 tumor xenografts.
Data from Alternate MHC I Antigen Presentation Pathways Allow CD8+ T-cell Recognition and Killing of Cancer Cells in the Absence of β2M or TAP
Authors: Cruz Freidrich M. , Orellano Laura A. A. , Chan Amanda , Rock Kenneth L.
Published: January 2025

Abstract
MHC I antigen presentation allows CD8+ T cells to detect and eliminate cancerous or virally infected cells. The MHC I pathway is not essential for cell growth and viability, so cancers and viruses can evade control by CD8+ T cells by inactivating antigen presentation. In cancers, two common ways for this evasion are the loss of either the MHC I light chain [β2 microglobulin (β2M)] or the transporter-associated with antigen processing (TAP). β2M-null cells are generally thought to lack the MHC I pathway because the MHC I heavy chain by itself lacks the proper conformation for peptide display. TAP-null cells are thought to have severely defective MHC I antigen presentation because they are incapable of supplying peptides from the cytosol to MHC I molecules in the endoplasmic reticulum (ER). However, we have found that highly reactive memory CD8+ T cells could still recognize cells that completely lacked β2M or TAP. This was at least in part because in TAP-null cells, the Sec62 component of the Sec61 translocon supported the transfer of cytosolic peptides into the ER. In β2M-negative cells, free MHC I heavy chains were able to bind peptides and assume a conformation that was sufficiently recognized by CD8+ T cells. This process required ER chaperones and the peptide-loading complex. We found that these mechanisms supported antigen presentation at a level that was sufficient for memory CD8+ T cells to kill melanoma cells both in vitro and in tumor-bearing mice. The implications for tumor immunotherapy are discussed.
Data from Deleting Trim33 in Myeloid Cells Improves the Efficiency of Radiotherapy through an IFNβ-Dependent Antitumor Immune Response
Authors: Assouvie Anaïs , Gerbé-de-Thoré Marine , Torres Claire , Ménard Véronique , Alfaro Alexia , Deutsch Eric , Mondini Michele , Rousselet Germain
Published: January 2025

Abstract
Radiotherapy (RT) triggers an immune response that contributes to antitumor effects. Induction of IFNβ is a key event in this immunogenicity of RT. We have previously shown that TRIM33, a chromatin reader, restrains IFNβ expression in Toll-like receptor–activated myeloid cells. In this study, we explored whether deleting Trim33 in myeloid cells might improve the radio-induced immune response and subsequent efficiency of RT. We first established that Trim33−/− bone marrow–derived macrophages showed increased expression of IFNβ in response to direct irradiation, or to treatment with irradiated cancer cells, further supporting our hypothesis. We then tested the efficiency of a single-dose RT in three subcutaneous tumor models and one orthotopic tumor model. In all models, myeloid deletion of Trim33 led to a significantly improved response after RT, leading to a complete and durable response in most of the treated mice bearing orthotopic oral tumors. This effect required the involvement of the type I IFN pathway and the presence of CD8+ T lymphocytes but not NK cells. In addition, cured mice were capable of rejecting a secondary tumor challenge, demonstrating an in situ vaccination effect. We conclude that deleting Trim33 in myeloid cells improves RT efficiency, through a mechanism involving the type I IFN pathway and the immune response. Our work suggests that myeloid Trim33 is a host factor affecting the tumor response to RT, thus representing a new potential therapeutic target for modifying RT responses.
Data from Level of Expression of MHCI-Presented Neoepitopes Influences Tumor Rejection by Neoantigen-Specific CD8+ T Cells
Authors: Deng Li , Walsh Scott R. , Nguyen Andrew , Inkol Jordon M. , Westerveld Michael J. , Chen Lan , El-Sayes Nader , Mossman Karen L. , Workenhe Samuel T. , Wan Yonghong
Published: January 2025

Abstract
Neoantigen-targeted therapy holds an array of benefits for cancer immunotherapy, but the identification of peptide targets with tumor rejection capacity remains a limitation. To better define the criteria dictating tumor rejection potential, we examined the capacity of high-magnitude T-cell responses induced toward several distinct neoantigen targets to regress MC38 tumors. Despite their demonstrated immunogenicity, vaccine-induced T-cell responses were unable to regress established MC38 tumors or prevent tumor engraftment in a prophylactic setting. Although unable to kill tumor cells, T cells showed robust killing capacity toward neoantigen peptide–loaded cells. Tumor-cell killing was rescued by saturation of target peptide–loaded MHCs on the cell surface. Overall, this study demonstrates a pivotal role for target protein expression levels in modulating the tumor rejection capacity of neoantigens. Thus, inclusion of this metric, in addition to immunogenicity analysis, may benefit antigen prediction techniques to ensure the full antitumor effect of cancer vaccines.
Table 1 from Clonal Hematopoiesis of Indeterminate Potential and its Association with Treatment Outcomes and Adverse Events in Patients with Solid Tumors
Authors: Krishnan Tharani , Solar Vasconcelos Joao Paulo , Titmuss Emma , Vanner Robert J. , Schaeffer David F. , Karsan Aly , Lim Howard , Ho Cheryl , Gill Sharlene , Yip Stephen , Chia Stephen K. , Kennecke Hagen F. , Jonker Derek J. , Chen Eric X. , Renouf Daniel J. , O’Callaghan Chris J. , Loree Jonathan M.
Published: January 2025

Baseline characteristics of the included patients
Figure 4 from Clonal Hematopoiesis of Indeterminate Potential and its Association with Treatment Outcomes and Adverse Events in Patients with Solid Tumors
Authors: Krishnan Tharani , Solar Vasconcelos Joao Paulo , Titmuss Emma , Vanner Robert J. , Schaeffer David F. , Karsan Aly , Lim Howard , Ho Cheryl , Gill Sharlene , Yip Stephen , Chia Stephen K. , Kennecke Hagen F. , Jonker Derek J. , Chen Eric X. , Renouf Daniel J. , O’Callaghan Chris J. , Loree Jonathan M.
Published: January 2025

CHIP and adverse events. A, Percentage of patients on each treatment that had an adverse event on therapy, split by cohort and treatment. B, Proportions of patients with adverse events split by CHIP status. Lighter shades indicate no adverse event, and darker shades indicate an adverse event. P values were determined by Fisher exact tests.
Figure 2 from Clonal Hematopoiesis of Indeterminate Potential and its Association with Treatment Outcomes and Adverse Events in Patients with Solid Tumors
Authors: Krishnan Tharani , Solar Vasconcelos Joao Paulo , Titmuss Emma , Vanner Robert J. , Schaeffer David F. , Karsan Aly , Lim Howard , Ho Cheryl , Gill Sharlene , Yip Stephen , Chia Stephen K. , Kennecke Hagen F. , Jonker Derek J. , Chen Eric X. , Renouf Daniel J. , O’Callaghan Chris J. , Loree Jonathan M.
Published: January 2025

Prevalence of CHIP variants across cohorts and CHIP association with age. A, Percentage of patients with CHIP variants in each cohort. Insert shows the breakdown by tumor type in the PREDiCT-l cohort. B, Number of patients with a CHIP variant in each gene; DNMT3A, TET2, and ASXL1. C, Protein position of coding variants by gene. Each lollipop represents a patient, multiple dots show patients with the same variant position, and red outlines show variants of high impact (frameshift or stop gain). Orange bars along the length of the genes show functional domains. D, Percentage of patients with CHIP variants by age group. E, Age difference between patients with CHIP (CHIP+) and without CHIP (CHIP−). P value was determined by the Wilcoxon rank sum test.
Data from Clonal Hematopoiesis of Indeterminate Potential and its Association with Treatment Outcomes and Adverse Events in Patients with Solid Tumors
Authors: Krishnan Tharani , Solar Vasconcelos Joao Paulo , Titmuss Emma , Vanner Robert J. , Schaeffer David F. , Karsan Aly , Lim Howard , Ho Cheryl , Gill Sharlene , Yip Stephen , Chia Stephen K. , Kennecke Hagen F. , Jonker Derek J. , Chen Eric X. , Renouf Daniel J. , O’Callaghan Chris J. , Loree Jonathan M.
Published: January 2025

Abstract
Clonal hematopoiesis of indeterminate potential (CHIP) is the clonal expansion of hematopoietic stem cells from somatic mutations. It is a common incidental finding in cell-free DNA (cfDNA). We investigated the incidence of CHIP in cfDNA from patients with solid tumors and explored its association with treatment outcomes and adverse events. We reviewed cfDNA results from a local prospective solid tumor cohort (PREDiCT-l) and two randomized trials: Canadian Cancer Trials Group CO.26 [durvalumab + tremelimumab (D + T) or best supportive care in metastatic colorectal cancer] and Canadian Cancer Trials Group PA.7 (gemcitabine and nab-paclitaxel ± D + T in metastatic pancreatic adenocarcinoma). CHIP+ was defined as any mutation in DNMT3A, TET2, or ASXL1 with a variant allele frequency ≥2%. Presumed germline variants (variant allele frequency >40%) were removed. The first line of treatment after cfDNA was reviewed for grade ≥3 and dose-limiting toxicities. The prevalence of CHIP in the 465 included patients was 10% to 30%, and it was more common as age increased (P = 0.003). DNMT3A was the gene most frequently mutated in all cohorts. Patients with CHIP in PA.7 treated with immunotherapy showed an improved progression-free survival versus CHIP− [HR = 0.55 (0.28–1.07); P = 0.079, P-interaction = 0.098 (multivariable)]. However, patients with CHIP treated with chemotherapy in PREDiCT-l showed a trend toward worse progression-free survival [HR = 1.82 (0.98–3.38); P = 0.059]. There was no difference in adverse event rates between CHIP ± groups for those treated with chemotherapy or immunotherapy. CHIP is common in patients with solid tumors. Although not appearing to affect rates of adverse events, CHIP may affect outcomes from immunotherapy or chemotherapy.
Significance:
Liquid biopsy is increasingly being used in oncology for tumor molecular characterization. CHIP is a common incidental finding in cfDNA, and its prevalence increases with age. This study builds on growing evidence of common CHIP variants in patients with solid tumors. The results suggest a possible clinical impact of CHIP on treatment outcomes from immunotherapy or chemotherapy. This may have implications for treatment selection for patients with solid tumors.
Are Εἴδωλα Idols?
Authors: Chantziantoniou Alexander
Published: January 2025

It has long been taken for granted that the use of εἴδωλον in the language of the Septuagint and its reception in early Jewish texts was unique within the history of postclassical Greek, imbued with pejorative meaning as a technical term of “Jewish Greek” that refers not to “images” but to “idols.” In this article, I interrogate the issues involved with this lexicographical commonplace and the translation practices it informs, and offer a critical reexamination of the literary and documentary evidence in which εἴδωλον occurs. I argue that the use of εἴδωλον in early Jewish Greek literature, from the Greek Pentateuch to Paul’s letters, was in fact remarkably unexceptional and readily recognisable as one lexical option among many in the diverse lexicon of cult images (e.g., ἄγαλμα, ἀνδριάς, ἀφίδρυμα, εἰκών, ἵδρυμα, ξόανον), just as it was in postclassical Greek more broadly. I conclude that transliterating εἴδωλον as “idol,” rather than translating it as “image,” keeps the illusion of uniqueness alive by inviting negative associations that closely align with its later lexicographical legacy but that do not clearly correspond to any known use of εἴδωλον in its own time and place.
Molecular and taxonomical study of the genus Chara (Linnaeus 1753) in Israel
Authors: Khasdan Vadim , Yehuda Guy , Žvingila Donatas , Ovadia Ofer
Published: January 2025

Israel’s climate is characterized by hot and dry summers and cool, rainy winters in the northern and coastal regions, whereas the southern and eastern regions are arid. The aquatic macrophyte Chara is a common genus in Israel, and its distribution varies across Israel’s climatic gradient. Although few studies described the abundance and taxonomy of the local Chara species in Israel, only little is known about the molecular taxonomy of this group in the region. We sampled Chara species along Israel’s climatic gradient and identified specimens using the classical taxonomy key and molecular identification methods. We characterized the molecular taxonomy of four Chara species: C. vulgaris, C. contraria, C. gymnophylla, and C. globata. Notably, the latter species, which was found in a hyper-arid area, was last recorded in Israel ~50 years ago on the northern Mediterranean coast and Judaean Mountains. Chara gymnophylla was more abundant in northern Israel, while C. vulgaris and C. contraria were common in southern Israel. We developed Inter Simple Sequence Repeat markers to identify the four species and sequenced their chloroplast gene rbcL. The phylogenetic trees generated using the rbcL sequences and ISSR-based dendrogram were consistent with the classical taxonomy of Chara.
Genetic improvement of farmed insect species: programmes, progress, and prospects
Authors: Gowda K.B. , Jerry D.R. , Zenger K.R.
Published: January 2025

Like other animal farming systems that aim for maximum productivity and economic sustainability, the cultivation of insects for food and feed sectors requires the use of high-performance genetic lines that are adapted to specific rearing conditions. Therefore, investing in genetics and breeding programmes to domesticate and develop insect strains suitable for commercial production is imperative: if implemented appropriately, breeding programmes can achieve significant returns on investment. Developing genetic improvement programmes for insects entails considering various factors, including biology, reproduction, production system, and identifying breeding goals optimal for available resources. This review summarises the various techniques available for implementing selective breeding programmes in insects, as well as their current applications and developments in four insect species: the honey bee, silkworm, black soldier fly and mealworm.
Evaluating pelvic rotator strength: Investigating asymmetry and its correlation with pelvic rotation angle during active straight leg raise
Authors: Jeon Joo-Young , Kwon Oh-Yun , Yi Chung-Hwi , Ha Sung-Min , Kim Jun-Hee , Han Seung-Yoon
Published: January 2025

Background

Although lumbopelvic rotation control muscle is important to maintain pelvic neutral alignment during active straight leg raise (ASLR), pelvic rotator strength has not been evaluated. Thus, a novel method is needed to measure pelvic rotator strength and to determine whether pelvic rotator muscle asymmetry is related to side difference in transverse plane pelvic rotation angle (TrPRA) during ASLR.

Objective

To find average pelvic rotator strength, verify the reliability of pelvic rotator strength measurement method, and identify the correlation between pelvic rotator strength asymmetry and side difference in TrPRA during ASLR.

Methods

Forty healthy participants were enrolled. Pelvic rotator strength was measured using a hand-held dynamometer. TrPRA was measured using a smart KEMA motion sensor. Reliability was analyzed using intraclass correlation coefficient (ICC). The correlation between pelvic rotator strength asymmetry and side difference in TrPRA during ASLR was analyzed using Pearson's correlation coefficient.

Results

The average pelvic rotator strength was 120.3 N (72.9–202.2) for males and 94.4 N (58–125.8) for females. The reliability of pelvic rotator strength measurement demonstrated good to excellent intra- (ICC = 0.87–0.97) and inter-rater (ICC = 0.93–0.98) values. A significant moderate relationship existed between pelvic rotator strength asymmetry and side difference in TrPRA during ASLR (r = 0.39, p < 0.05).

Conclusion

The pelvic rotator muscle strength measurement method can be clinically used with good to excellent intra- and inter-rater reliability. Pelvic rotator strength asymmetry should be considered to evaluate and manage the pelvic rotation control during ASLR.
Benefit Finding in Craniofacial Conditions: A Qualitative Analysis of Patient and Parent Perspectives
Authors: Choi Alyssa K. , Korhummel Megan , Belza Caitlyn C. , Herrera Eguizabal Josseline , Olfus Sydney , Rapoport Chelsea S. , Blum Jessica , Tapia Viridiana J. , Drizin Julia H. , Gosman Amanda , Malcarne Vanessa L.
Published: January 2025

Objective

Craniofacial conditions (CFCs) can be associated with adverse effects on quality of life (QoL). However, few studies have examined perceived benefits related to CFCs. This study described perceived benefits in an international sample of children and adolescents with CFCs and their parents.

Design

Semistructured qualitative interviews were completed in English or Spanish as part of a larger study. Deductive content analysis described and quantified perceived benefits associated with CFCs.

Setting

Interviews were during standard visits at Rady Children's Hospital-San Diego in the USA and the Hospital Infantil de las Californias in Tijuana, Baja California, Mexico.

Participants

Patients were ages 7 to 20 years ( n = 32) with CFCs (cleft lip and/or palate, craniosynostosis, microtia, hemifacial microsomia, dermatologic conditions/neurovascular malformations, and trauma-acquired CFC), and parents ( n = 71) had children ages 5 months to 23 years with CFCs. Of the total sample, there were 14 patient-parent dyads.

Results

A total of 230 benefits were identified. Of the patients (47%) and parents (73%) who identified at least 1 benefit, themes included personal growth (40%), understanding or helping others facing challenges (25%), social relationships (23%), spiritual or religious beliefs (4%), philanthropy (4%), material or external gains (3%), and personal health (1%).

Conclusions

Patients with CFCs and their parents report multiple positive effects of CFCs on their QoL. These findings indicate that benefit finding is a common experience in this population and may be leveraged by clinicians to help promote positive adjustment to living with a CFC.
Instructional leadership and student achievement across UAE schools: Mediating role of professional development and cognitive activation in teaching
Authors: Bellibaş Mehmet Şükrü , Polatcan Mahmut , Alzouebi Khadeegha
Published: January 2025

While instructional school leadership remains a focus of scholarly inquiry due to persuasive evidence regarding its contribution to school improvement, most of the existing literature on the influence of leadership on school improvement and student learning has been based predominantly on a more developed Western context. To establish a comprehensive international knowledge repository on instructional leadership across diverse social and cultural contexts, the present study aims to explore the influence of instructional leadership on teachers’ professional learning and instructional practices as well as student achievement as measured by standardized testing in the United Arab Emirates. We conducted multilevel structural equation modeling using the Program for International Student Assessment 2022 dataset that includes 8715 teachers and 21,176 students from 724 schools. We found that instructional leadership is indirectly related to student math achievement, mediated by two dominant types of teacher professional development (traditional and reform-based) that influence teachers’ teaching strategies to activate students cognitively. This paper adds to the growing international literature on international educational leadership by investigating a previously underexplored context within the Gulf region. It suggests that instructional leadership could be a pivotal practice in fostering both reform-based and traditional teacher professional development activities, student-centered teaching and math achievement.
The IQGAP-related RasGAP IqgC regulates cell–substratum adhesion in Dictyostelium discoideum
Authors: Mijanović Lucija , Putar Darija , Mimica Lucija , Klajn Sabina , Filić Vedrana , Weber Igor
Published: January 2025

Proper adhesion of cells to their environment is essential for the normal functioning of single cells and multicellular organisms. To attach to the extracellular matrix (ECM), mammalian cells form integrin adhesion complexes consisting of many proteins that together link the ECM and the actin cytoskeleton. Similar to mammalian cells, the amoeboid cells of the protist Dictyostelium discoideum also use multiprotein adhesion complexes to control their attachment to the underlying surface. However, the exact composition of the multiprotein complexes and the signaling pathways involved in the regulation of adhesion in D. discoideum have not yet been elucidated. Here, we show that the IQGAP-related protein IqgC is important for normal attachment of D. discoideum cells to the substratum. Mutant iqgC-null cells have impaired adhesion, whereas overexpression of IqgC promotes directional migration. A RasGAP C-terminal (RGCt) domain of IqgC is sufficient for its localization in the ventral adhesion focal complexes, while RasGAP activity of a GAP-related domain (GRD) is additionally required for the proper function of IqgC in adhesion. We identify the small GTPase RapA as a novel direct IqgC interactor and show that IqgC participates in a RapA-regulated signaling pathway targeting the adhesion complexes that include talin A, myosin VII, and paxillin B. On the basis of our results, we propose that IqgC is a positive regulator of adhesion, responsible for the strengthening of ventral adhesion structures and for the temporal control of their subsequent degradation.
Percutaneous closure of a traumatic ventricular septal defect: a case report and literature review
Authors: Calderon-Miranda Camilo Andres , Reyes-Cardona Maria Juliana , Lopez-Mora Gabriel Roberto , Guerrero-Pinedo Fernando Andrés , Sanchez-Blanco Jairo , Vesga-Reyes Carlos Enrique , Zambrano-Franco Jorge Alexander , Olaya Pastor
Published: January 2025

Background

Penetrating cardiac trauma is an entity with high pre and intrahospital mortality due to complications such as cardiac tamponade and massive hemothorax. A ventricular septal defect (VSD) occurs in 1–5% of cases and can present early or late. The management strategy for VSD resulting from penetrating cardiac trauma is uncertain.

Case presentation

A 19-year-old man was admitted in cardiorespiratory arrest after a precordial stab wound. Cardiopulmonary resuscitation was initiated achieving return of spontaneous circulation. eFAST evaluation revealed cardiac tamponade, he was taken to emergency left thoracotomy finding a perforation of the free wall of the left ventricle and a tear of the upper lobe of the left lung that were sutured. The patient was discharged and six days later was readmitted with fever and dyspnea. During treatment for a surgical site infection a new-onset pansystolic murmur was found: A transthoracic echocardiogram revealed a 13-mm VSD with left-to-right shunt. A multidisciplinary team recommended percutaneous closure of the defect which was successfully performed without complications.

Conclusions

Traumatic VSD is a rare complication of penetrating cardiac trauma. A thorough clinical and echocardiographic evaluation is essential for its diagnosis and characterization. Symptomatic septal defects, those 10 mm or larger, with Qp: Qs greater than 1.5, or causing complications such as pulmonary hypertension or valvular involvement, are usually closed to prevent progression of heart failure. Management of traumatic VSD has traditionally been surgical. However, a percutaneous intervention is a viable alternative in selected stable patients. Unlike ischemic VSD, early intervention after patient stabilization generally yields favorable outcomes.
Real-world evidence of remdesivir in formerly hospitalized COVID-19 patients: patient-reported and functional outcomes
Authors: Fésü Dorottya , Bárczi Enikő , Csoma Balázs , Polivka Lőrinc , Boga Márton , Horváth Gábor , Varga János Tamás , Sebők Szilvia , Müller Veronika
Published: January 2025

Background

Post-COVID condition (PCC) is characterized by persisting symptoms after the resolution of acute COVID-19. Remdesivir (RDV), a broad-spectrum antiviral drug, has been widely used in patients hospitalized with COVID-19 requiring oxygen therapy. We aimed to evaluate the effects of RDV on PCC by assessing patient-reported and functional outcomes.

Methods

We used the data from a single-center registry, including formerly hospitalized post-COVID patients (N = 293). Propensity score matching (PSM) was used (16 criteria, 1:1 ratio) to obtain two comparable groups: those who received standard-of-care (SOC, N = 94) and those treated with RDV in addition to SOC (SOC + RDV, N = 94). Primary outcomes were asymptomatic status and at least 50% symptom score reduction at post-COVID follow-up. Secondary outcomes included results of pulmonary function (PF) tests, 6-minute walk test (6MWT), and quality-of-life (QoL) questionnaires.

Results

After PSM, baseline patient characteristics showed no significant differences between the two groups. Most patients were still symptomatic (60% vs. 66%). In the SOC + RDV group, the use of oxygen supplementation (94 vs. 80%, p = 0.005) and steroids (97 vs. 88%, p = 0.027) during infection were higher, while patients presented at their post-COVID visits earlier (median 68 vs. 97 days, p = 0.003). Complete or at least 50% symptom resolution were reported at a significantly earlier stage after infection in the SOC + RDV group compared to the SOC group (multivariable-adjusted HR = 2.28, 95% CI = 1.33–3.92, p = 0.003; and HR = 2.08, 95% CI = 1.43–3.02, p < 0.001; respectively). In the SOC + RDV group, fewer patients experienced sleep disturbances at PCC, and sleep-related questionnaires (Pittsburg Sleep Quality Index, PSQI) results showed significantly better sleep quality (14 vs. 27% and 5.9 vs. 7.7 points, respectively). There were no notable differences in results of PF tests, 6MWT, and other QoL questionnaires.

Conclusion

In this propensity score matched cohort, the use of RDV was associated with earlier patient reported symptom resolution during the PCC period, while there were no notable differences in functional outcomes. Our results indicate a possible beneficial effect of RDV in terms of faster symptom resolution after COVID19 infection.

Graphical abstract
Intervention strategies to prevent mental health problems and improve resilience in employed parents from conception until the child is 5 years of age: a scoping review
Authors: Crombag Neeltje , Bollen Bieke , Vancoppenolle Eline , Vandendriessche Thomas , Versmissen Dagmar , Paisi Martha , Shawe Jill , Garthus-Niegel Susan , Bogaerts Annick
Published: January 2025

Aim

To understand the extent and type of evidence in relation to the effectiveness of intervention strategies targeting working pregnant women, and their partners, for the prevention of mental health problems (depression, anxiety) and improving resilience, from conception until the child is 5 years of age.

Methods

A scoping review was conducted searching Pubmed (including Medline), Embase, Web of Science Core Collection and Scopus. Inclusion criteria were based on population (employed parents), context (from -9 months to 5 years postpartum) and concept (mental health problems, resilience and prevention/ preventative interventions).

Results

Of the 17,699 papers screened, 3 full text papers were included. Studies focused on intervention strategies for working parents which showed a relationship with a reduction in mental health problems (depression and/or anxiety). The intervention strategies extracted from the literature referred to ‘social support’. Social support provided by both the social and the work environment correlated with prenatal stress and depressive symptoms in the postpartum period, and supports a healthy work-family balance.

Conclusion

Social support seems to have a positive association with the reduction of mental health problems. However, there are still important gaps in the literature such as a lack of RCT designs to test effectiveness of interventions and systematic reviews. Findings from this study may provide a roadmap for future research to close these gaps in knowledge.
An item response theory analysis of the Dissociative Experiences Scale II: examining psychometric properties and longitudinal stability among Japanese adults
Authors: Ikeda Tatsuya , Urano Yuhei
Published: January 2025

Background

The Dissociative Experiences Scale (DES-II) is widely used globally. However, psychometric properties of the scale have not been adequately examined. The present study aimed to examine the psychometric properties and longitudinal stability of the DES-II.

Method

We collected data at two time points, approximately three and a half years apart. At Time 1 (T1), 1029 participants (515 females, 514 males) with a mean age of 44.64 (± 14.02) responded to the survey. Out of the T1 participants, 210 individuals (105 females, 105 males) also responded to the T2 survey. We conducted item parameters of the DES-II with item response theory (IRT).

Results

Our results showed that the DES-II is suitable for measuring strong dissociative traits, with all items displaying high discriminative power. The cut-off points for the DES-II were within a good range of measurement accuracy, and longitudinal stability over approximately three and a half years was adequate.

Conclusion

In the present study, we applied item response theory (IRT) to the DES-II, which has traditionally been interpreted using classical test theory (CTT). Results suggested the need for item-focused assessment rather than relying solely on mean scores or cut-off points. Specifically, results suggested that the severity levels differed across item ratings, and to set cut-off points for each item based on the severity of the ratings. Furthermore, the possibility of cultural differences in response patterns of the DES-II was indicated. However, few studies have discussed cultural differences based on IRT; hence, further research should examine response patterns of the DES-II across various cultures. In conclusion, the DES-II is a valuable tool for assessing dissociative symptoms, with adequate psychometric properties from an item response theory perspective. Clinicians should consider item-specific responses in their assessments, and further research is needed to explore the scale's applicability across diverse populations.
Measuring a family sense of coherence: a rasch-based study extending dyadic data analyses
Authors: Möllerberg Marie-Louise , Årestedt Kristofer , Hagell Peter , Melin Jeanette
Published: January 2025

Background

Family sense of coherence (FSOC) seems to reduce distress in the family and promote the well-being of the family. Therefore, getting accurate measurements for families with long-term illnesses is of particular interest. This study explores dyadic data analysis from the dyadic- and single-informant perspectives, and the measurement properties of the FSOC-S12 according to the Rasch model.

Methods

Racked and stacked data from 151 dyads were analyzed according to the polytomous Rasch model.

Results

Notably, both the dyadic- and single-informant perspectives (i.e., racked and stacked data set-ups) showed measurement properties with minor deviations from the Rasch model according to fit statistics. However, most items had disordered thresholds and some problems with local dependency. Item hierarchies were similar in both set-ups and there was no differential item functioning (DIF) by role from the dyadic informant perspective. Four items showed DIF by informant role in the single-informant perspective.

Conclusions

Our approach to handling dyadic data has shown both strengths and limitations in the evaluation of FSOC-S12, and the understanding of FSOC as a construct from the family’s view of the family’s ability as a whole (dyadic-informant perspective) and patient’s and family member’s separate views of the family’s ability as a whole (single-informant perspective).
Learning from experience: does providing end-of-life care support for relatives boost personal end-of-life health literacy?
Authors: Meier Clément , Wieczorek Maud , Vilpert Sarah , Borrat-Besson Carmen , Jox Ralf J. , Maurer Jürgen
Published: January 2025

Background

Despite the critical role of health literacy in utilizing palliative care and engaging in advance care planning, limited research exists on the determinants of end-of-life health literacy. This study investigates the association between individuals’ experiences with end-of-life care support to relatives and their end-of-life health literacy among a population-based sample of adults aged 58 and older.

Method

We used data from 1,548 respondents in Switzerland to Wave 8 (2019/2020) of the Survey on Health, Ageing, and Retirement in Europe. Their ability to understand medical jargon, find information, communicate, and make decisions about end-of-life care options was measured with the validated Subjective End-of-Life Health Literacy Scale. Experiences with end-of-life care support include having made medical decisions as healthcare proxy, accompanied, or cared for relatives at the end of life. Associations were estimated using ordinary least squares regressions, controlling for socio-demographic, health, and regional characteristics.

Results

Respondents who experienced being a healthcare proxy (p < 0.001), who accompanied (p < 0.001), or who cared for a relative at the end of life (p < 0.001) tended to have higher levels of end-of-life health literacy. These results remained significant when the three variables were simultaneously included in the multivariable model (p < 0.001, p < 0.001 and p < 0.05).

Conclusions

Our findings suggest that providing end-of-life care support to relatives is associated with higher end-of-life health literacy. Thus, as caregivers gain experience caring for others, targeted interventions could leverage their skills and encourage them to think of engaging in end-of-life planning for themselves.
Explainable unsupervised anomaly detection for healthcare insurance data
Authors: De Meulemeester Hannes , De Smet Frank , van Dorst Johan , Derroitte Elise , De Moor Bart
Published: January 2025

Background

Waste and fraud are important problems for health insurers to deal with. With the advent of big data, these insurers are looking more and more towards data mining and machine learning methods to help in detecting waste and fraud. However, labeled data is costly and difficult to acquire as it requires expert investigators and known care providers with atypical behavior.

Methods

In this work we show how recent advances in machine learning can be used to set up a workflow that can aid investigators in discovering practitioners or groups of practitioners with unusual resource use in order to more efficiently combat waste and fraud. We combine three different techniques, which have not been used in the context of healthcare insurance anomaly detection: categorical embeddings to deal with high-cardinality categorical variables, state-of-the-art unsupervised anomaly detection techniques to detect anomalies and Shapley additive explanations (SHAP) to explain the model output.

Results

The method has been evaluated on providers with a known anomalous profile and with the help of experts of the largest health insurance fund in Belgium. The quantitative experiments show that categorical embeddings offer a significant improvement compared to standard methods and that the state-of-the-art unsupervised anomaly detection techniques generally show an improvement over traditional methods. In a practical setting, the proposed workflow with SHAP was able to detect a previously unknown, anomalous trend among general practitioners.

Conclusions

The proposed workflow is able to detect known care providers with atypical behaviour and helps expert investigators in making informed decisions concerning possible fraud or overconsumption in the health insurance field.
Evaluation of a national framework for rational use of medicines in Kazakhstan and its role in improving medicine use practices at the organizational and national levels
Authors: Zhussupova Gulzira , Aiypkhanova Ainur , Zhaldybayeva Saule , Satmbekova Dinara , Akhayeva Tamila , Kaliyeva Sholpan
Published: January 2025

Background

Kazakhstan inherited the Semashko health system model, known for the centralized adoption of rules at the Ministry of Health (MoH) level that regulate the healthcare system. In 2019 MoH established a national framework with indicators aimed at collecting qualitative and quantitative data from healthcare organizations as part of their annual self-evaluation, and biannual external evaluation by the National Research Center for Health Development (NRCHD). The purpose of this study was to pilot the MoH framework on rational use of medicines and evaluate its effects on medicine use practices in health care organizations and at the national level.

Materials and methods

This cross-sectional study was conducted from October to December 2019 at 22 state-owned primary health care organizations (polyclinics) serving adults and children in Astana, Kazakhstan. Data were collected by trained surveyors visiting each organization. Data were converted to numeric values to arrive at compliance scores for each organization and analyzed to assess each organization’s compliance with set indicators.

Results

The evaluation showed the rational use of medicines was assessed as “excellent” (90% < compliant) in 2 organizations (9% of the sample), “good” (75–89% compliant) in 7 organizations (32%), and “satisfactory” (50–74% compliant) in 13 organizations (59%), with an average compliance rate of 71% across the sample. 22 organization-specific evaluation reports were developed by the evaluator (NRCHD) and sent to health care organizations for corrective actions. Evaluation data triggered two improvements at the national level: correction of the default setting for trade names to international nonproprietary names within the physician ordering feature of the national health information system for medicines, and adoption of a national policy that allowed the exchange of unused stocks of medicines between polyclinics.

Conclusions

Using the national framework allowed the evaluator agency and healthcare organizations to identify organization-specific gaps and triggered improvements in the use of medicines.
Putative effects of moringa oil or its nano-emulsion on the growth, physiological responses, blood health, semen quality, and the sperm antioxidant-related genes in ram
Authors: Ismail Rehab F. S. A. , Khalil Wael A. , Grawish Sara I. , Mahmoud Karima Gh. M. , Abdelnour Sameh A. , Gad Alaa M. A.
Published: January 2025

Phytochemicals have been effectively used to enhance the growth and productivity of farm animals, while the potential roles of essential oils and their nano-emulsions are limited. This plan was proposed to investigate the impacts of orally administered moringa oil (MO) or its nano-emulsion (NMO) on the growth, physiological response, blood health, semen attributes, and sperm antioxidant-related genes in rams. A total of 15 growing Rahmani rams were enrolled in this study and allotted into three groups. The 1st control group received a basal diet only and treated orally one mL of distilled water, while the 2nd, and 3rd groups received a basal diet and were orally treated with 1 mL of NMO or 2 mL of MO /head/day for 4 months, respectively. Growth, physiological response, blood health, semen quality, and antioxidant genes in sperm were assessed. The MO and NMO treatments had no significant effect on growth indices (final body weight and weight gain ) and physiological response (rectal temperature, pulse, and respiration rates) (P > 0.05). The NMO group had the lowest levels of MCV (mean corpuscular volume) (P < 0.05), while all treated groups produced higher levels of mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) compared to those in the control group (P < 0.05). Aspartate transferase (AST) and total cholesterol were significantly reduced in the MO and NMO groups, while total protein and glucose levels were significantly improved in NMO group (P < 0.05). Serum and seminal interstitial-cell-stimulating hormone (ICSH) levels were significantly improved (P < 0.0001) in the NMO group. Testosterone in serum and seminal plasma was significantly improved (P < 0.0001) in the MO group. Total antioxidant capacity (TAC) levels showed a tendency to increase in both the MO and NMO groups, but this increase was not significant compared to the untreated group (P > 0.05). On the other hand, the MO group exhibited lower levels of AST and malondialdehyde (MDA), while the alanine aminotransferase (ALT) levels were the lowest in the NMO group (P > 0.05). Mass motility, viability, membrane integrity and sperm concentration were significantly improved in the MO group (P < 0.0001) compared to the other groups. The NMO group had worse expressions of superoxide dismutase 1 (SOD1) compared to the control and MO groups. MO group significantly upregulated the catalase gene compared to the other groups (P < 0.001). The expression of Caspase-3 was highest in the group that received NMO compared to the other groups (P < 0.001). This study suggests that MO may serve as a novel therapeutic agent for improving the reproductive health in Rahmani rams.
Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects
Authors: Cao Zhipeng , Quazi Sadia , Arora Sakshi , Osellame Laura D. , Burvenich Ingrid J. , Janes Peter W. , Scott Andrew M.
Published: January 2025

Research into cancer treatment has been mainly focused on developing therapies to directly target cancer cells. Over the past decade, extensive studies have revealed critical roles of the tumour microenvironment (TME) in cancer initiation, progression, and drug resistance. Notably, cancer-associated fibroblasts (CAFs) have emerged as one of the primary contributors in shaping TME, creating a favourable environment for cancer development. Many preclinical studies have identified promising targets on CAFs, demonstrating remarkable efficacy of some CAF-targeted treatments in preclinical models. Encouraged by these compelling findings, therapeutic strategies have now advanced into clinical evaluation. We aim to provide a comprehensive review of relevant subjects on CAFs, including CAF-related markers and targets, their multifaceted roles, and current landscape of ongoing clinical trials. This knowledge can guide future research on CAFs and advocate for clinical investigations targeting CAFs.
Country economic status is strongly associated with burn survival - validation of the (modified) ABSI
Authors: Elrod Julia , Mohr Christoph , Branski Ludvik , Peterson Joshua M. , Wood Fionna M. , Edgar Dale W. , Agbenorku Pius , Chamania Shobha , Sharma Anant , Novaes Flavio N. , Katabogama Jean Bosco , Boettcher Michael , Reinshagen Konrad , Koenigs Ingo
Published: January 2025

Background

Predicting burn-related mortality is vital for family counseling, triage, and resource allocation. Several of the burn-specific mortality prediction scores have been developed, including the Abbreviated Burn Severity Index (ABSI) in 1982. However, these scores are not tested for accuracy to support contemporary estimates of the global burden of burn injury. This study compares burn mortality across countries with varying economic levels, as indicated by the Human Development Index (HDI), to assess if a modified ABSI (mABSI) offers enhanced predictive accuracy.

Methods

A retrospective study was performed, including over 90,000 patients from seven sources in five continents, including two burn registries and five referral burn centers. Data from 2015 to 2019 were collected, including age, gender, presence of inhalation injury, full-thickness burn, percentage of total body surface area, and outcome. The participating countries were classified based on the HDI and mortality was predicted using both the original and the modified ABSI.

Results

After removal of incomplete data, 74,460 sets remained for the analysis. Significant variations in population demographics, sample sizes, total body surface area (TBSA), and age distributions across the studied regions were noted. The modified ABSI demonstrated a smaller deviation from the 95% CI of the true survival probability than the original ABSI in countries with a very high or high HDI, indicating improved accuracy here. In these countries, the original ABSI overestimates mortality. Conversely, in countries with a middle or low HDI, the original ABSI remains more accurate, reflecting the significantly greater burn related mortality in countries with a low HDI.

Conclusion

In burn patients, the probability of survival remains highly dependent on the level of development of a country. Our results support the use of the modified ABSI in countries with a (very) high HDI, yet in resource constraint settings, the original ABSI seems to provide more accurate predictions. These findings underscore the need for adaptive models that take into account socioeconomic variables, potentially guiding health policy adjustments and emphasizing the necessity of resource allocation and training in lower HDI countries. Such adaptations could enhance clinical outcomes and reduce disparities in burn care effectiveness globally.