bluuebunny/crossref_metadata_2025 huggingface dataset:
Single fiber pull-out investigation at different temperature and humidity conditions: Experimental characterization of the fiber-matrix interface in carbon fiber reinforced polyamide 6
Authors: Christ Nicolas , Gumbsch Peter , Hohe Jörg
Published: January 2025

This study investigates the effects of varying environmental conditions on the interfacial properties of carbon fiber-reinforced polyamide 6 (CF-PA6). The primary focus is the impact of temperature and humidity on the Interfacial Shear Strength (IFSS), debonding fracture toughness, and surface-specific work of friction. The study reveals that caused by polymer swelling both temperature and humidity lead to a relaxation of the radial residual stress within the interface and a subsequent reduction in IFSS. Notably, the effects of these factors appear to be superimposed up to the debonding of the fiber-matrix interface. Furthermore, while the debonding fracture toughness also follows a declining trend with an increase in both environmental factors, it displays non-linear characteristics, implying a coupled effect between temperature and humidity. The study also identifies that humidity alone significantly decreases the surface-specific work of friction, irrespective of the surrounding temperature, so that after debonding a simple superposition is not feasible. To ensure precise results, a microscale climate chamber was developed using the principle of deliquescence to maintain a constant relative humidity during testing. The findings offer valuable insights into the performance of CF-PA6 under varying environmental conditions, informing potential improvements in its design and application.
Bilateral Renal Fungal Bezoars and Perinephric Abscess in an Infant With Arthrogryposis-Renal Dysfunction-Cholestasis Syndrome: A Clinico-pathologic Case Report
Authors: Darouich Sihem , Darouich Samia , Khemiri Ahmed , Bellamine Houda
Published: January 2025

The patients with Arthrogryposis-Renal dysfunction-Cholestasis (ARC) syndrome have genetic susceptibility to the opportunistic infections due to the involvement of VPS33B (vacuolar protein sorting 33 homolog B) in phagolysosome fusion in macrophages. Detailed pathologic studies in ARC patients are missing in literature due to the lack of autopsy. We described the first autopsy case of ARC syndrome in a 2-month-old male infant. His death was due to recurrent sepsis and multiorgan failure despite the appropriate poly-antibiotic therapy and supportive care. The autopsy showed invasive renal candidiasis including bilateral destructive pyelonephritis, pelvic obstructive fungal bezoars, and right large perinephric abscess. The main other findings included severe chronic liver changes and pneumonia. Liver exhibited intrahepatocyte cholestasis, large multinucleated hepatocytes, diffuse portal, bridging and perivenular fibrosis, and interlobular bile duct proliferation. The neuropathologic examination was unremarkable. This case report highlights 3 novel findings. The ARC syndrome-related immunodeficiency may predispose to renal fungal bezoars and perinephric abscess. Cholestatic stress may result in the proliferation of interlobular ducts as an adaptive response. Absence of spinal motor neuron degeneration suggests that the neurogenic amyotrophy is due to the lack of synaptic vesicle trafficking and membrane fusion rather than the defect in cell survival-related autophagosome-lysosome fusion.
Healthcare Resource Utilization Among Patients With Generalized Pustular Psoriasis: The Impact of Flares and Disease Severity
Authors: Noe Megan H. , Lavasani Layla , Rasouliyan Lawrence , Laouri Marianne , Rhoads Jamie L. W.
Published: January 2025

Background

Generalized pustular psoriasis (GPP) is a rare, chronic, often unpredictable, severe multisystemic autoinflammatory skin disease from which patients can experience flares, episodes of widespread eruptions of painful, sterile pustules often accompanied by systemic symptoms. The impact of GPP flares and underlying GPP severity on the healthcare resource utilization (HCRU) is not well characterized.

Objective

To quantify HCRU among US GPP patients by flare status and underlying severity.

Methods

Outpatient electronic health record (EHR) data (2017-2023) from the OMNY Health platform were linked with claims. Patients were indexed at first EHR GPP diagnosis code and followed for 1 year. GPP flares were identified from a previously developed algorithm. All-cause hospitalizations, emergency department/urgent care (ED/UC), and outpatient visits were summarized by flare status and underlying severity. Pharmacy and total gross charges were described by number of flares.

Results

A total of 335 patients were included. Patients who flared in the follow-up period (n = 205) had more hospitalizations than patients who did not flare (n = 130; 12.2% vs 6.9%; mean: 0.26 vs 0.09). ED/UC visits were similar between groups (22.9% vs 27.7%; mean: 0.54 vs 0.45), while outpatient visits were greater among patients who did not flare (69.8% vs 78.5%; mean: 5.37 vs 6.56). For patients with 0, 1, and ≥2 flares with HCRU, mean pharmacy charges ($19,887, $25,180, and $57,674, respectively) and total gross charges ($29,196, $40,079, and $52,940, respectively) increased monotonically.

Conclusion

GPP patients who flared and had more severe disease had greater HCRU and charges.
Penalized landmark supermodels (penLM) for dynamic prediction for time-to-event outcomes in high-dimensional data
Authors: Fries Anya H. , Choi Eunji , Han Summer S.
Published: January 2025

Background

To effectively monitor long-term outcomes among cancer patients, it is critical to accurately assess patients’ dynamic prognosis, which often involves utilizing multiple data sources (e.g., tumor registries, treatment histories, and patient-reported outcomes). However, challenges arise in selecting features to predict patient outcomes from high-dimensional data, aligning longitudinal measurements from multiple sources, and evaluating dynamic model performance.

Methods

We provide a framework for dynamic risk prediction using the penalized landmark supermodel (penLM) and develop novel metrics (
$$\:\overline{AUC}_{w}\:$$
and
$$\:\overline{BS}_{w}\:$$
) to evaluate and summarize model performance across different timepoints. Through simulations, we assess the coverage of the proposed metrics’ confidence intervals under various scenarios. We applied penLM to predict the updated 5-year risk of lung cancer mortality at diagnosis and for subsequent years by combining data from SEER registries (2007–2018), Medicare claims (2007–2018), Medicare Health Outcome Survey (2006–2018), and U.S. Census (1990–2010).

Results

The simulations confirmed valid coverage (~ 95%) of the confidence intervals of the proposed summary metrics. Of 4,670 lung cancer patients, 41.5% died from lung cancer. Using penLM, the key features to predict lung cancer mortality included long-term lung cancer treatments, minority races, regions with low education attainment or racial segregation, and various patient-reported outcomes beyond cancer staging and tumor characteristics. When evaluated using the proposed metrics, the penLM model developed using multi-source data (
$$\:\overline{AUC}_{w}\:$$
of 0.77 [95% confidence interval: 0.74–0.79]) outperformed those developed using single-source data (
$$\:\overline{AUC}_{w}\:$$
range: 0.50–0.74).

Conclusions

The proposed penLM framework with novel evaluation metrics offers effective dynamic risk prediction when leveraging high-dimensional multi-source longitudinal data.
Application of GUHA data mining method in cohort data to explore paths associated with premature death: a 29-year follow-up study
Authors: Nosraty Lily , Turunen Esko , Kyrönlahti Saila , Nygård Clas-Håkan , KC Prakash , Neupane Subas
Published: January 2025

Background and Method

This study set out to identify the factors and combinations of factors associated with the individual’s premature death, using data from the Finnish Longitudinal Study on Ageing Municipal Employees (FLAME) which involved 6,257 participants over a 29-year follow-up period. Exact dates of death were obtained from the Finnish population register. Premature death was defined as a death occurring earlier than the age- and sex-specific actuarial life expectancy indicated by life tables for 1981, as the baseline, with the threshold period of nine months. Explanatory variables encompassed sociodemographic characteristics, health and functioning, health behaviors, subjective experiences, working conditions, and work abilities. Data were mined using the General Unary Hypothesis Automaton (GUHA) method, implemented with LISp-Miner software. GUHA involves an active dialogue between the user and the LISp-Miner software, with parameters tailored to the data and user interests. The parameters used are not absolute but depend on the data to be mined and the user’s interests.

Results

Over the follow-up period, 2,196 deaths were recorded, of which 70.4% were premature. Seven single factors and 67 sets of criteria (paths) were statistically significantly associated with premature mortality, passing the one-sided Fisher test. Single predicates of premature death included smoking, consuming alcohol a few times a month or once a week, poor self-rated fitness, incompetence to work and poor assured workability in two years’ time, and diseases causing work disability. Notably, most of the factors selected as single predicates of premature mortality did not appear in the multi-predicate paths. Factors appearing in the paths were smoking more than 20 cigarettes a day, symptoms that impaired functioning, past smoking, absence of musculoskeletal diseases, poor self-rated health, having pain, male sex, being married, use of medication, more physical strain compared to others, and high life satisfaction, intention to retire due to reduced work ability caused by diseases and demanding work. Sex-specific analysis revealed similar findings.

Conclusion

The findings indicate that associations between single predictors and premature mortality should be interpreted with caution, even when adjusted for a limited number of other factors. This highlights the complexity of premature mortality and the need for comprehensive models considering multiple interacting factors.
The effect of transcranial direct current stimulation and inhibitory control training on depression and anxiety among post-stroke individuals
Authors: Kazinczi Csaba , Szepfalusi Noemi , Nemeth Viola Luca , Holczer Adrienn , Jakab Katalin , Vecsei Laszlo , Klivenyi Peter , Must Anita , Racsmany Mihaly
Published: January 2025

Background

Recent research has highlighted the role of fronto-parietal brain networks and cognitive control in mood disorders. Transcranial direct current stimulation (tDCS) and computer-based cognitive training are used in post-stroke rehabilitation. This study examined the combined effects ofof computer-based inhibitory control training (ICCT) and anodal tDCS on post-stroke depression and anxiety.

Methods

Thirty-five participants were randomly assigned to one of three groups: active tDCS treatment (A), sham tDCS treatment with ICCT (T), or active tDCS with ICCT (AT), for a duration of ten days. Primary outcome measures included the Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAM-D), and Spielberger’s State-Trait Anxiety Inventory (STAI-S/T). Statistical analysis was performed using a Mixed-model Analysis of Variance, with supplementary Bayesian analysis.

Results

The AT group showed a significant improvement in BDI scores (p < .001), whereas no significant effects were observed on the HAM-D, STAI-T, or STAI-S scales.

Conclusions

The combination of tDCS and ICCT reduced depressive symptoms as measured by the BDI; while no significant effects were found with either treatment alone. Further research is needed to explore the mechanisms behind the synergistic effects in the treatment of post-stroke mood disorders.
The association of travel distance and other patient characteristics with breast cancer stage at diagnosis and treatment completion at a rural Rwandan cancer facility
Authors: Bhangdia Kayleigh , Natarajan Abirami , Rudolfson Niclas , Verguet Stéphane , Castro Marcia C. , Dusengimana Jean-Marie Vianney , Shyirambere Cyprien , Schleimer Lauren E. , Shulman Lawrence N. , Umwizerwa Aline , Kigonya Catherine , Butonzi John , MacDuffie Emily , Fadelu Temidayo , O’Neil Daniel S. , Nguyen Cam , Mpunga Tharcisse , Keating Nancy L. , Pace Lydia E.
Published: January 2025

Background

Butaro Cancer Center of Excellence (BCCOE) was founded to serve Rwanda’s rural low-income population, providing subsidized cancer diagnosis and treatment with transport stipends for the lowest-income patients. We examined whether travel distance to BCCOE was associated with advanced-stage diagnoses and treatment completion.

Methods

We conducted a retrospective cohort study using medical record data from BCCOE patients with pathologically-confirmed breast cancer from 2012–2016. Women with no prior surgery were included in the stage analysis; those with non-metastatic disease were included in the treatment analysis. We calculated travel distances using spatial analytic software and used multivariable logistic regression to examine the association of distance and other patient characteristics with late-stage diagnoses and treatment completion within one year of diagnosis.

Results

The analytic cohort for stage included 426 patients; 75.1% had late-stage (stage 3 or 4) disease. In univariable analyses, patients residing in BCCOE’s surrounding district had a lower proportion of late-stage diagnoses compared to those residing outside the district (57.9% v 76.8%, p = 0.02). In adjusted analyses, odds of late-stage diagnosis were 2.46 (95% CI:1.21–5.12) times higher among those in distance quartile 4 (> 135.8 km) versus 1 (< 55.7 km); the effect of distance was less strong in sensitivity analyses excluding patients from BCCOE’s surrounding district. Patients from sectors with > 50% poverty had 2.33 times higher odds of late-stage diagnoses (95% CI:1.07–5.26) relative to those with poverty < 30%. In the treatment completion cohort (n = 348), 49.1% of patients completed surgery and chemotherapy within a year. In adjusted analyses, travel distance and poverty were not linearly associated with treatment completion.

Conclusions

At Rwanda’s first public cancer facility, sector-level poverty and longer travel distances were associated with late-stage breast cancer diagnoses, but less clearly associated with treatment completion, perhaps partly due to travel stipends provided to the lowest-income individuals undergoing treatment. Our findings support further investigation into wider use of travel stipends to facilitate early diagnosis and treatment completion.
Contribution of vitamin B 6 deficiency to anemia in children on regular hemodialysis
Authors: Atia Fatma , Bazaraa Hafez , Abdelatty Yara , Lotfy Sarah , Eryan Eman
Published: January 2025

Background

Anemia is prevalent among pediatric patients diagnosed with end-stage kidney disease (ESKD). In addition, erythropoiesis-stimulating agents (ESA) and iron supplementation are considered the cornerstones in the management of anemia. However, a significant proportion of patients remain anemic. Vitamin B6 plays a vital role in the biosynthesis of heme and may be deficient in children with chronic kidney disease (CKD), particularly those on regular hemodialysis (HD). We aimed to evaluate serum vitamin B6 concentration in those children and determine its correlation with anemia indices.

Methods

The current cross-sectional study included 39 children on regular HD and 43 healthy controls. Clinical data were collected, including anthropometric measurements, blood pressure, iron, and erythropoietin therapy. Laboratory investigations included hemoglobin (Hb) indices, iron profile, and vitamin B6 level.

Results

The median Hb level in our cohort was 10.5 g/dL, and nine patients had Hb levels at or above the target Hb of 11 g/dl. They had a median Serum Vitamin B6 concentration of 28.2 ng/ml (IQR = 22.8–52.9) compared to a median of 27.5 ng/ml(IQR = 20–34) in controls, with no substantial differences between both groups. There was no statistically significant correlation between vitamin B6 and Hb levels or erythropoietin dose.

Conclusion

It is evident that the majority of our patients did not meet the desired threshold for anemia control. However, it is noteworthy that the average hemoglobin (Hb) level approached the intended target. The incidence of Vitamin B6 deficiency was not found to be statistically significant within our study population. Therefore, we could not establish a correlation between vitamin B6 deficiency and anemia in children on HD.
Association of LPCAT1-rs8352 genetic variant with susceptibility and severity of pediatric bronchial asthma: a case-control study
Authors: Mohany Khalid M. , Gamal Yasser , Raheem Yaser F. Abdel
Published: January 2025

Background

This study aimed to investigate the possible association of LPCAT1-rs8352 genetic variant (single nucleotide change C to G) with the onset and severity of pediatric asthma. Additionally, the study examined the influence of LPCAT1-rs8352 genotypes on asthma-related biomarkers including blood eosinophils count (BEC), eosinophil cationic protein (ECP), high-sensitivity C-reactive protein (hs-CRP), and immunoglobulin E (IgE) and on lung function [forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC)].

Patients and methods

The study included ninety-six participant grouped into two groups: G1 (46 asthmatics) and G2 (50 healthy controls). ECP, hs-CRP, and total IgE serum levels were measured using their corresponding ELISA kits. Neonatal blood DNA was extracted using the Gene JET™ Whole Blood Genomic DNA Purification Mini Kit. Genotyping was performed by RT-PCR.

Results

A significantly higher proportion of individuals in G1 had the LPCAT1-rs8352 CC and GC genotypes compared to G2 (p < 0.001). Individuals with the CC genotype exhibited significantly more severe asthma, along with elevated levels of BEC, ECP, hs-CRP, and total IgE. Those with the GC genotype demonstrated a similar, though less severe, pattern, followed by individuals with the GG genotype. The FEV1 and FVC values showed the opposite trend, with individuals having the GG genotype exhibiting the highest lung function values.

Conclusion

The LPCAT1-rs8352 allele C is associated with pediatric asthma onset and severity. Further research on the LPCAT1 genetic variants may provide a deeper understanding of pediatric bronchial asthma mechanisms and lead to improved management strategies.
Evaluation of the impact of acidic medications and fluoride-containing mouthwash on the enamel surface using quantitative light-induced fluorescence, microhardness, and scanning electron microscopy: an in vitro study
Authors: Bhasin Saanya , Singh Simran , Thomas Manuel Sebastian , Mahabala Karuna Yarmunja , Shenoy Ramya
Published: January 2025

Background

Due to their acidic nature, certain medications can have deleterious effects on tooth enamel. Fluoride is a popular method for reversing these effects. Therefore, this study aimed to assess the impact of acidic medications, specifically anti-asthmatic drugs and vitamin C tablets, on enamel surfaces and to investigate the effects of fluoride following drug exposure.

Methods

An in vitro experimental study was conducted on ninety-six healthy human posterior teeth. Forty-eight samples were tested for surface demineralization via quantitative laser fluorescence (QLF), and the other forty-eight samples were tested for enamel microhardness via a Vickers hardness tester. The samples were divided into six groups: (i) Group DW_NF- samples immersed in distilled water with no fluoride exposure; (ii) Group DW_F- samples immersed in distilled water with intermittent fluoride exposure; (iii) Group VC_NF- samples treated with vitamin C only; (iv) Group VC_F- samples treated with vitamin C and fluoride mouthwash; (v) Group SB_NF- samples exposed to salbutamol inhaler with no fluoride exposure; (vi) Group SB_NF- samples exposed to salbutamol inhaler followed by fluoride exposure. For the evaluation of surface morphology by scanning electron microscopy (SEM), two random samples used for QLF from each group were taken. The Wilcoxon signed-rank test, Kruskal‒Wallis test, and post hoc test were applied as appropriate. The p value was set at 0.05.

Results

Following exposure to medication, significantly higher QLF values were observed in Group VC_F and Group SB_F than in Group DW-NF (control group) (p = 0.15 and 0.004, respectively). The difference in the QLF values was significantly greater in Group VC_NF than in the control group DW-NF, indicating greater demineralization with acidic medications (p = 0.034). Significant changes in surface microhardness were detected in Group VC_F compared with the control group (p = 0.024). Qualitative analysis of SEM images revealed erosion at the enamel surface in all groups except the control group, with the most prominent erosion in the vitamin C- and fluoride-treated groups (VC_F group).

Conclusion

This study demonstrated the erosive potential of vitamin C tablets on enamel surfaces. Furthermore, the use of acidic fluoride mouthwash immediately after exposure to acidic medication exacerbates enamel demineralization.
Nursing professionalism and associated factors in Ethiopia: a systematic review and meta-analysis
Authors: Abebe Moges Tadesse , Zeleke Agerie Mengistie , Ferede Yeshiwas Ayale , Gonete Yosef Aragaw , Tassew Worku Chekol
Published: January 2025

Background

A higher level of nursing professionalism improves autonomy among nurses, the quality of nursing care, and patient outcomes. However, inconsistent findings on the prevalence of nursing professionalism and associated factors have been reported among studies conducted in Ethiopia, and a meta-analysis of pooled results have not been performed. Therefore, the aim of this systematic review and meta-analysis was to determine the pooled prevalence of higher levels of nursing professionalism and factors associated with it.

Methods

PubMed, Science Direct, HINARI, African Journals Online, Google Scholar, and university online institutional repositories in Ethiopia were accessed from 15/10/2024–30/10/2024. The items were assessed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The quality of the included studies was assessed via the Newcastle–Ottawa Scale. Cross-sectional studies were included without time period limits. Data extraction was conducted via Microsoft Excel and analyzed with STATA 17. The Galbraith plot, I2 statistic and meta-regression were used to determine heterogeneity. We used a random effects model in the presence of heterogeneity. Publication bias was assessed via funnel plots and Egger’s based regression. We also computed a sensitivity analysis and subgroup analysis by sample size and study period.

Results

Twelve primary studies involving 3710 nurses were included in this systematic review and meta-analysis. The pooled prevalence of higher levels of nursing professionalism was 43%. Bachelor's degree and above educational status (POR: 1.80, CI: 1.38, 2.33), learning from government colleges (POR: 2.14, CI: 1.34, 3.42), better payment (POR: 1.85, CI: 1.16, 2.98), long years of work experience (POR: 2.15, CI: 1.73, 2.68), positive self-image (POR: 3.85, CI: 2.17, 6.84), job satisfaction (POR: 2.42, CI: 1.49, 3.95) and training opportunities (POR: 2.88, CI: 1.14, 7.32) were factors that determined higher levels of nursing professionalism in Ethiopia.

Conclusion

The pooled prevalence of higher levels of nursing professionalism in Ethiopia was low. Educational status, and attending college, payment, work experience, self-image, job satisfaction, and training were factors that determined the level of professionalism. These factors can be modified to increase the level of nursing professionalism in Ethiopia.
Evaluating the impact, implementation experience and political economy of primary care networks in Kenya: protocol for a mixed methods study
Authors: Amboko Beatrice , Nzinga Jacinta , Tsofa Benjamin , Mugo Peter , Musiega Anita , Maritim Beryl , Wong Ethan , Mazzilli Caitlin , Ng’ang’a Wangari , Hagedorn Brittany , Turner Gillian , Musuva Anne , Murira Felix , Ravishankar Nirmala , Hussein Salim , Barasa Edwine
Published: January 2025

Background

Primary care networks (PCNs) are increasingly being adopted in low- and middle-income countries (LMICs) to improve the delivery of primary health care (PHC). Kenya has identified PCNs as a key reform to strengthen PHC delivery and has passed a law to guide its implementation. PCNs were piloted in two counties in Kenya in 2020 and implemented nationally in October 2023. This protocol outlines methods for a study that examines the impact, implementation experience and political economy of the PCN reform in Kenya.

Methods

We will adopt the parallel databases variant of convergent mixed methods study design to concurrently but separately collect quantitative and qualitative data. The two strands will be mixed during data collection to refine questions, with findings triangulated during analysis and interpretation to provide a comprehensive understanding of PCN implementation. The quantitative study will use a controlled before and after study design and collect data using health facility and client exit surveys. The primary outcome measure will be the service delivery readiness of PHC facilities. We will use a random sample of 228 health facilities and 2560 clients in four currently implementing PCNs, four planning to implement and four control counties at baseline and post-implementation. We shall undertake a preliminary cross-sectional analysis of the data at baseline from October to December 2023, followed by a difference-in-difference analysis at the endline from October to December 2024 to compare the outcome differences between the intervention and control counties over a 12-month period. The qualitative study will include a cross-sectional process evaluation and political economy analysis (PEA) using document reviews and approximately 80 in-depth interviews with national and sub-national stakeholders. The process evaluation will assess the emergence of PCN reforms, the implementation experience, the mechanism of impact and how the context affects implementation and outcomes. The PEA will examine the interaction of structural factors, institutions and actors/stakeholders’ interests and power relations in implementing PCNs. We will also examine the gendered effects of the PCNs, including power relations and norms, and their implications on PHC from the supply and demand sides. We shall undertake a thematic analysis of the qualitative data.

Discussion

This evaluation will contribute robust evidence on the impact, implementation experience, political economy and gendered implications of PCNs in a LMIC setting, as well as guide the refining of PCN implementation in Kenya and other LMICs implementing or planning to implement PCNs to enhance their effectiveness.
External validation of a multivariable prediction model for positive resection margins in breast-conserving surgery
Authors: Manhoobi Irina Palimaru , Ellbrant Julia , Bendahl Pär-Ola , Redsted Søren , Bodilsen Anne , Tramm Trine , Christiansen Peer , Rydén Lisa
Published: January 2025

Objectives

Positive resection margins after breast-conserving surgery (BCS) most often demands a repeat surgery. To preoperatively identify patients at risk of positive margins, a multivariable model has been developed that predicts positive margins after BCS with a high accuracy. This study aimed to externally validate this prediction model to explore its generalizability and assess if additional preoperatively available variables can further improve its predictive accuracy. The validation cohort included 225 patients with invasive breast cancer who underwent BCS at Aarhus University Hospital, Aarhus, Denmark during 2020–2022. Receiver operating characteristic (ROC) and calibration analysis were used to validate the prediction model. Univariable logistic regression was used to evaluate if additional variables available in the validation cohort were associated with positive margins and backward elimination to explore if these variables could further improve the model´s predictive accuracy.

Results

The AUC of the model was 0.60 (95% CI: 0.50–0.70) indicating a lower discriminative capacity in the external cohort. We found weak evidence for an association between increased preoperative breast density on mammography and positive resection margins after BCS (p = 0.027), but the AUC of the model did not improve, when mammographic breast density was included as an additional variable in the model.
Chemotherapy in synergy with innate immune agonists enhances T cell priming for checkpoint inhibitor treatment in pancreatic cancer
Authors: Niu Nan , Li Keyu , Wang Junke , Funes Vanessa , Espinoza Birginia , Li Pan , Wang Jianxin , Lyman Melissa , He Mengni , Herbst Brian , Wichroski Michael , Novosiadly Ruslan , Shoucair Sami , Mou Yiping , Zheng Lei
Published: January 2025

Background

The combination of conventional chemotherapy and immune checkpoint inhibitors (ICIs) has been unsuccessful for pancreatic ductal adenocarcinoma (PDAC). Administration of maximum tolerated dose of chemotherapy drugs may have immunosuppressive effects.

Methods

We thus tested, by using the preclinical model of PDACs including the genetically engineered mouse KPC spontaneous pancreatic tumor model and the pancreatic KPC tumor orthotopic implant model, the combinations of synthetic innate immune agonists including STING and NLRP3 agonist, respectively, and ICIs with or without chemotherapy.

Results

We found that innate agonists potentiate the role of chemotherapy in inducing effector T cells and subsequently to prime the tumor microenvironment (TME) better for ICI treatments. Triple combination of chemotherapy, innate agonists, and ICIs is superior to single modalities or double modalities in antitumor efficacies. Adding chemotherapy to innate agonists enhances the infiltration of overall CD8+ T cells and the memory cytotoxic subtype. NLRP3 agonist has a less effect than STING agonist on driving the T cell exhaustion. Adding chemotherapy to innate agonists enhances the infiltration of dendritic cells (DCs) in the tumors and CD86+ mature DCs in tumor draining lymph nodes. RNA sequencing analysis of the pancreatic tumors demonstrates the role of the combination of STING/NLRP3 agonist and chemotherapy, but not either treatment modality alone, in upregulating the T cell activation signaling. The NLRP3 agonist-mediated T cell activation is likely through regulating the nitrogen metabolism pathways.

Conclusion

This study supports the clinical testing of both STING and NLRP3 agonists, respectively, in combination with chemotherapy to sensitize PDAC patients for ICI treatments.
Appropriateness of learning environments in preprimary educational institutions: the case of preschools in Bahir Dar city, Ethiopia
Authors: Worku Mulugeta Yayeh
Published: January 2025

This study aimed to examine the appropriateness of learning environments in preprimary institutions, specifically focusing on preschools in Bahir Dar city, Ethiopia. To achieve this, a mixed-methods research approach was employed, guided by an adapted framework for assessing learning environments. Participants included preschool teachers and leaders who were selected through a comprehensive sampling technique. Data were collected using questionnaires and observations, and analyzed both quantitatively (using means, standard deviations, one-sample t-tests, and independent samples t-tests) and qualitatively through a thematic analysis approach. The findings revealed several challenges related to the physical environments, facilities, and classroom conditions within the preschools. The study concludes that, despite some positive efforts, preschools in Bahir Dar city were struggling to provide preprimary education in environments that are unsuitable for children. Finally, the article offers recommendations aimed at improving the learning environments of these institutions.
Greenhouse gas emissions (GHGE), water footprint and nitrogen loss associated with food consumption among adults: findings from the updated LEBANese natiONal food consumption survey (LEBANON-FCS)
Authors: Hoteit Maha , Khattar Maroun , Antar Esraa , Malli Dana ,   The Adults-Lebanon-FCS Group, Fadlallah Zahraa , Khadra Razan , Chahine Mohamad , Poh Omasyarifa Binti Jamal , Tzenios Nikolaos , Al Manasfi Elham , Chahine Abdulrahman
Published: January 2025

Background

Lebanon is grappling with numerous environmental challenges, including water scarcity, landfill waste, deforestation, and rising air pollution. Food choices significantly influence global greenhouse gas emissions and environmental impacts, making it crucial to evaluate the environmental footprints (EFPs) of Lebanon’s current dietary habits. This study aimed to assess food consumption patterns and their EFPs among a nationally representative sample of Lebanese adults.

Methods

A cross-sectional survey was conducted from May to September 2022, involving 444 Lebanese adults aged 18 to 64 years. The sample was representative, and participants were distributed across the eight Lebanese governorates. Sociodemographic and medical data were collected via a questionnaire, food consumption was assessed through a validated Food Frequency Questionnaire (FFQ) and two non-consecutive 24-hour recalls, and anthropometric measurements were also taken. EFPs were derived from databases and repositories.

Results

The typical EFPs of an average Lebanese adult included water usage of 2,862.39 ± 1,617.88 L/day, greenhouse gas emissions of 4.43 ± 2.29 kg CO2-eq/day, and nitrogen use of 12.72 ± 6.76 g/day. Animal products were the primary contributors to greenhouse gas emissions, while vegetable products had the highest water footprint and nitrogen loss impact on the environment. Grains and cereals, the most consumed food category, significantly influenced the water footprint and nitrogen loss. Additionally, meat consumption notably drove greenhouse gas emissions.

Conclusion

Lebanon must address its environmental challenges and the impact of dietary choices on greenhouse gas emissions and EFPs. By evaluating and understanding the environmental consequences of current dietary patterns, Lebanon can take proactive steps towards promoting sustainable food practices and mitigating environmental degradation.
RNA binding protein ILF3 increases CEP55 mRNA stability to enhance malignant potential of breast cancer cells and suppress ferroptosis
Authors: Chen Sheng , Luo Yangyong , Ruan Simin , Su Guosen , Huang Guoxing
Published: January 2025

Background

Ferroptosis has emerged as a promising therapeutic target in cancer treatment. CEP55, a key regulator of cell mitosis, plays a significant role in the tumorigenesis of many malignancies. In this study, we elucidated the function of CEP55 in the ferroptosis of breast cancer (BC).

Methods

The protein levels of CEP55 and ILF3 were detected by immunoblotting or immunohistochemistry, and their mRNA levels were assessed by quantitative PCR. Cell invasion and migration were evaluated by transwell assay. Cell apoptosis and colony formation were tested by flow cytometry and colony formation assays, respectively. RNA immunoprecipitation (RIP) experiment and CEP55 mRNA stability assay were used to validate the relationship between ILF3 and CEP55 mRNA. Subcutaneous xenograft studies were performed to analyze the role of ILF3 depletion in tumor growth.

Results

CEP55 and ILF3 were upregulated in most of human BC samples and MDA-MB-231 and MCF-7 BC cells. The depletion of CEP55 or ILF3 impaired the growth, invasion, and migration of MDA-MB-231 and MCF-7 cells, while promoted their ferroptosis and apoptosis. Mechanistically, ILF3 stabilized CEP55 mRNA to regulate CEP55 expression in BC cells. CEP55 restoration partially rescued the malignant potential defects of ILF3-depleted BC cells and attenuates their ferroptosis. Moreover, ILF3 depletion enhanced the anti-tumor growth activity of the ferroptosis inducer erastin in MDA-MB-231 subcutaneous xenograft tumors.

Conclusion

Our observations indicate that the depletion of ILF3 impairs the malignant potential of BC cells and promotes their ferroptosis by downregulating CEP55 expression. Silencing ILF3 or CEP55 could represent a potential therapeutic strategy for BC treatment.

Graphical abstract
HSP90 inhibitors promote cell death by degrading Met and BCR::ABL1 in both imatinib-resistant and -sensitive chronic myeloid leukemia cells
Authors: Tsubaki Masanobu , Matsuo Taira , Komori Rie , Nagai Noriaki , Yamamoto Tetsushi , Nishida Shozo
Published: January 2025

Background

Chronic myeloid leukemia is associated with a more favorable prognosis following treatment with BCR::ABL1 tyrosine kinase inhibitors (TKIs). Nonetheless, about 40% of affected individuals with CML display resistance or intolerance towards BCR::ABL1 TKIs. Heat shock protein 90 (HSP90) functions as a molecular chaperone and is known for its overexpression in various types of cancer, thereby HSP90 is a potential candidate for the treatment of BCR::ABL1 TKI-resistant and -sensitive CML. In present study, we aimed to investigate whether HSP90 inhibitors promote cell death in imatinib-resistant and -sensitive CML cells.

Results

KW-2478 and NVP-AUY922, which are HSP90 inhibitors, promoted cell death in both imatinib-resistant and -sensitive CML cells. Imatinib-resistant cells showed greater sensitivity to HSP90 inhibitors in comparison to imatinib-sensitive cells. KW-2478 inhibited the activation of Akt, extracellular regulated protein kinase 1/2, and c-Jun N-terminal kinase 1/2 in imatinib-resistant and -sensitive CML cells by promoting Met and BCR::ABL1 degradation.

Conclusion

These findings indicate inhibition of HSP90 such as KW-2478 and NVP-AUY922 as potential candidates for CML therapy.
Exploring the relationship between dissociative experiences and recovery in psychosis: cross-sectional study
Authors: Calciu Claudia , Macpherson Rob , Rees Kerry J. , Chen Sui Yung , Ruxton Sarah , White Rhiannon , Almaskati Mazen , Hill Francesca , Vasilis-Peter Anca , Desando Sebastian , Pennell Oliver , Nasubuga Carolyn , Webb Jackie , Walker Mark , Soponaru Camelia
Published: January 2025

Aims and method

This study explored the association among dissociative experiences, recovery from psychosis and a range of factors relevant to psychosis and analysed whether dissociative experiences (compartmentalisation, detachment and absorption) could be used to predict specific stages of recovery. A cross-sectional design was used, and 75 individuals with psychosis were recruited from the recovery services of the Gloucestershire Health and Care NHS Foundation Trust. Five questionnaires were used – the Dissociative Experiences Scale – II (DES), Detachment and Compartmentalisation Inventory (DCI), Questionnaire about the Process of Recovery, Stages of Recovery Instrument (STORI), and Positive and Negative Syndrome Scale – and a proforma was used to collect demographic data.

Results

Our findings indicated that compartmentalisation, detachment and absorption, as measured by DES and DCI, do not predict stages of recovery as measured by the STORI.

Clinical implications

The results of this study suggest that there is no simple relationship between dissociative and psychotic symptoms. They also suggest a need to assess these symptoms separately in practice and indicate that special approaches to treatment of psychosis may be needed in cases where such symptoms have a significant role.
The association between experiences of racism and mental health on children and young people in the UK: rapid scoping review
Authors: Ghezae Fiyory Tzeggai , Zungu Zonke , John Ann , Abdinasir Kadra , Bhui Kamaldeep , Adebiyi Adenike , Creswell Cathy
Published: January 2025

Background

Racism is increasingly recognised as a key contributor to poor mental health. However, the existing literature primarily focuses on its effects on adults.

Aim

To identify literature on the association between experiences of racism and mental health in children and young people in the UK.

Method

Inclusion criteria were: (a) peer-reviewed publications containing original data; (b) UK-based research; (c) included examination of associations between mental health and experiences of direct or indirect racism (quantitative or qualitative); (d) inclusion of an assessment of mental health outcomes; (e) participant ages up to and including 18 years of age or (if the range went beyond 18) with a mean age of 17 years or less. Six databases were searched between 2000 and 2022; an initial 11 522 studies were identified with only eight meeting the inclusion criteria.

Results

Five of the identified studies provided quantitative data and three provided qualitative data. The majority of studies (7/8) focused on children and young people aged 10 years and over; only one focused on children under the age of 10 years. Measurements of racism varied among the studies providing quantitative data. Only four studies directly focused on the effects of racism on the mental health of children and young people.

Conclusion

Although the included studies highlighted potential negative impacts of experiences of racism on children and young people in the UK, this review shows the lack of available literature to inform policy and practice. No studies examined the impact of internalised racism, systemic and institutional racism, or intersectionality.
Therapeutic alliance in a stepped digital psychosocial intervention for breast cancer patients: findings from a multicentre randomised controlled trial
Authors: Flix-Valle Aida , Medina Joan Carles , Souto-Sampera Arnau , Arizu-Onassis Alejandra , Juan-Linares Eva , Serra-Blasco Maria , Ciria-Suárez Laura , Feixas Guillem , Ochoa-Arnedo Cristian
Published: January 2025

Background

Action mechanisms of therapeutic alliance in stepped and digital interventions remain unclear.

Aims

(a) To compare the development of therapeutic alliance between psychosocial treatment as usual (PTAU) and a stepped digital intervention designed to prevent distress in cancer patients; (b) to analyse the level of agreement between patients’ and therapists’ therapeutic alliance ratings; and (c) to explore variables associated with therapeutic alliance in the digital intervention.

Method

A multicentre randomised controlled trial with 184 newly diagnosed breast cancer women was conducted. Patients were assigned to digital intervention or PTAU. Therapeutic alliance was assessed at 3, 6 and 12 months after inclusion using the working alliance inventory for patients and therapists. Age, usability (system usability scale), satisfaction (visual analogue scale), type and amount of patient–therapist communication were analysed as associated variables.

Results

Patients and therapists established high therapeutic alliance in the digital intervention, although significantly lower compared with PTAU. The development of patients’ therapeutic alliance did not differ between interventions, unlike that of the therapists. No agreement was found between patients’ and therapists’ therapeutic alliance ratings. Patients’ therapeutic alliance was associated with usability and satisfaction with app, whereas therapists’ therapeutic alliance was associated with satisfaction with monitoring platform.

Conclusions

A stepped digital intervention for cancer patients could develop and maintain strong therapeutic alliance. Neither the type nor amount of communication affected patients’ therapeutic alliance, suggesting that flexible and available digital communication fosters a sense of care and connection. The association between usability and satisfaction with digital tools highlights their importance as key therapeutic alliance components in digital settings.
Personalized oncogenomic analysis of metastatic squamous cell carcinoma of the anus: Utilizing whole-genome sequencing to guide clinical decision-making.
Authors: Peixoto Renata D'Alpino , McConechy Melissa , Lim Howard J. , Marra Marco A , Xu Jing , Wee Kathleen , Pleasance Erin D. , Laskin Janessa J.
Published: January 2025

11

Background:
Metastatic squamous cell carcinoma of the anus (SCCA) is associated with significant morbidity and mortality. Due to its relative rarity, there is limited evidence to support systemic therapy regimens informed by genomic data. This study aims to utilize whole-genome and transcriptome sequencing to enhance the understanding of the genetic alterations driving metastatic SCCA and to identify potentially actionable therapeutic targets.
Methods:
This report examines nine cases of metastatic SCCA in patients enrolled in the Personalized Oncogenomics (POG) Program at the BC Cancer Agency. Comprehensive genomic profiling, including whole-genome and transcriptome analysis (WGTA) was conducted on fresh tumor biopsy or formalin fixed paraffin embedded (FFPE) tissue. Tumor genomic alterations were analyzed in detail including: SNVs, indels, copy number alterations, structural variants, mutation signatures, viral presence, tumor mutation burden (TMB), expression outliers, and immune cell scores. The somatic alterations were integrated with existing knowledge of drug-target interactions to identify actionable therapeutic targets.
Results:
Of the nine patients, eight were found to be HPV-positive, with one exhibiting high tumor mutational burden (TMB>10mut/Mb). Mutation signatures included seven cases with AID/APOBEC signatures (commonly seen with HPV), and one case with an ID2 DNA replication slippage signature. The PI3K/AKT/mTOR pathway was the most commonly affected signaling pathway (n=4), followed by FGFR amplification and overexpression (n=3), and RAS/RAF alterations (
BRAF
mutation and
KRAS
overexpression, n=2). EGFR amplification was identified in two cases, one of which also exhibited
EGFR
overexpression. Additionally,
FBXW7
mutations were present in two cases. Immunotherapy was recommended for all nine patients: eight based on HPV positivity, either alone or in combination with other alterations, such as high TMB, SWI/SNF complex alterations, and presence of immune infiltrating cells, and the remaining case based on a SWI/SNF complex mutation. Only two patients ultimately received immunotherapy, both of whom derived clinical benefit. One patient, treated with atezolizumab as part of the phase II CAPTIV-8 trial (NCT04273061), demonstrated progression-free survival (PFS) of 10 months (ongoing), while the other, treated with nivolumab, achieved a PFS of 6 months.
Conclusions:
Genomic analysis using WGTA supported the recommendation of immunotherapy for all patients in this cohort. Although only two patients received immunotherapy, both experienced clinical benefit, underscoring the potential of personalized genomic-guided treatment in metastatic SCCA.