bluuebunny/crossref_metadata_2025 huggingface dataset:
Recursive parameter estimation for the on-line monitoring of delamination growth in composite structures
Authors: Cumbo Roberta , De Gregoriis Daniel , Danzi Federico , Kumar Abhishek , Naets Frank
Published: December 2024

One of the main failure phenomena in composite materials is delamination, which consists of the progressive separation of plies. An augmented extended Kalman filter (KF) approach for joint input-parameter estimation is proposed and demonstrated in this work for delamination growth monitoring. In particular, a novel recursive estimation scheme for parameter identification is proposed within the joint input-parameter scheme which allows for a substantial reduction of the number of required sensors, enabling the use of the proposed KF approach. The proposed methodology also allows for the full-field response reconstruction, interface stiffness degradation monitoring and critical load identification. The methodology is validated on both simulated as well experimental data of a carbon fiber double Cantilever beam specimen, showcasing good accuracy for both cases.
A Hybrid 2D Gaussian Filter and Deep Learning Approach with Visualization of Class Activation for Automatic Lung and Colon Cancer Diagnosis
Authors: Turk Omer , Acar Emrullah , Irmak Emrah , Yilmaz Musa , Bakis Enes
Published: December 2024

Cancer is a significant public health issue due to its high prevalence and lethality, particularly lung and colon cancers, which account for over a quarter of all cancer cases. This study aims to enhance the detection rate of lung and colon cancer by designing an automated diagnosis system. The system focuses on early detection through image pre-processing with a 2D Gaussian filter, while maintaining simplicity to minimize computational requirements and runtime. The study employs three Convolutional Neural Network (CNN) models-MobileNet, VGG16, and ResNet50-to diagnose five types of cancer: Colon Adenocarcinoma, Benign Colonic Tissue, Lung Adenocarcinoma, Benign Lung Tissue, and Lung Squamous Cell Carcinoma. A large dataset comprising 25 000 histopathological images is utilized. Additionally, the research addresses the need for safety levels in the model by using Class Activation Mapping (CAM) for explanatory purposes. Experimental results indicate that the proposed system achieves a high diagnostic accuracy of 99.38% for lung and colon cancers. This high performance underscores the effectiveness of the automated system in detecting these types of cancer. The findings from this study support the potential for early diagnosis of lung and colon cancers, which can facilitate timely therapeutic interventions and improve patient outcomes.
World Stroke Organization: Global Stroke Fact Sheet 2025
Authors: Feigin Valery L , Brainin Michael , Norrving Bo , Martins Sheila O , Pandian Jeyaraj , Lindsay Patrice , F Grupper Maria , Rautalin Ilari
Published: December 2024

Background:

Among non-communicable disorders (NCDs), stroke remains the second leading cause of death and the third leading cause of death and disability combined (as expressed by disability-adjusted life-years lost—DALYs) in the world.

Aims:

The study was aimed to estimate global, regional and nationa burden of stroke and its risk factors from 1990 to 2021.

Methods:

Finding presented in this paper were derived mainly from the Global Burden of Disease 2021 Study on stroke burden published in The Lancet Neurology 2024:23:973-1003.

Results:

The estimated global cost of stroke is over US$890 billion (0.66% of the global GDP). From 1990 to 2021, the burden (in terms of the absolute number of cases) increased substantially (70.0% increase in incident strokes, 44.0% deaths from stroke, 86.0% prevalent strokes, and 32% DALYs), with the bulk of the global stroke burden (87.0% of deaths and 89.0% of DALYs) residing in lower-income and lower-middle-income countries (LMICs). Stroke attributable to metabolic risks constituted 69.0% of all strokes, environmental risks constituted 37.0%, and behavioral risks constituted 35.0%.

Conclusion:

This World Stroke Organization (WSO) Global Stroke Fact Sheet 2025 provides the most updated information that can be used to inform communication with all internal and external stakeholders; all statistics have been reviewed and approved for use by the WSO Executive Committee and leaders from the Global Burden of Disease research group.
HIV Preexposure Prophylaxis Practice among Urban Female Sex Workers in Northwest Ethiopia: Using Generalized Structural Equation Modeling
Authors: Asmare Lakew , Goshu Atalay , Alemu Tihtna , Gebeye Ejigu
Published: December 2024

Background

Acquired immunodeficiency syndrome, caused by the human immunodeficiency virus, has remained a public health threat for the last decades with significantly high burden. Despite the introduction of various human immunodeficiency virus (HIV) prevention strategies targeting high-risk populations, including preexposure prophylaxis, there remains a notable gap in the literature regarding Pre-Exposure Prophylaxis (PrEP) practice among female sex workers (FSWs) in Ethiopia, particularly using advanced analytical methods like structural equation modeling. This study aimed to assess practice and associated factors of preexposure prophylaxis among urban female sex workers in Northwest Ethiopia.

Methods

A cross-sectional study was carried out at organizations of Organizations for Social Service, Health Development, Mehabere Hiwot for Social Development, and African Network for the Prevention and Protection Against Child Abuse and Neglect that serve FSWs. Systematic random sampling technique was employed among 549 FSWs. An interviewer-administered questionnaire was used to collect the data. Generalized structural equation modeling was employed to identify factors associated with PrEP practice. As the mediation of effects was present, the direct, indirect, and total effects were determined. A final model was selected based on the statistical significance of the path coefficient.

Results

In this study, the practice of preexposure prophylaxis was 28.00% with 95% CI = 25.34% to 32.72%. Thus, female sex workers with an education level of college and above had both direct and indirect positive effects on PrEP practice when mediated by knowledge, knowledge had both direct and indirect effects on PrEP practice when mediated by attitude. Whereas, FSWs who had duration of sex work for 3 to 5 years had only a positive direct effect on PrEP practice compared to those who were living in sex work for less than three years duration.

Conclusion

However, HIV remains a public health problem, and the practice of preexposure prophylaxis in this study was found to be low. FSWs having higher education levels, attitudes, and knowledge demonstrate a significantly positive effect on their likelihood to practice PrEP. They suggested enhancing their health outcomes and reducing the risk of HIV transmission. The result of this study was also significant for communities that are serving in a given organization targeting integrated HIV testing and counseling services among key populations.
Validity and Reliability of the Turkish Version of the Medial Tibial Stress Syndrome Score
Authors: Demir Benli Merve , Winters Marinus , Arslan Aynur S. , Ceylan Ebru , Benli Cenk , Ergün Metin
Published: December 2024

Background:

Medial tibial stress syndrome (MTSS) is a common leg injury in military personnel and athletes and is especially related to running and jumping. A patient-reported outcome measure, the MTSS score, was developed to determine the severity of MTSS.

Purpose:

To translate, culturally adapt, and validate the MTSS score for the Turkish language.

Study Design:

Cohort study (diagnosis); Level of evidence, 2.

Methods:

Established guidelines were used for translation and adaptation. The Turkish version of the MTSS (MTSS-Tr) score was completed twice with a 1-week interval between assessments. In the first assessment, patients also completed the Turkish version of the 36-Item Short-Form Survey (SF-36-Tr) and a visual analog scale (VAS) for pain. Test-retest reliability and internal consistency of the MTSS-Tr were measured with the intraclass correlation coefficient (ICC) and Cronbach α coefficient, respectively. The construct validity was demonstrated with the Spearman correlation coefficient ( rS).

Results:

A total of 48 participants were included in the study. The test-retest reliability was good and internal consistency was good (ICC, 0.9; Cronbach α, 0.884). The MTSS-Tr score was highly negatively correlated with the physical component score of the SF-36-Tr ( rS = −0.716; P < .001). There was a moderate correlation between the MTSS-Tr score and the VAS pain score ( rS = 0.465; P = .001).

Conclusion:

The translated MTSS-Tr score has good internal consistency and good reliability and validity. Therefore, the MTSS-Tr score is useful to evaluate symptoms in patients with MTSS.

Registration:

NCT05400668 (ClinicalTrials.gov identifier).
A comparative analysis of strategies for multiplication and division of fractions between elementary preservice teachers in the United States and Korea
Authors: Kang Hyun Jung , Breiten Grace
Published: December 2024

The present comparative analysis study conducted an examination of 46 U.S. and 30 South Korean elementary preservice teachers (PSTs), assessing their overall performances and comparing problem-solving strategies across 11 fraction multiplication and division problems. The tasks spanned across three domains: posing story problems, solving word problems, and illustrating visual models. This study’s purpose is to relay common misconceptions held by elementary PSTs regarding fraction multiplication and division between the U.S. and South Korea. The overall performance results indicated that South Korean PSTs demonstrated higher proficiency in all three areas (i.e., posing story problems, solving word problems, and illustrating visual models). However, both groups of U.S. and South Korean PSTs encountered the most difficulty in representing visual models. Strategy analysis highlighted that the application of properties of multiplication and clearer representation of the unit were key factors contributing to the success of South Korean PSTs. Such results contribute to the growing literature supporting the importance of elementary PSTs’ influence on students to develop necessary foundational skills in mathematics. The study also discusses implications for teacher educators based on these findings.
Using the task analysis guide as a lens to examine curriculum reform
Authors: O’Sullivan Brendan , O’Shea Ann , Breen Sinéad
Published: December 2024

Over the last 15 years, a significant reform of the secondary school mathematics curriculum in Ireland took place. A major aim of the reform was to move away from instrumental learning and to develop mathematical proficiency and problem-solving skills in line with international trends. In this article, we study textbook tasks from popular textbook series in use before and after the reform. Our purpose is to use the task analysis guide to investigate the level of cognitive demand of the tasks, and the opportunities they offer students and teachers to achieve the aims of the curriculum reform. Our analysis shows that the vast majority of the 7635 tasks studied have a low level of cognitive demand; consequently, they mainly offer students opportunities to develop procedural fluency. We note that the post-reform textbooks do contain more tasks with high levels of cognitive demand than their pre-reform counterparts, however, the increases are small. This study will be of relevance to countries where textbooks are not designed or approved by curriculum developers.
Therapeutic Effect and Molecular Mechanism of the Ultra-Low Molecule Compound K on Multiple Myeloma
Authors: Shin Myung Geun , Kim Hye Ran , Lee Young Eun , Lim Ha Jin , Shin Jong Hee
Published: December 2024

Introduction: Multiple myeloma (MM) is an incurable hematologic cancer that originates from plasma cells and occurs primarily in patients over 60. The prognosis of MM has improved after the introduction of new treatments, such as thalidomide, bortezomib, and lenalidomide. However, in recurrent and refractory MM patients, factors such as age and drug toxicity are important when choosing treatment options. Therefore, new drugs with little toxicity are needed. Through previous research, we confirmed that the triterpene compound series has a killing effect on multiple myeloma cells, and conducted a nonclinical trial.

Methods: The killing effect of the hit compounds on MM cell lines (ARH77, U266, and RPMI8226) was examined using a sulforhodamine B assay. Apoptosis mechanisms were investigated in vitro by western blot and apoptotic protein array. Complex immunocompromised mice were established by injecting RPMI8226-GFP-FLuc cells through the tail vein. Efficacy of the KBB-N1 activity was assessed following daily oral administration (20 mg/kg/day) for 3 weeks and tail vein (7 mg/kg/day) infusions for 3 days a week at daily intervals. Toxicity, pharmacokinetics, and molecular docking analyses were performed according to the established protocols.

Results: KBB-N1 was identified as an MM-targeted hit compound with cytotoxic effects. Severe suppression of normal hematopoietic stem cell function was observed with lenalidomide administration at a concentration of 25 μM. However, this toxicity was not observed when KBB-N1 was administered at doses up to 60 μM. KBB-N1 activity involves PARP cleavage and caspase activation in the apoptotic pathway. Furthermore, KBB-N1 inhibited cell growth and exerted cytotoxicity. KBB-N1 induced apoptosis by activating the P53 apoptosis pathway in MM cells. In vivo, all untreated tumor-bearing mice showed rapid tumor growth and severe plasmacytomas, which led to death within 7 weeks. Mice treated with KBB-N1 had significantly inhibited tumor growth and longer survival times. The molecular docking assay revealed the optimal docking conformation binding energy of KBB-N1 with docking scores (kcal/M) of -7.6 for phosphorylated p53.

Conclusions: This study demonstrated that KBB-N1, an ultra-low molecular weight ginsenoside compound K, effectively treated MM by increasing the expression of phosphorylated p53. Given its minimal toxicity to hematopoietic stem cells and major organs, KBB-N1 is a promising new drug for treating MM in older patients.
Erythropoietin-Induced Bone Loss Is Driven By an M-CSF Surge in the Bone Marrow As Assessed By Time-Course Studies in a Murine Model
Authors: Gorodov Anton , Kolomansky Albert (Alex) , Ben-Califa Nathalie , Lezerovich Lior , Piper Michelle , Gabet Yankel , Neumann Drorit
Published: December 2024

Bone tissue constantly undergoes a process of remodeling that simultaneously involves bone resorption by osteoclasts and bone formation by osteoblasts. Osteoclasts are multinuclear cells that originate primarily from myeloid precursors, while macrophage colony-stimulating factor (M-CSF) is essential for their survival and differentiation. Osteoblasts originate from mesenchymal cells and differentiate into osteocytes (mineralized bone resident cells). The balance between bone resorption and bone formation determines changes in bone mass.

A wide variety of therapeutic interventions can affect bone metabolism. Erythropoietin (EPO), a primary regulator of red cell lineage, is commonly used in the clinic to treat anemia in certain clinical conditions and is sometimes administered to non-anemic patients before surgery to reduce the need for perioperative blood transfusion. We have previously shown that multidose (2-week) exposure to EPO significantly reduces bone mass in mice.

In this study, we explored the dynamics of the response to a single high-dose EPO treatment in bone and bone marrow (BM) microenvironment in mice. Bone parameters were examined at four time points (16 hours, 48 hours, 1 week, and 2 weeks) following a single EPO injection (180 U) in young (9 weeks) female mice. We found that this single dose of EPO led to a 32% decrease in bone volume/total volume (BV/TV) in the distal femur within 1 week, as assessed by µCT analysis. Serum M-CSF levels increased by 180% 16 hours after EPO administration. This increase was accompanied by a 2-fold increase in soluble M-CSF in the BM extracellular matrix, which returned to baseline levels 48 hours after EPO administration. M-CSF-receptor (CD115) positive cells in the BM increased by 32% and 39% 48 hours and 1 week following EPO injection, respectively. Osteoclast precursor cells (Lin− CD11b− Ly6Chi CD115+) increased by 32%, 32% and 46%, two days, 1 week and 2 weeks after EPO injection, respectively. In line with these findings, serum levels of tartrate resistance acid phosphatase 5b (TRAP5b), a marker of bone-resorbing osteoclasts, increased in EPO-treated mice by ~20% 1 week after EPO injection, compared to diluent injected controls. Bone formation was also significantly affected by EPO treatment, as reflected by a ~80% decrease in procollagen type I N-terminal propeptide (P1NP) within 48 hours after EPO injection and returned to baseline one-week post-treatment.

This study sheds light on the dynamic bone response to EPO, showing for the first time that even a single dose of EPO may have significant implications for bone metabolism. These findings are highly relevant in the case of EPO administration to non-anemic patients before surgery for potential avoidance of allogeneic transfusions.
Tyrosine Kinase Inhibitors Short Exposure in Pregnant Female Patients with Chronic Myeloid Leukemia
Authors: Zu Yingling , Zhao Huifang , Chen Jianling , Dang Huibing , Shi Yanrong , Liang Lixin , Mei Shuhao , Lu Wenyi , Zhou Jian , Song Yongping , Zhang Yanli
Published: December 2024

Introduction In the era of tyrosine kinase inhibitor (TKI), improving the quality of life has become the main therapeutic goal for patients with chronic myeloid leukemia (CML). Unintended pregnancy for female patients with chronic myeloid leukemia (CML) raises the discussion of treatment choices due to the teratogenicity of tyrosine kinase inhibitor (TKI). Method We reported 51 accidental pregnant CML chronic phase (CP) patients with TKI withdrawal immediately after pregnancy from December 2010 to February 2024 to observe the effect of short exposure to TKI on the fetus and the infant outcomes.

Results 59 pregnancies resulted in 100% normal childbirth without birth abnormalities. The median TKI exposure duration was 4 (4-20) weeks in 58 pregnancies, and one pregnancy avoided TKI exposure due to treatment discontinuation of the patient with treatment-free remission (TFR). All newborns had normal birth weight except one premature infant with low birth weight less than the 10th percentile. Up to now, all the children are in good health. 13 (25.5%) and 30 (58.8%) patients had achieved major molecular response (MMR) and deep molecular response (DMR) at pregnancy, respectively. After TKI discontinuation, loss of MMR and complete hematologic response occurred in 6 (11.8%) and 2 (3.9%) patients at delivery, respectively. 38 patients resumed TKI treatment after delivery, and 13 patients sustained TFR after delivery. The median time to regain MMR and DMR were 3 (2-6) months and 6 (1-28) months, respectively.

Conclusion These results demonstrate that TKI discontinuation during pregnancy is feasible for CML-CP patients, and short TKI exposure of pregnant patients has little influence on children's growth and development.
Lysosome Acidification Facilitates the Expansion of Circulating Hematopoietic Stem and Progenitor Cells
Authors: Yulin Xu , Zhang Meng , Lu Jianghuan , Huo Dawei , Jiang Penglei , Tie Ruxiu , Chen Yijin , Zeng Xiangjun , Qian Pengxu , Huang He
Published: December 2024

Despite present in steady-state peripheral blood (SSPB) with high readily accessibility, circulating hematopoietic stem and progenitor cells (cHSPCs) is significantly limited in clinic application and basic research for their rarity and unclear molecular mechanisms. Here, we developed a monocyte-incubation system for human cHSPC expansion, and achieved phenotypically and functional primitive CD34+ cHSPCs. The system produced a 100-fold increase in LIN-CD45RA-CD34+CD38- HSPC frequency, and the expanded cells were capable of hematopoietic repopulation for at least 9 months in immunocompromised mice. Mapping landscape comparison of the incubated and non-incubated cHSPC culture was revealed at transcriptome and proteome level including single-cell sequencing and label-free quantitative mass spectrometry analysis respectively. An integrative analysis combined with factor-inhibitor/agonist tests demonstrated that the effects of monocyte-incubation on HSPC expansion might resulted from a lysosome acidification and HIF-1-siganl-dependent manner. Finally, we validated that monocyte-incubation also promoted the expansion of umbilical cord blood-derived HSPCs (UCB-HSPCs), and improved the repopulation capacity of UCB-HSPCs. Monocyte-incubated system on HSPCs will facilitate the clinical application of steady-state peripheral blood- or umbilical cord blood-based therapies.
Clinical Outcomes for Female Patients Following Hematopoietic Stem Cell Transplant: An Analysis of the National Inpatient Sample
Authors: Thor Danielle C , Elias Tony , Polineni Vineet , Brik Ben
Published: December 2024

Background: As hematopoietic stem cell transplant (HSCT) grows in accessibility and utility, it remains imperative to understand outcomes for its recipients. Limited data is available on the sex-based correlations for this steadily increasing patient population. We sought to examine the National Inpatient Sample (NIS) database to describe in-hospital outcomes among the female population who have received a HSCT.

Methods: Data were extracted from the NIS Database from 2019 and 2020. The NIS was searched for hospitalizations of all patients greater than 18 years old who had previously received a HSCT and were hospitalized thereafter. We then analyzed the outcomes of female patients. Multivariate logistic regression analysis was used to adjust for confounders; SPSS software was used for statistical analysis. The primary outcome was inpatient mortality and secondary outcomes are listed below.

Results: This study included 8,302 patients who had received a HSCT, of which 3636 (43.8%) were identified as female. Female recipients of a HSCT had a slightly higher prevalence of obesity (7.5% versus 7.0%, p<0.001), as well as lower prevalence of smoking (16.5% versus 20.5%, p<0.001), hypertension (21.8% versus 23.7%, p<0.001), and chronic kidney disease (19.3% versus 21.3%, p<0.001). Multivariate regression demonstrated that female recipients of a HSCT had higher inpatient mortality (OR 1.721, CI 1.572-1.884, p<0.001). On secondary analysis, female HSCT recipients were found to be more likely to have anemia (OR 1.790, CI 1.746-1.836, p<0.001), thrombocytopenia (OR 1.692, CI 1.621-1.765, p<0.001), hypertension (OR 1.674, CI 1.615-1.736, p<0.001), acute kidney failure (OR 1.698, CI 1.635-1.764, p<0.001), all-cause arrhythmias (OR 1.588, CI 1.502-1.680, p<0.001), all-cause heart block (OR 1.441, CI 1.323-1.570, p<0.001), all-cause sepsis (OR 1.859, CI 1.789-1.932, p<0.001), all-cause coagulopathies (OR 1.744, CI 1.605-1.895, p<0.001), and acute heart failure (OR 1.734, CI 1.658-1.815, p<0.001).

Conclusion: In this nationally-representative, population-based retrospective cohort study, female patients who have received a HSCT and were subsequently hospitalized were associated with higher mortality and worse outcomes.
Efficacy and Safety of Mepolizumab in Eosinophilic Granulomatosis with Polyangiitis: A Systematic Review and Meta-Analysis
Authors: Ejaz Hassan , Sajjad Maha , Hasan Sajjad Ul , Khan Malik W.Z. , Hussain Amna , Ali Aizaz , Azeem Touba , Afridi Abdullah , Sajjad Ayema , Javed Muhammad Arsham , Qudrat Salma , Khan Salman , Niazi Muhammad Raphay , Yetiskul Ekrem , Ali Shandana
Published: December 2024

Introduction:

Eosinophilic granulomatosis with polyangiitis (EGPA), known previously as Churg-Strauss syndrome, is a systemic vasculitis involving small to medium-sized vessels. Corticosteroids and immunosuppressive therapies historically managed EGPA, but these therapies are often associated with adverse effects and a high likelihood of relapse. Recently, mepolizumab (MPZ), a monoclonal antibody that targets interleukin-5 (IL-5) has shown promising results, especially for those EGPA patients who are refractory to conventional corticosteroid therapy.

Methods:

A systematic literature search was conducted on PubMed, Cochrane Library, Science Direct, Google Scholar, ClinicalTrials.gov, and the American Society of Hematology (ASH) from inception to June 01, 2024, using MeSH terms and keywords used for “Churg-Strauss syndrome”, “EGPA”, “Eosinophilic Granulomatosis with Polyangiitis”, “Allergic Granulomatosis”, and “Mepolizumab”. Clinical remission and adverse effects were the primary outcomes. Secondary outcomes were prednisolone-free remission, serious adverse effects, relapses, and asthma exacerbations. The random-effects model with the Freeman Tukey double arcsine transformation was used to pool overall prevalence with 95% CI for dichotomous variables in MetaXL version 5.3.

Results:

Seventeen studies were included (n = 1,075 patients). Nine studies (178 out of 311 patients) reported data on clinical remission with a pooled prevalence of 65% (95% CI: 49%-79%, I2=86%). Twelve studies (385 out of 853 patients) reported data on any adverse effects after treatment with a pooled prevalence of 52% (95% CI: 25%-77%, I2 =98%). Three studies reported remission in both 100 mg and 300 mg subgroups with a pooled prevalence of 50% (95% CI: 22%-78%, I2 =85%) and 72% (95% CI: 56%-86%, I2 =7%) respectively. Seven studies (73 out of 238 patients) reported prednisolone-free remission with a pooled prevalence of 32% (95% CI: 21%-43%, I2=65%).

Conclusion:

The systematic review and meta-analysis suggests that MPZ is effective and safe for treating patients with EGPA. Subgroup analysis by dosage regimen indicated that 100 mg could be more effective for inducing prednisolone-free remission with fewer serious adverse effects and fewer relapses.
Retention of Young Adults with Sickle Cell Disease in Outpatient Adult Care
Authors: Pavkov Isabela , Kutlar Abdullah , Gollan Siera
Published: December 2024

Introduction

As the life expectancy of people with sickle cell disease (SCD) increases (Payne 2020), focus has been on preparing the transition from pediatric to adult care, with success measured as attendance at the first adult appointment. The handoff to adult care typically marks the end of transition support. However, people with SCD aged 25-35 have the highest rates of healthcare utilization (Benenson 2017). Little is known about how to retain young adults in adult care in the years following transition. Our objective is to examine current literature for strategies used by adult clinics to support young adults with SCD to remain engaged in specialist care after the first adult appointment.

Methods

Following guidelines established by Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) (Tricco 2018), we reviewed the literature for interventions aimed at retaining young adults (age 18-24) with SCD in outpatient care after their first adult appointment following transition from pediatric care. We queried multiple online databases (PubMed, CINAHL, Web of Science) for articles published between January 2010 to April 2024. Articles did not need to include success of intervention. The initial search with focus on SCD returned limited findings, prompting us to broaden the review and include care continuity of young adults with any chronic illness.

Results

The scoping review identified several studies which employ an intervention to retain young adults with chronic illnesses in adult specialist care. Some studies show success with co-located adult and pediatric care for retention of patients with SCD and human immunodeficiency virus. Other institutions employed a transition navigator who provides pre-transition support and limited post-transition follow-up. A study including young adults with any chronic physical illness used a mobile app to foster engagement with adult healthcare services.

Conclusions

The number of studies documenting interventions for retaining young adults with SCD in outpatient care following the initial adult visit is severely limited. While it is possible that more interventions exist that are not published, it is not unreasonable to consider applying interventions from other chronic illnesses to SCD. However, the approach with the most success, that of the co-location model, may not be feasible for most institutions. Technology-based interventions, such as mobile applications, would likely be more widely implementable. More interventions to ensure young adults engage with adult outpatient specialty care are much needed. Continuity of care in young adults with any chronic illness is important, and it is especially necessary in the SCD population. Adults with SCD require long-term specialist care to minimize the devastating complications that characterize the natural course of their disease and elevate quality of life.
Treating sleep disordered breathing for cardiovascular outcomes: observational and randomised trial evidence
Authors: Bradley T. Douglas , Logan Alexander G. , Floras John S.
Published: December 2024

Sleep disordered breathing (SDB) is considered a risk factor for cardiovascular disease (CVD). Obstructive sleep apnoea (OSA) can be treated with continuous positive airway pressure (CPAP), and central sleep apnoea (CSA), in patients with heart failure with reduced ejection fraction (HFrEF), by peak flow-triggered adaptive servo-ventilation. Presently, there is equipoise as to whether treating SDB prevents cardiovascular events. Some propose treatment for this indication, based on observational data, while others argue against because of the lack of randomised trial evidence. This review evaluates literature concerning the cardiovascular effects of treating SDB with PAP devices in individuals with and without CVDs. Nine observational studies report significantly lower cardiovascular event rates in those treated, than in those not treated, for SDB. Conversely, 12 randomised trials in which excessive daytime sleepiness was generally an exclusion criterion showed no reduction in cardiovascular event rates. The SERVE-HF trial showed an increase in mortality with use of minute ventilation-triggered adaptive servo-ventilation for CSA in patients with HFrEF. In the ADVENT-HF trial, treating HFrEF patients with coexisting OSA or CSA using peak flow-triggered adaptive servo-ventilation was safe and improved sleep structure and heart failure-related quality of life but did not reduce all-cause mortality or cardiovascular events. More evidence is required to determine whether treating CSA in patients with HFrEF prevents cardiovascular events and improves survival. Presently, the rationale for treating SDB with PAP remains improving sleep structure and quality of life, as well as relieving excessive daytime sleepiness, but not reducing cardiovascular events.
GOLD Science Committee recommendations for the use of pre- and post-bronchodilator spirometry for the diagnosis of COPD
Authors: Singh Dave , Stockley Robert , Anzueto Antonio , Agusti Alvar , Bourbeau Jean , Celli Bartolome R. , Criner Gerard J. , Han MeiLan K. , Martinez Fernando J. , Montes de Oca Maria , Ozoh Obianuju B. , Papi Alberto , Pavord Ian , Roche Nicolas , Salvi Sandeep , Sin Don D. , Troosters Thierry , Wedzicha Jadwiga , Zheng Jinping , Volgelmeier Claus , Halpin David
Published: December 2024

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) report states that the diagnosis of COPD should be considered in individuals with chronic respiratory symptoms and/or exposure to risk factors. Forced spirometry demonstrating airflow obstruction after bronchodilation is required to confirm the diagnosis using a threshold of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7. This GOLD Science Committee review weighs the evidence for using pre- or post-bronchodilator (BD) spirometry to diagnose COPD. Cohort studies have shown that pre- and post-BD spirometry give concordant diagnostic results in most cases, although the prevalence of COPD is up to 36% lower with post-BD values. Discordant results may occur in “volume” or “flow” responders. Volume responders have reduced FVC due to gas trapping causing FEV1/FVC ≥0.7 pre-BD, but a volume response occurs post-BD with a greater improvement in FVC relative to FEV1decreasing the ratio to <0.7. Flow responders show a greater FEV1improvement relative to FVC which may increase FEV1/FVC from <0.7 pre-BD to ≥0.7 post-BD; these individuals have an increased likelihood of developing post-BD obstruction during follow-up and require monitoring longitudinally. GOLD 2025 recommends using pre-BD spirometry to rule out COPD and post-BD measurements to confirm the diagnosis. This will reduce clinical workload. Post-BD results close to the threshold should be repeated to ensure a correct diagnosis is made. Post-BD measurements ensure that volume responders are not overlooked and limit COPD overdiagnosis.
Dynamic regulation of proximal tubular autophagy from injury to repair after ischemic kidney damage
Authors: Gong Yuhong , Zhu Wei , Li Yongqiang , Lu Tao , Tan Jiexing , He Changsheng , Yang Luodan , Zhu Yufeng , Gong Li
Published: December 2024

Background

The role of proximal tubular autophagy in repairing kidney injury following ischemia remains unclear.

Methods

In this study, we utilized mice with conditional deletion of the Atg5 gene in proximal tubules and monitored the long-term dynamic regulation of autophagy following ischemic acute kidney injury (AKI).

Results

The results showed that Atg5-deficient proximal tubule epithelial cells exhibited damaged mitochondria, concentric membranes, and lysosomal accumulation 24 h after ischemia/reperfusion. However, 28 days after ischemia/reperfusion, concentric membrane bodies remained, but lysosomal accumulation was no longer observed. Notably, the absence of Atg5 in renal tubular epithelial cells impaired renal function and led to increased tubular cell proliferation and oxidative stress in the early stage of injury. However, during the repair period following AKI, Atg5 deficiency exhibited no significant difference in the expression of proliferating cell nuclear antigen (PCNA) and 4-hydoxynonenal (4HNE), suggesting that the improvement in renal fibrosis associated with Atg5 deficiency is unlikely to result from its effect on cell proliferation or reactive oxygen species levels. Additionally, Atg5 deficiency inhibits the secretion of profibrotic factor fibroblast growth factor 2 (FGF2) from the early stage of renal injury to the recovery stage of AKI, indicating that autophagy-specific regulation of FGF2 secretion is a dynamic process overlapping with other stages of injury. Furthermore, increased co-localization of ATG5 with 4HNE and FGF2 was observed in patient samples.

Conclusion

In summary, our results suggest that the dynamic regulation of autophagy on key molecules involved in kidney injury and repair varies with the stage of kidney injury.

Graphical Abstract
A natural history study of pediatric patients with early onset of GM1 gangliosidosis, GM2 gangliosidoses, or gaucher disease type 2 (RETRIEVE)
Authors: Héron Bénédicte , Batzios Spyros , Mengel Eugen , Giugliani Roberto , Patterson Marc , Gautschi Matthias , Cornelisse Peter , Trokan Luba , Schwierin Barbara , Rohrbach Marianne
Published: December 2024

Background

The GM1 and GM2 gangliosidoses and type 2 Gaucher disease (GD2) are inherited lysosomal storage disorders with most cases having symptom onset in infancy and reduced life expectancy. The conditions are rare, and there is therefore a need for accurate and up to date information concerning the disease course and survival to assist in the design of clinical trials. RETRIEVE is a natural history study aiming to: (1) collect data on the survival of patients with early-onset (onset of first neurological manifestation before 24 months of age) GM1, GM2, or GD2; (2) collect data that could constitute a historical control group for future clinical trials; and (3) evaluate whether the conditions can be assessed together in a single interventional clinical trial. Group A included patients who were deceased or with unknown survival status at enrollment and was thus limited to retrospective data. Group B included patients who were alive at enrollment, who were followed prospectively with additional retrospective data collection.

Results

Group A included 185 patients (60 with GM1, 78 with GM2, and 47 with GD2), and Group B included 40 patients (18 with GM1, 16 with GM2, and 6 with GD2). Mean and median age at diagnosis and age at onset of first neurological manifestation were youngest in patients with GD2 and oldest in patients with GM2 in both groups. In Group A, median (95% CI) survival was 19.0 (18.0, 22.0), 44.0 (37.0, 51.9) and 14.0 (10.0, 16.0) months in patients with GM1, GM2 and GD2, respectively. In Group B, hypotonia was experienced by most patients with GM1 (17/18, 94.4%), and was less common in patients with GM2 (12/16, 75.0%) and GD2 (4/6, 66.7%). Strabismus and splenomegaly were reported in all six patients with GD2.

Conclusions

RETRIEVE is one of the largest natural history studies of GM1, GM2, and GD2. Results were generally consistent with the published literature, with differences potentially due to variation in inclusion criteria. The difference in median survival between patients with early-onset GM1, GM2, and GD2 reported in this study suggests that the three diseases should not be pooled for study in clinical trials.
Global longitudinal strain in pre-symptomatic patients with mutation for transthyretin amyloidosis
Authors: Canciello Grazia , Tozza Stefano , Todde Gaetano , Nolano Maria , Borrelli Felice , Palumbo Giovanni , Lombardi Raffaella , Cassano Emanuele , Acampa Wanda , Esposito Giovanni , Manganelli Fiore , Losi Maria Angela
Published: December 2024

Background

Hereditary transthyretin (ATTRv) amyloidosis is rare, autosomal dominant disease with a fatal outcome if left untreated. Early stages detection is crucial for intervention. We aimed identifying early indexes of cardiac involvement and their eventual correlation with neurological indexes, in pre-symptomatic subjects with TTR gene mutation.

Methods

Sixteen TTR-mutation carriers (mean age 51 ± 9 years, 6 males, 7 with Val30Met and 9 with Phe64Leu mutation) without left ventricular hypertrophy were studied. Predicted Age of Disease Onset (PADO) and time to PADO (Time-to PADO = PADO-age at evaluation) were computed. Subjects underwent: cardiological and echocardiographic assessment including global longitudinal strain (GLS); tactile and thermal quantitative sensory testing (QST); Perugini score by bone scintigraphy.

Results

Time to PADO was 30 ± 15 years. Nine subjects showed abnormal GLS (> −20%), unrelated to age, LVMi, MWT, E/e’, NT-proBNP or Time-to PADO. QST findings were abnormal in most subjects. At a worse cold pain threshold corresponded a worse GLS (r = 0.786, p < 0.001). Perugini score was positive in 1 subject.

Conclusions

GLS and QST findings support an early involvement of heart and small nerve fibers even many years before PADO. Interestingly, cardiac impairment seems to parallel that of small, nerve fibers, at least in the earliest stage of disease.
A child opportunity index in Italy: a pilot proposal
Authors: Ferrara Pietro , Cipolla Domenico , Corsello Giovanni , Lagalla Luca M. , Tantillo Matilde , Galione Giusyelisa , Martorana Chiara , Mazzone Teresa , Zona Margherita , Cammisa Ignazio
Published: December 2024

Background

The Child Opportunity Index (COI) is a new and innovative tool designed to assess the environment in which children grow up, offering a broad evaluation of the opportunities available to them in different neighborhoods. This initiative aims to ensure improvements in children’s living conditions and future health outcomes.

Methods

The study was performed in the cities of Palermo and Rome. Our Italian COI consists of three main domains: education, health and environment, and economy, each subdivided into specific indicators. We collected information, when available, useful for our indicators from institutional sites and municipal archives. Furthermore, in the city of Rome, we distributed a questionnaire through local pediatricians, collecting data in 2 randomly chosen neighborhoods with questions on children’s health and quality of life, proposing an initial approach that, when implemented using data provided by the government and public and private health institutions, aims to evaluate the correlation between socio-economic opportunities and the psycho-physical health of children, as demonstrated in the literature.

Results

As a result, many aspects, such as the rate of air pollution or the illegal occupation of houses, were not taken into consideration. We therefore consider our COI proposal only a starting model that will have to be implemented once all the necessary information has been obtained. However, what can be deduced from this first descriptive study is how the opportunities in different neighborhoods are not the same for all children. The number of educational opportunities as well as the number of environmental opportunities differs between the various districts and is not homogeneous between different cities or within the same city.

Conclusions

In conclusion, it is not simple to analyze in a scientific manner the child’s health impact of living in different areas. The COI could be a useful and simple tool that can give us this information. Pediatricians could collaborate with institutions to implement intervention plans and to reduce existing differences, social and health inequalities. Future studies will have to implement this pilot study to create and validate an Italian model of COI to be used as a useful tool in children’s assistance.
Assessment of vascular invasion of pancreatic ductal adenocarcinoma based on CE-boost black blood CT technique
Authors: Lin Yue , Liu Tongxi , Hu Yingying , Xu Yinghao , Wang Jian , Guo Sijia , Xie Sheng , Sun Hongliang
Published: December 2024

Objectives

To explore the diagnostic efficacy of advanced intelligent clear-IQ engine (AiCE) and adaptive iterative dose reduction 3D (AIDR 3D), combination with and without the black blood CT technique (BBCT), for detecting vascular invasion in patients diagnosed with nonmetastatic pancreatic ductal adenocarcinoma (PDAC).

Methods

A total of 35 consecutive patients diagnosed with PDAC, proceeding with contrast-enhanced abdominal CT scans, were enrolled in this study. The arterial and portal venous phase images were reconstructed using AiCE and AIDR 3D. The corresponding BBCT images were established as AiCE–BBCT and AIDR 3D–BBCT, respectively. Two observers scored the image quality independently. Cohen’s kappa (k) value or intraclass correlation coefficient (ICC) was used to analyze consistency. The diagnostic performance of four algorithms in detecting vascular invasion in PDAC patients was assessed using the area under the curve (AUC).

Results

The AiCE and AiCE–BBCT groups demonstrated superior image noise and diagnostic acceptability compared with AIDR 3D and AIDR 3D–BBCT groups (all p < 0.001), and the k value was 0.861–0.967 for both reviewers. In terms of diagnostic capability for vascular invasion in PDAC, the AiCE–BBCT group exhibited higher specificity (95.0%) and sensitivity (93.3%) compared to the AIDR 3D and AIDR 3D–BBCT groups, with an AUC of 0.942 (95% CI: 0.849–1.000, p < 0.05). Furthermore, all vascular evaluations conducted using AiCE–BBCT demonstrated better consistency (ICC: 0.847–0.935).

Conclusion

The BBCT technique in conjunction with AiCE could lead to notable enhancements in both the image quality of PDAC images and the diagnostic performance for tumor vascular invasion.

Critical relevance statement

Better diagnostic accuracy of vascular invasion of PDAC based on BBCT in combination with an AiCE is a critical factor in determining treatment strategies and patient outcomes.

Key Points

Identifying vascular invasion of PDAC is important for prognostication.

Combined images provide improved image quality and higher diagnostic accuracy.

Combined images can excellently display the vascular wall and invasion.

Graphical Abstract
Prevalence and molecular characterization of ESBL-producing Enterobacteriaceae in Egypt: a systematic review and meta-analysis of hospital and community-acquired infections
Authors: Azzam Ahmed , Khaled Heba , Samer Dareen , Nageeb Wedad M.
Published: December 2024

Background

ESBL-producing Enterobacteriaceae (ESBL-PE) represent a significant global health threat. In response to this growing concern and the lack of a surveillance system for ESBL-PE infections in Egypt, we conducted this meta-analysis. In this study, we aimed to quantify the prevalence of ESBL-PE based on the source of infection and characterize their molecular dissemination. Additionally, we sought to uncover temporal trends to assess the spread of ESBL-PE over time.

Methods

A comprehensive literature search was conducted in PubMed, Scopus, Google Scholar, Web of Science, and the Egyptian Knowledge Bank to identify studies that: (1) report the prevalence of ESBL-PE in Egypt; (2) use valid detection methods; (3) involve clinical specimens; and (4) were published between 2010 and 2024. The quality of the included studies was evaluated using the “Joanna Briggs Institute Critical Appraisal Checklist”. Meta-analysis was performed using the R meta package, reporting pooled prevalence with 95% confidence intervals (CI) via a random effects model.

Results

This meta-analysis included 34 studies with 4,528 isolates, spanning 2007 to 2023. The overall prevalence of ESBL-PE in Egypt was 60% (95% CI: 54–65). The leave-one-out meta-analysis demonstrated the absence of influential outliers and Egger’s test indicated no evidence of publication bias (P = 0.25). The prevalence of ESBL-PE was 62% (95% CI: 55–68) in nosocomial infections and 65% (95% CI: 52–75) in community-acquired infections, with no statistically significant difference (P = 0.68). The prevalence of ESBL producers in E. coli (64%) and K. pneumoniae (63%) is higher than in Proteus mirabilis (46%) (P = 0.06). Temporal analysis showed a stable ESBL prevalence over time. Moreover, in phenotypically confirmed ESBL-producing, E. coli harboring blaCTX−M was most prevalent (73%), followed by blaTEM (60%) and blaSHV (22%), with significant differences (P < 0.01). Subsequent analysis identified blaCTX−M−15 as the predominant variant of the blaCTX−M gene.

Conclusions

The prevalence of ESBL-PE in Egypt is alarmingly high at 60%. The observed high rates in both hospital and community-acquired infections underscore the need for public health strategies targeting both settings. One limitation of this study is the high heterogeneity, which partly attributed to regional and institutional variations in antibiotic use and stewardship practices.