bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining what works for whom and how in mindfulness-based cognitive therapy (MBCT) for recurrent depression: moderated-mediation analysis in the PREVENT trial
Authors: Montero-Marin Jesus , Hinze Verena , Maloney Shannon , van der Velden Anne Maj , Hayes Rachel , Watkins Edward R. , Byford Sarah , Dalgleish Tim , Kuyken Willem
Published: November 2024

Background

Personalised management of recurrent depression, considering individual patient characteristics, is crucial.

Aims

This study evaluates the potentially different mediating role of mindfulness skills in managing recurrent depression using mindfulness-based cognitive therapy (MBCT) among people with varying depression severity.

Method

Data from the Prevention of Depressive Relapse or Recurrence (PREVENT) trial, comparing MBCT (with antidepressant medication (ADM) tapering support, MBCT-tapering support) versus maintenance-ADM, were used. The study included pre, post, 9-, 12-, 18- and 24-month follow-ups. Adults with ≥3 previous major depressive episodes, in full/partial remission (below threshold for a current episode), on ADM, were assessed for eligibility in primary care practices in the UK. People were randomised (1:1) to MBCT-tapering support or maintenance-ADM. We used the Beck Depression Inventory-II to evaluate depressive symptom changes over the six time points. Pre-post treatment, we employed the Five Facets of Mindfulness Questionnaire to gauge mindfulness skills. Baseline symptom and history variables were used to identify individuals with varying severity profiles. We conducted Latent Profile Moderated-Mediation Growth Mixture Models.

Results

A total of 424 people (mean (s.d.) age = 49.44 (12.31) years; with 325 (76.7%) self-identified as female) were included. A mediating effect of mindfulness skills, between trial arm allocation and the linear rate of depressive symptoms change over 24 months, moderated by depression severity, was observed (moderated-mediation index = −0.27, 95% CI = −0.66, −0.03). Conditional indirect effects were −0.42 (95% CI = −0.78, −0.18) for higher severity (expected mean BDI-II reduction = 10 points), and −0.15 (95% CI = −0.35, −0.02) for lower severity (expected mean BDI-II reduction = 3.5 points).

Conclusions

Mindfulness skills constitute a unique mechanism driving change in MBCT (versus maintenance-ADM). Individuals with higher depression severity may benefit most from MBCT-tapering support for residual symptoms. It is unclear if these effects apply to those with a current depressive episode. Future research should investigate individuals who are not on medication. This study provides preliminary evidence for personalised management of recurrent depression.

Trial Registration:

ISRCTN26666654.
Impact of DPP-4 Inhibitors on Interleukin Levels in Type 2 Diabetes Mellitus
Authors: Feng Yiduo , Shang Beibei , Yang Yu , Zhang Donglei , Liu Changbin , Qin Zheng , Zhou Yilun , Meng Jie , Liu Xin
Published: November 2024

Background and Objective

Accumulating evidence had implicated pathological involvement of interleukins (ILs) in progression and complications in patients with type 2 diabetes mellitus (T2DM). Dipeptidyl peptidase-4 inhibitors (DPP-4i) produced favorable effects on glucose homeostasis in T2DM. This study aimed to evaluate the impact of DPP-4i on IL concentrations in T2DM.

Data Sources

PubMed, Embase, and the Cochrane library were systematically searched for relevant articles from inception to May 31, 2024. The search included DPP-4i, T2DM, and randomized controlled trials (RCTs) and related terms.

Study Selection and Data Extraction

Placebo- or active agents-controlled human studies were screened. All the RCTs were identified if they provided detailed information on changes of ILs during DPP-4i treatment.

Data Synthesis

A total of 14 RCTs involving 850 participants were identified. Pooled estimates revealed that DPP-4i significantly lowered IL-6 concentrations (−0.54 pg/mL; 95% CI, −0.82 to −0.25; I2 = 10%, P = .0003) compared to placebo. Similar effects were demonstrated for IL-1β (−16.33 pg/mL; 95% CI, −19.56 to −13.11; I2 = 0%, P < .00001), whereas the effect on IL-18 was not statistically significant (−13.55 pg/mL; 95% CI, −76.95 to 49.85; I2 = 0%, P = .68). Subgroup analysis on IL-6 demonstrated that marked effects were found in groups of basal IL-6 concentrations (< 5 pg/mL), body mass index (≥ 28 kg/m2) and type of DPP-4i (linagliptin).

Conclusion

DPP-4i favorably decreased IL-6 levels in patients with T2DM. The impact of DPP-4i on IL-1β and IL-18 needed to be explored with more studies. Further trials should be performed to elucidate this anti-inflammatory effect of DPP-4i during treatment of T2DM.
Homozygous Familial Hypercholesterolemia in Spain: Data From Registry of the Spanish Atherosclerosis Society
Authors: Sánchez-Hernández Rosa M , Ibarretxe Daiana , Fuentes Jiménez Francisco , Martínez-Hervás Sergio , Blanco-Echevarría Agustín , Cortés Rodríguez Begoña , Rodríguez-Carnero Gemma , Martín Ordiales María Mercedes , Pérez Antonio , González-Bustos Pablo , Argüeso Armesto Rosa , Sánchez-Sobrino Paula , Masana Luis , Civeira Fernando
Published: November 2024

Context

Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by the presence of 2 pathogenic variants in the LDLR, APOB, PCSK9, or LDLRAP1 genes, which cause very high levels of LDL-cholesterol and premature atherosclerotic cardiovascular disease (ASCVD).

Objective

To analyze the current situation regarding diagnosis, cardiovascular disease, lipid-lowering treatment, and degree of control of lipids in patients with HoFH in the National Dyslipidemia Registry of the Spanish Atherosclerosis Society.

Methods

Subjects with HoFH, confirmed by the presence of 2 pathogenic variants in the genes mentioned above, included in the registry from 2013 to June 2023 with an updated review were analyzed.

Results

Of 71 included subjects with HoFH, 40.8% were women, aged 52 [24-62] years, 57 adults and 13 children. The median follow-up was 7 [4-13] years. Age of diagnosis was 14 [2-26] years, with 10% of ASCVD at diagnosis and 27% of current ASCVD at 40.6 (13.4) years of age; 38% were on PCSK9 inhibitors, 9 patients on lomitapide, 9 on LDL apheresis, and 1 patient on evinacumab. Subjects with more than 4 therapies achieved >80% reduction in LDLc. In the last visit, the median LDLc was 139.3 [89.4-204.2] mg/dL. ASCVD was strongly associated with male sex and family history of ASCVD, relative risk 5.26 (1.53-18.10) and 2.53 (1.03-6.26), P < .05, respectively. Only 18% and 10% meet the recommended LDLc goal in primary and secondary prevention respectively.

Conclusion

The current situation of HoFH in Spain is better than expected, with marked reductions in LDLc levels with new treatments. In this population, recommended LDLc goals are difficult to achieve despite maximum lipid-lowering therapy. ASCVD has been reduced and delayed by 2 decades.
RNA-first Approach Identifies Deep Intronic PHEX Variants in X-linked Hypophosphatemic Rickets
Authors: Ludwig Karissa , Wu Zenghui , Bardai Ghalib , Miranda Valancy , Alos Nathalie , Ward Leanne M , Rauch Frank
Published: November 2024

Context

Up to 20% of patients with X-linked hypophosphatemic rickets (XLH) have no causative variant identified on routine molecular diagnostic testing.

Objective

To identify intronic variants causing PHEX mis-splicing in patients with XLH.

Setting

The metabolic bone clinic of a pediatric orthopedic hospital.

Participants

Four patients (age 6 to 12 years; 3 girls) with clinically diagnosed XLH and no PHEX variant on routine testing.

Main Outcome Measures

RNA and DNA sequence analysis of PHEX.

Methods

Urine-derived cells were cultured, and mRNA was extracted and transcribed to cDNA. PHEX cDNA was amplified by PCR, followed by sequencing of PCR products. Sequencing of PHEX intronic DNA regions was performed to identify variants causing mis-splicing observed on RNA analysis.

Results

PHEX mis-splicing was identified in 3 of the 4 participants, and an intronic variant was identified in all 3 cases. In a 12-year-old boy, transcript analysis showed skipping of PHEX exon 13, while sequencing of PHEX intronic regions revealed a de novo 18 bp deletion in intron 13. In a 7-year-old girl, a pseudoexon in PHEX intron 17 was found, associated with a de novo deep intronic variant (c.1768 + 173A > G) that activated a cryptic splice donor site. Finally, an 84 bp pseudoexon in PHEX intron 21 caused by a recurrent de novo deep intronic variant (c.2147 + 1197A > G) was identified in an 11-year-old girl.

Conclusion

Analysis of RNA from urine-derived cells combined with sequencing of PHEX introns can identify deep intronic variants in individuals with XLH without a detectable PHEX variant in routine exon-centric molecular diagnosis.
F2-Isoprostanes Are Associated With Increased Fracture Risk in Type 2 Diabetes
Authors: Wang Bowen , Dhaliwal Ruban , Ewing Susan K , Schwartz Ann V , Vashishth Deepak
Published: November 2024

Context

Fracture risk is higher in type 2 diabetes (T2D) for a given bone mineral density (BMD) level. Increased oxidative stress in T2D induces diabetic complications and may affect T2D bone fragility.

Objective

To investigate whether the levels of plasma F2-isoprostanes, a reliable oxidative stress marker, are associated with incident clinical fracture risk in older adults with diabetes.

Methods

An observational cohort study was conducted in a well-characterized cohort from Health, Aging, and Body Composition study.

Participants

Older Black and White ambulatory adults with baseline plasma F2-isoprostanes measurements (baseline age 70-79 years, T2D: N = 132; nondiabetes: N = 571) were selected from the study cohort of 3075 individuals. Risk of incident clinical fractures was assessed.

Results

In the Cox proportional hazard model with multivariate adjustments (including BMD, medications, and other risk factors), a 93% increase in incident clinical fracture risk was significantly associated with each SD increase in log plasma F2-isoprostanes in the T2D group (hazard ratio [HR] = 1.93 [95% CI, 1.26-2.9] P = .002), but there was no evidence of an association in the nondiabetes group (HR = 0.98 [95% CI 0.81-1.18] P = .79, P for interaction <.001). Log plasma F2-isoprostanes were moderately correlated with a decline in baseline total hip BMD (r = −0.25, P = .003), and with a 4-year decrease in total hip BMD (r = −0.28, P = .008) in T2D. There was no evidence of correlation between log plasma F2-isoprostanes and circulating glycoxidation markers or bone turnover markers in either group.

Conclusion

Plasma F2-isoprostanes levels in individuals with diabetes are associated with increased incident clinical fracture risk independently of baseline BMD.
Genetics and Bone Mineral Density Predict the Fractures in Adults With Osteogenesis Imperfecta: A Prospective Study
Authors: Blandin Camille , Collet Corinne , Ostertag Agnes , Funck-Brentano Thomas , Cohen-Solal Martine
Published: November 2024

Context

Osteogenesis imperfecta (OI) is a rare genetic bone disorder characterized by recurrent fractures. In adults, the value of bone mineral density (BMD) in fracture risk is unknown.

Objective

We prospectively investigated changes in BMD over time and analyzed the determinants of fracture in OI.

Methods

Among 106 individuals with grade 1 and 4 OI in the Reference Centre of Rare Bone Diseases in Paris, we included those with BMD measurements at 1 or more skeletal sites (hip, lumbar spine, radius) from 2000 to 2022.

Results

For 71 individuals with reliable measurements (44 women, 8 postmenopausal; mean age 41.4 ± 13.7 years), baseline BMD was low at the lumbar spine only (mean Z-score −2.3 ± 1.5), affecting mainly men (mean Z-score −3 ± 1.6). Longitudinal changes were assessed for a median follow-up of 5.1 years (interquartile range 3.2-8.8). On adjustment for age, sex, and body mass index, BMD did not significantly change at any site. Logistic regression analysis revealed a high probability of fracture with baseline BMD Z-score <−2 SD vs ≥−2 SD [odds ratio 4.38, 95% confidence interval (CI) 1.10-21.75, P = .048] and harboring splicing, stop codon, and frameshift variants of COL1 gene (odds ratio 29.8, 95% CI 2.56-1503, P = .024).

Conclusion

Our OI cohort showed low BMD at the lumbar spine but no significant change at any site after a median of 5.0 years of follow-up. The probability of fracture was associated with baseline BMD Z-score <−2 SD vs ≥−2 SD and harboring COL1 splicing, stop codon, and frameshift variants.
Establishment of CRISPR/Cas9-based knock-in in a hemimetabolous insect: targeted gene tagging in the cricket Gryllus bimaculatus
Authors: Matsuoka Yuji , Nakamura Taro , Watanabe Takahito , Barnett Austen A. , Tomonari Sayuri , Ylla Guillem , Whittle Carrie A. , Noji Sumihare , Mito Taro , Extavour Cassandra G.
Published: November 2024

Studies of traditional model organisms such as the fruit fly Drosophila melanogaster have contributed immensely to our understanding of the genetic basis of developmental processes. However, the generalizability of these findings cannot be confirmed without functional genetic analyses in additional organisms. Direct genome editing using targeted nucleases has the potential to transform hitherto poorly understood organisms into viable laboratory organisms for functional genetic study. To this end, we present a method to induce targeted genome knockout and knock-in of desired sequences in an insect that serves as an informative contrast to Drosophila, the cricket Gryllus bimaculatus. The efficiency of germline transmission of induced mutations is comparable with that reported for other well-studied laboratory organisms, and knock-ins targeting introns yield viable, fertile animals in which knock-in events are directly detectable by visualization of a fluorescent marker in the expression pattern of the targeted gene. Combined with the recently assembled and annotated genome of this cricket, this knock-in/knockout method increases the viability of G. bimaculatus as a tractable system for functional genetics in a basally branching insect.
Differential vegfc expression dictates lymphatic response during zebrafish heart development and regeneration
Authors: Duca Sierra , Xia Yu , Abd Elmagid Laila , Bakis Isaac , Qiu Miaoyan , Cao Yingxi , Guo Ylan , Eichenbaum James V. , McCain Megan L. , Kang Junsu , Harrison Michael R. M. , Cao Jingli
Published: November 2024

Vascular endothelial growth factor C (Vegfc) is crucial for lymphatic and blood vessel development, yet its cellular sources and specific functions in heart development remain unclear. To address this, we created a vegfc reporter and an inducible overexpression line in zebrafish. We found vegfc expression in large coronary arteries, circulating thrombocytes, cardiac adipocytes, and outflow tract smooth muscle cells. Notably, although coronary lymphangiogenesis aligns with Vegfc-expressing arteries in juveniles, it occurs only after coronary artery formation. Vegfc overexpression induced ectopic lymphatics on the ventricular surface prior to arterial formation, indicating that Vegfc abundance, rather than arterial presence, drives lymphatic development. However, this overexpression did not affect coronary artery coverage, suggesting a specific role for Vegfc in lymphatic, rather than arterial, development. Thrombocytes emerged as the initial Vegfc source during inflammation following heart injuries, transitioning to endocardial and myocardial expression during regeneration. Lower Vegfc levels in an amputation model corresponded with a lack of lymphatic expansion. Importantly, Vegfc overexpression enhanced lymphatic expansion and promoted scar resolution without affecting cardiomyocyte proliferation, highlighting its role in regulating lymphangiogenesis and promoting heart regeneration.
Shear stress-stimulated AMPK couples endothelial cell mechanics, metabolism and vasodilation
Authors: Cronin Nicholas M. , Dawson Logan W. , DeMali Kris A.
Published: November 2024

Endothelial cells respond to mechanical force by stimulating cellular signaling, but how these pathways are linked to elevations in cell metabolism and whether metabolism supports the mechanical response remains poorly understood. Here, we show that the application of force to endothelial cells stimulates VE-cadherin to activate liver kinase B1 (LKB1; also known as STK11) and AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis. VE-cadherin-stimulated AMPK increases eNOS (also known as NOS3) activity and localization to the plasma membrane, reinforcement of the actin cytoskeleton and cadherin adhesion complex, and glucose uptake. We present evidence for the increase in metabolism being necessary to fortify the adhesion complex, actin cytoskeleton and cellular alignment. Together, these data extend the paradigm for how mechanotransduction and metabolism are linked to include a connection to vasodilation, thereby providing new insight into how diseases involving contractile, metabolic and vasodilatory disturbances arise.
Topology surveillance of the lanosterol demethylase CYP51A1 by signal peptide peptidase
Authors: Sergejevs Nikita , Avci Dönem , van de Weijer Michael L. , Corey Robin A. , Lemberg Marius K. , Carvalho Pedro
Published: November 2024

Cleavage of transmembrane segments on target proteins by the aspartyl intramembrane protease signal peptide peptidase (SPP, encoded by HM13) has been linked to immunity, viral infection and protein quality control. How SPP recognizes its various substrates and specifies their fate remains elusive. Here, we identify the lanosterol demethylase CYP51A1 as an SPP substrate and show that SPP-catalysed cleavage triggers CYP51A1 clearance by endoplasmic reticulum-associated degradation (ERAD). We observe that SPP targets only a fraction of CYP51A1 molecules, and we identify an amphipathic helix in the CYP51A1 N terminus as a key determinant for SPP recognition. SPP recognition is remarkably specific to CYP51A1 molecules with the amphipathic helix aberrantly inserted in the membrane with a type II orientation. Thus, our data are consistent with a role for SPP in topology surveillance, triggering the clearance of certain potentially non-functional conformers.
Systematic review of ethics and legislation of a Global Patient co-Owned Cloud (GPOC)
Authors: Lidströmer Niklas , Herlenius Eric
Published: November 2024

Background The use of cloud-based storage for personal health records (PHRs) has significantly increased globally over the past thirty years. The four recently published GPOC Series articles introduced the concept of a Global Patient co-Owned Cloud (GPOC) for personal health records. The series includes a systematic review and meta-analysis, a summit, a sandbox, and a survey, with 100% participation from UN member states and key international health organisations. GPOC aims to establish patient co-ownership of PHRs, addressing integration and access challenges. Methods This study is built upon the published GPOC systematic review and meta-analysis that focused on examining cloud-based personal health records and elements such as data security, efficiency, performance, privacy and cost-based factors. However, this study selectively reviews the ethical, legislative and potential human rights dimensions of GPOC. Thus, it includes ethical aspects of co-ownership, rights, privacy, policies, and AI integration. The original study was PROSPERO registered with CRD42022342597, which serves as the foundation for the current study. Results This study offers a comprehensive global overview of ethics, legislation and initiatives by states and organisations. We analyse AI integration and future challenges for GPOC implementation. We present principles from ‘Ethics by Design’ and the ‘Principles of Biomedical Ethics’ by Beauchamp and Childress alongside the European General Data Protection Regulation (GDPR). The study presents a global overview of the relevant global latticework of legislation. Conclusions This study suggests that GPOC could potentially establish a new human right to patient co-ownership of personal health information. GPOC aims to facilitate global AI integration in healthcare and address existing challenges in PHR integration. A decentralised GPOC, supported by blockchain consensus, may offer benefits such as enhanced data security, interoperability, and equitable access to healthcare information globally. Thus, GPOC may have a positive impact on global health.
Association between Hematological Parameters and Severity of COVID-19 disease
Authors: Krishnan Gokul , Karanth Shubhada , Vidyasagar Sudha , Aggarwal Archit , Udupi Anurupa , Karanth Suresh , Kaniyoor Nagri Shivashankara
Published: November 2024

Background This study aimed to determine the relationships between hematological parameters- hemoglobin, Total Leucocyte Counts (TLC), platelet counts, Absolute Neutrophil Counts (ANC), Absolute Lymphocyte Counts (ALC), Neutrophil Lymphocyte Ratio (NLR), Systemic Immune Inflammatory Index (SII), Neutrophil Monocyte Ratio (NMR), Platelet Lymphocyte Ratio (PLR) and the severity of COVID-19 disease and their use in predicting severity of COVID-19 disease. Methods and Material This was a prospective, observational, single-center study of 573 symptomatic adult inpatients of COVID 19 admitted to our tertiary care center. Statistical analysis used The above-mentioned hematological parameter levels were noted and compared between the two categories of COVID-19 disease, namely non-severe and severe COVID-19 using logistic regression methods. Their cut-off values were detected using the ROC curve. Results The median TLC, ANC, NLR, SII, NMR, PLR were notably higher in patients with severe COVID-19 than in those with non-severe COVID-19. Logistic regression analysis showed that NMR (OR=1.029, p=0.006) and ALC (OR=0.999, p=0.002) were statistically significant independent predictors of COVID-19 severity. Conclusions The hematological parameters mentioned, can be used for predicting severe COVID-19 disease at admission. ALC and NMR levels could be used as hematological markers to predict severity of COVID-19 in adult patients with their cut off values being < 1105 cells/cubic millimeter and > 10.434 respectively.
Migration, Urbanism and Health: Moving Toward Systems-Informed Policy and Practice
Authors: Immordino Palmira , Sà Machado Rita , Hargreaves Sally , Honsell Furio , Lau Karen , Pascut Stefania , Torres Irene , Xiao Yang , Ziersch Anna , Zimmerman Cathy
Published: November 2024

Migration and displacement are pivotal determinants of urban health, influencing both direct and indirect health outcomes. Migrants may face unique health risks, often exacerbated by economic, social, and environmental factors encountered during transit or upon resettlement. As migration patterns shift due to geopolitical, climatic, and economic pressures, they reshape the global and urban policy landscapes in unpredictable ways, presenting challenges that will continue to evolve in the coming decades. Current legal frameworks, in many cases, do not adequately account for migrant populations, hindering policy responses and complicating the protection of migrant health. Therefore, effective urban health interventions must be inclusive of migrant populations and expand beyond healthcare services. A systems-thinking approach that recognizes the broader determinants of health—including housing, employment, social services, and urban infrastructure—is essential to address the intersecting challenges migrants face. Despite these challenges, migration remains crucial to the functioning of urban environments. Migrant workers consistently contribute to the healthy operation of cities, underpinning key infrastructure and services. However, to optimize policy responses and improve urban health outcomes, more robust data and evidence on the health risks and outcomes of migrants, as well as the structural drivers of migration, are needed. Moreover, macro factors such as climate change, future pandemics, and geopolitical shifts are likely to influence both migration dynamics and migrant health. To anticipate and respond to these evolving challenges, a systems-informed and holistic vision of urban health is required—one that integrates migration into the broader urban policy and planning frameworks to foster healthier, more resilient cities.
Antibiotics in honey: a comprehensive review on occurrence and analytical methodologies.
Authors: Rodrigues Helena , Leite Marta , Oliveira Beatriz , Freitas Andreia
Published: November 2024

Honey is a food of great nutritional importance and has always been used for human consumption. The production of honey and other beekeeping products depends on the proper functioning of this extremely important sector, as it has a direct impact on other sectors such as agriculture. The decline in bee colony numbers has been linked, among other factors, to bacterial diseases affecting bees, including American and European foulbrood, and Nosema spp. disease. In this matter, prophylactic or therapeutic use of veterinary drugs in apiculture is common but can lead to their accumulation in bees and in honey. Consumption of contaminated honey can have adverse effects such as allergic or hypersensitivity reactions, carcinogenicity, reproductive effects, and teratogenicity. Commission Regulation (EU) N⍛ 37/2010 sets MRLs for antibiotics in various foods, but these limits are not set for api-products. The lack of harmonized rules has led some countries to set recommended concentrations and minimum performance limits. Nonetheless, to achieve this goal, development of accurate and precise analytical methodologies is crucial. In recent years, the analysis of antibiotics in honey has led to the development of methods in an extensive range of families, including aminoglycosides, amphenicols, lincosamides, macrolides, nitroimidazoles, quinolones, sulfonamides, tetracyclines and nitrofurans. This review work entails an in-depth exploration of occurrence studies, extraction methodologies, and analytical techniques for the determination of antibiotics in apiculture products. It was found that the most used extraction methods include solid-phase extraction, dispersed solid or liquid phase extraction and QuEChERS. Due to the complexity of the honey matrix, samples are often diluted or acidified using McIlvaine buffer, H2O, MeOH, acidified ACN and TCA solution. This is usually followed by a purification step using SPE cartridges or PSA. Golden analytical methodologies include high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer (MS/MS) with Orbitrap or Q-ToF detectors.
Numerical model of a top-blown rotary converter preheating and charge heating with an oxy-fuel burner
Authors: Semenov Sergey , Namy Patrick , Kale Aditya , Tsebe Sello
Published: November 2024

Background The present work is conducted in the framework of the SisAl Pilot EU project, which aims to optimize silicon production in Europe by recycling materials and using carbon-emission-friendly technology. Silicon production experiments were conducted on laboratory and pilot scales in different types of furnaces, including top-blown rotary converters (TBRC) used as chemical reactors for molten slag-metal mixtures. In addition to experimental work, process optimization also relies on numerical modelling. Methods In this study, COMSOL Multiphysics® was used for the numerical testing of a new thermal design of TBRC by simulating its preheating and charge heating owing to an external heat source provided by an oxy-fuel burner. Results and conclusions The risk of slag solidification in TBRC during the aluminothermic reduction of silica was assessed. The model predicts that, with a useful burner power of 600 kW, the empty TBRC can be preheated to 1650°C in less than 30 min. Based on this model, the optimum burner power for maintaining the TBRC charge in a liquid state was determined. The influence of the TBRC inclination angle and its rotation frequency was studied numerically.
Advanced photodetector for hybrid PET-MRI systems
Authors: Isayev K , Rasulov O , Sadigova N
Published: November 2024

Background Currently, a wide variety of silicon photomultipliers (SiPMs) are available, each designed for specific applications in fields such as science, medicine, and industry. Advances in production technology have led to the development of more sensitive and efficient photodiodes, which are critical for applications requiring precision, such as medical imaging. Methods A research group has been working on designing a highly sensitive photodiode to enhance the capabilities of next-generation PET-MRI scanners. This involves integrating micropixel avalanche photodiodes (MAPDs) to improve image resolution. The chosen design features deep-immersion MAPDs with a pixel size of 12 microns and a density of 1000 pixels per square millimeter, allowing for high-detail photon detection. The 4x4 mm2 active area is optimized to balance sensitivity and size for high-resolution medical imaging. To produce these photodiodes, the group has outlined a production plan involving 20-inch silicon wafers grown using multiple techniques to enhance material properties. The Malaysian Institute of Microelectronic Systems (MIMOS), renowned for its expertise in optical microelectronics, was selected as the production center. With MIMOS' state-of-the-art facilities, the project aims to meet stringent medical diagnostics standards. Results The experimental results demonstrated that the MAPD-3NM photodiode achieved an amplification factor 1.8 times greater than the MAPD-3NK under optimal conditions. Its overvoltage range increased by 100%, reaching 4 V, enhancing photon detection and amplification. The MAPD-3NM also showed a significant reduction in dark current, about 3.5 times lower than the MAPD-3NK, improving performance in low-light environments. Additionally, the MAPD-3NM had a capacitance of 200 pF compared to 176 pF for the MAPD-3NK, contributing to its superior performance. These improvements make the MAPD-3NM more efficient and sensitive for scientific and medical applications. Conclusions This project represents a major advancement in photodetector technology for medical diagnostics, aiming to develop more accurate and efficient PET-MRI scanners that enhance patient outcomes with improved imaging capabilities.
A protocol for linking participants’ retailer ‘loyalty card’ records into the Avon Longitudinal Study of Parents and Children (ALSPAC)
Authors: Skatova Anya , Boyd Andy
Published: November 2024

Longitudinal population studies (LPS) have a long history of providing insights into how individual consumption patterns and other lifestyle choices affect health and socio-economic outcomes. LPS typically operate as research databanks, integrating rich and deep phenotypic data - covering diverse aspects of individual, family and household status - with genomic data and linked records on health and socio-economic outcomes. However, individual consumption and behavioural choices are traditionally studied solely using self-report methods which are prone to known biases. We propose to enrich LPS databanks with a new form of digital footprint data – individual shopping history records. These are collected by supermarkets through “loyalty” card schemes and can provide a new perspective on real world behaviours and history of consumption. However, as a novel class of data in the context of longitudinal research, our ability to assess the quality and completeness of the data is unknown, as is our ability to effectively triangulate between self-reported and linked data. This paper describes a protocol for linking individual level shopping history data into a LPS using Avon Longitudinal Study of Parents and Children (ALSPAC) as a testbed. The protocol covers the process of establishing participant fair processing, an ethical and legal basis for the linkage framework itself, and how these data will be integrated into the ALSPAC databank. It does not cover the subsequent research use of these data. The protocol was built on an extensive participant engagement and acceptability work and has been approved by the ALSPAC Law and Ethics committee.
Improving health outcomes among older adults in India: effectiveness and implementability of a novel comprehensive geriatric assessment based intervention
Authors: Kshatri Jaya Singh , Shenkin Susan , Mercer Stewart , Weller David , Palo Subrata Kumar , Pati Sandipana , Janssen Daisy , Pati Sanghamitra
Published: November 2024

Background There is significant evidence on the benefits of comprehensive assessment in older adults. But this evidence is primarily from western countries and in secondary care settings. National policies in India recognize this need and envision community-based screening and facility-based assessment programs integrated into the care pathways for the elderly. However, this is yet to translate into specific interventions, primarily due to lack of complex interventions necessary and evidence of their effectiveness. This study aims to design and pilot an integrated (Community + Facility) Elderly Health Status Assessment and Screening (EHSAS) intervention to improve health outcomes of older adults and assess its feasibility for implementation in Indian rural settings. Methods We propose a hybrid design where we will build the complex intervention, develop and validate the tools needed, pilot it using an exploratory cluster randomized trial and evaluate its implementatbility using the Exploration-Preparation-Implementation-Sustainment (EPIS) framework. Conclusions This study will fill critical gaps in evidence regarding the effectiveness of geriatric screening and assessment in community and primary care settings in low-middle income countries and provide validated tools and implementation models for adoption into national programs. Registration CTRI/2023/07/055661
The influence of maternal long term health conditions including multimorbidity on child oral health: A scoping review and evidence gap map protocol
Authors: Campbell Faith , McGregor Scott , Marryat Louise , Stewart Ryan , Clarkson Jan , Cassie Heather
Published: November 2024

Objective This scoping review will map the extent and type of evidence in relation to the association between maternal long term health conditions (LTCs), including multimorbidity, and child oral health. Introduction Newer theories are emerging that detail the many factors that can influence child oral health at child, family and community levels. More recently, the association between maternal general health and child oral health has been explored, with preliminary evidence suggesting a link between shared environmental factors and diet/substance use during pregnancy causing childhood caries. Inclusion criteria All published studies that describe the relationship between maternal LTCs (including multimorbidity) and child oral health. There will be no limitation on the date of publication due to the limited number of studies available from the initial search of PubMed. The review will exclude case studies, abstracts, and grey literature. Literature must be in English language. Methods The following databases will be searched; CINAHL, Cochrane Library, Maternity and Infant Care, Medline via PubMed, Scopus, Web of Science. The search will include sources in English only and will be undertaken between April and July 2024. Studies to be included will be of any type of study design that describe a relationship between maternal long term health conditions, including maternal long term oral health conditions, and child oral health. Data extraction will be undertaken using tabulation of results by at least two independent reviewers. Narrative analysis of the evidence will be undertaken, and results will be presented in a narrative and tabular manner due to the heterogenous and limited evidence base found in the test search. This review has been registered prospectively on Open Science Framework, (https://doi.org/10.17605/OSF.IO/ECSWJ). The review will also inform an Evidence Gap Map (EGM) to illustrate the current evidence base regarding maternal health factors that influence child oral health.
Alterations of Hepcidin and Iron Markers Associated with Obesity and Obesity-related Diabetes in Gambian Women
Authors: Siemonsma Meike , Cerami Carla , Darboe Bakary , Verhoef Hans , Prentice Andrew M. , Jobe Modou
Published: November 2024

Aims Obesity, type 2 diabetes (T2D), and chronic inflammation are associated with disturbances in iron metabolism. Hepcidin is hypothesized to play a role in these alterations owing to its strong association with inflammation via the JAK-STAT3 pathway. The current study investigated the differences between inflammatory markers and iron indices and their association with hepcidin in lean women, women with obesity, and women with obesity and T2D (obesity-T2D) in The Gambia. Materials and methods In a cross-sectional study design, fasted blood samples were collected from three groups of women: lean women (n=42, body mass index (BMI)=20.9 kg/m2), women with obesity (n=48, BMI=33.1 kg/m2) and women with obesity-T2D (n=30, BMI=34.5 kg/m2). Markers of inflammation (IL-6 and CRP) and iron metabolism [hepcidin, iron, ferritin, soluble transferrin receptor (sTfR), transferrin, transferrin saturation, and unsaturated iron-binding capacity (UIBC)] were compared using linear regression models. Simple regression analyses were performed to assess the association between hepcidin levels and respective markers. Results Women with obesity and obesity-T2D showed elevated levels of inflammatory markers. There was no evidence that markers of iron metabolism differed between lean women and obese women, but women with obesity-T2D had higher transferrin saturation, higher serum iron concentration, and lower UIBC. Serum hepcidin concentrations were similar in all the groups. Hepcidin was not associated with markers of inflammation but was strongly associated with all other iron indices (all P<0.002). Conclusion Contrary to our original hypothesis, hepcidin was not associated with markers of inflammation in the three groups of Gambian women, despite the presence of chronic inflammation in women with obesity and obesity-T2D.
CDK4/6 inhibitors display a class effect in inducing differentiation of neuroblastoma cells
Authors: Ferguson Kirsty M. , Abou Grealy Fiona M. Y. , Philpott Anna
Published: November 2024

Background Neuroblastoma is the most common extracranial solid tumour in infants and children, accounting for approximately 15% of paediatric cancer mortality. These tumours are unique in that a subset, namely stage MS, frequently undergo spontaneous regression or differentiation. Differentiation therapy, where cancer cells are re-routed back down their correct developmental pathway, is therefore a promising therapeutic avenue. We have previously shown that the CDK4/6 inhibitor palbociclib induces both decreased proliferation and enhanced neuronal differentiation of neuroblastoma cells in vitro. When combined with retinoic acid, already used clinically for maintenance therapy, this differentiation is enhanced. Methods Here, we investigate two additional CDK4/6 inhibitors, abemaciclib and ribociclib, to induce differentiation of the relapsed, high-risk MYCN-amplified neuroblastoma cell line SK-N-BE(2)C, with and without retinoic acid. We culture SK-N-BE(2)C cells in both adherent and three-dimensional culture and monitor proliferation and differentiation using readouts including live-imaging, immunocytochemistry, qRT-PCR and EdU incorporation. Results We find the CDK4/6 inhibitors palbociclib, abemaciclib and ribociclib all enhance retinoic acid-induced differentiation in both adherent SK-N-BE(2)C cells and 3D spheroids. Conclusions CDK4/6 inhibitors display a class effect in inducing neuronal differentiation together with retinoic acid, both in adherent neuroblastoma cell lines and three-dimensional tumour spheroids. This is an important consideration for potentially developing CDK inhibitor-induced differentiation as a therapy in the clinic.
The genome sequence of the jet ant, Lasius fuliginosus (Latreille, 1798)
Authors: Crowley Liam M. ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: November 2024

We present a genome assembly from an individual female Lasius fuliginosus (the jet ant; Arthropoda; Insecta; Hymenoptera; Formicidae). The genome sequence is 256.2 megabases in span. Most of the assembly is scaffolded into 14 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 18.75 kilobases in length.
The genome sequence of the Purple Bar moth, Cosmorhoe ocellata (Linnaeus, 1758)
Authors: Januszczak Inez , Broad Gavin R. ,   Natural History Museum Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: November 2024

We present a genome assembly from an individual female Cosmorhoe ocellata (the Purple Bar moth; Arthropoda; Insecta; Lepidoptera; Geometridae). The genome sequence has a total length of 327.70 megabases. Most of the assembly (99.54%) is scaffolded into 32 chromosomal pseudomolecules, including the Z and W sex chromosomes. The mitochondrial genome has also been assembled and is 16.09 kilobases in length.
Poemat prozą w Polsce
Authors: Kluba Agnieszka
Published: November 2024

Poemat prozą wiódł dotąd w Polsce żywot utajony. Pozostawał formą rozpoznawaną i podejmowaną przez nielicznych wtajemniczonych, zazwyczaj znawców poezji francuskiej, która ten sposób pisania wynalazła w XIX wieku. Dla pozostałych był czymś w pewnym sensie niewidocznym, nie dość wyczuwalnym i nierzadko mylonym z innymi formami literackimi. O tym nieodczytaniu zdecydowały także przewrotna, dyskretna i stroniąca od pochwytności natura poematu prozą, celowa labilność tożsamości, mylenie tropów, prowadzących zarówno do prozy, jak i do poezji, a może tak naprawdę jeszcze gdzie indziej… „Proza poetów” – tak między innymi mówi się o tej formie, ponieważ z zagadkowych powodów właśnie Ci, którzy piszą wiersze, odczuwają niekiedy potrzebę zwrócenia się ku prozie. Tak jak dwudziestu czterech bohaterów tej książki, pierwszej monografii poematu prozą w Polsce.
Przepisywanie historii. Powstanie styczniowe w powieści polskiej w perspektywie pamięci kulturowej
Authors: Małochleb Paulina
Published: November 2024

Przepisywanie historii. Powstanie styczniowe w powieści polskiej w perspektywie pamięci kulturowej to próba przedstawienia nurtu prozatorskiego poświęconego wydarzeniom 1863 roku obejmująca utwory powstałe na przestrzeni dziesięcioleci, aż do lat osiemdziesiątych XX wieku. Autorka stara się także odpowiedzieć na pytanie o specyfikę polskiej tożsamości narodowej, filary naszej pamięci i wyobrażenie przeszłości. Mit walki zbrojnej oraz ciągła gotowość do instrukcji to najważniejszy aspekt podjętej tu refleksji badawczej. Celem książki jest również ukazanie roli tych wyobrażeń i przyczyn ich trwałości w dobie zaborów, a później PRL-u. W tym kontekście istotne są narodziny mitu klęski styczniowej w XIX wieku, a także próby przewartościowania, jakim poddawano wyobrażenie powstania w dwudziestoleciu międzywojennym i PRL-u. Te trzy warstwy tworzą całość kulturowego testu, wspólnie istnieją w pamięci społecznej. Przedmiotem analizy stają się powieści wybitne, ale też drugorzędne i popularne, utwory krytyczne wobec polskiej tradycji, jak również teksty serwilistyczne czy reżimowe. Dopiero ich zestawienie pokazuje przemiany naszej pamięci narodowej.
Making Appreciative Inquiry as Natural as Breathing
Authors: Heap Nick
Published: November 2024

We can see when we watch a small child exploring life that Appreciative Inquiry works well when we use it naturally. The contributors to this issue share how they have done so, making Appreciative Inquiry part of the fabric of their lives, their work, their organisations. The stories range from the personal through small teams to organisation and societal change. The settings include family, couples, churches, work with the dying, healthcare and what has traditionally been called ‘heavy industry’.
Bettina’s Dance: Long-buried Possibilities Resurface in a Doctor’s Waiting Room
Authors: Diezi Reto
Published: November 2024

In this short article, the author describes an encounter in a doctor’s waiting room in Germany. In a crowded waiting room, Bettina helps an elderly woman relying on a walker by encouraging her to hum a favourite tune. They gently dance together to the tune, earning applause from the other patients.
A Pilgrim’s Tale: Walking the Camino de Santiago
Authors: Couto Hugo
Published: November 2024

The author describes his experience of pilgrimage to Santiago de Compostela in Spain, an opportunity to rediscover the self, to heal, grow and learn in ways that defy modern learning methods. It is learning with others through movement, direct contact and engaged communication. The simplicity of life while walking the trail, the discomforts and the common goal trigger a sense of community that reawakens an openness towards nature and other people.
Environmental Attitudes in Children: An Exploratory Study of Their Relationships with Future Perspectives and Values
Authors: Soares Ana Karla Silva , Do Nascimento Eduardo França , Costa Renata Tereza dos Passos
Published: November 2024

The present study aims to assess the extent and direction in which future perception and human values are related to environmental attitudes in a sample of children. The participants were 406 Brazilian children, most of them female (56.3 %) with a mean age of 10.23. The results indicated that environmental attitudes of preservation were positively related to all factors of the future perspective scale and the excitement, suprapersonal, existence, interactive, and normative values. The utilization attitudes correlated with the promotion, suprapersonal, existence, interactive, and normative values, but were not significantly correlated with future perspective. The analysis of predictive power showed that optimism towards the future, suprapersonal, normative, and existence values predicted preservation attitudes, while promotion, existence, and interactive values predicted utilization attitudes. The results support the importance of human values and time perspective in environmental attitudes from childhood.
Eduardo Vasco Gutiérrez, la puericultura y la aplicación de la higiene mental a la infancia en Colombia (1930-1948)
Authors: Márquez Valderrama Jorge , Giraldo Gallego Erika
Published: November 2024

Este capítulo es una contribución a la historia de los procesos de medicalización y normalización de la infancia en Colombia, del período 1930-1948, a partir del estudio de la obra de Eduardo Vasco Gutiérrez (1894-1982).1 El interés por la vida de este médico radica en su influencia intelectual en las nuevas prácticas médicas, pedagógicas y psiquiátricas respecto a la infancia. Con su trabajo en diversas instituciones, Vasco fue uno de los pioneros en nuevos métodos provenientes de la psiquiatría infantil, la psicopedagogía y la psicología experimental.