bluuebunny/crossref_metadata_2025 huggingface dataset:
A Complete Globe Dislocation without Orbital Wall Fracture
Authors: Tashbayev Behzod , Utheim Tor Paaske , Tsigkris Panagiotis , Shanks Guy
Published: November 2024

Introduction: The complete globe dislocation is a rare type of trauma in clinical practice of ophthalmologists. Case Presentation: In this report, we present a case of complete globe dislocation with optic nerve avulsion caused by a fall onto a wooden chair edge. Interesting fact was that despite the complete avulsion of the optic nerve and total luxation of the globe, there was no orbital fracture. The report discusses characteristics of trauma and its surgical management. Conclusion: Even though the globe was completely dislocated with avulsion of optic nerve and five extraocular muscles the orbit was intact. Unfortunately, the magnitude of trauma warranted enucleation. The extent of the soft tissue damage and swelling precluded a primary orbital implant. In such cases, relatively early secondary surgery with an orbital implant may help reduce the negative psychological impact.
Socioeconomic and demographic inequalities in off-label prescription of glucagon-like peptide-1 (GLP-1) receptor agonists – a Swedish descriptive cohort study
Authors: Pazzagli Laura , Trolle Lagerros Ylva
Published: November 2024

Introduction
In Sweden, glucagon like peptide-1 (GLP-1) receptor agonists are subsidized for diabetes indication but not for obesity. Unregulated off-label prescription of GLP-1 receptor agonists for obesity treatment may raise concerns about potential inequalities for both patient groups. This study aims to describe socioeconomic and demographic characteristics of on- and off-label users of GLP-1 receptor agonists in persons without a diagnosis of diabetes.
Methods
Swedish descriptive register-based cohort study of persons who filled a prescription of a GLP-1 receptor agonist at least once during 2018-2022. Individuals were excluded from the study population if they had a diagnosis of diabetes or previous prescription fills of insulin/analogs at any time prior to the first filled prescription of a GLP-1 receptor agonist. Socioeconomic and demographic characteristics were described overall and stratified by sex and prior use of anti-obesity medications. Off-label use was defined by filled prescriptions of GLP-1 receptor agonists which are indicated for diabetes treatment.
Results
The study population included 16,436 individuals, of which 70.1% were women, 30.7% had previously filled a prescription of anti-obesity medications, 65.3% had Sweden as country of origin and 17.2% an Asian country. In the analyses stratified by sex women were more likely to have an education longer than 9 years (84.8% vs 78.3% in men). Nonetheless, women had lower annual individual (2891.3 vs 4004.9 in men) and family disposable income (5645.5 vs 6092.5 in men). Overall, on-label prescription was higher in women (49.2% vs 30.9% in men), while off-label was more common among men (69% vs 51% in women).
Conclusion
High family disposable income, and male sex are common among off-label glucagon-like peptide-1 receptor agonist users compared to users of the only on-label glucagon-like peptide-1 receptor agonist in Sweden. Regional differences indicate different clinical practices and guideline interpretations.
An updated checklist of snakes (Reptilia: Squamata) in northeastern India derived from a review of recent literature
Authors: Basfore Bijay , Kalita Manab Jyoti , Sharma Narayan , Boro Ananda Ram
Published: November 2024

This paper reviews studies of the snakes of northeastern India published between 2001­­­­­­­ and 2024 identified from searchable databases, covering diversity, range extension, distribution records, new genus, new species, redescription, rediscovery, and taxonomic revision. This analysis of the literature and publicly available information presents an updated checklist of 126 snake species representing 12 families and 46 genera, along with their distribution across states in northeastern India and their IUCN Red List status. The study also reveals a research gap in some northeastern states that provides opportunities for further regional studies.
Unbalanced Coordination: Soviet–Czechoslovak Relations during the Second World War
Authors: Smetana Vít
Published: November 2024

In December 1943, Czechoslovakia became the first country in Central and Eastern Europe to conclude a treaty of alliance and postwar cooperation with the Soviet Union. The signature of this treaty was a voluntary decision taken by the Czechoslovak government-in-exile in London despite considerable British reservations. The main aim was to secure Czechoslovakia from a repeat of what happened in 1938 with the Nazi German threat and the willingness of the Western powers to accommodate Germany at the Munich showdown. Czechoslovak leaders also wanted to establish a treaty that would oblige the Soviet Union to refrain from interfering in the internal affairs of Czechoslovakia. Based on research in the archives of five countries, this article shows how mechanisms of repeated Czechoslovak submission to Soviet “wishes” were already taking shape during the war. Czechoslovakia played a significant role in Soviet geopolitical plans and helped Soviet partners achieve their goals vis-à-vis other allies. Unlike most of the literature on Soviet–Czechoslovak wartime relations, the analysis here presents the exiled Czechoslovak government as an active partner and sincere supporter of Soviet foreign policy aims rather than a victim of a great-power deal at its expense.
West Germany, Guatemala, and the Transnational Dynamics of Cold War Police Assistance
Authors: Bennewitz Fabian , Müller Markus-Michael
Published: November 2024

This article assesses the police-building program designed by the Federal Republic of Germany (FRG) for Guatemala in 1986–1991. By drawing on interviews and declassified archival evidence collected in Germany, Guatemala, and the United States and applying analytical insights from recent literature in International Relations regarding “transnational fields,” the article shows that the FRG's police-building program was shaped by the contingent convergence of international and domestic political conditions in the FRG and Guatemala, mediated by the agency of various Guatemalan actors. The resulting interactions determined the project's trajectory, leading to many adaptations and revisions of the program to suit the agency of Guatemalan actors. Over time, the cumulative weight of these modifications kept the program from succeeding.
TAT as a new marker and its use for noninvasive chemical biopsy in NASH diagnosis
Authors: Jo Sihyang , Kim Jin-Mo , Li Minshu , Kim Han Sun , An Yong Jin , Park Sunghyouk
Published: November 2024

Background

Early diagnosis of Nonalcoholic steatohepatitis (NASH) is crucial to prevent its progression to hepatocellular carcinoma, but its gold standard diagnosis still requires invasive biopsy. Here, a new marker-based noninvasive chemical biopsy approach is introduced that uses urine-secreted tyrosine metabolites.

Methods

We first identified NASH-specific decrease in TAT expression, the first enzyme in the tyrosine degradation pathway (TDP), by employing exometabolome-transcriptome correlations, single-cell RNA -seq, and tissue staining on human NASH patient samples. A selective extrahepatic monitoring of the TAT activity was established by the chemical biopsy exploiting the enzyme’s metabolic conversion of D2-tyrosine into D2-4HPP. The approach was applied to a NASH mouse model using the methionine-choline deficient diet, where urine D2-4HPP level was measured with a specific LC-MS detection, following oral administration of D2-tyrosine.

Results

The noninvasive urine chemical biopsy approach could effectively differentiate NASH from normal mice (normal = 14, NASH = 15, p = 0.0054), correlated with the NASH pathology and TAT level decrease observed with immunostaining on the liver tissue. In addition, we showed that the diagnostic differentiation could be enhanced by measuring the downstream metabolites of TDP. The specificity of the TAT and the related TDP enzymes in NASH were also addressed in other settings employing high fat high fructose mouse NASH model and human obesity vs. NASH cohort.

Conclusions

Overall, we propose TAT and TDP as pathology-relevant markers for NASH and present the urine chemical biopsy as a noninvasive modality to evaluate the NASH-specific changes in urine that may help the NASH diagnosis.
Impact of dementia on post-hip fracture walking ability: a stratified analysis based on pre-fracture mobility in Swedish cohorts of older adults
Authors: Linder Philip D. G. Burenstam , Religa Dorota D. , Gustavsson Fredrik , Eriksdotter Maria , Hedström Margareta , Hägg Sara
Published: November 2024

Background

Hip fractures are a major health concern for older adults, often leading to reduced walking ability. Individuals with dementia may experience worse recovery outcomes. This study aims to explore whether dementia is associated with greater declines in walking ability following hip fractures.

Methods

This register study used data from the Swedish Hip Fracture Register, including data on four-months follow-up on walking ability. The register data was linked to information on dementia diagnosis from other national registers prior to the fracture. All patients > 60 years who suffered a hip fracture in Sweden between 2010 and 2018 were included. Binary logistic regression was used to analyze the loss of walking ability after the hip fracture with adjustment for confounding factors. Stratified analyses were done in four groups based on pre-fracture walking ability: Alone outdoors, Assisted outdoors, Alone indoors, and Assisted indoors.

Results

The analysis included 59,402 patients with a hip fracture, of which 17% had dementia prior to the fracture. Having dementia was associated with a complete loss of walking ability four months after hip fracture; the multivariable-adjusted odds ratio for complete loss of walking ability in the dementia group, using the non-dementia group as a reference, was 1.60 (95% Confidence Interval [CI] 1.49–1.72. In analyses stratified by pre-fracture walking ability, the odds ratios were 2.34 (95% Confidence Interval [CI] 2.03–2.69) for Alone outdoors, 1.53 (95% CI 1.29–1.81) for Assisted outdoors, 1.41 (95% CI 1.27–1.56) for Alone indoors, and 1.29 (95% CI 1.09–1.51) for Assisted indoors.

Conclusions

This study demonstrates that patients with dementia have a greater risk of complete loss of walking ability. The most notable difference was observed in patients who had high walking ability prior to the fracture. These findings suggest the need for tailored rehabilitation programs and enhanced post-operative care protocols for patients with dementia undergoing hip fracture surgery, particularly for those who had high walking ability before the fracture.
Psychometric properties of the Maternal Postnatal Attachment Scale and the Postpartum Bonding Questionnaire in three German samples
Authors: Göbel Ariane , Lüersen Lisa , Asselmann Eva , Arck Petra , Diemert Anke , Garthus-Niegel Susan , Mudra Susanne , Martini Julia
Published: November 2024

Background

Forming an emotional bond towards the infant is an important developmental aspect of the mother-child relationship. Two questionnaires frequently used for the assessment of mother-infant bonding, namely the Maternal Postnatal Attachment Scale (MPAS) and the Postpartum Bonding Questionnaire (PBQ), have shown inconclusive psychometric properties. To ensure comparability of results across studies, it is crucial to examine the replicability of psychometric properties and previously proposed factor structures of measurements when adapted to other languages.

Aim

The study aim was to investigate the psychometric properties of the German versions of both MPAS and PBQ, across three different German-speaking study samples.

Methods

Maternal data from three longitudinal studies from Hamburg, Germany (PAULINE-PRINCE study, N = 229), and Dresden, Germany (MARI study, N = 286; DREAM study, N = 1,968), were used to investigate the psychometric properties (descriptive statistics, item difficulty, inter-item correlations) and the factorial structure (confirmatory factor analysis, CFA; principal axis factoring, PAF) of both MPAS and PBQ. Correlations with maternal-fetal bonding, adult romantic attachment style, attachment style to one’s own mother, postpartum depressive symptoms, and education level were investigated.

Results

Across the three samples, both MPAS and PBQ showed convincing results regarding the psychometric properties for their total scores, with satisfying to excellent internal consistencies. A strong correlation between the MPAS and PBQ total scores was observed (r=-.71, p < .001). In PAF, for both questionnaires, factor structures on subscale level differed across samples and assessment points. For MPAS and PBQ total scores, significant small to medium-sized associations in the expected directions with maternal-fetal bonding and depressive symptoms, as well as for MPAS with adult romantic attachment style, and for PBQ with attachment towards one’s own mother were found. In two samples, higher educated participants reported less optimal MIB.

Conclusion

The results across the three included samples provide evidence for the validity of the construct assessed with the German adaptations of both MPAS and PBQ. However, the factor analytical results on subscale level highlight the need to further investigate the concept of mother-infant bonding in the first year after birth as well as to develop instruments applicable for use in clinical and community samples with satisfying psychometric properties.
Does the association between physical activity during work and leisure and blood pressure differ across sex? A cross-sectional compositional data analysis in a Danish population-based cohort
Authors: Johansson Melker S. , Mortensen Ole Steen , Hougaard Charlotte Ørsted , Olsen Michael Hecht , Korshøj Mette
Published: November 2024

Background

A proposed risk factor for cardiovascular disease is high occupational physical activity (OPA), which seems to increase blood pressure (BP), in contrast to leisure time physical activity. Increased BP may lead to hypertension that increase the risk of cardiovascular disease and premature death. Exposures to OPA differ across sex and also within occupational group. Thus, we aimed to investigate associations between OPA and LTPA and BP among men and women using compositional data analysis.

Methods

This population-based cross-sectional study, used data from the Copenhagen Aging and Midlife Biobank. OPA and LTPA were self-reported time spent in light physical activity (LPA) during work = standing or walking work; moderate-to-vigorous physical activity (MVPA) during work = heavy manual work; LPA during leisure = light physical activity during leisure; MVPA during leisure = biking or walking as commute to work + daily amount of MVPA during leisure, and sleep. Systolic and diastolic BP (SBP, DBP; mmHg) was measured during sitting rest. We used linear regression models to investigate the association between OPA and LTPA, expressed as isometric log-ratios, and BP. The models were used to predict the BP for reallocated physical activity (PA) compositions (i.e., theoretically ‘moving’ time from sitting to PA within each domain). Specifically, we predicted the BP for each reallocated PA compositions and calculated the difference in BP between the reallocated compositions and the mean composition.

Results

In total, 1,334 women and 2,983 men (mean age 55.1 and 52.5 years, respectively) were included in the analyses. About 50% of the women, and 66% of the men, had hypertension. The linear regressions based on the compositional data analysis, showed no association between OPA and LTPA and SBP among women or men. Among men, less time spent sitting and more time spent in LTPA, compared to the mean composition, was associated with a lower DBP (e.g., 60 min less sitting and 60 min more LTPA: -0.25, 95% CI: -0.05, -0.45 mmHg).

Conclusion

No association between OPA and LTPA and BP was observed across sexes, except between LTPA and DBP among men. This could be due to information bias and lack of precision in self-reported time use data of PA.

Trial registration

None.
Health literacy interventions for pregnant women with limited language proficiency in the country they live in: a systematic review
Authors: Khan Marya , Dave Arti , Benton Madeleine , Moss Ngawai , Kaler Mandeep Kaur
Published: November 2024

Background

Low health literacy can present significant risks throughout pregnancy, impacting both maternal and fetal health outcomes. Those who do not speak the main language of their country of residence are more likely to have lower health literacy. Considering the heightened challenges faced by this demographic in accessing, understanding, and engaging with health information and services, designing and implementing tailored interventions is crucial to mitigate health disparities. This review aims to identify and examine health literacy interventions developed for pregnant women whose first language differs from the language predominantly spoken in their residing country.

Methods

Electronic databases of Embase and Medline were searched using relevant search terms from their inception to July 2023. Data were extracted and analysed using narrative synthesis.

Results

Of the 1964 identified records, three were included. The studies were conducted in Australia and Denmark, and ranged in design, including: a cluster randomised controlled trial, mixed methods design; and qualitative design. Health literacy intervention modalities included midwifery education combined with a smartphone application and leaflet, culturally adapted group classes, and informative videos. The interventions were translated into various languages to cater to the target populations. Two studies used the Health Literacy Questionnaire to assess the intervention effectiveness, yielding contrasting results: one showed no improvement, while the other reported increased post-intervention health literacy scores. The third had not yet evaluated intervention effectiveness.

Conclusions

This review identifies a significant scarcity in health literacy interventions for pregnant women whose first language differs to the predominant language of the country they live in, despite their greater need for support. While few studies were found, their diversity suggests multiple strategies for enhancing health literacy. Bridging this health literacy gap for linguistically diverse pregnant populations could reduce disparities in maternal and fetal outcomes, underscoring the need for targeted, evaluated interventions that actively engage affected women and their support networks.

Trial registration

Registered with PROSPERO: CRD42023475511. Date of registration: 10.11.23.
Do Danish medical students feel prepared to deliver healthcare to patients with backgrounds different from their own? A cross-sectional survey
Authors: Sorensen J. , Hindhede A.L. , Ohlendorff J.S. , de Montgomery C.J. , Maheswaran S. , Norredam M. , Krasnik A.
Published: November 2024

Background

Migrant and ethnic minority populations in Europe are growing, leading to a demand for health systems and health educations to accommodate the growing diversity. Research indicates that health professionals feel inadequately prepared to care for diverse populations, and medical education has gaps in addressing these issues. The aim of the study is to explore whether Danish medical students and newly graduated physicians feel prepared to meet the needs of the increasingly diverse populations.

Methods

An online survey was emailed to students in the four medical Master’s programs in Denmark and to newly graduated physicians in clinical internships. Data was collected spring 2023. Descriptive statistics reported overall numbers, and multivariate logistic regression was used to model the association between survey answers and the background variables: semester, gender/sex, parent’s education, self-identified ethnicity.

Results

Many medical students and newly graduated physicians feel unprepared to care for patients of backgrounds different from their own. For all items women reported feeling more unprepared than men. Among the medical students and newly graduated physicians with enough clinical experience to answer the question, 34.2% reported feeling helpless at times or often in the past year when treating culturally different patients. Men were less likely than women to report feeling helpless (OR = 0.42; 95% CI 0.28 to 0.64); and self-identified ethnic minorities were 2.59 times more likely than Danish/European medical students and newly graduated physicians to report feeling helpless (95% CI 1.32–5.07).

Conclusion

Our findings indicate shortcomings in medical students and newly graduated physicians feeling of preparedness to provide care to patients of backgrounds different from their own. These findings can assist medical education management with identifying curriculum gaps.
Navigating end-of-life care dilemmas: a qualitative inquiry of nurses’ and midwives’ knowledge of euthanasia and circumstantial factors influencing euthanasia in a resource-constraint setting
Authors: Mumuni Hadiru Iddris , Iddrisu Merri , Laari Luke , Dzansi Gladys , Aziato Lydia
Published: November 2024

Background

Deaths can be caused by terminal illnesses, accidents, or natural disasters. However, medically, death can be hastened by healthcare providers, patients themselves, or their relatives. In advanced cancers where the patient’s quality of life is compromised, Euthanasia can be used to hasten death. Inadequate medical resources and low socioeconomic status have been cited as factors influencing Euthanasia. This study sought to explore nurses’ and midwives’ knowledge and perspectives on Euthanasia in resource-constrained health facilities.

Methods

A qualitative exploratory, descriptive design was used to recruit 24 nurses and midwives from three major referral hospitals, two regional hospitals, and one district hospital. Data was collected through individual in-depth face-to-face and telephone interviews. Braun and Clarke’s (2006) thematic data analysis approach was used.

Findings

: Three main themes and eight subthemes were generated from the data: the main themes include Knowledge of Euthanasia, health system resource constraint-driven euthanasia and family resource constraint-motivated euthanasia. The findings indicate that nurses and midwives lack understanding of some terminologies related to the act. Strict policy decisions, inadequate resources, and misunderstanding of palliative care resulted in the practice of Euthanasia. Additionally, unbearable pains and financial constraints of families of critically ill patients made them request Euthanasia in the health facilities.

Conclusion

The study highlights the challenges of end-of-life care in resource-constrained settings, emphasizing the need for provider training, increased healthcare capacity, and clearer national guidelines for ethical decision-making.
Factors influencing provider deviation from national HIV and nutritional guidelines for HIV-exposed children in western Kenya: a qualitative study
Authors: Coe Megan M. , Yoshioka Emily , Odhiambo Damaris , Masheti Mary , Amam Phlona , Nyaoke Julius , Oduor Emmanuel , Serede Marline , Ndirangu Agnes , Singa Benson , Means Arianna Rubin
Published: November 2024

Background

Malnutrition and HIV interact in a vicious cycle for HIV-exposed infants (HEIs), increasing vulnerability and the severity of each condition and contributing to poor health outcomes. We identified multi-level factors influencing provider adherence to Kenyan HIV and nutrition guidelines for HEIs.

Methods

We conducted six focus group discussions and seven in-depth interviews using a semi-structured question guide. Participants were selected through purposive maximum variation sampling of health workers involved in maternal and child health services and outpatient nutrition programs at two facilities in western Kenya. Data collection and analysis were guided by the Theoretical Domains Framework (TDF). Transcripts were coded by two primary coders using both deductive and inductive thematic analysis.

Results

TDF domains that drove guideline adherence included: environmental context and resources, beliefs about capabilities, and social influences. While participants praised attempts to integrate HIV and nutritional services through teamwork and service colocation, challenges in the successful referral of patients between services persisted. Participants described siloed HIV and nutrition-related knowledge across staff, leading to missed or delayed care if certain providers were unavailable. Participants emphasized understaffing as a major contributor to gaps in care. Inconsistent material resource availability also disrupted linkages between HIV and nutrition services for patients. While participants frequently expressed high intention and internal motivation to link children between services, they described minimal structured supervision or positive reinforcement from supervisors and feeling demoralized when resource constraints interfered with care provision. Lastly, participants described patient-level factors that made it challenging for families to seek or remain in care, including poverty and HIV and malnutrition-related stigma. Participants made several recommendations, including training multiple cadres in the fundamentals of both HIV and nutritional care to address siloed services and understaffing.

Conclusions

This study details the factors that facilitate or hinder health workers as they implement national guidelines and link HEIs between HIV and nutritional services, including the impact of physical integration of service sites, human and material resource constraints, and health worker motivation. Future interventions can address these challenges by expanding access to needed resources, task sharing, and testing implementation strategies that increase the efficiency of service delivery to improve linkages in care for vulnerable infants.
Male partner involvement in delivery care service and associated factors in Ethiopia: a systematic review and meta-analysis
Authors: Mulugeta Chalie , Emagneneh Tadele , Kumie Getinet , Sisay Assefa , Alamrew Abebaw
Published: November 2024

Introduction

Promoting the involvement of male partners in skilled delivery care is a strategy supported by the World Health Organization (WHO) to improve maternal and infant health outcomes. This systematic review and meta-analysis aimed to estimate the pooled prevalence of male partner involvement in delivery care service in Ethiopia and its contributing factors.

Methods

We retrieved observational studies conducted in Ethiopia from PubMed, Google Scholar, Embase, Cochrane Library, Hinari, and Mednar using Boolean search terms. The Newcastle Ottawa 2016 Critical Appraisal Checklist assessed the methodological quality of the studies. Publication bias was evaluated with a funnel plot and Egger’s test, and heterogeneity was checked using the I-squared test. Data were extracted into Microsoft Excel and analyzed using Stata 11 software.

Results

10 articles with 5,307 participants were included for analysis. The pooled prevalence of male partner involvement in delivery care service was 52.99% (95% CI: 40.63–65.35). Paternal secondary education and above (OR 1.99, 95% CI: 1.69, 2.30), paternal knowledge (OR 3.129, 95% CI: 1.901, 4.356), partner attitude (OR 2.39, 95% CI: 1.45–3.34), having ANC accompanying experience (OR 8.09, 95% CI: 3.14, 19.32), and urban residence (OR 2.12, 95% CI: 1.61, 2.64) were significantly associated with male partner involvement in delivery care service in Ethiopia.

Conclusion

This study found that more than half of male partners in Ethiopia were involved in delivery care services. The key contributing factors for male partner involvement in delivery care services were paternal secondary education and above, paternal knowledge, partner attitude, ANC accompanying experience, and urban residence. Campaigns should be organized to improve knowledge, attitude, and effectively recognize men’s involvement in skilled birth care.
Mechanism of efficacy of trabectedin against myxoid liposarcoma entails detachment of the FUS-DDIT3 transcription factor from its DNA binding sites
Authors: Craparotta Ilaria , Mannarino Laura , Zadro Riccardo , Ballabio Sara , Marchini Sergio , Pavesi Giulio , Russo Marta , Renne Salvatore Lorenzo , Meroni Marina , Ponzo Marianna , Bello Ezia , Sanfilippo Roberta , Casali Paolo G. , D’Incalci Maurizio , Frapolli Roberta
Published: November 2024

Background

The marine drug trabectedin has shown unusual effectiveness in the treatment of myxoid liposarcoma (MLPS), a liposarcoma characterized by the expression of the FUS-DDIT3 chimera. Trabectedin elicits a significant transcriptional response in MLPS resulting in cellular depletion and reactivation of adipogenesis. However, the role of the chimeric protein in the mechanism of action of the drug is not entirely understood.

Methods

FUS-DDIT3-specific binding sites were assessed through Chromatin Immunoprecipitation Sequencing (ChIP-Seq). Trabectedin-induced effects were studied on pre-established patient-derived xenograft models of MLPS, one sensitive to (ML017) and one resistant against (ML017ET) trabectedin at different time points (24 and 72 h, 15 days). Data were integrated with RNA-Seq from the same models.

Results

Through ChIP-Seq, here we demonstrate that trabectedin inhibits the binding of FUS-DDIT3 to its target genes, restoring adipocyte differentiation in a patient-derived xenograft model of MLPS sensitive to trabectedin. In addition, complementary RNA-Seq data on the same model demonstrates a two-phase effect of trabectedin, characterized by an initial FUS-DDIT3-independent cytotoxicity, followed by a transcriptionally active pro-differentiation phase due to the long-lasting detachment of the chimera from the DNA. Interestingly, in a trabectedin-resistant MLPS model, the effect of trabectedin on FUS-DDIT3 rapidly decreased over time, and prolonged treatment was no longer able to induce any transcription or post-transcriptional modifications.

Conclusions

These findings explain the unusual mechanism underlying trabectedin's effectiveness against MLPS by pinpointing the chimera's role in inducing the differentiation block responsible for MLPS pathogenesis. Additionally, the findings hint at a potential mechanism of resistance acquired in vivo.

Graphical Abstract
Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast: results from the KARISMA randomised controlled trial
Authors: Göransson Sara , Hernández-Varas Pablo , Hammarström Mattias , Hellgren Roxanna , Bäcklund Magnus , Lång Kristina , Rosendahl Ann H. , Eriksson Mikael , Borgquist Signe , Strömblad Staffan , Czene Kamila , Hall Per , Gabrielson Marike
Published: November 2024

Background

Tissue stiffness, dictated by organisation of interstitial fibrillar collagens, increases breast cancer risk and contributes to cancer progression. Tamoxifen is a standard treatment for receptor-positive breast cancer and is also aproved for primary prevention. We investigated the effect of tamoxifen and its main metabolites on the breast tissue collagen organisation as a proxy for stiffness and explored the relationship between mammographic density (MD) and collagen organisation.

Material and methods

This sub-study of the double-blinded dose-determination trial, KARISMA, included 83 healthy women randomised to 6 months of 20, 10, 5, 2.5, and 1 mg of tamoxifen or placebo. Ultrasound-guided core-needle breast biopsies collected before and after treatment were evaluated for collagen organisation by polarised light microscopy.

Results

Tamoxifen reduced the amount of organised collagen and overall organisation, reflected by a shift from heavily crosslinked thick fibres to thinner, less crosslinked fibres. Collagen remodelling correlated with plasma concentrations of tamoxifen metabolites. MD change was not associated with changes in amount of organised collagen but was correlated with less crosslinking in premenopausal women.

Conclusions

In this study of healthy women, tamoxifen decreased the overall organisation of fibrillar collagens, and consequently, the breast tissue stiffness. These stromal alterations may play a role in the well-established preventive and therapeutic effects of tamoxifen.

Trial registration ClinicalTrials.gov ID: NCT03346200. Registered November 1st, 2017. Retrospectively registered.
Choriocapillaris flow deficit is associated with disease duration in type 2 diabetic patients without retinopathy: a cross-sectional study
Authors: Vidal-Oliver Lourdes , Herzig-de Almeida Elisa , Spissinger Sabrina , Finger Robert P
Published: November 2024

Background

Diabetes mellitus (DM) causes microvascular damage due to long-term hyperglycemia, even before the onset of retinal changes. We aimed to investigate the association between optical coherence tomography angiography (OCTA) metrics and disease duration in type 2 diabetic patients without retinopathy.

Methods

Eighty-two eyes of 82 type 2 diabetic patients without diabetic retinopathy (DR) were included. Choriocapillaris flow deficit (CC FD%), vessel density (VD), vessel length density (VLD) in the superficial (SVP) and deep vascular plexus (DVP) were calculated and compared between different sectors of the macula. Foveal avascular zone circularity (FAZc) was also calculated. Linear regression was used to study the association of each vascular parameter with disease duration both in a univariate and multivariate design adjusting for age, sex, Hb1Ac and arterial hypertension.

Results

CC FD% increased by 3.7, 2.3, 3.8 and 4.6% in the nasal, superior, temporal and inferior sectors per decade of disease duration, after adjusting for confounders. Mean values of VD and VLD in the SVP and DVP, as well as FAZc decreased with increased duration of DM, but the association was weaker. Only the VD in the superior and temporal sectors of the SVP were significant in the multivariate analysis (ß=-0.12 (95% CI -0.24 to -0.01) and − 0.13 (95%CI -0.25 to -0.002), respectively).

Conclusion

CC FD% is independently associated with disease duration in type 2 diabetes independent of the presence of clinical retinopathy. Further longitudinal studies are needed to investigate the role of choroidal changes in predicting DR onset in order to individualize screening protocols.
Novel Therapies for Pancreatic Cancer
Authors: Chung Victoria , Mizrahi Jonathan D. , Pant Shubham
Published: November 2024

Pancreatic adenocarcinoma (PDAC) unfortunately remains a highly fatal disease with a 5-year survival rate of only 11%. If surgical resection is not possible, systemic chemotherapy represents the standard-of-care approach to management. Combination chemotherapy regimens using fluorouracil (fluorouracil, oxaliplatin, leucovorin, and irinotecan; and fluorouracil, leucovorin, and oxaliplatin) or gemcitabine with albumin-bound paclitaxel have the potential to improve overall survival for patients with advanced disease. With the increasing understanding of the molecular drivers of pancreatic cancer, novel therapeutic approaches have made incremental progress for these patients. The molecular landscape of PDAC has been studied extensively. Approximately 90% of PDACs harbor mutations in the KRAS gene, a driver mutation that has long been considered undruggable. However, novel KRAS inhibitors have shown therapeutic promise in early-phase clinical trials, with larger studies ongoing. Less frequently encountered genomic aberrations that have therapeutic potential include NRG, BRAF, NTRK, HER2, BRCA, PALB2, and claudin. Immune checkpoint inhibitors have unfortunately yielded disappointing efficacy for the majority of patients with pancreatic cancer, except for those with tumors exhibiting deficiency in mismatch repair proteins. Alternative approaches to incorporate immunotherapy have shown more promise such as use of immune checkpoint inhibitors for selected patients in the maintenance setting and potential vaccine therapies in the postsurgery adjuvant setting. It is vital to perform molecular profiling in all patients with PDAC to identify potential treatment targets, and to enroll patients in clinical trials whenever possible.
Increased Ambient Temperature and Hyponatremia Presentations: A 10-Year Retrospective Study at an Australian Hospital
Authors: Nicholls Thomas , Hoermann Rudolf , Wootton Elizabeth , Mansouri Negar , Stevens Meg , Vo Hung , Grossmann Mathis , Warren Annabelle M
Published: November 2024

Objective

To determine the relationship between ambient air temperature and the incidence of hyponatremia in a heat-prone region.

Methods

We conducted a retrospective study that correlated serum sodium concentrations documented at the Austin Hospital in Melbourne over 10 years from January 2014 to December 2023 with publicly available temperature data from the Australian Bureau of Meteorology. The main outcome measures were serum sodium concentrations and incidence of hyponatremia admissions when correlated to temperature, and, following heatwave events, defined as temperature above 30 °C over 5 consecutive days.

Results

Over this period, 45 718 low serum sodium results were identified from 26 557 unique patients. Serum sodium concentrations in January (Australian summer) were 0.55 mmol/L lower (95% CI 0.36 to 0.77, P < .001) than in September (Australian early spring). Women had lower sodium concentrations than men (−0.21 mmol/L, 95% CI −0.29 to −0.12, P < .001), as did patients older than 80 years when compared with those younger than 65 years (−0.39 mmol, 95% CI −0.50 to −0.29, P < .001). Hospital admissions with hyponatremia were more frequent during summer months. Profound hyponatremia admissions (sodium ≤125 mmol/L) were more frequent following a heatwave than without (7.6% vs 6.5%, P = .04).

Conclusion

Our study demonstrates that serum sodium concentrations are lower and profound hyponatremia-related hospital admissions higher when ambient temperatures are warmer. This suggests that hyponatremia is a climate-associated health issue. Local public health advice for water consumption during heatwaves should consider this risk, and prompt action to limit climate change is required to mitigate this risk.
Prediction of Shunt Malfunction Using Automated Ventricular Volume Analysis and Radiomics
Authors: Kellogg Ryan T. , Vargas Jan , Nguyen Matthew , Nwanko Anthony , Patel Sohil , Ghimire Kanchan , Feng Xue
Published: November 2024

BACKGROUND AND OBJECTIVES:

The assessment of ventricle size is crucial in diagnosing hydrocephalus and in detecting shunt malfunctions. Current methods primarily involve 2-dimensional measurements or ratios. We evaluated the accuracy of volumetric analysis and radiomics in diagnosing hydrocephalus and shunt malfunction.

METHODS:

We identified patients that underwent shunt surgery between January 2018 and August 2020 and collected head CTs from patients who were imaged before the placement of their shunt, with a functional shunt, or with a shunt malfunction. We performed automated ventricle segmentation on the computed tomography (CT) scans to compute ventricle volumes. For each patient, the ventricular volume was compared against a reference normative data set to determine if the ventricular volume was within a given range of SDs. Radiomics analyses were performed on the pathological and a normal data set, combined with clinical features, and used to train classifiers to identify patients with a malfunctioning shunt.

RESULTS:

A total of 145 head CTs from 66 patients were collected and segmented. Comparing pathological ventricular volumes to a normative data set yielded an accuracy of 70% to 73%, depending on the SD cutoff (area under the curve [AUC] of 0.772). When radiomics analysis was performed on 145 pathological and 73 normal scans, the best performing model was a support vector machine model that predicted malfunctioning shunt with an AUC of 0.92 and F1-score of 0.848. Furthermore, the support vector machine model was tested using a held-out testing data set that achieved an AUC of 0.933.

CONCLUSION:

Automated ventricle segmentation using convolutional neural networks combined with radiomics analysis can be used with age and sex to assist in the diagnosis of hydrocephalus and shunt malfunctions when combined with a reference normative data set. It offers a time-efficient alternative to manual segmentation, reduces interobserver variability, and holds promise in improving patient outcomes by facilitating early and accurate diagnosis of hydrocephalus/shunt malfunction.
SLC25A1 regulates placental development to ensure embryonic heart morphogenesis
Authors: Fan Wenli , Li Zixuan , He Xueke , Wang Xiaodong , Sun Ming , Yang Zhongzhou
Published: November 2024

22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion syndrome. Congenital heart defects are prevalent in 22q11.2DS but the etiology is still poorly understood. In this study, we aimed to gain mechanistic insights into the heart defects that result from 22q11.2 deletion, with a focus on Slc25a1, which is located in the deletion segment. Whereas global knockout of Slc25a1 in mice produced a variety of heart malformations, cardiac deletion of Slc25a1 had little effect on heart development. We then found that trophoblast-specific Slc25a1 deletion recapitulated heart anomalies in the global knockout mice. Further study identified SLC25A1 as a regulator of trophoblast and placental development through modulation of histone H3K27 acetylation at the promoters and enhancers of key genes involved in trophoblast differentiation. Finally, administration of recombinant human pregnancy-specific glycoprotein 1 (PSG1), a trophoblast-derived secretory glycoprotein, partially corrected placental and embryonic heart defects. This study defines the role of SLC25A1 in heart development by regulating placental development, and provides new insights to understand the etiology of 22q11.2DS.
Large Shocks Travel Fast
Authors: Cavallo Alberto , Lippi Francesco , Miyahara Ken
Published: November 2024

We document a sizeable increase in the frequency of price adjustments following the large energy shocks of 2022. We use a tractable New Keynesian model, calibrated to the preshock data, to interpret such a pattern. The calibration highlights the state dependence of firms’ decisions: prices are adjusted rapidly when markups are misaligned. In the model, a large cost shock triggers a swift increase in the frequency of price adjustments, causing a rapid pass-through from costs to prices. Time-dependent models, such as the Calvo model, miss this frequency response, failing to capture the sudden inflation surge after a large shock. (JEL D22, E12, E31, L11, L66, Q43)
The AI Dilemma: Growth versus Existential Risk
Authors: Jones Charles I.
Published: November 2024

Advances in artificial intelligence (AI) are a double-edged sword. On the one hand, they may increase economic growth as AI augments our ability to innovate. On the other hand, many experts worry that these advances entail existential risk: creating a superintelligence misaligned with human values could lead to catastrophic outcomes, even possibly human extinction. This paper considers the optimal use of AI technology in the presence of these opportunities and risks. Under what conditions should we continue the rapid progress of AI, and under what conditions should we stop? (JEL D11, D81, H43, I31, O31)
Noise-Tolerant Community Enforcement and the Strength of Small Stakes
Authors: Fudenberg Drew , Wolitzky Alexander
Published: November 2024

We study community enforcement in a large population with noisy monitoring. We focus on equilibria in the prisoner’s dilemma that are coordination proof, meaning that matched partners never play a Pareto-dominated Nash equilibrium in the one-shot game induced by the equilibrium continuation payoffs at their current histories. We show that a noise-tolerant version of contagion strategies is optimal among all coordination-proof equilibria. Welfare under tolerant contagion strategies decreases in the noise level and the gain from defection faster than welfare in a fixed partnership does. Thus, community enforcement has a comparative advantage in supporting “ low-stakes”relationships. (JEL C72, C73, C78, Z13)
Σύγχρονα ψηφιακά μουσειακά περιβάλλοντα
Authors: Κουκούλης Κωνσταντίνος
Published: November 2024

Στο παρελθόν, τα μουσεία χρησιμοποιούσαν παραδοσιακές μεθόδους όπως ετικέτες, ηχητικούς οδηγούς και έντυπα φυλλάδια για να παρέχουν πληροφορίες στους επισκέπτες. Ωστόσο, με την πρόοδο της τεχνολογίας, τα μουσεία έχουν αρχίσει να ενσωματώνουν νέες και καινοτόμες τεχνολογίες τόσο στις λειτουργίες τους (έρευνα, συλλογή, διατήρηση, ερμηνεία και έκθεση) όσο και στις προσφερόμενες εμπειρίες (εκπαίδευση, ψυχαγωγία, ανταλλαγή γνώσης και αναστοχασμό). Σε ένα πλαίσιο ραγδαίου ψηφιακού μετασχηματισμού που επιταχύνθηκε από την πανδημία του Covid19, τα μικρότερα μουσεία φαίνεται να υποφέρουν περισσότερο, καθώς συχνά δεν διαθέτουν επαρκείς ικανότητες και πόρους για να αντιμετωπίσουν την ταχεία τεχνολογική πρόοδο. Σε αυτό το πλαίσιο, τα βασικά μας ερωτήματα κινήθηκαν γύρω από την υιοθέτηση των ψηφιακών τεχνολογιών από μουσεία και οργανισμούς που έχουν ως στόχο την προβολή, διαχείριση και αξιοποίηση του πολιτισμικού τους αποθέματος. Θα μπορούσαν οι μικροί οργανισμοί να ακολουθήσουν τις τεχνολογικές εξελίξεις; Υπάρχουν τεχνολογίες που θα μπορούν να χρησιμοποιηθούν χωρίς μεγάλο κόστος για την δημιουργία εφαρμογών; Ποιες είναι οι υπηρεσίες που μπορούν να προσφερθούν; Μπορεί να υπάρξει ένας κοινός σχεδιασμός που να καλύπτει τις απαιτήσεις αυτών των μουσειακών περιβαλλόντων; Ποιος είναι ο σκοπός της αξιολόγησης σε ένα ψηφιακό μουσειακό περιβάλλον; Υπάρχουν μεθοδολογίες που προορίζονται για την αξιολόγηση αυτών των περιβαλλόντων; Πώς θα μπορούσαμε να αξιολογήσουμε ψηφιακά περιβάλλοντα που έχουν δημιουργηθεί για να καλύψουν τις ανάγκες των μουσείων; Ποιες είναι οι εκπαιδευτικές προοπτικές από τη χρήση της τεχνολογίας; Στην προσπάθεια να απαντηθούν αυτά τα ερωτήματα καταγράψαμε τις επικρατέστερες τεχνολογίες που αποτελούν μέρος της καθημερινότητας των ανθρώπων, τεχνολογίες που φαίνεται πως θα χρησιμοποιηθούν σε ευρεία κλίμακα στα επόμενα χρόνια. Στη συνέχεια προσπαθήσαμε να εντοπίσουμε τη χρήση αυτών των τεχνολογιών σε μουσειακά περιβάλλοντα και σε εργασίες που χρησιμοποιούν αυτές τις τεχνολογίες σε ερευνητικό επίπεδο. Η διαδικασία αυτή κατέληξε σε μια ταξινόμηση της χρήσης των τεχνολογιών και τα συμπεράσματα ήταν πολύτιμα για την δημιουργία αρχών σχεδίασης μουσειακών περιβαλλόντων που θα συμπεριλαμβάνουν χρήσιμες υπηρεσίες για τους χρήστες τους. Για να δοκιμάσουμε το σχεδιασμό και τις υπηρεσίες που προτείνουμε να υπάρχουν σε ένα μουσειακό περιβάλλον, σχεδιάσαμε, αναπτύξαμε, παρουσιάσαμε, υλοποιήσαμε και αξιολογήσαμε υπηρεσίες που αφορούν τη δημιουργία ψηφιακών εκθέσεων με αναφορά σε οργανισμούς που είτε διέθεταν τις αντίστοιχες φυσικές συλλογές είτε στόχευαν σε εκθέσεις που περιλάμβαναν μόνο ψηφιακό περιεχόμενο. Πέρα από τις υπηρεσίες που βοηθούν στην δημιουργία εκθέσεων και στα πλαίσια ενός ερευνητικού προγράμματος που συμμετείχαμε, μελετήσαμε πως οι τεχνολογίες εκτεταμένης πραγματικότητας μπορούν να χρησιμοποιηθούν για τη δημιουργία εκθέσεων τέχνης εστιάζοντας στις εκπαιδευτικές προοπτικές.