bluuebunny/crossref_metadata_2025 huggingface dataset:
Mulheres em série(s): presenças e materialidades femininas em ficções seriadas contemporâneas
Authors: Alves Gabriela Santos , Garcia Claudia , Cypriano Dyone Arruda , Bastos Raabe , Costa Regina Lúcia Trindade
Published: January 2025

This study seeks to highlight, based on collective writing and the result of dissertations developed in the Comunicação, Imagem e Afeto (Cia/UFES) research group, thepresences and materializations of female representations linked to lesbianism, the appearance and aging of female bodies, the loneliness of Black women, and the culture of rape in recent audiovisual productions. Such reflections are considered pertinent to contribute to interdisciplinary research between contemporary feminist theory and criticism and audiovisual studies, especially on serial fiction. The works covered are the telenovela Vai na fé, from 2023, by Rosane Svartman, and the TV series And Just Like That, from 2021, by Darren Star and collaborators, Insecure, from 2016, by Issa Rae, and The Handmaid’s Tale, from 2017, by Margareth Atwood and collaborators. The main objective is to bring diverse female experiences to the fore, based on Balogh and Moura’s methodology for analyzing serial narratives. It can be seen that the works analyzed are part of a scenario of serial narrative marked by greater female protagonism on screen, even if it is still insufficient in terms of intersectionality.
A estética armorial em A Pedra do Reino, de Luiz Fernando Carvalho
Authors: Ulhôa Marco Túlio
Published: January 2025

Este artigo analisa alguns dos conceitos estéticos produzidos pelo Movimento Armorial, abordando a obra e o pensamento do escritor, poeta e dramaturgo, Ariano Suassuna, na exposição das relações existentes entre a arte armorial, o barroco, o regionalismo e a cultura popular. Por meio de tal procedimento, o objetivo deste texto é investigar o processo de adaptação do Romance d’A Pedra do Reino, do ano de 1971, na série A Pedra do Reino, de 2007, dirigida por Luiz Fernando Carvalho, definindo a estética armorial e os seus reflexos na produção televisiva.
Abstract 091: Efficacy and Safety of Andexanet Alpha Versus Four Factor Prothrombin Complex Concentrate for Emergent Reversal of Factor Xa Inhibitor Associated Intracranial Hemorrhage: A Systematic Review and Meta‐Analysis
Authors: Sarhan K. , Mohamed R. G. , Elmahdi R. , Mohsen Y. , Elsayed A. , Zayed D. , Elkholi M. A. , Gabr N. , El-Bialy E. M. , Serag I.
Published: January 2025

Introduction

Factor Xa inhibitors (FXaI) are increasingly used for anticoagulation therapy, yet their association with intracranial hemorrhage poses a significant challenge. While Andexanet alpha (AA) and four factor prothrombin complex concentrate (4F‐PCC) have shown promise in reversing FXaI effects their comparative efficacy and safety remain uncertain.

Methods

Following the PRISMA guidelines, we conducted a literature search on electronic databases to obtain the relevant studies until 16
th
of May 2024. Our primary outcomes were successful anticoagulation reversal, overall mortality including 30‐day and in hospital mortality, and thromboembolic events. Secondary outcomes were length of hospital and ICU stay and hematoma volume expansion. Data was pooled using random effects model.

Results

We included 16 eligible studies including the ANNEXA‐1 trial with a total of 2977 patients. A statistically significant improvement in hemostatic efficacy rates were in favor of the AA group (RR 1.10, 95% CI [1.01, 1.20], P = 0.02). Lower overall mortality rates were found in the AA group (RR 0.67, 95% CI [0.51, 0.88], P = 0.004). However, no difference was found in 30‐day mortality rates (RR 0.82, 95% CI [0.58, 1.16], P = 0.26). In terms of thromboembolic events, more events were found in the AA group (RR 1.47, 95% CI [1.01, 2.15], P = 0.046). AA was associated with a longer duration of hospital stay compared to 4F‐PCC (MD 0.64, 95% CI [0.07, 1.22], P = 0.03). Neither a significant difference in length of ICU stays (MD 0.25, 95% CI [‐0.36, 0.86], P = 0.41) nor in hematoma volume expansion was reported (MD ‐0.89, 95% CI [‐3.11, 1.34], P = 0.435).

Conclusion

Our results suggest that AA is superior to 4F‐PCC in enhancing the hemostatic efficacy and reducing the overall and in‐hospital mortality rates. More thromboembolic events are thought to be associated with the use of AA. However, more studies are required to validate whether the better results of AA in improving hemostatic efficacy are enough to make up for their higher cost and their possible risk of thromboembolic events.
On the intriguing Q phyllosoma larva (Decapoda, Scyllaridae): A visitor from the deep sea?
Authors: Canto-García Ashanti A.
Published: January 2025

A peculiar phyllosoma larva at an intermediate stage was collected in 2006 during a plankton survey in the Mexican Caribbean. Its body length was 7.3 mm. This phyllosoma resembles those of species of Scyllaridae Latreille, 1825 with characters including a pear-shaped cephalic shield, the presence of pereiopod 5 with setae, and traits typical of Scyllarus Fabricius, 1775 at early stages viz., uniramous antenna, circular thorax, and a shallow abdomen. Previously, this phyllosoma had only been reported from Florida, but at a more advanced stage of development. Based on morphological comparison with records of Atlantic phyllosoma larvae, it is considered unlikely that this individual belongs to any of the species previously reported from the Caribbean subregion. Instead, it is proposed that this peculiar larva belongs to the deep-living scyllarid genus Bathyarctus Holthuis, 2002, as it seems more likely that this deep-living larva was vertically transported to the epipelagic layers of the Caribbean.
Calea breviflora (Asteraceae): a new species endemic to white sand ecosystems of easternmost Amazon, Maranhão, Brazil
Authors: SILVA MIZALENE SILVA DA , BUENO VINICIUS RESENDE , SCATIGNA ANDRÉ VITO , MARINHO LUCAS CARDOSO
Published: January 2025

During field expeditions on white sand patches in northwestern Maranhão, Brazil, we found specimens of Calea characterized by minute florets and pappuses, common to Calea divaricata clade species. After thorough analysis, we concluded that those specimens represent a new species, which is described here as Calea breviflora. Its description, distribution map, illustrations, taxonomic comments, information on the habitat and a preliminary conservation assessment are provided. Moreover, we present an identification key for the Calea divaricata clade species.
Current developments in T-cell receptor therapy for Acute Myeloid Leukaemia
Authors: Gore Sayali , Blyth Emily , Bleakley Marie , Lee Koon , Micklethwaite Kenneth P , Gowrishankar Kavitha
Published: January 2025

T-cell receptor (TCR) therapies are a promising modality for the treatment of cancers, with significant efforts being directed towards acute myeloid leukaemia (AML), a particularly challenging disease. Chimeric antigen receptor (CAR) T-cells targeting single surface antigens have shown remarkable efficacy for B-cell lymphoblastic leukaemia, lymphomas and multiple myeloma. However, AML presents formidable obstacles to the effectiveness of CAR T-cells due to the widespread expression of heterogenous leukaemia immunophenotypes and surface antigen targets additionally present on normal myeloid cells. TCR therapies are an evolving field of cell therapies that allow targeting intracellular antigenic peptides presented via HLA molecules. The development of TCR therapy for AML is progressing rapidly through preclinical research and successful clinical trials. This review specifically explores the antigens targeted in AML, the diverse methodologies and strategies employed in TCR identification and preclinical TCR T-cell development. The review also discusses innovative molecular designs to improve functional efficacy, mitigate safety concerns and overcome HLA restriction. Specific outcomes of early clinical trials targeting important antigens WT1, PRAME and HA-1 are also highlighted. Ultimately, this review underscores why TCR therapy is poised to become an indispensable component of AML immunotherapy.
N-glycan shielded CUB domains of ADAMTS13 prevent binding of C-terminal antibodies in patients with immune-mediated TTP
Authors: Postmus Tim , Schilder Nelly , Ferreira de Santana Juliana , Langerhorst Pieter , Kaijen Paul , Coppo Paul , Joly Bérangère S , Veyradier Agnès , Vanhoorelbeke Karen , Voorberg Jan
Published: January 2025

In Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP), patients develop antibodies against ADAMTS13. The majority of patients exhibit inhibitory anti-spacer antibodies. Non-inhibitory antibodies binding to the carboxy-terminal CUB domains have been suggested to enhance the clearance of ADAMTS13 in iTTP. Furthermore, anti-CUB antibodies induce an open conformation, which has been shown to be an important biomarker for disease severity and relapse risk. We explored whether introduction of N-glycans in the CUB domains of ADAMST13 can reduce the binding of pathogenic anti-CUB autoantibodies. The binding of a panel of iTTP patient derived anti-CUB monoclonal antibodies to newly designed N-glycan modified ADAMTS13 CUB domain variants was assessed by ELISA. Additionally, a subset of these variants was screened against plasma samples of iTTP patients which primarily contain antibodies directed towards the carboxy-terminal domains of ADAMTS13. Introduction of N-glycans at amino acid positions of 1251, 1255 and 1368 in the CUB1/2 domains of ADAMTS13 can effectively reduce binding of 6 out of 7 iTTP patient-derived anti-CUB antibodies. Reduced binding to CUB N-glycan variants was observed in 8 out of 9 patient samples. Binding was decreased from 81% to 47% for NGLY3+CUB-NGLY and 60% to 28% for 5ALA+CUB-NGLY variants. Collectively our findings show that the introduction of N-glycans within the CUB-domain of ADAMTS13 is able to prevent the binding of anti-CUB antibodies in patients with iTTP. Based on these findings, we propose that CUB-NGLY modified ADAMTS13 variants can be used for improved treatment of patients with iTTP.
Molecular switch of the dendrite-to-spine transport of TDP-43/FMRP-bound neuronal mRNAs and its impairment in ASD
Authors: Majumder Pritha , Chatterjee Biswanath , Akter Khadiza , Ahsan Asmar , Tan Su Jie , Huang Chi-Chen , Chu Jen-Fei , Shen Che-Kun James
Published: January 2025

Background

Regulation of messenger RNA (mRNA) transport and translation in neurons is essential for dendritic plasticity and learning/memory development. The trafficking of mRNAs along the hippocampal neuron dendrites remains translationally silent until they are selectively transported into the spines upon glutamate-induced receptor activation. However, the molecular mechanism(s) behind the spine entry of dendritic mRNAs under metabotropic glutamate receptor (mGluR)-mediated neuroactivation and long-term depression (LTD) as well as the fate of these mRNAs inside the spines are still elusive.

Method

Different molecular and imaging techniques, e.g., immunoprecipitation (IP), RNA-IP, Immunofluorescence (IF)/fluorescence in situ hybridization (FISH), live cell imaging, live cell tracking of RNA using beacon, and mouse model study are used to elucidate a novel mechanism regulating dendritic spine transport of mRNAs in mammalian neurons.

Results

We demonstrate here that brief mGluR1 activation-mediated dephosphorylation of pFMRP (S499) results in the dissociation of FMRP from TDP-43 and handover of TDP-43/Rac1 mRNA complex from the dendritic transport track on microtubules to myosin V track on the spine actin filaments. Rac1 mRNA thus enters the spines for translational reactivation and increases the mature spine density. In contrast, during mGluR1-mediated neuronal LTD, FMRP (S499) remains phosphorylated and the TDP-43/Rac1 mRNA complex, being associated with kinesin 1-FMRP/cortactin/drebrin, enters the spines owing to Ca2+-dependent microtubule invasion into spines, but without translational reactivation. In a VPA-ASD mouse model, this regulation become anomalous.

Conclusions

This study, for the first time, highlights the importance of posttranslational modification of RBPs, such as the neurodevelopmental disease-related protein FMRP, as the molecular switch regulating the dendrite-to-spine transport of specific mRNAs under mGluR1-mediated neurotransmissions. The misregulation of this switch could contribute to the pathogenesis of FMRP-related neurodisorders including the autism spectrum disorder (ASD). It also could indicate a molecular connection between ASD and neurodegenerative disease-related protein TDP-43 and opens up a new perspective of research to elucidate TDP-43 proteinopathy among patients with ASD.
Investigation of chitin grafting: thermal, antioxidant and antitumor properties
Authors: Çankaya Nevin , Temüz Mehmet Mürşit , Can Burak
Published: January 2025

In this study, firstly chitin was reacted with chloracetyl chloride to synthesize the macroinitiator chitinchloroacetate (Ch.ClAc). Then, graft copolymers of methacrylamide (MAM), diacetone acrylamide (DAAM), N-(4-nitrophenyl)acrylamide (NPA), and 2-hydroxyethyl methacrylate (HEMA) monomers were synthesized by atom transfer radical polymerization (ATRP). All of the polymers were characterized by FTIR spectra and elemental analysis. According to the elemental analysis results, the mole percent (y) of the macro initiator was found to be 17.39%. The thermal stability of all the polymers (chitin, Ch.ClAc and its graft copolymers) was determined by thermogravimetric analysis (TGA) method and the highest thermal stability was observed in the ungrafted raw chitin. DPPH• scavenging activity and antitumor activity of all polymers were then investigated. Ch.ClAc was found to be the polymer that inhibited the proliferation of tumor cells more than chitin and graft copolymers. It was observed that the antitumor (L1210 cell lines) effect increased with increasing time and concentration in all polymers.
Behavioral, biochemical, immune, and histological responses of Nile tilapia (Oreochromis niloticus Linnaeus, 1758) to lead, mercury, and pendimethalin exposure: individual and combined effects
Authors: Reda Rasha M. , Zaki Eman M. , A. A. Aioub Ahmed , Metwally Mohamed M. M. , Yassin Aya M. , Mahsoub Fatma
Published: January 2025

The aquaculture sector is facing environmental issues because of rising chemical pollution of aquatic systems, which may be caused by man-made or natural causes. The combined action of these mixtures can produce an effect that is either severalfold higher or severalfold lower than the overall toxicity of the individual components. The objective of this study is to evaluate the impact of three individual toxicants: lead (Pb 0.088 mg L−1), mercury (Hg 0.084 mg L−1), and pendimethalin (PM 0.355 mg L−1) and their combinations on the behavior, oxidative stress, immunology, biochemistry, and histopathological changes in Nile tilapia. The results show that mortality was evident across all treatment groups and was highest in the mixture (MIX) group, at 33.4%. Some of these behavioral changes included increased mucus secretion, fin rot, and dark skin coloration of the fish, all of which were evidently exacerbated in the MIX group. The erythrocyte and hemoglobin indices presented marked reductions in the MIX and PM groups in comparison to the control group. The MIX group had higher levels of serum creatinine and urea, as well as the liver enzymes alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. They also had higher levels of malondialdehyde and lower levels of total antioxidant capacity, which showed oxidative stress. The stress biomarkers, cortisol and glucose, showed greater impact on the MIX and PM groups. The neurobehavioral assessment demonstrated noticeable decreased acetylcholinesterase levels in PM and MIX-exposed groups. In the serum immunological parameters, levels of nitric oxide and lysozyme were lower, especially in the MIX and PM groups. In all experimental groups, especially the MIX group, the levels of spleen pro-inflammatory cytokine genes were higher. The histopathological examination revealed marked lesions in the gills, liver, and brains in the form of inflammation, necrosis, and circulatory alterations. Among the exposed groups, the MIX group exhibited the highest histopathological changes. Collectively, our findings demonstrated significant toxic effects of heavy metals and herbicides on Nile tilapia, revealing a synergistic impact on both physiological and histopathological responses resulting from combined exposures. The data evidently indicate the ecological hazards associated with heavy metals and herbicides in aquatic ecosystems.
Continuous high-soy protein soymilk intake affects ordinary walking speed in the Japanese pre-frail and frail elderly: a randomized controlled trial
Authors: Sato Nene , Terashima Yuji , Sugawara Makoto , Unno Ryoichi , Asao Hiroaki , Iwasaki Mitsuhiro , Watanabe Tomoyuki , Uno Tomoko , Maruyama Mitsuo
Published: January 2025

Background

To investigate whether continuous intervention using soymilk containing high soy protein improves physical frailty, a randomized controlled trial was conducted among the Japanese pre-frail and frail elderly.

Methods

Japanese pre-frail and frail elderly participants (n = 73) were randomly assigned to the high-soy protein and control groups, who then ingested soymilk containing 14.5 g/200 ml and 3.2 g/200 ml of soy protein, respectively. Before and after the 12-week intervention, walking speed, skeletal muscle mass, grip strength, and the revised Japanese CHS questionnaire regarding fatigue and physical activity were examined to evaluate the impact of each soymilk on physical frailty and compare the variation between the two groups. Physical activity (monitored using a pedometer), dietary intake (determined by questionnaire), and estimated protein intake (determined by casual urine testing) were also recorded before and after the intervention.

Results

For the final analysis of the entire cohort (n = 70), there were no significant differences in the endpoints between the two groups. In the subgroup analysis, among participants with a walking speed of at least 1 m/s (n = 35, P = 0.012) and at least 5,000 steps/day before intervention (n = 27, P = 0.0083), the variation in walking speed after the 12-week intervention was significantly higher in the high-soy protein group than in the control group. Estimated protein intake was also significantly higher in the high-soy protein group than in the control group after the intervention. Regarding physical activity and dietary intake, no significant differences were observed between the groups before or after the intervention.

Conclusion

The continuous 12-week intervention of high soy protein increased the walking speed among the Japanese pre-frail and frail elderly participants who had an ordinarily high walking speed and high step counts.

Trial registration

UMIN Clinical Trials Registry, UMIN000044999. Registered July 29, 2021; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000051409.
Latent class analysis of the capacity of countries to manage diabetes and its relationship with diabetes-related deaths and healthcare costs
Authors: Akyirem Samuel , Ekpor Emmanuel , Kwanin Charles Boakye
Published: January 2025

Background

The prevalence of diabetes is escalating globally, underscoring the need for comprehensive evidence to inform health systems in effectively addressing this epidemic. The purpose of this study was to examine the patterns of countries’ capacity to manage diabetes using latent class analysis (LCA) and to determine whether the patterns are associated with diabetes-related deaths and healthcare costs.

Methods

Eight indicators of country-level capacity were drawn from the World Health Organization Global Health Observatory dataset: the widespread availability of hemoglobin A1C (HbA1c) testing, existence of diabetes registry, national diabetes management guidelines, national strategy for diabetes care, blood glucose testing, diabetic retinopathy screening, sulfonylureas, and metformin in the public health sector. We performed LCA of these indicators, testing 1–5 class solutions, and selecting the best model based on Bayesian Information Criteria (BIC), entropy, corrected Akaike Information Criteria (cAIC), as well as theoretical interpretability. Multivariable linear regression was used to assess the association between capacity to manage diabetes (based on the latent class a country belongs) and diabetes-related deaths and healthcare costs.

Results

We included 194 countries in this secondary analysis. Countries were classified into “high capacity” (88.7%) and “limited capacity” (11.3%) countries based on the two-class solution of the LCA (entropy = 0.91, cAIC = 1895.93, BIC = 1862.93). Limited capacity countries were mostly in Africa. Limited capacity countries had significantly higher percentage of their deaths attributable to diabetes (adjusted beta = 1.34; 95% CI: 0.15, 2.53; p = 0.027) compared to high capacity countries even after adjusting for income status and diabetes prevalence.

Conclusions

Our findings support the report by the Lancet commission on diabetes, which suggests that differences in diabetes outcomes among countries may be explained by variations in the capacity of and investments made in their health systems. Future studies should evaluate initiatives such as the WHO Global Diabetes Compact that are currently underway to improve the capacity of resource-limited countries.
Exploring the barriers to cervical screening and perspectives on new self-sampling methods amongst under-served groups
Authors: Gillibrand Stephanie , Gibson Helen , Howells Kelly , Urwin Sean , Davies Jennifer C. , Crosbie Emma J. , Sanders Caroline
Published: January 2025

Background

Cervical screening rates have fallen in recent years in the UK, representing a health inequity for some under-served groups. Self-sampling alternatives to cervical screening may be useful where certain barriers prohibit access to routine cervical screening. However, there is limited evidence on whether self-sampling methods address known barriers to cervical screening and subsequently increase uptake amongst under-screened groups. Addressing this research gap, the study aims to understand experiences during and barriers to attending cervical screening for under-screened groups and; explore the views of individuals eligible for screening towards self-sampling (vaginal swabbing and urine sampling) as alternative screening methods and how this may address existing barriers to screening.

Methods

We draw on three integrated theoretical frameworks (access to primary care services, intersectional and feminist perspectives) to examine participants’ barriers to screening and views toward self-sampling methods. We undertook primary qualitative data collection (interviews and focus groups) with 46 participants, facilitated by collaborations with the VCSE sector which successfully enhanced reach to under-served communities.

Results

Known barriers to cervical screening persist for under-screened participant groups, but we also find numerous examples of good practice where some participants’ needs were met throughout the screening process. Both positive and negative experiences tend to centre around experiences with healthcare professionals, with negative experiences also centring around the use of the speculum. Self-sampling methods (vaginal swab and urine collection) were positively received by participants, and may address some existing barriers through the proponents of enhanced choice – between method and location (which also dovetailed with convenience) leading to greater empowerment. The removal of the speculum and lack of invasive examination by a healthcare professional was also positively received.

Conclusions

Whilst barriers to cervical screening remain for under-served groups, examples of good practice are prevalent. Such examples should be implemented more widely to ensure consistency in patient experience and to ensure needs are better met for under-served groups. The introduction of self-sampling alongside traditional methods may reduce barriers to screening, and may boost screening rates for under-screened groups but only if they are implemented with appropriate information and sufficient communication. Failure to implement self-sampling without these considerations may threaten to undermine the identified and important benefits of self-sampling methods.
Scale-up of CHO cell cultures: from 96-well-microtiter plates to stirred tank reactors across three orders of magnitude
Authors: Neuss Anne , Steimann Thomas , Tomas Borges Jacinta Sofia , Dinger Robert , Magnus Jørgen Barsett
Published: January 2025

Background

For process development in mammalian cell cultivations, scale-up approaches are essential. A lot of studies concern the scale transfer between different-sized stirred tank reactors. However, process development usually starts in even smaller cultivation vessels like microtiter plates or shake flasks. A scale-up from those small shaken devices to a stirred tank reactor is barely stated in literature for mammalian cells. Thus, this study aims to address data-driven scale-up for CHO DP12 cells. The oxygen transfer rate is used as a database.

Results

The cultivation conditions in microtiter plates and shake flasks are comparable when choosing the maximum oxygen transfer capacity as a scale-up parameter. The minimum cultivation volume was reduced to 400 µL in round and square 96-deep-well microtiter plates. Using a scale-up based on the maximum oxygen transfer capacity to a stirred tank reactor led to conditions with excessive hydromechanical stress. However, cultivation conditions could be reproduced in a stirred tank reactor by utilizing the volumetric power input as a scale-up parameter. Key metabolites behaved the same in all three scales and the final antibody titer was equal.

Conclusion

This study presents a successful replication of cultivation results for mammalian cells in microtiter plates, shake flasks and stirred tank reactors. The working volumes ranged from 0.4 to 50 and 600 mL. It offers the opportunity to adapt the method to other, more sensitive mammalian cells and to perform cost- and time-effective experiments in high-throughput.
Targeting of the G9a, DNMT1 and UHRF1 epigenetic complex as an effective strategy against pancreatic ductal adenocarcinoma
Authors: Oyon Daniel , Lopez-Pascual Amaya , Castello-Uribe Borja , Uriarte Iker , Orsi Giulia , Llorente Sofia , Elurbide Jasmin , Adan-Villaescusa Elena , Valbuena-Goiricelaya Emiliana , Irigaray-Miramon Ainara , Latasa Maria Ujue , Martinez-Perez Luz A. , Bonetti Luca Reggiani , Prosper Felipe , Ponz-Sarvise Mariano , Vicent Silvestre , Pineda-Lucena Antonio , Ruiz-Clavijo David , Sangro Bruno , Larracoechea Urko Aguirre , Tian Tian V. , Casadei-Gardini Andrea , Amat Irene , Arechederra Maria , Berasain Carmen , Urman Jesus M. , Avila Matias A. , Fernandez-Barrena Maite G.
Published: January 2025

Background

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options and a poor prognosis. The critical role of epigenetic alterations such as changes in DNA methylation, histones modifications, and chromatin remodeling, in pancreatic tumors progression is becoming increasingly recognized. Moreover, in PDAC these aberrant epigenetic mechanisms can also limit therapy efficacy. This study aimed to investigate the expression and prognostic significance of a key epigenetic complex encompassing DNA methyltransferase-1 (DNMT1), the histone methyltransferase G9a, and the scaffold protein UHRF1 in PDAC. We also evaluated the therapeutic potential of an innovative inhibitor targeting these epigenetic effectors.

Methods

Immunohistochemical analysis of DNMT1, G9a, and UHRF1 expression was conducted in human PDAC tissue samples. Staining was semi-quantitatively scored, and overexpression was defined as moderate to strong positivity. The prognostic impact was assessed by correlating protein expression with patient survival. The antitumoral effects of the dual DNMT1-G9a inhibitor CM272 were tested in PDAC cell lines, followed by transcriptomic analyses to identify underlying mechanisms. The in vivo antitumoral efficacy of CM272 was evaluated in PDAC xenograft and syngeneic mouse models, both alone and in combination with anti-PD1 immunotherapy.

Results

DNMT1, G9a, and UHRF1 were significantly overexpressed in PDAC cells and stroma compared to normal pancreatic tissues. Simultaneous overexpression of the three proteins was associated with significantly reduced survival in resected PDAC patients. CM272 exhibited potent antiproliferative activity in PDAC cell lines, inducing apoptosis and altering key metabolic and cell cycle-related genes. CM272 also enhanced chemotherapy sensitivity and significantly inhibited tumor growth in vivo without detectable toxicity. Combination of CM272 with anti-PD1 therapy further improved antitumor responses and immune cell infiltration, particularly CD4 + and CD8 + T cells.

Conclusions

The combined overexpression of DNMT1, G9a, and UHRF1 in PDAC is a strong predictor of poor prognosis. CM272, by targeting this epigenetic complex, shows promising therapeutic potential by inducing apoptosis, reprogramming metabolic pathways, and enhancing immune responses. The combination of CM272 with immunotherapy offers a novel, effective treatment strategy for PDAC.
Peripheral oxygen saturation levels as a guide to avoid hyperoxia: an observational study
Authors: Stolmeijer Renate , ter Maaten Jan C. , Ligtenberg Jack , ter Avest Ewoud
Published: January 2025

Background

As iatrogenic hyperoxia has been related to adverse outcomes in critically ill patients, guidelines advise to titrate oxygen to physiological levels. In the prehospital setting where partial arterial oxygen (PaO2) values are often not readily available, titration of oxygen is based on peripheral oxygen saturations (SpO2). In this study we aimed to investigate the efficacy of SpO2 guided oxygen titration in the prevention of hyperoxia.

Methods

In a retrospective observational cohort study of patients included in the Acutelines data- and biobank of the University Medical Center Groningen between September 2020 and March 2023, we collected blood gas samples and triage data of sequentially included patients who received oxygen at the moment they were presented in the emergency department (ED). PaO2 values were compared to (concurrently measured) SpO2 values, and to patient- and treatment characteristics and P/F ratios were calculated in order to investigate the efficacy of SpO2 based oxygen titration for various subgroups.

Results

Blood gas samples were obtained for 1042 patients, of which 178 (17.1%) had hyperoxia (PaO2 levels > 13.5 kPa). SpO2 readings were available for 170 of these, 68 of which (40%) had SpO2 values above the recommended target range (94–98%; 88–92% for patients with COPD) whereas 102 patients (60%) had SpO2 values within- or even below the recommended target range. Many of these patients (44.1%) received oxygen through a low-flow device (nasal canula), and these patients almost invariably (84.4%) were not compromised in their ventilation (P/F ratio’s > 300).

Conclusion

When oxygen is titrated based on SpO2 levels, this results in hyperoxemia in a significant proportion of the patients. Health care providers should especially be reluctant to administer (low flow) oxygen as a standard of care to patients who do not have clear respiratory compromise, as these patients are at a high risk of developing (occult) hyperoxia.
Diagnostic performance of CT for extrarenal fat invasion in renal cell carcinoma: a meta-analysis and systematic review
Authors: Ma Junchao , Yuan Enyu , Feng Shijian , Yao Jin , He Chunlei , Chen Yuntian , Song Bin
Published: January 2025

Objectives

Renal cell carcinoma (RCC) with extrarenal fat (perinephric or renal sinus fat) invasion is the main evidence for the T3a stage. Currently, computed tomography (CT) is still the primary modality for staging RCC. This study aims to determine the diagnostic performance of CT in RCC patients with extrarenal fat invasion.

Methods

The PubMed, Web of Science, Cochrane Library, and EMBASE databases were systematically searched up to October 11, 2023. Study quality was assessed by the QUADAS-2 tool. Standard methods recommended for meta-analyses of diagnostic evaluation were used. Heterogeneity was analyzed through meta-regression analysis.

Results

Fifteen studies were included in this meta-analysis. Among them, six studies focused on perinephric fat invasion (PFI) only, four on renal sinus fat invasion (RSFI) only, and five on both. Pooled weighted estimates of sensitivity, specificity, area of SROC curve, PLR, and negative likelihood ratio (NLR) of CT for PFI were 0.69 (95% CI: 0.55–0.79), 0.82 (95% CI: 0.69–0.90), 0.81 (95% CI: 0.77–0.84), 3.85 (95% CI: 2.22–6.67), and 0.38 (95% CI: 0.27–0.55). Pooled weighted estimates of sensitivity, specificity, area of SROC curve, PLR, and NLR of CT for RSFI were 0.81 (95% CI: 0.76–0.85), 0.79 (95% CI: 0.66–0.88), 0.82 (95% CI: 0.78–0.85), 3.91 (95% CI: 2.26–6.77), and 0.24 (95% CI: 0.18–0.31).

Conclusion

CT has the ability to detect the PFI and RSFI in patients with RCC. However, the diagnostic performance of CT has suffered from the limitation of slightly lower accuracy, resulting from the low positive sample in the current studies. Additionally, the current PLR is low.

Critical relevance statement

This study provides radiologists and urologists with a systematic and comprehensive summary of CT and CT-related morphological features in assessing extrarenal fat invasion in patients with RCC.

Key Points

CT can detect extrarenal fat invasion in patients with RCC, but the diagnostic performance is inconsistent.

The diagnostic performance of CT is acceptable, but primarily affected by the low positive rate of included patients.

Further large-scale trials are necessary to determine the true diagnostic capabilities of CT for extrarenal fat invasion.

Graphical Abstract
Poikiloderma with neutropenia: a case report
Authors: Chekr Jebran , Andraws Jan , Elias Jubran , Alasmar Diana
Published: January 2025

Background

Poikiloderma with neutropenia is a rare genetic disorder primarily characterized by the presence of poikiloderma and congenital chronic neutropenia. Mutations in the C16orf57 gene, which encodes the USB1 protein, are implicated as the underlying cause of poikiloderma with neutropenia.

Case presentation

Our patient, an 11-year-old Syrian male child who presented with poikiloderma, palmoplantar keratoderma, pachyonychia, recurrent infections, and neutropenia, is considered to be the first documented case in Syria. Clinical examinations, laboratory tests, radiographic imaging, and genetic analyses have been conducted, with the latter being essential and definitive for diagnosis.

Conclusion

This study aimed to evaluate whether poikiloderma with neutropenia should be considered for differential diagnosis because of its diagnostic complexity, emphasizing the importance of follow-up for the early identification of potential complications.
Activation of endogenous tolerance to bleaching stress by high salinity in cloned endosymbiotic dinoflagellates from corals
Authors: Chen Ching-Nen Nathan , Yong Tze Ching , Wang Jih-Terng
Published: January 2025

Background

Large-scale coral bleaching events have become increasingly frequent in recent years. This process occurs when corals are exposed to high temperatures and intense light stress, leading to an overproduction of reactive oxygen species (ROS) by their endosymbiotic dinoflagellates. The ROS buildup prompts corals to expel these symbiotic microalgae, resulting in the corals’ discoloration. Reducing ROS production and enhancing detoxification processes in these microalgae are crucial to prevent the collapse of coral reef ecosystems. However, research into the cell physiology and genetics of coral symbiotic dinoflagellates has been hindered by challenges associated with cloning these microalgae.

Results

A procedure for cloning coral symbiotic dinoflagellates was developed in this study. Several species of coral symbionts were successfully cloned, with two of them further characterized. Experiments with the two species isolated from Turbinaria sp. showed that damage from light intensity at 340 μmol photons/m2/s was more severe than from high temperature at 36 °C. Additionally, preincubation in high salinity conditions activated their endogenous tolerance to bleaching stress. Pretreatment at 50 ppt salinity reduced the percentage of cells stained for ROS by 59% and 64% in the two species under bleaching stress compared to those incubated at 30 ppt. Furthermore, their Fv’/Fm’ during the recovery period showed a significant improvement compared to the controls.

Conclusions

These findings suggest that intense light plays a more important role than high temperatures in coral bleaching by enhancing ROS generation in the symbiotic dinoflagellates. The findings also suggest the genomes of coral symbiotic dinoflagellates have undergone evolutionary processes to develop mechanisms, regulated by gene expression, to mitigate damages caused by high temperature and high light stress. Understanding this gene expression regulation could contribute to strengthening corals’ resilience against the impact of global climate change.
Application of physics-informed neural networks (PINNs) solution to coupled thermal and hydraulic processes in silty sands
Authors: Feng Yuan , Eun Jongwan , Kim Seunghee , Kim Yong-Rak
Published: January 2025

The accurate modeling of water and heat transport in soils is crucial for both geo-environmental and geothermal engineering. Traditional modeling methods are problematic because they require well-defined boundaries and initial conditions. Recently, physics-informed neural networks (PINNs), which incorporate partial differential equations (PDEs) to solve forward and inverse problems, have attracted increasing attention in machine learning research. In this study, we applied PINNs to tackle hydraulic and thermal transport coupling forward problems in silty sands. A fully connected deep neural network was utilized for training. This neural network model leverages automatic differentiation to apply the governing equations as constraints, based on the mathematical approximations established by the neural network itself. We conducted forward problems and compared the solutions derived from PINNs with those from Finite Element Method (FEM) simulations. The forward problem results demonstrate the PINNs model’s capability in predicting hydraulic transport, heat transport, and thermal–hydraulic coupling in silty sands under various boundary conditions. The PINNs exhibited great performance in simulating the thermal–hydraulic coupling problem. The accuracy of the PINNs solutions shows its potential for simulation in geotechnical engineering.
Refugee securitization and the challenges of formal integration: case of Somali refugees in Kenya and Ethiopia
Authors: Ikanda Fred N. , Muhumad Abdirahman A. , Kuhnt Jana
Published: January 2025

Securitization of refugees and migrants is a growing global phenomenon that is well illustrated by how refugee camps have emerged as governmental technologies of control in major host countries across the world. Policymakers and the media prominently feature the migration-security connection and depict refugees as threats to internal security, linking their presence to acts of terrorism and crime. This article examines how the securitization of Somali refugees in Kenya and Ethiopia, the two main host countries for this refugee group, has hindered their formal integration and exacerbated policies of encampment in these countries. Drawing on securitization theory, we highlight the discrimination of Somali refugees in Kenya and Ethiopia by demonstrating how this refugee group is seen as a specific security threat and treated differently from other refugee groups in these countries. A history of border conflicts that shaped the relationship between refugee hosting areas and the national governments long before the advent of camps, coupled with shared Somaliness between locals and refugees in hosting areas, and the back-and-forth refugee movements across international borders have created a confluence of factors that reinforce suspicion and distrust towards Somali refugees. The article adds a normative empirical dimension to securitization theory by providing a nuanced understanding of the concept as it applies to different refugee groups in similar contexts. It also contributes to refugee and migration literature by arguing that although shared Somaliness with locals has strengthened the informal integration of Somali refugees in the two study contexts, the same ties have also provided justification for securitizing this refugee group and denied it from benefitting from progressive laws on formal integration that are being implemented for other refugee groups.
CLINTERVENTIONAL protocol: a randomized controlled trial to evaluate clinical consultations and audiovisual tools for interventional radiology
Authors: García Jurado Pedro Blas , Espejo Herrero Juan José , Lombardo Galera María Sagrario , Pérez Montilla María Eugenia , Barranco Acosta Sara , García-Revillo José , Font Ugalde Pilar , Álvarez Benito Marina
Published: January 2025

Interventional radiology (IR) has evolved rapidly, but the clinical integration of interventional radiologists has not kept pace with technical advancements. This trial will address a gap in the literature by providing a robust investigation into specific measures for enhancing the clinical role of interventional radiologists, with potential implications for improving patient experiences and outcomes. The single-center randomized controlled trial will include 428 patients undergoing IR procedures. The control group will receive information about the procedure from the ordering physician, while the experimental group will have an additional consultation with an interventional radiologist and be shown procedure-specific explanatory videos. The primary outcomes are patients’ knowledge, satisfaction with the information and communication, and anxiety. Data collection will involve specific questionnaires and scales. This trial is designed to investigate the importance of proactive clinical roles in patient care within IR. The study explores the potential of consultations and audiovisual tools, highlighting their role in educating patients about procedures. The results may help foster a more widespread acceptance of clinical responsibilities in IR and underscore the pivotal role of audiovisual aids in patient education and satisfaction.

Trial registration

NCT05461482 at clinicaltrials.gov.

Relevance statement

This randomized controlled trial will assess the impact of clinical consultations and explanatory audiovisual tools on patient understanding, satisfaction, and anxiety in interventional radiology. The findings could help establish a more proactive clinical role for interventional radiologists and improve the overall quality of patient-centered care.

Key Points

We describe the protocol of an interventional radiology randomized clinical trial.

The control group will receive procedure information from the referring physician and the experimental group receives additional consultation with interventionalists and views a video.

Knowledge, satisfaction with information, and patient anxiety will be evaluated.

This study will provide insights about the benefits of consultations and videos in interventional radiology.

Graphical Abstract
Asian seabass (Lates calcarifer) larval rearing using cyclopoid copepod (Apocyclops royi) live feed: A new approach
Authors: Vijayaraj Radha , Jayaprakashvel Mani , Altaff Kareem
Published: January 2025

Background

The Apocyclops species are gaining importance as suitable live feed for augmenting growth and survival of marine finfish larvae. In the present study, as a new approach Apocyclops royi is mass cultured using monoalgal diet (Chloroidium saccharophilum) and its nutritive value is assed and used as supplementary diet in the Asian seabass Lates calcarifer larval rearing.

Results

Mass culture of A. royi with C. saccharophilum diet reached population density of 12,700 ± 454 ind./L on 21 days culture period. A. royi showed high ratio of DHA:EPA and EPA: ARA. Rearing experiments of the Asian seabass (Lates. calcarifer) 11 DPH larvae with copepod, Artimia nauplii and their combination diets recorded faster growth and maximum survival (90%) with A. royi + Artemia nauplii diet compared to A. royi and Artemia nauplii lone feeds. Seabass larval length and weight gain showed significant (p < 0.05) difference among the three dietary treatments. Significantly high content of essential fatty acids in the L. calcarifer larvae have been reported in A. royi + Artemia nauplii fed seabass larvae compared to individual A. royi and Artemia nauplii fed larvae.

Conclusions

Our finding highlights the importance of incorporating A. royi as a supplementary feed for seabass larvae, which will bring improvement in their growth and survival leading to sustainable seed production of this fish.
Leadership and Karma: doing good or doing well?
Authors: Singh Swaran P.
Published: January 2025

Modern management has much to learn from ancient wisdoms. Management structures based on corporate trends were transferred from business to services such as healthcare to promote cost-efficiency and productivity. In this article, I argue that the short-term approach of corporate leaders being brought into healthcare for ‘transformation’ has led to a trail of service dismemberment with no discernible clinical gain for those we seek to serve. Bhagwad Gita, the ancient Hindu scripture on right conduct, is an exemplar of how the primary aim of leaders should be to provide better service rather than serve personal interests or those of the ‘business’ of healthcare.
Exploring the experiences of minoritised groups at life sciences conferences in the UK: new perspectives and actions to improve inclusivity in the sector
Authors: Dutta Ireena , Bishop Michelle , Rayner Julian C. , Creavin Treasa , Ahmed Saher , Clissold Hayley , Cornish Tinu , Wilson Kathlyn , Christoffersen Ashlee , Prentice Janice , Penda Victor
Published: January 2025

Attending and participating in scientific research meetings and conferences is a key mechanism for researchers to share information and knowledge, build networks, and establish relationships and collaborations to support career development. In the UK, researchers from minoritised or underrepresented groups may have a different experience at a conference than their peers. As a high profile provider of genomics-focussed life science conferences, Wellcome Connecting Science is committed to ensuring that our events are as inclusive as possible. Here we summarise the findings of a project to explore the experiences of minoritised groups, with a focus on race and ethnicity, and discuss how we are seeking to improve access and inclusion at our conferences.
Archivo, memoria y conciencia afroamericana: Traveling While Black (Roger Ross Williams, 2019).
Authors: del Caz Pérez Beatriz , Moral Martín Javier
Published: January 2025

En este trabajo se analizan los fundamentos retóricos y formales de Traveling While
Black (2019). Situando al usuario en el Ben’s Chili Bowl, auténtico lugar de memoria,
la experiencia propone una revisión de la historia afroamericana de la segunda
mitad del s. XX. La yuxtaposición de archivos históricos sobre la discriminación y
testimonios actuales subrayan el uso de la memoria como instrumento de acción
social sobre el presente.