bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel antiseizure medications in the development pipeline: promising candidates and recent failures
Authors: Löscher W.
Published: November 2024

In the past decade, we have observed a paradigm shift in the discovery of novel antiseizure medications (ASMs), which is a consequence of significant progress in epilepsy genetics, the availability of novel disease models, drug-screening technologies, the discovery of new mechanisms of action, expanding existing drugs into new populations, or new routes of delivery. This resulted in a very rich pipeline of potential future treatments for epilepsy, including gene-modifying treatments for rare genetic epilepsies and mechanistically guided precision treatments. Hopes are high that this pipeline may bring therapeutic breakthroughs similar to those recently achieved with cenobamate for the common drug-resistant focal epilepsy and fenfluramine for seizures in Dravet syndrome. Furthermore, we stand at the beginning of a new era of epilepsy treatment expansion, from traditional seizure suppression to disease prevention and modification. This review discusses the most advanced and promising candidates in the clinical development pipeline but also describes recent failures in the development of novel ASMs.
Iron-loaded activated carbon cloth as CDI electrode material for selective recovery of phosphate
Authors: Sharker Tanzila , Gamaethiralalage Jayaruwan G. , Qu Qiyang , Xiao Xinxin , Dykstra Jouke E. , de Smet Louis C. P. M. , Muff Jens
Published: November 2024

This study investigated the efficacy of oxidised iron-loaded activated carbon cloth (Fe-ACC) for selective recovery of phosphorous. The capacitive deionisation (CDI) technology was employed, for rapid removal of phosphate, with the aim of reducing the reliance on high alkalinity environment for the regeneration of Fe-ACC electrode. Multiple experimental parameters, including applied potential, pH, and co-existing ions, were studied. Additionally, the CDI system was tested on a real water matrix (Lake Ormstrup, Denmark) to elucidate the electrodes’ performance on selective recovery of phosphate. About 69 ± 10% of the adsorbed phosphate were released at pH 12 via pure chemical desorption, which was ~ 50% higher than that at pH 9. The CDI system successfully demonstrated the selective removal of phosphate from the lake water. It reduced the concentration of phosphate from 1.69 to 0.49 mg/L with a 71% removal efficiency, while the removal percentages of other anions, namely chloride, sulphate, bromide, nitrite, nitrate, and fluoride, were 10%, 7%, 1%, 1.5%, 4%, and 7%, respectively.
Eosinophile Ösophagitis – aktuelles und zukünftiges Management
Authors: Kreienbühl Andrea , Straumann Alex
Published: November 2024

Leitsymptom der eosinophilen Ösophagitis (EoE) ist die Dysphagie bei soliden Speisen. Die Diagnose wird durch die histologische Untersuchung von Stufenbiopsien aus dem Ösophagus gestellt, wobei die Dichte der Eosinophilen ≥ 15 Zellen/hochauflösendes Gesichtsfeld (HPF) betragen muss. Nichtinvasive Methoden zur Diagnosesicherung konnten sich bislang nicht durchsetzen. Das therapeutische Spektrum der EoE kann auf folgende 3 Kategorien heruntergebrochen werden: Medikamente (topisch wirksame Kortikosteroide, Protonenpumpenhemmer, Biologika), Eliminationsdiäten sowie Dilatation (Bougierung des Ösophagus). Neben der „klassischen“ EoE zeigen sich vermehrt „EoE-Varianten“ mit EoE-typischen Beschwerden ohne Nachweis einer signifikanten Gewebeeosinophilie. Mittels der heute zugelassenen Medikamente können 60–80 % der Patient in eine Remission gebracht werden. Das medikamentöse Armamentarium wird in den kommenden Jahren erweitert werden. Unter anderem könnten topisch wirksame Immunsuppressiva, monoklonale Antikörper gegen Thymic Stromal Lymphopoietin (TSLP), kleine Moleküle und S1P-Rezeptor-Modulatoren Eingang in die EoE-Therapie finden.
Characterising Cancer Cell Responses to Cyclic Hypoxia Using Mathematical Modelling
Authors: Celora Giulia L. , Nixson Ruby , Pitt-Francis Joe M. , Maini Philip K. , Byrne Helen M.
Published: November 2024

In vivo observations show that oxygen levels in tumours can fluctuate on fast and slow timescales. As a result, cancer cells can be periodically exposed to pathologically low oxygen levels; a phenomenon known as cyclic hypoxia. Yet, little is known about the response and adaptation of cancer cells to cyclic, rather than, constant hypoxia. Further, existing in vitro models of cyclic hypoxia fail to capture the complex and heterogeneous oxygen dynamics of tumours growing in vivo. Mathematical models can help to overcome current experimental limitations and, in so doing, offer new insights into the biology of tumour cyclic hypoxia by predicting cell responses to a wide range of cyclic dynamics. We develop an individual-based model to investigate how cell cycle progression and cell fate determination of cancer cells are altered following exposure to cyclic hypoxia. Our model can simulate standard in vitro experiments, such as clonogenic assays and cell cycle experiments, allowing for efficient screening of cell responses under a wide range of cyclic hypoxia conditions. Simulation results show that the same cell line can exhibit markedly different responses to cyclic hypoxia depending on the dynamics of the oxygen fluctuations. We also use our model to investigate the impact of changes to cell cycle checkpoint activation and damage repair on cell responses to cyclic hypoxia. Our simulations suggest that cyclic hypoxia can promote heterogeneity in cellular damage repair activity within vascular tumours.
A decision tree for predicting the causative pathogens of community-acquired pneumonia from thin-section computed tomography
Authors: Sato Haruka , Okada Fumito , Nakao Yusuke , Asayama Yoshiki
Published: November 2024

Purpose

To determine whether decision trees are useful for predicting organisms that cause community-acquired pneumonia (CAP).

Materials and methods

We developed a decision tree for predicting the organisms that cause CAP based on previously reported characteristic computed tomography findings. Sixteen readers (two student doctors, six residents, and eight radiologists) separately diagnosed 68 randomly selected cases of CAP using chest computed tomography. The first, second, and third most likely causative organisms were estimated for each case, and the percentages of correct answers were evaluated for consistency with the isolated organisms. The same 68 cases were then read again using the decision tree, with the first three most likely organisms again being estimated, and the percentage of agreement was evaluated as the percentage of correct responses after using the decision tree.

Results

For student doctors, residents, and radiologists, the percentage of correct responses increased significantly (p < 0.0001) when the decision tree was used to predict the first, second, and third most probable causative organism. The radiologists all obtained an accuracy rate of 80% or higher when estimating up to three candidate organisms using the decision tree. The organism for which the decision tree was most useful was Mycoplasma pneumoniae, followed by Haemophilus influenzae and Chlamydophila pneumoniae (p < 0.001).

Conclusion

Use of the decision tree made it possible to estimate the organisms responsible for CAP with a high correct response rate.
Adjusting the significance of daily climate responses in tree-ring proxies
Authors: Torbenson Max C. A. , Stagge James H. , Chen Feng , Ziaco Emanuele , Esper Jan
Published: November 2024

Correlating tree-ring parameters with daily resolved climate data is becoming increasingly common for understanding the complex relationships between tree growth and the surrounding environment. However, with an increased number of calculated correlations, there is an inherent risk of spurious significance. In this study, we present an analysis using synthetic weather and tree-ring data mimicking the statistical properties of ten real-world sites across Europe to quantify the extent to which numerous comparisons may inflate maximum correlations. Comparisons of different tree-ring proxies, considering varying overlapping period lengths and seasons, revealed 95th percentile correlation differences reaching 0.25 by chance. Using synthetic tree-ring chronologies with an assigned non-signal (r = 0.00), spurious correlations can reach statistical significance in over 60% of tests. Correlation inflation is greater when: (1) the climate-proxy relationship is weaker; (2) comparison periods are shorter; and (3) the length of seasonal windows is longer. Autocorrelation in the proxy records does not appear to have a major effect. These findings indicate that caution should be exercised when computing high numbers of correlations with limited observations. We provide tables listing correlation inflations for precipitation- and temperature-sensitive tree-ring chronologies that can inform interpretations of significance.
Diagnostic value of systematic compression ultrasonography for the detection of unrecognized venous thromboembolism in patients admitted to an internal medicine ward for dyspnea
Authors: Sola Daniele , Bonometti Ramona , Comola Giulia , Manfredi Giulia Francesca , Perazzi Mattia , Patrucco Filippo , Gavelli Francesco , Scacchi Massimo , Prina Elisa , Pirisi Mario , Bellan Mattia
Published: November 2024

The diagnosis of venous thromboembolism (VTE) is complex, and many cases of pulmonary embolism (PE) and deep vein thrombosis (DVT) go undetected despite validated diagnostic algorithms. This study evaluated the diagnostic performance of compression ultrasound (CUS) when systematically performed in patients admitted to an internal medicine department for dyspnea and/or respiratory failure. We conducted a prospective observational cohort study of consecutive adult hospitalized patients admitted for dyspnea and/or respiratory failure with at least one of the following: tachycardia (> 100 bpm), tachypnea (> 20/min), chest pain, cough, syncope, or hemoptysis. Patients with a previous diagnosis of VTE or who underwent computed tomography pulmonary angiography (CTPA) or CUS during evaluation in the emergency department were excluded. The study included 263 patients (50.2% women, average age 84 years). CUS was positive in 31 patients (11.8%); Bilateral DVT was diagnosed in two patients and unilateral DVT in 29 patients. Of these, 10 underwent CT scan, with PE confirmed in 9 cases. Using the Wells score for DVT (cut-off ≥ 2), only 8 patients (25.8%) were at high risk. The accuracy of the Wells score in identifying PE was suboptimal, as 5 of 9 patients (55.5%) with confirmed PE were in the low-risk group (three-level interpretation) and 8 (89.9%) were in the “EP unlikely” group (two-level interpretation). The systematic use of CUS as a point-of-care tool can improve the diagnostic accuracy for VTE in patients admitted to internal medicine departments with dyspnea/respiratory failure.
Evaluating stress resilience of cyanobacteria through flow cytometry and fluorescent viability assessment
Authors: Kroupová Zuzana , Slaninová Eva , Mrázová Kateřina , Krzyžánek Vladislav , Hrubanová Kamila , Fritz Ines , Obruča Stanislav
Published: November 2024

Cyanobacteria are prokaryotic organisms characterised by their complex structures and a wide range of pigments. With their ability to fix CO2, cyanobacteria are interesting for white biotechnology as cell factories to produce various high-value metabolites such as polyhydroxyalkanoates, pigments, or proteins. White biotechnology is the industrial production and processing of chemicals, materials, and energy using microorganisms. It is known that exposing cyanobacteria to low levels of stressors can induce the production of secondary metabolites. Understanding of this phenomenon, known as hormesis, can involve the strategic application of controlled stressors to enhance the production of specific metabolites. Consequently, precise measurement of cyanobacterial viability becomes crucial for process control. However, there is no established reliable and quick viability assay protocol for cyanobacteria since the task is challenging due to strong interferences of autofluorescence signals of intercellular pigments and fluorescent viability probes when flow cytometry is used. We performed the screening of selected fluorescent viability probes used frequently in bacteria viability assays. The results of our investigation demonstrated the efficacy and reliability of three widely utilised types of viability probes for the assessment of the viability of Synechocystis strains. The developed technique can be possibly utilised for the evaluation of the importance of polyhydroxyalkanoates for cyanobacterial cultures with respect to selected stressor—repeated freezing and thawing. The results indicated that the presence of polyhydroxyalkanoate granules in cyanobacterial cells could hypothetically contribute to the survival of repeated freezing and thawing.
Almost the same, but not quite: an analysis of Late Bronze Age swords in the Balearic Islands
Authors: Perelló Mateo Laura , Llull Estarellas Bartomeu , Calvo Trías Manuel
Published: November 2024

In the present work we carry out a study of all the Late Bronze Age swords recorded in the Balearic Islands. They represent a set of local practices and traditions alongside foreign ideas and archetypes. To carry out the study, we employ a strategy that joins technological and archaeometric analyses with approaches that consider isotopes and typologies. Of note among the data considered is the importance of metal coming from deposits in Linares, followed by Menorca and Mallorca, and finally, more marginally, Sardinia. A technological analysis of the manufacturing processes provides evidence, in a local context, of the use of the lost-wax casting technique, compound objects, and ternary bronzes, all technologies foreign to the Balearic Islands. Finally, we reflect on the local practices in which these objects were embroiled. All of this allows us to provide an in-depth examination of the interaction networks as well as the changes that took place in local metallurgical practices as the result of the circulation of ideas and knowledge.
Towards biocultural realism: Connecting conservation with historical ecology and common sense. A European perspective
Authors: Bobiec Andrzej , Rotherham Ian D. , Kırca Simay , Molnár Zsolt , Agnoletti Mauro
Published: November 2024

In this perspective, we present and discuss four major causes of the worldwide nature conservation failure: 1) ideologies based on nature–culture dualism, 2) the bias prioritising forests in conservation, 3) the illusory objectiveness of selected biological indicators, and 4) the mismanagement of rural agricultural landscapes. All of these relate to ignorance of historical ecology and neglect of the role past plays in shaping landscapes and fostering biodiversity. These led to a false anthropology focussed on the broader human economy (including agriculture) as the absolute culprit of biodiversity loss. It is believed, therefore, that biodiversity preservation depends on conservation policies and actions providing protection against human activities, such as farming. In this way, nature conservation has been detached from the rich experiences of long and fruitful coexistence of people with other elements of nature. The bio-cultural legacy includes biodiversity-rich rural landscapes, whose habitats are often either neglected or wrongly interpreted as “remnants of natural ecosystems”. Consequently, conservation efforts are frequently ineffective or worse still, counter-effective. In the face of policies favouring subsidised intensive agribusiness at the cost of destroying smallholder family farming, even expensive conservation projects are usually nothing more than a “fig leaf” to cover failure. We advocate re-focussing of conservation planning to put more emphasis on landscapes’ historical ecology responsible for their bio-cultural diversity. It implies the need for new principles in policies necessary to secure the economic and cultural sovereignty of local socio-ecological systems responsible for the world’s bio-cultural diversity.
The Effect of Biochar on Tomato (Solanum lycopersicum) Cultivar Micro-Tom Grown under Continuous Light
Authors: Nicholas Larissa , Devine Aisling , Robertson Iain , Mabbett Ian
Published: November 2024

Continuous lighting (CL) has the potential to increase crop yield in greenhouse production. Tomato plants, however, when exposed to CL develop inter-vascular chlorosis, a leaf injury which causes a reduction in chlorophyll content and necrosis. The application of biochar can reduce physiological stress in plants, we examine if biochar also reduces necrosis in tomatoes when grown under CL. Faecal sludge biochar was applied to an acidic soil to examine plant growth and yield in Micro-Tom tomato plants grown under continuous light. We examined soil and plant growth properties of three soil application treatments: a control soil, biochar treatment (4%w/w) (Biochar), and a combined biochar (2% w/w) and fertilizer (2% w/w) treatment (Biochar + Fert). Faecal sludge biochar addition produced plant heights 216% greater than control and above ground biomass 583% greater than control. The biochar and fertilizer treatment group produced a 487% increase in leaf number compared to biochar. The combined biochar and fertilizer treatment produced a 398% increase in dried above ground biomass and a 177% increase in dried fruit yield compared with biochar. Plants in the biochar and fertilizer treatment group showed less visual evidence of continuous light induced leaf injury.Biochar addition did not limit continuous light induced leaf chlorosis whereas combined biochar and fertilizer treatment resulted in a significant reduction in leaf injury and death. Overall, the application of biochar and biochar and fertilizer combined increased crop yield.
How Chinese adolescents present themselves online regarding physical activity
Authors: Cui Min , Frühauf Anika , Demetriou Yolanda
Published: November 2024

Digital tools with social networking features are often utilised to promote physical activity among adolescents. However, the need to improve users’ experiences, motivation and engagement with these tools pointed out the need to explore experiences from adolescents’ perspectives. This study is a qualitative study exploring adolescents’ online culture, norms, self-presentation, and self-exposure regarding their physical activity, taking Chinese adolescents as the target population in a collectivist culture context. Inspired by Goffman’s dramaturgical model and Boyd’s concept of self-representation in digital media, we aim to explore how Chinese adolescents construct their online physical activity self-presentation, as well as what and how socio-cultural norms play a role in this process. After drawing a population sample from Chinese adolescents (aged 14–19 years, 50% female) and conducting 13 focus group discussions, our results suggested that Chinese adolescents are willing to construct an active, encouraging, modest and safe physical activity self-presentation on social media, but they also perceived body dissatisfaction, online comparison and privacy intrusion as potential dangers in physical activity self-presentation at the same time. The results demonstrated that Chinese adolescents’ physical activity self-presentation is the result of the interplay and negotiation between personal norms and sociocultural norms.
The inhibitory effect of Hypericum japonicum on H9N2 avian influenza virus
Authors: Hu Huiqiong , Li Jingmin , Zheng Shumei , Zhao Keyu , Xia Yongbo , Wei Xiaona , Han Mingzheng , Zhao Yukun , Peng Ouyang , Zhao Zhiqing , Chen Zexin , Su Weiwei , Cao Yongchang , Wang Yonggang , Xue Chunyi
Published: November 2024

The H9N2 subtype of avian influenza virus (AIV) causes severe immunosuppression and high mortality in view of its frequent co-infection with other pathogens, resulting in significant economic losses in the poultry industry. Current vaccines provide suboptimal immune protection against H9N2 AIV owing to antigenic variations, highlighting the urgent need for safe and effective antiviral drugs for the prevention and treatment of this virus. This study aimed to investigate the inhibitory effects of Hypericum japonicum extract on H9N2 AIV. Our findings revealed that the extract obtained through resin column separation using 60% ethanol (S06-60%) inhibited H9N2 AIV replication in Madin-Daby canine kidney cells in a dose-dependent manner. The maximum safe concentration of the water-soluble S06-60% extract was determined to be 0.05 mg/mL. Time-course experiments indicated that S06-60% primarily exerted its antiviral effects during the viral pretreatment and adsorption stages. Furthermore, in vivo experiments conducted on specific pathogen-free chickens confirmed the effectiveness of S06-60% in inhibiting H9N2 AIV infection and mitigating associated damage to tracheal and lung tissues. Overall, our study highlights the therapeutic potential of Hypericum japonicum extract S06-60% as a viable antiviral candidate against H9N2 AIV, offering promising implications for its application in poultry health management to reduce the economic impact on the poultry industry.
Comparative study of the W UMa type binaries S Ant and ε CrA
Authors: Bakış Volkan , Budding Edwin , Erdem Ahmet , Love Tom , Blackford Mark G. , Wu Zihao , Tang Adam , Rhodes Michael , Banks Timothy S.
Published: November 2024

Contact binaries challenge contemporary stellar astrophysics with respect to their incidence, structure, and evolution. We explore these issues through a detailed study of two bright examples: S Ant and

$\varepsilon$

CrA, that permit high-resolution spectroscopy at a relatively good S/N ratio. The availability of high-quality photometry, including data from the TESS satellite as well as Gaia parallaxes, allows us to apply the Russell paradigm to produce reliable up-to-date information on the physical properties of these binaries. As a result, models of their interactive evolution, such as the thermal relaxation oscillator scenario, can be examined. Mass transfer between the components is clearly evidenced, but the variability of the O’Connell effect over relatively short-time scales points to irregularities in the mass transfer or accretion processes. Our findings indicate that S Ant may evolve into an R CMa type Algol, while the low mass ratio of

$\varepsilon$

CrA suggests a likely merger of its components in the not-too-distant future.
(In)definites, pronouns and bare nouns: How Turkish/Swedish bilingual 4-to-7-year-olds introduce characters in narratives in Swedish
Authors: Lindgren Josefin , Bohnacker Ute
Published: November 2024

This study investigates the referential forms children use to introduce characters in Swedish, in a cross-sectional sample of oral narratives by 100 Turkish/Swedish bilinguals aged 4 to 7 and in a longitudinal sample from age 4 to 6 (N = 10). We analysed development with age and how language proficiency (expressive vocabulary) and exposure affect children’s use of referring expressions, with a focus on referential appropriateness. In addition, a qualitative analysis of the characteristics of high- and low-performing children was carried out. The results show significant effects of age and language proficiency, but not of language exposure on appropriate use of referring expressions. At age 7, 69% of the characters were introduced with an indefinite NP. The Turkish/Swedish bilinguals were found to lag behind in their use of indefinite NPs in comparison to Swedish-speaking children investigated in previous studies, with little crosslinguistic influence from L1 Turkish.
Smooth and proper maps with respect to a fibration
Authors: Anel Mathieu , Weinberger Jonathan
Published: November 2024

This paper explain how the geometric notions of local contractibility and properness are related to the
$\Sigma$
-types and
$\Pi$
-types constructors of dependent type theory. We shall see how every Grothendieck fibration comes canonically with such a pair of notions—called smooth and proper maps—and how this recovers the previous examples and many more. This paper uses category theory to reveal a common structure between geometry and logic, with the hope that the parallel will be beneficial to both fields. The style is mostly expository, and the main results are proved in external references.
Robotic capital - skill complementarity
Authors: Battisti Michele , Del Gatto Massimo , Gravina Antonio Francesco , Parmeter Christopher F.
Published: November 2024

Relying upon an original (country-sector-year) measure of robotic capital (

$RK$

), we investigate the degree of complementarity/substitutability between robots and workers at different skill levels. We employ nonparametric methods to estimate elasticity of substitution patterns between

$RK$

and skilled/unskilled labor over the period 1995–2009. We show that: i) on average,

$RK$

exhibits less substitutability with skilled workers compared to unskilled workers, indicating a phenomenon of “RK-Skill complementarity”. This pattern holds in a global context characterized by significant heterogeneity; ii) the dynamic of “RK-Skill complementarity” has increased since the early 2000s; iii) the observed strengthening is more prominent in OECD countries, as opposed to non-OECD countries, and in the Manufacturing sector, compared to non-Manufacturing industries.
RATIONAL REPRESENTATIONS AND RATIONAL GROUP ALGEBRA OF VZ
$\boldsymbol {p}$
-GROUPS
Authors: CHOUDHARY RAM KARAN , PRAJAPATI SUNIL KUMAR
Published: November 2024

In this article, we study rational matrix representations of VZ p-groups (p is any prime). Using our findings on VZ p-groups, we explicitly obtain all inequivalent irreducible rational matrix representations of all p-groups of order
$\leq p^4$
. Furthermore, we establish combinatorial formulae to determine the Wedderburn decompositions of rational group algebras for VZ p-groups and all p-groups of order
$\leq p^4$
, ensuring simplicity in the process.
Did the pandemic lead to a change in attitudes towards cCBT? A service evaluation looking at the impact of the pandemic on practitioner beliefs regarding the routine use of cCBT within an NHS Talking Therapies Service
Authors: Ragan Kathryn , Kelly Claire , Thwaites Richard
Published: November 2024

Computerised CBT (cCBT) is an established and evidence-based treatment for depression and some anxiety disorders. This paper aimed to replicate the study of Meisel et al. (2018), to understand more about therapist beliefs regarding offering cCBT within a service-evaluation. Meisel et al. (2018) found that although most staff in an inner-city IAPT service were confident offering cCBT to clients, staff believed there was not a strong evidence-base, and training on cCBT was identified as a solution to low cCBT uptake. The unexpected COVID-19 pandemic provided an opportunity to collect additional data to understand the impact of significant societal changes and service delivery methods to see if this led to a change in attitudes towards cCBT as Wind et al. (2020) hypothesised.

Data on staff beliefs about the provision of cCBT from one rural UK Talking Therapies service is presented across three time points: pre-COVID pandemic, post-COVID pandemic, and following additional cCBT training. Staff completed a survey at each time point, containing agree/disagree ratings and free-text questions, obtaining perspectives on cCBT including advantages, barriers/problems, and confidence. This paper reports staff opinions with commentary on how they have changed over time. Between time points 1 and 3, agreement with the statement ‘supporting clients using cCBT requires a high level of skill’ increased by 29%. Several beliefs did not change, despite moving towards more remote working in the pandemic, and training. Although the paper illustrates some changes in beliefs over time, it does not provide support for changes in therapist beliefs, with reasons for this examined.

Key learning aims

(1)

Following reading this paper, the reader will understand changes in staff beliefs and attitudes towards cCBT that occurred between pre-pandemic and post-pandemic time points in one NHS Talking Therapies service.

(2)

The reader will also be aware of the beliefs that have not changed following both the pandemic and additional staff training on cCBT and will be able to consider why this might be and whether it may be generalisable across wider services.

(3)

The reader will be aware of potential interventions that could be introduced to try and address the ‘stubborn beliefs’ around cCBT that are not consistent with the evidence-base and may limit patient access to this option.
The East London Classics Summer School 2024
Authors: Merali-Smith Sarah
Published: November 2024

This is a review of the activities and successes of the 4th East London Classics Summer School, which took place in Hackney from Monday 29th July to Friday 2nd August 2024. Specifically, it covers our typical teaching arrangement, lectures and trips, and it also acknowledges the generosity of those supporting our initiative.
Constraints on the Projected Tropical Pacific Sea Surface Temperature Warming Pattern by the Tropical North Atlantic Cold SST Bias in CMIP6 Models
Authors: Ying Jun , Collins Matthew , Chadwick Robin , Ma Jian , Lian Tao
Published: November 2024

Reliable projections of the tropical Pacific sea surface temperature (SST) warming (TPSW) patterns are critically important for exploring the future climate change. However, climate models suffer from long‐standing common biases in simulating the present‐day climate, raising doubts about the model projected TPSW patterns. Here by using outputs from 30 CMIP6 models, we find the projected TPSW patterns are significantly correlated with the simulated present‐day SST in the tropical North Atlantic (TNA), with higher present‐day TNA SSTs tending to project more weakened zonal SST gradients by producing more present‐day low‐level clouds and the resultant positive cloud–shortwave–SST feedbacks over the eastern equatorial Pacific. An emergent constraint using observed TNA SST reveals a consistent El Niño‐like warming pattern in all models with more weakened zonal SST gradient than before in most models, together with a reduction of the inter‐model uncertainty in the zonal SST gradient change by more than 20%.
KIF1A promotes neuroendocrine differentiation in prostate cancer by regulating the OGT-mediated O-GlcNAcylation
Authors: Zhou Qianqian , Yang Muyi , Fu Jiawei , Sun Xinyu , Wang Jiajia , Zhang Hanwen , Hu Jing , Han Bo
Published: November 2024

Neuroendocrine prostate cancer (NEPC) arises from prostate adenocarcinoma after endocrine treatment failure and implies lethality and limited therapeutic options. Deciphering the molecular mechanisms underlying transdifferentiation from adenocarcinoma to NEPC may provide valuable therapeutic strategies. We performed a pan-cancer differential mRNA abundance analysis and identified that Kinesin-like protein (KIF1A) was highly expressed in NEPC. KIF1A knockdown impaired neuroendocrine(NE) features, including NE marker gene expression, stemness, and epithelial–mesenchymal transition (EMT), whereas KIF1A overexpression promoted these processes. Targeting KIF1A inhibited the growth of NE differentiated prostate cancer (PCa) cells in vitro and in vivo. Mechanistically, KIF1A bound with O-linked N-acetylglucosamine transferase (OGT) and regulated its protein expression and activity. Nuclear accumulation of OGT induced by KIF1A overexpression promoted intranuclear O-GlcNAcylation of β-catenin and OCT4 in nucleus. More importantly, our data revealed that OGT was critical for KIF1A induced NE differentiation and aggressive tumor growth. An OGT inhibitor, OSMI-1, can significantly inhibited NE differentiated PCa cell proliferation in vitro and tumor growth in vivo. Our findings showed that KIF1A promotes NE differentiation to NEPC by regulating the OGT-mediated O-GlcNAcylation. Targeting O-GlcNAcylation may impede the development of NEPC for a group of PCa patients with elevated KIF1A expression.
Phenotypic and genetic characteristics of retinal vascular parameters and their association with diseases
Authors: Ortín Vela Sofía , Beyeler Michael J. , Trofimova Olga , Iuliani Ilaria , Vargas Quiros Jose D. , de Vries Victor A. , Meloni Ilenia , Elwakil Adham , Hoogewoud Florence , Liefers Bart , Presby David , Ramdas Wishal D. , Tomasoni Mattia , Schlingemann Reinier , Klaver Caroline C. W. , Bergmann Sven
Published: November 2024

Fundus images allow for non-invasive assessment of the retinal vasculature whose features provide important information on health. Using a fully automated image processing pipeline, we extract 17 different morphological vascular phenotypes, including median vessels diameter, diameter variability, main temporal angles, vascular density, central retinal equivalents, the number of bifurcations, and tortuosity, from over 130,000 fundus images of close to 72,000 UK Biobank subjects. We perform genome-wide association studies of these phenotypes. From this, we estimate their heritabilities, ranging between 5 and 25%, and genetic cross-phenotype correlations, which mostly mirror the corresponding phenotypic correlations, but tend to be slightly larger. Projecting our genetic association signals onto genes and pathways reveals remarkably low overlap suggesting largely decoupled mechanisms modulating the different phenotypes. We find that diameter variability, especially for the veins, associates with diseases including heart attack, pulmonary embolism, and age of death. Mendelian Randomization analysis suggests a causal influence of blood pressure and body mass index on retinal vessel morphology, among other results. We validate key findings in two independent smaller cohorts. Our analyses provide evidence that large-scale analysis of image-derived vascular phenotypes has sufficient power for obtaining functional and causal insights into the processes modulating the retinal vasculature.
Orangutans and chimpanzees produce morphologically varied laugh faces in response to the age and sex of their social partners
Authors: Crepaldi Fabio , Rocque Florence , Dezecache Guillaume , Proops Leanne , Davila-Ross Marina
Published: November 2024

Laugh faces of humans play a key role in everyday social interactions as a pervasive tool of communication across contexts. Humans often vary the degree of mouth opening and teeth exposure when producing these facial expressions, which may depend on who their social partner is (e.g., their gender and age as well as their social relationship), serving this way different functions. Although it was found that laugh faces show evolutionary continuity across humans and non-human great apes according to the Principle of Maximum Parsimony, little is known about the function of laugh face variations from an evolutionary perspective. Hence, the present work examined the morphology of laugh faces in orangutan and chimpanzee dyadic play to test if they are modified with dependence on the playmate’s characteristics (sex, age and social relationship). In total, we analysed over 600 facial expressions of 14 orangutans and 17 chimpanzees by coding the specific muscle activations (Action Units, i.e. AUs) contributing to these expressions, using OrangFACS and ChimpFACS, respectively. Our results suggest that age difference and, to a lesser extent, playmate sex influence laugh face morphology in both taxa, but in opposite ways. While the orangutans of our study seem to expose their upper teeth (with AU10) and to pull the mouth corners (with AU12) more towards weaker partners (younger and female), possibly to communicate non-hostility, the chimpanzees showed both upper and lower teeth exposure (with AU10 and AU16) more often when interacting with the stronger partners (older individuals), possibly to communicate submissiveness. These findings suggest that the ability of humans to modify laugh faces with dependence on social partner characteristics has most likely evolved from pre-existing traits, going back at least to the last common ancestor of today’s great apes, including humans.
Microbial education plays a crucial role in harnessing the beneficial properties of microbiota for infectious disease protection in Crassostrea gigas
Authors: Dantan Luc , Carcassonne Prunelle , Degrémont Lionel , Morga Benjamin , Travers Marie-Agnès , Petton Bruno , Mege Mickael , Maurouard Elise , Allienne Jean-François , Courtay Gaëlle , Romatif Océane , Pouzadoux Juliette , Lami Raphaël , Intertaglia Laurent , Gueguen Yannick , Vidal-Dupiol Jeremie , Toulza Eve , Cosseau Céline
Published: November 2024

The increase in marine diseases, particularly in economically important mollusks, is a growing concern. Among them, the Pacific oyster (Crassostrea gigas) production faces challenges from several diseases, such as the Pacific Oyster Mortality Syndrome (POMS) or vibriosis. The microbial education, which consists of exposing the host immune system to beneficial microorganisms during early life stages is a promising approach against diseases. This study explores the concept of microbial education using controlled and pathogen-free bacterial communities and assesses its protective effects against POMS and Vibrio aestuarianus infections, highlighting potential applications in oyster production. We demonstrate that it is possible to educate the oyster immune system by adding microorganisms during the larval stage. Adding culture based bacterial mixes to larvae protects only against the POMS disease while adding whole microbial communities from oyster donors protects against both POMS and vibriosis. The efficiency of immune protection depends both on oyster origin and on the composition of the bacterial mixes used for exposure. No preferential protection was observed when the oysters were stimulated with their sympatric strains. Furthermore, the added bacteria were not maintained into the oyster microbiota, but this bacterial addition induced long term changes in the microbiota composition and oyster immune gene expression. Our study reveals successful immune system education of oysters by introducing beneficial microorganisms during the larval stage. We improved the long-term resistance of oysters against critical diseases (POMS disease and Vibrio aestuarianus infections) highlighting the potential of microbial education in aquaculture.
Acute kidney injury in hematological patients treated with CAR-T cells: risk factors, clinical presentation and impact on outcomes
Authors: Russo Elisa , Gambella Massimiliano , Raiola Anna Maria , Beltrametti Elena , Zanetti Valentina , Chirco Giuseppe , Viazzi Francesca , Angelucci Emanuele , Esposito Pasquale
Published: November 2024

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, yet it carries significant risks, including acute kidney injury (AKI). In this study, we investigated the risk factors and clinical impact of AKI in patients undergoing CAR-T cell therapy. This retrospective study involved hematologic patients treated with CAR-T therapy. Clinical and laboratory data were collected, and clinical outcomes were monitored during follow-up after CAR-T infusion. AKI was defined according to KDIGO criteria. The outcome measures included early mortality, overall survival (OS), and disease-free survival (DFS). Among the 48 patients analyzed, 14 (29%) developed AKI, with a mean onset of 6 days after CAR-T infusion. The risk of AKI was associated with baseline performance status (OR 8.65, IC95% 6.2–12, p = 0.032) and the development of severe cytokine release syndrome post-therapy (OR 16.4 95%CI 1.9-138.5, p = 0.01). Patients with AKI more frequently required intensive care. Furthermore, severe AKI was independently associated with worse clinical outcomes, including reduced OS and DFS (HR 18.2, 95%CI 2.6–27.3, p = 0.003). Additionally, patients who developed AKI post-CAR-T therapy were more likely to progress to chronic kidney disease during follow-up. In conclusion, frail patients undergoing CAR-T therapy are at an increased risk of developing AKI, which can significantly affect both short- and long-term outcomes. Preventive strategies and early recognition of AKI are essential in these patients.
Inhibiting ADAM17 enhances the efficacy of olaparib in ovarian cancer spheroids
Authors: Rogmans Christoph , Dittrich Jan , Hamm Emily , Weimer Jörg Paul , Holthaus David , Arnold Norbert , Flörkemeier Inken , Maass Nicolai , Jansen Peer , Dempfle Astrid , Bauerschlag Dirk O. , Hedemann Nina
Published: November 2024

Acquired or de novo resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) is a major challenge to ovarian cancer treatment. Therefore, strategies to overcome PARPi resistance are critical to improve prognosis. The purpose of this study is to evaluate whether inhibition of ADAM17 sensitizes ovarian cancer to treatment with olaparib, a PARPi, thereby bypassing resistance mechanisms and improving treatment response. Thus, we analyzed the effect of olaparib in combination with the ADAM17 inhibitor GW280264X in ovarian cancer using a 2D monolayer and a 3D spheroid model followed by a multicontent readout (viability, caspase activation and cytotoxicity). To emphasize the translational aspect of our work, we performed corresponding experiments on primary cells derived from ovarian cancer patients initially screened for their mutation status of the breast cancer gene (BRCA 1/2). In 2D, we observed a significant reduction in cell viability and a subsequent increase in apoptosis of the combined treatment (olaparib + GW280264X) compared with olaparib mono-treatment. The combined treatment allows a substantial dose reduction of olaparib rendering a strong synergistic effect. Using a 3D spheroid model from primary cells, we confirmed the 2D monoculture results and demonstrated not only increased caspase activity under the combined treatment but also a substantial gain in cytotoxicity compared to the mono-treatment. Our study proposes ADAM17 inhibition sensitizing ovarian cancer to olaparib treatment and improving treatment response.
Experimental and theoretical insights into the adsorption mechanism of methylene blue on the (002) WO3 surface
Authors: Hkiri Khaoula , Mohamed Hamza Elsayed Ahmed , Abodouh Mohamed Mahrous , Maaza Malik
Published: November 2024

This work investigates the efficiency of green-synthesized WO3 nanoflakes for the removal of methylene blue dye. The synthesis of WO3 nanoflakes using Hyphaene thebaica fruit extract results in a material with a specific surface area of 13 m2/g and an average pore size of 19.3 nm. A combined theoretical and experimental study exhibits a complete understanding of the MB adsorption mechanism onto WO3 nanoflakes. Adsorption studies revealed a maximum methylene blue adsorption capacity of 78.14 mg/g. The pseudo-second-order model was the best to describe the adsorption kinetics with a correlation coefficient (R2) of 0.99, suggesting chemisorption. The intra-particle diffusion study supported a two-stage process involving surface adsorption and intra-particle diffusion. Molecular dynamic simulations confirmes the electrostatic attraction mechanism between MB and the (002) WO3 surface, with the most favorable adsorption energy calculated as -0.68 eV. The electrokinetic study confirmed that the WO3 nanoflakes have a strongly negative zeta potential of -31.5 mV and a uniform particle size of around 510 nm. The analysis of adsorption isotherms exhibits a complex adsorption mechanism between WO3 and MB, involving both electrostatic attraction and physical adsorption. The WO3 nanoflakes maintained 90% of their adsorption efficiency after five cycles, according to the reusability tests.
Three diverse motives for information sharing
Authors: Vellani Valentina , Glickman Moshe , Sharot Tali
Published: November 2024

Knowledge is distributed over many individuals. Thus, humans are tasked with informing one another for the betterment of all. But as information can alter people’s action, affect and cognition in both positive and negative ways, deciding whether to share information can be a particularly difficult problem. Here, we examine how people integrate potentially conflicting consequences of knowledge, to decide whether to inform others. We show that participants (Exp1: N = 114, Pre-registered replication: N = 102) use their own information-seeking preferences to solve complex information-sharing decisions. In particular, when deciding whether to inform others, participants consider the usefulness of information in directing action, its valence and the receiver’s uncertainty level, and integrate these assessments into a calculation of the value of information that explains information sharing decisions. A cluster analysis revealed that participants were clustered into groups based on the different weights they assign to these three factors. Within individuals, the relative influence of each of these factors was stable across information-seeking and information-sharing decisions. These results suggest that people put themselves in a receiver position to determine whether to inform others and can help predict when people will share information.
Dominant HPAIV H5N1 genotypes of Germany 2021/2022 are linked to high virulence in Pekin ducklings
Authors: Piesche Ronja , Breithaupt Angele , Pohlmann Anne , Ahrens Ann Kathrin , Beer Martin , Harder Timm , Grund Christian
Published: November 2024

Highly pathogenic avian influenza viruses (HPAIV) of H5 clade 2.3.4.4b pose an ongoing threat worldwide. It remains unclear whether this panzootic situation would favor low virulent phenotypes expected by the ‘avirulence hypothesis’ of viral evolution. Assessing virulence in Pekin ducklings in an intramuscular infection model revealed that the two genotypes that dominated the epidemiological situation in Germany during the period 2021 and 2022 (EU-RL:CH and EU-RL:AB) were of high virulence. In contrast, rare genotypes were of intermediate virulence. The genetic constellation of these reassortants pointed to an important role of the viral polymerase complex (RdRP), particularly the PB1 genome segment, in shaping virulence in ducklings. Occulo-nasal infection of ducklings confirmed the phenotypes for two representative viruses and indicated a more efficient replication for the high virulence strain. These observations would be in line with the ‘virulence-transmission trade-off’ model for describing HPAIV epidemiology in wild birds in Germany.
Future cities demand smart and equitable infrastructure resilience modeling perspectives
Authors: Padgett J. E. , Rincon R. , Panakkal P.
Published: November 2024

Risk-informed decisions that promote infrastructure resilience (or the ability to withstand, recover from, and adapt to stressors like natural hazards) require confident predictions of system performance now and into the future. We propose a perspective shift–one capable of handling uncertain and dynamic conditions, leveraging emerging observations from smart systems, and guided by demands for social equity. This shift requires collective efforts, but our future cities demand and deserve it.
An integrated model of electric bus energy consumption and optimised depot charging
Authors: Hendriks Johannes N. , Sturmberg Björn. C. P.
Published: November 2024

The electrification of buses, and the depots servicing them, is a high priority for sustainability but is hindered by challenges at the intersection of the mobility and electricity systems, such as trade-offs of charging infrastructure and scheduling with the stress placed on the grid. This paper presents a model for studying and co-optimise these variables. The model has two standout features. Firstly, that it integrates a data-driven model for predicting the energy consumption of electric buses based on route details with a bus depot charging optimisation algorithm that minimises the loading on the grid. Secondly, it is compatible with the publicly available route and schedule data published by bus operators and is available open-source for extension. The results foreground the impact of route topology, temperature, and traffic congestion on energy consumption, and the interdependencies of these with timetabling, charging infrastructure and battery designs in driving grid loading.