bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of Ferrite Morphology and Ferrite-Ferrite Grain Boundary Characteristics with Cooling Rate in a Continuously Cooled 0.09C-0.08V-0.02N Microalloyed Steel
Authors: Church Adam J. , Tselikova Anastasiya , Schmidt Rolf , Cho Lawrence , De Moor Emmanuel , Findley Kip O.
Published: December 2024

Continuously cooled HSLA steels produce mixed ferritic and bainitic microstructures with multiple constituents present within the same prior-austenite grain. Conventional methods of distinguishing these constituents have relied on size and morphology characteristics, which have inherent subjectivity in identifying constituents. In this study, grain boundary misorientation distributions were utilized to more objectively identify different quasi-polygonal ferritic, acicular ferritic, bainitic, and martensitic microstructures within a continuously cooled V-microalloyed HSLA steel. It was determined that the slower-cooled morphology of acicular ferrite commonly observed in line-pipe steels produced approximately equal 55 and 60 deg peaks in the misorientation distribution, while the more lenticular faster-cooled acicular ferrite produced at a cooling rate of 25 °C/s had a stronger peak at the 60 deg misorientation. The P2/P1 ratio, which quantified the ratio of these two misorientation peaks, was employed to differentiate these two acicular ferrite morphologies. These constituents also exhibited different axis/angle misorientation distributions in the high-angle grain boundary misorientation regime than both quasi-polygonal ferrite and martensitic/bainitic microstructures.
Managing Intracranial Pressure Crisis
Authors: Viarasilpa Tanuwong
Published: December 2024

Purpose of Review

The objective of this review is to provide a comprehensive management protocol for the treatment of intracranial pressure (ICP) crises based on the latest evidence.

Recent Findings

The review discusses updated information on various aspects of critical care management in patients experiencing ICP crises, including mechanical ventilation, fluid therapy, hemoglobin targets, and hypertonic saline infusion, the advantages of ICP monitoring, the critical ICP threshold, and bedside neuromonitoring.

All aspects of critical care treatment, including hemodynamic and respiratory support and adjustment of ICP reduction therapy, may impact patient outcomes. ICP monitoring allows ICP values, trends, waveforms, and CPP calculation, which are helpful to guide patient care. Advanced neuromonitoring devices are available at the bedside to diagnose impaired intracranial compliance and intracranial hypertension, assess brain function, and optimize cerebral perfusion. Future research should focus on developing appropriate intervention protocols for both invasive and noninvasive neuromonitoring in managing ICP crisis patients.
Predictive model for HBsAg clearance rate in chronic hepatitis B patients treated with pegylated interferon α-2b for 48 weeks
Authors: Tan Zhili , Kong Nan , Zhang Qiran , Gao Xiaohong , Shang Jia , Geng Jiawei , You Ruirui , Wang Tao , Guo Ying , Wu Xiaoping , Zhang Wenhong , Qu Lihong , Zhang Fengdi
Published: December 2024

Background and Aims

Chronic hepatitis B (CHB) is a major global health concern. This study aims to investigate the factors influencing hepatitis B surface antigen (HBsAg) clearance in CHB patients treated with pegylated interferon α-2b (Peg-IFNα-2b) for 48 weeks and to establish a predictive model.

Methods

This analysis is based on the “OASIS” project, a prospective real-world multicenter study in China. We included CHB patients who completed 48 weeks of Peg-IFNα-2b treatment. Patients were randomly assigned to a training set and a validation set in a ratio of approximately 4:1 by spss 26.0, and were divided into clearance and non-clearance groups based on HBsAg status at 48 weeks. Clinical data were analyzed using SPSS 26.0, employing chi-square tests for categorical data and Mann–Whitney U tests for continuous variables. Significant factors (p < 0.05) were incorporated into a binary logistic regression model to identify independent predictors of HBsAg clearance. The predictive model’s performance was evaluated using ROC curve analysis.

Results

We included 868 subjects, divided into the clearance group (187 cases) and the non-clearance group (681 cases). They were randomly assigned to a training set (702 cases) and a validation set (166 cases). Key predictors included female gender (OR = 1.879), lower baseline HBsAg levels (OR = 0.371), and cirrhosis (OR = 0.438). The final predictive model was:

Logit(P) = 0.92 + Gender (Female) * 0.66 - HBsAg (log) * 0.96 - Cirrhosis * 0.88. ROC analysis showed an AUC of 0.80 for the training set and 0.82 for the validation set, indicating good predictive performance.

Conclusion

Gender, baseline HBsAg levels, and cirrhosis are significant predictors of HBsAg clearance in CHB patients after 48 weeks of Peg-IFNα-2b therapy. The developed predictive model demonstrates high accuracy and potential clinical utility.
Experts’ perspectives on human gene editing in Switzerland
Authors: Berlincourt Jade , Gächter Sumanie , Vayena Effy , Ormond Kelly E
Published: December 2024

Despite many specialized studies on the views of the public or stakeholders who face inherited conditions that may be treatable by HGE, limited studies have focused on experts’ views towards Human Gene Editing (HGE). Therefore, in this study we conducted exploratory interviews with 14 experts (scientists, clinicians, social scientists, lawyers) in Switzerland to assess their views towards HGE and how they expect the Swiss public to view HGE. We found general acceptance of Somatic Gene Editing (SGE), but opinions towards Germline Gene Editing (GGE) were more divided. Participants emphasized patient autonomy and informed decision-making in pursuing gene editing treatments, and described a need for regulation, as with any other new therapy. Only a few participants (mostly lawyers and ethicists) described the regulations that currently prohibit GGE in Switzerland. Some expressed concern that restrictive regulations would lead to healthcare outsourcing and medical tourism to other nearby countries, as it has in the past with other restricted technologies. The analysis explored the unique Swiss context that is shaped by cultural diversity, conservative attitudes towards new medical technologies, and a democratic system that engages the public in policy and law making. Given that our findings identify areas of difference from that published in other countries, we emphasize the value in conducting similar research across different countries in order to achieve a global sense of attitudes towards HGE, so that regulations can be tailored to the diverse needs of citizens around the world.
“Men don’t feel comfortable with successful female leaders”: exploring participatory exclusion in community-based fisheries management, South Coast of Kenya
Authors: Chambon Mouna , Wambiji Nina , Wandiga Joe Ngunu , Reyes-Garcia Victoria , Ziveri Patrizia
Published: December 2024

While community-based fisheries management (CBFM) is promoted as a promising approach to achieving sustainable fisheries management, its inclusiveness is increasingly questioned in the literature. Studies that explore the inclusion of gender along other intersectional social identities in CBFM are scarce. This research gap may limit a comprehensive understanding of power dynamics in fisheries settings, while reinforcing exclusive approaches in fisheries governance. In this study, we draw on literature on participatory exclusion, intersectionality and lived experiences, to examine gender-inclusiveness in CBFM through a case study on the South Coast of Kenya. We applied qualitative data collection methods, combining participant observation, semi-structured interviews (n=18), focus group discussions (n=6) and relief maps (n= 32). Our findings indicate that women’s participation in CBFM is limited and systematically lower than men’s participation. Barriers to women’s participation in CBFM are complex and interlaced, including socio-cultural, economic, and institutional barriers, and specific restrictions to women’s access to leadership. In addition, our findings highlight the intersected nature of lived experiences related to CBFM places and suggest that CBFM may sustain and reinforce social inequalities in fishing communities. Overall, our results tend to confirm the relevance of the participatory exclusion concept to CBFM in coastal Kenya. Our study demonstrates the importance of applying an intersectional framework to study the complexity of power relationships in CBFM contexts, as well as fisheries management and governance. We conclude by providing key recommendations towards inclusive management approaches in fisheries settings.
Optimising manufacturing growth: when to decouple from global value chains?
Authors: Banga Karishma , Goldar Bishwanath
Published: December 2024

In this paper, we empirically examine how increasing forward and backward global value chains (GVC) linkages affect manufacturing growth in a set of low- and middle-income countries for the period 1995–2018. Using panel data methodologies of fixed-effects, quantile, and threshold regressions, we find that the relationship between these linkages and manufacturing growth is nonlinear. Our results reveal that there is a positive relationship between backward linkages (BL) and manufacturing growth, but once BL exceed the 11–20% range, the relationship becomes negative. Similarly, FL can drive manufacturing growth up to a certain threshold, beyond which it no longer boosts growth and may even start to reduce it. The negative relationship between GVC linkages and manufacturing growth is attributed to the ‘in–out–in’ theory of GVC participation. Based on these findings, we identify countries that can benefit from increasing GVC participation and those that will benefit from a decoupling from GVCs.
Das Schichtenkonzept kontextabhängiger Vulnerabilität im Gesundheitswesen
Authors: Mainka Christine Sibylle
Published: December 2024

Zuschreibungen von Vulnerabilität können Schaden verursachen, wenn nicht die individuelle Lage einzelner Menschen betrachtet wird. Um die spezifische Vulnerabilität, die für einen bestimmten Menschen in einer bestimmten Situation liegt, zu verstehen und zu erfassen, schlägt Florencia Luna die Analyse vorliegender unterschiedlicher Schichten von Vulnerabilität vor, die sich gegenseitig beeinflussen können. In Verbindung mit dem Konzept pathogener Vulnerabilitäten von Catriona Mackenzie, Wendy Rogers und Susan Dodds ergibt sich ein feministisches Verständnis kontextabhängiger Vulnerabilität, mit dem nicht nur Forschungsstudiensettings, sondern ebenfalls Therapiepläne sowie Präventionsmaßnahmen auf Zugänglichkeit, Umsetzbarkeit und potenzielle Risiken hin untersucht werden können. Dieses Schichtenkonzept kontextabhängiger Vulnerabilität vermeidet essentialistische Zuschreibungen und macht sprach- und handlungsfähig in Hinblick auf individuelle Risiken und Unterstützungsbedarfe im Gesundheitswesen. Die vielfältige Anwendbarkeit wird im letzten Teil der vorliegenden Untersuchung anhand des Beispiels der gemeinsamen Behandlungsplanung in der onkologischen Therapie sowie der Nutzung von mobilen Gesundheitstechnologien verdeutlicht.
Optimization of cementitious mixes through response surface method: a systematic review
Authors: Hurtado-Alonso Nerea , Manso-Morato Javier , Revilla-Cuesta Víctor , Skaf Marta , Ortega-López Vanesa
Published: December 2024

The pursuit of cement-based materials with enhanced mechanical performance in the construction industry involves formulating numerous mixtures with varied contents of raw materials. However, the scarcity or contamination of these materials demands optimization methods to minimize the number of trials required. Response Surface Methodology (RSM) is a statistical experimental optimization method with which relations between sets of factors and responses can be established. This systematic review aims to analyze the existing literature on RSM models developed to achieve optimum levels in cementitious mixes. Over 100 papers were analyzed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) format. A comprehensive review of the RSM analyses in those studies and their effectiveness is conducted, through the evaluation of their optimized factors and responses, the selection of their design models, their use of ANalysis Of VAriance (ANOVA), and the determination of their coefficients of determination (R
2). Factors such as water/cement ratio and binder content prevailed in most models, the predominant responses of which were, respectively, compressive strength and workability. Although the use of ANOVA is commonly used to demonstrate the validity of the models, the studies replicating the mix with optimal levels of all factors are necessary to validate the results. On the basis of this review and depending on the responses that need to be maximized or minimized, the application of RSM can clearly be very crucial when quantifying the effects of new raw materials, whether recovered waste or natural resources, on mix behaviour.
Type I and Type II photosensitization of DNA etheno adducts
Authors: Lizondo-Aranda Paloma , Rodríguez-Muñiz Gemma M. , Miranda Miguel A. , Heyne Belinda , Lhiaubet-Vallet Virginie
Published: December 2024

Photophysical and photochemical studies were carried out to examine the photoreactivity of etheno adducts, 1,N
6-ethenoadenine (εdA) and 1,N
2-ethenoguanine (εdG), in the presence of two well-known photosensitizers acting by Type I and/or Type II mechanisms such as 4-carboxybenzophenone (CBP) and rose Bengal (RB), respectively. Steady-state photolysis experiments combined with HPLC and mass spectroscopy measurements lead to photoproducts that correspond to the repaired nucleosides. To determine the mechanism of this photooxidation processes, phosphorescence spectroscopy, direct detection of singlet oxygen luminescence and laser flash photolysis were carried out. This work establishes that εdG and εdA are sensitive to both types of processes (Type I and II).

Graphical abstract
Synthesis of multifunctional nano composites incorporating halloysite nanoclay
Authors: Zohoori Salar , Torabi Narges , Gholami Elham , Rastgoo Fatemeh , Rad Maryam , Pourheidari Roya
Published: December 2024

This study was conducted in which an innovative technique was utilized to extract the active components from cloves. These active substances were subsequently employed to formulate a nanocomposite, both with and without the inclusion of Halloysite nanoclay, utilizing an electrospinning apparatus. The morphology of the resulting nanocomposite was analyzed through FESEM, confirming the appropriateness of the electrospinning method and its conditions. Additionally, the effectiveness of both nanocomposite samples in reducing inflammation was evaluated. A comparative assessment was conducted to evaluate the strength, abrasion resistance, and bactericidal properties of the samples produced in accordance with AATCC standards. The findings revealed an enhancement of over 2.5 times in strength, an increase in abrasion resistance exceeding 91%, and notable antibacterial properties reaching up to 99%. In summary, the nanofiber derived from cloves exhibited promising attributes that may be applicable across various industries.
What next for the Australian Atlas of Healthcare Variation series? Focusing the system on appropriate and sustainable health care
Authors: Giles Gillian , Buchan Heather , Hullick Carolyn , Overs Marge , Duggan Anne
Published: December 2024

Mapping, identifying and reducing unwarranted healthcare variation is integral to improving the appropriateness of care – minimising wasteful or unnecessary care and redirecting care to those who could benefit most (J Eval Clin Pract 26: 687–696, 2020). The Australian Atlas of Healthcare Variation series has examined variation in healthcare use since 2015. The findings reported in the Atlas series have led to important system changes. National safety and quality standards, mandatory for all hospitals and day procedure services, now require health service organisations to monitor and investigate variation and address unwarranted variation. Clinical care standards have been developed for clinical conditions in which the Atlas series has identified considerable variation. But the overuse of low-value care and underuse of high-value care persists, as suggested by the marked variation the Atlas series continues to uncover. We must now develop an approach that systematically links reporting of data and investigation of variation with a suite of responses to address unwarranted variation. This paper focuses on efforts to reduce low value-care, so that resources can be redirected to supporting high-value care as well as reducing waste and cutting carbon emissions from health care (Med J Aust 216: 67–68, 2022).
The journey from natural language processing to large language models: key insights for radiologists
Authors: Fanni Salvatore Claudio , Tumminello Lorenzo , Formica Valentina , Caputo Francesca Pia , Aghakhanyan Gayane , Ambrosini Ilaria , Francischello Roberto , Faggioni Lorenzo , Cioni Dania , Neri Emanuele
Published: December 2024

Artificial intelligence (AI) has undergone cycles of enthusiasm and stagnation, often referred to as “AI winters.” The introduction of large language models (LLMs), such as OpenAI’s ChatGPT in late 2022, has revitalized interest in AI, particularly within health-care applications, including radiology. The roots of AI in language processing can be traced back to Alan Turing’s 1950 work, which established foundational principles for natural language processing (NLP). Early iterations of NLP primarily concentrated on natural language understanding (NLU) and natural language generation (NLG), but they faced significant challenges related to contextual comprehension and the handling of lengthy text sequences. Recent advancements in NLP have demonstrated considerable promise in automating the analysis of unstructured data, including electronic health records and radiology reports. LLMs, which are based on the transformer architecture introduced in 2017, excel at capturing complex language dependencies and facilitating tasks, such as report generation and clinical decision support. This review critically examines the evolution from traditional NLP to LLMs, highlighting their transformative potential within the field of radiology. Despite the advantages presented by LLMs, challenges persist, including concerns regarding data privacy, the potential for generating misinformation, and the imperative for rigorous validation protocols. Addressing these challenges is crucial for harnessing the full potential of LLMs to enhance diagnostic precision and workflow efficiency in radiology, ultimately improving patient care and outcomes.
In vitro assessment of effect of initial specimen diversion device on detection of central venous catheter contamination or colonization
Authors: Rupp Mark E. , Fey Paul D. , Lyden Elizabeth , Handke Luke
Published: December 2024

The role of initial specimen diversion devices (ISDDs) in preventing contamination of central venous catheter (CVC) blood cultures is undefined. A model to simulate CVC colonization and contamination compared standard cultures with ISDD technique. ISDD detected 100% of colonized CVCs while decreasing false-positive cultures from 36% to 16%.
Impact of daily prompt to vaccinate inpatients awaiting rehabilitation against SARS-CoV-2 and influenza
Authors: Linkenheld Amber , Williams Victoria R. , Chan Karen , Carating Helene , Marchesano Romina , Do Jennifer , Sullivan Sherri , Beechinor Danette , Silverstein William K. , Leis Jerome A.
Published: December 2024

A daily prompt to offer vaccination to inpatients awaiting transfer to rehabilitation resulted in increased SARS-CoV-2 (OR 5.64, 95% CI 3.3–10.15; P < 0.001) and influenza (OR 3.80, 95% CI 2.45–6.06; P < 0.001) vaccination. Compared to baseline, this intervention was associated with reduced incidence of viral respiratory infection during subsequent admission to rehabilitation.
OPEN INNOVATION: TOWARD AN ORGANIZATIONAL DIGITAL INNOVATION
Authors: Rengkung Leonardus Ricky , Maweikere Audrey Julia Maria , Memah Melsje Yellie , Loho Agnes Estephina , Benu Noortje Marsellanie
Published: December 2024

Organizations are utilizing digital technologies to modernize their innovations in today’s competitive and rapidly changing market environment. This study’s goal is to explore the influence of open innovation on firms’ digital technology integration, aiming to enhance their innovation skills and produce competitive, adaptable digital solutions. The methods used include analysis, synthesis, and generalization. Organizations can enhance open innovation by acquiring knowledge, capabilities, ideas, technologies, and information for new products and services, with the relationship between open innovation and digital innovation accelerating their capabilities. The study emphasizes the challenges organizations face in modern IT, emphasizing open innovation, access to external knowledge, and the need for improved internal production efficiency and competitiveness. The practical value of this study is manifested in the identification of strategies for optimizing open innovation for their transformation into digital solutions.
On quasi and weak Steinberg characters of general linear groups
Authors: Kaur Surinder
Published: December 2024

Let G be a finite group and r be a prime divisor of the order of G. An irreducible character of G is said to be quasi r-Steinberg if it is non-zero on every r-regular element of G. A quasi r-Steinberg character of degree

$\displaystyle |Syl_r(G)|$

is said to be weak r-Steinberg if it vanishes on the r-singular elements of

$G.$

In this article, we classify the quasi r-Steinberg cuspidal characters of the general linear group

$GL(n,q).$

Then we characterize the quasi r-Steinberg characters of

$GL(2,q)$

and

$GL(3,q).$

Finally, we obtain a classification of the weak r-Steinberg characters of

$GL(n,q).$
Visual Field Asymmetries in Responses to ON and OFF Pathway Biasing Stimuli
Authors: Scott Martin Timothy Wilkinson , Yakovleva Alexandra , Norcia Anthony Matthew
Published: December 2024

Recent reports suggest the ON and OFF pathways are differentially susceptible to selective vision loss in glaucoma. Thus, perimetric assessment of ON- and OFF-pathway function may serve as a useful diagnostic. However, this necessitates a developed understanding of normal ON/OFF pathway function around the visual field and as a function of input intensity. Here, using electroencephalography, we measured ON- and OFF-pathway biased contrast response functions in the upper and lower visual fields. Using the steady-state visually evoked potential paradigm, we flickered achromatic luminance probes according to a saw-tooth waveform, the fast phase of which biased responses towards the ON or OFF pathways. Neural responses from the upper and lower visual fields were simultaneously measured using frequency tagging - probes in the upper visual field modulated at 3.75 Hz, while those in the lower visual field modulated at 3 Hz. We find that responses to OFF/decrements are larger than ON/increments, especially in the lower visual field. In the lower visual field, both ON and OFF responses were well described by a sigmoidal non-linearity. In the upper visual field, the ON pathway function was very similar to that of the lower, but the OFF pathway function showed reduced saturation and more cross-subject variability. Overall, this demonstrates that the relationship between the ON and OFF pathways depends on the visual field location and contrast level, potentially reflective of natural scene statistics.
Aerosols Could Be Weakening Summertime Circulation
Authors: Owen Rebecca
Published: December 2024

Anthropogenic aerosol emissions may be a culprit behind weakening jet streams and weather systems in the Northern Hemisphere.
Integrated Rock Mass Characterization of the Lower Continental Crust Along the ICDP‐DIVE 5071_1_B Borehole in the Ivrea‐Verbano Zone
Authors: Li J. , Caspari E. , Greenwood A. , Pierdominici S. , Lemke K. , Venier M. , Kück J. , Baron L. , Pistone M. , Petri B. , Ziberna L. , Hetényi G.
Published: December 2024

The first borehole 5071_1_B of the ICDP‐Drilling the Ivrea‐Verbano zonE (DIVE) project in Italy, which intersects the Massone antiform, provides a unique opportunity to integrate downhole geophysical measurements with observations from 100% recovered drill core in rarely drilled lithologies. The objective of this study is to petrophysically and structurally characterize the rock mass and constrain factors influencing the seismic velocity in the lower continental crust. A comprehensive data set, comprising core, well log and vertical seismic profiling data, was collected. The structural analysis indicates that the axial plane of the intersected tightly folded antiform is slightly tilted at the borehole location and thus the borehole intersects the hinge zone at the top and its limb in the lower part of 5071_1_B. Numerous open natural fractures with variable dips and two dominant dip azimuthal orientations are identified along the borehole, which affect the electrical and acoustic properties. The velocities at the core, well log and seismic scale are consistent but lower than intrinsic seismic velocities of the lower continental crust, since they are not only affected by fractures but also by micro cracks at the 5071_1_B in situ conditions. A systematic lithology correlation is not evident for these properties. However, a cluster analysis of gamma ray and magnetic susceptibility logs shows an excellent agreement with the logged core lithologies in the presence of remarkable spatial variability. Furthermore, the main lithologies are grouped into three distinct clusters, suggesting two types of kinzigites with distinct magnetic and radiogenic properties.
Upward, MeV‐Class Electron Beams Over Jupiter's Main Aurora
Authors: Mauk B. H. , Ma Q. , Becker H. N. , Jørgensen J. L. , Denver T. , Connerney J. E. P. , Allegrini F. , Bagenal F. , Bolton S. J. , Clark G. , Haggerty D. K. , Kollmann P. , Paranicas C. P.
Published: December 2024

Jupiter's poleward (Zone II) main aurora exhibits bi‐directional electron acceleration; upward acceleration dominates but downward acceleration generates strong aurora. During Juno's first perijove (PJ1), the upward acceleration manifested as narrow electron angular beams (within ∼5° of the magnetic field) over the 30–1,200 keV energy range of Juno's Jupiter Energetic Particle Detector Investigation (JEDI). These beams can be simply connected (non‐uniquely) to >10 to perhaps 100's of MeV electrons that penetrated the radiation shielding of the camera head of the Magnetometer Investigation's Advanced Stellar Compass (ASC). The most intense of those multiple MeV populations are shown to have been highly directional and propagating upwards. How auroral processes generate such beams is unknown. With azimuthal symmetry assumed (not demonstrated here), these beams provided >1026 s−1 of >30 keV electrons to Jupiter's vast magnetosphere, a possibly critical and dominating source of energetic electrons to that region and ultimately to Jupiter's radiation belts.
Modeling the Onset of Earthquake‐Triggered Landslides on Slip Surfaces Governed by Rate‐And‐State Friction
Authors: Lestrelin H. , Ampuero J. P. , Mercerat E. D. , Courboulex F.
Published: December 2024

Earthquake‐triggered landslides are a severe hazard and contribute to landscape evolution. To understand their process and controlling factors, we model the onset of seismically‐triggered slip on pre‐existing slip surfaces governed by laboratory‐based rate‐and‐state friction, including wave propagation effects. Through numerical simulations and theoretical analysis, we identify how friction properties, landslide thickness and incident wave attributes (frequency, duration, amplitude) control slope stability. We find that the frictional state variable tracks the cyclic fatigue of the slip surface, its progressive weakening with each wave cycle. Wave propagation effects introduce two regimes depending on frequency relative to the two‐way travel time across the landslide thickness: the stability criterion is well approximated by a threshold on incident peak acceleration at low frequencies, and on peak velocity at high frequencies. We derive analytical approximations, validated by simulations, suitable to apply the model to evaluate landslide stability under arbitrary input motions.
Prenatal exposure to endocrine disrupting chemicals and the association with behavioural difficulties in 7-year-old children in the SELMA study
Authors: Stratmann Marlene , Özel Fatih , Marinopoulou Maria , Lindh Christian , Kiviranta Hannu , Gennings Chris , Bornehag Carl-Gustaf
Published: December 2024

Background

Endocrine disrupting chemicals (EDCs) can cross the placenta and thereby expose the fetus, which may lead to developmental consequences. It is still unclear which chemicals are of concern regarding neurodevelopment and specifically behaviour, when being exposed to a mixture.

Objective

The objective is to determine associations between prenatal exposure to EDCs and behavioural difficulties. Furthermore, we investigated sex-specific associations and determined chemicals of concern in significant regressions.

Methods

Associations between prenatal exposure to EDCs (both as single compounds and their mixtures) and behavioural outcomes using the Strengths and Difficulties Questionnaire (SDQ) were estimated in 607 mother-child pairs in the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy (SELMA) study. Levels for chemical compounds were measured in either urine or serum (median of 10 weeks of gestation). Associations were estimated for the total SDQ score (quasipoisson regression) and a 90th percentile cut-off (logistic regression). Exposure for EDC mixtures (phenols, phthalates, PFAS and persistent chlorinated) was studied using weighted quantile sum (WQS) regression with deciles and with and without repeated holdout validation techniques. The models were adjusted for selected covariates.

Results

The odds for behavioural difficulties increased in girls with higher chemical exposures (OR 1.77, 95% CI 1.67, 1.87) using the full sample and borderline for the validation set (OR 1.31, 95% CI 0.93, 1.85) with 94/100 positive betas in the 100 repeated holdout validations. Chemicals of concern for girls are mostly short-lived chemicals and more specifically plasticizers. No pattern of significant associations was detected for boys.

Significance

There is an indication of increased behavioural difficulties for girls in the SELMA population with higher exposure to mixtures of EDCs. Using the repeated holdout validation techniques, the inference is more stable, reproducible and generalisable. Prenatal exposure to mixtures of environmental chemicals should be considered when assessing the safety of chemicals.

Impact

Growing evidence points towards a “mixture effect” where different environmental chemicals might act jointly where individual compounds may be below a level of concern, but the combination may have an effect on human health. We are constantly exposed to a complicated mixture pattern that is individual for every person as this mixture depends on personal choices of lifestyle, diet and housing to name a few. Our study suggests that prenatal exposure to EDCs might adversely affect the behaviour of children and especially girls. Hence, risk assessment needs to improve and sex-specific mechanisms should be included in assessments.
The accuracy of fluorine 18-labelled prostate-specific membrane antigen PET/CT and MRI for diagnosis of prostate cancer in PSA grey zone
Authors: Luo Liang , Wang Ruiyan , Bai Lu , Shang Jin , Wang Xinyi , Chang Ruxi , Dong Weixuan , Li Yang , Li Yan , Liang Hua , Xie Hongjun , Duan Xiaoyi
Published: December 2024

Background

The diagnostic utility of prostate biopsy is limited for prostate cancer (PCa) in the prostate-specific antigen (PSA) grey zone. This study aims to evaluate the diagnostic performance of multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) for PSA grey zone PCa and clinically significant PCa (csPCa).

Methods

A total of 82 patients with PSA levels ranging from 4 to 10 ng/mL who underwent 18F-PSMA-1007 PET/CT, mpMRI, and prostate biopsy were prospectively enrolled. For 18F-PSMA-1007 PET/CT and mpMRI in detecting PCa and csPCa, sensitivity, specificity, and area under the curve (AUC) were assessed using biopsy histology as the standard.

Results

18F-PSMA-1007 PET/CT demonstrated better diagnostic performance for PCa than mpMRI (AUC 0.81 vs. 0.63, P = 0.02). 11.0% of patients with PI-RADS 3-5 had no PCa on biopsy, of whom 77.8% were correctly differentiated by 18F-PSMA-1007 PET/CT. Combined 18F-PSMA-1007 PET/CT + mpMRI improved sensitivity (92.5% vs. 73.6%) and negative predictive value (NPV, 78.9% vs. 53.3%) compared with mpMRI alone.

Conclusions

18F-PSMA-1007 PET/CT outperformed mpMRI for detecting PCa in the grey zone level of PSA. 18F-PSMA-1007 PET/CT in combination with mpMRI has additional improvement in sensitivity and NPV for csPCa detection.

Clinical Trial Registration: NCT05958004, 2024-07.
PP2C phosphatases—terminators of suicidal thoughts
Authors: Lagorgette Lisa , Bogdanova Daria A. , Belotserkovskaya Ekaterina V. , Garrido Carmen , Demidov Oleg N.
Published: December 2024

Cell death and related signaling pathways are essential during development and in various physiological and pathological conditions. Post-translational modifications such as ubiquitination and phosphorylation play an important role in these signaling pathways. The involvement of kinases - enzymes that catalyze protein phosphorylation - in cell death signaling has been extensively studied. On the other hand, not many studies have been devoted to analyzing the role in cell death of phosphatases, enzymes involved in the removal of phosphorylated residues added to proteins by kinases. Obviously, the two opposite reactions, phosphorylation and dephosphorylation, are equally important in the regulation of protein functions and subsequently in the execution of the cell death program. Here, we have summarized recent work on the involvement of serine-threonine PP2C phosphatases in cell death pathways, senescence and autophagy, focusing in particular on the most studied phosphatase PPM1D (PP2Cδ) as an example of the regulatory role of PP2Cs in cell death. The review should help to draw attention to the importance of PP2C family phosphatases in cell death checkpoints and to discover new targets for drug development.
A family of NADPH/NADP+ biosensors reveals in vivo dynamics of central redox metabolism across eukaryotes
Authors: Scherschel Marie , Niemeier Jan-Ole , Jacobs Lianne J. H. C. , Hoffmann Markus D. A. , Diederich Anika , Bell Christopher , Höhne Pascal , Raetz Sonja , Kroll Johanna B. , Steinbeck Janina , Lichtenauer Sophie , Multhoff Jan , Zimmermann Jannik , Sadhanasatish Tanmay , Rothemann R. Alexander , Grashoff Carsten , Messens Joris , Ampofo Emmanuel , Laschke Matthias W. , Riemer Jan , Roma Leticia Prates , Schwarzländer Markus , Morgan Bruce
Published: December 2024

The NADPH/NADP+ redox couple is central to metabolism and redox signalling. NADP redox state is differentially regulated by distinct enzymatic machineries at the subcellular compartment level. Nonetheless, a detailed understanding of subcellular NADP redox dynamics is limited by the availability of appropriate tools. Here, we introduce NAPstars, a family of genetically encoded, fluorescent protein-based NADP redox state biosensors. NAPstars offer real-time, specific measurements, across a broad-range of NADP redox states, with subcellular resolution. NAPstar measurements in yeast, plants, and mammalian cell models, reveal a conserved robustness of cytosolic NADP redox homoeostasis. NAPstars uncover cell cycle-linked NADP redox oscillations in yeast and illumination- and hypoxia-dependent NADP redox changes in plant leaves. By applying NAPstars in combination with selective impairment of the glutathione and thioredoxin antioxidative pathways under acute oxidative challenge, we find an unexpected and conserved role for the glutathione system as the primary mediator of antioxidative electron flux.
Age- and sex-related variations in extracellular vesicle profiling for the assessment of cardiovascular risk: the EVaging index
Authors: Burrello Jacopo , Goi Jessica , Burrello Alessio , Vacchi Elena , Rendon-Angel Azucena , Lazzarini Edoardo , Bianco Giovanni , Limongelli Vittorio , Vassalli Giuseppe , Cereda Carlo W. , Monticone Silvia , Mulatero Paolo , Bussolati Benedetta , Alimonti Andrea , Camici Giovanni G. , Melli Giorgia , Osto Elena , Pedrazzini Giovanni , Lucio Barile
Published: December 2024

Extracellular vesicles (EVs) offer valuable diagnostic and prognostic insights for cardiovascular (CV) diseases, but the influence of age-related chronic inflammation (“inflammaging”) and sex differences on EV profiles linked to CV risk remains unclear. This study aimed to use EV profiling to predict age and stratify patients by CV risk. We developed an EVaging index by analyzing surface antigen profiles of serum EVs from 625 participants, aged 20 to 94 years, across varying CV risk groups. The EVaging index was associated with age in healthy individuals and distinguished CV risk profiles in patients, correlating with CV outcomes and likelihood of fatal CV events according to the European Society of Cardiology (ESC) SCORE, and reflecting age-associated comorbidities. While changes in disease-related EV fingerprint adds complexity in CV patients, EV profiling may help assess biological aging and CV risk, emphasizing EVs’ roles in inflammaging.
Chemical ordering and magnetism in face-centered cubic CrCoNi alloy
Authors: Ghosh Sheuly , Ueltzen Katharina , George Janine , Neugebauer Jörg , Körmann Fritz
Published: December 2024

The impact of magnetism on chemical ordering in face-centered cubic CrCoNi medium entropy alloy is studied by a combination of ab initio simulations, machine learning potentials, and Monte Carlo simulations. Large magnetic energies are revealed for some mixed L12/L10 type ordered configurations, which are rooted in strong nearest-neighbor magnetic exchange interactions and chemical bonding among the constituent elements. There is a delicate interplay between magnetism and stability of MoPt2 and L12/L10 type of order, which may explain opposing experimental and theoretical findings.
Psychomotor slowing in schizophrenia is associated with aberrant postural control
Authors: Nuoffer Melanie G. , Schindel Anika , Lefebvre Stephanie , Wüthrich Florian , Nadesalingam Niluja , Kyrou Alexandra , Kerkeni Hassen , Kalla Roger , Bernard Jessica , Walther Sebastian
Published: December 2024

Motor abnormalities, including psychomotor slowing, are prevalent in a large proportion of individuals with schizophrenia. While postural control deficits have been observed in this population, the impact of motor abnormalities on postural stability remains unclear. This study aimed to objectively evaluate postural stability in patients with and without psychomotor slowing and healthy controls. Seventy-three schizophrenia patients with psychomotor slowing (PS; Salpêtrière Retardation Rating Scale (SRRS) ≥ 15), 25 schizophrenia patients without psychomotor slowing (non-PS; SRRS < 15), and 27 healthy controls (HC) performed four conditions on the Kistler force plate: eyes open (EO), eyes closed (EC), head reclined with eyes open (EOHR), and head reclined with eyes closed (ECHR). Larger sway areas and higher Root Mean Square (RMS) values indicate lower postural stability, while a lower Complexity Index (CI) reflects reduced adaptability, flexibility, and dynamic functioning of postural control. PS exhibited larger sway areas and higher RMS compared to the other groups. Both PS and non-PS showed reduced complexity in postural control compared to healthy controls, without differences between the two patient groups. Reduced postural stability and complexity were associated with greater expert-rated motor abnormalities, as well as more severe negative symptoms. Additionally, lower complexity was linked to reduced physical activity levels. These findings suggest that psychomotor slowing is associated with lower postural stability, potentially reflecting impaired cerebellar function. Furthermore, the loss of complexity in postural control highlights reduced flexibility, adaptability, and efficiency in the postural control network of individuals with schizophrenia.
Replicating RNA vaccine confers durable immunity against Crimean Congo hemorrhagic fever virus challenge in mice
Authors: Leventhal Shanna S. , Shaia Carl , Rao Deepashri , Lewis Matthew , Meade-White Kimberly , Erasmus Jesse H. , Feldmann Heinz , Hawman David W.
Published: December 2024

Spread by Hyalomma genus ticks, Crimean-Congo hemorrhagic fever virus (CCHFV) causes a severe hemorrhagic disease endemic throughout Southern and Eastern Europe, Asia, and Africa. To date, there are no widely approved vaccines for CCHFV and treatment for disease is largely supportive. Due to this lack of intervention, the WHO lists CCHFV as a high-priority pathogen. Recently, we described a highly efficacious self-replicating RNA vaccine which is protective against CCHFV disease in mice and non-human primates. This vaccine induces high titers of non-neutralizing anti-nucleoprotein (NP) antibodies and a robust T-cell response against the viral glycoprotein. Here, we assess the durability of this vaccine in mice by monitoring the immunogenicity and efficacy of this vaccine up to 1 year post vaccination. We found that while glycoprotein-specific T-cell responses and anti-NP antibody titers waned over time, mice remained protected against lethal CCHFV challenge for at least 1 year post vaccination.
A reinforced lunar dynamo recorded by Chang’e-6 farside basalt
Authors: Cai Shuhui , Qi Kaixian , Yang Saihong , Fang Jie , Shi Pingyuan , Shen Zhongshan , Zhang Min , Qin Huafeng , Zhang Chi , Li Xiaoguang , Chen Fangfang , Chen Yi , Li Jinhua , He Huaiyu , Deng Chenglong , Li Chunlai , Pan Yongxin , Zhu Rixiang
Published: December 2024

The evolution of the lunar dynamo is essential for deciphering the deep interior structure, thermal history and surface environment of the Moon1–4. Previous palaeomagnetic investigations on samples returned from the nearside of the Moon have established the general variation of the lunar magnetic field5–7. However, limited spatial and temporal palaeomagnetic constraints leave the evolution of the lunar dynamo ambiguous. The Chang’e-6 mission returned the first farside basalts dated at about 2.8 billion years ago (Ga) (refs. 8,9), offering an opportunity to investigate a critical spatiotemporal gap in the evolution of the global lunar dynamo. Here we report palaeointensities (around 5–21 μT) recovered from the Chang’e-6 basalts, providing the first constraint on the magnetic field from the lunar farside and a critical anchor within the large gap between 3 Ga and 2 Ga. These results record a rebound of the field strength after its previous sharp decline of around 3.1 Ga, which attests to an active lunar dynamo at about 2.8 Ga in the mid-early stage and argues against the suggestion that the lunar dynamo may have remained in a low-energy state after 3 Ga until its demise. The results indicate that the lunar dynamo was probably driven by either a basal magma ocean or a precession, supplemented by other mechanisms such as core crystallization.
First-principles study of the magneto-Raman effect in van der Waals layered magnets
Authors: Kong Xiangru , Ganesh Panchapakesan , Liang Liangbo
Published: December 2024

Magneto-Raman spectroscopy has been used to study spin-phonon coupling in two-dimensional (2D) magnets. Raman spectra of CrI3 show a strong dependence on the magnetic order within a layer and between the layers. Here we carry out the first systematic theoretical investigation of the magneto-Raman effect in 2D magnets by performing density functional theory calculations and developing a generalized polarizability model. Our first-principles simulations well reproduce experimental Raman spectra of CrI3 with different magnetic states. The model reveals how the change of spin orientation in each layer is coupled to the layer’s vibration to induce or eliminate the spin-dependent anti-symmetric off-diagonal terms in the Raman tensor for altering the selection rules. We also uncover that the correlation between phonon modes and magnetic orders is a universal phenomenon, which should exist in other phonon modes and 2D magnets. Our predictive simulations and modeling are expected to guide the research in 2D magnets.
A deep learning framework deploying segment anything to detect pan-cancer mitotic figures from haematoxylin and eosin-stained slides
Authors: Shen Zhuoyan , Simard Mikaël , Brand Douglas , Andrei Vanghelita , Al-Khader Ali , Oumlil Fatine , Trevers Katherine , Butters Thomas , Haefliger Simon , Kara Eleanna , Amary Fernanda , Tirabosco Roberto , Cool Paul , Royle Gary , Hawkins Maria A. , Flanagan Adrienne M. , Collins-Fekete Charles-Antoine
Published: December 2024

Mitotic activity is an important feature for grading several cancer types. However, counting mitotic figures (cells in division) is a time-consuming and laborious task prone to inter-observer variation. Inaccurate recognition of MFs can lead to incorrect grading and hence potential suboptimal treatment. This study presents an artificial intelligence-based approach to detect mitotic figures in digitised whole-slide images stained with haematoxylin and eosin. Advances in this area are hampered by the small size and variety of datasets available. To address this, we create the largest dataset of mitotic figures (N = 74,620), combining an in-house dataset of soft tissue tumours with five open-source datasets. We then employ a two-stage framework, named the Optimised Mitoses Generator Network (OMG-Net), to identify mitotic figures. This framework first deploys the Segment Anything Model to automatically outline cells, followed by an adapted ResNet18 that distinguishes mitotic figures. OMG-Net achieves an F1 score of 0.84 in detecting pan-cancer mitotic figures, including human breast carcinoma, neuroendocrine tumours, and melanoma. It outperforms previous state-of-the-art models in hold-out test sets. To summarise, our study introduces a generalisable data creation and curation pipeline and a high-performance detection model, which can largely contribute to the field of computer-aided mitotic figure detection.
Functional biosynthetic stereodivergence in a gene cluster via a dihydrosydnone N-oxide
Authors: Ren Jiajun , Mathew Anugraha , Rodríguez-García María , Kohler Tobias , Blacque Olivier , Linden Anthony , Eberl Leo , Sieber Simon , Gademann Karl
Published: December 2024

Chirality plays a critical role in the biochemistry of life and often only one enantiomeric series is observed (homochirality). Only a few natural products have been obtained as racemates, e.g. the signalling molecule valdiazen produced by Burkholderia cenocepacia H111. In this study, we investigated the ham biosynthetic gene cluster and discovered that both the enantiomerically pure (R)-fragin and the racemic valdiazen result from the same pathway. This stereodivergence is based on the unusual heterocyclic intermediate dihydrosydnone N-oxide, as evident from gene knockout, stable isotope feeding experiments, and mass spectrometry experiments. Both non-enzymatic racemisation via keto-enol tautomerisation and enzyme-mediated dynamic kinetic resolution were found to be crucial to this stereodivergent pathway. This novel mechanism underpins the production of configurationally and biologically distinct metabolites from a single gene cluster. Our findings highlight the intricate design of an intertwined biosynthetic pathway and provide a deeper understanding of microbial secondary metabolism related to microbial communication.