bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Memantine in Limiting Cochleotoxicity in Rats
Authors: Pavlidis Pavlos , Tseriotis Vasilis Spyridon , Papadopoulou Kyriaki , Karachrysafi Sophia , Sardeli Chrysanthi , Gouveris Haralampos , Malliou Faye , Kavvadas Dimitrios , Papamitsou Theodora , Sioga Antonia , Anastasiadou Penelope , Kouvelas Dimitrios
Published: February 2024

Οur aim was to test whether amikacin’s well-known cochleotoxic effects could be suppressed, depending on whether an NMDA-antagonist (memantine) was administered simultaneously with or after amikacin treatment. Forty Wistar rats were used in this experiment. Ten rats acted as controls and received no medication (group A). Amikacin (200 mg/kg) was administered intraperitoneally (i.p.) once daily for 14 days to 10 animals in group B; amikacin (200 mg/kg) was administered concurrently with memantine (10 mg/kg, i.p., once daily) to the same 10 animals in group C. Group D was given intraperitoneal memantine (10 mg/kg, once daily) for 14 days following a 2-week amikacin treatment. The cochlear activity of the right ear was tested using DPOAE in conscious animals. All animals were sacrificed at the conclusion of the experiment and both cochleae were collected for histological and immunohistochemical analysis. All groups treated with amikacin showed decreased cochlear activity, as testified by decreased DPOAE-amplitudes compared to the pre-treatment state. In the rats of group B, the DPOAE reduction was more pronounced. On histologic exam, the cochlear structures of group C rats and, although to a lesser extent, group D rats showed less severe cochlea damage. Memantine plays a protective role, resulting in restoring partially cochlear structures when administered either simultaneously with or after completion of amikacin i.p. treatment in rats.
Biocarbon-Enhanced Flexible Nanofiber Mats for Sustainable Energy Generation and Wearable Device Applications
Authors: Ali Nehal , Mostafa Elham M.
Published: February 2024

A broad diversity of nanofillers and polymers have been used to prepare polymer nanocomposites having potential applications in transportation, sports materials, aerospace, electronics, communication, energy, environment, and biomedical. Polyvinylidene fluoride (PVDF) finds a remarkable place in energy applications attributed to its highest known piezo- and pyroelectric properties. Like most carbon materials, Biochar has excellent electrical conductivity, since it comprises graphene layers with a great amount of carbon content. This study explores the behavior of composite nanofibers fabricated from rice straw-derived biochar-PVDF as wearable mats to harvest body energy into electricity. The composite nanofiber mats were fabricated using the electrospinning technique to get the benefit of both the piezoelectric properties of PVDF and the excellent electric properties of Biochar. The research found that incorporating 12 wt % of Biochar greatly enhances the piezoelectric content of the nanofiber mats without noteworthy loss in flexibility. In addition, the effects of membrane thickness (0.5, 0.9, and 1 mm) on their output voltages as a performance factor of the nanogenerator were measured. Results indicated that the effect of thickness was most influential in the thickness of 1 mm of PVDF/biochar nanofibers generator. The results of this work imply promising application development of such flexible composite piezoelectric nanofibrous membranes for environmentally sustainable energy generation and wearable self-powered electrical devices.
Significant augmentation of proton conductivity in low sulfonated polyether sulfone octyl sulfonamide membranes through the incorporation of hectorite clay
Authors: Mabrouk Walid , Charradi Khaled , Kacem Imen Ben , Lafi Ridha , Bellakhal Nizar , Marzouki Riadh , Keshk Sherif M. A. S.
Published: February 2024

An innovative methodology was employed to fabricate ion exchange membranes tailored for fuel cell applications. This approach entailed blending low sulfonated polyether sulfone octyl sulfonamide (LSPSO) with Hectorite (Hect) clay at varying weight percentages (1 wt%, 3 wt%, and 6 wt%). The resultant composite membranes underwent comprehensive characterization via Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and thermogravimetric analysis, aiming to assess their surface morphology and thermal resilience. Remarkably, the thermal stability of the composite membrane exhibited a substantial enhancement in comparison to the pristine LSPSO membrane. Moreover, the incorporation of 6 wt% Hectorite into the composite membrane yielded a noteworthy amplification in proton conductivity, achieving a fourfold increase (141.66 mS/cm) as opposed to the LSPSO membrane in isolation (35.04 mS/cm). Consequently, the Hect/LSPSO composite membrane exhibits remarkable potential as an electrolyte membrane for fuel cells operating at temperatures surpassing 100 °C.
The “we” factor in improvisational statecraft: frontline repair of the state in Indonesia’s crisis response amidst resource constraints
Authors: Ningrum Ayu Puspita , Lotta Gabriela
Published: February 2024

Street-level bureaucrats, confined by meager discretion, often find themselves reconciling the challenging terrain of inflexible policies with messy frontline realities. With a phenomenological lens, we examine how Indonesia’s frontline healthcare workers exercise discretion and improvise informal practices to adapt policies and deliver care despite scarce resources during the COVID-19 crisis. As formal emergency protocols lie encumbered under conditions of austerity, a grassroots motivation for communal action occurs from exchanges between peers mired in resource quandaries, encapsulating an improvisational “we” cohering frontline allies. Manifesting through focused responses drawing on unwritten collegial knowledge, these collaborative efforts embody the relational essence and defining contours of frontline policy repair, as opposed to isolated discretion. Probing further into these repair processes surfaces how shared struggles have the power to ignite collective capacity, empowering bureaucrats to govern complexity in concert, construct agency despite constraints, and promote equity in times of scarcity. Our findings champion tending to institutional receptivity and solidarity-anchored creative frontline initiatives, endorsing agile, adaptive processes finely tuned to situational realities that contests paradigms fixated solely on compliance.
Topological Duality for Distributive Lattices
Authors: Gehrke Mai , van Gool Sam
Published: February 2024

Introducing Stone–Priestley duality theory and its applications to logic and theoretical computer science, this book equips graduate students and researchers with the theoretical background necessary for reading and understanding current research in the area. After giving a thorough introduction to the algebraic, topological, logical, and categorical aspects of the theory, the book covers two advanced applications in computer science, namely in domain theory and automata theory. These topics are at the forefront of active research seeking to unify semantic methods with more algorithmic topics in finite model theory. Frequent exercises punctuate the text, with hints and references provided.
Explainable and transparent artificial intelligence for public policymaking
Authors: Papadakis Thanasis , Christou Ioannis T. , Ipektsidis Charalampos , Soldatos John , Amicone Alessandro
Published: February 2024

Nowadays public policymakers are offered with opportunities to take data-driven evidence-based decisions by analyzing the very large volumes of policy-related data that are generated through different channels (e.g., e-services, mobile apps, social media). Machine learning (ML) and artificial intelligence (AI) tehcnologies ease and automate the analysis of large policy-related datasets, which helps policymakers to realize a shift toward data-driven decisions. Nevertheless, the deployment and use of AI tools for public policy development is also associated with significant technical, political, and operation challenges. For instance, AI-based policy development solutions must be transparent and explainable to policymakers, while at the same time adhering to the mandates of emerging regulations such as the AI Act of the European Union. This paper introduces some of the main technical, operational, regulatory compliance challenges of AI-based policymaking. Accordingly, it introduces technological solutions for overcoming them, including: (i) a reference architecture for AI-based policy development, (ii) a virtualized cloud-based tool for the specification and implementation of ML-based data-driven policies, (iii) a ML framework that enables the development of transparent and explainable ML models for policymaking, and (iv) a set of guidelines for using the introduced technical solutions to achieve regulatory compliance. The paper ends up illustrating the validation and use of the introduced solutions in real-life public policymaking cases for various local governments.
Rising and settling 2-D cylinders with centre-of-mass offset
Authors: Assen Martin P.A. , Will Jelle B. , Ng Chong Shen , Lohse Detlef , Verzicco Roberto , Krug Dominik
Published: February 2024

Rotational effects are commonly neglected when considering the dynamics of freely rising or settling isotropic particles. Here, we demonstrate that particle rotations play an important role for rising as well as for settling cylinders in situations when mass eccentricity, and thereby a new pendulum time scale, is introduced to the system. We employ two-dimensional simulations to study the motion of a single cylinder in a quiescent unbounded incompressible Newtonian fluid. This allows us to vary the Galileo number, density ratio, relative moment of inertia (MOI) and centre-of-mass (COM) offset systematically and beyond what is feasible experimentally. For certain buoyant density ratios, the particle dynamics exhibits a resonance mode, during which the coupling via the Magnus lift force causes a positive feedback between translational and rotational motions. This mode results in vastly different trajectories with significantly larger rotational and translational amplitudes and an increase of the drag coefficient easily exceeding a factor two. We propose a simple model that captures how the occurrence of the COM offset induced resonance regime varies, depending on the other input parameters, specifically the density ratio, the Galileo number and the relative MOI. Remarkably, depending on the input parameters, resonance can be observed for COM offsets as small as a few per cent of the particle diameter, showing that the particle dynamics can be highly sensitive to this parameter.
A new wall function method for hypersonic laminar boundary layers
Authors: Mo Fan , Gao Zhenxun
Published: February 2024

A new wall function method for hypersonic laminar boundary layers (HLBLs) is proposed to reduce the near-wall grid dependence of skin friction

$c_f$

and wall heat flux

$q_w$

in numerical simulations, aiming for fast and accurate predictions. First, an analytic laminar velocity law of the wall is derived, which achieves a universal scaling of the near-wall velocity of HLBLs. Then an accurate temperature–velocity relation is deduced by introducing the general recovery factor to address the invalidation of the Walz relation under the cold wall effect. Based on the laminar laws of the wall, a new wall function method for HLBLs is proposed. To avoid introducing the boundary layer edge quantities, the laminar laws of the wall are reformed by modifying the outer boundary conditions of the differential equation in deriving the temperature–velocity relation. Unlike the wall function method in turbulence, the new wall function obtains directly the accurate

$c_f$

and

$q_w$

by post-processing without being involved in the simulation iteration. The numerical experiments of a Mach 8 HLBL over the flat plate show that effectively, the new wall function can enlarge the distance of the first grid point off the wall

$\Delta y_1$

from

$10^{-6}$

m to

$10^{-3}$

m, which brings a 50 times enhancement of the simulation efficiency. Meanwhile, the simulation errors of

$c_f$

and

$q_w$

of the mesh with

$\Delta y_1=10^{-3}$

m are reduced significantly from 24.2 % and 18.5 % to 0.5 % and 0.1 %, respectively. Due to the new wall function removing the boundary layer edge quantities, success is also achieved under the curved walls.
Association between dietary macronutrient composition and plasma one-carbon metabolites and B-vitamin cofactors in patients with stable angina pectoris
Authors: Bråtveit Marianne , Van Parys Anthea , Olsen Thomas , Strand Elin , Marienborg Ingvild , Laupsa-Borge Johnny , Haugsgjerd Teresa Risan , McCann Adrian , Dhar Indu , Ueland Per Magne , Dierkes Jutta , Dankel Simon Nitter , Nygård Ottar Kjell , Lysne Vegard
Published: February 2024

Elevated plasma concentrations of several one-carbon metabolites are associated with increased CVD risk. Both diet-induced regulation and dietary content of one-carbon metabolites can influence circulating concentrations of these markers. We cross-sectionally analysed 1928 patients with suspected stable angina pectoris (geometric mean age 61), representing elevated CVD risk, to assess associations between dietary macronutrient composition (FFQ) and plasma one-carbon metabolites and related B-vitamin status markers (GC–MS/MS, LC–MS/MS or microbiological assay). Diet-metabolite associations were modelled on the continuous scale, adjusted for age, sex, BMI, smoking, alcohol and total energy intake. Average (geometric mean (95 % prediction interval)) intake was forty-nine (38, 63) energy percent (E%) from carbohydrate, thirty-one (22, 45) E% from fat and seventeen (12, 22) E% from protein. The strongest associations were seen for higher protein intake, i.e. with higher plasma pyridoxal 5’-phosphate (PLP) (% change (95 % CI) 3·1 (2·1, 4·1)), cobalamin (2·9 (2·1, 3·7)), riboflavin (2·4 (1·1, 3·7)) and folate (2·1 (1·2, 3·1)) and lower total homocysteine (tHcy) (–1·4 (–1·9, −0·9)) and methylmalonic acid (MMA) (–1·4 (–2·0, −0·8)). Substitution analyses replacing MUFA or PUFA with SFA demonstrated higher plasma concentrations of riboflavin (5·0 (0·9, 9·3) and 3·3 (1·1, 5·6)), tHcy (2·3 (0·7, 3·8) and 1·3 (0·5, 2·2)) and MMA (2·0 (0·2, 3·9) and 1·7 (0·7, 2·7)) and lower PLP (–2·5 (–5·3, 0·3) and −2·7 (–4·2, −1·2)). In conclusion, a higher protein intake and replacing saturated with MUFA and PUFA were associated with a more favourable metabolic phenotype regarding metabolites associated with CVD risk.
Naturally acquired immunity to Plasmodium pitheci in Bornean orangutans (Pongo pygmaeus)
Authors: Sánchez Karmele Llano , Baird John Kevin , Nielsen Aileen , Nurillah Andini , Agustina Fitria , Komara  , Fadilah Fina , Prameswari Wendi , Nugraha Raden Taufiq Purna , Saputra Sugiyono , Nurkanto Arif , Dharmayanthi Anik Budhi , Pratama Rahadian , Exploitasia Indra , Greenwood Alex D.
Published: February 2024

Naturally acquired immunity to the different types of malaria in humans occurs in areas of endemic transmission and results in asymptomatic infection of peripheral blood. The current study examined the possibility of naturally acquired immunity in Bornean orangutans, Pongo pygmaeus, exposed to endemic Plasmodium pitheci malaria. A total of 2140 peripheral blood samples were collected between January 2017 and December 2022 from a cohort of 135 orangutans housed at a natural forested Rescue and Rehabilitation Centre in West Kalimantan, Indonesia. Each individual was observed for an average of 4.3 years during the study period. Blood samples were examined by microscopy and polymerase chain reaction for the presence of plasmodial parasites. Infection rates and parasitaemia levels were measured among age groups and all 20 documented clinical malaria cases were reviewed to estimate the incidence of illness and risk ratios among age groups. A case group of all 17 individuals that had experienced clinical malaria and a control group of 34 individuals having an event of >2000 parasites μL−1 blood but with no outward or clinical sign of illness were studied. Immature orangutans had higher-grade and more frequent parasitaemia events, but mature individuals were more likely to suffer from clinical malaria than juveniles. The case orangutans having patent clinical malaria were 256 times more likely to have had no parasitaemia event in the prior year relative to asymptomatic control orangutans. The findings are consistent with rapidly acquired immunity to P. pitheci illness among orangutans that wanes without re-exposure to the pathogen.
Are specialist-provided end-of-life scenarios key to initiation of advance care planning in primary care? A mixed-methods study
Authors: Poelman Sophie W. , Ermers Daisy J.M. , Schers Henk J. , Vissers Kris C.P. , Veldhoven Carel M.M. , Kuip Evelien J.M. , Perry Marieke
Published: February 2024

Objectives

Specialist-provided end-of-life scenarios (SP-EOLS) may improve advance care planning (ACP) implementation in primary care by helping overcome barriers such as uncertain prognosis and poor interprofessional collaboration. We aimed to explore the current use and potential impact of SP-EOLS on ACP in Dutch primary care.

Methods

We performed a mixed-methods study. From patients discussed in a hospital-based academic palliative care multidisciplinary team meeting between 2016 and 2019 and died, we collected primary care electronic medical records data on SP-EOLS, actual EOLS, and ACP initiation and applied descriptive and comparative analyses. Subsequently, we interviewed general practitioners (GPs) and thematically analyzed the transcripts.

Results

In 69.7% of 66 reviewed patient files, SP-EOLS were found. In patients whose GP had received SP-EOLS, ACP conversations were more often reported (92.0 vs. 61.0%, p = 0.006). From 11 GP interviews, we identified 4 themes: (1) SP-EOLS guide GPs, patients, and relatives when dealing with an uncertain future perspective; (2) SP-EOLS provide continuity of care between primary and secondary/tertiary care; (3) SP-EOLS should be tailored to the individual patient; and (4) SP-EOLS need to be personalized and uniformly transferred to GPs.

Significance of results

SP-EOLS may facilitate ACP conversations by GPs. They have the potential to help overcome existing barriers to ACP implementation by providing guidance and supporting interprofessional collaboration. Future research should focus on improving SP-EOLS and tailor them to the needs of all end users, focusing on improving their effect on ACP conversations.
Extending Conquest History:Lesser-Known Events and the Fringes of European Conquest
Authors: Vergara Teresa , Quiroz Francisco
Published: February 2024

Certain characters and their roles in the European conquest of America are well known: Christopher Columbus, Hernando Cortés, Francisco Pizarro, Gonzalo Jiménez de Quesada, and a few others. Likewise, scholarly interest in the conquest has focused on the centers of great political, economic, and cultural entities such as the Aztec Empire in Mesoamerica and the Inca Empire in the Central Andes.
Mysterious Seafloor Pits May Be Made on Porpoise
Authors: Chapman Andrew
Published: February 2024

Some shallow seafloor depressions off the coast of Germany that look like those associated with methane might instead be the work of porpoises.
The Twists and Turns of Helicity Studies
Authors: Kuzanyan Kirill , Yokoi Nobumitsu Yokoi , Georgoulis Manolis , Stepanov Rodion
Published: February 2024

A new book explores the fundamental role that helicities play in different astrophysical and geophysical phenomena and presents perspectives from various scientific disciplines that study them.
Health‐Damaging Climate Events Highlight the Need for Interdisciplinary, Engaged Research
Authors: Stowell Jennifer D. , Anenberg Susan , Zaitchik Benjamin F. , Tong Daniel Q. , Horwell Claire J. , Stolle Dennis P. , Colwell Rita R. , McEntee Christine
Published: February 2024

In 2023 human populations experienced multiple record‐breaking climate events, with widespread impacts on human health and well‐being. These events include extreme heat domes, drought, severe storms, flooding, and wildfires. Due to inherent lags in the climate system, we can expect such extremes to continue for multiple decades after reaching net zero carbon emissions. Unfortunately, despite these significant current and future impacts, funding for research in climate and health has lagged behind that for other geoscience and biomedical research. While some initial efforts from funding agencies are evident, there is still a significant need to increase the resources available for multidisciplinary research in the face of this issue. As a group of experts at this important intersection, we call for a more concerted effort to encourage interdisciplinary and policy‐relevant investigations into the detrimental health effects of continued climate change.
Occupational exposure to organic solvents and risk of bladder cancer
Authors: Xie Shuai , Friesen Melissa C. , Baris Dalsu , Schwenn Molly , Rothman Nathaniel , Johnson Alison , Karagas Margaret R. , Silverman Debra T. , Koutros Stella
Published: February 2024

Background

Bladder cancer has been linked to several occupations that involve the use of solvents, including those used in the dry-cleaning industry.

Objectives

We evaluated exposure to solvents and risk of bladder cancer in 1182 incident cases and 1408 controls from a population-based study.

Methods

Exposure to solvents was quantitatively assessed using a job-exposure matrix (CANJEM). Exposure to benzene, toluene and xylene often co-occur. Therefore, we created two additional sets of metrics for combined benzene, toluene and xylene (BTX) exposure: (1) CANJEM-based BTX metrics and (2) hybrid BTX metrics, using an approach that integrates the CANJEM-based BTX metrics together with lifetime occupational histories and exposure-oriented modules that captured within-job, respondent-specific details about tasks and chemicals. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated using logistic regression.

Results

Bladder cancer risks were increased among those ever exposed to benzene (OR = 1.63, 95% CI: 1.14–2.32), toluene (OR = 1.60, 95% CI: 1.06–2.43), and xylene (OR = 1.67, 95% CI: 1.13–2.48) individually. We further observed a statistically significant exposure-response relationship for cumulative BTX exposure, with a stronger association using the hybrid BTX metrics (ORQ1vsUnexposed = 1.26, 95% CI: 0.83–1.90; ORQ2vsUnexposed = 1.52, 95% CI: 1.00–2.31; ORQ3vsUnexposed = 1.88, 95% CI: 1.24–2.85; and ORQ4vsUnexposed = 2.23, 95% CI: 1.35–3.69) (p-trend=0.001) than using CANJEM-based metrics (p-trend=0.02).

Impact

There is limited evidence about the role of exposure to specific organic solvents, alone or in combination on the risk of developing bladder cancer. In this study, workers with increasing exposure to benzene, toluene, and xylene as a group (BTX) had a statistically significant exposure-response relationship with bladder cancer. Future evaluation of the carcinogenicity of BTX and other organic solvents, particularly concurrent exposure, on bladder cancer development is needed.
Genetic architecture of childhood speech disorder: a review
Authors: Morgan Angela T. , Amor David J. , St John Miya D. , Scheffer Ingrid. E. , Hildebrand Michael S.
Published: February 2024

Severe speech disorders lead to poor literacy, reduced academic attainment and negative psychosocial outcomes. As early as the 1950s, the familial nature of speech disorders was recognized, implying a genetic basis; but the molecular genetic basis remained unknown. In 2001, investigation of a large three generational family with severe speech disorder, known as childhood apraxia of speech (CAS), revealed the first causative gene; FOXP2. A long hiatus then followed for CAS candidate genes, but in the past three years, genetic analysis of cohorts ascertained for CAS have revealed over 30 causative genes. A total of 36 pathogenic variants have been identified from 122 cases across 3 cohorts in this nascent field. All genes identified have been in coding regions to date, with no apparent benefit at this stage for WGS over WES in identifying monogenic conditions associated with CAS. Hence current findings suggest a remarkable one in three children have a genetic variant that explains their CAS, with significant genetic heterogeneity emerging. Around half of the candidate genes identified are currently supported by medium (6 genes) to strong (9 genes) evidence supporting the association between the gene and CAS. Despite genetic heterogeneity; many implicated proteins functionally converge on pathways involved in chromatin modification or transcriptional regulation, opening the door to precision diagnosis and therapies. Most of the new candidate genes for CAS are associated with previously described neurodevelopmental conditions that include intellectual disability, autism and epilepsy; broadening the phenotypic spectrum to a distinctly milder presentation defined by primary speech disorder in the setting of normal intellect. Insights into the genetic bases of CAS, a severe, rare speech disorder, are yet to translate to understanding the heritability of more common, typically milder forms of speech or language impairment such as stuttering or phonological disorder. These disorders likely follow complex inheritance with polygenic contributions in many cases, rather than the monogenic patterns that underly one-third of patients with CAS. Clinical genetic testing for should now be implemented for individuals with CAS, given its high diagnostic rate, which parallels many other neurodevelopmental disorders where this testing is already standard of care. The shared mechanisms implicated by gene discovery for CAS highlight potential new targets for future precision therapies.
CircUSP1 as a novel marker promotes gastric cancer progression via stabilizing HuR to upregulate USP1 and Vimentin
Authors: Li Rong , Wang Junyi , Xie Zhenfan , Tian Xinyu , Hou Jie , Wang Dongli , Qian Hui , Shen Han , Xu Wenrong
Published: February 2024

Circular RNAs (circRNAs) play a crucial role in regulating various tumors. However, their biological functions and mechanisms in gastric cancer (GC) have not been well understood. Here, we discovered a stable cytoplasmic circRNA named circUSP1 (hsa_circ_000613) in GC. CircUSP1 upregulation in GC tissues was correlated with tumor size and differentiation. We observed that circUSP1 promoted GC growth and metastasis. Mechanistically, circUSP1 mainly interacted with the RRM1 domain of an RNA-binding protein (RBP) called HuR, stabilizing its protein level by inhibiting β-TrCP-mediated ubiquitination degradation. The oncogenic properties of HuR mediated promotive effects of circUSP1 in GC progression. Moreover, we identified USP1 and Vimentin as downstream targets of HuR in post-transcriptional regulation, mediating the effects of circUSP1. The parent gene USP1 also enhanced the viability and mobility of GC cells. Additionally, tissue-derived circUSP1 could serve as an independent prognostic factor for GC, while plasma-derived circUSP1 showed promise as a diagnostic biomarker, outperforming conventional markers including serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA19-9). Our study highlights that circUSP1 promotes GC progression by binding to and stabilizing oncogenic HuR, thereby facilitating the upregulation of USP1 and Vimentin at the post-transcriptional level. These findings suggest that circUSP1 could be a potential therapeutic target and a diagnostic and prognostic biomarker for GC.
Falls in oxygen saturations accompany electrographic seizures in term neonates: an observational study
Authors: Wertheim David , Kage Anup C. , Lancoma-Malcolm Ivone , Francia Caroline , Yoong Michael , Shah Divyen K.
Published: February 2024

Background

Effective seizure detection is important however, clinical signs of seizure activity may be subtle in neonates. This study aimed to systematically investigate SpO2 and respiratory pattern changes associated with EEG seizures in term-born neonates.

Method

An observational study in term neonates at risk of seizures admitted to a single tertiary level neonatal intensive care unit. Synchronised high-resolution physiological data (ECG, pulse oximetry, respiration) and EEG/amplitude-integrated EEG (aEEG) monitoring were recorded. Sections of traces with evidence of clear EEG seizure activity were compared with physiological data recorded at the same time.

Results

22/44 (50%) neonates who had aEEG monitoring were noted to have electrographic seizures. Physiologic download measurements were available for 11 of these neonates. In nine of these, an acute drop in oxygen saturation (SpO2) of at least 5% was noted in at least one seizure. Accompanying apnoeas were noted in three neonates.

Conclusion

Acute decreases in SpO2 were seen in term neonates associated with seizures and these were not always accompanied by an apnoeic episode. Physiologic download in association with EEG monitoring may assist in improving seizure detection. Unexplained drops in SpO2 could indicate further investigation for possible seizures in at-risk neonates.

Impact

A decrease in blood oxygen saturation (SpO2) associated with EEG seizures can occur in term infants with HIE or perinatal stroke.

Drops in SpO2 associated with EEG seizures in term infants with HIE or stroke may occur in the absence of apnoeas.

Unexplained acute falls in SpO2 in sick neonates may suggest possible seizures.

Drops in SpO2 associated with seizures in term infants can occur over less than 3 minutes.

Physiological monitoring alongside EEG monitoring could help to improve seizure detection.
M6A RNA methylation in biliary tract cancer: the function roles and potential therapeutic implications
Authors: Bai Xuesong , Huang Jianhao , Jin Yiqun , Chen Jiemin , Zhou Shengnan , Dong Liangbo , Han Xianlin , He Xiaodong
Published: February 2024

Biliary tract cancers (BTCs) are relatively rare malignancies with a poor prognosis. For advanced BTCs, the efficacy of current chemotherapeutic approaches is limited. Consequently, there is an urgent need to deepen our understanding of the molecular mechanisms underlying BTC tumorigenesis and development for the exploration of effective targeted therapies. N6-methyladenosine (m6A), the most abundant RNA modifications in eukaryotes, is found usually dysregulated and involved in tumorigenesis, progression, and drug resistance in tumors. Numerous studies have confirmed that aberrant m6A regulators function as either oncogenes or tumor suppressors in BTCs by the reversible regulation of RNA metabolism, including splicing, export, degradation and translation. In this review, we summarized the current roles of the m6A regulators and their functional impacts on RNA fate in BTCs. The improved understanding of m6A modification in BTCs also provides a reasonable outlook for the exploration of new diagnostic strategies and efficient therapeutic targets.
Dimensional control of interface coupling-induced ferromagnetism in CaRuO3/SrCuO2 superlattices
Authors: Zhe Li , Wenxiao Shi , Jine Zhang , Jie Zheng , Mengqin Wang , ZhaoZhao Zhu , Furong Han , Hui Zhang , Liming Xie , Chen Yunzhong , Hu Fengxia , Shen Baogen , Chen Yuansha , Sun Jirong
Published: February 2024

Due to the strong interactions from multiple degrees of freedom at the interfaces, electron-correlated oxide heterostructures have provided a promising platform for creating exotic quantum states. Understanding and controlling the coupling effects at the oxide interface are prerequisites for designing emergent interfacial phases with desired functionalities. Here, we report the dimensional control of the interface coupling-induced ferromagnetic (FM) phase in perovskite-CaRuO3/infinite-layered-SrCuO2 superlattices. Structural analysis reveals the occurrence of chain-type to planar-type structural transitions for the SrCuO2 layer as the layer thickness increases. The Hall and magnetoresistance measurements indicate the appearance of an interfacial FM state in the originally paramagnetic CaRuO3 layers when the CaRuO3 layer is in proximity to the chain-type SrCuO2 layers; this superlattice has the highest Curie temperature of ~75 K and perpendicular magnetic anisotropy. Along with the thickness-driven structural transition of the SrCuO2 layers, the interfacial FM order gradually deteriorates and finally disappears. As shown by the X-ray absorption results, the charge transfer at the CaRuO3/chain-SrCuO2 and CaRuO3/plane-SrCuO2 interfaces are different, resulting in dimensional control of the interfacial magnetic state. The results from our study can be used to facilitate a new method to manipulate interface coupling and create emergent interfacial phases in oxide heterostructures.
Simulated microgravity attenuates myogenesis and contractile function of 3D engineered skeletal muscle tissues
Authors: Ren Zhanping , Ahn Eun Hyun , Do Minjae , Mair Devin B. , Monemianesfahani Amir , Lee Peter H. U. , Kim Deok-Ho
Published: February 2024

While the effects of microgravity on inducing skeletal muscle atrophy have been extensively studied, the impacts of microgravity on myogenesis and its mechanisms remain unclear. In this study, we developed a microphysiological system of engineered muscle tissue (EMT) fabricated using a collagen / Matrigel composite hydrogel and murine skeletal myoblasts. This 3D EMT model allows non-invasive quantitative assessment of contractile function. After applying a 7-day differentiation protocol to induce myotube formation, the EMTs clearly exhibited sarcomerogenesis, myofilament formation, and synchronous twitch and tetanic contractions with electrical stimuli. Using this 3D EMT system, we investigated the effects of simulated microgravity at 10−3 G on myogenesis and contractile function utilizing a random positioning machine. EMTs cultured for 5 days in simulated microgravity exhibited significantly reduced contractile forces, myofiber size, and differential expression of muscle contractile, myogenesis regulatory, and mitochondrial biogenesis-related proteins. These results indicate simulated microgravity attenuates myogenesis, resulting in impaired muscle function.
Polygenic effects on brain functional endophenotype for deficit and non-deficit schizophrenia
Authors: Fang Jin , Lv Yiding , Xie Yingying , Tang Xiaowei , Zhang Xiaobin , Wang Xiang , Yu Miao , Zhou Chao , Qin Wen , Zhang Xiangrong
Published: February 2024

Deficit schizophrenia (DS) is a subtype of schizophrenia (SCZ). The polygenic effects on the neuroimaging alterations in DS still remain unknown. This study aims to calculate the polygenic risk scores for schizophrenia (PRS-SCZ) in DS, and further explores the potential associations with functional features of brain. PRS-SCZ was calculated according to the Whole Exome sequencing and Genome-wide association studies (GWAS). Resting-state fMRI, as well as biochemical features and neurocognitive data were obtained from 33 DS, 47 NDS and 41 HCs, and association studies of genetic risk with neuroimaging were performed in this sample. The analyses of amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were performed to detect the functional alterations between DS and NDS. In addition, correlation analysis was used to investigate the relationships between functional features (ALFF, ReHo, FC) and PRS-SCZ. The PRS-SCZ of DS was significantly lower than that in NDS and HC. Compared to NDS, there was a significant increase in the ALFF of left inferior temporal gyrus (ITG.L) and left inferior frontal gyrus (IFG.L) and a significant decrease in the ALFF of right precuneus (PCUN.R) and ReHo of right middle frontal gyrus (MFG.R) in DS. FCs were widely changed between DS and NDS, mainly concentrated in default mode network, including ITG, PCUN and angular gyrus (ANG). Correlation analysis revealed that the ALFF of left ITG, the ReHo of right middle frontal gyrus, the FC value between insula and ANG, left ITG and right corpus callosum, left ITG and right PCUN, as well as the scores of Trail Making Test-B, were associated with PRS-SCZ in DS. The present study demonstrated the differential polygenic effects on functional changes of brain in DS and NDS, providing a potential neuroimaging-genetic perspective for the pathogenesis of schizophrenia.
A divergent intermediate strategy yields biologically diverse pseudo-natural products
Authors: Bag Sukdev , Liu Jie , Patil Sohan , Bonowski Jana , Koska Sandra , Schölermann Beate , Zhang Ruirui , Wang Lin , Pahl Axel , Sievers Sonja , Brieger Lukas , Strohmann Carsten , Ziegler Slava , Grigalunas Michael , Waldmann Herbert
Published: February 2024

The efficient exploration of biologically relevant chemical space is essential for the discovery of bioactive compounds. A molecular design principle that possesses both biological relevance and structural diversity may more efficiently lead to compound collections that are enriched in diverse bioactivities. Here the diverse pseudo-natural product (PNP) strategy, which combines the biological relevance of the PNP concept with synthetic diversification strategies from diversity-oriented synthesis, is reported. A diverse PNP collection was synthesized from a common divergent intermediate through developed indole dearomatization methodologies to afford three-dimensional molecular frameworks that could be further diversified via intramolecular coupling and/or carbon monoxide insertion. In total, 154 PNPs were synthesized representing eight different classes. Cheminformatic analyses showed that the PNPs are structurally diverse between classes. Biological investigations revealed the extent of diverse bioactivity enrichment of the collection in which four inhibitors of Hedgehog signalling, DNA synthesis, de novo pyrimidine biosynthesis and tubulin polymerization were identified from four different PNP classes.
Cellular uptake and in vivo distribution of mesenchymal-stem-cell-derived extracellular vesicles are protein corona dependent
Authors: Liam-Or Revadee , Faruqu Farid N. , Walters Adam , Han Shunping , Xu Lizhou , Wang Julie Tzu-Wen , Oberlaender Jennifer , Sanchez-Fueyo Alberto , Lombardi Giovanna , Dazzi Francesco , Mailaender Volker , Al-Jamal Khuloud T.
Published: February 2024

Extracellular vesicles (EVs) derived from mesenchymal stem cells are promising nanotherapeutics in liver diseases due to their regenerative and immunomodulatory properties. Nevertheless, a concern has been raised regarding the rapid clearance of exogenous EVs by phagocytic cells. Here we explore the impact of protein corona on EVs derived from two culturing conditions in which specific proteins acquired from media were simultaneously adsorbed on the EV surface. Additionally, by incubating EVs with serum, simulating protein corona formation upon systemic delivery, further resolved protein corona–EV complex patterns were investigated. Our findings reveal the potential influences of corona composition on EVs under in vitro conditions and their in vivo kinetics. Our data suggest that bound albumin creates an EV signature that can retarget EVs from hepatic macrophages. This results in markedly improved cellular uptake by hepatocytes, liver sinusoidal endothelial cells and hepatic stellate cells. This phenomenon can be applied as a camouflage strategy by precoating EVs with albumin to fabricate the albumin-enriched protein corona–EV complex, enhancing non-phagocytic uptake in the liver. This work addresses a critical challenge facing intravenously administered EVs for liver therapy by tailoring the protein corona–EV complex for liver cell targeting and immune evasion.
Quantum measurement enables single biomarker sensitivity in flow cytometry
Authors: Sabines-Chesterking J. , Burenkov I. A. , Polyakov S. V.
Published: February 2024

We present the first unambiguous experimental method enabling single-fluorophore sensitivity in a flow cytometer using quantum properties of single-photon emitters. We use a quantum measurement based on the second-order coherence function to prove that the optical signal is produced by individual biomarkers traversing the interrogation volume of the flow cytometer from the first principles. This observation enables the use of the quantum toolbox for rapid detection, enumeration, and sorting of single fluorophores in large cell populations as well as a ‘photons-to-moles’ calibration of this measurement modality.
Laser-assisted see-through technology for locating sound sources inside a structure
Authors: Wu Sean F. , Lu Yazhong , Ernest Cameron , Zhao Yang , Chen Lingguang
Published: February 2024

A laser-assisted see-through technology is developed to locate sound sources inside a structure and to analyze the interior sound field. Six lasers were employed to measure simultaneously the normal velocities on the exterior surface. These input data were used to locate sound sources inside a solid structure using a passive sonic detection and ranging algorithm, and then to reconstruct the interior sound field using the Helmholtz equation least squares method, and finally to observe the changes of the interior sound field over time through computer tomography. If signals are time invariant, all these can be accomplished with two lasers, one being fixed and another moving around to measure the normal surface velocity sequentially to establish transfer function with respect to the stationary laser. Once the transfer functions are established, they can be multiplied by any segment of time-domain signals measured by the fixed laser to acquire multiple normal surface velocities, as if they were measured simultaneously. This laser-assisted see-through technology has been validated experimentally and employed to observe the aerodynamically-induced sound field generated by a blower inside a projector. This development is important as it signifies a significant advancement in sound source localization, and opens the door to a class of applications presently unattainable.
The nightscape of the Arctic winter shapes the diving behavior of a marine predator
Authors: Chambault Philippine , Teilmann Jonas , Tervo Outi , Sinding Mikkel Holger S. , Heide-Jørgensen Mads Peter
Published: February 2024

Predator–prey interactions in marine ecosystems are dynamically influenced by light, as demonstrated by diel vertical migrations of low-trophic level organisms. At high latitudes, the long winter nights can provide foraging opportunities for marine predators targeting vertically migrating prey closer to the surface at night. However, there is limited documentation of such diel patterns in marine predators under extreme light regimes. To address this, we recorded the diving behavior of 17 harbour porpoises just south of the Arctic circle in West Greenland, from summer to winter. Unlike classical diel vertical migration, the porpoises dove 24–37% deeper at night and the frequency of deep dives (> 100 m) increased tenfold as they entered the darkest months. The daily mean depth was negatively correlated with daylength, suggesting an increased diving activity when approaching the polar night. Our findings suggest a light-mediated strategy in which harbour porpoises would either target (i) benthic prey, (ii) pelagic prey migrating seasonally towards the seafloor, or (iii) vertically migrating prey that may be otherwise inaccessible in deeper waters at night, therefore maximizing feeding activity during extended periods of darkness. Extreme light regimes observed at high latitudes are therefore critical in structuring pelagic communities and food webs.
Prevalence of mental health symptoms and potential risk factors among Austrian psychotherapists
Authors: Schaffler Yvonne , Probst Thomas , Pieh Christoph , Haid Barbara , Humer Elke
Published: February 2024

This research focused on the intricacies of mental health within the psychotherapist community, a domain currently understudied. A recent study suggests a better overall mental health profile for Austrian psychotherapists compared to the general population. However, a substantial proportion of psychotherapists still exhibited scores beyond the cut-off for clinically significant mental disorders, potentially undermining the efficacy of patient outcomes. A cross-sectional study was conducted between April to June 2023, enrolling a cohort of 502 Austrian psychotherapists (79.7% female; mean age: 53.4 ± 9.26 years). The analysis leveraged indicators for symptoms of depression (PHQ-2), anxiety (GAD-2), insomnia (ISI-2), stress (PSS-4), and overall well-being (WHO-5). Key correlations were revealed using multivariable logistic regressions incorporating sociodemographic, work-related, and health behavior variables. Mental health symptoms in psychotherapists were associated with lower income, lesser physical activity, employment in outpatient facilities, less experience in the field, and a smaller patient load. Notably, physical activity emerged as a significant protective component, underscoring regular exercise as a vital self-care routine for psychotherapists. Adequate income also presented as a crucial contributor to mental health stability. These findings augment our understanding of the complex dynamics influencing psychotherapists' mental health, potentially enhancing their well-being and optimizing professional output.
Electrospun silk fibroin/fibrin vascular scaffold with superior mechanical properties and biocompatibility for applications in tissue engineering
Authors: Yang Lei , Wang Xu , Xiong Man , Liu Xinfang , Luo Sidong , Luo Jinxian , Wang Yeyang
Published: February 2024

Electrospun scaffolds play important roles in the fields of regenerative medicine and vascular tissue engineering. The aim of the research described here was to develop a vascular scaffold that mimics the structural and functional properties of natural vascular scaffolding. The mechanical properties of artificial vascular tissue represent a key issue for successful transplantation in small diameter engineering blood vessels. We blended silk fibroin (SF) and fibrin to fabricate a composite scaffold using electrospinning to overcome the shortcomings of fibrin with respect to its mechanical properties. Subsequently, we then carefully investigated the morphological, mechanical properties, hydrophilicity, hemocompatibility, degradation, cytocompatibility and biocompatibility of the SF/fibrin (0:100), SF/fibrin (15:85), SF/fibrin (25:75), and SF/fibrin (35:65) scaffolds. Based on these in vitro results, we implanted SF/fibrin (25:75) vascular scaffold subcutaneously and analyzed its in vivo degradation and histocompatibility. The fiber structure of the SF/fibrin hybrid scaffold was smooth and uniform, and its fiber diameters were relatively small. Compared with the fibrin scaffold, the SF/fibrin scaffold clearly displayed increased mechanical strength, but the hydrophilicity weakened correspondingly. All of the SF/fibrin scaffolds showed excellent blood compatibility and appropriate biodegradation rates. The SF/fibrin (25:75) scaffold increased the proliferation and adhesion of MSCs. The results of animal experiments confirmed that the degradation of the SF/fibrin (25:75) scaffold was faster than that of the SF scaffold and effectively promoted tissue regeneration and cell infiltration. All in all, the SF/fibrin (25:75) electrospun scaffold displayed balanced and controllable biomechanical properties, degradability, and good cell compatibility. Thus, this scaffold proved to be an ideal candidate material for artificial blood vessels.