bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex hormones and risk of lung and colorectal cancers in women: a Mendelian randomization study
Authors: Denos Marion , Sun Yi-Qian , Brumpton Ben , Li Yafang , Albanes Demetrius , Burnett-Hartman Andrea , Campbell Peter T , Küry Sébastien , Li Christopher I , White Emily , Samadder Jewel N , Jenkins Mark , Mai Xiao-Mei
Published: April 2024

The roles of sex hormones such as estradiol, testosterone, and sex hormone-binding globulin (SHBG) in the etiology of lung and colorectal cancers in women, among the most common cancers after breast cancer, are unclear. This Mendelian randomization (MR) study evaluated such potential causal associations in women of European ancestry. We used summary statistics data from genome-wide association studies (GWASs) on sex hormones and from the Trøndelag Health (HUNT) Study and large consortia on cancers. There was suggestive evidence of genetically predicted 1-standard deviation increase in total testosterone levels being associated with a lower risk of lung non-adenocarcinoma (hazard ratio (HR) 0.60, 95% CI 0.37–0.98) in the HUNT Study. However, this was not confirmed by using data from a larger consortium. In general, we did not find convincing evidence to support a causal role of sex hormones on risk of lung and colorectal cancers in women of European ancestry.
Clusters of post-acute COVID-19 symptoms: a latent class analysis across 9 databases and 7 countries
Authors: Prieto-Alhambra Daniel , Güell Kim López , Català Martí , Dedman Daniel , Duarte-Salles Talita , Kolde Raivo , López-Blasco Raúl , Martínez Álvaro , Mercier Gregoire , Abellan Alicia , Arinze Johnmary , Burkard Theresa , Burn Edward , Cuccu Zara , Delmestri Antonella , Delseny Dominique , Khalid Sara , Kim Chungsoo , Kim Ji-woo , Kostka Kristin , Loste Cora , Mayer Miguel , Meléndez-Cardiel Jaime , Mercadé-Besora Nuria , Mosseveld Mees , Nishimura Akihiko , Nordeng Hedvig ME , Oyinlola Jessie O , Paredes Roger , Pérez-Crespo Laura , Pineda-Moncusí Marta , Ramírez-Anguita Juan Manuel , Trinh Nhung TH , Uusküla Anneli , Valdivieso Bernardo , Xie Junqing , Mateu Lourdes , Jödicke Annika
Published: April 2024

Prior evidence has suggested the multisystem symptomatic manifestations of post-acute COVID-19 condition (PCC). Here we conducted a network cluster analysis of 24 WHO proposed symptoms to identify potential latent subclasses of PCC. Individuals with a positive test of or diagnosed with SARS-CoV-2 after 09/2020 and with at least one symptom within ≥ 90 to 365 days following infection were included. Sub-analyses were conducted among people with ≥ 3 different symptoms. Summary characteristics were provided for each cluster. All analyses were conducted separately in 9 databases from 7 countries, including data from primary care, hospitals, national health claims and national health registries, allowing to validate clusters across the different healthcare settings. 787,078 persons with PCC were included. Single-symptom clusters were common across all databases, particularly for joint pain, anxiety, depression and allergy. Complex clusters included anxiety-depression and abdominal-gastrointestinal symptoms. Substantial heterogeneity within and between PCC clusters was seen across healthcare settings. Current definitions of PCC should be critically reviewed to reflect this variety in clinical presentation.
Global, regional, and national burden of liver cancer due to non-alcoholic steatohepatitis, 1990–2019: An analysis of the Global Burden of Disease Study
Authors: Huang Minshan , Chen Hang , Wang Hui , Wang Xianmei , Wang Da , Li Yu , Zhou Qingqing , Zhang Dan , Li Mengwei , Ma Lanqing
Published: April 2024

Nonalcoholic steatohepatitis (NASH) has rapidly become the most common cause of hepatocellular carcinoma (HCC). We aimed to report the global, regional, and national burden of NASH-related HCC and its attributable risk factors between 1990 and 2019, by age, sex, and sociodemographic index. In 2019, 46.8 thousand prevalent cases of NASH-related HCC were reported globally, with NASH-related HCC accounting for 34.7 thousand deaths and 795.8 thousand disability-adjusted life year (DALY). The global age standardised point prevalence, death, and DALY rates for NASH-related HCC were 0.6, 0.4, and 9.6 per 100 000 population. The death and DALY were 5.3%, 15.1% lower than in 1990, respectively, while the prevalence was 19.8% higher than 1900. High-income Asia Pacific (1.5) had the highest age standardised point prevalence of NASH-related HCC. Australasia (265.1%), Central Asia (256.8%), and High-income North America (207%) showed the largest increases in age standardised point prevalence across the study period. In 2019, Southern Sub-Saharan Africa (0.8) had the highest and Tropical Latin America (0.2), Central Sub-Saharan Africa (0.2), Eastern Europe (0.2), and Southern Latin America (0.2) had the lowest age standardised death rates per 100 000. Southern Sub-Saharan Africa (19.1) and Tropical Latin America (3.6) had the highest and lowest age standardised DALY rates per 100 000, respectively. The burden of NASH-related HCC will rise slightly over the next decade, and this disease, which is not associated with SDI, remains a major public health problem. In addition, the escalating rates of obesity, demographic shifts, and an aging population could position NASH as a leading factor in liver cancer cases, surpassing viral hepatitis. It's imperative, therefore, that the forthcoming years see the implementation of strategic interventions aimed at the early detection and prevention of liver cancer associated with NASH.
Age-dependent alterations in the human striatum identify a PPP1R15B-miR-196a node as a modifier of Huntington’s disease phenotypes
Authors: Yoo Andrew , Church Victoria , Krzyzosiak Agnieszka , Chen Shawei , Kwon Ji-Sun , Victor Matheus , Miao Benpeng , Zhang Bo , Dahiya Sonika , Bertolotti Anne
Published: April 2024

Polyglutamine expansion in Huntingtin (HTT) causes its aggregation and progressive loss of striatal neurons in Huntington’s disease (HD). HD is a mostly adult-onset neurodegenerative disorder with no disease-modifying therapies. Here we found that human striatal aging is associated with a global upregulation of genes involved in translation, including the translation and proteostasis regulator PPP1R15B (R15B). We used the R15B inhibitor Raphin1 to investigate if the age-associated changes could modify HD pathology. R15B inhibition rescued early learning and late motor deficits in HDYAC128 mice. In striatal medium spiny neurons directly reprogrammed from fibroblasts of symptomatic HD patients (HD-MSNs), Raphin1 reduced the formation of mutant HTT aggregates and neuronal death. Genetic knockdown of R15B also protected HD-MSNs from neurodegeneration whereas its overexpression exacerbated disease phenotypes. Moreover, both human striatum and reprogrammed MSNs exhibited age-dependent decline of miR-196a, a microRNA that directly targets non-conserved sites in human R15B 3’UTR and overexpressing miR-196a lowered mutant HTT aggregation. This work identifies age-dependent alterations in miR-196a and its target R15B and demonstrates the therapeutic potential of reversing these changes in diverse models and readouts of HD. We propose miR-196a and R15B as disease-modifying targets in HD.
Social Presence in Online Live Learning Improves Learners’ Mentalizing: An fMRI Study
Authors: Cheng Siqi , Yu Guoming , Liu Jia
Published: April 2024

As the use of live and pre-recorded learning platforms becomes increasingly prevalent, it is crucial for educators and learners to effectively leverage these formats, acknowledging their distinct educational implications. This study aims to understand how different online learning formats—live and per-recorded—impact students’ perceptions of social presence, likability, credibility, and academic performance, while maintaining consistent instructional quality. Moreover, it explores how these two learning formats uniquely affect cognitive processing in the brain. Behavioral experiments assessed the influence on learning experiences and outcomes, complemented by fMRI analysis to monitor real-time cerebral activity during participant engagement with both learning modalities. Behaviorally, participants reported a heightened sense of social presence and a more favourable attitude during live online learning. From a neural perspective, the precuneus, a cortical region engaged in mentalizing, showed a significantly higher activation during live online learning than that during pre-recorded online learning. In summary, our study suggests that the perception of social presence in live learning environments may automatically enhance individuals’ mentalizing capacity, which may guide strategies for effectively implementation of diverse online learning formats in practical scenarios.
Nickel toxicity to safflower seed germination and seedling morpho-anatomy
Authors: Baran Uğurcan , Tanık Sude , Vardar Mert Can , Ülger Güray , Aksoy Ahmet
Published: April 2024

The safflowers (Carthamus tinctorius L. cv Olas) grown hydroponically under nickel (Ni) conditions have been studied in this work. The effects of 0, 0.75, 1.0, 3.0, 5.0, 10.0-, and 15.0-mM Ni on seed germination rate, protein, and pigment content of germinating seeds were investigated. Also, the toxicity of 0.75 mM Ni on plant growth, malondialdehyde (MDA) amount, and anatomy of 21-day-old safflower seedlings’ roots, stems, and leaves were determined. While Ni (especially higher than 3.0 mM) adversely affected the germination rate, radicle length, protein, and pigment content of safflower seeds, it also negatively affected the biomass production, plant length, leaf number, MDA amount, as well as some cell size/structure of roots (endodermis, phloem, trachea), stems (trachea and tracheid), and leaves (epidermis and sponge parenchyma) of safflower seedlings. Our results revealed that seedling growth was more sensitive to Ni exposure than germination. Although severe toxic effects were observed in 0.75 mM Ni treatment for plant growth parameters, seed germination only started to be highly affected at concentrations higher than 3.0 mM Ni.
Investigation and drug sensitivity analysis of reproductive tract infection in 7073 infertile patients
Authors: Wang Hong , AL-AMEER WAIL HUSSEIN AHMED , Zhou Lina , Huang Wen
Published: April 2024

Objectives To research the pathogen distribution and Mycoplasma resistance of reproductive tract infection in infertile women in Wenzhou in recent years, and to provide experimental basis for clinical medication.
Methods Infertility patients diagnosed in the Second Affiliated Hospital of Wenzhou Medical University from January 2020 to December 2021 were selected. Cervical secretions were collected for pathogen detection and mycoplasma drug sensitivity test.
Results 4154 cases of reproductive tract infection were detected in 7073patients, with an infection rate of 58.73%. Mycoplasma infection(49.88%) was the most common, the main mode of CT infection was CT+UU with a positive rate of 1.40%. 595 cases were infected with two or more pathogens, and the mixed infection rate was 8.41%.The infection rates of UU, CT, UU+MH, UU+CT, UU+MH+CT (67.21%, 0.59%, 7.83%, 2.26%, 0.95%) in women with tubal infertility were higher than those in women with non-tubal infertility (P<0.05). There was no difference in the incidence of MH and NG between the two groups (P>0.05). The drug sensitivity test showed that there were many sensitive drugs to UU, including minocycline (98.57%), doxycycline (98.50%), josamycin (94.51%), azithromycin (78.82%) and erythromycin (70.69%). However, UU+MH mixed infection was severely resistant sensitive to azithromycin, erythromycin, clarithromycin and rohong, only sensitive to minocycline (98.05%), doxycycline (98.70%) and josamycin (88.50%).
Conclusion Common venereal pathogens genital tract infection is closely related to infertility, UU infection is the most common, multiple pathogens mixed infection is very common and serious drug resistant. It is suggested to select sensitive antibiotics to reduce the generation of drug-resistance strains according to the results of drug sensitivity test.
The Impact of the Polysidpersed Fuel Distribution on the Ignition Characteristic
Authors: Hareli Shlomo , Nave OPhir , Gol'dshtein Vladimir
Published: April 2024

Determining the thermal profile of the ignition is an important goal, as the desired ignition behavior varies with the objective. For example, extended ignition helps prolong the time that the engine run. On the other hand, fast ignition offers higher power gain. Another important aspect is the pollution caused by an undesirable chemical reaction determined by the ignition profile. Based on a procedure developed in an earlier article, we examined the impact of different theoretical PSD distributions on the thermal ignition profile. We have compared different particle size distributions (PSD) of polydispersed fuel spray with normal distribution with various means, each with the same amount of fuel volume. Our results reveal a significant dependency of thermal ignition on the PSD distribution. Systems that consist of only low radii droplets do not reach ignition, while systems with only high radii take a long time to establish ignition. Moreover, the change in droplet means radius shows an unexpected result of a double hump in the maximums temperature of the combustion process.
Microbiological desymmetrization of difficult-to- reduce bulky-bulky ketones
Authors: Kołodziejska Renata , Pawluk Hanna , Tafelska-Kaczmarek Agnieszka , Studzińska Renata , Baumgart Szymon , Kwit Marcin
Published: April 2024

This report presents the desymmetrization of prochiral bulky-bulky pyrimidine bases in the presence of commercial or home-made enzyme preparations as biocatalysts. Based on the experiments carried out, it was shown that commonly used baker’s yeast is a catalyst for 1N- and 3N-phenacyl derivatives of trimethyleneuracils. The substrate concentration and pH of the reaction medium were important for the selectivity and efficiency of the process. 1N derivatives were reduced with the highest degree of enantiomeric purity and a moderate degree of conversion for a substrate concentration of 5×10-4 mol/dm3, in a solution with pH 7.0 and 5.0. In the case of 3N-phenacyl derivatives for a concentration of 1×10-3 mol/dm3 in a solution with pH 6.0 and 7.0. Biotransformations catalyzed by Saccharomyces cerevisiae provided the corresponding (R)- or (S)-products with high optical purity (up to 99% ee).
Assessment of Tanzania Magnesite’s Suitability for the Struvite Recovery and Other Industrial Applications
Authors: Illakwahhi Daniel Tsingay , Vegi Maheswara Rao , Srivast Bajarang Bali Lal
Published: April 2024

Magnesite (MgCO3) is a valuable mineral with wide industrial applications; thus, geochemical familiarity and deposit quality are critical for making the best use of these resources. Tanzania is reported to have magnesite deposits in at least 12 different locations; however, four of these were chosen at random for study. This study aimed to examine the mineralogical and elemental composition of rock samples from Chambogo (KL), Muriatata (AR), Lobolosoiti (MN), and Chikaza (DM) using x-ray fluorescence (XRF) and powder x-ray diffraction (XRD). XRF examination revealed that sample KL, AR, MN, and DM, respectively, contain 45.21%, 46.06%, 43.21%, and 43.21% of magnesium oxide. Besides MgO, all samples contained SiO2, Fe2O3, Al2O3, CaO and several trace elements as impurities, with only calcium oxide, iron, arsenic and chromium identified as impurities of concern. However, XRD analysis indicated magnesite as the major mineral phase in samples KL, AR, MN, and DM, with percentage concentrations of 65.2, 68.14, 63.87, and 68, respectively. In all samples, strong peaks at 2θ~ 33o, 43o, 54o and 55o, confirmed the crystalline nature of magnesite. Calcination of these samples however, resulted in peak shift and phase change, with main diffraction peaks generated at 2θ~ 36.9o, 42.9o and 62.3o, confirming the formation of crystalline MgO. Despite considerable contamination levels of CaO, iron, chromium, and arsenic in the samples, all samples had enough magnesite to be mined for industrial use.
Effect of Soft Chain Types on Polycarbonate Diol-based Polyurethane Elastomers
Authors: Pang Jiahong , Zhang Xingfei , Zhong Jiachun , Wang Qi , Yang Yuhao , Yang Kaijie , Yue Mengjie , Pu Zejun
Published: April 2024

Polyurethane elastomers (PUEs) have been synthesized with polycarbonate diol synthesized from 1, 4-butanediol (C4PCDL) and 1, 6-butanediol (C6PCDL), polycaprolactone diol (PCL) as well as polytetrahydrofuran ether diol (PTMG) as soft segments respectively, with Isopharone diisocyanate (IPDI) and 1, 4-butanediol as hard segments. The PUEs composed of four different soft chains are called PUE1, PUE2, PUE3 and PUE4, whose structure, mechanical and thermal properties and light transmittance have been tested with the aim to analyze the effect of the structure of the soft chain on the properties. The experimental results indicate that PUEs successfully be synthesized with the prepolymer method. The stronger the polarity of the soft chains is, the greater the tensile strength, hardness and heat-resistant quality of the PUEs is. With the increase of the flexibility of the soft chain of the PUEs, its elongation at break will increase and Tg will decrease and the light transmittance of it is affected by the degree of phase separation. Specifically, the greater the degree of phase separation is, the lower the transmittance is. The tensile strength of PUE1 reaches 39.82 MPa, the hardness reaches 93.9 Shore A, and the Td5% reaches 308.9 ℃. Without this, its transmittance also reached 92.31%.
Blockchain-based decentralized storage scheme with verifiable fair payment for smart cities
Authors: Zhou Yuan , Zhang YaLing
Published: April 2024

In smart cities, Internet of Things (IoT) technology can enable intelligence in various fields such as urban transportation, energy, environment, and security. While a large number of terminals collect data to bring efficiency and convenience, the problem of data security is becoming increasingly severe. Although existing centralized cloud services can provide powerful computing and storage resources, they also present risks such as data congestion, single points of failure, and privacy leakage. In order to address the above challenges, this paper proposes a blockchain-based decentralized storage management scheme for IoT data in smart cities scenario to improve data storage security. The scheme uses a non-interactive verification mechanism, combined with smart contracts, to realize automatic data verification. Set rewards and penalties to ensure fairness in IoT data storage transactions. The security analysis shows that the data verification mechanism proposed in this paper can effectively mitigate multiple attacks. We deploy smart contracts on the Ethereum platform and conduct experimental evaluations, then write smart contracts on the chain and test the Gas consumption of the contracts. We also evaluate the time efficiency of the algorithms off the chain, and the experimental results prove the practicality of the proposed scheme.
Effects of attention on the asymmetric serial dependences between form and motion patterns and their computational processes
Authors: Sun Qi , Wang Si-Yu , Sun Meng-Ying , You Fan-Huan , Ran Ping , Sun Qian
Published: April 2024

Recent studies have revealed that serial dependences are asymmetric in the estimation of the focus of expansion (FoE) in the global static form and dynamic optic flow displays. Here, we conducted two experiments to examine whether and how attention affected the serial dependences between the two displays. We found that when all attentional resources are allocated to the FoE estimation task, the serial dependence of the form FoE estimation on the previous flow FoE (SDEflow_form) still existed even as the flow FoE was 40°, while the serial dependence of the flow FoE estimation on the previous form FoE (SDEform_flow) disappeared as the form FoE was beyond 30°. When attentional resources are distributed by other tasks, the SDEflow_form tended to be stronger than the SDEform_flow. Therefore, the SDEflow_form and SDEform_flow are asymmetric regardless of observers’ attentional states. Lastly, we developed two Bayesian models based on the proposal that attention modulated the certainty of sensory representations of currently presented features. Besides, one model took the effects of working memory on previously presented features in consideration. We found that the model with working memory predicted participants’ performances better than the model without considering working memory. In summary, the current study demonstrated attention and working memory affected the serial dependences between form and flow displays and the effects could be quantitatively predicted by Bayesian inference models.
A hierarchical model system of biomass and carbon storage for all forest types in China
Authors: Zeng Weisheng , Zou WenTao , Chen XinYun , Yang XueYun
Published: April 2024

Forest biomass and carbon storage models are crucial for inventorying, monitoring, and assessing forest resources. This study develops models specific to China's diverse forests, offering a methodological foundation for national carbon storage estimation and a reference for regional and global carbon sequestration projections. Utilizing data from 52,700 permanent plots obtained during China's 9th national forest inventory, we calculated biomass and carbon storage per hectare for 35 tree species groups using respective biomass models and carbon factors. We then constructed a hierarchical volume-based model system for forest biomass and carbon storage, applying weighted regression, dummy variable modeling, and simultaneous equations with error-in-variables. This system encompasses a single population, three forest categories (level I), 20 forest types (level II), and 74 forest sub-types (level III). Finally, assessment of these models was carried out with six evaluation indices, and comparative analyses with previously established biomass models were conducted. Determination coefficients (R²) for the population average, level I, II, and III dummy models exceed 0.78, 0.85, 0.92, and 0.95, respectively, with corresponding mean percent standard errors (MPSE) of approximately 22%, 21%, 15%, and 12%. Furthermore, mean prediction errors (MPE) have consistently lessened to below 0.5%, and total relative errors (TRE) approximate zero. Models for 20 forest types and 74 sub-types yield R² values above 0.87 and 0.85, with MPE values below 3% and 5%, respectively. Notably, the estimates of previous biomass models demonstrated considerable uncertainty, with TRE ranging from − 20–74%. However, accuracy has improved with larger sample sizes. In total biomass and carbon storage estimations, the R² values of dummy models for levels I, II, and III progressively increase and MPSE values decrease, whereas MPE and TRE remain relatively stable. The tiered model system of simultaneous equations developed herein offer a quantitative framework for precise evaluations of biomass and carbon storage across China's forests. For enhanced accuracy in such estimations, applying level III models is recommended whenever feasible.
Novel GNAI3 mutation in a Chinese auriculocondylar syndrome family and treatment of severe dentofacial deformities: A 5-years follow-up case report
Authors: Shi Yulin , Rong Liang , Liu Siying , Liu Yiwen , Zong Chunlin , Lu Jinbiao , Shang Hongtao , Xue Yang , Tian Lei
Published: April 2024

Background
Auriculocondylar syndrome (ARCND) is an extremely rare autosomal dominant or recessive condition and the typical triad manifestations of ARCND are question mark ears (QMEs), mandibular condyle hypoplasia, and micrognathia. This severe dental and maxillofacial malformations have caused great trouble to patient’s life and clinical treatment. Now only a few ARCND cases are reported in the world, but most of them are about genetic mutations, clinical symptoms, and ear correction, reports concerning treatment of dentofacial deformity are few.
Case presentation
We here present a rare Chinese family case with ARCND. A novel insertional mutation in guanine nucleotide-binding protein alpha-inhibiting activity polypeptide 3 (GNAI3) was identified in the patient and the patient’s brother by whole-exome sequencing. After multidisciplinary consultation and examination, sequential orthodontic treatment and craniofacial surgery including distraction osteogenesis (DO) and orthognathic surgery were performed with the aid of three-dimensional (3D) digital technology to treat the patient’s dentofacial deformity. A good prognosis was achieved in 5-years follow-up, and the patient returned to normal life.
Conclusion
ARCND is a monogenic and rare condition, it could be diagnosed by its clinical triad core features. Molecular diagnosis plays a crucial role in patients who has unconspicuous clinical features. We present a novel insertion variation of GNAI3 which was identified in exon 2 of chromosome 110116384 in a Chinese family. The sequential therapy of preoperative orthodontic treatment combined with DO and orthognathic surgery guided by 3D digital technology could be a practical and effective method to treat ACSND.
Freeze-dried fecal microorganisms as an effective biomaterial for the treatment of calves suffering from diarrhea
Authors: Nochi Tomonori , Islam Jahidul , Ohtani Natsuki , Shimizu Yu , Tanimizu Masae , Goto Yoshiaki , Sato Masumi , Makino Eiji , Shimada Toru , Ueda Chise , Matsuo Ayumi , Suyama Yoshihisa , Sakai Yoshihisa , Karrow Niel , Yoneyama Hiroshi , Hirakawa Ryota , Furukawa Mutsumi , Tanaka Hidekazu
Published: April 2024

Fecal microbiota transplantation (FMT) is a therapeutic modality for treating neonatal calf diarrhea. Several practical barriers, including donor selection, fecal collection, and a limited timeframe for FMT, are the main constraints to using fresh feces for implementing on-farm FMT. We report the utility of FMT with pretreated ready-to-use frozen (F) or freeze-dried (FD) microorganisms for treating calf diarrhea. In total, 19 FMT (F-FMT, n = 10 and FD-FMT, n = 9) treatments were conducted. Both FMT treatments were 100% clinically effective; however, multi-omics analysis showed that FD-FMT was superior to F-FMT. Machine learning analysis with SourceTracker confirmed that donor microbiota was retained four times better in the recipient calves treated with FD-FMT than F-FMT. A predictive model based on receiver operating characteristic curve analysis and area under the curve showed that FD-FMT was more discriminative than F-FMT of the observed changes in microbiota and metabolites during disease recovery. These results provide new insights into establishing methods for preparing fecal microorganisms to increase the quality of FMT in animals and may contribute to FMT in humans.
AAV vectors trigger DNA damage responses and STING-dependent inflammation in human CNS cells
Authors: Costa-Verdera Helena , Meneghini Vasco , Fitzpatrick Zachary , Alezz Monah Abou , Fabyanic Emily , Huang Xin , Dzhashiashvili Yulia , Ahiya Avantika , Mangiameli Elisabeth , Valeri Erika , Crivicich Giovanni , Cuccovillo Ivan , Caccia Roberta , Bertin Berangere , Ronzitti Giuseppe , Engel Esteban , Merelli Ivan , Mingozzi Federico , Gritti Angela , Kuranda Klaudia , Kajaste-Rudnitski Anna
Published: April 2024

Adeno-associated viral (AAV) vector-based gene therapy is gaining foothold as a treatment option for a variety of genetic neurological diseases with encouraging clinical results. Nonetheless, dose-dependent toxicities and severe adverse events have emerged in recent clinical trials through mechanisms that remain unclear. We have modelled here the impact of AAV transduction in the context of cell models of the human central nervous system (CNS), taking advantage of induced pluripotent stem cell-based technologies. Our work uncovers vector-induced cell-intrinsic innate immune mechanisms that contribute to apoptosis in 2D and 3D models. While empty AAV capsids were well tolerated, the AAV genome triggered p53-dependent DNA damage responses across CNS cell types followed by induction of IL-1R- and STING-dependent inflammatory responses. In addition, transgene expression led to MAVS-dependent signaling and activation of type I interferon (IFN) responses. Cell-intrinsic and paracrine apoptosis onset could be prevented by inhibiting p53 or acting downstream of STING- and IL-1R-mediated responses. Activation of DNA damage, type I IFN and CNS inflammation were confirmed in vivo, in a mouse model. Together, our work identifies the cell-autonomous innate immune mechanisms of vector DNA sensing that can potentially contribute to AAV-associated neurotoxicity.
Experimental Investigation on Anisotropic Shear Properties of Artificial Columnar Jointed Rock Mass Based on Three-Dimensional Printing Method
Authors: tao zhang
Published: April 2024

The anisotropic shear mechanical characteristics of columnar jointed rock mass (CJRM) were studied. Specimens were taken from the geometric structure of the CJRM of the dam foundation at the Baihetan hydropower station. A water-soluble material was used by three-dimensional printing technology to establish a columnar jointed network structure with different joint dip angles. The CJRM specimens were prepared with rock-like materials. The anisotropy characteristics of CJRM specimens with positive and negative joint dip angles under shear stress were analyzed by direct shear tests, and observed under scanning electron microscopy (SEM). The results show that the anisotropy of CJRM specimens depends on the joint dip angle. The anisotropy degree of the characteristic stresses and peak friction angle of CJRM specimens with positive joint dip angles is greater than that of negative joint dip angles. Four failure modes are observed, depending on the joint dip angle. The research results provide a reference for the anisotropic shear mechanical properties of CJRM in geotechnical engineering.
The detection of absence seizures using cross-frequency coupling analysis with a deep learning network
Authors: Medvedev Andrei V. , Lehmann Bar
Published: April 2024

High frequency oscillations are important novel biomarkers of epileptogenic tissue. The interaction of oscillations across different time scales is revealed as cross-frequency coupling (CFC) representing a high-order structure in the functional organization of brain rhythms. New artificial intelligence methods such as deep learning neural networks can provide powerful tools for automated analysis of EEG. Here we present a Stacked Sparse Autoencoder (SSAE) trained to recognize absence seizure activity based on the cross-frequency patterns within scalp EEG. We used EEG records from the Temple University Hospital database. Absence seizures (n = 94) from 12 patients were taken into analysis along with segments of background activity. Half of the records were selected randomly for network training and the second half were used for testing. Power-to-power coupling was calculated between all frequencies 2-120 Hz pairwise using the EEGLAB toolbox. The resulting CFC matrices were used as training or testing inputs to the autoencoder. The trained network was able to recognize background and seizure segments (not used in training) with a sensitivity of 96.3%, specificity of 99.8% and overall accuracy of 98.5%. Our results provide evidence that the SSAE neural networks can be used for automated detection of absence seizures within scalp EEG.
Contention-aware Greedy Heuristic Method and Learning based Method for Load Balancing through Scheduling for Containers in Cloud Computing Environments
Authors: Gogineni Neelima , S Saravanan. M.
Published: April 2024

Containerization became indispensable in distributed environments for packaging software and dependencies in a lightweight executable container. In the era of big data and availability of cloud infrastructure, it is more so as distributed applications are more resource and data-intensive. Such High Performance Computing (HPC) applications are deployed in containerized services. However, data-intensive nature of those applications lead to poor performance unless scheduler considers it. In this paper, not only load balancing of containers but also performance of underlying applications is considered. Towards this end, a scheduling algorithm with unified optimization considering load balancing and also application performance is proposed. This algorithm, named Contention-aware Greedy Heuristic Scheduling and Load Balancing for Containers (CGHSLBC), helps in improving performance of containerization in distributed environments. Problems associated with containerization in terms of balancing load and also application performance are NP-hard. CGHSLBC has heuristics to deal with such issues. Empirical study has revealed that CGHSLBC better application performance besides balancing load of containerized services in cloud infrastructure. We also proposed a learning based methodology to schedule and balance load for containers. It is based on Deep Reinforcement Learning (DRL) where state change is continuously monitored while making well informed scheduling decisions. An algorithm named Reinforcement Learning based Dynamic Scheduling (RLbDS) is proposed and empirical study has revealed that it shows better performance over state of the art methods.
Mesenchymal stem cell derived proteome can target multiple signalling pathways to ameliorate rheumatoid arthritis: network pharmacology and molecular docking based approach
Authors: Tariq Muhammad Hamza , Farid Nouran , Kohli Nupur
Published: April 2024

Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease with a global prevalence of approximately 1%. Mesenchymal stem cells (MSCs) have been thoroughly investigated for the treatment of RA; however, their clinical use is limited due to issues related to cell engraftment. It is now well established that MSCs exert their regenerative effect through the paracrine mechanism of their secreted factors (called the secretome); however, the mechanism by which secretome proteins target diseases is still unclear. This study aimed to investigate the potential of the proteome of the MSC secretome in targeting the key molecular signatures of RA. Secretome from primary human bone marrow MSCs was collected, and proteomic analysis was performed using label-free tandem mass spectrometry. A network pharmacology approach was used to identify the target genes of the MSC proteome as well as therapeutic targets of RA. Proteomic analysis of the MSC secretome confirmed the presence of 187 unique proteins, with 136 direct human gene targets. 52 of the identified genes were common with the 1922 identified targets of RA. Functional annotations of the 52 genes revealed their involvement in multiple RA-related KEGG pathways, such as ECM-receptor interaction, focal adhesion, the PI3K-AKT SIGNALLING pathway, the phagosome, and the p53 pathway. Molecular docking of the top 10 hub proteins with the PI3K-AKT pathway revealed a strong binding affinity forall the hub proteins, indicating the potential mechanism by which the MSC proteome can be used as a therapeutic cocktail to ameliorate RA.
Water and Seawater Splitting with MgB2 Plasmonic Metal-Based Photocatalyst
Authors: Kravets Vasyl , Grigorenko Alexander
Published: April 2024

Plasmonic nanostructures can help to drive chemical photocatalytic reactions powered by sunlight. These reactions involve excitation of plasmon resonances and subsequent charge transfer to molecular orbitals under study. Here we engineered photoactive plasmonic nanostructures with enhanced photocatalytic performance using non-noble metallic MgB2 high-temperature superconductor which represents a new family of photocatalysts. Ellipsometric study of fabricated MgB2 nanostructures demonstrates that this covalent binary metal with layered graphite-like structure could effectively absorb visible and infrared light by excitation of multi-wavelengths surface plasmon resonances. We show that a MgB2 plasmonic metal-based photocatalyst exhibit fundamentally different behaviour compared to that of a semiconductor photocatalyst and provides several advantages in photovoltaics applications. Excitation of localised surface plasmon resonances in MgB2 nanostructures allows one to overcome the limiting factors of photocatalytic efficiency observed in semiconductors with a wide energy bandgap due to the usage of a broader spectrum range of solar radiation for water splitting catalytic reactions conditioned by enhanced local electromagnetic fields of localised plasmons. Excitation of localised surface plasmon resonances induced by absorption of light in MgB2 nanosheets could help to achieve near full-solar spectrum harvesting in this photocatalytic system. We demonstrate a conversion efficiency of ~5% at bias voltage of Vbias = 0.3 V for magnesium diboride working as a catalyst for the case of plasmon-photoinduced seawater splitting. Our work could result in inexpensive and stable photocatalysts that can be produced in large quantities using a mechanical rolling mill procedure.
Biomineralized bacterial outer membrane vesicles exert pleiotropic immunoferroptotic effects on immune-deserted liver cancer
Authors: Luo Ying , Xu Zhongsheng , Du Qianying , Xu Lian , Wang Yi , Xu Jie , Wang Junrui , Chen Sijin , Zhang Wenli , Liu Bo , Liu Jia , Guo Dajing , Liu Yun
Published: April 2024

The immune landscape of late-stage liver cancer is featured by severe immunosuppression that is characterized by poor immunogenicity, T-cell exhaustion, and infiltration of a large number of immunosuppressive cells, leading to compromised therapeutic efficacy of mainstream immunotherapies. Herein, we developed a pleiotropic immunoferroptotic mobilization strategy to treat intractable advanced liver cancer. In this study, immunogenic bacteria-derived outer membrane vesicles (OMVs) were exploited as a vector to deposit Cu and Mn with mixed valence states via one-step biomineralization, followed by platelet membrane camouflage to enhance the circulation time and reduce systemic side effects of the metal biomineralized OMVs, which are denoted as OPCM. Mechanistically, the metal-deposited OPCM possesses POD, CAT, and GPX-like activities, thereby stimulating immunogenic ferroptosis, cGAS-STING activation, and tumor hypoxia alleviation, ultimately leading to pleiotropic immunoferroptotic mobilization to combat tumor growth, recurrence, and metastasis. Notably, the combination with typical αPD-L1 augmented the tumor suppression effect, since the administration of αPD-L1 not only rescued exhausted T cells, but also amplified the intensity of ferroptosis due to IFN-γ secretion by activated T cells. Overall, the metal biomineralized OPCMs in combination with αPD-L1 formed a closed-loop therapy that cycles from immunotherapy and ferroptosis therapy, providing new insights for treating immunosuppressive liver cancer.
Insight Into the Relationship Between Motor and Cognitive Symptoms in Essential Tremor
Authors: Paparella Giulia , Angelini Luca , Margiotta Roberta , Passaretti Massimiliano , Birreci Daniele , Costa Davide , Cannavacciuolo Antonio , De Riggi Martina , Fegatelli Danilo Alunni , Bologna Matteo
Published: April 2024

Introduction:Essential tremor (ET) is a heterogeneous disorder characterized by bilateral upper limbs action tremor and, possibly, neurological signs of uncertain significance, including voluntary movement abnormalities and cognitive disturbances, i.e., the so-called ‘soft’ signs configuring ET-plus definition. While motor and cognitive disturbances often coexist in ET, their interrelationship remains largely unexplored. Here we aim to further investigate the relationship between motor symptoms, objectively assessed through kinematic analysis, and cognitive dysfunctions in ET.Methods:70 ET patients underwent clinical examination, as well as kinematic recordings of tremor and finger tapping and a thorough cognitive assessment. We then tested clinic-demographic and kinematic differences between patients with and without cognitive abnormalities, i.e., with mild cognitive impairment (MCI). Correlation analysis served to explore potential associations between kinematic and cognitive data.Results:43 ET patients (61.42%) had MCI. ET-MCI patients exhibited reduced movement velocity during finger tapping compared to those with normal cognition (p<0.001). Lower movement velocity during finger tapping was associated with poorer cognitive performance. Namely, we observed a correlation between movement velocity and performance on the Babcock Story Immediate and Delayed Recall Test (r=0.52 and r=0.45, both p<0.001), as well as the interference memory task at 10 and 30 seconds (r=0.3, p=0.008 and r=0.2, p=0.03).Conclusions:In this study, we have provided data for a better pathophysiological interpretation of motor and cognitive signs in ET, including the role played by the cerebellum or extra-cerebellar areas, which possibly underpin both signs.
An applied noise model for scintillation-based CCD detectors in transmission electron microscopy
Authors: Zietlow Christian , Lindner Jörg K. N.
Published: April 2024

Measurements in general are limited in accuracy by the presence of noise. This also holds true for highly sophisticated scintillation-based CCD cameras, as they are used in medical applications, astronomy or transmission electron microscopy (TEM). Further, signals measured with pixelated detectors are convolved with the inherent detector point spread function (PSF). The Poisson noise, arising from the quantized nature of the beam electrons, gets correlated by this convolution, which allows to reconstruct the detector PSF based on the Wiener–Khinchin theorem and the Pearson correlation coefficients under homogeneous illumination conditions. However, correlation also has a strong impact on the noise statistics of basic operations like the binning of signals, as it is usually done in electron energy-loss spectroscopy (EELS). Thus, this paper aims to give an insight into the different noise contributions occurring on such detectors, into their underlying statistics and their correlation. Detectors usually suffer from gain non-linearities and quantum efficiency deviations, which must be corrected for optimal results. All these operations influence the noise and are influenced by it, vice versa. In this work, we mathematically describe all these changes and show them experimentally. Methods on how to measure individual noise and correlation parameters are described allowing readers to implement routines for finding them. Sufficient knowledge on the noise of a measurement is not only crucial for classifying its quality and meaningfulness, but also allows for better post-processing operations like deconvolution, which is a common practice in spectroscopy to enhance signals.
A pH-Triggered self-releaseing humic acids hydrogels loaded with porcine interferon α/γ achieves anti-PRV effects by oral administration
Authors: Sun Mao-Yuan , Shi Yong-li , Lei Bai-Shi , Zhang Wu-Chao , Feng Jing-Jing , Ge Sheng-Hu , Yuan Wan-Zhe , Zhao Kuan
Published: April 2024

Interferon α (IFNα) and interferon γ (IFNγ) are cytokines that mediate important biological functions, including antiviral activity and immune regulation. However, the function of monomer IFN was limited and the administration route completely depends on injection. To solve this problem, recombinant porcine IFN-α and IFN-γ fusion protein (rPoIFNα/γ) was expressed, purified, and used to develop an effective oral rPoIFNα/γ humic acid hydrogel delivery system triggered by pH to protect the IFNα/γ from gastric acid destruction. Neither the humic acid hydrogel nor rPoIFNα/γ showed cytotoxicity in vitro for porcine kidney-15 (PK-15) cells. rPoIFNα/γ inhibited the replication of vesicular stomatitis virus (VSV) and pseudorabies virus (PRV), with an antiviral activity of approximately 104 U/mL. Scanning electron microscopy revealed that the humic acid (HA) hydrogel had a loose and porous honeycomb structure. rPoIFNα/γ was adsorbed by the hydrogel (IFNα/γ@PAMgel) and measured using Fourier transform infrared spectroscopy, and the results indicated a good IFN-loading effect. In vitro experiments showed that IFNα/γ@PAMgel swelled and released the IFNα/γ rapidly at pH 7.4 but not at pH 1.2. Mice oral administered IFNα/γ@PAMgel had enhanced proliferation and differentiation of CD4+ and CD8+ cells, whereas mice infected with PRV and treated with IFNα/γ@PAMgel had increased interferon stimulating genes (ISGs) transcription levels in the serum, lower mortality, lower viral loads in different tissues, and lower levels of organ damage. Conclusively, this study demonstrates that oral administered IFNα/γ@PAMgel has antiviral and immunomodulatory effects and is a potential antiviral agent for PRV infection.
Research on the Impact and Mechanism of Digital Empowerment on Agricultural Carbon Emissions: Evidence from China
Authors: Song Jianfeng , Ma mingguo , Li Jiafen
Published: April 2024

Whether digital empowerment can promote the dual-carbon process in agriculture and how its specific mechanisms of action work is a significant proposition that deserves in-depth research. Based on panel data from 30 provincial-level regions in China from 2012 to 2021, this paper calculates the level of digital empowerment in regional agriculture using the input-output method. Based on clarifying the theoretical mechanism of the impact of digital empowerment development on agricultural carbon emissions, it employs methods such as the two-way fixed effect model, dynamic panel model, mediation effect model, and spatial econometric model to multidimensionally empirically explore the impact of digital empowerment development on agricultural carbon emissions and its mechanisms. The study finds that: (1) From 2012 to 2021, the level of digital empowerment in Chinese agriculture has been on an upward trend, but only in economically developed regions is this upward momentum apparent. At the same time, China's agricultural carbon emissions from 2012 to 2021 show a clear trend of initially increasing and then decreasing. (2) The development of digital empowerment has a significant inverted U-shaped non-linear impact on agricultural carbon emissions, and at present, the level of agricultural digital empowerment in most provinces in China has not yet crossed the inflection point of inhibiting agricultural carbon emissions, which still holds after endogeneity tests and robustness tests. (3) The mechanism analysis results show that digital empowerment reduces agricultural carbon emissions by optimizing carbon-intensive factor inputs and improving factor allocation efficiency. (4) Heterogeneity analysis results indicate that digital empowerment has a significant inverted U-shaped impact on agricultural carbon emissions in economically developed areas, while its impact on moderately developed and less developed economic areas is not significant; in non-grain main producing areas, the inhibitory effect of digital empowerment is more pronounced. (5) Further discussion reveals that digital empowerment has an inverted U-shaped spatial spillover effect on agricultural carbon emissions in neighboring areas. The aforementioned research results provide substantial empirical evidence for policymakers on how to better promote the development of digital empowerment and enhance the coordination of China's digital infrastructure in regional environmental governance.