bluuebunny/crossref_metadata_2025_split huggingface dataset:
YAP-mediated trophoblast dysfunction: the common pathway underlying pregnancy complications
Authors: Lin Qimei , Cao Jiasong , Yu Jing , Zhu Yu , Shen Yongmei , Wang Shuqi , Wang Yixin , Liu Zhen , Chang Ying 
Published: December 2023

AbstractYes-associated protein (YAP) is a pivotal regulator in cellular proliferation, survival, differentiation, and migration, with significant roles in embryonic development, tissue repair, and tumorigenesis. At the maternal–fetal interface, emerging evidence underscores the importance of precisely regulated YAP activity in ensuring successful pregnancy initiation and progression. However, despite the established association between YAP dysregulation and adverse pregnancy outcomes, insights into the impact of aberrant YAP levels in fetal-derived, particularly trophoblast cells, and the ensuing dysfunction at the maternal–fetal interface remain limited. This review comprehensively examines YAP expression and its regulatory mechanisms in trophoblast cells throughout pregnancy. We emphasize its integral role in placental development and maternal–fetal interactions and delve into the correlations between YAP dysregulation and pregnancy complications. A nuanced understanding of YAP's functions during pregnancy could illuminate intricate molecular mechanisms and pave the way for innovative prevention and treatment strategies for pregnancy complications.
Caregiver-child interaction as an effective tool for identifying autism spectrum disorder: evidence from EEG analysis
Authors: Deng Lin , He Wei-zhong , Zhang Qing-li , Wei Ling , Dai Yuan , Liu Yu-qi , Chen Zi-lin , Ren Tai , Zhang Lin-li , Gong Jing-bo , Li Fei 
Published: December 2023

Abstract
Background
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that affects individuals across their lifespan. Early diagnosis and intervention are crucial for improving outcomes. However, current diagnostic methods are often time-consuming, and costly, making them inaccessible to many families. In the current study, we aim to test caregiver-child interaction as a potential tool for screening children with ASD in clinic.

Methods
We enrolled 85 preschool children (Mean age: 4.90 ± 0.65 years, 70.6% male), including ASD children with or without developmental delay (DD), and typical development (TD) children, along with their caregivers. ASD core symptoms were evaluated by Childhood Autism Rating Scale (CARS) and Autism Diagnostic Observation Schedule-Calibrated Severity Scores (ADOS-CSS). Behavioral indicators were derived from video encoding of caregiver-child interaction, including social involvement of children (SIC), interaction time (IT), response of children to social cues (RSC), time for caregiver initiated social interactions (GIS) and time for children initiated social interactions (CIS)). Power spectral density (PSD) values were calculated by EEG signals simultaneously recorded. Partial Pearson correlation analysis was used in both ASD groups to investigate the correlation among behavioral indicators scores and ASD symptom severity and PSD values. Receiver operating characteristic (ROC) analysis was used to describe the discrimination accuracy of behavioral indicators.

Results
Compared to TD group, both ASD groups demonstrated significant lower scores of SIC, IT, RSC, CIS (all p values < 0.05), and significant higher time for GIS (all p values < 0.01). SIC scores negatively correlated with CARS (p = 0.006) and ADOS-CSS (p = 0.023) in the ASD with DD group. Compared to TD group, PSD values elevated in ASD groups (all p values < 0.05), and was associated with SIC (theta band: p = 0.005; alpha band: p = 0.003) but not IQ levels. SIC was effective in identifying both ASD groups (sensitivity/specificity: ASD children with DD, 76.5%/66.7%; ASD children without DD, 82.6%/82.2%).

Conclusion
Our results verified the behavioral paradigm of caregiver-child interaction as an efficient tool for early ASD screening.
Nutlin-3a induces KRAS mutant/p53 wild type lung cancer specific methuosis-like cell death that is dependent on GFPT2
Authors: Kim Dasom , Min Dongwha , Kim Joohee , Kim Min Jung , Seo Yerim , Jung Byung Hwa , Kwon Seung‑Hae , Ro Hyunju , Lee Seoee , Sa Jason K. , Lee Ji-Yun 
Published: December 2023

Abstract
Background
Oncogenic KRAS mutation, the most frequent mutation in non-small cell lung cancer (NSCLC), is an aggressiveness risk factor and leads to the metabolic reprogramming of cancer cells by promoting glucose, glutamine, and fatty acid absorption and glycolysis. Lately, sotorasib was approved by the FDA as a first-in-class KRAS-G12C inhibitor. However, sotorasib still has a derivative barrier, which is not effective for other KRAS mutation types, except for G12C. Additionally, resistance to sotorasib is likely to develop, demanding the need for alternative therapeutic strategies.

Methods
KRAS mutant, and wildtype NSCLC cells were used in vitro cell analyses. Cell viability, proliferation, and death were measured by MTT, cell counting, colony analyses, and annexin V staining for FACS. Cell tracker dyes were used to investigate cell morphology, which was examined by holotomograpy, and confocal microscopes. RNA sequencing was performed to identify key target molecule or pathway, which was confirmed by qRT-PCR, western blotting, and metabolite analyses by UHPLC-MS/MS. Zebrafish and mouse xenograft model were used for in vivo analysis.

Results
In this study, we found that nutlin-3a, an MDM2 antagonist, inhibited the KRAS-PI3K/Akt-mTOR pathway and disrupted the fusion of both autophagosomes and macropinosomes with lysosomes. This further elucidated non-apoptotic and catastrophic macropinocytosis associated methuosis-like cell death, which was found to be dependent on GFPT2 of the hexosamine biosynthetic pathway, specifically in KRAS mutant /p53 wild type NSCLC cells.

Conclusion
These results indicate the potential of nutlin-3a as an alternative agent for treating KRAS mutant/p53 wild type NSCLC cells.
Modulation of mitochondrial function with near-infrared light reduces brain injury in a translational model of cardiac arrest
Authors: Wider Joseph M. , Gruley Erin , Morse Paul T. , Wan Junmei , Lee Icksoo , Anzell Anthony R. , Fogo Garrett M. , Mathieu Jennifer , Hish Gerald , O’Neil Brian , Neumar Robert W. , Przyklenk Karin , Hüttemann Maik , Sanderson Thomas H. 
Published: December 2023

Abstract
Background
Brain injury is a leading cause of morbidity and mortality in patients resuscitated from cardiac arrest. Mitochondrial dysfunction contributes to brain injury following cardiac arrest; therefore, therapies that limit mitochondrial dysfunction have the potential to improve neurological outcomes. Generation of reactive oxygen species (ROS) during ischemia–reperfusion injury in the brain is a critical component of mitochondrial injury and is dependent on hyperactivation of mitochondria following resuscitation. Our previous studies have provided evidence that modulating mitochondrial function with specific near-infrared light (NIR) wavelengths can reduce post-ischemic mitochondrial hyperactivity, thereby reducing brain injury during reperfusion in multiple small animal models.

Methods
Isolated porcine brain cytochrome c oxidase (COX) was used to investigate the mechanism of NIR-induced mitochondrial modulation. Cultured primary neurons from mice expressing mitoQC were utilized to explore the mitochondrial mechanisms related to protection with NIR following ischemia–reperfusion. Anesthetized pigs were used to optimize the delivery of NIR to the brain by measuring the penetration depth of NIR to deep brain structures and tissue heating. Finally, a model of out-of-hospital cardiac arrest with CPR in adult pigs was used to evaluate the translational potential of NIR as a noninvasive therapeutic approach to protect the brain after resuscitation.

Results
Molecular evaluation of enzyme activity during NIR irradiation demonstrated COX function was reduced in an intensity-dependent manner with a threshold of enzyme inhibition leading to a moderate reduction in activity without complete inhibition. Mechanistic interrogation in neurons demonstrated that mitochondrial swelling and upregulation of mitophagy were reduced with NIR treatment. NIR therapy in large animals is feasible, as NIR penetrates deep into the brain without substantial tissue heating. In a translational porcine model of CA/CPR, transcranial NIR treatment for two hours at the onset of return of spontaneous circulation (ROSC) demonstrated significantly improved neurological deficit scores and reduced histologic evidence of brain injury after resuscitation from cardiac arrest.

Conclusions
NIR modulates mitochondrial function which improves mitochondrial dynamics and quality control following ischemia/reperfusion. Noninvasive modulation of mitochondria, achieved by transcranial treatment of the brain with NIR, mitigates post-cardiac arrest brain injury and improves neurologic functional outcomes.

Graphical abstract
HER2 amplification level by in situ hybridization predicts survival outcome in advanced HER2-positive breast cancer treated with pertuzumab, trastuzumab, and docetaxel regardless of HER2 IHC results
Authors: Seo Jeongmin , Koh Jiwon , Lee Dae-Won , Kim Jinyong , Ryu Han Suk , Lee Kyung-Hun , Kim Tae-Yong , Im Seock-Ah 
Published: December 2023

Abstract
Background
The role of HER2 amplification level in predicting the effectiveness of HER2-directed therapies has been established. However, its association with survival outcomes in advanced HER2-positive breast cancer treated with dual HER2-blockade remains unexplored.

Methods
This is a single-center retrospective study of patients with advanced HER2-positive breast cancer treated with first-line pertuzumab, trastuzumab, and docetaxel. The primary objective was to ascertain the relationship between treatment outcomes and the level of HER2 amplification by in situ hybridization (ISH).

Results
A total of 152 patients were included with a median follow-up duration of 50.0 months. Among the 78 patients who received ISH, a higher HER2/CEP17 ratio correlated significantly with longer PFS (HR 0.50, p = 0.022) and OS (HR 0.28, p = 0.014) when dichotomized by the median. A higher HER2 copy number also correlated significantly with better PFS (HR 0.35, p < 0.001) and OS (HR 0.27, p = 0.009). In multivariate analysis, the HER2/CEP17 ratio was an independent predictive factor for PFS (HR 0.66, p = 0.004) and potentially for OS (HR 0.64, p = 0.054), along with HER2 copy number (PFS HR 0.85, p = 0.004; OS HR 0.84, p = 0.049). Furthermore, the correlation between HER2 amplification level by ISH with PFS and OS was consistent across the HER2 IHC 1+/2+ and 3+ categories.

Conclusions
This is the first study to report that a higher level of HER2 amplification by ISH is associated with improved PFS and OS in advanced HER2-positive breast cancer treated with dual HER2-blockade. Notably, HER2 amplification level had a predictive role regardless of IHC results. Even in patients with HER2 protein expression of 3+, treatment outcome to HER2-directed therapy was dependent on the level of HER2 gene amplification.
A dual-antigen malaria vaccine targeting Pb22 and Pbg37 was able to induce robust transmission-blocking activity
Authors: Gao Wenyan , Qiu Yue , Zhu Liying , Yu Xinxin , Yang Fan , Chen Muyan , He Gang , Liu Yinjie , Cui Liwang , Liu Fei , Zhu Xiaotong , Cao Yaming 
Published: December 2023

Abstract
Background
Despite years of effort to develop an effective vaccine against malaria infection, a vaccine that provides individuals with sufficient protection against malaria illness and death in endemic areas is not yet available. The development of transmission-blocking vaccines (TBVs) is a promising strategy for malaria control. A dual-antigen malaria vaccine targeting both pre- and post-fertilization antigens could effectively improve the transmission-blocking activity of vaccines against the sexual stages of the parasite.

Methods
A chimeric recombinant protein Pb22-Pbg37 (Plasmodium berghei 22-P. berghei G37) composed of 19–218 amino acids (aa) of Pb22 and the N-terminal 26–88 aa of Pbg37 was designed and expressed in the Escherichia coli expression system. The antibody titers of the fusion (Pb22-Pbg37) and mixed (Pb22+Pbg37) antigens, as well as those of Pb22 and Pbg37 single antigens were evaluated by enzyme-linked immunosorbent assay. Immunofluorescence and western blot assays were performed to test the reactivity of the antisera with the native proteins in the parasite. The induction of transmission-blocking activity (TBA) by Pb22-Pbg37 and Pb22+Pbg37 were evaluated by in vitro gametocyte activation, gamete and exflagellation center formation, ookinete conversion, and in the direct mosquito feeding assay.

Results
The Pb22-Pbg37 fusion protein was successfully expressed in vitro. Co-administration of Pb22 and Pbg37 as a fusion or mixed protein elicited comparable antibody responses in mice and resulted in responses to both antigens. Most importantly, both the mixed and fusion antigens induced antibodies with significantly higher levels of TBA than did each of the individual antigens when administered alone. In addition, the efficacy of vaccination with the Pb22-Pbg37 fusion protein was equivalent to that of vaccination with the mixed single antigens.

Conclusions
Dual-antigen vaccines, which expand/lengthen the period during which the transmission-blocking antibodies can act during sexual-stage development, can provide a promising higher transmission-reducing activity compared to single antigens.

Graphical Abstract
The secretome of Staphylococcus aureus strains with opposite within-herd epidemiological behavior affects bovine mononuclear cell response
Authors: Di Mauro Susanna , Filipe Joel , Facchin Alessia , Roveri Laura , Addis Maria Filippa , Monistero Valentina , Piccinini Renata , Sala Giulia , Pravettoni Davide , Zamboni Clarissa , Ceciliani Fabrizio , Lecchi Cristina 
Published: December 2023

AbstractStaphylococcus aureus modulates the host immune response directly by interacting with the immune cells or indirectly by secreting molecules (secretome). Relevant differences in virulence mechanisms have been reported for the secretome produced by different S. aureus strains. The present study investigated the S. aureus secretome impact on peripheral bovine mononuclear cells (PBMCs) by comparing two S. aureus strains with opposite epidemiological behavior, the genotype B (GTB)/sequence type (ST) 8, associated with a high within-herd prevalence, and GTS/ST398, associated with a low within-herd prevalence. PBMCs were incubated with different concentrations (0%, 0.5%, 1%, and 2.5%) of GTB/ST8 and GTS/ST398 secretome for 18 and 48 h, and the viability was assessed. The mRNA levels of pro- (IL1-β and STAT1) and anti-inflammatory (IL-10, STAT6, and TGF-β) genes, and the amount of pro- (miR-155-5p and miR-125b-5p) and anti-inflammatory (miR-146a and miR-145) miRNAs were quantified by RT-qPCR. Results showed that incubation with 2.5% of GTB/ST8 secretome increased the viability of cells. In contrast, incubation with the GTS/ST398 secretome strongly decreased cell viability, preventing any further assays. The GTB/ST8 secretome promoted PBMC polarization towards the pro-inflammatory phenotype inducing the overexpression of IL1-β, STAT1 and miR-155-5p, while the expression of genes involved in the anti-inflammatory response was not affected. In conclusion, the challenge of PBMC to the GTS/ST398 secretome strongly impaired cell viability, while exposure to the GTB/ST8 secretome increased cell viability and enhanced a pro-inflammatory response, further highlighting the different effects exerted on host cells by S. aureus strains with epidemiologically divergent behaviors.
LINE-1 global DNA methylation, iron homeostasis genes, sex and age in sudden sensorineural hearing loss (SSNHL)
Authors: Tisato Veronica , Castiglione Alessandro , Ciorba Andrea , Aimoni Claudia , Silva Juliana Araujo , Gallo Ines , D’Aversa Elisabetta , Salvatori Francesca , Bianchini Chiara , Pelucchi Stefano , Secchiero Paola , Zauli Giorgio , Singh Ajay Vikram , Gemmati Donato 
Published: December 2023

Abstract
Background
Sudden sensorineural hearing loss (SSNHL) is an abrupt loss of hearing, still idiopathic in most of cases. Several mechanisms have been proposed including genetic and epigenetic interrelationships also considering iron homeostasis genes, ferroptosis and cellular stressors such as iron excess and dysfunctional mitochondrial superoxide dismutase activity.

Results
We investigated 206 SSNHL patients and 420 healthy controls for the following genetic variants in the iron pathway: SLC40A1 − 8CG (ferroportin; FPN1), HAMP − 582AG (hepcidin; HEPC), HFE C282Y and H63D (homeostatic iron regulator), TF P570S (transferrin) and SOD2 A16V in the mitochondrial superoxide dismutase-2 gene. Among patients, SLC40A1 − 8GG homozygotes were overrepresented (8.25% vs 2.62%; P = 0.0015) as well SOD2 16VV genotype (32.0% vs 24.3%; P = 0.037) accounting for increased SSNHL risk (OR = 3.34; 1.54–7.29 and OR = 1.47; 1.02–2.12, respectively). Moreover, LINE-1 methylation was inversely related (r2 = 0.042; P = 0.001) with hearing loss score assessed as pure tone average (PTA, dB HL), and the trend was maintained after SLC40A1 − 8CG and HAMP − 582AG genotype stratification (ΔSLC40A1 = + 8.99 dB HL and ΔHAMP = − 6.07 dB HL). In multivariate investigations, principal component analysis (PCA) yielded PC1 (PTA, age, LINE-1, HAMP, SLC40A1) and PC2 (sex, HFEC282Y, SOD2, HAMP) among the five generated PCs, and logistic regression analysis ascribed to PC1 an inverse association with moderate/severe/profound HL (OR = 0.60; 0.42–0.86; P = 0.0006) and with severe/profound HL (OR = 0.52; 0.35–0.76; P = 0.001).

Conclusion
Recognizing genetic and epigenetic biomarkers and their mutual interactions in SSNHL is of great value and can help pharmacy science to design by pharmacogenomic data classical or advanced molecules, such as epidrugs, to target new pathways for a better prognosis and treatment of SSNHL.
Is it now time to iron out the wrinkles? Health of Shar Pei dogs under primary veterinary care in the UK
Authors: O’Neill Dan G. , Engdahl Karolina S. , Leach Alice , Packer Rowena M. A. , Church David B. , Brodbelt Dave C. 
Published: December 2023

Abstract
Background
The Shar Pei is a common dog breed with a distinctive appearance caused by hyaluronosis that has been linked with several health conditions. Anonymised primary-care veterinary clinical records were explored to extract data on the demography, common disorders and mortality of Shar Pei in the UK in 2013.

Results
The study population of 455,557 dogs included 1913 (0.42%) Shar Pei. The mean adult bodyweight was 22.26 kg. The most prevalent fine-level precision disorders were entropion (prevalence 17.88%, 95% CI: 16.16-19.59), otitis externa (16.36%, 95% CI: 14.70-18.02), ear disorders (6.69%, 95% CI: 5.57-7.81), aggression (5.23%, 95% CI: 4.23-6.22), and pyoderma (4.29%, 95% CI: 3.38-5.19). The most prevalent disorder groups were ophthalmologic (prevalence = 22.27%, 95% CI: 20.40-24.13), dermatological (21.01%, 95% CI: 19.19-22.84), aural (18.66%, 95% CI: 16.92-20.41), traumatic injury (7.53%, 95% CI: 6.35-8.71) and behavioural (7.21%, 95% CI: 6.05-8.37). The median longevity of 190 Shar Pei that died during the study period was 7.28 years (IQR 5.04-10.05, range 0.04-15.04). Of 184 deaths with a recorded method of death, 157 (85.33%) deaths involved euthanasia and 27 (14.67%) deaths were unassisted. Among 136 (71.58%) deaths with a recorded biomedical cause of death, the most common causes of death at group level precision were neoplasia (15.44%, 95% CI: 9.37-21.51), renal disorders (13.24%, 95% CI: 7.54-18.93), and behavioural disorders (11.03%, 95% CI: 5.76-16.29).

Conclusions
Almost one fifth of Shar Pei receive veterinary care each year for entropion, a condition linked strongly with the extreme conformation of thickened and folded skin and bristly hair that characterises the Shar Pei breed. Several other common disorders are also linked to hyaluronosis. Current UK legislation can help support efforts to avoid breeding or acquiring animals with extreme conformations and to promote adequate veterinary care for already-owned animals with extreme conformations.
Climatology of mesosphere and lower thermosphere diurnal tides over Jicamarca (12$$^\circ$$S, 77$$^\circ$$W): observations and simulations
Authors: Suclupe Jose , Chau Jorge L. , Conte J. Federico , Milla Marco , Pedatella N. M. , Kuyeng K. 
Published: December 2023

AbstractThis work shows a 3-year climatology of the horizontal components of the solar diurnal tide, obtained from wind measurements made by a multistatic specular meteor radar (SIMONe) located in Jicamarca, Peru (12$$^\circ$$

∘

S, 77$$^\circ$$

∘

W). Our observations show that the meridional component is more intense than the zonal component, and that it exhibits its maxima shifted with respect to the equinox times (i.e., the largest peak occurs in August–September, and the second one in April–May). The zonal component only shows a clear maximum in August–September. This observational climatology is compared to a climatology obtained with the Whole Atmosphere Community Climate Model with thermosphere and ionosphere extension (WACCM-X). Average comparisons indicate that the model amplitudes are 50% smaller than the observed ones. The WACCM-X results are also used in combination with observed altitude profiles of the tidal phases to understand the relative contributions of migrating and non-migrating components. Based on this, we infer that the migrating diurnal tide (DW1) dominates in general, but that from June until September (November until July) the DE3 (DW2) may have a significant contribution to the zonal (meridional) component. Finally, applying wavelet analysis to the complex amplitude of the total diurnal tide, modulating periods between 5 and 80 days are observed in the SIMONe measurements and the WACCM-X model. These modulations might be associated to planetary waves and intraseasonal oscillations in the lower tropical atmosphere.
Graphical Abstract
Soilkin
Authors: Toland Alexandra Regan 
Published: December 2023

AbstractDrawing on ideas from the history and philosophy of soil science, Fluxus performance, and queer-feminist STS, this article responds to a question posed by environmental researcher Hugo Reinert: “What modes of passionate immersion—or love, or intimacy—could a stone afford?” Situated in a fluid space between environmental humanities and artistic research, the Soilkin project develops a series of relational exercises to frame three basic propositions: (1) a non-normative, animistic understanding of geologic subjectivity could trouble accepted criteria for life on earth, leading to kinship with geogenic entities; (2) soil formation (pedogenesis) could be interpreted as a performative process of learning and becoming, rather than simply weathering and aging, with appreciable ontological implications; and (3) soil kinship is situated within a dynamic interplay of resistance and consent, demanding that the terms of reciprocity between humans and soils be mutually beneficial and appropriate to the slowed-down timescale of events in which soil-beings live and operate. The article integrates theoretical provocations with performative scores to expand and sensitize soil-scientific knowledge while, at the same time, contributing to multispecies scholarship on kin-making with geogenic and pedogenic others.