bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRIM21 mediates the synergistic effect of Olaparib and Sorafenib by degrading BRCA1 through ubiquitination in TNBC
Authors: Huang Ning , Li Peng , Sun Xiaolin , Tong Li , Dong Xinyi , Zhang Xuemei , Duan Jifeng , Sheng Xia , Xin Hong 
Published: October 2023

AbstractTriple-negative breast cancer (TNBC) is a heterogeneous and aggressive type of breast cancer with a poor prognosis and a high recurrence rate. Chemotherapy is still the mainstay of treatment for cancer patients without a genetic BRCA mutation, despite the approval of Olaparib, an inhibitor of the poly (ADP-ribose) polymerase (PARP) enzyme. Tripartite motif containing-21 (TRIM21) is one of the TRIM family members that has been investigated in various types of cancer. Here, we found that a low TRIM21 expression level was correlated with poor overall survival of TNBC patients. Knockout of TRIM21 promoted the proliferation of TNBC cells in vivo and in vitro, as well as migratory and invasive capabilities in vitro. Importantly, breast cancer susceptibility gene 1 (BRCA1) was identified as a ubiquitination substrate of TRIM21. It was confirmed that BRCA1 was upregulated after Olaparib treatment, which may explain the relative resistance of BRCA1-proficient TNBC cells to Olaparib. Moreover, Sorafenib, a standard treatment for hepatocellular carcinoma, increased the sensitivity of TNBC cells to Olaparib by promoting TRIM21-mediated ubiquitination degradation of BRCA1. Thus, a synergic effect of Olaparib and Sorafenib was found in vitro and in vivo. This combined treatment also aggravated DNA damage, cell cycle arrest, and apoptosis of TNBC cells. In summary, the findings verified the synergistic effect of Olaparib and Sorafenib and revealed TRIM21 as a potential target for TNBC therapy.
Systematic review and meta-analysis of the factors affecting waning of post-vaccination neutralizing antibody responses against SARS-CoV-2
Authors: Jacobsen Henning , Sitaras Ioannis , Katzmarzyk Maeva , Cobos Jiménez Viviana , Naughton Robert , Higdon Melissa M. , Deloria Knoll Maria 
Published: October 2023

AbstractMass COVID-19 vaccination and continued introduction of new SARS-CoV-2 variants increased prevalence of hybrid immunity at various stages of waning protection. We systematically reviewed waning of post-vaccination neutralizing antibody titers in different immunological settings to investigate differences. We searched published and pre-print studies providing post-vaccination neutralizing antibody responses against the Index strain or Omicron BA.1. We used random effects meta-regression to estimate fold-reduction from months 1 to 6 post last dose by primary vs booster regimen and infection-naïve vs hybrid-immune cohorts. Among 26 eligible studies, 65 cohorts (range 3–21 per stratum) were identified. Month-1 titers varied widely across studies within each cohort and by vaccine platform, number of doses and number of prior infections. In infection-naïve cohorts, the Index strain waned 5.1-fold (95%CI: 3.4–7.8; n = 19 cohorts) post-primary regimen and 3.8-fold (95%CI: 2.4–5.9; n = 21) post-booster from months 1 to 6, and against Omicron BA.1 waned 5.9-fold (95%CI: 3.8–9.0; n = 16) post-booster; Omicron BA.1 titers post-primary were too low to assess. In hybrid-immune, post-primary cohorts, titers waned 3.7-fold (95%CI: 1.7–7.9; n = 8) against the Index strain and 5.0-fold (95%CI: 1.1–21.8; n = 6) against Omicron BA.1; post-booster studies of hybrid-immune cohorts were too few (n = 3 cohorts each strain) to assess. Waning was similar across vaccination regimen and prior-infection status strata but was faster for Omicron BA.1 than Index strains, therefore, more recent sub-variants should be monitored. Wide differences in peak titers by vaccine platform and prior infection status mean titers drop to non-protective levels sooner in some instances, which may affect policy.
The NOAA NCEI marine microplastics database
Authors: Nyadjro Ebenezer S. , Webster Jennifer A. B. , Boyer Tim P. , Cebrian Just , Collazo Leonard , Kaltenberger Gunnar , Larsen Kirsten , Lau Yee H. , Mickle Paul , Toft Tiffany , Wang Zhankun 
Published: October 2023

AbstractMicroplastics (<5 mm) pollution is a growing problem affecting coastal communities, marine ecosystems, aquatic life, and human health. The widespread occurrence of marine microplastics, and the need to curb its threats, require expansive, and continuous monitoring. While microplastic research has increased in recent years and generated significant volumes of data, there is a lack of a robust, open access, and long-term aggregation of this data. The National Oceanic and Atmospheric Administration (NOAA) National Centers for Environmental Information (NCEI) now provides a global open access to marine microplastics data on an easily discoverable and accessible GIS web map and data portal (https://www.ncei.noaa.gov/products/microplastics). The objective of this data portal is to develop a repository where microplastics data are aggregated, archived, and served in a user friendly, consistent, and reliable manner. This work contributes to NCEI’s efforts towards data standardization, integration, harmonization, and interoperability among national and international collaborators for monitoring global marine microplastics. This paper describes the NOAA NCEI global marine microplastics database, its creation, quality control procedures, and future directions.
Effects of oxytocin on the hair growth ability of dermal papilla cells
Authors: Kageyama Tatsuto , Seo Jieun , Yan Lei , Fukuda Junji 
Published: October 2023

AbstractOxytocin (OXT) is a neuropeptide hormone termed “love hormone” produced and released during childbirth and lactation. It is also produced in response to skin stimulation (e.g., during hugging and massaging) and music therapy. The effects of OXT on various organs have been revealed in recent years; however, the relationship between hair follicles and OXT remains unclear. In this study, we examined the effects of OXT on dermal papilla (DP) cells that control hair growth by secreting growth/regression signals. Gene expression analysis revealed that DP signature markers were significantly upregulated in DP cells treated with OXT. In addition, we tested the hair growth-promoting effects of OXT using in vitro hair follicle organoids. OXT promoted the growth of hair peg-like sprouting by upregulating the expression of growth-promoting factors, including genes encoding vascular endothelial growth factor A (VEGFA). This study highlights the positive effects of OXT in hair follicles and may assist in the development of new treatments for alopecia.
Expression of TNFR1, VEGFA, CD147 and MCT1 as early biomarkers of diabetes complications and the impact of aging on this profile
Authors: Raimundo Joyce Regina Santos , da Costa Aguiar Alves Beatriz , Encinas Jéssica Freitas Araujo , Siqueira Andressa Moreira , de Gois Katharyna Cardoso , Perez Matheus Moreira , Petri Giuliana , dos Santos José Francisco Ramos , Fonseca Fernando Luiz Affonso , da Veiga Glaucia Luciano 
Published: October 2023

AbstractHyperglycemia leads to microvascular lesions in various tissues. In diabetic nephropathy—DN, alterations in usual markers reflect an already installed disease. The study of new biomarkers for the early detection of diabetic complications can bring new prevention perspectives. Rats were divided into diabetic adult—DMA—or elderly—DME and control sham adult—CSA—or control sham elderly—CSE. Blood and urine samples were collected for biochemical analysis. Bulbar region, cardiac, hepatic and renal tissues were collected for target gene expression studies. As result, DMA showed decreased TNFR1, MCT1 and CD147 expression in the bulbar region, TNFR1 in the heart, VEGFA and CD147 in the kidney and TNFR1 in blood. Positive correlations were found between TNFR1 and MCT1 in the bulbar region and HbA1c and plasma creatinine, respectively. DME showed positive correlation in the bulbar region between TNFR1 and glycemia, in addition to negative correlations between CD147 in the heart versus glycemia and urea. We concluded that the initial hyperglycemic stimulus already promotes changes in the expression of genes involved in the inflammatory and metabolic pathways, and aging alters this profile. These changes prior to the onset of diseases such as DN, show that they have potential for early biomarkers studies.
In silico design and cell-based evaluation of two dual anti breast cancer compounds targeting Bcl-2 and GPER
Authors: Morelos-Garnica Loreley-A. , Guzmán-Velázquez Sonia , Padilla-Martínez Itzia-I. , García-Sánchez José-R. , Bello Martiniano , Bakalara Norbert , Méndez-Luna David , Correa-Basurto José 
Published: October 2023

AbstractAccording to WHO statistics, breast cancer (BC) disease represents about 2.3 million diagnosed and 685,000 deaths globally. Regarding histological classification of BC, the Estrogen (ER) and Progesterone (PR) receptors negative-expression cancer, named Triple-Negative BC (TNBC), represents the most aggressive type of this disease, making it a challenge for drug discovery. In this context, our research group, applying a well-established Virtual Screening (VS) protocol, in addition to docking and molecular dynamics simulations studies, yielded two ligands identified as 6 and 37 which were chemically synthesized and evaluated on MCF-7 and MDA-MB-231 cancer cell lines. Strikingly, 37 assayed on MDA-MB-231 (a TNBC cell model) depicted an outstanding value of 18.66 μM much lower than 65.67 μM yielded by Gossypol Bcl-2 inhibitor whose main disadvantage is to produce multiple toxic effects. Highlighted above, enforce the premise of the computational tools to find new therapeutic options against the most aggressive forms of breast cancer, as the results herein showed.
Photophysiologically active green, red, and brown macroalgae living in the Arctic Polar Night
Authors: Summers Natalie , Fragoso Glaucia M. , Johnsen Geir 
Published: October 2023

AbstractArctic macroalgae species have developed different growth strategies to survive extreme seasonal changes in irradiance in polar regions. We compared photophysiological parameters such as the light saturation parameter (Ek) and pigment composition of green, red, and brown macroalgae collected in January (Polar Night) and October 2020 (end of the light season). Macroalgae in January appeared healthier (morphologically) and had longer lamina (new growth) than those in October. EK values for red, and brown algae were higher with lower maximum quantum yield of PS II fluorescence (Fv/Fm) in January versus October. Furthermore, in January, new tissues in kelp species had higher EK than the older tissue. Higher EK and lower Fv/Fm during the Polar Night indicates that the photosynthetic apparatus is active but slow. Furthermore, we discuss Chlorophyll (Chl) a emission spectra under blue and green excitation light to determine the ratio of Chl a in photosystem II (PS II) vs photosystem I (PS I). Absorbance spectra of P. palmata was used to interpret the emission spectra. The observed spectral shifts in the absorbance and reflectance spectra of different macroalgae is discussed. Photophysiological methods provide health information complementary to future mapping and monitoring of macroalgae. These results reveal that macroalgae grow new tissue in darkness.
Effect of morpholine, and 4-methylmorpholine on urethane formation: a computational study
Authors: Waleed Hadeer Q. , Hadjadj Rachid , Viskolcz Béla , Fiser Béla 
Published: October 2023

AbstractA theoretical study of urethane formation through the reaction of phenyl isocyanate and butan-1-ol was carried out, without and in the presence of morpholine, and 4-methylmorpholine catalysts. The reaction with and without catalysts was studied at BHandHLYP/6-31G(d) and G3MP2BHandHLYP levels of theories. The reaction mechanism in the presence of catalysts differs significantly from the catalyst-free case and includes seven steps. The catalyst-free system was investigated along with the catalytic process, the geometries were optimized, and the corresponding thermodynamic properties were calculated. Calculated reactant complexes were compared with crystal structures of morpholine, and 4-methylmorpholine complexed with diols found in the literature. The structures were strikingly similar and thus, the validity of the proposed and studied general organocatalytic reaction mechanism was partially verified. Meanwhile, an irregularity in the energy profile occurred due to the zwitterionic nature of an intermediate. To handle the irregularity, a correction was implemented which handles the appearance of a zwitterionic structure and the corresponding energetic properties. The results showed that morpholine is less effective catalyst compared to 4-methylmorpholine, which can be associated with the difference in their PA (1523.95 and 963.07 kJ/mol, respectively). The current results prove the important role of amine catalysts in urethane synthesis which can be applied in polyurethane catalyst design and development.
Hypofibrinogenemia is an independent predictor of hemophagocytic lymphohistiocytosis in children with sepsis
Authors: Luo Xin , Zhou Chentao , Ji Cunwei , Lu Chunmin , Luo Yasha , Chen Zhenhui , Zhong Tianhua , Ye Ruoting , Zeng Liwei , Luo Mingyong 
Published: October 2023

AbstractHemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening condition in children with sepsis. We herein aimed to identify clinical and laboratory predictors of HLH in children with sepsis. We conducted a retrospective study of 568 children with sepsis admitted to Guangdong Women and Children Hospital from January 2019 to June 2022. HLH, while rare (6.34%), proved to be a highly fatal complication (37.14%) in children with sepsis. Children with HLH had higher levels of aspartate aminotransferase, lactate dehydrogenase, triglycerides, and ferritin than children without HLH; conversely, they displayed decreased levels of neutrophils, hemoglobin, platelets, fibrinogen, and albumin. Additionally, the HLH group showed higher rates of prolonged fever (> 10 days), hepatomegaly, and splenomegaly than the non-HLH group. Our retrospective analysis identified hypofibrinogenemia (OR = 0.440, P = 0.024) as an independent predictor for the development of HLH in patients with sepsis. The optimal cutoff value for fibrinogen was found to be < 2.43 g/L. The area under the curve for diagnosing HLH was 0.80 (95% confidence interval: 0.73–0.87, P < 0.0001), with a sensitivity of 72.41% and specificity of 76.27%. Thus, hypofibrinogenemia emerges as a potentially valuable predictor for HLH in children with sepsis.
Transfer learning for accurate fetal organ classification from ultrasound images: a potential tool for maternal healthcare providers
Authors: Ghabri Haifa , Alqahtani Mohammed S. , Ben Othman Soufiene , Al-Rasheed Amal , Abbas Mohamed , Almubarak Hassan Ali , Sakli Hedi , Abdelkarim Mohamed Naceur 
Published: October 2023

AbstractUltrasound imaging is commonly used to aid in fetal development. It has the advantage of being real-time, low-cost, non-invasive, and easy to use. However, fetal organ detection is a challenging task for obstetricians, it depends on several factors, such as the position of the fetus, the habitus of the mother, and the imaging technique. In addition, image interpretation must be performed by a trained healthcare professional who can take into account all relevant clinical factors. Artificial intelligence is playing an increasingly important role in medical imaging and can help solve many of the challenges associated with fetal organ classification. In this paper, we propose a deep-learning model for automating fetal organ classification from ultrasound images. We trained and tested the model on a dataset of fetal ultrasound images, including two datasets from different regions, and recorded them with different machines to ensure the effective detection of fetal organs. We performed a training process on a labeled dataset with annotations for fetal organs such as the brain, abdomen, femur, and thorax, as well as the maternal cervical part. The model was trained to detect these organs from fetal ultrasound images using a deep convolutional neural network architecture. Following the training process, the model, DenseNet169, was assessed on a separate test dataset. The results were promising, with an accuracy of 99.84%, which is an impressive result. The F1 score was 99.84% and the AUC was 98.95%. Our study showed that the proposed model outperformed traditional methods that relied on the manual interpretation of ultrasound images by experienced clinicians. In addition, it also outperformed other deep learning-based methods that used different network architectures and training strategies. This study may contribute to the development of more accessible and effective maternal health services around the world and improve the health status of mothers and their newborns worldwide.
Establishment of a novel indicator of pyroptosis regulated gene transcription level and its application in pan-cancer
Authors: Xu Jin-Zhou , Xia Qi-Dong , Sun Jian-Xuan , Liu Chen-Qian , Lu Jun-Lin , Xu Meng-Yao , An Ye , Xun Yang , Liu Zheng , Hu Jia , Li Cong , Wang Shao-Gang 
Published: October 2023

AbstractPyroptosis is a type of programmed cell death and plays a dual role in distinct cancers. It is elusive to evaluate the activation level of pyroptosis and to appraise the involvement of pyroptosis in the occurrence and development of diverse tumors. Accordingly, we herein established an indicator to evaluate pyroptosis related gene transcription levels based on the expression level of genes involved in pyroptosis and tried to elaborated on the association between pyroptosis and tumors across diverse tumor types. We found that pyroptosis related gene transcription levels could predict the prognosis of patients, which could act as either a favorable or a dreadful factor in diverse cancers. According to signaling pathway analyses we observed that pyroptosis played a significant role in immune regulation and tumorigenesis and had strong links with other forms of cell death. We also performed analysis on the crosstalk between pyroptosis and immune status and further investigated the predictive potential of pyroptosis level for the efficacy of immunotherapy. Lastly, we manifested that pyroptosis status could serve as a biomarker to the efficacy of chemotherapy across various cancers. In summary, this study established a quantitative indicator to evaluate pyroptosis related gene transcription levels, systematically explored the role of pyroptosis in pan-cancer. These results could provide potential research directions targeting pyroptosis, and highlighted that pyroptosis may be used to develop a novel strategy for the treatment of cancer.
Primate-specific isoform of Nedd4-1 regulates substrate binding via Ser/Thr phosphorylation and 14-3-3 binding
Authors: Kefalas George , Rotin Daniela 
Published: October 2023

AbstractNedd4 (Nedd4-1) is an E3 ubiquitin ligase involved in crucial biological processes such as growth factor receptor signaling. While canonical Nedd4-1 comprises a C2-WW(4)-HECT domain architecture, alternative splicing produces non-canonical isoforms that are poorly characterized. Here we characterized Nedd4-1(NE), a primate-specific isoform of Nedd4-1 that contains a large N-terminal Extension (NE) that replaces most of the C2 domain. We show that Nedd4-1(NE) mRNA is ubiquitously expressed in human tissues and cell lines. Moreover, we found that Nedd4-1(NE) is more active than the canonical Nedd4-1 isoform, likely due to the absence of a C2 domain-mediated autoinhibitory mechanism. Additionally, we identified two Thr/Ser phosphoresidues in the NE region that act as binding sites for 14-3-3 proteins, and show that phosphorylation on these sites reduces substrate binding. Finally, we show that the NE region can act as a binding site for the RPB2 subunit of RNA polymerase II, a unique substrate of Nedd4-1(NE) but not the canonical Nedd4-1. Taken together, our results demonstrate that alternative splicing of the ubiquitin ligase Nedd4-1 can produce isoforms that differ in their catalytic activity, binding partners and substrates, and mechanisms of regulation.
Rapid improvements and subsequent effects in major depressive disorder patients with somatic pain using rTMS combined with sertraline
Authors: Sun Yuanfeng , Lei Fei , Zou Ke , Zheng Zhong 
Published: October 2023

AbstractThis study aims to explore changes in depression and pain for major depressive disorder (MDD) patients with somatic pain after repetitive transcranial magnetic stimulation (rTMS) using the event-related potentials (ERPs) technique. Eighty MDD patients with somatic pain were randomly assigned to drug therapy (DT) and combined therapy (CT) groups. CT group underwent intermittent theta burst stimulation over the left dorsolateral prefrontal cortex (DLPFC) with 800 pulses and 1 Hz over the right DLPFC with 800 pulses, 5 times a week for 3 weeks. All patients were given sertraline at 50–100 mg per day. All subjects were evaluated at baseline and at weeks three and six of therapy using the Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Scale (HAMA), and Numerical Rating Scales (NRS), and the latency and amplitude of P300 and mismatch negativity (MMN) were measured. There were no significant differences in all indices between groups at baseline. At 3 weeks, HAMD subscale scores of Cognitive Impairment and NRS scores were significantly lower in the CT group than in the DT group. At 6 weeks, NRS and HAMD total scores in the CT group decreased significantly in the CT group compared with the DT group, especially for anxiety and pain, and the MMN and P300 latencies and P300 amplitude showed greater improvements. Our findings highlight that rTMS in combination with antidepressants is a rapid method of symptom improvement in patients with somatic pain with MDD and is helpful for cognitive impairment and anxiety.
Effects of skin moisturization on various aspects of touch showing differences with age and skin site
Authors: Dione Mariama , Watkins Roger Holmes , Aimonetti Jean-Marc , Jourdain Roland , Ackerley Rochelle 
Published: October 2023

AbstractThe human body is encompassed by a thin layer of tissue, the skin, which is heterogenous and highly specialized to protect the body and encode interactions with the external world. There is a fundamental scientific drive to understand its function, coupled with the need to preserve skin as we age, which impacts on our physiological and psychological well-being. In the present study, we aimed to define differences in touch perception between age groups and with skin cream application. We investigated touch on the finger, the forearm and cheek in younger (20–28 years, n = 22) and older (65–75 years, n = 22) females. We measured skin hydration, touch detection, finger spatial discrimination, forearm tactile pleasantness together with electrodermal activity, and perceptual ratings about cream use, skin dryness, and cosmetic habits. Glabrous finger skin became drier and touch performance was impaired with age, but these aspects were preserved in hairy skin. Skin moisturization immediately increased hydration levels, but did not significantly change touch perception. We also found that touch appreciation increased with age. We conclude that reduced finger capacity may impact self-evaluation of the skin and that long-term skin care strategies should focus on hydrating the hand to preserve touch capacities.