bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracerebral gadolinium deposition following blood–brain barrier disturbance in two different mouse models
Authors: Kromrey M. L. , Oswald S. , Becher D. , Bartel J. , Schulze J. , Paland H. , Ittermann T. , Hadlich S. , Kühn J. P. , Mouchantat S. 
Published: June 2023

AbstractTo evaluate the influence of the blood–brain barrier on neuronal gadolinium deposition in a mouse model after multiple intravenous applications of the linear contrast agent gadodiamide. The prospective study held 54 mice divided into three groups: healthy mice (A), mice with iatrogenic induced disturbance of the blood–brain barrier by glioblastoma (B) or cerebral infarction (C). In each group 9 animals received 10 iv-injections of gadodiamide (1.2 mmol/kg) every 48 h followed by plain T1-weighted brain MRI. A final MRI was performed 5 days after the last contrast injection. Remaining mice underwent MRI in the same time intervals without contrast application (control group). Signal intensities of thalamus, pallidum, pons, dentate nucleus, and globus pallidus-to-thalamus and dentate nucleus-to-pons ratios, were determined. Gadodiamide complex and total gadolinium amount were quantified after the last MR examination via LC–MS/MS and ICP-MS. Dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios showed no significant increase over time within all mice groups receiving gadodiamide, as well as compared to the control groups at last MR examination. Comparing healthy mice with group B and C after repetitive contrast administration, a significant SI increase could only be detected for glioblastoma mice in globus pallidus-to-thalamus ratio (p = 0.033), infarction mice showed no significant SI alteration. Tissue analysis revealed significantly higher gadolinium levels in glioblastoma group compared to healthy (p = 0.013) and infarction mice (p = 0.029). Multiple application of the linear contrast agent gadodiamide leads to cerebral gadolinium deposition without imaging correlate in MRI.
Cross-reactivity trends when selecting scFv antibodies against snake toxins using a phage display-based cross-panning strategy
Authors: Sørensen Christoffer V. , Ledsgaard Line , Wildenauer Helen H. K. , Dahl Camilla H. , Ebersole Tasja W. , Bohn Markus-Frederik , Ljungars Anne , Jenkins Timothy P. , Laustsen Andreas H. 
Published: June 2023

AbstractAntibodies with cross-reactive binding and broad toxin-neutralizing capabilities are advantageous for treating indications such as infectious diseases and animal envenomings. Such antibodies have been successfully selected against closely related antigens using phage display technology. However, the mechanisms driving antibody cross-reactivity typically remain to be elucidated. Therefore, we sought to explore how a previously reported phage display-based cross-panning strategy drives the selection of cross-reactive antibodies using seven different snake toxins belonging to three protein (sub-)families: phospholipases A2, long-chain α-neurotoxins, and short-chain α-neurotoxins. We showcase how cross-panning can increase the chances of discovering cross-reactive single-chain variable fragments (scFvs) from phage display campaigns. Further, we find that the feasibility of discovering cross-reactive antibodies using cross-panning cannot easily be predicted by analyzing the sequence, structural, or surface similarity of the antigens alone. However, when antigens share the (exact) same functions, this seems to increase the chances of selecting cross-reactive antibodies, which may possibly be due to the existence of structurally similar motifs on the antigens.
The histone H2B Arg95 residue efficiently recruits the transcription factor Spt16 to mediate Ste5 expression of the pheromone response pathway
Authors: Sulaiman Abdallah Alhaj , Ali Reem , Ramotar Dindial 
Published: June 2023

AbstractIn yeast Saccharomyces cerevisiae, the immunosuppressant rapamycin inhibits the TORC1 kinase causing rapid alteration in gene expression and leading to G1 arrest. We recently reported the isolation and characterization from the histone mutant collection of a histone H2B R95A mutant that displays resistance to rapamycin. This mutant is defective in the expression of several genes belonging to the pheromone response pathway including STE5 encoding a scaffold protein that promotes the activation of downstream MAP kinases. Cells lacking Ste5 cannot arrest the cell cycle in response to rapamycin and as a consequence exhibit similar resistance to rapamycin as the H2B R95A mutant. Herein, we show that the H2B R95A mutation weakens the association of H2B with Spt16 a component of the FACT complex (FAcilitates Chromatin Transcription), and an essential factor that interacts with the histone H2A-H2B dimer to promote transcription and preserve chromatin integrity. From a collection of spt16 mutants, spt16 E857K and spt16-11 showed striking sensitivity to rapamycin as compared to the parent strain. spt16 E857K and spt16-11 expressed distinct forms of Ste5, while a suppressor mutation H2B A84D of the spt16-11 mutant prevents the expression of Ste5 and confers marked resistance to rapamycin. We interpret these findings to suggest that the Arg95 residue of histone H2B is required to recruit Spt16 to maintain the expression of STE5, which performs a role to arrest cells in the G1 phase in response to rapamycin.
Risk factors for insulin resistance related to polycystic ovarian syndrome in Iranian population
Authors: Mansour Asieh , Mirahmad Maryam , Mohajeri-Tehrani Mohammad Reza , Jamalizadeh Mahdieh , Hosseinimousa Sedigheh , Rashidi Fatemeh , Asili Pooria , Sajjadi-Jazi Sayed Mahmoud 
Published: June 2023

AbstractPolycystic ovary syndrome (PCOS) has significant metabolic sequelae linked to insulin resistance. This study aimed to compare clinical, metabolic, and hormonal characteristics of PCOS women with and without insulin resistance. The second aim was to compare the clinico-biochemical profiles of the various PCOS phenotypes. In this cross-sectional secondary analysis, we combined the baseline data from two separate randomized controlled trials (RCTs) in women diagnosed with PCOS. PCOS patients were categorized into the four Rotterdam PCOS phenotypes according to the presence of at least two criteria of oligomenorrhea/anovulation (O), hyperandrogenism (H), and polycystic ovary morphology (P): O–H–P, H–P, O–H, and O–P. Participants were categorized into two groups according to the homeostasis model assessment index of insulin resistance (HOMA-IR) levels: < 3.46, and ≥ 3.46. The correlation between the HOMA-IR and biometric, clinical, and biochemical variables was assessed in normal weight (BMI < 25) and overweight/obese (BMI ≥ 25) PCOS women. Then, the association between PCOS phenotypes and insulin resistance was investigated using logistic regression analysis. A total of 125 PCOS patients aged 18–40 years were included in the present study. Based on our results, the HOMA-IR index was positively correlated with diastolic blood pressure, free androgen index, and triglycerides levels; and negatively correlated with sex hormone-binding globulin in overweight/obese PCOS women. In addition, the HOMA-IR index was found to be positively correlated with alanine transaminase and negatively correlated with diastolic blood pressure in normal weight PCOS women. Moreover, individuals with O–H–P phenotype (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.02–6.24) had about two-fold increased risk of insulin resistance. In conclusion, the full-blown PCOS (O–H–P) phenotype has an increased risk of insulin resistance. Accordingly, phenotype division may help physicians to predict adverse metabolic outcomes.
Transcriptomic analysis reveals distinct adaptive molecular mechanism in the hippocampal CA3 from rats susceptible or not-susceptible to hyperthermia-induced seizures
Authors: Bando Silvia Y. , Bertonha Fernanda B. , Menezes Pedro H. N. , Takahara André K. , Khaled Nathália A. , Santos Paula , S. Junqueira Mara , Cesar Roberto M. , Moreira-Filho Carlos A. 
Published: June 2023

AbstractFebrile seizures during early childhood are a relevant risk factor for the development of mesial temporal lobe epilepsy. Nevertheless, the molecular mechanism induced by febrile seizures that render the brain susceptible or not-susceptible to epileptogenesis remain poorly understood. Because the temporal investigation of such mechanisms in human patients is impossible, rat models of hyperthermia-induced febrile seizures have been used for that purpose. Here we conducted a temporal analysis of the transcriptomic and microRNA changes in the ventral CA3 of rats that develop (HS group) or not-develop (HNS group) seizures after hyperthermic insult on the eleventh postnatal day. The selected time intervals corresponded to acute, latent, and chronic phases of the disease. We found that the transcriptional differences between the HS and the HNS groups are related to inflammatory pathways, immune response, neurogenesis, and dendritogenesis in the latent and chronic phases. Additionally, the HNS group expressed a greater number of miRNAs (some abundantly expressed) as compared to the HS group. These results indicate that HNS rats were able to modulate their inflammatory response after insult, thus presenting better tissue repair and re-adaptation. Potential therapeutic targets, including genes, miRNAs and signaling pathways involved in epileptogenesis were identified.
Global risk assessment of compound hot-dry events in the context of future climate change and socioeconomic factors
Authors: Tabari Hossein , Willems Patrick 
Published: June 2023

AbstractCompound hot-dry events have the potential to cause significant damages and propel socioeconomic systems towards tipping points by overwhelming the ability of natural and human systems to cope with the combined stressors. As climate change continues to alter hazard patterns, the impacts of these events will be further compounded by changes in exposure and vulnerability. However, the future risk of these events and the role of these components remain poorly understood. Using a multimodel ensemble, we find that by the end of the 21st century, an additional 0.7–1.7 billion people globally will be exposed to amplified compound events, depending on the scenarios. Additionally, the cropland exposure to these events is projected to increase by 2–5.7 million km². Our findings also suggest that countries with weak governance will experience a twice larger increase in the risk of compound events than those with good governance. This underscores the importance of effective governance in mitigating and managing the escalating risks of compound events.
A two-stage strategy for upcycling chlorine-contaminated plastic waste
Authors: Kots Pavel A. , Vance Brandon C. , Quinn Caitlin M. , Wang Cong , Vlachos Dionisios G. 
Published: June 2023

AbstractChemical upcycling of polyolefin plastic waste to lubricant, wax and fuel-range hydrocarbons over metal-based catalysts is a crucial technological solution to the enormous environmental threat posed by plastic waste. However, currently available methods are incompatible with chlorine-contaminated feedstocks. Here we report a two-stage strategy for upcycling chlorine-contaminated polypropylene. First, magnesia–alumina mixed oxide at 30 bar H2 and 250 °C serves as a chlorine trap by rapidly forming solid chloride, resulting in nearly complete chlorine extraction from the polyolefin melt. This enables the upcycling of plastic waste with up to 10% polyvinyl chloride content to lubricants over ruthenium-based catalysts, in the second stage. The strategy is also applicable to chlorinated aromatics and alkanes. The proposed strategy renders hydrocracking and hydrogenolysis catalysts less sensitive to the chlorine impurities in feedstocks while eliminating HCl emissions and chlorine contamination in products. It could incentivize further progress in plastics upcycling.
Maturational networks of human fetal brain activity reveal emerging connectivity patterns prior to ex-utero exposure
Authors: Karolis Vyacheslav R. , Fitzgibbon Sean P. , Cordero-Grande Lucilio , Farahibozorg Seyedeh-Rezvan , Price Anthony N. , Hughes Emer J. , Fetit Ahmed E. , Kyriakopoulou Vanessa , Pietsch Maximilian , Rutherford Mary A. , Rueckert Daniel , Hajnal Joseph V. , Edwards A. David , O’Muircheartaigh Jonathan , Duff Eugene P. , Arichi Tomoki 
Published: June 2023

AbstractA key feature of the fetal period is the rapid emergence of organised patterns of spontaneous brain activity. However, characterising this process in utero using functional MRI is inherently challenging and requires analytical methods which can capture the constituent developmental transformations. Here, we introduce a novel analytical framework, termed “maturational networks” (matnets), that achieves this by modelling functional networks as an emerging property of the developing brain. Compared to standard network analysis methods that assume consistent patterns of connectivity across development, our method incorporates age-related changes in connectivity directly into network estimation. We test its performance in a large neonatal sample, finding that the matnets approach characterises adult-like features of functional network architecture with a greater specificity than a standard group-ICA approach; for example, our approach is able to identify a nearly complete default mode network. In the in-utero brain, matnets enables us to reveal the richness of emerging functional connections and the hierarchy of their maturational relationships with remarkable anatomical specificity. We show that the associative areas play a central role within prenatal functional architecture, therefore indicating that functional connections of high-level associative areas start emerging prior to exposure to the extra-utero environment.
miR-27b targets MAIP1 to mediate lipid accumulation in cultured human and mouse hepatic cells
Authors: Sakai Eiko , Imaizumi Tsutomu , Suzuki Ruruka , Taracena-Gándara Marcos , Fujimoto Toshiki , Sakurai Fuminori , Mizuguchi Hiroyuki 
Published: June 2023

AbstractNon-alcoholic liver disease (NAFLD) is a condition caused by excessive fat accumulation in the liver and developed via multiple pathways. miR-27b has been suggested to play crucial roles in the development of NAFLD, assuming via targeting genes involved in lipid catabolism and anabolism. However, other pathways regulated by miR-27b are largely unknown. Here we show that lipid accumulation was induced in miR-27b–transfected human and mouse hepatic cells and that knockdowns of three miR-27b–target genes, β-1,4-galactosyltransferase 3 (B4GALT3), matrix AAA peptidase interacting protein 1 (MAIP1) and PH domain and leucine rich repeat protein phosphatase 2 (PHLPP2), induced lipid accumulation. We also show that B4GALT3 and MAIP1 were direct targets of miR-27b and overexpression of MAIP1 ameliorated miR-27b−induced lipid accumulation. In addition, we show that hepatic Maip1 expression declined in mice fed a high-fat diet, suggesting the involvement of decreased Maip1 expression in the condition of fatty liver. Overall, we identified MAIP1/miR-27b axis as a mediator of hepatic lipid accumulation, a potential therapeutic target for NAFLD.
Rising vulnerability of compound risk inequality to ageing and extreme heatwave exposure in global cities
Authors: Chen Mingxing , Chen Liangkan , Zhou Yuan , Hu Maogui , Jiang Yanpeng , Huang Dapeng , Gong Yinghua , Xian Yue 
Published: June 2023

AbstractContinued warming trends lead to an increasing risk of exposure to extreme heatwaves, which threaten the health of urban residents, especially the ageing population. Here, we project the spatiotemporal trend of future exposure risk across 9188 global urban settlements between 2020 and 2100 under the shared socioeconomic pathway (SSP) 2-4.5 and SSP5-8.5 scenarios. Results show that urban heatwave exposure risk increases by 619% and 1740% for SSP2-4.5 and SSP5-8.5, respectively, and by 1642% to 5529% for the elderly. Notably, 69% of the elderly exposure risk comes from middle-income countries, where the increasing trend on the regional average is 1.2 times higher than that of high-income countries. There is an increasing trend towards greater concentration on large cities, especially in low- and lower-middle-income countries. In high-income countries, climate effects contribute 39% to 58% of increasing exposure for elderly individuals, whereas ageing effects play more prominent role in lower-income countries. This emphasizes the disproportionately higher heat-related burden for elderly individuals and inequitable trends in lower income countries. Understanding the vulnerable and priority regions in future heatwave exposure will inform adaptation strategies to support urban climate-resilient development.
Large obliquity-paced Antarctic ice-volume fluctuations suggest melting by atmospheric and ocean warming during late Oligocene
Authors: Brzelinski Swaantje , Bornemann André , Liebrand Diederik , van Peer Tim E. , Wilson Paul A. , Friedrich Oliver 
Published: June 2023

AbstractThe late Oligocene (~27.8–23 My ago) offers an opportunity to study past climate variability under high-CO2, warmer-than-present and the unipolar (Antarctic) glaciated state. Here, we present new high-resolution geochemical records from exquisitely well-preserved benthic foraminifera for the late Oligocene, an interval for which Antarctic ice-sheet size and stability are debated. Our records indicate four obliquity-paced glacial-interglacial cycles with ice-volume changes of up to ~70% of the modern Antarctic ice-sheet. The amplitude of ice-volume change during these late Oligocene glacial-interglacial cycles is comparable to that of the late Pliocene and early Pleistocene. Ice-volume estimates for interglacials are small enough to be accommodated by a land-based Antarctic ice-sheet but, for three of the four glacials studied, our calculations imply that ice sheets likely advanced beyond the Antarctic coastline onto the shelves. Our findings suggest an Antarctic ice-sheet vulnerable to melting driven by both bottom-up (ocean) and top-down (atmospheric) warming under late Oligocene warmer-than-present climate conditions.
Relationship between 233 colorectal cancer risk loci and survival in 1926 patients with advanced disease
Authors: Wills Christopher , Houseman Amy , Watts Katie , Maughan Timothy S. , Fisher David , Houlston Richard S. , West Hannah D. , Escott-Price Valentina , Cheadle Jeremy P. 
Published: June 2023

Abstract
Background
Genome, transcriptome and methylome-wide association studies have identified single-nucleotide polymorphisms (SNPs) or genes at 258 loci associated with colorectal cancer (CRC) risk. We studied the relationship between these and patient outcome.

Methods
We studied 1926 unrelated patients with advanced CRC from COIN and COIN-B. Of 205 CRC-risk SNPs, 19 were directly genotyped and 162 were imputed, and of 53 risk genes, 52 were tested. An additive Cox model for overall survival was adjusted for known prognostic factors. For nominally significant SNPs or genes, we considered a recessive model with a Bonferroni corrected threshold of P = 2.1 × 10−4. We examined SNPs as expression quantitative trait loci (eQTL) and the relationship between gene expression in colorectal tumours and survival in 597 unrelated patients.

Results
Eleven SNPs or genes were nominally associated with survival under an additive model. Only rs117079142 mapping to UTP23 and EIF3H (Hazard Ratio [HR] = 2.79, 95% Confidence Intervals [CI] = 1.70–4.58, P = 4.7 × 10−5) and rs9924886 mapping to CDH1 and CDH3 (HR = 1.24, 95% CI = 1.12–1.38, P = 5.2 × 10−5) passed the multiple testing threshold under a recessive model. rs117079142 was an eQTL for UTP23 and rs9924886 for CDH1, CDH3 and ZFP90. Decreased CDH1 expression in CRCs was associated with worse survival (HR = 2.18, 95% CI = 1.3–3.5, P = 1.8 × 10−3).

Conclusion
rs117079142 and rs9924886 may represent potential prognostic biomarkers for CRC.
Trans-palmitoleic acid, a dairy fat biomarker, stimulates insulin secretion and activates G protein-coupled receptors with a different mechanism from the cis isomer
Authors: Korkus Eliza , Szustak Marcin , Madaj Rafal , Chworos Arkadiusz , Drzazga Anna , Koziołkiewicz Maria , Dąbrowski Grzegorz , Czaplicki Sylwester , Konopka Iwona , Gendaszewska-Darmach Edyta 
Published: June 2023

Trans- and cis palmitoleic acids stimulate insulin secretion from pancreatic β cells with a similar potency. Both isomers activate GPR40, GPR55, GPR119, and GPR120 receptors with similar potency but with activation of different signaling pathways.
Anatomical Step-by-Step Dissection of Complex Skull Base Approaches for Trainees: Surgical Anatomy of the Endoscopic Endonasal Middle-Inferior Clivectomy, Odontoidectomy, and Far-Medial Approach
Authors: Agosti Edoardo , Alexander A. Yohan , Leonel Luciano C. P. C. , Gompel Jamie J. Van , Link Michael J. , Choby Garret , Pinheiro-Neto Carlos D. , Peris-Celda Maria 
Published: June 2023

Abstract
Introduction The clival, paraclival, and craniocervical junction regions are challenging surgical targets. To approach these areas, endoscopic endonasal transclival approaches (EETCAs) and their extensions (far-medial approach and odontoidectomy) have gained popularity as they obviate manipulating and working between neurovascular structures. Although several cadaveric studies have further refined these contemporary approaches, few provide a detailed step-by-step description. Thus, we aim to didactically describe the steps of the EETCAs and their extensions for trainees.
Methods Six formalin-fixed cadaveric head specimens were dissected. All specimens were latex-injected using a six-vessel technique. Endoscopic endonasal middle and inferior clivectomies, far-medial approaches, and odontoidectomy were performed.
Results Using angled endoscopes and surgical instruments, an endoscopic endonasal midclivectomy and partial inferior clivectomy were performed without nasopharyngeal tissue disruption. To complete the inferior clivectomy, far-medial approach, and partially remove the anterior arch of C1 and odontoid process, anteroinferior transposition of the Eustachian–nasopharynx complex was required by transecting pterygosphenoidal fissure tissue, but incision in the nasopharynx was not necessary. Full exposure of the craniocervical junction necessitated bilateral sharp incision and additional inferior mobilization of the posterior nasopharynx. Unobstructed access to neurovascular anatomy of the ventral posterior fossa and craniocervical junction was provided.
Conclusion EETCAs are a powerful tool for the skull-base surgeon as they offer a direct corridor to the ventral posterior fossa and craniocervical junction unobstructed by eloquent neurovasculature. To facilitate easier understanding of the EETCAs and their extensions for trainees, we described the anatomy and surgical nuances in a didactic and step-by-step fashion.
Facial Feminization Surgery: Preoperative Planning and Surgical Technique for a Harmonious Outcome
Authors: Asokan Arjun , Sudheendran Madhu K. , Mohandas Manu , George Pearl Sara , Nair Reshmi Madhavan 
Published: June 2023

AbstractFeminization of the face is as important as genital or chest surgeries in alleviating gender incongruence in transgender individuals. It comprises a myriad of procedures that address the skeletal and/or soft tissue components to give a harmonious result. The surgeries are custom-tailored for each individual based on facial anatomy as well as her desired changes for optimal results. A thorough understanding of the differences in male and female facial anatomy is crucial.The use of computed tomographic imaging with three-dimensional reconstruction and stereolithography models can greatly improve the planning as well as execution of these surgeries. There is an increase in demand for these surgeries, with a paucity of centers providing them. The aim of this article is to highlight the comprehensive facial feminization procedures, which have a high patient as well as surgeon satisfaction rate.