bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the Effect of 3D Wave Propagation on 2D Regional‐Scale Velocity Model Building
Authors: Górszczyk Andrzej , Brossier Romain , Métivier Ludovic 
Published: February 2024

AbstractActive seismic surveys are routinely employed by academia to study geological structure of the crust and upper mantle. Wavefields generated during these surveys are sampled at the receiver locations, but the wave‐paths traveled from a source to a sensor remains unknown. Although seismic acquisition layouts designed to investigate complex crustal‐scale environments are often two‐dimensional, the seismogram recorded at the receiver location represents information gathered along the three‐dimensional wavepaths that might offset from the 2D source/receiver profile along its transverse direction. This so‐called 3D‐effect distorts the results of 2D seismic imaging, which is unable to handle the out‐of‐plane propagation. Despite the numerous 2D seismic imaging case studies, the assessment of this issue is often overlooked. However, the problem exists ‐ especially for crustal‐scale profiles, where seismic energy propagates over distances of hundreds of kilometers and probes different crustal units. In this work we investigate the impact of 3D‐effect on the results of 2D velocity model building from the academic ocean‐bottom seismometer data. We show with polarization analysis how the 3D‐effect can manifest itself in the data domain. Using various scenarios of acquisition we evaluate the imprint of the out‐of‐plane propagation on the data and the results of full‐waveform inversion. We show that 2D velocity model building from the seismic profiles acquired in the complex geological setting can lead to wrong solution. Looking for the remedy to this issue we couple different configurations of acquisition geometries with 3D full‐waveform inversion that allow to handle the 3D effect and provide correct model reconstruction.
Climate Variability and Glacier Dynamics Linked to Fjord Productivity Changes Over the Last ca. 3300 Years in Nuup Kangerlua, Southwest Greenland
Authors: Oksman M. , Kvorning A. B. , Pearce C. , Korsgaard N. J. , Lea J. M. , Seidenkrantz M.‐S. , Ribeiro S. 
Published: February 2024

AbstractGreenlandic fjords, located between the ice sheet and the ocean, are dynamic systems that can sustain highly variable levels of primary productivity and are sensitive to climate change. In our current climate trajectory, meltwater discharge is expected to significantly increase but its long‐term effects on fjord productivity are still poorly constrained. Paleo‐archives can offer valuable insights into long‐term effects. Here, we present two marine sediment core records from Nuup Kangerlua, Southwest Greenland. Our goal is to better understand to what extent, and on what time‐scales, climate fluctuations and associated glacier dynamic changes have impacted fjord productivity over the past ca. 3300 years. Our multiproxy records include diatom fluxes and assemblage composition, sediment biogeochemistry, and grain‐size distribution. Our study reveals that fjord productivity is tightly linked to regional climate variability; relatively higher productivity levels coincided with mild climate periods whereas the climate cooling of the last millennium led to a decrease in productivity. The diatom records suggest that lower productivity is associated with shorter or less intense summer blooms, increased sea‐ice cover and/or a stratified water column. Diatom assemblages demonstrate cold sea‐surface conditions around 1600 CE that might be linked to local advance of glaciers. Cold conditions and decreasing productivity culminated at 1850 CE, when glaciers in the fjord retreated and high glacial meltwater discharge would have altered the fjord hydrography, likely leading to limited nutrient availability. Our long‐term records support the idea that changing climate and cryosphere conditions have a non‐linear impact on the productivity of Greenlandic fjords.
Long-term outcomes after upfront second-generation tyrosine kinase inhibitors for chronic myeloid leukemia: managing intolerance and resistance
Authors: Claudiani Simone , Chughtai Farhan , Khan Afzal , Hayden Chloe , Fernando Fiona , Khorashad Jamshid , Orovboni Victoria , Scandura Glenda , Innes Andrew , Apperley Jane F. , Milojkovic Dragana 
Published: February 2024

AbstractSecond-generation tyrosine kinase inhibitors (2GTKI) are more effective in inducing rapid molecular responses than imatinib when used first-line in patients with chronic myeloid leukemia in chronic phase (CML-CP). However, failure of first line-2GTKI (1L-2GTKI) still occurs and there is no consensus regarding subsequent management. We retrospectively analyzed the outcome of 106 CML-CP patients treated with 1L-2GTKI and with a median follow-up of 91 months. 45 patients (42.4%) switched to an alternative TKI, 28 for intolerance (26.4%) and 17 (16%) for resistance. Most patients who remained on 1L-2GTKI achieved deep molecular responses (DMR) and 15 (14.1%) are in treatment-free remission (TFR). Intolerant patients also obtained DMR, although most required multiple TKI changes and were slower to respond, particularly if treated with 2L-imatinib. Inferior outcomes were observed in resistant patients, who failed alternative 2L-2GTKI and required 3/4GTKI and/or allogeneic hematopoietic stem cell transplant (alloSCT). 7yr-OS was significantly lower for these individuals (66.1%) than for intolerant patients and those who remained on 1L-2GTKI (100% and 97.9%, respectively; p = 0.001). It is apparent that failure of 1L-2GTKI is a challenging problem in modern CML therapy. Intolerance can be effectively managed by switching to an alternative 2GTKI, but resistance requires early consideration of 3/4GTKI.
Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry
Authors: Horna Pedro , Weybright Matthew J. , Ferrari Mathieu , Jungherz Dennis , Peng YaYi , Akbar Zulaikha , Tudor Ilca F. , Otteson Gregory E. , Seheult Jansen N. , Ortmann Janosch , Shi Min , Maciocia Paul M. , Herling Marco , Pule Martin A. , Olteanu Horatiu 
Published: February 2024

AbstractThe diagnosis of leukemic T-cell malignancies is often challenging, due to overlapping features with reactive T-cells and limitations of currently available T-cell clonality assays. Recently developed therapeutic antibodies specific for the mutually exclusive T-cell receptor constant β chain (TRBC)1 and TRBC2 isoforms provide a unique opportunity to assess for TRBC-restriction as a surrogate of clonality in the flow cytometric analysis of T-cell neoplasms. To demonstrate the diagnostic utility of this approach, we studied 164 clinical specimens with (60) or without (104) T-cell neoplasia, in addition to 39 blood samples from healthy donors. Dual TRBC1 and TRBC2 expression was studied within a comprehensive T-cell panel, in a fashion similar to the routine evaluation of kappa and lambda immunoglobulin light chains for the detection of clonal B-cells. Polytypic TRBC expression was demonstrated on total, CD4+ and CD8+ T-cells from all healthy donors; and by intracellular staining on benign T-cell precursors. All neoplastic T-cells were TRBC-restricted, except for 8 cases (13%) lacking TRBC expression. T-cell clones of uncertain significance were identified in 17 samples without T-cell malignancy (13%) and accounted for smaller subsets than neoplastic clones (median: 4.7 vs. 69% of lymphocytes, p < 0.0001). Single staining for TRBC1 produced spurious TRBC1-dim subsets in 24 clinical specimens (15%), all of which resolved with dual TRBC1/2 staining. Assessment of TRBC restriction by flow cytometry provides a rapid diagnostic method to detect clonal T-cells, and to accurately determine the targetable TRBC isoform expressed by T-cell malignancies.
Single-cell RNA sequencing reveals myeloid and T cell co-stimulation mediated by IL-7 anti-cancer immunotherapy
Authors: Eum Hye Hyeon , Jeong Dasom , Kim Nayoung , Jo Areum , Na Minsu , Kang Huiram , Hong Yourae , Kong Jin-Sun , Jeong Gi Heon , Yoo Seung-Ah , Lee Hae-Ock 
Published: February 2024

Abstract
Background
Immune checkpoint inhibitors unleash inhibitory signals on T cells conferred by tumors and surrounding stromal cells. Despite the clinical efficacy of checkpoint inhibitors, the lack of target expression and persistence of immunosuppressive cells limit the pervasive effectiveness of the therapy. These limitations may be overcome by alternative approaches that co-stimulate T cells and the immune microenvironment.

Methods
We analyzed single-cell RNA sequencing data from multiple human cancers and a mouse tumor transplant model to discover the pleiotropic expression of the Interleukin 7 (IL-7) receptor on T cells, macrophages, and dendritic cells.

Results
Our experiment on the mouse model demonstrated that recombinant IL-7 therapy induces tumor regression, expansion of effector CD8 T cells, and pro-inflammatory activation of macrophages. Moreover, spatial transcriptomic data support immunostimulatory interactions between macrophages and T cells.

Conclusion
These results indicate that IL-7 therapy induces anti-tumor immunity by activating T cells and pro-inflammatory myeloid cells, which may have diverse therapeutic applicability.
Ranolazine: a potential anti-metastatic drug targeting voltage-gated sodium channels
Authors: Djamgoz Mustafa B. A. 
Published: February 2024

Abstract
Background
Multi-faceted evidence from a range of cancers suggests strongly that de novo expression of voltage-gated sodium channels (VGSCs) plays a significant role in driving cancer cell invasiveness. Under hypoxic conditions, common to growing tumours, VGSCs develop a persistent current (INaP) which can be blocked selectively by ranolazine.

Methods
Several different carcinomas were examined. We used data from a range of experimental approaches relating to cellular invasiveness and metastasis. These were supplemented by survival data mined from cancer patients.

Results
In vitro, ranolazine inhibited invasiveness of cancer cells especially under hypoxia. In vivo, ranolazine suppressed the metastatic abilities of breast and prostate cancers and melanoma. These data were supported by a major retrospective epidemiological study on breast, colon and prostate cancer patients. This showed that risk of dying from cancer was reduced by ca.60% among those taking ranolazine, even if this started 4 years after the diagnosis. Ranolazine was also shown to reduce the adverse effects of chemotherapy on heart and brain. Furthermore, its anti-cancer effectiveness could be boosted by co-administration with other drugs.

Conclusions
Ranolazine, alone or in combination with appropriate therapies, could be reformulated as a safe anti-metastatic drug offering many potential advantages over current systemic treatment modalities.
Sub-gluteal ligation of the internal pudendal vein for management of veno-occlusive erectile dysfunction (Shaeer’s Vein Ligation–I): the cadaveric study
Authors: Shaeer Osama , El-Shaarawy Ehab A. A. , Emam Hossam Y. , Elsisi Islam , Sokar Eslam , Shaeer Kamal 
Published: February 2024

AbstractVein ligation for veno-occlusive erectile dysfunction is being abandoned due to the recurrence rate. Among the reasons for failure is inability to ligate the deep system of veins; the internal pudendal vein. The vein exits the pelvis in the gluteal region, from the lesser sciatic foramen to the greater sciatic foramen, coursing over the ischial spine and sacro-spinous ligament, under the gluteus maximus. This work aims to verify feasibility of the first surgical procedure to ligate the internal pudendal vein through the gluteal approach. This cadaveric study involved five formalin-fixed cadavers. A surface anatomical landmark was designed to identify the ischial spine, at the intersection of two lines: a vertical line from posterior superior iliac spine to ischial tuberosity, and a horizontal line extending from sacro-coccygeal joint, laterally. An incision is cut encompassing the target point. Subcutaneous fat is dissected down to the gluteus maximus, which is split along the direction of its fibers. The vein can be found crossing over the ischial spine. “Shaeer’s Vein Ligation – I” appears to be surgically feasible. A protocol for a surgical study is registered at clinicaltrials.gov, and is open for participation.
PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature in C9orf72 ALS/FTD neurons
Authors: Milioto Carmelo , Carcolé Mireia , Giblin Ashling , Coneys Rachel , Attrebi Olivia , Ahmed Mhoriam , Harris Samuel S. , Lee Byung Il , Yang Mengke , Ellingford Robert A. , Nirujogi Raja S. , Biggs Daniel , Salomonsson Sally , Zanovello Matteo , de Oliveira Paula , Katona Eszter , Glaria Idoia , Mikheenko Alla , Geary Bethany , Udine Evan , Vaizoglu Deniz , Anoar Sharifah , Jotangiya Khrisha , Crowley Gerard , Smeeth Demelza M. , Adams Mirjam L. , Niccoli Teresa , Rademakers Rosa , van Blitterswijk Marka , Devoy Anny , Hong Soyon , Partridge Linda , Coyne Alyssa N. , Fratta Pietro , Alessi Dario R. , Davies Ben , Busche Marc Aurel , Greensmith Linda , Fisher Elizabeth M. C. , Isaacs Adrian M. 
Published: February 2024

AbstractDipeptide repeat proteins are a major pathogenic feature of C9orf72 amyotrophic lateral sclerosis (C9ALS)/frontotemporal dementia (FTD) pathology, but their physiological impact has yet to be fully determined. Here we generated C9orf72 dipeptide repeat knock-in mouse models characterized by expression of 400 codon-optimized polyGR or polyPR repeats, and heterozygous C9orf72 reduction. (GR)400 and (PR)400 knock-in mice recapitulate key features of C9ALS/FTD, including cortical neuronal hyperexcitability, age-dependent spinal motor neuron loss and progressive motor dysfunction. Quantitative proteomics revealed an increase in extracellular matrix (ECM) proteins in (GR)400 and (PR)400 spinal cord, with the collagen COL6A1 the most increased protein. TGF-β1 was one of the top predicted regulators of this ECM signature and polyGR expression in human induced pluripotent stem cell neurons was sufficient to induce TGF-β1 followed by COL6A1. Knockdown of TGF-β1 or COL6A1 orthologues in polyGR model Drosophila exacerbated neurodegeneration, while expression of TGF-β1 or COL6A1 in induced pluripotent stem cell-derived motor neurons of patients with C9ALS/FTD protected against glutamate-induced cell death. Altogether, our findings reveal a neuroprotective and conserved ECM signature in C9ALS/FTD.
Enhanced tetracycline degradation with TiO2/natural pyrite S-scheme photocatalyst
Authors: Hasham Firooz Masoumeh , Naderi Azra , Moradi Masoud , Kalantary Roshanak Rezaei 
Published: February 2024

AbstractIn this study, TiO2 nanoparticles were employed as a photocatalyst for the degradation of tetracycline (TC) under visible light irradiation. The TiO2 nanoparticles were decorated on natural pyrite (TiO2/NP) and characterized using XRD, FTIR, and SEM–EDX methods. This study evaluated the impacts of various operational parameters such as pH, catalyst dosage, initial TC concentration, and light intensity on TC removal. The findings revealed that under optimal conditions (pH 7, catalyst: 2 g/L, TC: 30 mg/L, and light intensity: 60 mW/cm2), 100% of TC and 84% of TOC were removed within 180 min. The kinetics of TC elimination followed a first-order model. The dominant oxidation species involved in the photocatalytic elimination of TC was found to be ·OH radicals in the TiO2/NP system. The reuse experiments showed the high capability of the catalyst after four consecutive cycles. This study confirmed that the TiO2/NP system has high performance in photocatalytic TC removal under optimized experimental conditions.
Former smoking associated with epigenetic modifications in human granulosa cells among women undergoing assisted reproduction
Authors: Tang Ziyin , Gaskins Audrey J. , Hood Robert B. , Ford Jennifer B. , Hauser Russ , Smith Alicia K. , Everson Todd M. 
Published: February 2024

AbstractSmoking exposure during adulthood can disrupt oocyte development in women, contributing to infertility and possibly adverse birth outcomes. Some of these effects may be reflected in epigenome profiles in granulosa cells (GCs) in human follicular fluid. We compared the epigenetic modifications throughout the genome in GCs from women who were former (N = 15) versus never smokers (N = 44) undergoing assisted reproductive technologies (ART). This study included 59 women undergoing ART. Smoking history including time since quitting was determined by questionnaire. GCs were collected during oocyte retrieval and DNA methylation (DNAm) levels were profiled using the Infinium MethylationEPIC BeadChip. We performed an epigenome-wide association study with robust linear models, regressing DNAm level at individual loci on smoking status, adjusting for age, ovarian stimulation protocol, and three surrogate variables. We performed differentially methylated regions (DMRs) analysis and over-representation analysis of the identified CpGs and corresponding gene set. 81 CpGs were differentially methylated among former smokers compared to never smokers (FDR < 0.05). We identified 2 significant DMRs (KCNQ1 and RHBDD2). The former smoking-associated genes were enriched in oxytocin signaling, adrenergic signaling in cardiomyocytes, platelet activation, axon guidance, and chemokine signaling pathway. These epigenetic variations have been associated with inflammatory responses, reproductive outcomes, cancer development, neurodevelopmental disorder, and cardiometabolic health. Secondarily, we examined the relationships between time since quitting and DNAm at significant CpGs. We observed three CpGs in negative associations with the length of quitting smoking (p < 0.05), which were cg04254052 (KCNIP1), cg22875371 (OGDHL), and cg27289628 (LOC148145), while one in positive association, which was cg13487862 (PLXNB1). As a pilot study, we demonstrated epigenetic modifications associated with former smoking in GCs. The study is informative to potential biological pathways underlying the documented association between smoking and female infertility and biomarker discovery for smoking-associated reproductive outcomes.
Facial asymmetry of the hard and soft tissues in skeletal Class I, II, and III patients
Authors: Li Jialing , Wu Sujuan , Mei Li , Wen Juan , Marra Jamie , Lei Lang , Li Huang 
Published: February 2024

AbstractTo investigate and compare the facial asymmetry (hard and soft tissues) among skeletal Class I, II, and III patients. A total of 221 subjects, including skeletal Class I (n = 80), skeletal Class II (n = 75), and skeletal Class III (n = 66), were included in the study. CBCT, 22 skeletal landmarks, and 10 soft tissue landmarks were used for the measurements and the asymmetry index was calculated to assess the facial asymmetry. Statistical analyses included one-way ANOVA, Kruskal–Wallis test, and Spearman correlation analysis. The skeletal Class III patients presented greater asymmetry than Class II patients for 10 hard tissue landmarks and 3 soft tissue landmarks (p < 0.05). High correlation of asymmetry was found between four soft tissue landmarks and their corresponding skeletal landmarks (rs ≥ 0.71), as well as Me and ANS (r > 0.86). The ANS and Me in 21.3% patients deviated to contralateral sides. The skeletal Class III patients had more facial asymmetry than the Class II patients. Soft tissues showed similar asymmetry as the underlying hard tissues rather than a compensation of the hard tissue asymmetry. The inconsistency in the deviation of Me and ANS may exacerbate facial asymmetry.
Binding and dimerization of PGLa peptides in anionic lipid bilayer studied by replica exchange molecular dynamics
Authors: Bowers Steven R. , Lockhart Christopher , Klimov Dmitri K. 
Published: February 2024

AbstractThe 21-residue PGLa peptide is well known for antimicrobial activity attributed to its ability to compromize bacterial membranes. Using all-atom explicit solvent replica exchange molecular dynamics with solute tempering, we studied PGLa binding to a model anionic DMPC/DMPG bilayer at the high peptide:lipid ratio that promotes PGLa dimerization (a two peptides per leaflet system). As a reference we used our previous simulations at the low peptide:lipid ratio (a one peptide per leaflet system). We found that the increase in the peptide:lipid ratio suppresses PGLa helical propensity, tilts the bound peptide toward the bilayer hydrophobic core, and forces it deeper into the bilayer. Surprisingly, at the high peptide:lipid ratio PGLa binding induces weaker bilayer thinning, but deeper water permeation. We explain these effects by the cross-correlations between lipid shells surrounding PGLa that leads to a much diminished efflux of DMPC lipids from the peptide proximity at the high peptide:lipid ratio. Consistent with the experimental data the propensity for PGLa dimerization was found to be weak resulting in coexistence of monomers and dimers with distinctive properties. PGLa dimers assemble via apolar criss-cross interface and become partially expelled from the bilayer residing at the bilayer-water boundary. We rationalize their properties by the dimer tendency to preserve favorable electrostatic interactions between lysine and phosphate lipid groups as well as to avoid electrostatic repulsion between lysines in the low dielectric environment of the bilayer core. PGLa homedimer interface is predicted to be distinct from that involved in PGLa-magainin heterodimers.
Analysis of the effect of the scorpion toxin AaH-II on action potential generation in the axon initial segment
Authors: Abbas Fatima , Blömer Laila Ananda , Millet Hugo , Montnach Jérôme , De Waard Michel , Canepari Marco 
Published: February 2024

AbstractThe toxin AaH-II, from the scorpion Androctonus australis Hector venom, is a 64 amino acid peptide that targets voltage-gated Na+ channels (VGNCs) and slows their inactivation. While at macroscopic cellular level AaH-II prolongs the action potential (AP), a functional analysis of the effect of the toxin in the axon initial segment (AIS), where VGNCs are highly expressed, was never performed so far. Here, we report an original analysis of the effect of AaH-II on the AP generation in the AIS of neocortical layer-5 pyramidal neurons from mouse brain slices. After determining that AaH-II does not discriminate between Nav1.2 and Nav1.6, i.e. between the two VGNC isoforms expressed in this neuron, we established that 7 nM was the smallest toxin concentration producing a minimal detectable deformation of the somatic AP after local delivery of the toxin. Using membrane potential imaging, we found that, at this minimal concentration, AaH-II substantially widened the AP in the AIS. Using ultrafast Na+ imaging, we found that local application of 7 nM AaH-II caused a large increase in the slower component of the Na+ influx in the AIS. Finally, using ultrafast Ca2+ imaging, we observed that 7 nM AaH-II produces a spurious slow Ca2+ influx via Ca2+-permeable VGNCs. Molecules targeting VGNCs, including peptides, are proposed as potential therapeutic tools. Thus, the present analysis in the AIS can be considered a general proof-of-principle on how high-resolution imaging techniques can disclose drug effects that cannot be observed when tested at the macroscopic level.