bluuebunny/crossref_metadata_2025 huggingface dataset:
APRTC: advanced precise rapid thermal cycling in blow molding by applying fuzzy controller on thermoelectric devices for cooling and heating applications
Authors: Safaryazdi Alireza , Ghaffari Ali
Published: February 2024

This study presents an innovative approach to enhance thermal control in the blow molding production process, specifically focusing on achieving rapid and precise temperature regulation. To address the significant time consumption during mold closure, strategically deploying thermoelectric modules (TEMs) arranged according to the mold’s geometry enables meticulous temperature monitoring through integrated thermocouples. The configuration forms a matrix of interconnected TEMs, thermocouples, and controllers, orchestrating precise temperature adjustments across the mold surface. The research integrates fuzzy algorithms to facilitate seamless communication between thermoelectric devices and thermocouples for precise mold temperature control. Simulation of thermoelectric devices using COMSOL Multiphysics and implementation of fuzzy controllers in Matlab, connected through a live-link, enables real-time. I have  adjustments and precise control. This integrated approach allows for a comprehensive analysis and optimization of the thermal control system, ensuring effective and adaptive temperature regulation. TEMs, operating as solid-state heat pumps, offer size versatility, adaptability to diverse mold shapes, and maintenance-free operation. Leveraging individual control capabilities significantly enhances heat transfer resolution, enabling precise manipulation of heat flux. Emphasizing the reduction of cooling time and achieving high-gloss surface quality, the study introduces the Advanced Precise Rapid Thermal Cycling in Blow Molding (APRTC) method. APRTC strategically employs TEMs to expedite cooling and elevate temperature determination accuracy, guaranteeing enhanced temperature resolution on the core mold surface. Furthermore, the study optimizes energy utilization through a closed-loop fluid circulation system, harnessing waste energy from other stages. Comparative analysis highlights APRTC's superiority, revealing a remarkable$$91 \%$$91%reduction in temperature differentials during the cooling cycle and an$$89 \%$$89%decrease in the heating stage. These findings underscore APRTC's efficacy in maintaining minimal temperature variations throughout the entire molding process.
Taking stock of far-right terrorism through manifestos: Glorification of identity
Authors: Demir Cenker Korhan , Çona Ömer
Published: February 2024

This research delves into the identity construction and violence justification within the context of far-right lone-actor terrorism, particularly motivated by white supremacist ideologies. Employing a qualitative analysis of manifestos compiled by five lone-actor terrorists, this study adopts a model to unveil the nuanced processes behind the justification of violence and glorification of collective identities. The model has been formed for the purpose of the study, drawing from social identity and identity fusion approaches, including steps such as group alignment, exclusion, threat, virtue, and celebration. The analysis of these manifestos illuminates a progression through each phase of the violent act, meticulously crafted through textual expression. Central to the terrorists’ objectives is the creation of a rhetorical platform aimed at fomenting violence against non-white, ethnic, and religious groups. Their motivation arises from the perceived threat of the ‘white race’ being supplanted by immigrant communities across various social, political, and economic domains. This justification of violence hinges on the portrayal of themselves as protectors of the majority society, pitted against these minority groups. Strikingly, the terrorists celebrate their actions by commemorating past white supremacists who employed violence against marginalised communities.
Air Pollution as a Whole: The Court of Justice Strengthens Environmental Standards in the Ambient Air Quality Directive over Contrasting Industrial Emissions Directive Derogations
Authors: Bruno Walter
Published: February 2024

On 9 March 2023, the Court of Justice (Second Chamber) delivered a preliminary ruling about the coordination of two European Union measures against air pollution: the Industrial Emissions Directive and the Ambient Air Quality Directive. Upon assessment, the Court reinforced the mandatory nature of the air quality limit values vis-à-vis possible derogations foreseen in the Industrial Emissions Directive. In this case, both AG Kokott and the Second Chamber affirmed the primacy of the air quality standards. However, this Case Note finds that slightly different reasoning between the AG Opinion and the final Judgment reveals differing underlying approaches. Whilst the AG focuses on air quality plans and leaves more room for discretion to national authorities, the final Judgment anchors the coordination of the two Directives to strict and objective pollution limit values, further strengthening the Ambient Air Quality Directive as an effective instrument of environmental protection litigation.
Investigation of near-wall particle statistics in CFD-DEM simulations of dense fluidised beds and derivation of an Eulerian particle dynamic wall boundary condition
Authors: Dupuy Dorian , Ansart Renaud , Simonin Olivier
Published: February 2024

In two-fluid simulations of gas–solid fluidised beds, the gaseous phase and the particulate phase are modelled as continuous media. The stress exerted by the particulate medium on the container walls should be modelled to predict accurately the bed dynamics. This paper addresses the modelling of sliding particle–wall contacts in two-fluid simulations, based on reference simulations coupling computational fluid dynamics with the discrete element method (CFD-DEM), in which the individual movement of the particles is tracked. The analysis of the CFD-DEM highlights the complex near-wall behaviour of the particles, which is not reproduced by two-fluid models. Nevertheless, the particle–wall shear stress can be expressed based on the total granular pressure within the first cell off the wall. The model is validated for the two-fluid simulation of a bubbling gas–solid fluidised bed of olefin particles in the dense-fluidisation regime.
Tensions in Sino-African labour relations: the view from the Karuma hydroelectric dam in Uganda
Authors: Wyrod Robert , Chang Kimberlee
Published: February 2024

Over the last decade China has become a dominant player in Africa's rapidly growing hydropower sector. These mega projects typically employ thousands of Africans yet research on labour relations at these sites remains extremely limited. This article provides a rare systematic analysis of workers’ experiences on a Chinese-financed-and-constructed hydroelectric dam in Africa. We find that chronic verbal abuse of African workers by Chinese managers is a defining feature of labour relations at this project in Uganda. This abuse has tainted many workers’ attitudes towards the Chinese contractor Sinohydro, the Chinese government, and to a lesser extent Chinese people themselves. Workers also perceive Ugandan organisations and the Ugandan government as complicit in these poor labour relations. These findings underscore the limits of accountability to labour standards by Chinese firms operating in Africa, especially in contexts where host organisations and governments fail to advocate aggressively for the rights of African workers.
The Gutnishsi-passive
Authors: Petzell Erik M.
Published: February 2024

The Gutnish-specificsi-passive combinesbeorbecomewith a participle, directly followed by the elementsi. Unlike regular periphrastic passives,si-passives focus on the process rather than the result, opening up the construction for unergatives, which are unattested in the regular type. However,si-passives are quite limited when it comes to the subject. Internal arguments can only become subjects if they strand a preposition or a particle. Otherwise, the subject is expletive. I argue thatsiis part of the participle ending in Aspo, where its phi-features block agreement with the internal argument, trapping itin situand depriving Aspoof a link to the result of the event. Originally a reflexive,siwas reanalysed as a marker of the participle rather than the infinitive in contexts where conjugational changes had made them ambiguous. These changes never affected Fårö, where thesi-passive is thus correctly predicted to be absent.
Simple preparation of specimens for X-ray powder diffraction analysis of radioactive materials: an illustrative example on irradiated granite
Authors: Aparicio Claudia , Rosnecký Vít , Halodová Patricie
Published: February 2024

Materials in a high radioactive environment undergo structural changes. X-ray diffraction (XRD) is commonly used to study the micro-structural changes of such materials. Therefore, a safe procedure is required for the preparation of specimens. In this paper, a simple methodology for the preparation of radioactive powder specimens to be analyzed in a non-nuclearized laboratory diffractometer is presented. The process is carried out inside a shielded glove box, where the milling of the radioactive sample and specimen preparation occurs. Minimum amount of sample is required (<20 mg), which is drop-casted on a polyether ether ketone (PEEK) foil and glue-sealed inside a disposable plastic holder for a safe handling of the specimen. One example using neutron-irradiated granite is shown, where unit-cell parameters and crystal density of the main phases were calculated. The developed methodology represents an easy and affordable way to study neutron irradiated materials with low activity at laboratory scale.
The Advancement in Spring Vegetation Phenology in the Northern Hemisphere Will Reverse After 2060 Under Future Moderate Warming Scenarios
Authors: Mo Yunhua , Chen Shouzhi , Wu Zhaofei , Tang Jing , Fu Yongshuo
Published: February 2024

Global warming has largely advanced spring vegetation phenology, which has subsequently affected terrestrial carbon and water cycles. However, further shifts in vegetation phenology under future climate change remain unclear. We estimated the start of the growing season (SOS) by applying multiple extraction methods based on the NDVI3g data set, and then parameterized and evaluated 11 spring vegetation phenology models that included chilling, forcing, and the photoperiod. Based on scenario data from three Shared Socioeconomic Pathways (SSP126, SSP245, and SSP585) derived from eight climate models, future vegetation phenology was predicted using the phenology models. Results showed that all the phenology models performed better than the NULL model (mean of the SOS), with the performance of one‐phase models broadly matching that of two‐phase models, although the best models varied by vegetation type. The spatial pattern of simulated SOS was similar among the models, and it explained >75% of the variation. Based on the mean predicted SOS, we found that spring vegetation phenology will continue to advance under strong warming conditions (SSP245 and SSP585), but that the trend of advance will reverse at around 2060 under the SSP126 scenario. The continued trend in SOS advance is likely related to rapid forcing fulfillment under stronger warming conditions. However, under moderate warming, chilling might be reduced and it might require longer to compensate for higher forcing, which ultimately would result in SOS delay. Our findings highlight that trends will likely change under different warming conditions, potentially causing widespread impact on species interaction, biodiversity, and ecosystem function.
Diffuse Venting and Near Seafloor Hydrothermal Circulation at the Lucky Strike Vent Field, Mid‐Atlantic Ridge
Authors: Wheeler Benjamin , Cannat Mathilde , Chavagnac Valérie , Fontaine Fabrice
Published: February 2024

We report on a 3 years monitoring experiment of low to medium temperature diffuse venting at two vent sites (Tour Eiffel and White Castle) of the Lucky Strike, black smoker‐type hydrothermal field, Mid‐Atlantic Ridge. Diffuse vents account for a large part of the energy flux of mid‐ocean ridges hydrothermal fields and provide key habitats for the hydrothermal fauna. We document the time and space variability of diffuse venting temperature and chemistry, describe the effect of tidal loading and currents and discuss the extent of mixing, cooling of black smoker fluids, heating of entrained seawater and anhydrite precipitation/dissolution in the substratum. We emphasize the role of a thin (<2 m) volcaniclastic formation capping the brecciated basalt substratum. This formation is porous, but becomes impermeable when indurated by hydrothermal precipitates. It forms an intermediate layer between the vents at the seabed and the fluids as they discharge out of the brecciated basalts. Diffuse fluids inferred to discharge out of meter‐spaced cracks in the brecciated basalts beneath this volcaniclastic layer are hot (>80°C) and contain >10% of the hot endmember fluid component, over distances of up to 25 m from the black smokers. These results provide a geologically integrated framework in which to study site‐scale, near seafloor hydrothermal circulation and associated vent habitats at Lucky Strike and other black smoker‐type hydrothermal fields. They suggest diffuse heat fluxes in the upper range of previously published estimates at the two studied Lucky Strike hydrothermal vent sites.
On the Effect of 3D Wave Propagation on 2D Regional‐Scale Velocity Model Building
Authors: Górszczyk Andrzej , Brossier Romain , Métivier Ludovic
Published: February 2024

Active 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

Greenlandic 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

Second-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

The 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

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

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

Vein 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

Dipeptide 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

In 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

Smoking 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

To 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

The 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

The 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.
Associations between lifestyle, health, and clinical characteristics and circulating oxysterols and cholesterol precursors in women diagnosed with breast cancer: a cross-sectional study
Authors: Decker Nina Sophia , Johnson Theron , Le Cornet Charlotte , Behrens Sabine , Obi Nadia , Kaaks Rudolf , Chang-Claude Jenny , Fortner Renée Turzanski
Published: February 2024

Despite increasing evidence that cholesterol precursors and oxysterols, oxidized cholesterol metabolites, play a role in numerous pathological processes and diseases including breast cancer, little is known about correlates of these sterols in women with breast cancer. In this study, 2282 women with breast cancer and blood draw post diagnosis were included and cross-sectional associations between circulating levels of 15 sterols/oxysterols and (a) lifestyle, anthropometric, reproductive characteristics, (b) comorbidities and medication use, and (c) breast cancer tumor and treatment characteristics were calculated using generalized linear models. Obesity was strongly associated with circulating levels of 7-dehydrocholesterol (DC) (body mass index ≥ 30 vs. 18.5–24.9 kg/m2: 51.7% difference) and 7-ketocholesterol (KC) (40.0% difference). After adjustment for BMI, comorbidities such as cardiovascular disease were associated with higher levels of 7-DC (26.1% difference) and lower levels of desmosterol (− 16.4% difference). Breast cancer tumor characteristics including hormone receptor status, tumor stage, and endocrine therapy were associated with lanosterol, 24-DHLan, 7b-HC, and THC (e.g., THC; tumor stage IIIa vs. I: 36.9% difference). Weaker associations were observed for lifestyle characteristics and for any of the other oxysterols. The findings of this study suggest that cholesterol precursors are strongly associated with metabolic factors, while oxysterols are associated with breast cancer tumor characteristics, warranting further investigation into the role of cholesterol precursors and oxysterols in women with breast cancer and other populations.
Population genomic analyses reveal that salinity and geographic isolation drive diversification in a free-living protist
Authors: Rengefors Karin , Annenkova Nataliia , Wallenius Joel , Svensson Marie , Kremp Anke , Ahrén Dag
Published: February 2024

Protists make up the vast diversity of eukaryotic life and play a critical role in biogeochemical cycling and in food webs. Because of their small size, cryptic life cycles, and large population sizes, our understanding of speciation in these organisms is very limited. We performed population genomic analyses on 153 strains isolated from eight populations of the recently radiated dinoflagellate genus Apocalathium, to explore the drivers and mechanisms of speciation processes. Species of this genus inhabit both freshwater and saline habitats, lakes and seas, and are found in cold temperate environments across the world. RAD sequencing analyses revealed that the populations were overall highly differentiated, but morphological similarity was not congruent with genetic similarity. While geographic isolation was to some extent coupled to genetic distance, this pattern was not consistent. Instead, we found evidence that the environment, specifically salinity, is a major factor in driving ecological speciation in Apocalathium. While saline populations were unique in loci coupled to genes involved in osmoregulation, freshwater populations appear to lack these. Our study highlights that adaptation to freshwater through loss of osmoregulatory genes may be an important speciation mechanism in free-living aquatic protists.
Response of Eurasian otters (Lutra lutra) to underwater acoustic harassment device sounds
Authors: Stepien Emilie Nicoline , Galatius Anders , Hansen Kirstin Anderson , Nabe-Nielsen Jacob , Teilmann Jonas , Wahlberg Magnus
Published: February 2024

Seal scarers (or acoustic harassment devices, AHDs) are designed to deter seals from fishing gear and aquaculture operations, as well as to prevent seals from entering rivers to avoid predation on valuable fish. Our study investigated the potential effects of AHDs on non-target species, specifically the Eurasian otters (Lutra lutra), by testing the reaction of two rehabilitated otters to simulated AHDs sounds at 1 and 14 kHz, with a received sound intensity of 105–145 dB re 1 µPa rms. The 1 kHz sounds were used to investigate alternative frequencies for scaring seals without scaring otters. The otters reacted to both 1 and 14 kHz tonal signals when retrieving fish from a feeding station 0.8 m below the surface. Their diving behaviour and time to extract food progressively increased as sound intensity increased for all tested sound levels. Notably, the sound levels used in our tests were significantly lower (40–80 dB) than the source levels from commercial AHDs. These findings highlight the importance of caution when using AHDs in river and sea habitats inhabited by otters, as AHDs can change their behaviour and potentially result in habitat exclusion.
Assessing the fate and contribution of Foxd1-expressing embryonic precursors and their progeny in palatal development, homeostasis and excisional repair
Authors: Nikoloudaki Georgia , Hamilton Douglas W.
Published: February 2024

Oral mucosal tissues heal rapidly with minimal scarring, although palatal mucosa can be associated with excessive fibrosis in response to injury. Investigations on the balance between neovascularization and tissue repair suggests regulation of angiogenesis is an important determinant of repair versus scarring. Associated with pericyte mediated fibrosis in kidney injury, FoxD1 is implicated in growth centres during cranio-facial development, although which cell lineages are derived from these embryonic populations in development and in adult animals is unknown. Using a lineage tracing approach, we assessed the fate of embryonic Foxd1-expressing progenitor cells and their progeny in palatal development and during wound healing in adult mice. During palatal development as well as in post-natal tissues, Foxd1-lineage progeny were associated with the vasculature and the epineurium. Post-injury, de novo expression of FoxD1 was not detectable, although Foxd1-lineage progeny expanded while exhibiting low association with the fibroblast/myofibroblast markers PDGFα, PDGFβ, vimentin, α-smooth muscle actin, as well as the neuronal associated markers S100β and p75NTR. Foxd1-lineage progeny were primarily associated with CD146, CD31, and to a lesser extent CD105, remaining in close proximity to developing neovascular structures. Our findings demonstrate that FoxD1 derived cells are predominantly associated with the palatal vasculature and provide strong evidence that FoxD1 derived cells do not give rise to populations involved directly in the scarring of the palate.
Anaemia and red blood cell transfusion in women with placenta accreta spectrum: an analysis of 38,060 cases
Authors: Kloka Jan Andreas , Friedrichson Benjamin , Jasny Thomas , Blum Lea Valeska , Choorapoikayil Suma , Old Oliver , Zacharowski Kai , Neef Vanessa
Published: February 2024

Placenta accreta spectrum (PAS) has become a significant life-threatening issue due to its increased incidence and associated morbidity and mortality. Pregnancy is often associated with states of anaemia, and severe maternal haemorrhage represents a major risk factor for red blood cell (RBC) transfusion. The present study retrospectively analyzed the prevalence of anaemia, transfusion requirements and outcome in women with PAS. Using data from the German Statistical Office pregnant patients with deliveries hospitalized between January 2012 and December 2021 were included. Primary outcome was the prevalence of anemia and administration of RBCs. Secondary outcome were complications in women with PAS who received RBC transfusion. In total 6,493,606 pregnant women were analyzed, of which 38,060 (0.59%) were diagnosed with PAS. The rate of anaemia during pregnancy (60.36 vs. 23.25%; p < 0.0001), postpartum haemorrhage (47.08 vs. 4.41%; p < 0.0001) and RBC transfusion rate (14.68% vs. 0.72%; p < 0.0001) were higher in women with PAS compared to women without PAS. Women with PAS who had bleeding and transfusion experienced significantly more peripartum complications than those who did not. A multiple logistic regression revealed that the probability for RBC transfusion in all pregnant women was positively associated with anaemia (OR 21.96 (95% CI 21.36–22.58)). In women with PAS, RBC transfusion was positively associated with the presence of renal failure (OR 11.27 (95% CI 9.35–13.57)) and congestive heart failure (OR 6.02 (95% CI (5.2–7.07)). Early anaemia management prior to delivery as well as blood conservation strategies are crucial in women diagnosed with PAS.
Stroke and suicide among people with severe mental illnesses
Authors: Liao Chun-Hui , Chang Chen-Shu , Kung Pei-Tseng , Chou Wen-Yu , Tsai Wen-Chen
Published: February 2024

The associations between people with severe mental illnesses (SMI) and the risks of stroke, suicide, and death remain unclear. We examined healthcare service usage among adults with and without SMI and explored the risk of stroke, suicide, and death. We divided 18–80-year-old adults with SMI into catastrophic and non-catastrophic illness groups. These groups were subjected to a 1:5:5 propensity score matching with people without SMI. Data on demographic characteristics, economic factors, environmental factors, comorbid conditions, self-injury behavior, the number of outpatients and ED visits, and hospitalization were collected. The primary outcomes were risks of stroke, suicide, and death. We included 19,570 people with catastrophic SMI, 97,850 with non-catastrophic SMI, and 97,850 controls. Patients with SMI, especially those with catastrophic illnesses, had higher stroke risk, suicide, and death than those without SMI. People with SMI used health services more frequently than those without SMI. Patients with a history of hospitalization or ED access had a higher risk of stroke, suicide, and death. Our data indicate that special attention should be given to patients with SMI, particularly those with a history of healthcare service utilization, such as through more extended hospital stays with high-intensity interventions.