bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential ABC transporter expression during hematopoiesis contributes to neutrophil-biased toxicity of Aurora kinase inhibitors
Authors: Chou David B. , Furlong Brooke A. , Posey Ryan R. , Kyprianou Christos , O’Sullivan Lucy R. , David Rhiannon , Randle Suzanne J. , Polanska Urszula M. , Travers Jon , Urosevic Jelena , Hutchinson John N. , Che Jianwei , Howley Anna M. , Hasserjian Robert P. , Prantil-Baun Rachelle , Ingber Donald E.
Published: October 2022

Drug-induced cytopenias are a prevalent and significant issue that worsens clinical outcomes and hinders the effective treatment of cancer. While reductions in blood cell numbers are classically associated with traditional cytotoxic chemotherapies, they also occur with newer targeted small molecules and the factors that determine the hematotoxicity profiles of oncologic drugs are not fully understood. Here, we explore why some Aurora kinase inhibitors cause preferential neutropenia. By studying drug responses of healthy human hematopoietic cells in vitro and analyzing existing gene expression datasets, we provide evidence that the enhanced vulnerability of neutrophil-lineage cells to Aurora kinase inhibition is caused by early developmental changes in ATP-binding cassette (ABC) transporter expression. These data show that hematopoietic cell-intrinsic expression of ABC transporters may be an important factor that determines how some Aurora kinase inhibitors affect the bone marrow.
Diffraction-engineered holography: Beyond the depth representation limit of holographic displays
Authors: Yang Daeho , Seo Wontaek , Yu Hyeonseung , Kim Sun Il , Shin Bongsu , Lee Chang-Kun , Moon Seokil , An Jungkwuen , Hong Jong-Young , Sung Geeyoung , Lee Hong-Seok
Published: October 2022

Holography is one of the most prominent approaches to realize true-to-life reconstructions of objects. However, owing to the limited resolution of spatial light modulators compared to static holograms, reconstructed objects exhibit various coherent properties, such as content-dependent defocus blur and interference-induced noise. The coherent properties severely distort depth perception, the core of holographic displays to realize 3D scenes beyond 2D displays. Here, we propose a hologram that imitates defocus blur of incoherent light by engineering diffracted pattern of coherent light with adopting multi-plane holography, thereby offering real world-like defocus blur and photorealistic reconstruction. The proposed hologram is synthesized by optimizing a wave field to reconstruct numerous varifocal images after propagating the corresponding focal distances where the varifocal images are rendered using a physically-based renderer. Moreover, to reduce the computational costs associated with rendering and optimizing, we also demonstrate a network-based synthetic method that requires only an RGB-D image.
Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19
Authors: de Prost Nicolas , Audureau Etienne , Heming Nicholas , Gault Elyanne , Pham Tài , Chaghouri Amal , de Montmollin Nina , Voiriot Guillaume , Morand-Joubert Laurence , Joseph Adrien , Chaix Marie-Laure , Préau Sébastien , Favory Raphaël , Guigon Aurélie , Luyt Charles-Edouard , Burrel Sonia , Mayaux Julien , Marot Stéphane , Roux Damien , Descamps Diane , Meireles Sylvie , Pène Frédéric , Rozenberg Flore , Contou Damien , Henry Amandine , Gaudry Stéphane , Brichler Ségolène , Timsit Jean-François , Kimmoun Antoine , Hartard Cédric , Jandeaux Louise-Marie , Fafi-Kremer Samira , Gabarre Paul , Emery Malo , Garcia-Sanchez Claudio , Jochmans Sébastien , Pitsch Aurélia , Annane Djillali , Azoulay Elie , Mekontso Dessap Armand , Rodriguez Christophe , Pawlotsky Jean-Michel , Fourati Slim
Published: October 2022

Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with rarer occurrence of severe disease requiring intensive care. Little information is available on comorbid factors, clinical conditions and specific viral mutational patterns associated with the severity of variant Omicron infection. In this multicenter prospective cohort study, patients consecutively admitted for severe COVID-19 in 20 intensive care units in France between December 7th 2021 and May 1st 2022 were included. Among 259 patients, we show that the clinical phenotype of patients infected with variant Omicron (n = 148) is different from that in those infected with variant Delta (n = 111). We observe no significant relationship between Delta and Omicron variant lineages/sublineages and 28-day mortality (adjusted odds ratio [95% confidence interval] = 0.68 [0.35–1.32]; p = 0.253). Among Omicron-infected patients, 43.2% are immunocompromised, most of whom have received two doses of vaccine or more (85.9%) but display a poor humoral response to vaccination. The mortality rate of immunocompromised patients infected with variant Omicron is significantly higher than that of non-immunocompromised patients (46.9% vs 26.2%; p = 0.009). In patients infected with variant Omicron, there is no association between specific sublineages (BA.1/BA.1.1 (n = 109) and BA.2 (n = 21)) or any viral genome polymorphisms/mutational profile and 28-day mortality.
RNF185 regulates proteostasis in Ebolavirus infection by crosstalk between the calnexin cycle, ERAD, and reticulophagy
Authors: Zhang Jing , Wang Bin , Gao Xiaoxiao , Peng Cheng , Shan Chao , Johnson Silas F. , Schwartz Richard C. , Zheng Yong-Hui
Published: October 2022

Virus infection affects cellular proteostasis and provides an opportunity to study this cellular process under perturbation. The proteostasis network in the endoplasmic reticulum (ER) is composed of the calnexin cycle, and the two protein degradation pathways ER-associated protein degradation (ERAD) and ER-to-lysosome-associated degradation (ERLAD/ER-phagy/reticulophagy). Here we show that calnexin and calreticulin trigger Zaire Ebolavirus (EBOV) glycoprotein GP1,2 misfolding. Misfolded EBOV-GP1,2 is targeted by ERAD machinery, but this results in lysosomal instead of proteasomal degradation. Moreover, the ER Ub ligase RNF185, usually associated with ERAD, polyubiquitinates EBOV-GP1,2 on lysine 673 via ubiquitin K27-linkage. Polyubiquinated GP1,2 is subsequently recruited into autophagosomes by the soluble autophagy receptor sequestosome 1 (SQSTM1/p62), in an ATG3- and ATG5-dependent manner. We conclude that EBOV hijacks all three proteostasis mechanisms in the ER to downregulate GP1,2 via polyubiquitination and show that this increases viral fitness. This study identifies linkages among proteostasis network components previously thought to function independently.
A conserved enzyme of smut fungi facilitates cell-to-cell extension in the plant bundle sheath
Authors: Ökmen Bilal , Jaeger Elaine , Schilling Lena , Finke Natalie , Klemd Amy , Lee Yoon Joo , Wemhöner Raphael , Pauly Markus , Neumann Ulla , Doehlemann Gunther
Published: October 2022

Smut fungi comprise one of the largest groups of fungal plant pathogens causing disease in all cereal crops. They directly penetrate host tissues and establish a biotrophic interaction. To do so, smut fungi secrete a wide range of effector proteins, which suppress plant immunity and modulate cellular functions as well as development of the host, thereby determining the pathogen’s lifestyle and virulence potential. The conserved effector Erc1 (enzyme required for cell-to-cell extension) contributes to virulence of the corn smut Ustilago maydis in maize leaves but not on the tassel. Erc1 binds to host cell wall components and displays 1,3-β-glucanase activity, which is required to attenuate β-glucan-induced defense responses. Here we show that Erc1 has a cell type-specific virulence function, being necessary for fungal cell-to-cell extension in the plant bundle sheath and this function is fully conserved in the Erc1 orthologue of the barley pathogen Ustilago hordei.
Key considerations to reduce or address respondent burden in patient-reported outcome (PRO) data collection
Authors: Aiyegbusi Olalekan Lee , Roydhouse Jessica , Rivera Samantha Cruz , Kamudoni Paul , Schache Peter , Wilson Roger , Stephens Richard , Calvert Melanie
Published: October 2022

Patient-reported outcomes (PROs) are used in clinical trials to provide evidence of the benefits and risks of interventions from a patient perspective and to inform regulatory decisions and health policy. The collection of PROs in routine practice can facilitate monitoring of patient symptoms; identification of unmet needs; prioritisation and/or tailoring of treatment to the needs of individual patients and inform value-based healthcare initiatives. However, respondent burden needs to be carefully considered and addressed to avoid high rates of missing data and poor reporting of PRO results, which may lead to poor quality data for regulatory decision making and/or clinical care.
Laser-driven multi-MeV high-purity proton acceleration via anisotropic ambipolar expansion of micron-scale hydrogen clusters
Authors: Jinno Satoshi , Kanasaki Masato , Asai Takafumi , Matsui Ryutaro , Pirozhkov Alexander S. , Ogura Koichi , Sagisaka Akito , Miyasaka Yasuhiro , Nakanii Nobuhiko , Kando Masaki , Kitagawa Nobuko , Morishima Kunihiro , Kodaira Satoshi , Kishimoto Yasuaki , Yamauchi Tomoya , Uesaka Mitsuru , Kiriyama Hiromitsu , Fukuda Yuji
Published: October 2022

Multi-MeV high-purity proton acceleration by using a hydrogen cluster target irradiated with repetitive, relativistic intensity laser pulses has been demonstrated. Statistical analysis of hundreds of data sets highlights the existence of markedly high energy protons produced from the laser-irradiated clusters with micron-scale diameters. The spatial distribution of the accelerated protons is found to be anisotropic, where the higher energy protons are preferentially accelerated along the laser propagation direction due to the relativistic effect. These features are supported by three-dimensional (3D) particle-in-cell (PIC) simulations, which show that directional, higher energy protons are generated via the anisotropic ambipolar expansion of the micron-scale clusters. The number of protons accelerating along the laser propagation direction is found to be as high as 1.6 $$\pm \,{0.3}$$

±

0.3

$$\times$$
×
10$$^9$$

9

/MeV/sr/shot with an energy of 2.8 $$\pm \,{1.9}$$

±

1.9

MeV, indicating that laser-driven proton acceleration using the micron-scale hydrogen clusters is promising as a compact, repetitive, multi-MeV high-purity proton source for various applications.
Needle bevel geometry influences the flexural deflection magnitude in ultrasound-enhanced fine-needle biopsy
Authors: Bunni Saif , Nieminen Heikki J.
Published: October 2022

It has been recently demonstrated that use of ultrasound increases the tissue yield in ultrasound-enhanced fine-needle aspiration biopsy (USeFNAB) as compared to conventional fine-needle aspiration biopsy (FNAB). To date, the association between bevel geometry and needle tip action has not been widely explored. In this study, we studied the needle resonance characteristics and deflection magnitude of various needle bevel geometries with varying bevel lengths. With a conventional lancet, having a 3.9 mm long bevel, the tip deflection-to-power ratio (DPR) in air and water was 220 and 105 µm/W, respectively. This was higher in comparison to an axi-symmetric tip, having a bevel length of 4 mm, which achieved a DPR of 180 and 80 µm/W in air and water, respectively. This study emphasised the importance of relationship between flexural stiffness of bevel geometry in the context of various insertion media and, thus, could provide understanding on approaches to control post-puncture cutting action by modifying the needle bevel geometry, essential for the USeFNAB application.
Global microRNA expression profile in laryngeal carcinoma unveils new prognostic biomarkers and novel insights into field cancerization
Authors: Popov Todor M. , Stancheva Gergana , Kyurkchiyan Silva G. , Petkova Veronika , Panova Stiliana , Kaneva Radka P. , Popova Diana P.
Published: October 2022

Laryngeal carcinoma is still a worldwide burden that has shown no significant improvement during the last few decades regarding definitive treatment strategies. The lack of suitable biomarkers for personalized treatment protocols and delineating field cancerization prevents further progress in clinical outcomes. In the light of this perspective, MicroRNAs could be promising biomarkers both in terms of diagnostic and prognostic value. The aim of this prospective study is to find strong prognostic microRNA biomarkers for advanced laryngeal carcinoma and molecular signatures of field cancerization. Sixty patients were enrolled and four samples were collected from each patient: tumor surface and depth, peritumor normal mucosa, and control distant laryngeal mucosa. Initially, a global microRNA profile was conducted in twelve patients from the whole cohort and subsequently, we validated a selected group of 12 microRNAs with RT-qPCR. The follow-up period was 24 months (SD ± 13 months). Microarray expression profile revealed 59 dysregulated microRNAs. The validated expression levels of miR-93-5p (χ2(2) = 4.68, log-rank p = 0.03), miR-144-3p (χ2(2) = 4.53, log-rank p = 0.03) and miR-210-3p (χ2(2) = 4.53, log-rank p = 0.03) in tumor samples exhibited strong association with recurrence-free survival as higher expression levels of these genes predict worse outcome. Tumor suppressor genes miR-144-3p (mean rank 1.58 vs 2.14 vs 2.29, p = 0.000) and miR-145-5p (mean rank 1.57 vs 2.15 vs 2.28, p = 0.000) were significantly dysregulated in peritumor mucosa with a pattern of expression consistent with paired tumor samples thus revealing a signature of field cancerization in laryngeal carcinoma. Additionally, miR-1260b, miR-21-3p, miR-31-3p and miR-31-5p were strongly associated with tumor grade. Our study reports the first global microRNA profile specifically in advanced laryngeal carcinoma that includes survival analysis and investigates the molecular signature of field cancerization. We report two strong biomarkers of field cancerization and three predictors for recurrence in advance stage laryngeal cancer.
Optic nerve sheath diameter is associated with outcome in severe Covid-19
Authors: Pansell Jakob , Rudberg Peter C. , Bell Max , Friman Ola , Cooray Charith
Published: October 2022

Neurological symptoms are common in Covid-19 and cerebral edema has been shown post-mortem. The mechanism behind this is unclear. Elevated intracranial pressure (ICP) has not been extensively studied in Covid-19. ICP can be estimated noninvasively with measurements of the optic nerve sheath diameter (ONSD). We performed a cohort study with ONSD ultrasound measurements in severe cases of Covid-19 at an intensive care unit (ICU). We measured ONSD with ultrasound in adults with severe Covid-19 in the ICU at Karolinska University Hospital in Sweden. Patients were classified as either having normal or elevated ONSD. We compared ICU length of stay (ICU-LOS) and 90 day mortality between the groups. 54 patients were included. 11 of these (20.4%) had elevated ONSD. Patients with elevated ONSD had 12 days longer ICU-LOS (95% CI 2 to 23 p = 0.03) and a risk ratio of 2.3 for ICU-LOS ≥ 30 days. There were no significant differences in baseline data or 90 day mortality between the groups. Elevated ONSD is common in severe Covid-19 and is associated with adverse outcome. This may be caused by elevated ICP. This is a clinically important finding that needs to be considered when deciding upon various treatment strategies.
Dynamics of alkannin/shikonin biosynthesis in response to jasmonate and salicylic acid in Lithospermum officinale
Authors: Ahmad Muhammad , Varela Alonso Alicia , Koletti Antigoni E. , Rodić Nebojša , Reichelt Michael , Rödel Philipp , Assimopoulou Andreana N. , Paun Ovidiu , Declerck Stéphane , Schneider Carolin , Molin Eva M.
Published: October 2022

Alkannin/shikonin and their derivatives are specialised metabolites of high pharmaceutical and ecological importance exclusively produced in the periderm of members of the plant family Boraginaceae. Previous studies have shown that their biosynthesis is induced in response to methyl jasmonate but not salicylic acid, two phytohormones that play important roles in plant defence. However, mechanistic understanding of induction and non-induction remains largely unknown. In the present study, we generated the first comprehensive transcriptomic dataset and metabolite profiles ofLithospermum officinaleplants treated with methyl jasmonate and salicylic acid to shed light on the underlying mechanisms. Our results highlight the diverse biological processes activated by both phytohormones and reveal the important regulatory role of the mevalonate pathway in alkannin/shikonin biosynthesis inL. officinale. Furthermore, by modelling a coexpression network, we uncovered structural and novel regulatory candidate genes connected to alkannin/shikonin biosynthesis. Besides providing new mechanistic insights into alkannin/shikonin biosynthesis, the generated methyl jasmonate and salicylic acid elicited expression profiles together with the coexpression networks serve as important functional genomic resources for the scientific community aiming at deepening the understanding of alkannin/shikonin biosynthesis.
Enhanced terrestrial Fe(II) mobilization identified through a novel mechanism of microbially driven cave formation in Fe(III)-rich rocks
Authors: Parker Ceth W. , Senko John M. , Auler Augusto S. , Sasowsky Ira D. , Schulz Frederik , Woyke Tanja , Barton Hazel A.
Published: October 2022

Most cave formation requires mass separation from a host rock in a process that operates outward from permeable pathways to create the cave void. Given the poor solubility of Fe(III) phases, such processes are insufficient to account for the significant iron formation caves (IFCs) seen in Brazilian banded iron formations (BIF) and associated rock. In this study we demonstrate that microbially-mediated reductive Fe(III) dissolution is solubilizing the poorly soluble Fe(III) phases to soluble Fe(II) in the anoxic zone behind cave walls. The resultant Fe(III)-depleted material (termed sub muros) is unable to maintain the structural integrity of the walls and repeated rounds of wall collapse lead to formation of the cave void in an active, measurable process. This mechanism may move significant quantities of Fe(II) into ground water and may help to explain the mechanism of BIF dissolution and REE enrichment in the generation of canga. The role of Fe(III) reducing microorganism and mass separation behind the walls (outward-in, rather than inward-out) is not only a novel mechanism of speleogenesis, but it also may identify a previously overlooked source of continental Fe that may have contributed to Archaean BIF formation.
Dynamic biological characteristics of human bone marrow hematopoietic stem cell senescence
Authors: Xiao Minhe , Zhou Peng , Wang Ziling , Xiao Hanxianzhi , Chen Xiao , Jiang Rong , Wang Yaping
Published: October 2022

Hematopoietic stem cells show biological manifestations of aging, diminished hematopoietic function and abnormal differentiation, which can lead to leukemia. It is therefore important to explore the mechanism underlying hematopoietic stem cell aging to develop strategies for delaying the process. Our evaluations revealed that the number of bone marrow hematopoietic cells (BMHCs) started to decrease significantly after 45 years of age, and the number of senescent BMHCs, as determined by senescence-associated beta-galactosidase staining, gradually increased with age. In addition, BMHCs from individuals over 45 years of age presented with notably reduced proliferative capacity, increased G1-phase cell cycle arrest, and significantly decreased generation of mixed colony forming units, which suggests that BMHCs enter senescence during middle age. Furthermore, we observed significantly lower antioxidant capacity and a significant increase in oxidative damage products, a gradual increase in the expression of senescence-associated proteins and genes, and a gradual decrease in the expression of cell cycle related proteins in BMHCs after middle age. Taken together, these findings offer both a theoretical and experimental basis for better understanding of the senescence progression of BMHCs and the optimal timing for anti-senescence drug interventions in clinical practice.
The effect of the surgical approach and cochlear implant electrode on the structural integrity of the cochlea in human temporal bones
Authors: Jwair Saad , Versnel Huib , Stokroos Robert J. , Thomeer Hans G. X. M.
Published: October 2022

Cochlear implants (CI) restore hearing of severely hearing-impaired patients. Although this auditory prosthesis is widely considered to be very successful, structural cochlear trauma during cochlear implantation is an important problem, reductions of which could help to improve hearing outcomes and to broaden selection criteria. The surgical approach in cochlear implantation, i.e. round window (RW) or cochleostomy (CO), and type of electrode-array, perimodiolar (PM) or lateral wall (LW), are variables that might influence the probability of severe trauma. We investigated the effect of these two variables on scalar translocation (STL), a specific type of severe trauma. Thirty-two fresh frozen human cadaveric ears were evenly distributed over four groups receiving either RW or CO approach, and either LW or PM array. Conventional radiological multiplanar reconstruction (MPR) was compared with a reconstruction method that uncoils the spiral shape of the cochlea (UCR). Histological analysis showed that RW with PM array had STL rate of 87% (7/8), CO approach with LW array 75% (6/8), RW approach with LW array 50% (4/8) and CO approach with PM array 29% (2/7). STL assessment using UCR showed a higher inter-observer and histological agreement (91 and 94% respectively), than that using MPR (69 and 74% respectively). In particular, LW array positions were difficult to assess with MPR. In conclusion, the interaction between surgical approach and type of array should be preoperatively considered in cochlear implant surgery. UCR technique is advised for radiological assessment of CI positions, and in general it might be useful for pathologies involving the inner ear or other complex shaped bony tubular structures.
NT157 exerts antineoplastic activity by targeting JNK and AXL signaling in lung cancer cells
Authors: de Miranda Lívia Bassani Lins , Lima Keli , Coelho-Silva Juan Luiz , Traina Fabiola , Kobayashi Susumu S. , Machado-Neto João Agostinho
Published: October 2022

Combination therapies or multi-targeted drugs have been pointed out as an option to prevent the emergence of resistant clones, which could make long-term treatment more effective and translate into better clinical outcomes for cancer patients. The NT157 compound is a synthetic tyrphostin that leads to long-term inhibition of IGF1R/IRS1-2-, STAT3- and AXL-mediated signaling pathways. Given the importance of these signaling pathways for the development and progression of lung cancer, this disease becomes an interesting model for generating preclinical evidence on the cellular and molecular mechanisms underlying the antineoplastic activity of NT157. In lung cancer cells, exposure to NT157 decreased, in a dose-dependent manner, cell viability, clonogenicity, cell cycle progression and migration, and induced apoptosis (p < 0.05). In the molecular scenario, NT157 reduced expression of IRS1 and AXL and phosphorylation of p38 MAPK, AKT, and 4EBP1. Besides, NT157 decreased expression of oncogenes BCL2, CCND1, MYB, and MYC and increased genes related to cellular stress and apoptosis, JUN, BBC3, CDKN1A, CDKN1B, FOS, and EGR1 (p < 0.05), favoring a tumor-suppressive cell signaling network in the context of lung cancer. Of note, JNK was identified as a key kinase for NT157-induced IRS1 and IRS2 phosphorylation, revealing a novel axis involved in the mechanism of action of the drug. NT157 also presented potentiating effects on EGFR inhibitors in lung cancer cells. In conclusion, our preclinical findings highlight NT157 as a putative prototype of a multitarget drug that may contribute to the antineoplastic arsenal against lung cancer.
Prediction of persistent acute kidney injury in postoperative intensive care unit patients using integrated machine learning: a retrospective cohort study
Authors: Jiang Xuandong , Hu Yongxia , Guo Shan , Du Chaojian , Cheng Xuping
Published: October 2022

Acute kidney injury (AKI) often occurs in patients in the intensive care unit (ICU). AKI duration is closely related to the prognosis of critically ill patients. Identifying the disease course length in AKI is critical for developing effective individualised treatment. To predict persistent AKI at an early stage based on a machine learning algorithm and integrated models. Overall, 955 patients admitted to the ICU after surgery complicated by AKI were retrospectively evaluated. The occurrence of persistent AKI was predicted using three machine learning methods: a support vector machine (SVM), decision tree, and extreme gradient boosting and with an integrated model. External validation was also performed. The incidence of persistent AKI was 39.4–45.1%. In the internal validation, SVM exhibited the highest area under the receiver operating characteristic curve (AUC) value, followed by the integrated model. In the external validation, the AUC values of the SVM and integrated models were 0.69 and 0.68, respectively, and the model calibration chart revealed that all models had good performance. Critically ill patients with AKI after surgery had high incidence of persistent AKI. Our machine learning model could effectively predict the occurrence of persistent AKI at an early stage.
Three-dimensional assessment of vascular cooling effects on hepatic microwave ablation in a standardized ex vivo model
Authors: Neizert C. A. , Do H. N. C. , Zibell M. , Rieder C. , Sinden D. , Niehues S. M. , Vahldiek J. L. , Lehmann K. S. , Poch F. G. M.
Published: October 2022

The aim of this study was a three-dimensional analysis of vascular cooling effects on microwave ablation (MWA) in an ex vivo porcine model. A glass tube, placed in parallel to the microwave antenna at distances of 2.5, 5.0 and 10.0 mm (A–V distance), simulated a natural liver vessel. Seven flow rates (0, 1, 2, 5, 10, 100, 500 ml/min) were evaluated. Ablations were segmented into 2 mm slices for a 3D-reconstruction. A qualitative and quantitative analysis was performed. 126 experiments were carried out. Cooling effects occurred in all test series with flow rates ≥ 2 ml/min in the ablation periphery. These cooling effects had no impact on the total ablation volume (p > 0.05) but led to changes in ablation shape at A–V distances of 5.0 mm and 10.0 mm. Contrary, at a A–V distance of 2.5 mm only flow rates of ≥ 10 ml/min led to relevant cooling effects in the ablation centre. These cooling effects influenced the ablation shape, whereas the total ablation volume was reduced only at a maximal flow rate of 500 ml/min (p = 0.002). Relevant cooling effects exist in MWA. They mainly depend on the distance of the vessel to the ablation centre.
Protecting boreal caribou habitat can help conserve biodiversity and safeguard large quantities of soil carbon in Canada
Authors: Johnson Cheryl A. , Drever C. Ronnie , Kirby Patrick , Neave Erin , Martin Amanda E.
Published: October 2022

Boreal caribou require large areas of undisturbed habitat for persistence. They are listed as threatened with the risk of extinction in Canada because of landscape changes induced by human activities and resource extraction. Here we ask: Can the protection of habitat for boreal caribou help Canada meet its commitments under the United Nations Convention on Biological Diversity and United Nations Framework Convention on Climate Change? We identified hotspots of high conservation value within the distribution of boreal caribou based on: (1) three measures of biodiversity for at risk species (species richness, unique species and taxonomic diversity); (2) climate refugia or areas forecasted to remain unchanged under climate change; and, (3) areas of high soil carbon that could add to Canada’s greenhouse gas emissions if released into the atmosphere. We evaluated the overlap among hotspot types and how well hotspots were represented in Canada’s protected and conserved areas network. While hotspots are widely distributed across the boreal caribou distribution, with nearly 80% of the area falling within at least one hotspot type, only 3% of the distribution overlaps three or more hotspots. Moreover, the protected and conserved areas network only captures about 10% of all hotspots within the boreal caribou distribution. While the protected and conserved areas network adequately represents hotspots with high numbers of at risk species, areas occupied by unique species, as well as the full spectrum of areas occupied by different taxa, are underrepresented. Climate refugia and soil carbon hotspots also occur at lower percentages than expected. These findings illustrate the potential co-benefits of habitat protection for caribou to biodiversity and ecosystem services and suggest caribou may be a good proxy for future protected areas planning and for developing effective conservation strategies in regional assessments.
PSD-95 in the anterior cingulate cortex contributes to neuropathic pain by interdependent activation with NR2B
Authors: Li Ang , Huang Chang-Jun , Gu Kai-Peng , Huang Yan , Huang Ya-Qin , Zhang Hui , Lin Jia-Piao , Liu Yu-Fan , Yang Yan , Yao Yong-Xing
Published: October 2022

Studies suggest that the scaffolding protein, postsynaptic density protein-95 (PSD-95), is involved in multiple neurological dysfunctions. However, the role of PSD-95 in the anterior cingulate cortex (ACC) in neuropathic pain (NP) has not been investigated. The current study addressed the role of PSD-95 in the ACC in NP and its modulating profile with NMDA receptor subunit 2B (NR2B). The NP model was established by chronic constriction injury (CCI) of the sciatic nerve, and mechanical and thermal tests were used to evaluate behavioral hyperalgesia. Protein expression and distribution were evaluated using immunohistochemistry and western blotting. The results showed that PSD-95 and NR2B were co-localized in neurons in the ACC. After CCI, both PSD-95 and NR2B were upregulated in the ACC. Inhibiting NR2B with Ro 25-6981 attenuated pain hypersensitivity and decreased the over-expression of PSD-95 induced by CCI. Furthermore, intra-ACC administration of PSD-95 antisense oligonucleotide not only attenuated pain hypersensitivity but also downregulated the NR2B level and the phosphorylation of cyclic AMP response element-binding protein. These results demonstrated that PSD-95 in the ACC contributes to NP by interdependent activation of NR2B.
Family cancer history and smoking habit associated with sarcoma in a Japanese population study
Authors: Araki Yoshihiro , Yamamoto Norio , Tanzawa Yoshikazu , Higashi Takahiro , Kuchiba Aya , Hayashi Katsuhiro , Takeuchi Akihiko , Miwa Shinji , Igarashi Kentaro , Endo Makoto , Kobayashi Eisuke , Tsuchiya Hiroyuki , Kawai Akira
Published: October 2022

Sarcoma is a rare cancer, and little is known about the etiology, lifestyle epidemiology, and actual circumstances of treatment in hospitals in Japan. Understanding these issues is essential for the effective prevention and treatment of sarcoma. We therefore investigated the incidence of a personal and family cancer history in a total of 1320 sarcoma patients at the National Cancer Center Hospital. In addition, obesity, hypertension, dyslipidemia, diabetes mellitus, drinking, smoking, age and sex were compared in a descriptive study of 1159 of these sarcoma patients who were ≥ 20 years of age, and 7738 controls derived from the National Health and Nutrition Examination Survey in Japan. A total of 8% of sarcoma patients had a personal history of another cancer, and 30% of soft tissue sarcoma patients had a family cancer history in a first-degree relative (malignant peripheral nerve sheath tumor, 52%; leiomyosarcoma, 46%). A smoking habit was associated with the development of sarcoma (odds ratio [OR], 2.05; 95% confidence interval, 1.78–2.37; p < 0.01). According to the histology, the ORs for undifferentiated pleomorphic sarcoma (UPS) of bone, UPS of soft tissue, and liposarcoma were 5.71, 3.04, and 2.92, respectively. A family cancer history may be associated with certain soft tissue sarcomas, and a smoking habit was significantly associated with the development of sarcomas; however, further studies are necessary.
Aortic stenosis and mitral regurgitation modify the effect of venoarterial extracorporeal membrane oxygenation on left ventricular function in cardiogenic shock
Authors: Ostadal Petr , Vondrakova Dagmar , Popkova Michaela , Hrachovina Matej , Kruger Andreas , Janotka Marek , Naar Jan , Kittnar Otomar , Neuzil Petr , Mlcek Mikulas
Published: October 2022

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is widely used in the treatment of patients experiencing cardiogenic shock (CS). However, increased VA-ECMO blood flow (EBF) may significantly impair left ventricular (LV) performance. The objective of the present study was to assess the effect of VA-ECMO on LV function in acute CS with concomitant severe aortic stenosis (AS) or mitral regurgitation (MR) in a porcine model. Eight female swine (45 kg) underwent VA-ECMO implantation under general anaesthesia and mechanical ventilation. Acute CS was induced by global myocardial hypoxia. Subsequently, severe AS was simulated by obstruction of the aortic valve, while severe MR was induced by mechanical destruction of the mitral valve. Haemodynamic and LV performance variables were measured at different rates of EBF rates (ranging from 1 to 4 L/min), using arterial and venous catheters, a pulmonary artery catheter, and LV pressure–volume catheter. Data are expressed as median (interquartile range). Myocardial hypoxia resulted in declines in cardiac output to 2.7 (1.9–3.1) L/min and LV ejection fraction to 15.2% (10.5–19.3%). In severe AS, increasing EBF from 1 to 4 L/min was associated with a significant elevation in mean arterial pressure (MAP), from 33.5 (24.2–34.9) to 56.0 (51.9–73.3) mmHg (P ˂ 0.01). However, LV volumes (end-diastolic, end-systolic, stroke) remained unchanged, and LV end-diastolic pressure (LVEDP) significantly decreased from 24.9 (21.2–40.0) to 19.1 (15.2–29.0) mmHg (P ˂ 0.01). In severe MR, increasing EBF resulted in a significant elevation in MAP from 49.0 (28.0–53.4) to 72.5 (51.4–77.1) mmHg (P ˂ 0.01); LV volumes remained stable and LVEDP increased from 17.1 (13.7–19.1) to 20.8 (16.3–25.6) mmHg (P ˂ 0.01). Results of this study indicate that the presence of valvular heart disease may alleviate negative effect of VA-ECMO on LV performance in CS. Severe AS fully protected against LV overload, and partial protection was also detected with severe MR, although at the cost of increased LVEDP and, thus, higher risk for pulmonary oedema.
Virtual data augmentation method for reaction prediction
Authors: Wu Xinyi , Zhang Yun , Yu Jiahui , Zhang Chengyun , Qiao Haoran , Wu Yejian , Wang Xinqiao , Wu Zhipeng , Duan Hongliang
Published: October 2022

To improve the performance of data-driven reaction prediction models, we propose an intelligent strategy for predicting reaction products using available data and increasing the sample size using fake data augmentation. In this research, fake data sets were created and augmented with raw data for constructing virtual training models. Fake reaction datasets were created by replacing some functional groups, i.e., in the data analysis strategy, the fake data as compounds with modified functional groups to increase the amount of data for reaction prediction. This approach was tested on five different reactions, and the results show improvements over other relevant techniques with increased model predictivity. Furthermore, we evaluated this method in different models, confirming the generality of virtual data augmentation. In summary, virtual data augmentation can be used as an effective measure to solve the problem of insufficient data and significantly improve the performance of reaction prediction.
Automatic stochastic 3D clay fraction model from tTEM survey and borehole data
Authors: Neven Alexis , Christiansen Anders Vest , Renard Philippe
Published: October 2022

In most urbanized and agricultural areas of central Europe, the shallow underground is constituted of Quaternary deposits which are often the most extensively used layers (water pumping, shallow geothermic, material excavation). All these deposits are often complexly intertwined, leading to high spatial variability and high complexity. Geophysical data can be a fast and reliable source of information about the underground. Still, the integration of these data can be time-consuming, it lacks realistic interpolation in a full 3D space, and the final uncertainty is often not represented. In this study, we propose a new methodology to combine boreholes and geophysical data with uncertainty in an automatic framework. A spatially varying translator function that predicts the clay fraction from resistivity is inverted using boreholes description as control points. It is combined with a 3D stochastic interpolation framework based on a Multiple Points Statistics algorithm and Gaussian Random Function. This novel workflow allows incorporating robustly the data and their uncertainty and requires less user intervention than the already existing workflows. The methodology is illustrated for ground-based towed transient electromagnetic data (tTEM) and borehole data from the upper Aare valley, Switzerland. In this location, a 3D realistic high spatial resolution model of clay fraction was obtained over the whole valley. The very dense data set allowed to demonstrate the quality of the predicted values and their corresponding uncertainties using cross-validation.
Resting-state functional connectivity predicts motor cortex stimulation-dependent pain relief in fibromyalgia syndrome patients
Authors: Argaman Yuval , Granovsky Yelena , Sprecher Elliot , Sinai Alon , Yarnitsky David , Weissman-Fogel Irit
Published: October 2022

MRI-based resting-state functional connectivity (rsFC) has been shown to predict response to pharmacological and non-pharmacological treatments for chronic pain, but not yet for motor cortex transcranial magnetic stimulation (M1-rTMS). Twenty-seven fibromyalgia syndrome (FMS) patients participated in this double-blind, crossover, and sham-controlled study. Ten daily treatments of 10 Hz M1-rTMS were given over 2 weeks. Before treatment series, patients underwent resting-state fMRI and clinical pain evaluation. Significant pain reduction occurred following active, but not sham, M1-rTMS. The following rsFC patterns predicted reductions in clinical pain intensity after the active treatment: weaker rsFC of the default-mode network with the middle frontal gyrus (r = 0.76, p < 0.001), the executive control network with the rostro-medial prefrontal cortex (r = 0.80, p < 0.001), the thalamus with the middle frontal gyrus (r = 0.82, p < 0.001), and the pregenual anterior cingulate cortex with the inferior parietal lobule (r = 0.79, p < 0.001); and stronger rsFC of the anterior insula with the angular gyrus (r =  − 0.81, p < 0.001). The above regions process the attentional and emotional aspects of pain intensity; serve as components of the resting-state networks; are modulated by rTMS; and are altered in FMS. Therefore, we suggest that in FMS, the weaker pre-existing interplay between pain-related brain regions and networks, the larger the pain relief resulting from M1-rTMS.
Polycrystalline silicon PhC cavities for CMOS on-chip integration
Authors: Iadanza S. , Devarapu G. C. R. , Blake A. , Alba P. Acosta , Pedini J.-M. , O’Faolain L.
Published: October 2022

In this work, we present an on-chip 2D and 3D photonics integration solution compatible with Front End of Line integration (FEOL) using deposited polycrystalline silicon (poly:Si) for optical interconnects applications. Deposited silicon integration on a bulk silicon wafer is here discussed in all its processing steps and configurations. Moreover, results of deposited silicon high-Q Photonic Crystal (PhC) resonators are shown, demonstrating the possibility to employ optical resonators patterned on this material in the next generation of 2D and 3D integrated optical interconnects.
Opinion analysis and aspect understanding during covid-19 pandemic using BERT-Bi-LSTM ensemble method
Authors: Wankhade Mayur , Rao Annavarapu Chandra Sekhara
Published: October 2022

Social media platforms significantly increase general information about disease severity and inform preventive measures among community members. To identify public opinion through tweets on the subject of Covid-19 and investigate public sentiment in the country over the period. This article proposed a novel method for sentiment analysis of coronavirus-related tweets using bidirectional encoder representations from transformers (BERT) bi-directional long short-term memory (Bi-LSTM) ensemble learning model. The proposed approach consists of two stages. In the first stage, the BERT model gains the domain knowledge with Covid-19 data and fine-tunes with sentiment word dictionary. The second stage is the Bi-LSTM model, which is used to process the data in a bi-directional way with context sequence dependency preserving to process the data and classify the sentiment. Finally, the ensemble technique combines both models to classify the sentiment into positive and negative categories. The result obtained by the proposed method is better than the state-of-the-art methods. Moreover, the proposed model efficiently understands the public opinion on the Twitter platform, which can aid in formulating, monitoring and regulating public health policies during a pandemic.
Parasitological and malacological surveys to identify transmission sites for Schistosoma mansoni in Gomma District, south-western Ethiopia
Authors: Bekana Teshome , Abebe Endegena , Mekonnen Zeleke , Tulu Begna , Ponpetch Keerati , Liang Song , Erko Berhanu
Published: October 2022

Schistosomiasis is a neglected tropical disease that disproportionately affects the poorest people in tropical and subtropical countries. It is a major parasitic disease causing considerable morbidity in Ethiopia. Despite significant control efforts, schistosomiasis transmission is still widespread in many rural areas of the country. The aim of this study was to determine the prevalence and intensity of intestinal schistosomiasis among schoolchildren, as well as to identify schistosomiasis transmission sites in Gomma District, southwestern Ethiopia. Between October 2018 and September 2019, cross-sectional parasitological and malacological surveys were conducted in the study area. The study comprised 492 school-children aged 6 to 15 years old from four primary schools in Gomma District. To identify and quantify eggs of Schistosoma mansoni from the children, stool specimens were collected and processed using double Kato-Katz thick smears. Water bodies adjacent to human settlements in the study area were surveyed for snail intermediate hosts of S. mansoni. Morphological identification of collected snails was conducted, followed by examining their infection status using a dissecting microscope. The overall prevalence of S. mansoni infection was 73.8% (95%CI: 69.9–77.7%) and 41.6% of them had moderate-to-heavy infections. The prevalence of S. mansoni infection differed considerably by age group, with the older age groups (12–15) having a higher prevalence than the younger age groups (6–11) (p < 0.001). The prevalence of infection also varied significantly among schools; Dedo Ureche had the highest prevalence (86.9%) (p = 0.034), while Goga Kilole had relatively the lowest prevalence of S. mansoni infection (59.6%) (p = 0.003). A total of 1463 Biomphalaria pfeifferi snails were collected from 11 survey sites throughout the study area, with 357 (24.4%) of the snails shedding schistosomes cercariae. Despite intensified efforts to scale up mass drug administration in Ethiopia, this study reported high levels of S. mansoni infection among schoolchildren and snail intermediate hosts in rural communities in Gomma. Such a high infection rate warrants pressing needs for targeted and integrated interventions to control the disease in the area.
Feasibility and impact of whole-body high-intensity interval training in patients with stable coronary artery disease: a randomised controlled trial
Authors: Kristiansen Jacobina , Sjúrðarson Tórur , Grove Erik Lerkevang , Rasmussen Jan , Kristensen Steen Dalby , Hvas Anne-Mette , Mohr Magni
Published: October 2022

Exercise training reduces cardiovascular mortality and improves quality of life in CAD patients. We investigated the feasibility and impact of 12 weeks of low-volume high-intensity interval training (HIIT) in CAD-patients. Patients with stable CAD were randomized 1:1 to supervised HIIT or standard care. HIIT sessions were completed three times weekly for 12 weeks on a rowing ergometer. Before and after the 12-week intervention, patients completed a physiological evaluation of cardiorespiratory performance and quality of life questionnaires. Mixed model analysis was used to evaluate differences between and within groups. A total of 142 patients (67 ± 9 years, nHIIT = 64, nStandard care = 78) completed the trial. Training adherence was 97% (range 86–100%). Six patients dropped out because of non-fatal adverse events. Weekly training duration was 54 min with an average power output of 138 W. HIIT increased peak oxygen uptake by 2.5 mL/kg/min (95% CI 2.1–3.0), whereas no change was observed in standard care (0.2 mL/kg/min, 95% CI − 0.2–0.6, P < 0.001). In addition, HIIT improved markers of quality of life, including physical functioning, limitations due to physical illness, general health and vitality (P < 0.05). Twelve weeks of low-volume whole-body HIIT increased cardiorespiratory capacity and improved quality of life in patients with stable CAD compared to standard care. In addition, our study demonstrates that the applied vigorous training regime is feasible for this patient group.

Clinical trial registration:www.clinicaltrials.gov. Identification number: NCT04268992.
Risk factors for globe removal after open-globe injury in agricultural regions
Authors: Aryasit Orapan , Tassanasunthornwong Chayut , Rattanalert Narisa , Tengtrisorn Supaporn , Singha Penny
Published: October 2022

This study aimed to identify the prevalence and risk factors for globe removal among patients with open-globe injuries (OGIs) in agricultural regions. A retrospective chart review of patients with OGIs was performed between January 2010 and December 2019. Univariable and multivariable logistic regression models were used to identify the factors associated with globe removal in OGI. This study included 422 patients (422 eyes). The highest prevalence of OGI was observed in the middle age group (> 20 to 40 years). The most common cause of OGIs was agriculture-related injury (54.7%), followed by industry or workplace-related injury (20.4%), and assault (5.0%). Intraocular foreign bodies, endophthalmitis, and panophthalmitis were reported in 57.6%, 28.4%, and 5.7% of cases, respectively. Eight eviscerations and 43 enucleations were performed, accounting for 12.1% of OGIs. The most common indication for globe removal was panophthalmitis. Multivariable analysis revealed that the predictive factors significantly associated with globe removal were assault injuries (adjusted odds ratio (aOR) = 5.53; p = 0.026), presenting logarithm of the minimum angle of resolution visual acuity (aOR = 311.79; p < 0.001), and endophthalmitis and panophthalmitis (aOR = 3.58 and 734.94, respectively; p < 0.001). This knowledge would aid in patient counseling and encourage health promotion.