bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Mars GDS 2018 on the Chemistry of Water, Nitrogenated and Deuterated Cluster Ions: NOMAD Observations
Authors: Shah Siddhi Y. , Haider S. A. , Korablev O.
Published: October 2023

The ExoMars Trace Gas Orbiter instruments, Nadir and Occultation for Mars Discovery and Atmospheric Chemistry Suite have provided vertical profiles of H2O and HDO mixing ratios in the presence and absence of Global Dust Storm 2018. These observations are carried out in the lower atmosphere at SZA ∼ 71° of northern mid latitude (∼55°N, 130°E). Using NOMAD observations, we developed chemical models 1 and 2 for dust and non‐dust storm conditions, respectively. The production/loss rates of H2O, HDO and D2O and the densities of water, nitrogenated and deuterated cluster ions (H2O+, D2O+, HDO+, H+(H2O)n, D+(D2O)n, H+(HDO)n, CO4−, CO3−, CO3−(H2O)n, CO3−(D2O)n, CO3−(HDO)n, NO2−(H2O), NO2−(HDO), and NO2−(D2O) (for n = 1 to 5)) are estimated from these models between 10 and 70 km. We have used two ionization sources: (a) Galactic Cosmic Rays (GCR) and (b) hard X‐ray in both models. The D peak density produced by GCR is lower by a factor of ∼5 than that produced by the hard X‐rays. In model 1, the electron densities were increased by a factor of ∼2–3 than that produced by model 2. The estimated production/loss rates of H2O, HDO, and D2O are also larger by an order of magnitude in model 1 than that estimated by model 2.
Decreased B4GALT1 promotes hepatocellular carcinoma cell invasiveness by regulating the laminin-integrin pathway
Authors: Chen Po-Da , Liao Ying-Yu , Cheng Yu-Chia , Wu Hsin-Yi , Wu Yao-Ming , Huang Min-Chuan
Published: October 2023

Beta1,4-galactosyltransferases (B4GALTs) play a crucial role in several diseases, including cancer. B4GALT1 is highly expressed in the liver, and patients with mutations in B4GALT1 exhibit hepatopathy. However, the role of B4GALT1 in liver cancer remains unclear. Here, we found that B4GALT1 was significantly downregulated in hepatocellular carcinoma (HCC) tissue compared with the adjacent liver tissue, and low B4GALT1 expression was associated with vascular invasion and poor overall survival in patients with HCC. Additionally, silencing or loss of B4GALT1 enhanced HCC cell migration and invasion in vitro and promoted lung metastasis of HCC in NOD/SCID mice. Moreover, B4GALT1 knockdown or knockout increased cell adhesion to laminin, whereas B4GALT1 overexpression decreased the adhesion. Through a mass spectrometry-based approach and Griffonia simplicifolia lectin II (GSL-II) pull-down assays, we identified integrins α6 and β1 as the main protein substrates of B4GALT1 and their N-glycans were modified by B4GALT1. Further, the increased cell migration and invasion induced by B4GALT1 knockdown or knockout were significantly reversed using a blocking antibody against integrin α6 or integrin β1. These results suggest that B4GALT1 downregulation alters N-glycosylation and enhances the laminin-binding activity of integrin α6 and integrin β1 to promote invasiveness of HCC cells. Our findings provide novel insights into the role of B4GALT1 in HCC metastasis and highlight targeting the laminin-integrin axis as a potential therapeutic strategy for HCC with low B4GALT1 expression.
Childbirth-related posttraumatic stress symptoms – examining associations with hair endocannabinoid concentrations during pregnancy and lifetime trauma
Authors: Bergunde Luisa , Karl Marlene , Schälicke Sarah , Weise Victoria , Mack Judith T. , von Soest Tilmann , Gao Wei , Weidner Kerstin , Garthus-Niegel Susan , Steudte-Schmiedgen Susann
Published: October 2023

Evidence has linked alterations of the endocannabinoid system with trauma exposure and posttraumatic stress disorder (PTSD). Childbirth-related PTSD symptoms (CB-PTSS) affect about every eighth woman and can negatively influence the entire family. While aetiological models of CB-PTSD include psychological risk factors such as maternal trauma history and negative subjective birth experience (SBE), they lack biological risk indicators. We investigated whether lifetime trauma and CB-PTSS were associated with long-term endocannabinoid concentrations during pregnancy. Further, we tested endocannabinoids as mediators between lifetime trauma and CB-PTSS and whether SBE moderated such mediational paths. Within the prospective cohort study DREAMHAIR, 263 expectant mothers completed trauma assessments and provided hair samples for quantification of long-term endocannabinoid levels (anandamide [AEA], 2-arachidonoylglycerol [1-AG/2-AG], and N-acyl-ethanolamides [NAE]) prior to their anticipated birth date. Two months postpartum, CB-PTSS and SBE were measured. Regression models controlling for relevant confounders showed no association between lifetime trauma and hair endocannabinoids during pregnancy, yet higher number of lifetime trauma events and lower hair AEA were significantly associated with CB-PTSS, with the latter finding not remaining significant when Bonferroni corrections due to multiple testing were applied. While hair AEA did not mediate the association between lifetime trauma and CB-PTSS, the effect of lower hair AEA on CB-PTSS was stronger upon negative SBE. Results suggest greater lifetime trauma and reduced maternal hair AEA during pregnancy may be associated with increased risk for CB-PTSS, particularly upon negative SBE. Findings confirm lifetime trauma as a CB-PTSS risk factor and add important preliminary insights on the role of endocannabinoid ligand alterations and SBE in CB-PTSS pathology.
The association between depressive symptoms and masked hypertension in participants with normotension measured at research center
Authors: Tokioka Sayuri , Nakaya Naoki , Nakaya Kumi , Kogure Mana , Hatanaka Rieko , Chiba Ippei , Kanno Ikumi , Nochioka Kotaro , Metoki Hirohito , Murakami Takahisa , Satoh Michihiro , Nakamura Tomohiro , Ishikuro Mami , Obara Taku , Hamanaka Yohei , Orui Masatsugu , Kobayashi Tomoko , Uruno Akira , Kodama Eiichi N. , Nagaie Satoshi , Ogishima Soichi , Izumi Yoko , Fuse Nobuo , Kuriyama Shinichi , Hozawa Atsushi
Published: October 2023

Masked hypertension is a risk factor for cardiovascular diseases. However, masked hypertension is sometimes overlooked owing to the requirement for home blood pressure measurements for diagnosing. Mental status influences blood pressure. To reduce undiagnosed masked hypertension, this study assessed the association between depressive symptoms and masked hypertension. This cross-sectional study used data from the Tohoku Medical Megabank Project Community-Based Cohort Study (conducted in Miyagi Prefecture, Japan, from 2013) and included participants with normotension measured at the research center (systolic blood pressure<140 mmHg and diastolic blood pressure <90 mmHg). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (Japanese version). Masked hypertension was defined as normotension measured at the research center and home hypertension (home systolic blood pressure ≥135 mmHg or home diastolic blood pressure ≥85 mmHg). The study comprised 6705 participants (mean age: 55.7 ± 13.7 years). Of these participants, 1106 (22.1%) without depressive symptoms and 393 (23.2%) with depressive symptoms were categorized to have masked hypertension. Sex-specific and age-adjusted least mean squares for home blood pressure, not for research blood pressure were significantly higher in the group with depressive symptoms in both sex categories. The multivariate odds ratio for masked hypertension in the patients with depressive symptoms was 1.72 (95% confidence interval: 1.26–2.34) in male participants and 1.30 (95% confidence interval: 1.06–1.59) in female ones. Depressive symptoms were associated with masked hypertension in individuals with normotension measured at the research center. Depressive symptoms may be one of the risk factors for masked hypertension.
Auxiliary sequential deposition enables 19%-efficiency organic solar cells processed from halogen-free solvents
Authors: Luo Siwei , Li Chao , Zhang Jianquan , Zou Xinhui , Zhao Heng , Ding Kan , Huang Hui , Song Jiali , Yi Jicheng , Yu Han , Wong Kam Sing , Zhang Guangye , Ade Harald , Ma Wei , Hu Huawei , Sun Yanming , Yan He
Published: October 2023

High-efficiency organic solar cells are often achieved using toxic halogenated solvents and additives that are constrained in organic solar cells industry. Therefore, it is important to develop materials or processing methods that enabled highly efficient organic solar cells processed by halogen free solvents. In this paper, we report an innovative processing method named auxiliary sequential deposition that enables 19%-efficiency organic solar cells processed by halogen free solvents. Our auxiliary sequential deposition method is different from the conventional blend casting or sequential deposition methods in that it involves an additional casting of dithieno[3,2-b:2’,3’-d]thiophene between the sequential depositions of the donor (D18-Cl) and acceptor (L8-BO) layers. The auxiliary sequential deposition method enables dramatic performance enhancement from 15% to over 18% compared to the blend casting and sequential deposition methods. Furthermore, by incorporating a branched-chain-engineered acceptor called L8-BO-X, device performance can be boosted to over 19% due to increased intermolecular packing, representing top-tier values for green-solvent processed organic solar cells. Comprehensive morphological and time-resolved characterizations reveal that the superior blend morphology achieved through the auxiliary sequential deposition method promotes charge generation while simultaneously suppressing charge recombination. This research underscores the potential of the auxiliary sequential deposition method for fabricating highly efficient organic solar cells using environmentally friendly solvents.
Graphene/silicon heterojunction for reconfigurable phase-relevant activation function in coherent optical neural networks
Authors: Zhong Chuyu , Liao Kun , Dai Tianxiang , Wei Maoliang , Ma Hui , Wu Jianghong , Zhang Zhibin , Ye Yuting , Luo Ye , Chen Zequn , Jian Jialing , Sun Chunlei , Tang Bo , Zhang Peng , Liu Ruonan , Li Junying , Yang Jianyi , Li Lan , Liu Kaihui , Hu Xiaoyong , Lin Hongtao
Published: October 2023

Optical neural networks (ONNs) herald a new era in information and communication technologies and have implemented various intelligent applications. In an ONN, the activation function (AF) is a crucial component determining the network performances and on-chip AF devices are still in development. Here, we first demonstrate on-chip reconfigurable AF devices with phase activation fulfilled by dual-functional graphene/silicon (Gra/Si) heterojunctions. With optical modulation and detection in one device, time delays are shorter, energy consumption is lower, reconfigurability is higher and the device footprint is smaller than other on-chip AF strategies. The experimental modulation voltage (power) of our Gra/Si heterojunction achieves as low as 1 V (0.5 mW), superior to many pure silicon counterparts. In the photodetection aspect, a high responsivity of over 200 mA/W is realized. Special nonlinear functions generated are fed into a complex-valued ONN to challenge handwritten letters and image recognition tasks, showing improved accuracy and potential of high-efficient, all-component-integration on-chip ONN. Our results offer new insights for on-chip ONN devices and pave the way to high-performance integrated optoelectronic computing circuits.
Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis
Authors: Ng Jia Q. , Jafarov Toghrul H. , Little Christopher B. , Wang Tongtong , Ali Abdullah M. , Ma Yan , Radford Georgette A. , Vrbanac Laura , Ichinose Mari , Whittle Samuel , Hunter David J. , Lannagan Tamsin R. M. , Suzuki Nobumi , Goyne Jarrad M. , Kobayashi Hiroki , Wang Timothy C. , Haynes David R. , Menicanin Danijela , Gronthos Stan , Worthley Daniel L. , Woods Susan L. , Mukherjee Siddhartha
Published: October 2023

Osteoarthritis (OA) is characterised by an irreversible degeneration of articular cartilage. Here we show that the BMP-antagonistGremlin 1(Grem1) marks a bipotent chondrogenic and osteogenic progenitor cell population within the articular surface. Notably, these progenitors are depleted by injury-induced OA and increasing age. OA is also caused by ablation ofGrem1cells in mice. Transcriptomic and functional analysis in mice found that articular surfaceGrem1-lineage cells are dependent onFoxo1and ablation ofFoxo1inGrem1-lineage cells caused OA. FGFR3 signalling was confirmed as a promising therapeutic pathway by administration of pathway activator, FGF18, resulting inGrem1-lineage chondrocyte progenitor cell proliferation, increased cartilage thickness and reduced OA. These findings suggest that OA, in part, is caused by mechanical, developmental or age-related attrition ofGrem1expressing articular cartilage progenitor cells. These cells, and the FGFR3 signalling pathway that sustains them, may be effective future targets for biological management of OA.
Inferring bacterial transmission dynamics using deep sequencing genomic surveillance data
Authors: Senghore Madikay , Read Hannah , Oza Priyali , Johnson Sarah , Passarelli-Araujo Hemanoel , Taylor Bradford P. , Ashley Stephen , Grey Alex , Callendrello Alanna , Lee Robyn , Goddard Matthew R. , Lumley Thomas , Hanage William P. , Wiles Siouxsie
Published: October 2023

Identifying and interrupting transmission chains is important for controlling infectious diseases. One way to identify transmission pairs – two hosts in which infection was transmitted from one to the other – is using the variation of the pathogen within each single host (within-host variation). However, the role of such variation in transmission is understudied due to a lack of experimental and clinical datasets that capture pathogen diversity in both donor and recipient hosts. In this work, we assess the utility of deep-sequenced genomic surveillance (where genomic regions are sequenced hundreds to thousands of times) using a mouse transmission model involving controlled spread of the pathogenic bacterium Citrobacter rodentium from infected to naïve female animals. We observe that within-host single nucleotide variants (iSNVs) are maintained over multiple transmission steps and present a model for inferring the likelihood that a given pair of sequenced samples are linked by transmission. In this work we show that, beyond the presence and absence of within-host variants, differences arising in the relative abundance of iSNVs (allelic frequency) can infer transmission pairs more precisely. Our approach further highlights the critical role bottlenecks play in reserving the within-host diversity during transmission.
SEI growth on Lithium metal anodes in solid-state batteries quantified with coulometric titration time analysis
Authors: Aktekin Burak , Riegger Luise M. , Otto Svenja-K. , Fuchs Till , Henss Anja , Janek Jürgen
Published: October 2023

Lithium-metal batteries with a solid electrolyte separator are promising for advanced battery applications, however, most electrolytes show parasitic side reactions at the low potential of lithium metal. Therefore, it is essential to understand how much (and how fast) charge is consumed in these parasitic reactions. In this study, a new electrochemical method is presented for the characterization of electrolyte side reactions occurring on active metal electrode surfaces. The viability of this new method is demonstrated in a so-called anode-free stainless steel ∣ Li6PS5Cl ∣ Li cell. The method also holds promise for investigating dendritic lithium growth (and dead lithium formation), as well as for analyzing various electrolytes and current collectors. The experimental setup allows easy electrode removal for post-mortem analysis, and the SEI’s heterogeneous/layered microstructure is revealed through complementary analytical techniques. We expect this method to become a valuable tool in the future for solid-state lithium metal batteries and potentially other cell chemistries.
Antigen presentation by B cells enables epitope spreading across an MHC barrier
Authors: Fahlquist-Hagert Cecilia , Wittenborn Thomas R. , Terczyńska-Dyla Ewa , Kastberg Kristian Savstrup , Yang Emily , Rallistan Alysa Nicole , Markett Quinton Raymond , Winther Gudrun , Fonager Sofie , Voss Lasse F. , Pedersen Mathias K. , van Campen Nina , Ferapontov Alexey , Jensen Lisbeth , Huang Jinrong , Nieland John D. , van der Poel Cees E. , Palmfeldt Johan , Carroll Michael C. , Utz Paul J. , Luo Yonglun , Lin Lin , Degn Søren E.
Published: October 2023

Circumstantial evidence suggests that B cells may instruct T cells to break tolerance. Here, to test this hypothesis, we used a murine model in which a single B cell clone precipitates an autoreactive response resembling systemic lupus erythematosus (SLE). The initiating clone did not need to enter germinal centers to precipitate epitope spreading. Rather, it localized to extrafollicular splenic bridging channels early in the response. Autoantibody produced by the initiating clone was not sufficient to drive the autoreactive response. Subsequent epitope spreading depended on antigen presentation and was compartmentalized by major histocompatibility complex (MHC). B cells carrying two MHC haplotypes could bridge the MHC barrier between B cells that did not share MHC. Thus, B cells directly relay autoreactivity between two separate compartments of MHC-restricted T cells, leading to inclusion of distinct B cell populations in germinal centers. Our findings demonstrate that B cells initiate and propagate the autoimmune response.
Gate-controlled suppression of light-driven proton transport through graphene electrodes
Authors: Huang S. , Griffin E. , Cai J. , Xin B. , Tong J. , Fu Y. , Kravets V. , Peeters F. M. , Lozada-Hidalgo M.
Published: October 2023

Recent experiments demonstrated that proton transport through graphene electrodes can be accelerated by over an order of magnitude with low intensity illumination. Here we show that this photo-effect can be suppressed for a tuneable fraction of the infra-red spectrum by applying a voltage bias. Using photocurrent measurements and Raman spectroscopy, we show that such fraction can be selected by tuning the Fermi energy of electrons in graphene with a bias, a phenomenon controlled by Pauli blocking of photo-excited electrons. These findings demonstrate a dependence between graphene’s electronic and proton transport properties and provide fundamental insights into molecularly thin electrode-electrolyte interfaces and their interaction with light.
Cyclic fasting bolsters cholesterol biosynthesis inhibitors’ anticancer activity
Authors: Khalifa Amr , Guijarro Ana , Ravera Silvia , Bertola Nadia , Adorni Maria Pia , Papotti Bianca , Raffaghello Lizzia , Benelli Roberto , Becherini Pamela , Namatalla Asmaa , Verzola Daniela , Reverberi Daniele , Monacelli Fiammetta , Cea Michele , Pisciotta Livia , Bernini Franco , Caffa Irene , Nencioni Alessio
Published: October 2023

Identifying oncological applications for drugs that are already approved for other medical indications is considered a possible solution for the increasing costs of cancer treatment. Under the hypothesis that nutritional stress through fasting might enhance the antitumour properties of at least some non-oncological agents, by screening drug libraries, we find that cholesterol biosynthesis inhibitors (CBIs), including simvastatin, have increased activity against cancers of different histology under fasting conditions. We show fasting’s ability to increase CBIs’ antitumour effects to depend on the reduction in circulating insulin, insulin-like growth factor-1 and leptin, which blunts the expression of enzymes from the cholesterol biosynthesis pathway and enhances cholesterol efflux from cancer cells. Ultimately, low cholesterol levels through combined fasting and CBIs reduce AKT and STAT3 activity, oxidative phosphorylation and energy stores in the tumour. Our results support further studies of CBIs in combination with fasting-based dietary regimens in cancer treatment and highlight the value of fasting for drug repurposing in oncology.
Organomediated electrochemical fluorosulfonylation of aryl triflates via selective C–O bond cleavage
Authors: Kong Xianqiang , Chen Yiyi , Chen Xiaohui , Ma Cheng , Chen Ming , Wang Wei , Xu Yuan-Qing , Ni Shao-Fei , Cao Zhong-Yan
Published: October 2023

Although aryl triflates are essential building blocks in organic synthesis, the applications as aryl radical precursors are limited. Herein, we report an organomediated electrochemical strategy for the generation of aryl radicals from aryl triflates, providing a useful method for the synthesis of aryl sulfonyl fluorides from feedstock phenol derivatives under very mild conditions. Mechanistic studies indicate that key to success is to use catalytic amounts of 9, 10-dicyanoanthracene as an organic mediator, enabling to selectively active aryl triflates to form aryl radicals via orbital-symmetry-matching electron transfer, realizing the anticipated C–O bond cleavage by overcoming the competitive S–O bond cleavage. The transition-metal-catalyst-free protocol shows good functional group tolerance, and may overcome the shortages of known methods for aryl sulfonyl fluoride synthesis. Furthermore, this method has been used for the modification and formal synthesis of bioactive molecules or tetraphenylethylene (TPE) derivative with improved quantum yield of fluorescence.
Revealing the role of double-layer microenvironments in pH-dependent oxygen reduction activity over metal-nitrogen-carbon catalysts
Authors: Li Peng , Jiao Yuzhou , Ruan Yaner , Fei Houguo , Men Yana , Guo Cunlan , Wu Yuen , Chen Shengli
Published: October 2023

A standing puzzle in electrochemistry is that why the metal-nitrogen-carbon catalysts generally exhibit dramatic activity drop for oxygen reduction when traversing from alkaline to acid. Here, taking FeCo-N6-C double-atom catalyst as a model system and combining the ab initio molecular dynamics simulation and in situ surface-enhanced infrared absorption spectroscopy, we show that it is the significantly distinct interfacial double-layer structures, rather than the energetics of multiple reaction steps, that cause the pH-dependent oxygen reduction activity on metal-nitrogen-carbon catalysts. Specifically, the greatly disparate charge densities on electrode surfaces render different orientations of interfacial water under alkaline and acid oxygen reduction conditions, thereby affecting the formation of hydrogen bonds between the surface oxygenated intermediates and the interfacial water molecules, eventually controlling the kinetics of the proton-coupled electron transfer steps. The present findings may open new and feasible avenues for the design of advanced metal-nitrogen-carbon catalysts for proton exchange membrane fuel cells.
The effect of metformin therapy on serum thyrotropin and free thyroxine concentrations in patients with type 2 diabetes: a meta-analysis
Authors: Amirabadizadeh Alireza , Amouzegar Atieh , Mehran Ladan , Azizi Fereidoun
Published: October 2023

Type 2 diabetes and thyroid function disorders are two common chronic endocrine disorders with the high prevalence in various populations. Metformin is well established as the first-line drug therapy for managing diabetes mellitus. In this meta-analysis, we aimed to determine the effect of metformin on serum TSH and FT4 concentrations in patients with type 2 diabetes. We searched PubMed, Scopus, web of science, Cochrane library, and google scholar to collect information on the effect of metformin on serum TSH and FT4 levels. Demographic and clinical information and serum TSH and FT4 concentrations before and after metformin treatment were extracted. Studies on patients over 18 years of age were included. A total of 11 studies including 1147 patients were selected for the final analysis. In hypothyroid patients, the TSH level decreased significantly after treatment with metformin (Hedges’s g:1.55, 95%CI 0.93–2.16, p-value < 0.001); FT4 level increased slightly after taking metformin, but the increase was not significant (Heddges’s g: − 0.30, 95%CI  − 0.90,0.31, p-value = 0.34). In euthyroid subjects, the slight decrease found in TSH and FT4 concentrations was not statistically significant. Metformin reduces TSH levels in hypothyroid patients; however, it has no effect on TSH levels in euthyroid patients. Metformin does not affect serum FT4 levels in euthyroid and hypothyroid patients.
Perceived financial well-being and its association with frontostriatal functional connectivity, real-life anticipatory experiences, and everyday happiness
Authors: Shin Won-Gyo , Jyung Mina , Choi Incheol , Sul Sunhae
Published: October 2023

Perceived financial well-being (FWB) is an important aspect of life that can affect one’s attitude toward future experiences and happiness. However, the relationship between FWB, anticipatory experiences, and happiness, and the brain’s functional architecture underlying this relationship remain unknown. Here, we combined an experience sampling method, multilevel modeling, and functional neuroimaging to identify the neural correlates of FWB and their associations with real-world anticipatory experiences and everyday happiness. Behaviorally, we found that individuals with greater FWB felt more positive and more interested when they expected positive events to occur, which in turn resulted in increased everyday happiness. Furthermore, the level of FWB was significantly associated with the strength of functional connectivity (FC) between the nucleus accumbens (NAc) and ventromedial prefrontal cortex (vmPFC) and the local coherence within the vmPFC. The frontostriatal FC and local coherence within the vmPFC were further predictive of everyday happiness via the anticipatory response involving interestedness during positive expectations. Our findings suggest that individual differences in FWB could be reflected in the functional architecture of brain’s reward system that may contribute to shaping positive anticipatory experiences and happiness in daily life.
The possible dual role of Ang-2 in the prognosis of pancreatic cancer
Authors: Roos-Mattila Matilda , Kaprio Tuomas , Mustonen Harri , Hagström Jaana , Saharinen Pipsa , Haglund Caj , Seppänen Hanna
Published: October 2023

Pancreatic ductal adenocarcinoma (PDAC) features a dense desmoplastic stroma, which raises the intratumoral interstitial pressure leading to vascular collapse and hypoxia, inducing angiogenesis. Vascular growth factors, such as vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), increase in PDAC. A high VEGF and a high circulating Ang-2 associate with shorter survival in PDAC. In addition to the circulatory Ang-2, PDAC endothelial and epithelial cells express Ang-2. No correlation between tumor epithelial nor endothelial cell Ang-2 expression and survival has been published. We aimed to examine Ang-2 expression and survival. This study comprised PDAC surgical patients at Helsinki University Hospital in 2000–2013. Ang-2 immunohistochemistry staining was completed on 168 PDAC patient samples. Circulating Ang-2 levels were measured using ELISA in the sera of 196 patients. Ang-2 levels were assessed against clinical data and patient outcomes. A low tumor epithelial Ang-2 expression predicted shorter disease-specific survival (DSS) compared with a high expression (p = 0.003). A high serum Ang-2 associated with shorter DSS compared with a low circulating Ang-2 (p = 0.016). Ang-2 seemingly plays a dual role in PDAC survival. Further studies are needed to determine the mechanisms causing tumor cell Ang-2 expression and its positive association with survival.
Assessment of pathogen removal efficiency of vertical flow constructed wetland treating septage
Authors: Singh Swati , Upadhyay Sweta , Rani Anju , Sharma Pradeep Kumar , Rawat Janhvi Mishra , Rawat Balwant , Prashant  , Bhattacharya Prosun
Published: October 2023

Septage refers to the semi-liquid waste material that accumulates in septic tanks and other onsite sanitation systems. It is composed of a complex mixture of human excreta, wastewater, and various solid particles. Septage is a potential source of water pollution owing to presence of high organic content, significant pathogen concentrations, and a range of nutrients like nitrogen and phosphorus. The harmful impacts of septage pollution poses significant risks to public health through the contamination of drinking water sources, eutrophication of water bodies and spread of water borne diseases. Conventional septage treatment technologies often face limitations such as high operational costs, energy requirements, and the need for extensive infrastructure. Therefore, with an aim to treat septage through an alternative cost effective and energy-efficient technology, a laboratory-scale constructed wetland (CW) system (0.99 m2) consisting of a sludge drying bed and a vertical flow wetland bed was utilized for the treatment of septage. The sludge drying bed and vertical flow beds were connected in series and filled with a combination of gravel with varying sizes (ranging from 5 to 40 mm) and washed sand. Canna indica plants were cultivated on both beds to facilitate phytoremediation process. The system was operated with intermittent dosing of 30 Ltrs of septage every day for 2 months. The HRT of the system was fixed at 48 h. The average inlet loads of Biochemical Oxygen Demand (BOD5), Chemical Oxygen Demand (COD), and Total Suspended Solids (TSS) were measured as 150 ± 65.7 g m−2 day−1, 713 ± 443.9 g m−2 day−1, and 309 ± 66.3 g m−2 day−1, respectively. After treatment, the final effluent had an average load of 6 g m−2 day−1 for BOD5, 15 g m−2 day−1 for COD, and 51 g m−2 day−1 for TSS, indicating that the CW system achieved an average removal efficiency of 88% for BOD, 87% for COD, and 65% for TSS. The average load of total coliforms and helminthes eggs in the influent was recorded as 4 × 108 Colony-Forming Units (CFU) m−2 day−1 and 3 × 107 eggs m−2 day−1, respectively. However, the CW system demonstrated significant effectiveness in reducing microbial contamination, with an average removal efficiency of 99% for both total coliforms and helminthes eggs. The vertical flow constructed wetland system, equipped with pretreatment by sludge drying bed, has proven to be efficient in treatment of septage.
HOPS, CORVET and newly-identified Hybrid tethering complexes contribute differentially towards multiple modes of endocytosis
Authors: Terawaki Seigo , Vasilev Filipp , Moriwaki Takahito , Otomo Takanobu
Published: October 2023

Vesicular transport driven by membrane trafficking systems conserved in eukaryotes is critical to cellular functionality and homeostasis. It is known that homotypic fusion and vacuole protein sorting (HOPS) and class C core endosomal vacuole tethering (CORVET) interact with Rab-GTPases and SNARE proteins to regulate vesicle transport, fusion, and maturation in autophagy and endocytosis pathways. In this study, we identified two novel “Hybrid” tethering complexes in mammalian cells in which one of the subunits of HOPS or CORVET is replaced with the subunit from the other. Substrates taken up by receptor-mediated endocytosis or pinocytosis were transported by distinctive pathways, and the newly identified hybrid complexes contributed to pinocytosis in the presence of HOPS, whereas receptor-mediated endocytosis was exclusively dependent on HOPS. Our study provides new insights into the molecular mechanisms of the endocytic pathway and the function of the vacuolar protein sorting-associated (VPS) protein family.
Comparison of the tidal volume by the recruitment maneuver combined with positive end-expiratory pressure for mechanically ventilated children
Authors: Tsukamoto Masanori , Goto Maho , Hitosugi Takashi , Matsuo Kazuya , Yokoyama Takeshi
Published: October 2023

The recruitment maneuver (RM) combined with PEEP to prevent atelectasis have beneficial effects. However, the change in tidal volume (VT) due to RM combined with PEEP in pediatric patients during the induction of general anesthesia is unknown. Therefore, we assessed the effects of RM combined with PEEP on VT. Pediatric patients were divided into three groups: infants, preschool children, and school children. The RM was performed by maintaining pressure control continuous mandatory ventilation (PC-CMV) with a 15 cmH2O and PEEP increase of 5 cmH2O. VT, respiratory function and hemodynamics were monitored before and after RM combined with PEEP. VT (mL) /ideal body weight (kg) before vs. after RM combined with PEEP were 9 vs 12 mL/kg (p < 0.05) in the infants, 9 vs 11 mL/kg (p < 0.05) in the preschool children, 8 vs 10 mL/kg (p < 0.05) in the school children, respectively. HR and BP before and after RM combined with PEEP increased by 2–3% and decreased by 4–7% in all groups. RM combined with PEEP resulted in an increase in VT per ideal body weight (1.1–1.2%). Therefore, this RM combined with PEEP method might improve the lung function in pediatric patients.
Significant up-regulation of lncRNAs in neuromyelitis optica spectrum disorder
Authors: Taheri Mohammad , Sadeghi Ahmad , Gharebaghi Alireza , Ghiasian Masoud , Eslami Solat , Khalilian Sheyda , Sayad Arezou , Ghafouri-Fard Soudeh
Published: October 2023

Neuromyelitis optica spectrum disorder (NMOSD) is an immune-related demyelinating defect. Long non-coding RNAs (lncRNAs) might influence the pathobiology and progression of NMOSD. The current study assessed expression level of NEAT1, PANDAR, MEG3 and TUG1 lncRNAs in the peripheral blood of NMOSD patients compared with healthy individuals. All mentioned lncRNAs were shown to be over-expressed in total NMOSD cases, male NMOSD cases and female NMOSD cases compared with the matching control subgroups. MEG3 had the most robust over-expression in patients subgroups compared with normal subjects. There was no noteworthy difference in the expression of any of lncRNAs between female and male patients. MEG3 had an ideal performance in the differentiation of NMOSD cases from healthy persons (Sensitivity and specificity values = 100%). Other lncRNAs could also efficiently separate NMOSD cases from control subjects (AUC values = 0.97, 0.89 and 0.88 for PANDAR, NEAT1 and TUG1, respectively). Cumulatively, NEAT1, PANDAR, MEG3 and TUG1 lncRNAs can be considered as appropriate disease markers for NMOSD.
Apelin is expressed in intimal smooth muscle cells and promotes their phenotypic transition
Authors: Cardoso Dos Santos Luís Miguel , Azar Pascal , Brun Cécile , König Stéphane , Roatti Angela , Baertschi Alex J. , Chaabane Chiraz , Bochaton-Piallat Marie-Luce
Published: October 2023

During atherosclerotic plaque formation, smooth muscle cells (SMCs) switch from a contractile/differentiated to a synthetic/dedifferentiated phenotype. We previously isolated differentiated spindle-shaped (S) and dedifferentiated rhomboid (R) SMCs from porcine coronary artery. R-SMCs express S100A4, a calcium-binding protein. We investigated the role of apelin in this phenotypic conversion, as well as its relationship with S100A4. We found that apelin was highly expressed in R-SMCs compared with S-SMCs. We observed a nuclear expression of apelin in SMCs within experimentally-induced intimal thickening of the porcine coronary artery and rat aorta. Plasmids targeting apelin to the nucleus (N. Ap) and to the secretory vesicles (S. Ap) were transfected into S-SMCs where apelin was barely detectable. Both plasmids induced the SMC transition towards a R-phenotype. Overexpression of N. Ap, and to a lesser degree S. Ap, led to a nuclear localization of S100A4. Stimulation of S-SMCs with platelet-derived growth factor-BB, known to induce the transition toward the R-phenotype, yielded the direct interaction and nuclear expression of both apelin and S100A4. In conclusion, apelin induces a SMC phenotypic transition towards the synthetic phenotype. These results suggest that apelin acts via nuclear re-localization of S100A4, raising the possibility of a new pro-atherogenic relationship between apelin and S100A4.
A fast direct solver for surface-based whole-head modeling of transcranial magnetic stimulation
Authors: Makaroff S. N. , Qi Z. , Rachh M. , Wartman W. A. , Weise K. , Noetscher G. M. , Daneshzand M. , Deng Zhi-De , Greengard L. , Nummenmaa A. R.
Published: October 2023

When modeling transcranial magnetic stimulation (TMS) in the brain, a fast and accurate electric field solver can support interactive neuronavigation tasks as well as comprehensive biophysical modeling. We formulate, test, and disseminate a direct (i.e., non-iterative) TMS solver that can accurately determine global TMS fields for any coil type everywhere in a high-resolution MRI-based surface model with ~ 200,000 or more arbitrarily selected observation points within approximately 5 s, with the solution time itself of 3 s. The solver is based on the boundary element fast multipole method (BEM-FMM), which incorporates the latest mathematical advancement in the theory of fast multipole methods—an FMM-based LU decomposition. This decomposition is specific to the head model and needs to be computed only once per subject. Moreover, the solver offers unlimited spatial numerical resolution. Despite the fast execution times, the present direct solution is numerically accurate for the default model resolution. In contrast, the widely used brain modeling software SimNIBS employs a first-order finite element method that necessitates additional mesh refinement, resulting in increased computational cost. However, excellent agreement between the two methods is observed for various practical test cases following mesh refinement, including a biophysical modeling task. The method can be readily applied to a wide range of TMS analyses involving multiple coil positions and orientations, including image-guided neuronavigation. It can even accommodate continuous variations in coil geometry, such as flexible H-type TMS coils. The FMM-LU direct solver is freely available to academic users.
The development and cross-national validation of the short health literacy for school-aged children (HLSAC-5) instrument
Authors: Paakkari Olli , Kulmala Markus , Lyyra Nelli , Torppa Minna , Mazur Joanna , Boberova Zuzana , Paakkari Leena
Published: October 2023

Health literacy is an asset for and indicator of adolescents’ health and wellbeing, and should therefore be monitored and addressed across countries. This study aimed to develop and validate a shorter version of the original 10-item health literacy for school-aged children instrument in a cross-national context, using data from the health behaviour in school-aged children 2017/18 survey. The data were obtained from 25 425 adolescents (aged 13 and 15 years) from seven European countries. Determination was made of the best item combination to form a shorter version of the health literacy instrument. Thereafter, the structural validity, reliability, measurement invariance, and criterion validity of the new 5-item instrument were examined. Confirmatory factor analysis showed a good model fit to the data across countries and in the total sample, confirming the structural validity (CFI = 0.995, TLI = 0.989, SRMR = 0.011, RMSEA = 0.031). The internal consistency of the instrument was at a good level across countries (α = 0.87–0.98), indicating that the instrument provided reliable scores. Configural and metric invariance was established across genders, ages, and countries. Scalar invariance was achieved for age and gender groups, but not between countries. This indicated that the factor structure of the scale was similar, but that there were differences between the countries in health literacy levels. Regarding criterion validity, structural equation modelling showed a positive association between health literacy and self-rated health in all the participating countries. The new instrument was found to be valid and reliable for the purposes of measuring health literacy among adolescents in a cross-national context.
An optimization case study for solving a transport robot scheduling problem on quantum-hybrid and quantum-inspired hardware
Authors: Leib Dominik , Seidel Tobias , Jäger Sven , Heese Raoul , Jones Caitlin , Awasthi Abhishek , Niederle Astrid , Bortz Michael
Published: October 2023

We present a comprehensive case study comparing the performance of D-Waves’ quantum-classical hybrid framework, Fujitsu’s quantum-inspired digital annealer, and Gurobi’s state-of-the-art classical solver in solving a transport robot scheduling problem. This problem originates from an industrially relevant real-world scenario. We provide three different models for our problem following different design philosophies. In our benchmark, we focus on the solution quality and end-to-end runtime of different model and solver combinations. We find promising results for the digital annealer and some opportunities for the hybrid quantum annealer in direct comparison with Gurobi. Our study provides insights into the workflow for solving an application-oriented optimization problem with different strategies, and can be useful for evaluating the strengths and weaknesses of different approaches.
Exploring the significance of interleukin-33/ST2 axis in minimal change disease
Authors: Kanazawa Nobuhiro , Iyoda Masayuki , Suzuki Taihei , Tachibana Shohei , Nagashima Ryuichi , Honda Hirokazu
Published: October 2023

Minimal change disease (MCD), a common cause of idiopathic nephrotic syndrome, has been postulated to exhibit an association with allergic conditions. Recent studies revealed the crucial role of interleukin (IL)-33 in type 2 innate immunity. We hypothesized that development of MCD involves an IL-33–related immune response. We examined 49 patients with biopsy-proven MCD, 6 healthy volunteers, and 29 patients in remission. In addition to clinical features, serum and urinary levels of IL-33 and soluble suppression of tumorigenicity 2 protein (sST2), a secreted form of the receptor of IL-33, were analyzed. Although IL-33 was barely detectable in either MCD or control samples, sST2 levels at diagnosis were elevated in MCD patients. Serum sST2 levels of MCD patients were correlated with serum total protein level (r =  − 0.36, p = 0.010) and serum creatinine level (r = 0.34, p = 0.016). Furthermore, the elevated sST2 levels were observed to decrease following remission. Immunofluorescence revealed IL-33 expression in the podocytes among MCD patients, with a significant increase compared with controls. In vitro, mouse podocyte cells incubated with serum from a MCD patient at disease onset showed increased IL-33 secretion. These results suggest an IL-33–related immune response plays a role in MCD.
Histological classification of Japanese IgA nephropathy with a small number of glomeruli using Bayes’ theorem
Authors: Nakata Takeshi , Tanigawa Masato , Fukuda Akihiro , Shibata Hirotaka
Published: October 2023

In Japan an original pathological classification of IgA nephropathy was used, while Oxford classification of IgA nephropathy was used globally. The Oxford classification requires ≥ 8 glomeruli while the Japanese classification requires ≥ 10. Ninety-nine patients diagnosed with IgA nephropathy were included. To determine the accuracy of histological staging, we calculated the posterior probability using Bayes' theorem and adopted three model of prior distribution. First, the actual staging distribution was reclassified using the beta distribution (reclassified distribution). Second a model with the same distribution (actual distribution) as the actual staging was used. Third, a model assuming that all cases are equally distributed (equal distribution) was used. The median number of collected glomeruli was 12 (8–19). There were 33 cases (33%) wherein the glomerular count was ≤ 9. When only cases with ≥ 10 glomeruli were included, the median posterior probability was 91% (74–99) (actual distribution, 90% [74–98]; equal distribution, 85% [73–96]). Even among the 33 cases with ≤ 9 glomeruli, there were approximately 7 cases in which the posterior probability was ≥ 90% for each model. Using Bayesian probabilistic analysis, it was possible to evaluate the histologic classification of IgA nephropathy, even when the number of obtained glomeruli was ≤ 9.
Comparison of anterior column reconstruction techniques after en bloc spondylectomy: a finite element study
Authors: Pokorni Agoston Jakab , Turbucz Mate , Kiss Rita Maria , Eltes Peter Endre , Lazary Aron
Published: October 2023

Total en bloc spondylectomy (TES) effectively treats spinal tumors. The surgery requires a vertebral body replacement (VBR), for which several solutions were developed, whereas the biomechanical differences between these devices still need to be completely understood. This study aimed to compare a femur graft, a polyetheretherketone implant (PEEK-IMP-C), a titan mesh cage (MESH-C), and a polymethylmethacrylate replacement (PMMA-C) using a finite element model of the lumbar spine after a TES of L3. Several biomechanical parameters (rotational stiffness, segmental range of motion (ROM), and von Mises stress) were assessed to compare the VBRs. All models provided adequate initial stability by increasing the rotational stiffness and decreasing the ROM between L2 and L4. The PMMA-C had the highest stiffness for flexion–extension, lateral bending, and axial rotation (215%, 216%, and 170% of intact model), and it had the lowest segmental ROM in the instrumented segment (0.2°, 0.5°, and 0.7°, respectively). Maximum endplate stress was similar for PMMA-C and PEEK-IMP-C but lower for both compared to MESH-C across all loading directions. These results suggest that PMMA-C had similar or better primary spinal stability than other VBRs, which may be related to the larger contact surface and the potential to adapt to the patient’s anatomy.
Transcriptome analysis of Corvus splendens reveals a repertoire of antimicrobial peptides
Authors: Kannoth Shalini , Ali Nemat , Prasanth Ganesh K. , Arvind Kumar , Mohany Mohamed , Hembrom Preety Sweta , Sadanandan Shemmy , Vasu Deepa Azhchath , Grace Tony
Published: October 2023

Multidrug resistance has become a global health problem associated with high morbidity and mortality. Antimicrobial peptides have been acknowledged as potential leads for prospective anti-infectives. Owing to their scavenging lifestyle, Corvus splendens is thought to have developed robust immunity to pathogens found in their diet, implying that they have evolved mechanisms to resist infection. In the current study, the transcriptome of C. splendens was sequenced, and de novo assembled to identify the presence of antimicrobial peptide genes. 72.09 million high-quality clean reads were obtained which were then de novo assembled into 3,43,503 transcripts and 74,958 unigenes. About 37,559 unigenes were successfully annotated using SwissProt, Pfam, GO, and KEGG databases. A search against APD3, CAMPR3 and LAMP databases identified 63 AMP candidates belonging to more than 20 diverse families and functional classes. mRNA of AvBD-2, AvBD-13 and CATH-2 were found to be differentially expressed between the three tested crows as well as among the tissues. We also characterized Corvus Cathelicidin 2 (CATH-2) to gain knowledge of its antimicrobial mechanisms. The CD spectroscopy of synthesized mature Corvus CATH-2 peptide displayed an amphipathic α-helical structure. Though the synthetic CATH-2 caused hemolysis of human RBC, it also exhibited antimicrobial activity against E. coli, S. aureus, and B. cereus. Docking simulation results revealed that this peptide could bind to the LPS binding site of MD-2, which may prevent LPS from entering the MD-2 binding pocket, and trigger TLR4 signaling pathway. The Corvus CATH-2 characterized in this study could aid in the development of novel therapeutics.