bluuebunny/crossref_metadata_2025 huggingface dataset:
The End of Loneliness: Guardini, Rilke, and the Communion of Saints
Authors: DeLorenzo Leonard J.
Published: October 2022

Romano Guardini read Rilke's Duino Elegies as a compelling eschatological vision for the modern world, but one that must be rejected. I argue that in Rilke's writing, Guardini detected the secular analogue to the substantial image at the end of the Christian eschatological imagination—that is, the communion of saints. Rilke's vision is coherent in that the end he perceives follows from the beginning he assumes; therefore, understanding Rilke's end requires his commentator to see all that precedes that end, beginning with Rilke's own beginning. In a time of increasing loneliness, Guardini's response to Rilke rings with renewed contemporary relevance to guard against the ultimate erasure of the human person.
Inheritance of strong mixing and weak dependence under renewal sampling
Authors: Brandes Dirk-Philip , Curato Imma Valentina , Stelzer Robert
Published: October 2022

Let X be a continuous-time strongly mixing or weakly dependent process and let T be a renewal process independent of X. We show general conditions under which the sampled process
$(X_{T_i},T_i-T_{i-1})^{\top}$
is strongly mixing or weakly dependent. Moreover, we explicitly compute the strong mixing or weak dependence coefficients of the renewal sampled process and show that exponential or power decay of the coefficients of X is preserved (at least asymptotically). Our results imply that essentially all central limit theorems available in the literature for strongly mixing or weakly dependent processes can be applied when renewal sampled observations of the process X are at our disposal.
The Political Uses of Food Protests: Analyzing the 1910 Meat Boycott
Authors: BÉJA ALICE
Published: October 2022

In 1910, a meat boycott spread through the United States. Tens of thousands of people pledged not to eat meat for thirty days to demand lower prices and protest the practices of the Meat Trust. The movement, though its outcomes were limited, was supported by consumer organizations, labor unions, lawmakers, suffragists, and women's clubs. It thus intersected with struggles that were at the heart of the Progressive Era's reform movements. This article will explore how various organizations (labor unions, the Socialist Party, suffragists, the National Consumers League) used, or did not use, this event to further their own goals. It will argue that food protests constitute a site from which to analyze particular transformations of the protest landscape of the time, such as the rise of consumer politics; it will also show that as transversal spaces of mobilization, food protests should be studied through the significance of their object. Food, as a meeting point between the individual body and society, can epitomize the blurring of the lines between private and public that characterized Progressive reform movements.
Beatific embodiment: An Augustinian appraisal of our end-time embodiment
Authors: Luke Sean
Published: October 2022

In this paper, I seek to articulate a positive role for the body in our eschatological joy in God. I draw on Augustine's thought to argue that the body makes a positive contribution to our joy in God by being a pedagogy for our imaginations, training us to imagine the beautiful character of God in Christ through embodiment. While Augustine might seem like a surprising choice for this task, I argue that his concepts of ubique totus and the totus Christus provide fertile soil for the growth of an eschatological theology of the body.
“How did they die?”: Bridging humanitarian and criminal-justice objectives in forensic science to advance the rights of families of the missing under international humanitarian law
Authors: Parrin Anjli
Published: October 2022

There are thousands of families of missing persons around the world who search for answers as to the fate and whereabouts of their loved ones, hoping to be reunited with them, or in the event that they are deceased, to be able to mourn and grieve their death with dignity. In practice when authorities speak with families to confirm that the missing person is deceased, two initial questions frequently arise. First, families generally want to know, “did you identify the body of my relative?” The second question, once they receive information that their loved one has been positively identified as deceased, is usually, “how did they die?” This article examines whether international humanitarian law requires providing families of the missing, who may know or believe that their relative is deceased, with an answer to this second question of “how did they die?” The article argues that under certain circumstances, it is a requirement of international humanitarian law to provide some information about the cause, manner and circumstances of death to families. It also argues that the International Red Cross and Red Crescent Movement can strengthen the rights of families of the missing by engaging confidentially (directly or indirectly) with judicial bodies that are charged with both identification of the missing and accountability for violations of international humanitarian law. While this is challenging, it is argued that it is often possible to do so while respecting and adhering to the fundamental principles of the Movement, and, in turn, advancing the fundamental principle of humanity.
The Dawn‐Dusk Tail Lobe Magnetotail Configuration and the Formation of Aurora Transpolar Arc
Authors: Li Wenhui , Angelopoulos Vassilis , Mieth Johannes , Wu Leyuan , Li Andrew
Published: October 2022

The magnetotail configuration includes a northern tail lobe, a southern tail lobe, and a plasma sheet when IMF directs southward, as a result of the Dungey cycle. However, it is little known about the magnetotail configuration for northward IMF (NIMF) conditions. Using in situ data and corresponding simulations, we show that the magnetotail forms into a dawnside tail lobe and a duskside tail lobe under NIMF with significant By conditions. The data shows signatures related to magnetotail reconnection under such conditions. Cusp reconnection and such magnetotail reconnection may form a dawn‐dusk tail lobe configuration and its version of Dungey cycle. Simulation results also show that aurora transpolar arc may be caused by a process of reconfiguration of the dawn‐dusk tail lobe structure as a result of an IMF By reversal.
Mapping the genetic architecture of cortical morphology through neuroimaging: progress and perspectives
Authors: van der Meer Dennis , Kaufmann Tobias
Published: October 2022

Cortical morphology is a key determinant of cognitive ability and mental health. Its development is a highly intricate process spanning decades, involving the coordinated, localized expression of thousands of genes. We are now beginning to unravel the genetic architecture of cortical morphology, thanks to the recent availability of large-scale neuroimaging and genomic data and the development of powerful biostatistical tools. Here, we review the progress made in this field, providing an overview of the lessons learned from genetic studies of cortical volume, thickness, surface area, and folding as captured by neuroimaging. It is now clear that morphology is shaped by thousands of genetic variants, with effects that are region- and time-dependent, thereby challenging conventional study approaches. The most recent genome-wide association studies have started discovering common genetic variants influencing cortical thickness and surface area, yet together these explain only a fraction of the high heritability of these measures. Further, the impact of rare variants and non-additive effects remains elusive. There are indications that the quickly increasing availability of data from whole-genome sequencing and large, deeply phenotyped population cohorts across the lifespan will enable us to uncover much of the missing heritability in the upcoming years. Novel approaches leveraging shared information across measures will accelerate this process by providing substantial increases in statistical power, together with more accurate mapping of genetic relationships. Important challenges remain, including better representation of understudied demographic groups, integration of other ‘omics data, and mapping of effects from gene to brain to behavior across the lifespan.
My tongue hurts
Authors: Porter Stephen , Escudier Michael , Fedele Stefano
Published: October 2022

This series of articles comprise of short reviews of clinical problems relevant to oral health care in the twenty-first century. The present article uses a composite of presenting case symptoms to hypothetically illustrate differential diagnoses of pain of the tongue and why there may, or may not be, links to aspects of infection of SARS-CoV-2 (COVID-19).
Drug toxicity assessment: cell proliferation versus cell death
Authors: Sazonova Elena V. , Chesnokov Mikhail S. , Zhivotovsky Boris , Kopeina Gelina S.
Published: October 2022

Analysis of the toxicity of chemotherapeutic drugs is one of the main tasks of clinical pharmacology. Decreased viability of tumor cells may reflect two important physiological processes, namely the arrest of proliferation associated with disturbances in cellular metabolism or actual cell death. Elucidation of the exact processes mediating a reduction in the number of cells is fundamentally important to establish the mechanisms of drug action. Only the use of a combination of cell biological and biochemical approaches makes it possible to understand these mechanisms. Here, using various lines of tumor cells and a set of methodological approaches, we carried out a detailed comparative analysis and demonstrated the possible ways to overcome the uncertainties in establishing the mechanisms of cell response to the action of chemotherapeutic drugs and their toxicity.
A novel protein RASON encoded by a lncRNA controls oncogenic RAS signaling in KRAS mutant cancers
Authors: Cheng Rongjie , Li Fanying , Zhang Maolei , Xia Xin , Wu Jianzhuang , Gao Xinya , Zhou Huangkai , Zhang Zhi , Huang Nunu , Yang Xuesong , Zhang Yaliang , Shen Shunli , Kang Tiebang , Liu Zexian , Xiao Feizhe , Yao Hongwei , Xu Jianbo , Yan Chao , Zhang Nu
Published: October 2022

Mutations of the RAS oncogene are found in around 30% of all human cancers yet direct targeting of RAS is still considered clinically impractical except for the KRASG12C mutant. Here we report that RAS-ON (RASON), a novel protein encoded by the long intergenic non-protein coding RNA 00673 (LINC00673), is a positive regulator of oncogenic RAS signaling. RASON is aberrantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) patients, and it promotes proliferation of human PDAC cell lines in vitro and tumor growth in vivo. CRISPR/Cas9-mediated knockout of Rason in mouse embryonic fibroblasts inhibits KRAS-mediated tumor transformation. Genetic deletion of Rason abolishes oncogenic KRAS-driven pancreatic and lung cancer tumorigenesis in LSL-KrasG12D; Trp53R172H/+ mice. Mechanistically, RASON directly binds to KRASG12D/V and inhibits both intrinsic and GTPase activating protein (GAP)-mediated GTP hydrolysis, thus sustaining KRASG12D/V in the GTP-bound hyperactive state. Therapeutically, deprivation of RASON sensitizes KRAS mutant pancreatic cancer cells and patient-derived organoids to EGFR inhibitors. Our findings identify RASON as a critical regulator of oncogenic KRAS signaling and a promising therapeutic target for KRAS mutant cancers.
Reprogramming of cancer-associated fibroblasts by apoptotic cancer cells inhibits lung metastasis via Notch1-WISP-1 signaling
Authors: Kim Hee Ja , Yang Kyungwon , Kim Kiyoon , Lee Ye‐Ji , Lee Sieun , Ahn Sung Yong , Ahn Young‐Ho , Kang Jihee Lee
Published: October 2022

The interplay between apoptotic cancer cells and the tumor microenvironment modulates cancer progression and metastasis. Cancer-associated fibroblasts (CAFs) play a crucial role in promoting these events through paracrine communication. Here, we demonstrate that conditioned medium (CM) from lung CAFs exposed to apoptotic cancer cells suppresses TGF-β1-induced migration and invasion of cancer cells and CAFs. Direct exposure of CAFs to apoptotic 344SQ cells (ApoSQ) inhibited CAF migration and invasion and the expression of CAF activation markers. Enhanced secretion of Wnt‐induced signaling protein 1 (WISP-1) by CAFs exposed to ApoSQ was required for these antimigratory and anti-invasive effects. Pharmacological inhibition of Notch1 activation or siRNA-mediated Notch1 silencing prevented WISP-1 production by CAFs and reversed the antimigratory and anti-invasive effects. Enhanced expression of the Notch ligand delta-like protein 1 on the surface of ultraviolet-irradiated apoptotic lung cancer cells triggered Notch1-WISP-1 signaling. Phosphatidylserine receptor brain-specific angiogenesis inhibitor 1 (BAI1)-Rac1 signaling, which facilitated efferocytosis by CAFs, participated in crosstalk with Notch1 signaling for optimal production of WISP-1. In addition, a single injection of ApoSQ enhanced WISP-1 production, suppressed the expression of CAF activation markers in isolated Thy1+ CAFs, and inhibited lung metastasis in syngeneic immunocompetent mice via Notch1 signaling. Treatment with CM from CAFs exposed to ApoSQ suppressed tumor growth and lung metastasis, whereas treatment with WISP-1-immunodepleted CM from CAFs exposed to ApoSQ reversed the antitumorigenic and antimetastatic effects. Therefore, treatment with CM from CAFs exposed to apoptotic lung cancer cells could be therapeutically applied to suppress CAF activation, thereby preventing cancer progression and metastasis.
High strength and damage-tolerance in echinoderm stereom as a natural bicontinuous ceramic cellular solid
Authors: Yang Ting , Jia Zian , Wu Ziling , Chen Hongshun , Deng Zhifei , Chen Liuni , Zhu Yunhui , Li Ling
Published: October 2022

Due to their low damage tolerance, engineering ceramic foams are often limited to non-structural usages. In this work, we report that stereom, a bioceramic cellular solid (relative density, 0.2–0.4) commonly found in the mineralized skeletal elements of echinoderms (e.g., sea urchin spines), achieves simultaneous high relative strength which approaches the Suquet bound and remarkable energy absorption capability (ca. 17.7 kJ kg−1) through its unique bicontinuous open-cell foam-like microstructure. The high strength is due to the ultra-low stress concentrations within the stereom during loading, resulted from their defect-free cellular morphologies with near-constant surface mean curvatures and negative Gaussian curvatures. Furthermore, the combination of bending-induced microfracture of branches and subsequent local jamming of fractured fragments facilitated by small throat openings in stereom leads to the progressive formation and growth of damage bands with significant microscopic densification of fragments, and consequently, contributes to stereom’s exceptionally high damage tolerance.
Immunopeptidomics-based design of mRNA vaccine formulations against Listeria monocytogenes
Authors: Mayer Rupert L. , Verbeke Rein , Asselman Caroline , Aernout Ilke , Gul Adillah , Eggermont Denzel , Boucher Katie , Thery Fabien , Maia Teresa M. , Demol Hans , Gabriels Ralf , Martens Lennart , Bécavin Christophe , De Smedt Stefaan C. , Vandekerckhove Bart , Lentacker Ine , Impens Francis
Published: October 2022

Listeria monocytogenesis a foodborne intracellular bacterial pathogen leading to human listeriosis. Despite a high mortality rate and increasing antibiotic resistance no clinically approved vaccine againstListeriais available. AttenuatedListeriastrains offer protection and are tested as antitumor vaccine vectors, but would benefit from a better knowledge on immunodominant vector antigens. To identify novel antigens, we screen forListeriapeptides presented on the surface of infected human cell lines by mass spectrometry-based immunopeptidomics. In between more than 15,000 human self-peptides, we detect 68Listeriaimmunopeptides from 42 different bacterial proteins, including several known antigens. Peptides presented on different cell lines are often derived from the same bacterial surface proteins, classifying these antigens as potential vaccine candidates. Encoding these highly presented antigens in lipid nanoparticle mRNA vaccine formulations results in specific CD8+ T-cell responses and induces protection in vaccination challenge experiments in mice. Our results can serve as a starting point for the development of a clinical mRNA vaccine againstListeriaand aid to improve attenuatedListeriavaccines and vectors, demonstrating the power of immunopeptidomics for next-generation bacterial vaccine development.
Induction of the hepatic aryl hydrocarbon receptor by alcohol dysregulates autophagy and phospholipid metabolism via PPP2R2D
Authors: Kim Yun Seok , Ko Bongsub , Kim Da Jung , Tak Jihoon , Han Chang Yeob , Cho Joo-Youn , Kim Won , Kim Sang Geon
Published: October 2022

Disturbed lipid metabolism precedes alcoholic liver injury. Whether and how AhR alters degradation of lipids, particularly phospho-/sphingo-lipids during alcohol exposure, was not explored. Here, we show that alcohol consumption in mice results in induction and activation of aryl hydrocarbon receptor (AhR) in the liver, and changes the hepatic phospho-/sphingo-lipids content. The levels of kynurenine, an endogenous AhR ligand, are elevated with increased hepatic tryptophan metabolic enzymes in alcohol-fed mice. Either alcohol or kynurenine treatment promotes AhR activation with autophagy dysregulation via AMPK. Protein Phosphatase 2 Regulatory Subunit-Bdelta (Ppp2r2d) is identified as a transcriptional target of AhR. Consequently, PPP2R2D-dependent AMPKα dephosphorylation causes autophagy inhibition and mitochondrial dysfunction. Hepatocyte-specific AhR ablation attenuates steatosis, which is associated with recovery of phospho-/sphingo-lipids content. Changes of AhR targets are corroborated using patient specimens. Overall, AhR induction by alcohol inhibits autophagy in hepatocytes through AMPKα, which is mediated by Ppp2r2d gene transactivation, revealing an AhR-dependent metabolism of phospho-/sphingo-lipids.
Tidewater-glacier response to supraglacial lake drainage
Authors: Stevens Laura A. , Nettles Meredith , Davis James L. , Creyts Timothy T. , Kingslake Jonathan , Hewitt Ian J. , Stubblefield Aaron
Published: October 2022

The flow speed of the Greenland Ice Sheet changes dramatically in inland regions when surface meltwater drains to the bed. But ice-sheet discharge to the ocean is dominated by fast-flowing outlet glaciers, where the effect of increasing surface melt on annual discharge is unknown. Observations of a supraglacial lake drainage at Helheim Glacier, and a consequent velocity pulse propagating down-glacier, provide a natural experiment for assessing the impact of changes in injected meltwater, and allow us to interrogate the subglacial hydrological system. We find a highly efficient subglacial drainage system, such that summertime lake drainage has little net effect on ice discharge. Our results question the validity of common remote-sensing approaches for inferring subglacial conditions, knowledge of which is needed for improved projections of sea-level rise.
Zinc isotopic evidence for recycled carbonate in the deep mantle
Authors: Zhang Xiao-Yu , Chen Li-Hui , Wang Xiao-Jun , Hanyu Takeshi , Hofmann Albrecht W. , Komiya Tsuyoshi , Nakamura Kentaro , Kato Yasuhiro , Zeng Gang , Gou Wen-Xian , Li Wei-Qiang
Published: October 2022

Carbonate, the major carbon reservoir on Earth’s surface, can enter into the mantle by subduction. However, evidence for recycled surficial carbonates in the deep mantle is still scarce. Ocean island basalts from Cook-Austral islands and St. Helena Island, widely called HIMU basalts because of their high μ = 238U/204Pb sources, are thought to be fed by mantle plumes originating in the lower mantle. Here we report exceptionally high δ66Zn values (δ66Zn = 0.38 ± 0.03‰) of these HIMU lavas relative to most published data for oceanic basalts (δ66Zn = 0.31 ± 0.10‰), which requires a source contributed by isotopically heavy recycled surficial carbonates. During subduction of the oceanic lithosphere, melting of mixed surficial carbonates and basaltic crust in the deep mantle generates carbonatite melts, which metasomatizes the nearby mantle and the resultant carbonated mantle ultimately evolves into a high-δ66Zn HIMU source. High-δ66Zn signatures of HIMU basalts, therefore, demonstrate that carbonates can be transported into Earth’s deep mantle.
The gut microbe Bacteroides fragilis ameliorates renal fibrosis in mice
Authors: Zhou Wei , Wu Wen-hui , Si Zi-lin , Liu Hui-ling , Wang Hanyu , Jiang Hong , Liu Ya-fang , Alolga Raphael N. , Chen Cheng , Liu Shi-jia , Bian Xue-yan , Shan Jin-jun , Li Jing , Tan Ning-hua , Zhang Zhi-hao
Published: October 2022

Renal fibrosis is an inevitable outcome of various manifestations of progressive chronic kidney diseases (CKD). The need for efficacious treatment regimen against renal fibrosis can therefore not be overemphasized. Here we show a novel protective role of Bacteroides fragilis (B. fragilis) in renal fibrosis in mice. We demonstrate decreased abundance of B. fragilis in the feces of CKD patients and unilateral ureteral obstruction (UUO) mice. Oral administration of live B. fragilis attenuates renal fibrosis in UUO and adenine mice models. Increased lipopolysaccharide (LPS) levels are decreased after B. fragilis administration. Results of metabolomics and proteomics studies show decreased level of 1,5-anhydroglucitol (1,5-AG), a substrate of SGLT2, which increases after B. fragilis administration via enhancement of renal SGLT2 expression. 1,5-AG is an agonist of TGR5 that attenuates renal fibrosis by inhibiting oxidative stress and inflammation. Madecassoside, a natural product found via in vitro screening promotes B. fragilis growth and remarkably ameliorates renal fibrosis. Our findings reveal the ameliorative role of B. fragilis in renal fibrosis via decreasing LPS and increasing 1,5-AG levels.
Genetic map of regional sulcal morphology in the human brain from UK biobank data
Authors: Sun Benjamin B. , Loomis Stephanie J. , Pizzagalli Fabrizio , Shatokhina Natalia , Painter Jodie N. , Foley Christopher N. ,   Biogen Biobank Team, Sun Benjamin , Tsai Ellen , Bronson Paola , Sexton David , John Sally , Marshall Eric , Patel Mehool , Duraisamy Saranya , Swan Timothy , Baird Dennis , Chen Chia-Yen , Eaton Susan , Gagnon Jake , Gao Feng , Gubbels Cynthia , Huang Yunfeng , Kupelian Varant , Li Kejie , Liu Dawei , Loomis Stephanie , McLaughlin Helen , Mitchell Adele , Jensen Megan E. , McLaren Donald G. , Chintapalli Sai Spandana , Zhu Alyssa H. , Dixon Daniel , Islam Tasfiya , Ba Gari Iyad , Runz Heiko , Medland Sarah E. , Thompson Paul M. , Jahanshad Neda , Whelan Christopher D.
Published: October 2022

Genetic associations with macroscopic brain structure can provide insights into brain function and disease. However, specific associations with measures of local brain folding are largely under-explored. Here, we conducted large-scale genome- and exome-wide associations of regional cortical sulcal measures derived from magnetic resonance imaging scans of 40,169 individuals in UK Biobank. We discovered 388 regional brain folding associations across 77 genetic loci, with genes in associated loci enriched for expression in the cerebral cortex, neuronal development processes, and differential regulation during early brain development. We integrated brain eQTLs to refine genes for various loci, implicated several genes involved in neurodevelopmental disorders, and highlighted global genetic correlations with neuropsychiatric phenotypes. We provide an interactive 3D visualisation of our summary associations, emphasising added resolution of regional analyses. Our results offer new insights into the genetic architecture of brain folding and provide a resource for future studies of sulcal morphology in health and disease.
Flexible active antenna arrays
Authors: Gal-Katziri Matan , Fikes Austin , Hajimiri Ali
Published: October 2022

Complex and dynamic control of radiated fields are advantageous for flexible radio systems, which naturally move, roll, bend, twist, deform, and vibrate. Practical challenges hinder the proliferation of these antenna arrays. This work shows how using radio-frequency microchips reduces system component count, decreases mass to ~0.1 g cm−2, and increases functionality and mechanical flexibility. We develop a general platform for large scale flexible arrays and demonstrate two different 256-elements, 30 × 30 cm2 flexible arrays. By varying supply distribution methods and radiators we show how performance can be optimized for maximum power delivery or physical flexibility. The demonstrated systems conform to curved surfaces with radii of curvatures as low as 23 cm and wirelessly deliver ~ 80 mW of DC power to a 6.7 cm × 11 cm-receiver over one meter away. This paves the way towards the integration of smart arrays in flexible wearables and deployable lightweight airborne systems.
Machine learning to predict the development of recurrent urinary tract infection related to single uropathogen, Escherichia coli
Authors: Jeng Shuen-Lin , Huang Zi-Jing , Yang Deng-Chi , Teng Ching-Hao , Wang Ming-Cheng
Published: October 2022

Recurrent urinary tract infection (RUTI) can damage renal function and has impact on healthcare costs and patients’ quality of life. There were 2 stages for development of prediction models for RUTI. The first stage was a scenario in the clinical visit. The second stage was a scenario after hospitalization for urinary tract infection caused by Escherichia coli. Three machine learning models, logistic regression (LR), decision tree (DT), and random forest (RF) were built for the RUTI prediction. The RF model had higher prediction accuracy than LR and DT (0.700, 0.604, and 0.654 in stage 1, respectively; 0.709, 0.604, and 0.635 in stage 2, respectively). The decision rules constructed by the DT model could provide high classification accuracy (up to 0.92 in stage 1 and 0.94 in stage 2) in certain subgroup patients in different scenarios. In conclusion, this study provided validated machine learning models and RF could provide a better accuracy in predicting the development of single uropathogen (E. coli) RUTI. Both host and bacterial characteristics made important contribution to the development of RUTI in the prediction models in the 2 clinical scenarios, respectively. Based on the results, physicians could take action to prevent the development of RUTI.
Prediction of prognosis, immune infiltration and immunotherapy response with N6-methyladenosine-related lncRNA clustering patterns in cervical cancer
Authors: Jia Haixia , Cao Meiting , Hao Suhua , Wang Jiahao , Wang Jintao
Published: October 2022

LncRNAs and tumor microenvironment (TME) exert an important effect in antitumor immunity. Nonetheless, the role of m6A-related lncRNA clustering patterns in prognosis, TME and immunotherapy of cervical cancer (CC) remains unknown. Here, based on 7 m6A-related prognostic lncRNAs obtained from TCGA-CC dataset, two m6AlncRNA clustering patterns were determined. m6AlncRNA clusterA was characterized by immune cell infiltrates and immune activation. m6AlncRNA clusterB was characterized by enrichment of immune evasion and tumorigenic activation pathways as well as survival and clinical stage disadvantage. Then, principal component analysis algorithms were used to construct m6AlncRNAscore based on prognostic differentially expressed genes between two m6AlncRNA clusters to quantify m6AlncRNA clustering patterns. m6AlncRNAscore was an independent prognostic protective factor. Higher Th2 and Treg cells and enrichment of immunosuppressive pathways were observed in the low-m6AlncRNAscore group, with poorer survival. High-m6AlncRNAscore was characterized by increased infiltration of activated CD8 T cell, enrichment of immune activation pathways, lower IL-10 and TGF-beta1 levels, and higher immunophenscore values, indicating inflamed TME and better anti-tumor immunotherapy efficacy. Quantitative Real-Time Polymerase Chain Reaction was used for detection of m6A-related prognostic lncRNAs. Collectively, we identified two m6AlncRNA clustering patterns which play a nonnegligible role in the prognosis, TME heterogeneity and immunotherapy of CC patients.
MHD micropolar hybrid nanofluid flow over a flat surface subject to mixed convection and thermal radiation
Authors: Lone Showkat Ahmad , Alyami Maryam Ahmed , Saeed Anwar , Dawar Abdullah , Kumam Poom , Kumam Wiyada
Published: October 2022

Hybrid nanofluids play a significant role in the advancement of thermal characteristics of pure fluids both at experimental and industrial levels. This work explores the mixed convective MHD micropolar hybrid nanofluid flow past a flat surface. The hybrid nanofluid flow is composed of alumina and silver nanoparticles whereas water is used as a base fluid. The plate has placed vertical in a permeable medium with suction and injection effects. Furthermore, viscous dissipation, thermal radiation and Joule heating effects are taken into consideration. Specific similarity variables have been used to convert the set of modeled equations to dimension-free form and then has solved by homotopy analysis method (HAM). It has revealed in this investigation that, fluid motion upsurge with growth in magnetic field effects and mixed convection parameter and decline with higher values of micropolar factor. Micro-rotational velocity of fluid is upsurge with higher values of micropolar factor. Thermal flow behavior is augmenting for expended values of magnetic effects, radiation factor, Eckert number and strength of heat source. The intensification in magnetic strength and mixed convection factors has declined the skin friction and has upsurge with higher values of micropolar parameter. The Nusselt number has increased with the intensification in magnetic effects, radiation factor and Eckert number.
Ecological-environmental challenges and restoration of aquatic ecosystems of the Middle-Eastern
Authors: Pirali zefrehei Ahmad Reza , Kolahi Mahdi , Fisher Judith
Published: October 2022

Water resource management has numerous environmental challenges, especially in aquatic ecosystems such as rivers due to the heterogeneous distribution of surface water resources, among other diverse impacting factors. In Iran (one of the countries of the Middle-East), population growth, development of urban communities and development of agricultural and industrial activities provide additional impacts on the functioning of aquatic ecosystems. The United Nations declared the third decade of this century (2021–2030) as the decade of ecosystem restoration. In this study, we have selected the Zayandehroud River as a case study and then evaluated the pathology of existing statuses. Strategies and approaches were studied and analyzed including the need to utilize integrated water resources management (IWRM), approaches for dealing with drought conditions, payment of water rights and dam alternatives, and the need for ecological landscape studies. Then, strategies and approaches appropriate from the perspective of restoration were identified, including the techniques used, and the experiences of different countries. The analysis showed that similar regions of Iran in the Middle-East need to change the paradigm of "nature control" to the paradigm of "nature management" and reduce reliance on structural and technological solutions in water resources management.
Self-referenced interferometry for single-shot detection of vector-vortex beams
Authors: Kumar Praveen , Nishchal Naveen K. , Omatsu Takashige , Rao A. Srinivasa
Published: October 2022

Vector-vortex (VV) beams are of significant interest for various applications. There have been substantial efforts toward developing a fast and efficient method for the characterization of generated VV beams which is crucial for their usage. Polarimetric approaches are commonly used to identify unknown VV beams but require multiple intensity recordings. This paper demonstrates a technique to detect VV beams and identify their parameters using the concept of self-referenced interferometry. The approach uses a single recorded interferogram to determine the beam parameters that allow rapid detection. The method even enables detection of VV beams having high-order optical vortices.
Effects of praziquantel on common carp embryos and larvae
Authors: Velisek Josef , Zuskova Eliska , Kubec Jan , Sandova Marie , Stara Alzbeta
Published: October 2022

This study aimed to assess the toxicity of praziquantel (anthelmintic drug) in different developmental stages of common carp (Cyprinus carpio) based on mortality, early ontogeny, growth, oxidative stress, antioxidant enzymes, histology and behaviour. Praziquantel at all tested concentrations ranging from 1 to 4 mg/L showed no significant adverse effects on mortality, the early ontogeny and behaviour locomotory (activity, moved distance and velocity) of carp after 35-day exposure. Concentrations of 3 and 4 mg/L caused significantly (P < 0.01) lower growth, total superoxide dismutase and catalase activities compared with controls. Praziquantel is safe for the early life of carp in concentrations ≤ 2 mg/L.
Spatiotemporal variation in irrigation water requirements in the China–Pakistan Economic Corridor
Authors: Li Yaqi , Chen Yaning , Duan Weili , Cao Mengzhu , Qin Jingxiu
Published: October 2022

Agricultural irrigation consumes most of the fresh water in the China–Pakistan Economic Corridor (CPEC), directly affecting water resource management and allocation. Irrigation water demand is a key component of regional water resources management. We analyzed spatiotemporal variation in irrigation water requirement, irrigation demand index (IDI), and the proposed regional optimization of irrigation water use based on the Bayesian probability network. Results showed that: (1) The IDI in the study area increased slightly (trend slope = 0.028 a−1) as the effective precipitation increased by 63% during this period, and total irrigation water requirement (IR) decreased from 277.61 km3 in 2000 to 240 km3 in 2015. (2) Cotton had the highest crop IDI, followed by maize and wheat. (3) According to the comprehensive scenario analysis, improving the crop planting structure (by moderately increasing the planting proportion of maize in the CPEC) is conducive to improving regional water and food security by enhancing the grain yield (+ 9%), reducing the malnourished proportion of the population (low state + 7.2%), and bolstering water-saving irrigation technologies in Pakistan as well as water conveyance systems in Pakistan. Our results form an important baseline in determining the way forward on sustainable water resource utilization management in the CPEC.
Convolutional neural network-based classification of cervical intraepithelial neoplasias using colposcopic image segmentation for acetowhite epithelium
Authors: Kim Jisoo , Park Chul Min , Kim Sung Yeob , Cho Angela
Published: October 2022

Colposcopy is a test performed to detect precancerous lesions of cervical cancer. Since cervical cancer progresses slowly, finding and treating precancerous lesions helps prevent cervical cancer. In particular, it is clinically important to detect high-grade squamous intraepithelial lesions (HSIL) that require surgical treatment among precancerous lesions of cervix. There have been several studies using convolutional neural network (CNN) for classifying colposcopic images. However, no studies have been reported on using the segmentation technique to detect HSIL. In present study, we aimed to examine whether the accuracy of a CNN model in detecting HSIL from colposcopic images can be improved when segmentation information for acetowhite epithelium is added. Without segmentation information, ResNet-18, 50, and 101 achieved classification accuracies of 70.2%, 66.2%, and 69.3%, respectively. The experts classified the same test set with accuracies of 74.6% and 73.0%. After adding segmentation information of acetowhite epithelium to the original images, the classification accuracies of ResNet-18, 50, and 101 improved to 74.8%, 76.3%, and 74.8%, respectively. We demonstrated that the HSIL detection accuracy improved by adding segmentation information to the CNN model, and the improvement in accuracy was consistent across different ResNets.
Design and function of targeted endocannabinoid nanoparticles
Authors: Barrie N. , Manolios N. , Stuart J. , Chew T. , Arnold J. , Sadsad R. , De Campo L. , Knott R. B. , White J. , Booth D. , Ali M. , Moghaddam M. J.
Published: October 2022

Nanoparticles and nano-delivery systems are constantly being refined and developed for biomedical applications such as imaging, gene therapy, and targeted delivery of drugs. Nanoparticles deliver beneficial effects by both release of their cargo and by liberation of their constitutive structural components. The N-acylethanolamines linoleoyl ethanolamide (LEA) and oleoyl ethanolamide (OEA) both exhibit endocannabinoid-like activity. Here, we report on their ability to form nanoparticles that when conjugated with tissue-specific molecules, are capable of localizing to specific areas of the body and reducing inflammation. The facilitation of pharmacological effects by endocannabinoids at targeted sites provides a novel biocompatible drug delivery system and a therapeutic approach to the treatment, patient management and quality of life, in conditions such as arthritis, epilepsy, and cancer.
Trans-oral trans-sheath forceps biopsy for patients with severe esophageal obstruction under fluoroscopy
Authors: Jiao Dechao , Xu Kaihao , Liu Yiming , Li Zongming , Wang Yanli , Ren Jianzhuang , Han Xinwei
Published: October 2022

To investigate the safety and effectiveness of trans-oral trans-sheath forceps biopsy (TTFB) for patients with severe esophageal obstruction under fluoroscopy. From November 2016 to November 2019, 35 patients with level III or IV dysphagia and a Karnofsky score of less than 60 were enrolled to undergo TTFB and esophageal nutrition tube insertion or stenting simultaneously. Data on diagnostic performance, early complications, and radiation dose were collected, and Karnofsky scores before and after the procedures were compared. The technical success of TTFB was 100%. The sensitivity, specificity and accuracy were 92.3% (24/26), 77.8% (7/9), and 88.6% (31/35), respectively. Complications occurred in two cases (5.7%). The mean procedure duration and irradiation dose were 23.2 min and 7.2 mSv, respectively. The Karnofsky scores significantly increased after 2–4 weeks (t = 11.22, P < 0.0001). TTFB is a safe and effective method for patients with severe esophageal obstruction under fluoroscopy, especially in those who cannot undergo or refuse endoscopy.
Metagenomic analysis of viromes in tissues of wild Qinghai vole from the eastern Tibetan Plateau
Authors: He Xiaozhou , Wang Xu , Fan Guohao , Li Fan , Wu Weiping , Wang Zhenghuan , Fu Meihua , Wei Xu , Ma Shuo , Ma Xuejun
Published: October 2022

Rodents are natural reservoirs of diverse zoonotic viruses and widely distributed on the Tibetan Plateau. A comprehensive understanding of the virome in local rodent species could provide baseline of viral content and assist in efforts to reduce the risk for future emergence of rodent related zoonotic diseases. A total of 205 tissue and fecal samples from 41 wild Qinghai voles were collected. Metagenomic analyses were performed to outline the characteristics of the viromes, and phylogenetic analyses were used to identify the novel viral genomes. The virome distribution among five tissues (liver, lung, spleen, small intestine with content and feces) was also compared. We identified sequences related to 46 viral families. Novel viral genomes from distinct evolutionary lineages with known viruses were characterized for their genomic and evolutionary characteristics, including Hepatovirus, Hepacivirus, Rotavirus, and Picobirnavirus. Further analyses revealed that the core virome harbored by rodent internal tissues were quite different from the virome found in intestine and fecal samples. These findings provide an overview of the viromes in wild Qinghai voles, which are unique and the most common rodent species in the eastern Tibetan Plateau. A high diversity of viruses is likely present in rodent species in this area.
Fabrication of a lattice structure with periodic open pores through three-dimensional printing for bone ingrowth
Authors: Park Jong Woong , Park Hyenmin , Kim June Hyuk , Kim Hong Moule , Yoo Chang Hyoung , Kang Hyun Guy
Published: October 2022

Lattice structures for implants can be printed using metal three-dimensional (3D)-printing and used as a porous microstructures to enhance bone ingrowth as orthopedic implants. However, designs and 3D-printed products can vary. Thus, we aimed to investigate whether targeted pores can be consistently obtained despite printing errors. The cube-shaped specimen was printed with one side 15 mm long and a full lattice with a dode-thin structure of 1.15, 1.5, and 2.0 mm made using selective laser melting. Beam compensation was applied, increasing it until the vector was lost. For each specimen, the actual unit size and strut thickness were measured 50 times. Pore size was calculated from unit size and strut thickness, and porosity was determined from the specimen’s weight. The actual average pore sizes for 1.15, 1.5, and 2.0 mm outputs were 257.9, 406.2, and 633.6 μm, and volume porosity was 62, 70, and 80%, respectively. No strut breakage or gross deformation was observed in any 3D-printed specimens, and the pores were uniformly fabricated with < 10% standard deviation. The actual micrometer-scaled printed structures were significantly different to the design, but this error was not random. Although the accuracy was low, precision was high for pore cells, so reproducibility was confirmed.
A proliferative subtype of colorectal liver metastases exhibits hypersensitivity to cytotoxic chemotherapy
Authors: Spurr Liam F. , Martinez Carlos A. , Katipally Rohan R. , Iyer Soumya C. , Pugh Sian A. , Bridgewater John A. , Primrose John N. , Domingo Enric , Maughan Timothy S. , D’Angelica Michael I. , Talamonti Mark , Posner Mitchell C. , Connell Philip P. , Weichselbaum Ralph R. , Pitroda Sean P.
Published: October 2022

Personalized treatment approaches for patients with limited liver metastases from colorectal cancer are critically needed. By leveraging three large, independent cohorts of patients with colorectal liver metastases (n = 336), we found that a proliferative subtype associated with elevated CIN70 scores is linked to immune exclusion, increased metastatic proclivity, and inferior overall survival in colorectal liver metastases; however, high CIN70 scores generate a therapeutic vulnerability to DNA-damaging therapies leading to improved treatment responses. We propose CIN70 as a candidate biomarker to personalize systemic treatment options for patients with metastatic colorectal cancer. These findings are potentially broadly applicable to other human cancers.
Leptin receptor co-expression gene network moderates the effect of early life adversity on eating behavior in children
Authors: de Lima Randriely Merscher Sobreira , Barth Barbara , Mar Arcego Danusa , de Mendonça Filho Euclides José , Patel Sachin , Wang Zihan , Pokhvisneva Irina , Parent Carine , Levitan Robert D. , Kobor Michael S. , de Vasconcellos Bittencourt Ana Paula Santana , Meaney Michael J. , Dalmaz Carla , Silveira Patrícia Pelufo
Published: October 2022

Leptin influences eating behavior. Exposure to early adversity is associated with eating behaviour disorders and metabolic syndrome, but the role of the leptin receptor on this relationship is poorly explored. We investigated whether individual differences in brain region specific leptin receptor (LepR) gene networks could moderate the effects of early adversity on eating behavior and metabolism. We created an expression-based polygenic risk score (ePRS) reflecting variations in the function of LepR gene network in prefrontal cortex and hypothalamus to investigate the interactions between a cumulative index of postnatal adversity on eating behavior in two independent birth cohorts (MAVAN and GUSTO). To explore whether variations in the prefrontal cortex or hypothalamic genetic scores could be associated with metabolic measurements, we also assessed the relationship between LepR-ePRS and fasting blood glucose and leptin levels in a third independent cohort (ALSPAC). We identified significant interaction effects between postnatal adversity and prefrontal-based LepR-ePRS on the Child Eating Behavior Questionnaire scores. In MAVAN, we observed a significant interaction effect on food enjoyment at 48 months (β = 61.58, p = 0.015) and 72 months (β = 97.78, p = 0.001); food responsiveness at 48 months (β = 83.79, p = 0.009) satiety at 48 months (β = −43.63, p = 0.047). Similar results were observed in the GUSTO cohort, with a significant interaction effect on food enjoyment (β = 30.48, p = 0.006) food fussiness score (β = −24.07, p = 0.02) and satiety score at 60 months (β = −17.00, p = 0.037). No effects were found when focusing on the hypothalamus-based LepR-ePRS on eating behavior in MAVAN and GUSTO cohorts, and there was no effect of hypothalamus and prefrontal cortex based ePRSs on metabolic measures in ALSPAC. Our study indicated that exposure to postnatal adversity interacts with prefrontal cortex LepR-ePRS to moderate eating behavior, suggesting a neurobiological mechanism associated with the development of eating behavior problems in response to early adversity. The knowledge of these mechanisms may guide the understanding of eating patterns associated with risk for obesity in response to fluctuations in stress exposure early in life.
Bacteria-on-a-bead: probing the hydrodynamic interplay of dynamic cell appendages during cell separation
Authors: Sauter Nora , Sangermani Matteo , Hug Isabelle , Jenal Urs , Pfohl Thomas
Published: October 2022

Surface attachment of bacteria is the first step of biofilm formation and is often mediated and coordinated by the extracellular appendages, flagellum and pili. The model organism Caulobacter crescentus undergoes an asymmetric division cycle, giving rise to a motile “swarmer cell” and a sessile “stalked cell”, which is attached to the surface. In the highly polarized predivisional cell, pili and flagellum, which are assembled at the pole opposite the stalk, are both activated before and during the process of cell separation. We explored the interplay of flagellum and active pili by growing predivisional cells on colloidal beads, creating a bacteria-on-a-bead system. Using this set-up, we were able to simultaneously visualize the bacterial motility and analyze the dynamics of the flagellum and pili during cell separation. The observed activities of flagellum and pili at the new cell pole of the predivisional cell result in a cooperating interplay of the appendages during approaching and attaching to a surface. Even in presence of a functioning flagellum, pili are capable of surface attachment and keeping the cell in position. Moreover, while flagellar rotation decreases the average attachment time of a single pilus, it increases the overall attachment rate of pili in a synergetic manner.