bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular matrix physical properties govern the diffusion of nanoparticles in tumor microenvironment
Authors: He Xiaocong , Yang Yuanyuan , Han Yulong , Cao Chunyu , Zhang Zhongbin , Li Lingxiao , Xiao Cailan , Guo Hui , Wang Lin , Han Lichun , Qu Zhiguo , Liu Na , Han Shuang , Xu Feng
Published: December 2022

Nanoparticles (NPs) are confronted with limited and disappointing delivery efficiency in tumors clinically. The tumor extracellular matrix (ECM), whose physical traits have recently been recognized as new hallmarks of cancer, forms a main steric obstacle for NP diffusion, yet the role of tumor ECM physical traits in NP diffusion remains largely unexplored. Here, we characterized the physical properties of clinical gastric tumor samples and observed limited distribution of NPs in decellularized tumor tissues. We also performed molecular dynamics simulations and in vitro hydrogel experiments through single-particle tracking to investigate the diffusion mechanism of NPs and understand the influence of tumor ECM physical properties on NP diffusion both individually and collectively. Furthermore, we developed an estimation matrix model with evaluation scores of NP diffusion efficiency through comprehensive analyses of the data. Thus, beyond finding that loose and soft ECM with aligned structure contribute to efficient diffusion, we now have a systemic model to predict NP diffusion efficiency based on ECM physical traits and provide critical guidance for personalized tumor diagnosis and treatment.
Beta-endoproteolysis of the cellular prion protein by dipeptidyl peptidase-4 and fibroblast activation protein
Authors: Castle Andrew R. , Kang Sang-Gyun , Eskandari-Sedighi Ghazaleh , Wohlgemuth Serene , Nguyen My-Anh , Drucker Daniel J. , Mulvihill Erin E. , Westaway David
Published: December 2022

The cellular prion protein (PrPC) converts to alternatively folded pathogenic conformations (PrPSc) in prion infections and binds neurotoxic oligomers formed by amyloid-β α-synuclein, and tau. β-Endoproteolysis, which splits PrPCinto N- and C-terminal fragments (N2 and C2, respectively), is of interest because a protease-resistant, C2-sized fragment (C2Sc) accumulates in the brain during prion infections, seemingly comprising the majority of PrPScat disease endpoint in mice. However, candidates for the underlying proteolytic mechanism(s) remain unconfirmed in vivo. Here, a cell-based screen of protease inhibitors unexpectedly linked type II membrane proteins of the S9B serine peptidase subfamily to PrPCβ-cleavage. Overexpression experiments in cells and assays with recombinant proteins confirmed that fibroblast activation protein (FAP) and its paralog, dipeptidyl peptidase-4 (DPP4), cleave directly at multiple sites within PrPC’s N-terminal domain. For wild-type mouse and human PrPCsubstrates expressed in cells, the rank orders of activity were human FAP ~ mouse FAP > mouse DPP4 > human DPP4 and human FAP > mouse FAP > mouse DPP4 >> human DPP4, respectively. C2 levels relative to total PrPCwere reduced in several tissues from FAP-null mice, and, while knockout of DPP4 lacked an analogous effect, the combined DPP4/FAP inhibitor linagliptin, but not the FAP-specific inhibitor SP-13786, reduced C2Scand total PrPSclevels in two murine cell-based models of prion infections. Thus, the net activity of the S9B peptidases FAP and DPP4 and their cognate inhibitors/modulators affect the physiology and pathogenic potential of PrPC.
Open-ended movements structure sensorimotor information in early human development
Authors: Kanazawa Hoshinori , Yamada Yasunori , Tanaka Kazutoshi , Kawai Masahiko , Niwa Fusako , Iwanaga Kougoro , Kuniyoshi Yasuo
Published: December 2022

Human behaviors, with whole-body coordination, involve large-scale sensorimotor interaction. Spontaneous bodily movements in the early developmental stage potentially lead toward acquisition of such coordinated behavior. These movements presumably contribute to the structuration of sensorimotor interaction, providing specific regularities in bidirectional information among muscle activities and proprioception. Whether and how spontaneous movements, despite being task-free, structure and organize sensorimotor interactions in the entire body during early development remain unknown. Herein, to address these issues, we gained insights into the structuration process of the sensorimotor interaction in neonates and 3-mo-old infants. By combining detailed motion capture and musculoskeletal simulation, sensorimotor information flows among muscle activities and proprioception throughout the body were obtained. Subsequently, we extracted spatial modules and temporal state in sensorimotor information flows. Our approach demonstrated that early spontaneous movements elicited body-dependent sensorimotor modules, revealing age-related changes in them, depending on the combination or direction. The sensorimotor interactions also displayed temporal non-random fluctuations analogous to those seen in spontaneous activities in the cerebral cortex and spinal cord. Furthermore, we found recurring state sequence patterns across multiple participants, characterized by a substantial increase in infants compared to the patterns in neonates. Therefore, early spontaneous movements induce the spatiotemporal structuration in sensorimotor interactions and subsequent developmental changes. These results implicated that early open-ended movements, emerging from a certain neural substrate, regulate the sensorimotor interactions through embodiment and contribute to subsequent coordinated behaviors. Our findings also provide a conceptual linkage between early spontaneous movements and spontaneous neuronal activity in terms of spatiotemporal characteristics.
Obesity triggers tumoral senescence and renders poorly immunogenic malignancies amenable to senolysis
Authors: Fournier Frédérik , Diaz-Marin Roberto , Pilon Frédérique , Neault Mathieu , Juneau Rachel , Girouard Gabrielle , Wilson Ariel M. , Larrivée Bruno , Mallette Frédérick A. , Crespo-Garcia Sergio , Sapieha Przemyslaw
Published: December 2022

Obesity is a major risk factor for cancer. Conventional thought suggests that elevated adiposity predisposes to heightened inflammatory stress and potentiates tumor growth, yet underlying mechanisms remain ill-defined. Here, we show that tumors from patients with a body mass index >35 carry a high burden of senescent cells. In mouse syngeneic tumor models, we correlated a pronounced accretion of senescent cancer cells with poorly immunogenic tumors when mice were subjected to diet-induced obesity (DIO). Highly immunogenic tumors showed lesser senescence burden suggesting immune-mediated elimination of senescent cancer cells, likely targeted as a consequence of their senescence-associated secretory phenotype. Treatment with the senolytic BH3 mimetic small molecule inhibitor ABT-263 selectively stalled tumor growth in mice with DIO to rates comparable to regular diet-fed mice. Thus, consideration of body adiposity in the selection of cancer therapy may be a critical determinant for disease outcome in poorly immunogenic malignancies.
Iontronic analog of synaptic plasticity: Hydrogel-based ionic diode with chemical precipitation and dissolution
Authors: Han Seok Hee , Kim Sung Il , Oh Min-Ah , Chung Taek Dong
Published: December 2022

In this study, an aqueous nonlinear synaptic element showing plasticity behavior is developed, which is based on the chemical processes in an ionic diode. The device is simple, fully ionic, and easily configurable, requiring only two terminals—for input and output—similar to biological synapses. The key processes realizing the plasticity features are chemical precipitation and dissolution, which occur at forward- or reverse-biased ionic diode junctions in appropriate reservoir electrolytes. Given that the precipitate acts as a physical barrier in the circuit, the above processes change the diode conductivity, which can be interpreted as adjusting “synaptic weight” of the system. By varying the operating conditions, we first demonstrate the four types of plasticity that can be found in biological system: long-term potentiation/depression and short-term potentiation/depression. The plasticity of the proposed iontronic device has characteristics similar to those of neural synapses. To demonstrate its potential use in comparatively complex information processing, we develop a precipitation-based iontronic synapse (PIS) capable of both potentiation and depression. Finally, we show that the postsynaptic signals from the multiple excitatory or inhibitory PISs can be integrated into the total “dendritic” current, which is a function of time and input history, as in actual hippocampal neural circuits.
Mapping the connectivity–conflict interface to inform conservation
Authors: Vasudev Divya , Fletcher Robert J. , Srinivas Nishanth , Marx Andrew J. , Goswami Varun R.
Published: December 2022

Balancing the competing, and often conflicting, needs of people and wildlife in shared landscapes is a major challenge for conservation science and policy worldwide. Connectivity is critical for wildlife persistence, but dispersing animals may come into conflict with people, leading to severe costs for humans and animals and impeding connectivity. Thus, conflict mitigation and connectivity present an apparent dilemma for conservation. We present a framework to address this dilemma and disentangle the effects of barriers to animal movement and conflict-induced mortality of dispersers on connectivity. We extend random-walk theory to map the connectivity–conflict interface, or areas where frequent animal movement may lead to conflict and conflict in turn impedes connectivity. We illustrate this framework with the endangered Asian elephantElephas maximus, a species that frequently disperses out of protected areas and comes into conflict with humans. We mapped expected movement across a human-dominated landscape over the short- and long-term, accounting for conflict mortality. Natural and conflict-induced mortality together reduced expected movement and connectivity among populations. Based on model validation, our conflict predictions that explicitly captured animal movement better explained observed conflict than a model that considered distribution alone. Our work highlights the interaction between connectivity and conflict and enables identification of location-specific conflict mitigation strategies that minimize losses to people, while ensuring critical wildlife movement between habitats. By predicting where animal movement and humans collide, we provide a basis to plan for broad-scale conservation and the mutual well-being of wildlife and people in shared landscapes.
Non–B-form DNA tends to form in centromeric regions and has undergone changes in polyploid oat subgenomes
Authors: Liu Qian , Yi Congyang , Zhang Zeyan , Su Handong , Liu Chang , Huang Yuhong , Li Wei , Hu Xiaojun , Liu Cheng , Birchler James A. , Liu Yang , Han Fangpu
Published: December 2022

Centromeres are the specialized regions of the chromosomes that direct faithful chromosome segregation during cell division. Despite their functional conservation, centromeres display features of rapidly evolving DNA and wide evolutionary diversity in size and organization. Previous work found that the noncanonical B-form DNA structures are abundant in the centromeres of several eukaryotic species with a possible implication for centromere specification. Thus far, systematic studies into the organization and function of non–B-form DNA in plants remain scarce. Here, we applied the oat system to investigate the role of non–B-form DNA in centromeres. We conducted chromatin immunoprecipitation sequencing using an antibody to the centromere-specific histone H3 variant (CENH3); this accurately positioned oat centromeres with different ploidy levels and identified a series of centromere-specific sequences including minisatellites and retrotransposons. To define genetic characteristics of oat centromeres, we surveyed the repeat sequences and found that dyad symmetries were abundant in oat centromeres and were predicted to form non–B-DNA structures in vivo. These structures including bent DNA, slipped DNA, Z-DNA, G-quadruplexes, and R-loops were prone to form within CENH3-binding regions. Dynamic conformational changes of predicted non–B-DNA occurred during the evolution from diploid to tetraploid to hexaploid oat. Furthermore, we applied the single-molecule technique of AFM and DNA:RNA immunoprecipitation with deep sequencing to validate R-loop enrichment in oat centromeres. Centromeric retrotransposons exhibited strong associations with R-loop formation. Taken together, our study elucidates the fundamental character of non–B-form DNA in the oat genome and reveals its potential role in centromeres.
ERK and c-Myc signaling in host-derived tumor endothelial cells is essential for solid tumor growth
Authors: Zuo Zehua , Liu Jie , Sun Zhihao , Cheng Yu-Wei , Ewing Michael , Bugge Thomas H. , Finkel Toren , Leppla Stephen H. , Liu Shihui
Published: December 2022

The limited efficacy of the current antitumor microenvironment strategies is due in part to the poor understanding of the roles and relative contributions of the various tumor stromal cells to tumor development. Here, we describe a versatile in vivo anthrax toxin protein delivery system allowing for the unambiguous genetic evaluation of individual tumor stromal elements in cancer. Our reengineered tumor-selective anthrax toxin exhibits potent antiproliferative activity by disrupting ERK signaling in sensitive cells. Since this activity requires the surface expression of the capillary morphogenesis protein-2 (CMG2) toxin receptor, genetic manipulation of CMG2 expression using our cell-type–specific CMG2 transgenic mice allows us to specifically define the role of individual tumor stromal cell types in tumor development. Here, we established mice with CMG2 only expressed in tumor endothelial cells (ECs) and determined the specific contribution of tumor stromal ECs to the toxin’s antitumor activity. Our results demonstrate that disruption of ERK signaling only within tumor ECs is sufficient to halt tumor growth. We discovered that c-Myc is a downstream effector of ERK signaling and that the MEK–ERK–c-Myc central metabolic axis in tumor ECs is essential for tumor progression. As such, disruption of ERK–c-Myc signaling in host-derived tumor ECs by our tumor-selective anthrax toxins explains their high efficacy in solid tumor therapy.
NADP(H)-dependent biocatalysis without adding NADP(H)
Authors: Herold Ryan A. , Reinbold Raphael , Schofield Christopher J. , Armstrong Fraser A.
Published: December 2022

Isocitrate dehydrogenase 1 (IDH1) naturally copurifies and crystallizes in a resting state with a molecule of its exchangeable cofactor, NADP
+
/NADPH, bound in each monomer of the homodimer. We report electrochemical studies with IDH1 that exploit this property to reveal the massive advantage of nanoconfinement to increase the efficiency of multistep enzyme-catalyzed cascade reactions. When coloaded with ferredoxin NADP
+
reductase in a nanoporous conducting indium tin oxide film, IDH1 carries out the complete electrochemical oxidation of 6 mM isocitrate (in 4mL) to 2-oxoglutarate (2OG), using only the NADP(H) that copurified with IDH1 and was carried into the electrode pores as cargo—the system remains active for days. The entrapped cofactor, now quantifiable by cyclic voltammetry, undergoes ~160,000 turnovers during the process. The results from a variety of electrocatalysis experiments imply that the local concentrations of the two nanoconfined enzymes lie around the millimolar range. The combination of crowding and entrapment results in a 10
2
to 10
3
-fold increase in the efficiency of NADP(H) redox cycling. The ability of the method to drive cascade catalysis in either direction (oxidation or reduction) and remove and replace substrates was exploited to study redox-state dependent differences in cofactor binding between wild-type IDH1 and the cancer-linked R132H variant that catalyzes the “gain of function” reduction of 2OG to 2-hydroxyglutarate instead of isocitrate oxidation. The combined results demonstrate the power of nanoconfinement for facilitating multistep enzyme catalysis (in this case energized and verified electrochemically) and reveal insights into the dynamic role of nicotinamide cofactors as redox (hydride) carriers.
Granular crystals as strong and fully dense architectured materials
Authors: Karuriya Ashta Navdeep , Barthelat Francois
Published: December 2022

Dense topologically interlocked panels are made of well-ordered, stiff building blocks interacting mainly by frictional contact. Under mechanical loads, the deformation of the individual blocks is small, but they can slide and rotate collectively, generating high strength, toughness, impact resistance, and damage tolerance. Here, we expand this construction strategy to fully dense, 3D architectured materials made of space filling building blocks or “grains.” We used mechanical vibrations to assemble 3D printed rhombic dodecahedral and truncated octahedral grains into fully dense face-centered cubic and body-centered cubic “granular crystals.” Triaxial compression tests revealed that these granular crystals are up to 25 times stronger than randomly packed spheres and that after testing, the grains can be recycled into new samples with no loss of strength. They also displayed a rich set of mechanisms: nonlinear deformations, crystal plasticity reminiscent of atomistic mechanisms, geometrical hardening, cross-slip, shear-induced dilatancy, and microbuckling. A most intriguing mechanism involved a pressure-dependent “granular crystal plasticity” with interlocked slip planes that completely forbid slip along certain loading directions. We captured these phenomena using a three-length scale theoretical model which agreed well with the experiments. Once fully understood and harnessed, we envision that these mechanisms will lead to 3D architectured materials with unusual and attractive combinations of mechanical performances as well as capabilities for repair, reshaping, on-site alterations, and recycling of the building blocks. In addition, these granular crystals could serve as “model materials” to explore unusual atomic scale deformation mechanisms, for example, non-Schmid plasticity.
Natural variation in the binding pocket of a parasitic flatworm TRPM channel resolves the basis for praziquantel sensitivity
Authors: Rohr Claudia M. , Sprague Daniel J. , Park Sang-Kyu , Malcolm Nicholas J. , Marchant Jonathan S.
Published: December 2022

The drug praziquantel (PZQ) is the key clinical therapy for treating schistosomiasis and other infections caused by parasitic flatworms. A schistosome target for PZQ was recently identified— a transient receptor potential ion channel in the melastatin subfamily (TRPM
PZQ
)—however, little is known about the properties of TRPM
PZQ
in other parasitic flatworms. Here, TRPM
PZQ
orthologs were scrutinized from all currently available parasitic flatworm genomes. TRPM
PZQ
is present in all parasitic flatworms, and the consensus PZQ binding site was well conserved. Functional profiling of trematode, cestode, and a free-living flatworm TRPM
PZQ
ortholog revealed differing sensitives (~300-fold) of these TRPM
PZQ
channels toward PZQ, which matched the varied sensitivities of these different flatworms to PZQ. Three loci of variation were defined across the parasitic flatworm TRPM
PZQ
pocketome with the identity of an acidic residue in the TRP domain acting as a gatekeeper residue impacting PZQ residency within the TRPM
PZQ
ligand binding pocket. In trematodes and cyclophyllidean cestodes, which display high sensitivity to PZQ, this TRP domain residue is an aspartic acid which is permissive for potent activation by PZQ. However, the presence of a glutamic acid residue found in other parasitic and free-living flatworm TRPM
PZQ
was associated with lower sensitivity to PZQ. The definition of these different binding pocket architectures explains why PZQ shows high therapeutic effectiveness against specific fluke and tapeworm infections and will help the development of better tailored therapies toward other parasitic infections of humans, livestock, and fish.
Bioprosthetic heart valve structural degeneration associated with metabolic syndrome: Mitigation with polyoxazoline modification
Authors: Abramov Alexey , Xue Yingfei , Zakharchenko Andrey , Kurade Mangesh , Soni Rajesh K. , Levy Robert J. , Ferrari Giovanni
Published: December 2022

Bioprosthetic heart valves (BHV), made from glutaraldehyde-fixed xenografts, are widely used for surgical and transcatheter valve interventions but suffer from limited durability due to structural valve degeneration (SVD). We focused on metabolic syndrome (MetS), a risk factor for SVD and a highly prevalent phenotype in patients affected by valvular heart disease with a well-recognized cluster of comorbidities. Multicenter patient data (N = 251) revealed that patients with MetS were at significantly higher risk of accelerated SVD and required BHV replacement sooner. Using a next-generation proteomics approach, we identified significantly differential proteomes from leaflets of explanted BHV from MetS and non-MetS patients (N = 24). Given the significance of protein infiltration in MetS-induced SVD, we then demonstrated the protective effects of polyoxazoline modification of BHV leaflets to mitigate MetS-induced BHV biomaterial degeneration (calcification, tissue cross-linking, and microstructural changes) in an ex vivo serum model and an in vivo with MetS rat subcutaneous implants.
Long-range adsorbate interactions mediated by two-dimensional Dirac fermions
Authors: Wang Xiaohui , Fu Zhen-Guo , Wang Zhigang , Chi Feng , Zhang Ping
Published: December 2022

We provide here an analytical formalism to describe the indirect interaction between adsorbed atom or molecule pairs mediated by two-dimensional (2D) Dirac fermions. We show that in contrast to the case of traditional 2D electron gas, in the 2D Dirac system, the long-range interaction behaves as 1/r
3 decaying Friedel oscillation. This analytical formalism is fully consistent with a tight-binding numerical calculation of honeycomb lattices. Our formalism is suitable for the realistic 2D Dirac materials, such as graphene and surface states of three-dimensional topological insulators.
Topological obstructions to the diagonalisation of pseudodifferential systems
Authors: Capoferri Matteo , Rozenblum Grigori , Saveliev Nikolai , Vassiliev Dmitri
Published: December 2022

Given a matrix pseudodifferential operator on a smooth manifold, one may be interested in diagonalising it by choosing eigenvectors of its principal symbol in a smooth manner. We show that diagonalisation is not always possible, on the whole cotangent bundle or even in a single fibre. We identify global and local topological obstructions to diagonalisation and examine physically meaningful examples demonstrating that all possible scenarios can occur.
EVlncRNA-Dpred: improved prediction of experimentally validated lncRNAs by deep learning
Authors: Zhou Bailing , Ding Maolin , Feng Jing , Ji Baohua , Huang Pingping , Zhang Junye , Yu Xue , Cao Zanxia , Yang Yuedong , Zhou Yaoqi , Wang Jihua
Published: December 2022

Long non-coding RNAs (lncRNAs) played essential roles in nearly every biological process and disease. Many algorithms were developed to distinguish lncRNAs from mRNAs in transcriptomic data and facilitated discoveries of more than 600 000 of lncRNAs. However, only a tiny fraction (<1%) of lncRNA transcripts (~4000) were further validated by low-throughput experiments (EVlncRNAs). Given the cost and labor-intensive nature of experimental validations, it is necessary to develop computational tools to prioritize those potentially functional lncRNAs because many lncRNAs from high-throughput sequencing (HTlncRNAs) could be resulted from transcriptional noises. Here, we employed deep learning algorithms to separate EVlncRNAs from HTlncRNAs and mRNAs. For overcoming the challenge of small datasets, we employed a three-layer deep-learning neural network (DNN) with a K-mer feature as the input and a small convolutional neural network (CNN) with one-hot encoding as the input. Three separate models were trained for human (h), mouse (m) and plant (p), respectively. The final concatenated models (EVlncRNA-Dpred (h), EVlncRNA-Dpred (m) and EVlncRNA-Dpred (p)) provided substantial improvement over a previous model based on support-vector-machines (EVlncRNA-pred). For example, EVlncRNA-Dpred (h) achieved 0.896 for the area under receiver-operating characteristic curve, compared with 0.582 given by sequence-based EVlncRNA-pred model. The models developed here should be useful for screening lncRNA transcripts for experimental validations. EVlncRNA-Dpred is available as a web server at https://www.sdklab-biophysics-dzu.net/EVlncRNA-Dpred/index.html, and the data and source code can be freely available along with the web server.
Auditory cortical connectivity in humans
Authors: Rolls Edmund T , Rauschecker Josef P , Deco Gustavo , Huang Chu-Chung , Feng Jianfeng
Published: December 2022

To understand auditory cortical processing, the effective connectivity between 15 auditory cortical regions and 360 cortical regions was measured in 171 Human Connectome Project participants, and complemented with functional connectivity and diffusion tractography. 1. A hierarchy of auditory cortical processing was identified from Core regions (including A1) to Belt regions LBelt, MBelt, and 52; then to PBelt; and then to HCP A4. 2. A4 has connectivity to anterior temporal lobe TA2, and to HCP A5, which connects to dorsal-bank superior temporal sulcus (STS) regions STGa, STSda, and STSdp. These STS regions also receive visual inputs about moving faces and objects, which are combined with auditory information to help implement multimodal object identification, such as who is speaking, and what is being said. Consistent with this being a “what” ventral auditory stream, these STS regions then have effective connectivity to TPOJ1, STV, PSL, TGv, TGd, and PGi, which are language-related semantic regions connecting to Broca’s area, especially BA45. 3. A4 and A5 also have effective connectivity to MT and MST, which connect to superior parietal regions forming a dorsal auditory “where” stream involved in actions in space. Connections of PBelt, A4, and A5 with BA44 may form a language-related dorsal stream.
Dynamic causal modeling of cerebello-cerebral connectivity when sequencing trait-implying actions
Authors: Pu Min , Ma Qianying , Haihambo Naem , Li Meijia , Baeken Chris , Baetens Kris , Deroost Natacha , Heleven Elien , Van Overwalle Frank
Published: December 2022

Prior studies suggest that the cerebellum contributes to the prediction of action sequences as well as the detection of social violations. In this dynamic causal modeling study, we explored the effective connectivity of the cerebellum with the cerebrum in processing social action sequences. A first model aimed to explore functional cerebello-cerebral connectivity when learning trait/stereotype-implying action sequences. We found many significant bidirectional connectivities between mentalizing areas of the cerebellum and the cerebrum including the temporo-parietal junction (TPJ) and medial prefrontal cortex (mPFC). Within the cerebrum, we found significant connectivity between the right TPJ and the mPFC, and between the TPJ bilaterally. A second model aimed to investigate cerebello-cerebral connectivity when conflicting information arises. We found many significant closed loops between the cerebellum and cerebral mentalizing (e.g. dorsal mPFC) and executive control areas (e.g. medial and lateral prefrontal cortices). Additional closed loops were found within the cerebral mentalizing and executive networks. The current results confirm prior research on effective connectivity linking the cerebellum with mentalizing areas in the cerebrum for predicting social sequences, and extend it to cerebral executive areas for social violations. Overall, this study emphasizes the critical role of cerebello-cerebral connectivity in understanding social sequences.
Each coin has 2 sides: a positive role of alien Potamopyrgus antipodarum (Grey, 1843) snails in reducing the infection of native lymnaeids with trematodes
Authors: Cichy Anna , Stanicka Anna , Żbikowska Elżbieta
Published: December 2022

The change in the distribution of organisms in freshwater ecosystems due to natural or manmade processes raises the question of the impact of alien species on local communities. Although most studies indicate a negative effect, the positive one is more difficult to discern, especially in multispecies systems, including hosts and parasites. The purpose of the study was to check whether the presence of an alien host, Potamopyrgus antipodarum, reduces the intensity of Echinoparyphium aconiatum metacercariae in a native host, Radix spp. We additionally tested the impact of water temperature and the biomass of the alien host on the dilution effect. We experimentally studied (1) the lifespan of echinostome cercariae in different temperatures, (2) the infectivity of cercariae toward the alien host and native host, and (3) the impact of different biomass of the alien host on the intensity of metacercariae in the native host. We found that cercarial survival and infectivity were temperature dependent. However, cercarial survival decreased with increasing temperature, contrary to cercarial infectivity. Echinostome cercariae entered the renal cavity of both the native host and alien host, and successfully transformed into metacercariae. The number of metacercariae in the native host decreased with the increasing biomass of the alien host. Our results indicate that lymnaeids may benefit from the co-occurrence with P. antipodarum, as the presence of additional hosts of different origins may reduce the prevalence of parasites in native communities. However, the scale of the dilution effect depends not only on the increased spectrum of susceptible hosts but also on the other variables of the environment, including water temperature and host density.
Learning curve for adoption of robot-assisted minimally invasive esophagectomy: a systematic review of oncological, clinical, and efficiency outcomes
Authors: Pickering Oliver J , van Boxel Gijs I , Carter Nick C , Mercer Stuart J , Knight Benjamin C , Pucher Philip H
Published: December 2022

Background: Robot-assisted minimally invasive esophagectomy (RAMIE) is gaining increasing popularity as an operative approach. Learning curves to achieve surgical competency in robotic-assisted techniques have shown significant variation in learning curve lengths and outcomes. This study aimed to summarize the current literature on learning curves for RAMIE. Methods: A systematic review was conducted in line with PRISMA guidelines. Electronic databases PubMed, MEDLINE, and Cochrane Library were searched, and articles reporting on learning curves in RAMIE were identified and scrutinized. Studies were eligible if they reported changes in operative outcomes over time, or learning curves, for surgeons newly adopting RAMIE. Results: Fifteen studies reporting on 1767 patients were included. Nine studies reported on surgeons with prior experience of robot-assisted surgery prior to adopting RAMIE, with only four studies outlining a specified RAMIE adoption pathway. Learning curves were most commonly analyzed using cumulative sum control chart (CUSUM) and were typically reported for lymph node yields and operative times, with significant variation in learning curve lengths (18–73 cases and 20–80 cases, respectively). Most studies reported adoption without significant impact on clinical outcomes such as anastomotic leak; significant learning curves were more likely in studies, which did not report a formal learning or adoption pathway. Conclusion: Reported RAMIE adoption phases are variable, with some authors suggesting significant impact to patients. With robust training through formal programmes or proctorship, however, others report RAMIE adoption without impact on clinical outcomes. A formalized adoption curriculum appears critical to prevent adverse effects on operative efficiency and patient care.
Pathological complete response in multimodal treatment of esophageal cancer: a retrospective cohort study
Authors: Hipp Julian , Kuvendjiska Jasmina , Hillebrecht Hans Christian , Timme-Bronsert Sylvia , Fichtner-Feigl Stefan , Hoeppner Jens , Diener Markus K
Published: December 2022

To evaluate pathological complete response (pCR, ypT0ypN0) after neoadjuvant treatment compared with non-complete response (non-CR) in patients with esophageal cancer (EC), and 393 patients were retrospectively analyzed. Survival probability was analyzed in patients with: (i) pCR vs non-CR; (ii) complete response of the primary tumor but persisting lymphatic metastases (non-CR-T0N+) and (iii) pCR and tumor-free lymphnodes exhibiting signs of postneoadjuvant regression vs. no signs of regression. (i) Median overall survival (mOS) was favorable in patients with pCR (pCR: mOS not reached vs. non-CR: 41 months, P < 0.001). Multivariate analysis revealed that grade of regression was not an independent predictor for prolonged survival. Instead, the achieved postneoadjuvant TNM-stage (T-stage: Hazard ratio [HR] ypT3-T4 vs. ypT0-T2: 1.837; N-stage: HR ypN1-N3 vs. ypN0: 2.046; Postneoadjuvant M-stage: HR ypM1 vs. ycM0: 2.709), the residual tumor (R)-classification (HR R1 vs. R0: 4.195) and the histologic subtype of EC (HR ESCC vs. EAC: 1.688) were prognostic factors. Patients with non-CR-T0N+ have a devastating prognosis, similar to those with local non-CR and lymphatic metastases (non-CR-T + N+) (non-CR-T0N+: 22.0 months, non-CR-T + N-: mOS not reached, non-CR-T + N+: 23.0 months; P-values: non-CR-T0N+ vs. non-CR-T + N-: 0.016; non-CR-T0N+ vs. non-CR-T + N+: 0.956; non-CR-T + N- vs. non-CR-T + N+: <0.001). Regressive changes in lymphnodes after neoadjuvant treatment did not influence survival-probability in patients with pCR (mOS not reached in each group; EAC-patients: P = 0.0919; ESCC-patients: P = 0.828). Particularly, the achieved postneoadjuvant ypTNM-stage influences the survival probability of patients with EC. Patients with non-CR-T0N+ have a dismal prognosis, and only true pathological complete response with ypT0ypN0 offers superior survival probabilities.
Differential response to isometric handgrip depending on the heart failure condition in patients with functional mitral regurgitation: a case report
Authors: Hamatani Yasuhiro , Ide Yuya , Watanabe Hirotoshi , Akao Masaharu
Published: December 2022

Background

Functional mitral regurgitation (MR) changes dynamically depending on the loading conditions and can cause acute heart failure (HF). Isometric handgrip is a simple stress test and can be performed during early phase of acute HF for the evaluation of MR.

Case summary

A 70-year-old woman with a prior myocardial infarction four months before, and with history of recurrent HF admission with functional MR, who received optimal HF medications, was hospitalized for acute HF. On the following day of the admission, isometric handgrip stress echocardiography was performed to evaluate functional MR. During the handgrip, MR deteriorated from moderate to severe and the tricuspid regurgitation pressure gradient increased from 45 to 60 mmHg. After HF stabilization 2 weeks after admission, repeat handgrip stress echocardiography showed that the degree of MR did not significantly change being moderate and the tricuspid regurgitation pressure gradient was only mildly elevated from 25 to 30 mmHg. She underwent transcatheter edge-to-edge mitral repair, and thereafter she has not experienced the rehospitalization for acute HF.

Discussion

Exercise stress test is recommended for the evaluation of functional MR in HF patients; however, exercise tests are difficult to perform during the early phase of acute HF. In this regard, handgrip test is an option to investigate the exacerbating impact of functional MR during early-phase acute HF. This case indicated that response to isometric handgrip can vary depending on HF condition, highlighting the importance of taking into account the timing of the handgrip procedure in patients with functional MR and HF.
Magnetic properties of surface soils in the upper and middle reaches of the Yarlung Zangbo River Basin, southern Tibetan Plateau, and their environmental significance
Authors: Wang Shuyuan , Chen Zixuan , Yang Junhuai , Gao Fuyuan , Tian Weidong , Ma Xingyue , Xia Dunsheng
Published: December 2022

The relationship between climate and the magnetic properties of surface soils on the Chinese Loess Plateau (CLP) have been widely used to provide the basis for palaeoclimatic reconstruction, based on the underlying loess/palaeosol sequences. To date, however, there are few investigations of variations in the magnetic properties of surface soils on the Tibetan Plateau (TP), especially on the southern TP. Therefore, it remains unclear whether magnetic properties could be used as proxies for palaeoclimatic reconstruction in the region. In this study, environmental magnetic parameters and bulk sediment grain-size measurements were made on a set of surface samples from the Yarlung Zangbo River Basin (YZRB), on the southern TP, and their environmental significance was evaluated. The results reveal spatial differences in the magnetic properties of the surface soils, likely caused by regional climatic factors. The input of primary magnetic minerals is the driver of the magnetic properties of the samples from the western (Gar-Saga) part of the YZRB, where the magnetic variations are controlled by the influence of wind intensity on the local source material. However, the samples from the eastern region (Gongga-Nyingchi) are significantly affected by the topographic and sedimentary conditions, and there is no relationship between the magnetic properties and climate. The samples from the central part of the study area (Saga-Gongga) show obvious signs of a pedogenic influence on magnetic properties and ultrafine superparamagnetic (SP) and single domain (SD) ferrimagnetic minerals dominate the magnetic susceptibility. Combined with the variation of grain size, this implies the influence of wind intensity and pedogenesis contribute to the magnetic enhancement. However, the pedogenic intensity closely related to precipitation and temperature could offer the possibility of using sedimentary magnetic properties for palaeoclimatic reconstruction. Furthermore, the existence of a distinct pedogenic alteration boundary in the Saga area is consistent with the location of the Indian summer monsoon, which may be the dominant control on the pedogenic intensity.
An empirical investigation into the impact of winner’s curse on estimates from Mendelian randomization
Authors: Jiang Tao , Gill Dipender , Butterworth Adam S , Burgess Stephen
Published: December 2022

Introduction

Genetic associations for variants identified through genome-wide association studies (GWASs) tend to be overestimated in the original discovery data set as, if the association was underestimated, the variant may not have been detected. This bias, known as winner’s curse, can affect Mendelian randomization estimates, but its severity and potential impact are unclear.

Methods

We performed an empirical investigation to assess the potential bias from winner’s curse in practice. We considered Mendelian randomization estimates for the effect of body mass index (BMI) on coronary artery disease risk. We randomly divided a UK Biobank data set 100 times into three equally sized subsets. The first subset was treated as the ‘discovery GWAS’. We compared genetic associations estimated in the discovery GWAS to those estimated in the other subsets for each of the 100 iterations.

Results

For variants associated with BMI at P < 5 × 10–8 in at least one iteration, genetic associations with BMI were up to 5-fold greater in iterations in which the variant was associated with BMI at P < 5 × 10–8 compared with its mean association across all iterations. If the minimum P-value for association with BMI was P = 10–13 or lower, then this inflation was <25%. Mendelian randomization estimates were affected by winner’s curse bias. However, bias did not materially affect results; all analyses indicated a deleterious effect of BMI on coronary artery disease risk.

Conclusions

Winner’s curse can bias Mendelian randomization estimates, although its practical impact may not be substantial. If avoiding sample overlap is infeasible, analysts should consider performing a sensitivity analysis based on variants strongly associated with the exposure.
Effects of a Saccharomyces cerevisiae fermentation product on fecal characteristics, metabolite concentrations, and microbiota populations of dogs subjected to exercise challenge
Authors: Oba Patrícia M , Carroll Meredith Q , Sieja Kelly M , de Souza Nogueira Juliana P , Yang Xiaojing , Epp Tammi Y , Warzecha Christine M , Varney Jessica L , Fowler Jason W , Coon Craig N , Swanson Kelly S
Published: December 2022

The objective of this study was to determine the fecal characteristics, microbiota, and metabolites of dogs fed a Saccharomyces cerevisiae fermentation product (SCFP) and subjected to exercise challenge in untrained and trained states. Thirty-six adult dogs (18 male, 18 female; mean age: 7.1 yr; mean body weight: 29.0 kg) were randomly assigned to control or SCFP-supplemented (250 mg/dog/d) diets and fed for 10 wk. After 3 wk, dogs were given an exercise challenge (6.5 km run), with fresh fecal samples collected pre- and post-challenge. Dogs were then trained by a series of distance-defined running exercise regimens over 7 wk (two 6.4 km runs/wk for 2 wk; two 9.7 km runs/wk for 2 wk; two 12.9 km runs/wk for 2 wk; two 3.2 km runs/wk). Dogs were then given exercise challenge (16 km run) in the trained state, with fresh fecal samples collected pre- and post-challenge. Fecal microbiota data were evaluated using QIIME2, while all other data were analyzed using the Mixed Models procedure of SAS. Effects of diet, exercise, and diet*exercise were tested with P < 0.05 considered significant. Exercise challenge reduced fecal pH and ammonia in both treatments, and in untrained and trained dogs. After the exercise challenge in untrained dogs, fecal indole, isobutyrate, and isovalerate were reduced, while acetate and propionate were increased. Following the exercise challenge in trained dogs, fecal scores and butyrate decreased, while isobutyrate and isovalerate increased. SCFP did not affect fecal scores, pH, dry matter, or metabolites, but fecal Clostridium was higher in controls than in SCFP-fed dogs over time. SCFP and exercise challenge had no effect on alpha or beta diversity in untrained dogs. However, the weighted principal coordinate analysis plot revealed clustering of dogs before and after exercise in trained dogs. After exercise challenge, fecal Collinsella, Slackia, Blautia, Ruminococcus, and Catenibacterium were higher and Bacteroides, Parabacteroides, Prevotella, Phascolarctobacterium, Fusobacterium, and Sutterella were lower in both untrained and trained dogs. Using qPCR, SCFP increased fecal Turicibacter, and tended to increase fecal Lactobacillus vs. controls. Exercise challenge increased fecal Turicibacter and Blautia in both untrained and trained dogs. Our findings show that exercise and SCFP may affect the fecal microbiota of dogs. Exercise was the primary cause of the shifts, however, with trained dogs having more profound changes than untrained dogs.
Glycine regulates lipid peroxidation promoting porcine oocyte maturation and early embryonic development
Authors: Gao Lepeng , Zhang Chang , Zheng Yingying , Wu Deyi , Chen Xinyuan , Lan Hainan , Zheng Xin , Wu Hao , Li Suo
Published: December 2022

In vitro-cultured oocytes are separated from the follicular micro-environment in vivo and are more vulnerable than in vivo oocytes to changes in the external environment. This vulnerability disrupts the homeostasis of the intracellular environment, affecting oocyte meiotic completion, and subsequent embryonic developmental competence in vitro. Glycine, one of the main components of glutathione (GSH), plays an important role in the protection of porcine oocytes in vitro. However, the protective mechanism of glycine needs to be further clarified. Our results showed that glycine supplementation promoted cumulus cell expansion and oocyte maturation. Detection of oocyte development ability showed that glycine significantly increased the cleavage rate and blastocyst rate during in vitro fertilization (IVF). SMART-seq revealed that this effect was related to glycine-mediated regulation of cell membrane structure and function. Exogenous addition of glycine significantly increased the levels of the anti-oxidant GSH and the expression of anti-oxidant-related genes (glutathione peroxidase 4 [GPX4], catalase [CAT], superoxide dismutase 1 [SOD1], superoxide dismutase 2 [SOD2], and mitochondrial solute carrier family 25, member 39 [SLC25A39]), decreased the lipid peroxidation caused by reactive oxygen species (ROS) and reduced the level of malondialdehyde (MDA) by enhancing the functions of mitochondria, peroxisomes and lipid droplets (LDs) and the levels of lipid metabolism-related factors (peroxisome proliferator activated receptor coactivator 1 alpha [PGC-1α], peroxisome proliferator-activated receptor γ [PPARγ], sterol regulatory element binding factor 1 [SREBF1], autocrine motility factor receptor [AMFR], and ATP). These effects further reduced ferroptosis and maintained the normal structure and function of the cell membrane. Our results suggest that glycine plays an important role in oocyte maturation and later development by regulating ROS-induced lipid metabolism, thereby protecting against biomembrane damage.
The Evolution of the ‘Trade and …’ ‘Debate’—A View from ASEAN
Authors: Hsu Locknie
Published: December 2022

This article explores the ‘Trade and …’ ‘Debate’ in the context of trade and environment issues. It provides an explanation of the evolution of discussions of such issues in a non-dispute settlement context, using developments in the Association of Southeast Asian Nations’ integration efforts as illustrations. It also highlights a number of opportunities for trade and environment collaboration in negotiations for free trade agreement and Digital Economy Partnership Agreements.
Assessing Liberal Democratic Values of Refugees in Germany and Their Origin Countries—Evidence for Cultural Self-Selection?
Authors: Fuchs Lukas M
Published: December 2022

Expanding on a new body of literature on cultural self-selection, the present study investigates how refugees who arrived in Germany since 2013 relate to the general population of their countries of origin in terms of liberal democratic values. The cultural self-selection literature suggests that more liberal individuals may be more likely to flee to Germany. To trace cultural self-selection amongst refugees, a series of analyses is conducted: first, refugees of Iraqi, Russian, and Pakistani descent in Germany (IAB-BAMF-SOEP) and the general populations of their origin countries (World Values Survey) are statistically matched on socio-demographic characteristics and their democratic values are compared. After matching the samples, refugees express significantly higher support for liberal democratic values than the general population of their countries of origin. Second, a series of regression models is calculated, tracing three potential mechanisms for the observable differences: (1) acculturation effects in Germany, (2) the experience of being forcibly displaced, and (3) cultural self-selection. The results speak to the theoretical conjectures of the cultural self-selection literature. Liberal democratic values are not correlated with the time spent in Germany (acculturation), flight reasons, and past traumatic experiences (flight experience) but are positively correlated with a critical stance towards the government in the country of origin as well as with positive feelings towards Germany as the receiving society.