bluuebunny/crossref_metadata_2025 huggingface dataset:
Microphysical Modeling of Fault Slip and Stability Transition in Hydrothermal Conditions
Authors: Mei Cheng , Rudnicki John W.
Published: July 2023

Field and laboratory observations indicate that the frictional behaviors of faults depend on hydrothermal conditions. We extend the microphysical Chen‐Niemeijer‐Spiers (CNS) model to hydrothermal conditions by using the observed temperature variation of indentation hardness to infer the temperature dependence of a microphysical parameter . This parameter is assumed constant in previous versions of the CNS model. A simple spring‐slider system is used to simulate the fault system and investigate the steady‐state frictional behaviors of wet granite gouges. Our numerical results quantitatively reproduce experimental data showing the frictional‐plastic transition. The results also describe the transition from velocity‐strengthening at low temperatures (<160°C), to velocity‐weakening at intermediate temperatures (160°C–370°C), then back to velocity‐strengthening at high temperatures (>370°C). In our extended CNS model, these results suggest that the dominant shear deformation mechanism does transition from frictional granular flow to fully plastic creep with increasing temperature.
The Role of Storm‐Driven Seaward Sediment Flux in Coastal Barrier Dynamics Is an Enduring Puzzle
Authors: Lazarus Eli D.
Published: July 2023

Coastal barrier systems are low‐lying environments that bear the brunt of storm impacts, with cumulative and complex consequences for barrier evolution. Most studies of barrier responses to storms examine what happens when water and sediment get driven landward across a barrier from its ocean side. Sherwood et al. (2023, https://doi.org/10.1029/2022jf006934) investigate the effects of overland flow and sediment transport forced across a barrier in the opposite direction—from its sheltered side, seaward. Using high‐resolution imagery of a barrier island observed before and after a hurricane, Sherwood et al. (2023, https://doi.org/10.1029/2022jf006934) show that “outwash” flow across the barrier shifted several times more sediment by volume than is typically reported for beach and dune erosion from onshore forcing. Their findings are remarkable because they are not exceptional: a related survey of barriers along the Atlantic and Gulf Coasts of the USA observed patterns of outwash morphology essentially everywhere. Insights into outwash morphology open exciting questions regarding the overlooked role of storm‐driven seaward sediment transport in barrier dynamics, with important implications for post‐storm barrier recovery and barrier evolution over decades to centuries.
Methane Emissions From Land and Aquatic Ecosystems in Western Siberia: An Analysis With Methane Biogeochemistry Models
Authors: Xi Xuan , Zhuang Qianlai , Kim Seungbum , Zhang Zhen
Published: July 2023

Western Siberia contains extensive wetlands and aquatic ecosystems, contributing a significant amount of methane (CH4) emissions to the atmosphere. However, estimates of CH4 fluxes over the region are poorly constrained partly due to the uncertainties from the inundated area data. This study applied two process‐based biogeochemistry models to quantify the emissions from land and aquatic ecosystems over the region within the period 2000–2021 using different inundation datasets. To drive land methane modeling, we use one static wetland map and one dynamic wetland area data set called Wetland Area and Dynamics for Methane Modeling (WAD2M) (2000–2020). To drive lake methane modeling, we use the surface area of aquatic ecosystems from three datasets: (a) HydroLAKES; (b) Global Surface Water (GSW); and (c) surface water inundation from Soil Moisture Active Passive (SMAP) (2016–2021). Using these datasets, we conduct four simulations to compare emissions over the region. We find that the net methane emissions from land using the static wetland map are larger than those using WAD2M. SMAP and GSW estimate larger emissions than HydroLAKES does from aquatic ecosystems. Total emissions over the region range from 4.80 ± 0.43 to 8.29 ± 0.81 Tg CH4/year from 2016 to 2020, which is the intersection period of four simulations. This study is among the first to investigate methane emissions from the whole landscape in the region. Our study highlights the importance of dynamic wetland and aquatic area data in quantifying regional methane emissions.
Differential contribution of nitrifying prokaryotes to groundwater nitrification
Authors: Krüger Markus , Chaudhari Narendrakumar , Thamdrup Bo , Overholt Will A , Bristow Laura A , Taubert Martin , Küsel Kirsten , Jehmlich Nico , von Bergen Martin , Herrmann Martina
Published: July 2023

The ecophysiology of complete ammonia-oxidizing bacteria (CMX) of the genus Nitrospira and their widespread occurrence in groundwater suggests that CMX bacteria have a competitive advantage over ammonia-oxidizing bacteria (AOB) and archaea (AOA) in these environments. However, the specific contribution of their activity to nitrification processes has remained unclear. We aimed to disentangle the contribution of CMX, AOA and AOB to nitrification and to identify the environmental drivers of their niche differentiation at different levels of ammonium and oxygen in oligotrophic carbonate rock aquifers. CMX ammonia monooxygenase sub-unit A (amoA) genes accounted on average for 16 to 75% of the total groundwater amoA genes detected. Nitrification rates were positively correlated to CMX clade A associated phylotypes and AOB affiliated with Nitrosomonas ureae. Short-term incubations amended with the nitrification inhibitors allylthiourea and chlorate suggested that AOB contributed a large fraction to overall ammonia oxidation, while metaproteomics analysis confirmed an active role of CMX in both ammonia and nitrite oxidation. Ecophysiological niche differentiation of CMX clades A and B, AOB and AOA was linked to their requirements for ammonium, oxygen tolerance, and metabolic versatility. Our results demonstrate that despite numerical predominance of CMX, the first step of nitrification in oligotrophic groundwater appears to be primarily governed by AOB. Higher growth yields at lower ammonia turnover rates and energy derived from nitrite oxidation most likely enable CMX to maintain consistently high populations.
Voice acoustics allow classifying autism spectrum disorder with high accuracy
Authors: Briend Frédéric , David Céline , Silleresi Silvia , Malvy Joëlle , Ferré Sandrine , Latinus Marianne
Published: July 2023

Early identification of children on the autism spectrum is crucial for early intervention with long-term positive effects on symptoms and skills. The need for improved objective autism detection tools is emphasized by the poor diagnostic power in current tools. Here, we aim to evaluate the classification performance of acoustic features of the voice in children with autism spectrum disorder (ASD) with respect to a heterogeneous control group (composed of neurotypical children, children with Developmental Language Disorder [DLD] and children with sensorineural hearing loss with Cochlear Implant [CI]). This retrospective diagnostic study was conducted at the Child Psychiatry Unit of Tours University Hospital (France). A total of 108 children, including 38 diagnosed with ASD (8.5 ± 0.25 years), 24 typically developing (TD; 8.2 ± 0.32 years) and 46 children with atypical development (DLD and CI; 7.9 ± 0.36 years) were enrolled in our studies. The acoustic properties of speech samples produced by children in the context of a nonword repetition task were measured. We used a Monte Carlo cross-validation with an ROC (Receiving Operator Characteristic) supervised k-Means clustering algorithm to develop a classification model that can differentially classify a child with an unknown disorder. We showed that voice acoustics classified autism diagnosis with an overall accuracy of 91% [CI95%, 90.40%-91.65%] against TD children, and of 85% [CI95%, 84.5%–86.6%] against an heterogenous group of non-autistic children. Accuracy reported here with multivariate analysis combined with Monte Carlo cross-validation is higher than in previous studies. Our findings demonstrate that easy-to-measure voice acoustic parameters could be used as a diagnostic aid tool, specific to ASD.
Genomic and evolutionary characteristics of metastatic gastric cancer by routes
Authors: Lee Jae Eun , Kim Ki Tae , Shin Su-Jin , Cheong Jae-Ho , Choi Yoon Young
Published: July 2023

Background

In gastric cancer (GC) patients, metastatic progression through the lymphatic, hematogenous, peritoneal, and ovarian routes, is the ultimate cause of death. However, the genomic and evolutionary characteristics of metastatic GC have not been widely evaluated.

Methods

Whole-exome sequencing data were analyzed for 99 primary and paired metastatic gastric cancers from 15 patients who underwent gastrectomy and metastasectomy.

Results

Hematogenous metastatic tumors were associated with increased chromosomal instability and de novo gain/amplification in cancer driver genes, whereas peritoneal/ovarian metastasis was linked to sustained chromosomal stability and de novo somatic mutations in driver genes. The genomic distance of the hematogenous and peritoneal metastatic tumors was found to be closer to the primary tumors than lymph node (LN) metastasis, while ovarian metastasis was closer to LN and peritoneal metastasis than the primary tumor. Two migration patterns for metastatic GCs were identified; branched and diaspora. Both molecular subtypes of the metastatic tumors, rather than the primary tumor, and their migration patterns were related to patient survival.

Conclusions

Genomic characteristics of metastatic gastric cancer is distinctive by routes and associated with patients’ prognosis along with genomic evolution pattenrs, indicating that both primary and metastatic gastric cancers require genomic evaluation.
Effects of altered glycolysis levels on CD8+ T cell activation and function
Authors: Cao Jiaying , Liao Shan , Zeng Feng , Liao Qianjin , Luo Gengqiu , Zhou Yanhong
Published: July 2023

CD8+ T cells are an important component of the body’s adaptive immune response. During viral or intracellular bacterial infections, CD8+ T cells are rapidly activated and differentiated to exert their immune function by producing cytokines. Alterations in the glycolysis of CD8+ T cells have an important effect on their activation and function, while glycolysis is important for CD8+ T cell functional failure and recovery. This paper summarizes the importance of CD8+ T cell glycolysis in the immune system. We discuss the link between glycolysis and CD8+ T cell activation, differentiation, and proliferation, and the effect of altered glycolysis on CD8+ T cell function. In addition, potential molecular targets to enhance and restore the immune function of CD8+ T cells by affecting glycolysis and the link between glycolysis and CD8+ T cell senescence are summarized. This review provides new insights into the relationship between glycolysis and CD8+ T cell function, and proposes novel strategies for immunotherapy by targeting glycolysis.
Impact of cell cycle on repair of ruptured nuclear envelope and sensitivity to nuclear envelope stress in glioblastoma
Authors: Kamikawa Yasunao , Wu Zuqian , Nakazawa Nayuta , Ito Taichi , Saito Atsushi , Imaizumi Kazunori
Published: July 2023

The nuclear envelope (NE) is often challenged by various stresses (known as “NE stress”), leading to its dysfunction. Accumulating evidence has proven the pathological relevance of NE stress in numerous diseases ranging from cancer to neurodegenerative diseases. Although several proteins involved in the reassembly of the NE after mitosis have been identified as the NE repair factors, the regulatory mechanisms modulating the efficiency of NE repair remain unclear. Here, we showed that response to NE stress varied among different types of cancer cell lines. U251MG derived from glioblastoma exhibited severe nuclear deformation and massive DNA damage at the deformed nuclear region upon mechanical NE stress. In contrast, another cell line derived from glioblastoma, U87MG, only presented mild nuclear deformation without DNA damage. Time-lapse imaging demonstrated that repairing of ruptured NE often failed in U251MG, but not in U87MG. These differences were unlikely to have been due to weakened NE in U251MG because the expression levels of lamin A/C, determinants of the physical property of the NE, were comparable and loss of compartmentalization across the NE was observed just after laser ablation of the NE in both cell lines. U251MG proliferated more rapidly than U87MG concomitant with reduced expression of p21, a major inhibitor of cyclin-dependent kinases, suggesting a correlation between NE stress response and cell cycle progression. Indeed, visualization of cell cycle stages using fluorescent ubiquitination-based cell cycle indicator reporters revealed greater resistance of U251MG to NE stress at G1 phase than at S and G2 phases. Furthermore, attenuation of cell cycle progression by inducing p21 in U251MG counteracted the nuclear deformation and DNA damage upon NE stress. These findings imply that dysregulation of cell cycle progression in cancer cells causes loss of the NE integrity and its consequences such as DNA damage and cell death upon mechanical NE stress.
The ELK3-DRP1 axis determines the chemosensitivity of triple-negative breast cancer cells to CDDP by regulating mitochondrial dynamics
Authors: Park Joo Dong , Jang Hye Jung , Choi Seung Hee , Jo Gae Hoon , Choi Jin-Ho , Hwang Sohyun , Park Wooram , Park Kyung-Soon
Published: July 2023

Triple-negative breast cancer (TNBC) is the most lethal form of breast cancer. TNBC patients have higher rates of metastasis and restricted therapy options. Although chemotherapy is the conventional treatment for TNBC, the frequent occurrence of chemoresistance significantly lowers the efficacy of treatment. Here, we demonstrated that ELK3, an oncogenic transcriptional repressor that is highly expressed in TNBC, determined the chemosensitivity of two representative TNBC cell lines (MDA-MB231 and Hs578T) to cisplatin (CDDP) by regulating mitochondrial dynamics. We observed that the knockdown of ELK3 in MDA-MB231 and Hs578T rendered these cell lines more susceptible to the effects of CDDP. We further demonstrated that the chemosensitivity of TNBC cells was caused by the CDDP-mediated acceleration of mitochondrial fission, excessive mitochondrial reactive oxygen species production, and subsequent DNA damage. In addition, we identified DNM1L, a gene encoding the dynamin-related protein 1 (a major regulator of mitochondrial fission), as a direct downstream target of ELK3. Based on these results, we propose that the suppression of ELK3 expression could be used as a potential therapeutic strategy for overcoming the chemoresistance or inducing the chemosensitivity of TNBC.
Reinforcement learning establishes a minimal metacognitive process to monitor and control motor learning performance
Authors: Sugiyama Taisei , Schweighofer Nicolas , Izawa Jun
Published: July 2023

Humans and animals develop learning-to-learn strategies throughout their lives to accelerate learning. One theory suggests that this is achieved by a metacognitive process of controlling and monitoring learning. Although such learning-to-learn is also observed in motor learning, the metacognitive aspect of learning regulation has not been considered in classical theories of motor learning. Here, we formulated a minimal mechanism of this process as reinforcement learning of motor learning properties, which regulates a policy for memory update in response to sensory prediction error while monitoring its performance. This theory was confirmed in human motor learning experiments, in which the subjective sense of learning-outcome association determined the direction of up- and down-regulation of both learning speed and memory retention. Thus, it provides a simple, unifying account for variations in learning speeds, where the reinforcement learning mechanism monitors and controls the motor learning process.
High-resolution cryo-EM structure of the Pseudomonas bacteriophage E217
Authors: Li Fenglin , Hou Chun-Feng David , Lokareddy Ravi K. , Yang Ruoyu , Forti Francesca , Briani Federica , Cingolani Gino
Published: July 2023

E217 is a Pseudomonas phage used in an experimental cocktail to eradicate cystic fibrosis-associated Pseudomonas aeruginosa. Here, we describe the structure of the whole E217 virion before and after DNA ejection at 3.1 Å and 4.5 Å resolution, respectively, determined using cryogenic electron microscopy (cryo-EM). We identify and build de novo structures for 19 unique E217 gene products, resolve the tail genome-ejection machine in both extended and contracted states, and decipher the complete architecture of the baseplate formed by 66 polypeptide chains. We also determine that E217 recognizes the host O-antigen as a receptor, and we resolve the N-terminal portion of the O-antigen-binding tail fiber. We propose that E217 design principles presented in this paper are conserved across PB1-like Myoviridae phages of the Pbunavirus genus that encode a ~1.4 MDa baseplate, dramatically smaller than the coliphage T4.
DNA 5-methylcytosine detection and methylation phasing using PacBio circular consensus sequencing
Authors: Ni Peng , Nie Fan , Zhong Zeyu , Xu Jinrui , Huang Neng , Zhang Jun , Zhao Haochen , Zou You , Huang Yuanfeng , Li Jinchen , Xiao Chuan-Le , Luo Feng , Wang Jianxin
Published: July 2023

Long single-molecular sequencing technologies, such as PacBio circular consensus sequencing (CCS) and nanopore sequencing, are advantageous in detecting DNA 5-methylcytosine in CpGs (5mCpGs), especially in repetitive genomic regions. However, existing methods for detecting 5mCpGs using PacBio CCS are less accurate and robust. Here, we present ccsmeth, a deep-learning method to detect DNA 5mCpGs using CCS reads. We sequence polymerase-chain-reaction treated and M.SssI-methyltransferase treated DNA of one human sample using PacBio CCS for training ccsmeth. Using long (≥10 Kb) CCS reads, ccsmeth achieves 0.90 accuracy and 0.97 Area Under the Curve on 5mCpG detection at single-molecule resolution. At the genome-wide site level, ccsmeth achieves >0.90 correlations with bisulfite sequencing and nanopore sequencing using only 10× reads. Furthermore, we develop a Nextflow pipeline, ccsmethphase, to detect haplotype-aware methylation using CCS reads, and then sequence a Chinese family trio to validate it. ccsmeth and ccsmethphase can be robust and accurate tools for detecting DNA 5-methylcytosines.
Global environmental implications of atmospheric methane removal through chlorine-mediated chemistry-climate interactions
Authors: Li Qinyi , Meidan Daphne , Hess Peter , Añel Juan A. , Cuevas Carlos A. , Doney Scott , Fernandez Rafael P. , van Herpen Maarten , Höglund-Isaksson Lena , Johnson Matthew S. , Kinnison Douglas E. , Lamarque Jean-François , Röckmann Thomas , Mahowald Natalie M. , Saiz-Lopez Alfonso
Published: July 2023

Atmospheric methane is both a potent greenhouse gas and photochemically active, with approximately equal anthropogenic and natural sources. The addition of chlorine to the atmosphere has been proposed to mitigate global warming through methane reduction by increasing its chemical loss. However, the potential environmental impacts of such climate mitigation remain unexplored. Here, sensitivity studies are conducted to evaluate the possible effects of increasing reactive chlorine emissions on the methane budget, atmospheric composition and radiative forcing. Because of non-linear chemistry, in order to achieve a reduction in methane burden (instead of an increase), the chlorine atom burden needs to be a minimum of three times the estimated present-day burden. If the methane removal target is set to 20%, 45%, or 70% less global methane by 2050 compared to the levels in the Representative Concentration Pathway 8.5 scenario (RCP8.5), our modeling results suggest that additional chlorine fluxes of 630, 1250, and 1880 Tg Cl/year, respectively, are needed. The results show that increasing chlorine emissions also induces significant changes in other important climate forcers. Remarkably, the tropospheric ozone decrease is large enough that the magnitude of radiative forcing decrease is similar to that of methane. Adding 630, 1250, and 1880 Tg Cl/year to the RCP8.5 scenario, chosen to have the most consistent current-day trends of methane, will decrease the surface temperature by 0.2, 0.4, and 0.6 °C by 2050, respectively. The quantity and method in which the chlorine is added, its interactions with climate pathways, and the potential environmental impacts on air quality and ocean acidity, must be carefully considered before any action is taken.
Spin-orbit coupling-enhanced valley ordering of malleable bands in twisted bilayer graphene on WSe2
Authors: Bhowmik Saisab , Ghawri Bhaskar , Park Youngju , Lee Dongkyu , Datta Suvronil , Soni Radhika , Watanabe K. , Taniguchi T. , Ghosh Arindam , Jung Jeil , Chandni U.
Published: July 2023

Recent experiments in magic-angle twisted bilayer graphene have revealed a wealth of novel electronic phases as a result of interaction-driven spin-valley flavour polarisation. In this work, we investigate correlated phases due to the combined effect of spin-orbit coupling-enhanced valley polarisation and the large density of states below half filling of the moiré band in twisted bilayer graphene coupled to tungsten diselenide. We observe an anomalous Hall effect, accompanied by a series of Lifshitz transitions that are highly tunable with carrier density and magnetic field. The magnetisation shows an abrupt change of sign near half-filling, confirming its orbital nature. While the Hall resistance is not quantised at zero magnetic fields—indicating a ground state with partial valley polarisation—perfect quantisation and complete valley polarisation are observed at finite fields. Our results illustrate that singularities in the flat bands in the presence of spin-orbit coupling can stabilise ordered phases even at non-integer moiré band fillings.
Parsing altered gray matter morphology of depression using a framework integrating the normative model and non-negative matrix factorization
Authors: Han Shaoqiang , Cui Qian , Zheng Ruiping , Li Shuying , Zhou Bingqian , Fang Keke , Sheng Wei , Wen Baohong , Liu Liang , Wei Yarui , Chen Huafu , Chen Yuan , Cheng Jingliang , Zhang Yong
Published: July 2023

The high inter-individual heterogeneity in individuals with depression limits neuroimaging studies with case-control approaches to identify promising biomarkers for individualized clinical decision-making. We put forward a framework integrating the normative model and non-negative matrix factorization (NMF) to quantitatively assess altered gray matter morphology in depression from a dimensional perspective. The proposed framework parses altered gray matter morphology into overlapping latent disease factors, and assigns patients distinct factor compositions, thus preserving inter-individual variability. We identified four robust disease factors with distinct clinical symptoms and cognitive processes in depression. In addition, we showed the quantitative relationship between the group-level gray matter morphological differences and disease factors. Furthermore, this framework significantly predicted factor compositions of patients in an independent dataset. The framework provides an approach to resolve neuroanatomical heterogeneity in depression.
Alleviation of Limosilactobacillus reuteri in polycystic ovary syndrome protects against circadian dysrhythmia-induced dyslipidemia via capric acid and GALR1 signaling
Authors: Li Shang , Zhai Junyu , Chu Weiwei , Geng Xueying , Wang Dongshuang , Jiao Luwei , Lu Gang , Chan Wai-Yee , Sun Kang , Sun Yun , Chen Zi-Jiang , Du Yanzhi
Published: July 2023

Knowledge gaps that limit the development of therapies for polycystic ovary syndrome (PCOS) concern various environmental factors that impact clinical characteristics. Circadian dysrhythmia contributes to glycometabolic and reproductive hallmarks of PCOS. Here, we illustrated the amelioration ofLimosilactobacillus reuteri(L. reuteri) on biorhythm disorder-ignited dyslipidemia of PCOS via a microbiota-metabolite-liver axis. A rat model of long-term (8 weeks) darkness treatment was used to mimic circadian dysrhythmia-induced PCOS. Hepatic transcriptomics certified by in vitro experiments demonstrated that increased hepatic galanin receptor 1 (GALR1) due to darkness exposure functioned as a critical upstream factor in the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway to suppress nuclear receptors subfamily 1, group D, member 1 (NR1D1) and promoted sterol regulatory element binding protein 1 (SREBP1), inducing lipid accumulation in the liver. Further investigations figured out a restructured microbiome-metabolome network followingL. reuteriadministration to protect darkness rats against dyslipidemia. Notably,L. reuteriintervention resulted in the decrease ofClostridium sensu stricto 1andRuminococcaceae UCG-010as well as gut microbiota-derived metabolite capric acid, which could further inhibit GALR1-NR1D1-SREBP1 pathway in the liver. In addition, GALR antagonist M40 reproduced similar ameliorative effects asL. reuterito protect against dyslipidemia. While exogenous treatment of capric acid restrained the protective effects ofL. reuteriin circadian disruption-induced PCOS through inhibiting GALR1-dependent hepatic lipid metabolism. These findings purport thatL. reutericould serve for circadian disruption-associated dyslipidemia. Manipulation ofL. reuteri–capric acid–GALR1 axis paves way for clinical therapeutic strategies to prevent biorhythm disorder-ignited dyslipidemia in PCOS women.
Proteome wide association studies of LRRK2 variants identify novel causal and druggable proteins for Parkinson’s disease
Authors: Phillips Bridget , Western Daniel , Wang Lihua , Timsina Jigyasha , Sun Yichen , Gorijala Priyanka , Yang Chengran , Do Anh , Nykänen Niko-Petteri , Alvarez Ignacio , Aguilar Miquel , Pastor Pau , Morris John C. , Schindler Suzanne E. , Fagan Anne M. , Puerta Raquel , García-González Pablo , de Rojas Itziar , Marquié Marta , Boada Mercè , Ruiz Agustin , Perlmutter Joel S. ,   Dominantly Inherited Alzheimer Network (DIAN) Consortia, Ibanez Laura , Perrin Richard J. , Sung Yun Ju , Cruchaga Carlos
Published: July 2023

Common and rare variants in the LRRK2 locus are associated with Parkinson’s disease (PD) risk, but the downstream effects of these variants on protein levels remain unknown. We performed comprehensive proteogenomic analyses using the largest aptamer-based CSF proteomics study to date (7006 aptamers (6138 unique proteins) in 3107 individuals). The dataset comprised six different and independent cohorts (five using the SomaScan7K (ADNI, DIAN, MAP, Barcelona-1 (Pau), and Fundació ACE (Ruiz)) and the PPMI cohort using the SomaScan5K panel). We identified eleven independent SNPs in the LRRK2 locus associated with the levels of 25 proteins as well as PD risk. Of these, only eleven proteins have been previously associated with PD risk (e.g., GRN or GPNMB). Proteome-wide association study (PWAS) analyses suggested that the levels of ten of those proteins were genetically correlated with PD risk, and seven were validated in the PPMI cohort. Mendelian randomization analyses identified GPNMB, LCT, and CD68 causal for PD and nominate one more (ITGB2). These 25 proteins were enriched for microglia-specific proteins and trafficking pathways (both lysosome and intracellular). This study not only demonstrates that protein phenome-wide association studies (PheWAS) and trans-protein quantitative trail loci (pQTL) analyses are powerful for identifying novel protein interactions in an unbiased manner, but also that LRRK2 is linked with the regulation of PD-associated proteins that are enriched in microglial cells and specific lysosomal pathways.
Controllable tunability of a Chern number within the electronic-nuclear spin system in diamond
Authors: Lee Junghyun , Arai Keigo , Zhang Huiliang , Ku Mark J. H. , Walsworth Ronald L.
Published: July 2023

Chern numbers characterize topological phases in a wide array of physical systems. However, the resilience of system topology to external perturbations makes it challenging experimentally to investigate transitions between different phases. In this study, we demonstrate the transitions of a Chern number from 0 to 3, synthesized in an electronic-nuclear spin system associated with the nitrogen-vacancy (NV) centre in diamond. The Chern number is characterized by the number of degeneracies enclosed in a control Hamiltonian parameter sphere. Topological transitions between different phases are realized by varying the radius and offset of the sphere such that the Chern number changes. We show that the measured topological phase diagram is consistent with numerical calculations and can also be mapped onto an interacting three-qubit system. The NV system may also allow access to even higher Chern numbers, which could be applied to exploring exotic topology or topological quantum information.
Strong majorization uncertainty relations and experimental verifications
Authors: Yuan Yuan , Xiao Yunlong , Hou Zhibo , Fei Shao-Ming , Gour Gilad , Xiang Guo-Yong , Li Chuan-Feng , Guo Guang-Can
Published: July 2023

In spite of enormous theoretical and experimental progress in quantum uncertainty relations, the experimental investigation of the most current, and universal formalism of uncertainty relations, namely majorization uncertainty relations (MURs), has not been implemented yet. A major problem is that previous studies of majorization uncertainty relations mainly focus on their mathematical expressions, leaving the physical interpretation of these different forms unexplored. To address this problem, we employ a guessing game formalism to reveal physical differences between diverse forms of majorization uncertainty relations. Furthermore, we tighter the bounds of MURs by using flatness processes. Finally, we experimentally verify strong MURs in the photonic system to benchmark our theoretical results.
Optical and structural characterization of femtosecond laser written micro-structures in germanate glass
Authors: Zaiter Rayan , Lancry Matthieu , Fargues Alexandre , Adamietz Frédéric , Dussauze Marc , Rodriguez Vincent , Poumellec Bertrand , Cardinal Thierry
Published: July 2023

We report on direct femtosecond laser writing in zinc barium gallo-germanate glasses. A combination of spectroscopic techniques allows to progress in the understanding of the mechanisms taking place depending on the energy. In the first regime (type I, isotropic local index change) up to 0.5 µJ, the main occurrence is the generation of charge traps inspected by luminescence, together with separation of charges detected by polarized second harmonic generation measurements. At higher pulse energies notably at the threshold corresponding to 0.8 µJ or in the second regime (type II modifications corresponding to nanograting formation energy domain), the main occurrence is a chemical change and re-organization of the network evidenced by the appearance of molecular O2 seen in the Raman spectra. In addition, the polarization dependence of the second harmonic generation in type II indicates that the organization of nanogratings may be perturbed by the laser-imprinted electric field.
Decentralized environmental applications of a smartphone-based method for chemical oxygen demand and color analysis
Authors: Cardozo Jussara Câmara , Barbosa Segundo Inalmar D. , Galvão Edney R. V. P. , da Silva Djalma R. , dos Santos Elisama V. , Martínez-Huitle Carlos A.
Published: July 2023

This study is focused on a proposal of a smartphone imaging-based quantification for providing a simple and rapid method for the analysis of chemical oxygen demand (COD) and color throughout the use of the HSV and/or RGB model in digital devices. For COD, calibration curves were done based on the theoretical values of potassium biphthalate for a proper comparison between the spectrophotometer and the smartphone techniques. The smartphone camera and application attain an average accuracy higher than the analysis in the spectrophotometer (98.3 and 96.2%, respectively). In the color analysis, it was demonstrated that only the UV–vis bands measurement is not feasible to perform the real abatement of the dye in the water because the limiting concentration that allows obtaining a linear relationship in this equipment related to the dye concentration is about 10 mg L−1. Above this value, the spectrophotometer can not reach the real difference of color in the solution. Meanwhile, the smartphone method by using the camera reaches linearity until 50 mg L−1. From an environmental point of view, smartphones have been used for monitoring several organic and inorganic pollutants, however, no attempts have been published related to their use to evaluate the color and COD during wastewater treatment. Therefore, this investigation also aims to assess the utilization of these methods, for the first time, when high-colored water polluted by methylene blue (MB) was electrochemically treated by using a boron-dopped diamond (BDD) as the anode, with different current densities (j = 30, 45, 60, and 90 mA cm−2). COD and color abatement results clearly showed that different organic matter/color removal efficiencies were achieved, depending on the j used. All the results are aligned with the studies already available in the literature, with the total removal of color in 120 min of electrolysis with 60 and 90 mA cm−2, and almost 80% of COD abatement with the higher j. Moreover, samples of real effluent from beauty salons were compared, with standard deviation varying from only 3 to 40 mg O2 L−1, which is acceptable for COD values close to 2000. Finally, the methods here presented can be a great benefit for public water monitoring policies, since it is cheap and has a decentralized characteristic, given that smartphones are very common and portable devices.
Pharmacokinetics, biodistribution and toxicology of novel cell-penetrating peptides
Authors: Reveret L. , Leclerc M. , Morin F. , Émond V. , Calon F.
Published: July 2023

Cell-penetrating peptides (CPPs) have been used in basic and preclinical research in the past 30 years to facilitate drug delivery into target cells. However, translation toward the clinic has not been successful so far. Here, we studied the pharmacokinetic (PK) and biodistribution profiles of Shuttle cell-penetrating peptides (S-CPP) in rodents, combined or not with an immunoglobulin G (IgG) cargo. We compared two enantiomers of S-CPP that contain both a protein transduction domain and an endosomal escape domain, with previously shown capacity for cytoplasmic delivery. The plasma concentration versus time curve of both radiolabelled S-CPPs required a two-compartment PK analytical model, which showed a fast distribution phase (t1/2α ranging from 1.25 to 3 min) followed by a slower elimination phase (t1/2β ranging from 5 to 15 h) after intravenous injection. Cargo IgG combined to S-CPPs displayed longer elimination half-life, of up to 25 h. The fast decrease in plasma concentration of S-CPPs was associated with an accumulation in target organs assessed at 1 and 5 h post-injection, particularly in the liver. In addition, in situ cerebral perfusion (ISCP) of L-S-CPP yielded a brain uptake coefficient of 7.2 ± 1.1 µl g−1 s−1, consistent with penetration across the blood–brain barrier (BBB), without damaging its integrity in vivo. No sign of peripheral toxicity was detected either by examining hematologic and biochemical blood parameters, or by measuring cytokine levels in plasma. In conclusion, S-CPPs are promising non-toxic transport vectors for improved tissue distribution of drug cargos in vivo.
Automated machine learning (AutoML) can predict 90-day mortality after gastrectomy for cancer
Authors: SenthilKumar Gopika , Madhusudhana Sharadhi , Flitcroft Madelyn , Sheriff Salma , Thalji Samih , Merrill Jennifer , Clarke Callisia N. , Maduekwe Ugwuji N. , Tsai Susan , Christians Kathleen K. , Gamblin T. Clark , Kothari Anai N.
Published: July 2023

Early postoperative mortality risk prediction is crucial for clinical management of gastric cancer. This study aims to predict 90-day mortality in gastric cancer patients undergoing gastrectomy using automated machine learning (AutoML), optimize models for preoperative prediction, and identify factors influential in prediction. National Cancer Database was used to identify stage I–III gastric cancer patients undergoing gastrectomy between 2004 and 2016. 26 features were used to train predictive models using H2O.ai AutoML. Performance on validation cohort was measured. In 39,108 patients, 90-day mortality rate was 8.8%. The highest performing model was an ensemble (AUC = 0.77); older age, nodal ratio, and length of inpatient stay (LOS) following surgery were most influential for prediction. Removing the latter two parameters decreased model performance (AUC 0.71). For optimizing models for preoperative use, models were developed to first predict node ratio or LOS, and these predicted values were inputted for 90-day mortality prediction (AUC of 0.73–0.74). AutoML performed well in predicting 90-day mortality in a larger cohort of gastric cancer patients that underwent gastrectomy. These models can be implemented preoperatively to inform prognostication and patient selection for surgery. Our study supports broader evaluation and application of AutoML to guide surgical oncologic care.
Jelly-Z: swimming performance and analysis of twisted and coiled polymer (TCP) actuated jellyfish soft robot
Authors: Matharu Pawandeep Singh , Gong Pengyao , Guntaka Koti Pramod Reddy , Almubarak Yara , Jin Yaqing , Tadesse Yonas T.
Published: July 2023

Monitoring, sensing, and exploration of over 70% of the Earth’s surface that is covered with water is permitted through the deployment of underwater bioinspired robots without affecting the natural habitat. To create a soft robot actuated with soft polymeric actuators, this paper describes the development of a lightweight jellyfish-inspired swimming robot, which achieves a maximum vertical swimming speed of 7.3 mm/s (0.05 body length/s) and is characterized by a simple design. The robot, named Jelly-Z, utilizes a contraction–expansion mechanism for swimming similar to the motion of a Moon jellyfish. The objective of this paper is to understand the behavior of soft silicone structure actuated by novel self-coiled polymer muscles in an underwater environment by varying stimuli and investigate the associated vortex for swimming like a jellyfish. To better understand the characteristics of this motion, simplified Fluid–structure simulation, and particle image velocimetry (PIV) tests were conducted to study the wake structure from the robot’s bell margin. The thrust generated by the robot was also characterized with a force sensor to ascertain the force and cost of transport (COT) at different input currents. Jelly-Z is the first robot that utilized twisted and coiled polymer fishing line (TCPFL) actuators for articulation of the bell and showed successful swimming operations. Here, a thorough investigation on swimming characteristics in an underwater setting is presented theoretically and experimentally. We found swimming metrics of the robot are comparable with other jellyfish-inspired robots that have utilized different actuation mechanisms, but the actuators used here are scalable and can be made in-house relatively easily, hence paving way for further advancements into the use of these actuators.
Overactive bladder syndrome symptoms in youth with abdominal pain-associated disorders of gut–brain interaction
Authors: Friesen Hunter J. , Thompson Pierce , Schurman Jennifer V. , Colombo Jennifer M. , Friesen Craig A.
Published: July 2023

The purpose of the current study was to assess the frequency of overactive bladder syndrome (OBS) symptoms and their relationship to gastrointestinal symptoms in youth with abdominal pain-associated disorders of gut–brain interaction (AP-DGBI). This is a retrospective study of 226 youth diagnosed with an AP-DGBI. As part of standard care, all patients completed a symptom questionnaire regarding gastrointestinal and non-gastrointestinal symptoms including increased urinary frequency, nighttime urination, and urinary urgency. Overall, 54% of patients reported at least one OBS symptom. Increased frequency of urination was reported by 19%, urinary urgency by 34%, and nighttime urination by 36%. Increased frequency of urination and urinary urgency were associated with a change in stool form, a change in stool frequency, and in those fulfilling criteria for IBS. Increased frequency of urination was reported more frequently in those reporting predominantly loose stools (33% vs. 12%). Urinary symptoms are common in youth with AP-DGBI. Increased urinary frequency and urinary urgency are specifically associated with IBS, with increased urinary frequency being primarily associated with diarrhea predominant IBS. Further studies are needed to determine the impact of OBS on AP-DGBI severity and quality of life, and whether they impact DGBI treatment.
Estimating vaccine coverage in conflict settings using geospatial methods: a case study in Borno state, Nigeria
Authors: Sbarra Alyssa N. , Rolfe Sam , Haeuser Emily , Nguyen Jason Q. , Adamu Aishatu , Adeyinka Daniel , Ajumobi Olufemi , Akunna Chisom , Amusa Ganiyu , Dahiru Tukur , Ekholuenetale Michael , Esezobor Christopher , Fowobaje Kayode , Hay Simon I. , Ibeneme Charles , Ibitoye Segun Emmanuel , Ilesanmi Olayinka , Kayode Gbenga , Krohn Kris , Lim Stephen S. , Medeiros Lyla E. , Mohammed Shafiu , Nwatah Vincent , Okoro Anselm , Olagunju Andrew T. , Olusanya Bolajoko O. , Osarenotor Osayomwanbo , Owolabi Mayowa , Pickering Brandon , Sufiyan Mu’awiyyah Babale , Uzochukwu Benjamin , Walker Ally , Mosser Jonathan F.
Published: July 2023

Reliable estimates of subnational vaccination coverage are critical to track progress towards global immunisation targets and ensure equitable health outcomes for all children. However, conflict can limit the reliability of coverage estimates from traditional household-based surveys due to an inability to sample in unsafe and insecure areas and increased uncertainty in underlying population estimates. In these situations, model-based geostatistical (MBG) approaches offer alternative coverage estimates for administrative units affected by conflict. We estimated first- and third-dose diphtheria-tetanus-pertussis vaccine coverage in Borno state, Nigeria, using a spatiotemporal MBG modelling approach, then compared these to estimates from recent conflict-affected, household-based surveys. We compared sampling cluster locations from recent household-based surveys to geolocated data on conflict locations and modelled spatial coverage estimates, while also investigating the importance of reliable population estimates when assessing coverage in conflict settings. These results demonstrate that geospatially-modelled coverage estimates can be a valuable additional tool to understand coverage in locations where conflict prevents representative sampling.
X-ray driven and intrinsic dynamics in protein gels
Authors: Timmermann Sonja , Anthuparambil Nimmi Das , Girelli Anita , Begam Nafisa , Kowalski Marvin , Retzbach Sebastian , Senft Maximilian Darius , Akhundzadeh Mohammad Sayed , Poggemann Hanna-Friederike , Moron Marc , Hiremath Anusha , Gutmüller Dennis , Dargasz Michelle , Öztürk Özgül , Paulus Michael , Westermeier Fabian , Sprung Michael , Ragulskaya Anastasia , Zhang Fajun , Schreiber Frank , Gutt Christian
Published: July 2023

We use X-ray photon correlation spectroscopy to investigate how structure and dynamics of egg white protein gels are affected by X-ray dose and dose rate. We find that both, changes in structure and beam-induced dynamics, depend on the viscoelastic properties of the gels with soft gels prepared at low temperatures being more sensitive to beam-induced effects. Soft gels can be fluidized by X-ray doses of a few kGy with a crossover from stress relaxation dynamics (Kohlrausch–Williams–Watts exponents $$k \approx 1.5$$

k
≈
1.5

to 2) to typical dynamical heterogeneous behavior ($$k<$$

k
<

1) while the high temperature egg white gels are radiation-stable up to doses of 15 kGy with $$k\ge 1.5$$

k
≥
1.5

. For all gel samples we observe a crossover from equilibrium dynamics to beam induced motion upon increasing X-ray fluence and determine the resulting fluence threshold values $$\Phi _D$$

Φ
D

. Surprisingly small threshold values of $$\Phi _D=(3 \pm 2)\times 10^{-3} \,\textrm{ph}\,$$

Φ
D

=

(
3
±
2
)

×

10

-
3

ph

s$$^{-1}$$

-
1

nm$$^{-2}$$

-
2

can drive the dynamics in the soft gels while for stronger gels this threshold is increased to $$\Phi _D=(0.9 \pm 0.3) \,\textrm{ph}$$

Φ
D

=

(
0.9
±
0.3
)

ph

s$$^{-1}$$

-
1

nm$$^{-2}$$

-
2

. We explain our observations with the viscoelastic properties of the materials and can connect the threshold dose for structural beam damage with the dynamic properties of beam-induced motion. Our results suggest that soft viscoelastic materials can display pronounced X-ray driven motion even for low X-ray fluences. This induced motion is not detectable by static scattering as it appears at dose values well below the static damage threshold. We show that intrinsic sample dynamics can be separated from X-ray driven motion by measuring the fluence dependence of the dynamical properties.
Predicting Kyasanur forest disease in resource-limited settings using event-based surveillance and transfer learning
Authors: Keshavamurthy Ravikiran , Charles Lauren E.
Published: July 2023

In recent years, the reports of Kyasanur forest disease (KFD) breaking endemic barriers by spreading to new regions and crossing state boundaries is alarming. Effective disease surveillance and reporting systems are lacking for this emerging zoonosis, hence hindering control and prevention efforts. We compared time-series models using weather data with and without Event-Based Surveillance (EBS) information, i.e., news media reports and internet search trends, to predict monthly KFD cases in humans. We fitted Extreme Gradient Boosting (XGB) and Long Short Term Memory models at the national and regional levels. We utilized the rich epidemiological data from endemic regions by applying Transfer Learning (TL) techniques to predict KFD cases in new outbreak regions where disease surveillance information was scarce. Overall, the inclusion of EBS data, in addition to the weather data, substantially increased the prediction performance across all models. The XGB method produced the best predictions at the national and regional levels. The TL techniques outperformed baseline models in predicting KFD in new outbreak regions. Novel sources of data and advanced machine-learning approaches, e.g., EBS and TL, show great potential towards increasing disease prediction capabilities in data-scarce scenarios and/or resource-limited settings, for better-informed decisions in the face of emerging zoonotic threats.