bluuebunny/crossref_metadata_2025 huggingface dataset:
De novo expression of gastrokines in pancreatic precursor lesions impede the development of pancreatic cancer
Authors: Steiner Sabrina , Seleznik Gitta M. , Reding Theresia , Stopic Matea , Lenggenhager Daniela , ten Buren Emiel , Eshmuminov Dilmurodjon , Endhardt Katharina , Hagedorn Catherine , Heidenblut Anna M. , Bratus-Neuenschwander Anna , Grossmann Jonas , Trachsel Christian , Jabbar Karolina S. , Hahn Stephan A. , Berg Johannes vom , Graf Rolf , Gupta Anurag
Published: January 2022

Molecular events occurring in stepwise progression from pre-malignant lesions (pancreatic intraepithelial neoplasia; PanIN) to the development of pancreatic ductal adenocarcinoma (PDAC) are poorly understood. Thus, characterization of early PanIN lesions may reveal markers that can help in diagnosing PDAC at an early stage and allow understanding the pathology of the disease. We performed the molecular and histological assessment of patient-derived PanINs, tumor tissues and pancreas from mouse models with PDAC (KC mice that harbor K-RAS mutation in pancreatic tissue), where we noted marked upregulation of gastrokine (GKN) proteins. To further understand the role of gastrokine proteins in PDAC development, GKN-deficient KC mice were developed by intercrossing gastrokine-deficient mice with KC mice. Panc-02 (pancreatic cancer cells of mouse origin) were genetically modified to express GKN1 for further in vitro and in vivo analysis. Our results show that gastrokine proteins were absent in healthy pancreas and invasive cancer, while its expression was prominent in low-grade PanINs. We could detect these proteins in pancreatic juice and serum of KC mice. Furthermore, accelerated PanIN and tumor development were noted in gastrokine deficient KC mice. Loss of gastrokine 1 protein delayed apoptosis during carcinogenesis leading to the development of desmoplastic stroma while loss of gastrokine 2 increased the proliferation rate in precursor lesions. In summary, we identified gastrokine proteins in early pancreatic precursor lesions, where gastrokine proteins delay pancreatic carcinogenesis.
Whole-genome sequencing reveals the evolutionary trajectory of HBV-related hepatocellular carcinoma early recurrence
Authors: Zhou Shao-Lai , Zhou Zheng-Jun , Song Cheng-Li , Xin Hao-Yang , Hu Zhi-Qiang , Luo Chu-Bin , Luo Yi-Jie , Li Jia , Dai Zhi , Yang Xin-Rong , Shi Ying-Hong , Wang Zheng , Huang Xiao-Wu , Fan Jia , Zhou Jian
Published: January 2022

Patients with hepatocellular carcinoma (HCC) have poor long-term survival following curative resection because of the high rate of tumor early recurrence. Little is known about the trajectory of genomic evolution from primary to early-recurrent HCC. In this study, we performed whole-genome sequencing (WGS) on 40 pairs of primary and early-recurrent hepatitis B virus (HBV)-related HCC tumors from patients who received curative resection, and from four patients whose primary and recurrent tumor were extensively sampled. We identified two recurrence patterns: de novo recurrence (18/40), which developed genetically independently of the primary tumor and carried different HCC drivers, and ancestral recurrence (22/40), which was clonally related to the primary tumor and progressed more rapidly than de novo recurrence. We found that the recurrence location was predictive of the recurrence pattern: distant recurrence tended to display the de novo pattern, whereas local recurrence tended to display the ancestral pattern. We then uncovered the evolutionary trajectories based on the subclonal architecture, driver-gene mutations, and mutational processes observed in the primary and recurrent tumors. Multi-region WGS demonstrated spatiotemporal heterogeneity and polyclonal, monophyletic dissemination in HCC ancestral recurrence. In addition, we identified recurrence-specific mutations and copy-number gains in BCL9, leading to WNT/β-catenin signaling activation and an immune-excluded tumor microenvironment, which suggests that BCL9 might serve as a new therapeutic target for recurrent HCC. Collectively, our results allow us to view with unprecedented clarity the genomic evolution during HBV-related HCC early recurrence, providing an important molecular foundation for enhanced understanding of HCC with implications for personalized therapy to improve patient survival.
Niche differentiation of sulfur-oxidizing bacteria (SUP05) in submarine hydrothermal plumes
Authors: Dede Bledina , Hansen Christian T , Neuholz Rene , Schnetger Bernhard , Kleint Charlotte , Walker Sharon , Bach Wolfgang , Amann Rudolf , Meyerdierks Anke
Published: January 2022

Hydrothermal plumes transport reduced chemical species and metals into the open ocean. Despite their considerable spatial scale and impact on biogeochemical cycles, niche differentiation of abundant microbial clades is poorly understood. Here, we analyzed the microbial ecology of two bathy- (Brothers volcano; BrV-cone and northwest caldera; NWC) and a mesopelagic (Macauley volcano; McV) plumes on the Kermadec intra-oceanic arc in the South Pacific Ocean. The microbial community structure, determined by a combination of 16S rRNA gene, fluorescence in situ hybridization and metagenome analysis, was similar to the communities observed in other sulfur-rich plumes. This includes a dominance of the vent characteristic SUP05 clade (up to 22% in McV and 51% in BrV). In each of the three plumes analyzed, the community was dominated by a different yet uncultivated chemoautotrophic SUP05 species, here, provisionally named, Candidatus Thioglobus vadi (McV), Candidatus Thioglobus vulcanius (BrV-cone) and Candidatus Thioglobus plumae (BrV-NWC). Statistical analyses, genomic potential and mRNA expression profiles suggested a SUP05 niche partitioning based on sulfide and iron concentration as well as water depth. A fourth SUP05 species was present at low frequency throughout investigated plume samples and may be capable of heterotrophic or mixotrophic growth. Taken together, we propose that small variations in environmental parameters and depth drive SUP05 niche partitioning in hydrothermal plumes.
Cytokines and tryptophan metabolites can predict depressive symptoms in pregnancy
Authors: Sha Qiong , Madaj Zach , Keaton Sarah , Escobar Galvis Martha L , Smart LeAnn , Krzyzanowski Stanislaw , Fazleabas Asgerally T. , Leach Richard , Postolache Teodor T. , Achtyes Eric D. , Brundin Lena
Published: January 2022

Depression during and after pregnancy affects up to 20% of pregnant women, but the biological underpinnings remain incompletely understood. As pregnancy progresses, the immune system changes to facilitate fetal development, leading to distinct fluctuations in the production of pro-inflammatory factors and neuroactive tryptophan metabolites throughout the peripartum period. Therefore, it is possible that depression in pregnancy could constitute a specific type of inflammation-induced depression. Both inflammatory factors and kynurenine metabolites impact neuroinflammation and glutamatergic neurotransmission and can therefore affect mood and behavior. To determine whether cytokines and kynurenine metabolites can predict the development of depression in pregnancy, we analyzed blood samples and clinical symptoms in 114 women during each trimester and the postpartum. We analyzed plasma IL-1β, IL-2, -6, -8, -10, TNF, kynurenine, tryptophan, serotonin, kynurenic- quinolinic- and picolinic acids and used mixed-effects models to assess the association between biomarkers and depression severity. IL-1β and IL-6 levels associated positively with severity of depressive symptoms across pregnancy and the postpartum, and that the odds of experiencing significant depressive symptoms increased by >30% per median absolute deviation for both IL-1β and IL-6 (both P = 0.01). A combination of cytokines and kynurenine metabolites in the 2nd trimester had a >99% probability of accurately predicting 3rd trimester depression, with an ROC AUC > 0.8. Altogether, our work shows that cytokines and tryptophan metabolites can predict depression during pregnancy and could be useful as clinical markers of risk. Moreover, inflammation and kynurenine pathway enzymes should be considered possible therapeutic targets in peripartum depression.
Clonal and subclonal TP53 molecular impairment is associated with prognosis and progression in multiple myeloma
Authors: Martello M. , Poletti A. , Borsi E. , Solli V. , Dozza L. , Barbato S. , Zamagni E. , Tacchetti P. , Pantani L. , Mancuso K. , Vigliotta I. , Rizzello I. , Rocchi S. , Armuzzi S. , Testoni N. , Marzocchi G. , Martinelli G. , Cavo M. , Terragna C.
Published: January 2022

Aberrations on TP53, either as deletions of chromosome 17p (del17p) or mutations, are associated with poor outcome in multiple myeloma (MM), but conventional detection methods currently in use underestimate their incidence, hindering an optimal risk assessment and prognostication of MM patients. We have investigated the altered status of TP53 gene by SNPs array and sequencing techniques in a homogenous cohort of 143 newly diagnosed MM patients, evaluated both at diagnosis and at first relapse: single-hit on TP53 gene, either deletion or mutation, detected both at clonal and sub-clonal level, had a minor effect on outcomes. Conversely, the coexistence of both TP53 deletion and mutation, which defined the so-called double-hit patients, was associated with the worst clinical outcome (PFS: HR 3.34 [95% CI: 1.37–8.12] p = 0.008; OS: HR 3.47 [95% CI: 1.18–10.24] p = 0.02). Moreover, the analysis of longitudinal samples pointed out that TP53 allelic status might increase during the disease course. Notably, the acquisition of TP53 alterations at relapse dramatically worsened the clinical course of patients. Overall, our analyses showed these techniques to be highly sensitive to identify TP53 aberrations at sub-clonal level, emphasizing the poor prognosis associated with double-hit MM patients.
Neonatal-lethal dilated cardiomyopathy due to a homozygous LMOD2 donor splice-site variant
Authors: Yuen Michaela , Worgan Lisa , Iwanski Jessika , Pappas Christopher T. , Joshi Himanshu , Churko Jared M. , Arbuckle Susan , Kirk Edwin P. , Zhu Ying , Roscioli Tony , Gregorio Carol C. , Cooper Sandra T.
Published: January 2022

Dilated cardiomyopathy (DCM) is characterized by cardiac enlargement and impaired ventricular contractility leading to heart failure. A single report identified variants in leiomodin-2 (LMOD2) as a cause of neonatally-lethal DCM. Here, we describe two siblings with DCM who died shortly after birth due to heart failure. Exome sequencing identified a homozygous LMOD2 variant in both siblings, (GRCh38)chr7:g.123656237G > A; NM_207163.2:c.273 + 1G > A, ablating the donor 5′ splice-site of intron-1. Pre-mRNA splicing studies and western blot analysis on cDNA derived from proband cardiac tissue, MyoD-transduced proband skin fibroblasts and HEK293 cells transfected with LMOD2 gene constructs established variant-associated absence of canonically spliced LMOD2 mRNA and full-length LMOD2 protein. Immunostaining of proband heart tissue unveiled abnormally short actin-thin filaments. Our data are consistent with LMOD2 c.273 + 1G > A abolishing/reducing LMOD2 transcript expression by: (1) variant-associated perturbation in initiation of transcription due to ablation of the intron-1 donor; and/or (2) degradation of aberrant LMOD2 transcripts (resulting from use of alternative transcription start-sites or cryptic splice-sites) by nonsense-mediated decay. LMOD2 expression is critical for life and the absence of LMOD2 is associated with thin filament shortening and severe cardiac contractile dysfunction. This study describes the first splice-site variant in LMOD2 and confirms the role of LMOD2 variants in DCM.
Utilizing museomics to trace the complex history and species boundaries in an avian-study system of conservation concern
Authors: Ernst Mario , Jønsson Knud A. , Ericson Per G. P. , Blom Mozes P. K. , Irestedt Martin
Published: January 2022

A taxonomic classification that accurately captures evolutionary history is essential for conservation. Genomics provides powerful tools for delimiting species and understanding their evolutionary relationships. This allows for a more accurate and detailed view on conservation status compared with other, traditionally used, methods. However, from a practical and ethical perspective, gathering sufficient samples for endangered taxa may be difficult. Here, we use museum specimens to trace the evolutionary history and species boundaries in an Asian oriole clade. The endangered silver oriole has long been recognized as a distinct species based on its unique coloration, but a recent study suggested that it might be nested within the maroon oriole-species complex. To evaluate species designation, population connectivity, and the corresponding conservation implications, we assembled a de novo genome and used whole-genome resequencing of historical specimens. Our results show that the silver orioles form a monophyletic lineage within the maroon oriole complex and that maroon and silver forms continued to interbreed after initial divergence, but do not show signs of recent gene flow. Using a genome scan, we identified genes that may form the basis for color divergence and act as reproductive barriers. Taken together, our results confirm the species status of the silver oriole and highlight that taxonomic revision of the maroon forms is urgently needed. Our study demonstrates how genomics and Natural History Collections (NHC) can be utilized to shed light on the taxonomy and evolutionary history of natural populations and how such insights can directly benefit conservation practitioners when assessing wild populations.
Differential roles for DNAJ isoforms in HTT-polyQ and FUS aggregation modulation revealed by chaperone screens
Authors: Rozales Kinneret , Younis Amal , Saida Naseeb , Meller Anatoly , Goldman Hodaya , Kellerman Lior , Heinrich Ronit , Berlin Shai , Shalgi Reut
Published: January 2022

Protein aggregation is a hallmark of neurodegeneration. Here, we find that Huntington’s disease-related HTT-polyQ aggregation induces a cellular proteotoxic stress response, while ALS-related mutant FUS (mutFUS) aggregation leads to deteriorated proteostasis. Further exploring chaperone function as potential modifiers of pathological aggregation in these contexts, we reveal divergent effects of naturally-occurring chaperone isoforms on different aggregate types. We identify a complex of the full-length (FL) DNAJB14 and DNAJB12, that substantially protects from mutFUS aggregation, in an HSP70-dependent manner. Their naturally-occurring short isoforms, however, do not form a complex, and lose their ability to preclude mutFUS aggregation. In contrast, DNAJB12-short alleviates, while DNAJB12-FL aggravates, HTT-polyQ aggregation. DNAJB14-FL expression increases the mobility of mutFUS aggregates, and restores the deteriorated proteostasis in mutFUS aggregate-containing cells and primary neurons. Our results highlight a maladaptive cellular response to pathological aggregation, and reveal a layer of chaperone network complexity conferred by DNAJ isoforms, in regulation of different aggregate types.
Mapping molecular subtype specific alterations in breast cancer brain metastases identifies clinically relevant vulnerabilities
Authors: Cosgrove Nicola , Varešlija Damir , Keelan Stephen , Elangovan Ashuvinee , Atkinson Jennifer M. , Cocchiglia Sinéad , Bane Fiona T. , Singh Vikrant , Furney Simon , Hu Chunling , Carter Jodi M. , Hart Steven N. , Yadav Siddhartha , Goetz Matthew P. , Hill Arnold D. K. , Oesterreich Steffi , Lee Adrian V. , Couch Fergus J. , Young Leonie S.
Published: January 2022

The molecular events and transcriptional plasticity driving brain metastasis in clinically relevant breast tumor subtypes has not been determined. Here we comprehensively dissect genomic, transcriptomic and clinical data in patient-matched longitudinal tumor samples, and unravel distinct transcriptional programs enriched in brain metastasis. We report on subtype specific hub genes and functional processes, central to disease-affected networks in brain metastasis. Importantly, in luminal brain metastases we identify homologous recombination deficiency operative in transcriptomic and genomic data with recurrent breast mutational signatures A, F and K, associated with mismatch repair defects, TP53 mutations and homologous recombination deficiency (HRD) respectively. Utilizing PARP inhibition in patient-derived brain metastatic tumor explants we functionally validate HRD as a key vulnerability. Here, we demonstrate a functionally relevant HRD evident at genomic and transcriptomic levels pointing to genomic instability in breast cancer brain metastasis which is of potential translational significance.
Hierarchical and nonhierarchical features of the mouse visual cortical network
Authors: D’Souza Rinaldo D. , Wang Quanxin , Ji Weiqing , Meier Andrew M. , Kennedy Henry , Knoblauch Kenneth , Burkhalter Andreas
Published: January 2022

Neocortical computations underlying vision are performed by a distributed network of functionally specialized areas. Mouse visual cortex, a dense interareal network that exhibits hierarchical properties, comprises subnetworks interconnecting distinct processing streams. To determine the layout of the mouse visual hierarchy, we have evaluated the laminar patterns formed by interareal axonal projections originating in each of ten areas. Reciprocally connected pairs of areas exhibit feedforward/feedback relationships consistent with a hierarchical organization. Beta regression analyses, which estimate a continuous hierarchical distance measure, indicate that the network comprises multiple nonhierarchical circuits embedded in a hierarchical organization of overlapping levels. Single-unit recordings in anaesthetized mice show that receptive field sizes are generally consistent with the hierarchy, with the ventral stream exhibiting a stricter hierarchy than the dorsal stream. Together, the results provide an anatomical metric for hierarchical distance, and reveal both hierarchical and nonhierarchical motifs in mouse visual cortex.
Boosting the electronic and catalytic properties of 2D semiconductors with supramolecular 2D hydrogen-bonded superlattices
Authors: Wang Can , Furlan de Oliveira Rafael , Jiang Kaiyue , Zhao Yuda , Turetta Nicholas , Ma Chun , Han Bin , Zhang Haiming , Tranca Diana , Zhuang Xiaodong , Chi Lifeng , Ciesielski Artur , Samorì Paolo
Published: January 2022

The electronic properties of two-dimensional semiconductors can be strongly modulated by interfacing them with atomically precise self-assembled molecular lattices, yielding hybrid van der Waals heterostructures (vdWHs). While proof-of-concepts exploited molecular assemblies held together by lateral unspecific van der Waals interactions, the use of 2D supramolecular networks relying on specific non-covalent forces is still unexplored. Herein, prototypical hydrogen-bonded 2D networks of cyanuric acid (CA) and melamine (M) are self-assembled onto MoS2 and WSe2 forming hybrid organic/inorganic vdWHs. The charge carrier density of monolayer MoS2 exhibits an exponential increase with the decreasing area occupied by the CA·M unit cell, in a cooperatively amplified process, reaching 2.7 × 1013 cm−2 and thereby demonstrating strong n-doping. When the 2D CA·M network is used as buffer layer, a stark enhancement in the catalytic activity of monolayer MoS2 for hydrogen evolution reactions is observed, outperforming the platinum (Pt) catalyst via gate modulation.
Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry
Authors: Claireaux Mathieu , Robinot Rémy , Kervevan Jérôme , Patgaonkar Mandar , Staropoli Isabelle , Brelot Anne , Nouël Alexandre , Gellenoncourt Stacy , Tang Xian , Héry Mélanie , Volant Stevenn , Perthame Emeline , Avettand-Fenoël Véronique , Buchrieser Julian , Cokelaer Thomas , Bouchier Christiane , Ma Laurence , Boufassa Faroudy , Hendou Samia , Libri Valentina , Hasan Milena , Zucman David , de Truchis Pierre , Schwartz Olivier , Lambotte Olivier , Chakrabarti Lisa A.
Published: January 2022

HIV elite controllers maintain a population of CD4 + T cells endowed with high avidity for Gag antigens and potent effector functions. How these HIV-specific cells avoid infection and depletion upon encounter with the virus remains incompletely understood. Ex vivo characterization of single Gag-specific CD4 + T cells reveals an advanced Th1 differentiation pattern in controllers, except for the CCR5 marker, which is downregulated compared to specific cells of treated patients. Accordingly, controller specific CD4 + T cells show decreased susceptibility to CCR5-dependent HIV entry. Two controllers carried biallelic mutations impairing CCR5 surface expression, indicating that in rare cases CCR5 downregulation can have a direct genetic cause. Increased expression of β-chemokine ligands upon high-avidity antigen/TCR interactions contributes to autocrine CCR5 downregulation in controllers without CCR5 mutations. These findings suggest that genetic and functional regulation of the primary HIV coreceptor CCR5 play a key role in promoting natural HIV control.
Optimising genomic approaches for identifying vancomycin-resistant Enterococcus faecium transmission in healthcare settings
Authors: Higgs Charlie , Sherry Norelle L. , Seemann Torsten , Horan Kristy , Walpola Hasini , Kinsella Paul , Bond Katherine , Williamson Deborah A. , Marshall Caroline , Kwong Jason C. , Grayson M. Lindsay , Stinear Timothy P. , Gorrie Claire L. , Howden Benjamin P.
Published: January 2022

Vancomycin-resistantEnterococcus faecium(VREfm) is a major nosocomial pathogen. Identifying VREfm transmission dynamics permits targeted interventions, and while genomics is increasingly being utilised, methods are not yet standardised or optimised for accuracy. We aimed to develop a standardized genomic method for identifying putative VREfm transmission links. Using comprehensive genomic and epidemiological data from a cohort of 308 VREfm infection or colonization cases, we compared multiple approaches for quantifying genetic relatedness. We showed that clustering by core genome multilocus sequence type (cgMLST) was more informative of population structure than traditional MLST. Pairwise genome comparisons using split k-mer analysis (SKA) provided the high-level resolution needed to infer patient-to-patient transmission. The more common mapping to a reference genome was not sufficiently discriminatory, defining more than three times more genomic transmission events than SKA (3729 compared to 1079 events). Here, we show a standardized genomic framework for inferring VREfm transmission that can be the basis for global deployment of VREfm genomics into routine outbreak detection and investigation.
Global climate-driven trade-offs between the water retention and cooling benefits of urban greening
Authors: Cuthbert M. O. , Rau G. C. , Ekström M. , O’Carroll D. M. , Bates A. J.
Published: January 2022

Urban greening can potentially help mitigate heat-related mortality and flooding facing the >4 billion urban population worldwide. However, the geographical variation of the relative combined hydrological and thermal performance benefits of such interventions are unknown. Here we quantify globally, using a hydrological model, how climate-driven trade-offs exist between hydrological retention and cooling potential of urban greening such as green roofs and parks. Using a Budyko framework, we show that water retention generally increases with aridity in water-limited environments, while cooling potential favors energy-limited climates. Our models suggest that common urban greening strategies cannot yield high performance simultaneously for addressing both urban heat-island and urban flooding problems in most cities globally. Irrigation, if sustainable, may enhance cooling while maintaining retention performance in more arid locations. Increased precipitation variability with climate change may reduce performance of thinner green-infrastructure more quickly compared to greened areas with thicker soils and root systems. Our results provide a conceptual framework and first-order quantitative guide for urban development, renewal and policymaking.
Bioinspired elastomer composites with programmed mechanical and electrical anisotropies
Authors: Ling Yun , Pang Wenbo , Liu Jianxing , Page Margaret , Xu Yadong , Zhao Ganggang , Stalla David , Xie Jingwei , Zhang Yihui , Yan Zheng
Published: January 2022

Concepts that draw inspiration from soft biological tissues have enabled significant advances in creating artificial materials for a range of applications, such as dry adhesives, tissue engineering, biointegrated electronics, artificial muscles, and soft robots. Many biological tissues, represented by muscles, exhibit directionally dependent mechanical and electrical properties. However, equipping synthetic materials with tissue-like mechanical and electrical anisotropies remains challenging. Here, we present the bioinspired concepts, design principles, numerical modeling, and experimental demonstrations of soft elastomer composites with programmed mechanical and electrical anisotropies, as well as their integrations with active functionalities. Mechanically assembled, 3D structures of polyimide serve as skeletons to offer anisotropic, nonlinear mechanical properties, and crumpled conductive surfaces provide anisotropic electrical properties, which can be used to construct bioelectronic devices. Finite element analyses quantitatively capture the key aspects that govern mechanical anisotropies of elastomer composites, providing a powerful design tool. Incorporation of 3D skeletons of thermally responsive polycaprolactone into elastomer composites allows development of an active artificial material that can mimic adaptive mechanical behaviors of skeleton muscles at relaxation and contraction states. Furthermore, the fabrication process of anisotropic elastomer composites is compatible with dielectric elastomer actuators, indicating potential applications in humanoid artificial muscles and soft robots.
Vertical graphene on flexible substrate, overcoming limits of crack-based resistive strain sensors
Authors: Na Hong Ryeol , Lee Hyun Joo , Jeon Jae Ho , Kim Han-Jin , Jerng Sahng-Kyoon , Roy Sanjib Baran , Chun Seung-Hyun , Lee Sunghun , Yun Yong Ju
Published: January 2022

Resistive strain sensors (RSS) with ultrasensitivity have attracted much attention as multifunctional sensors. However, since most ultrasensitive RSS are designed by cracked conductive metals, the sensing performance is severely degraded due to accumulated structural deformation with consecutive cycles. To overcome such limitation, newly designed structures have been suggested, but the development of mechanosensors exhibiting superior stability and ultrasensitivity still remains a challenge. Here, we demonstrate that vertical graphene (VG) RSS with high sensitivity (gauge factor greater than 5000), remarkable durability (>10,000 cycles), and extraordinary resilience can serve multifunctional applications. We find that well-defined cracks on tufted network structure result in highly reversible resistance variation, especially revivable status even after broken current path, confirmed by microscopic in situ monitoring. The VG integrated with a wireless sensing system exhibits excellent timbre recognition performance. Our findings provide inspirable insights for mechanosensing system, making VG a promising component for future practicable flexible sensor technologies.
Intestinal gluconeogenesis shapes gut microbiota, fecal and urine metabolome in mice with gastric bypass surgery
Authors: Vily-Petit Justine , Barataud Aude , Zitoun Carine , Gautier-Stein Amandine , Serino Matteo , Mithieux Gilles
Published: January 2022

Intestinal gluconeogenesis (IGN), gastric bypass (GBP) and gut microbiota positively regulate glucose homeostasis and diet-induced dysmetabolism. GBP modulates gut microbiota, whether IGN could shape it has not been investigated. We studied gut microbiota and microbiome in wild type and IGN-deficient mice, undergoing GBP or not, and fed on either a normal chow (NC) or a high-fat/high-sucrose (HFHS) diet. We also studied fecal and urine metabolome in NC-fed mice. IGN and GBP had a different effect on the gut microbiota of mice fed with NC and HFHS diet. IGN inactivation increased abundance ofDeltaproteobacteriaon NC and ofProteobacteriasuch asHelicobacteron HFHS diet. GBP increased abundance ofFirmicutesandProteobacteriaon NC-fed WT mice and ofFirmicutes,BacteroidetesandProteobacteriaon HFHS-fed WT mice. The combined effect of IGN inactivation and GBP increased abundance ofActinobacteriaon NC and the abundance ofEnterococcaceaeandEnterobacteriaceaeon HFHS diet. A reduction was observed in the amounf of short-chain fatty acids in fecal (by GBP) and in both fecal and urine (by IGN inactivation) metabolome. IGN and GBP, separately or combined, shape gut microbiota and microbiome on NC- and HFHS-fed mice, and modify fecal and urine metabolome.
Machine-learning techniques for quantifying the protolith composition and mass transfer history of metabasalt
Authors: Matsuno Satoshi , Uno Masaoki , Okamoto Atsushi , Tsuchiya Noriyoshi
Published: January 2022

The mass transfer history of rocks provides direct evidence for fluid–rock interaction within the lithosphere and is recorded by compositional changes, especially in trace elements. The general method adopted for mass transfer analysis is to compare the composition of the protolith/precursor with that of metamorphosed/altered rocks; however, in many cases the protolith cannot be sampled. With the aim of reconstructing the mass transfer history of metabasalt, this study developed protolith reconstruction models (PRMs) for metabasalt using machine-learning algorithms. We designed models to estimate basalt trace-element concentrations from the concentrations of a few (1–9) trace elements, trained with a compositional dataset for fresh basalts, including mid-ocean ridge, ocean-island, and volcanic arc basalts. The developed PRMs were able to estimate basalt trace-element compositions (e.g., Rb, Ba, U, K, Pb, Sr, and rare-earth elements) from only four input elements with a reproducibility of ~ 0.1 log10units (i.e., ± 25%). As a representative example, we present PRMs where the input elements are Th, Nb, Zr, and Ti, which are typically immobile during metamorphism. Case studies demonstrate the applicability of PRMs to seafloor altered basalt and metabasalt. This method enables us to analyze quantitative mass transfer in regional metamorphic rocks or alteration zones where the protolith is heterogeneous or unknown.
Characterisation of Temnocephalidae flatworms in common Australian freshwater prawn, Macrobrachium australiense
Authors: Shamsi Shokoofeh , Sibraa Lachlan , Zhu Xiaocheng , Barton Diane P.
Published: January 2022

Macrobrachium australiense, is one of Australia’s most widespread freshwater invertebrates. Although a significant amount of research has been conducted to understand the diversity of crustacean species in Australia, there has been considerably less effort focused on their Temnocephalidae symbionts. The present study aims to identify Temnocephalidae species found in M. australiense, along with determining their impacts on the fitness of their hosts. A total of 54 M. australiense (common Australian river prawn) were examined for evidence of infection with Temnocephalidae species, of which 96.3% showed at least one sign of infection with Temnocephalidae. Due to damage and immaturity of the worms collected from, they have been referred to as Temnocephalidae sp. based on the presence of tentacles on the anterior margin of the body, and pedunculate sucker located dorsally on the ventral surface. Possible mechanical damage to gill lamellae resulting from either egg deposition or autolysis is evident. In the phylogenetic tree built based on sequences of the 28S rRNA gene, specimens in the present study grouped separately from other Temnocephalidae species reported from Australia.
Mitochondrial-nuclear epistasis underlying phenotypic variation in breast cancer pathology
Authors: Bushel Pierre R. , Ward James , Burkholder Adam , Li Jianying , Anchang Benedict
Published: January 2022

The interplay between genes harboring single nucleotide polymorphisms (SNPs) is vital to better understand underlying contributions to the etiology of breast cancer. Much attention has been paid to epistasis between nuclear genes or mutations in the mitochondrial genome. However, there is limited understanding about the epistatic effects of genetic variants in the nuclear and mitochondrial genomes jointly on breast cancer. We tested the interaction of germline SNPs in the mitochondrial (mtSNPs) and nuclear (nuSNPs) genomes of female breast cancer patients in The Cancer Genome Atlas (TCGA) for association with morphological features extracted from hematoxylin and eosin (H&E)-stained pathology images. We identified 115 significant (q-value < 0.05) mito-nuclear interactions that increased nuclei size by as much as 12%. One interaction between nuSNP rs17320521 in an intron of the WSC Domain Containing 2 (WSCD2) gene and mtSNP rs869096886, a synonymous variant mapped to the mitochondrially-encoded NADH dehydrogenase 4 (MT-ND4) gene, was confirmed in an independent breast cancer data set from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). None of the 10 mito-nuclear interactions identified from non-diseased female breast tissues from the Genotype-Expression (GTEx) project resulted in an increase in nuclei size. Comparisons of gene expression data from the TCGA breast cancer patients with the genotype homozygous for the minor alleles of the SNPs in WSCD2 and MT-ND4 versus the other genotypes revealed core transcriptional regulator interactions and an association with insulin. Finally, a Cox proportional hazards ratio = 1.7 (C.I. 0.98–2.9, p-value = 0.042) and Kaplan–Meier plot suggest that the TCGA female breast cancer patients with low gene expression of WSCD2 coupled with large nuclei have an increased risk of mortality. The intergenomic dependency between the two variants may constitute an inherent susceptibility of a more severe form of breast cancer and points to genetic targets for further investigation of additional determinants of the disease.
Deep learning-based school attendance prediction for autistic students
Authors: Jarbou Mohammed , Won Daehan , Gillis-Mattson Jennifer , Romanczyk Raymond
Published: January 2022

Autism Spectrum Disorder is a neurodevelopmental disorder characterized by deficits in social communication and interaction as well as the presence of repetitive, restricted patterns of behavior, interests, or activities. Many autistic students experience difficulty with daily functioning at school and home. Given these difficulties,
regular school attendance is a primary source for autistic students to receive an appropriate range of needed educational and therapeutic interventions. Moreover, school absenteeism (SA) is associated with negative consequences such as school drop-out. Therefore, early SA prediction would help school districts to intervene properly to ameliorate this issue. Due to its heterogeneity, autistic students show within-group differences concerning their SA. A comprehensive statistical analysis performed by the authors shows that the individual and demographic characteristics of the targeted population are not predictive factors of SA. So, we used the students’ recent previous attendance to predict their future attendance. We introduce a deep learning-based framework for predicting short-and long-term SA of autistic students using the Long Short-Term Memory (LSTM) and Multilayer Perceptron (MLP) algorithms. The adopted algorithms outperform other machine learning algorithms. In detail, LSTM increased the accuracy and recall of short-term SA prediction by 20% and 13%, while the same scores of long-term SA prediction increased by 5% using MLP.
Entropy generation and thermal analysis of nanofluid flow inside the evacuated tube solar collector
Authors: Tabarhoseini S. Mojtaba , Sheikholeslami M.
Published: January 2022

In the current investigation, the thermal and thermodynamic behavior of a buoyancy-driven evacuated tube solar collector (ETSC) has undergone precise evaluation, and the efficacy of nanoparticle dispersion in the testing fluid was scrutinized. The natural convection process was analyzed in different vertical sections of the absorber tube. The outputs for water and the utilized nanofluid were compared at various cutting planes along the tube during the simulation time. In this problem, CuO nanoparticles with optimum thermal properties were distributed in the base fluid. According to the surveyed results, the temperature distribution analysis illustrates that the mean wall temperature experiences more enhancement when the nanofluid is used. The comparison of the heat transfer coefficient between the two simulated cases show the competency of utilizing CuO-$${\mathrm{H}}_{2}\mathrm{O}$$

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nanofluid and highlight its crucial character in improving the thermal treatment of the operate fluid through the collector pipe. Based on irreversibility assessment, the irreversibility due to fluid friction rises when the nanofluid is applied during the flow time. In contrast, the entropy generation of pure water owing to heat transfer surpasses the case with nanofluid. More specifically, the heat transfer entropy generation experience a reduction of about 6.3% (0.143–0.134 W/K) by utilization of CuO with a volume fraction of 5% after 1 h of flow time, whereas the entropy generation by fluid viscosity enhances up to 23% when the nanofluid is applied in the system. The irreversibility originated from heating and fluid viscosity has significant difference in value, owing to the fluid’s low-velocity range in the natural convection process.
Reduced decline of lung diffusing capacity in COPD patients with diabetes and metformin treatment
Authors: Kahnert Kathrin , Andreas Stefan , Kellerer Christina , Lutter Johanna I. , Lucke Tanja , Yildirim Önder , Lehmann Mareike , Seissler Jochen , Behr Jürgen , Frankenberger Marion , Bals Robert , Watz Henrik , Welte Tobias , Trudzinski Franziska C. , Vogelmeier Claus F. , Alter Peter , Jörres Rudolf A. ,   COSYCONET Study Group, Andreas Stefan , Bals Robert , Behr Jürgen , Kahnert Kathrin , Bahmer Thomas , Bewig Burkhard , Ewert Ralf , Stubbe Beate , Ficker Joachim H. , Grohé Christian , Held Matthias , Henke Markus , Herth Felix , Kirsten Anne-Marie , Watz Henrik , Koczulla Rembert , Kronsbein Juliane , Kropf-Sanchen Cornelia , Herzmann Christian , Pfeifer Michael , Randerath Winfried J. , Seeger Werner , Studnicka Michael , Taube Christian , Timmermann Hartmut , Alter Peter , Schmeck Bernd , Vogelmeier Claus , Welte Tobias , Wirtz Hubert
Published: January 2022

We studied whether in patients with COPD the use of metformin for diabetes treatment was linked to a pattern of lung function decline consistent with the hypothesis of anti-aging effects of metformin. Patients of GOLD grades 1–4 of the COSYCONET cohort with follow-up data of up to 4.5 y were included. The annual decline in lung function (FEV1, FVC) and CO diffusing capacity (KCO, TLCO) in %predicted at baseline was evaluated for associations with age, sex, BMI, pack-years, smoking status, baseline lung function, exacerbation risk, respiratory symptoms, cardiac disease, as well as metformin-containing therapy compared to patients without diabetes and metformin. Among 2741 patients, 1541 (mean age 64.4 y, 601 female) fulfilled the inclusion criteria. In the group with metformin treatment vs. non-diabetes the mean annual decline in KCO and TLCO was significantly lower (0.2 vs 2.3, 0.8 vs. 2.8%predicted, respectively; p < 0.05 each), but not the decline of FEV1 and FVC. These results were confirmed using multiple regression and propensity score analyses. Our findings demonstrate an association between the annual decline of lung diffusing capacity and the intake of metformin in patients with COPD consistent with the hypothesis of anti-aging effects of metformin as reflected in a surrogate marker of emphysema.
Residential radon and characteristics of chronic obstructive pulmonary disease
Authors: Pando-Sandoval Ana , Ruano-Ravina Alberto , Torres-Durán María , Dacal-Quintas Raquel , Valdés-Cuadrado Luis , Hernández-Hernández Jesús R. , Consuegra-Vanegas Angélica , Candal-Pedreira Cristina , Varela-Lema Leonor , Fernández-Villar Alberto , Pérez-Ríos Mónica
Published: January 2022

It is not known whether residential radon exposure may be linked to the development of chronic obstructive pulmonary disease (COPD) and/or have an influence on the functional characteristics or exacerbations of COPD. The aim of this study was therefore to ascertain whether there might be an association between residential radon concentrations and certain characteristics of COPD. We analyzed COPD cases drawn from a case–control study conducted in an area of high radon exposure. Data were collected on spirometric pulmonary function variables, hospital admissions, and smoking. Radon measurements were taken using alpha-track-type CR-39 detectors individually placed in patients’ homes. All statistical analyses were performed using the IBM SPSS v22 computer software program. The study included 189 COPD cases (79.4% men; median age 64 years). The median radon concentration was 157 Bq/m3. No differences were found between radon concentration and sex, age or severity of breathing obstruction as measured by FEV1%. It should be noted, however, that 48.1% of patients with FEV1% < 50 had radon concentrations below 100 Bq/m3, as compared to 35.6% with the same severity of obstruction who had over 300 Bq/m3. COPD cases with radon concentrations higher than > 600 Bq/m3 exhibited no different characteristics in lung function. Exposure to radon does not appear to have an influence on the clinical characteristics of smokers and ex-smokers with COPD. As exposure to residential radon increases, there is no trend towards a worsening of FEV1%. Further studies are thus needed to analyze this possible association in never-smokers with COPD.
Prevalence and antimicrobial susceptibility pattern of urinary tract infection among pregnant women attending Hargeisa Group Hospital, Hargeisa, Somaliland
Authors: Ali Abdikhaliq Hussein , Reda Dawit Yihdego , Ormago Moges Desta
Published: January 2022

The aim of this study was to determine the prevalence, antimicrobial susceptibility pattern and associated factors of urinary tract infection (UTI) among pregnant women attending Hargeisa Group Hospital (HGH), Hargeisa, Somaliland. A cross-sectional study was conducted at HGH, Hargeisa, Somaliland and participants were selected by systematic random sampling technique. Clean catch midstream urine samples were collected from 422 participants and cultured and antimicrobial susceptibility pattern was determined for the isolates. Univariable and multivariable logistic regression analyses were utilized to identify the independent risk factors for UTI. The prevalence of UTI was 16.4% (95% CI 13.3–19.9). The predominant bacteria isolate wasE. coli(43.5%) followed byCoagulase negative staphylococcus (CoNS)11(16%),S. aureus9(13%),K. pneumonia6(8.7%),Pseudomonas aeruginosa5(7.2%),Proteus mirabilis4(5.8%),Citrobacter spp3(4.4%) andM. morganii1(1.5%) Gram negative bacilli were resistant to ampicillin (96%) and tetracycline (71.4%) and Gram-positive cocci were also resistant to ampicillin (90%), tetracycline (55%). Multidrug resistance was observed in 85.5% of bacterial isolated. No formal education participants, previous history of catheterization and previous history of UTI had 3.18, 3.22 and 3.73 times respectively more likely to develop UTI than their counterparts. Culture and susceptibility test is vital for appropriate management of UTI in the study area.
Effect of data binning and frame averaging for micro-CT image acquisition on the morphometric outcome of bone repair assessment
Authors: Irie Milena Suemi , Spin-Neto Rubens , Borges Juliana Simeão , Wenzel Ann , Soares Priscilla Barbosa Ferreira
Published: January 2022

Despite the current advances in micro-CT analysis, the influence of some image acquisition parameters on the morphometric assessment outcome have not been fully elucidated. The aim of this study was to determine whether data binning and frame averaging affect the morphometric outcome of bone repair assessment using micro-CT. Four Wistar rats’ tibiae with a surgically created bone defect were imaged with micro-CT six times each, frame averaging set to 1 and 2, and data binning set to 1, 2 and 4, for each of the averaging values. Two-way ANOVA followed by Bonferroni tests assessed the significance of frame averaging and data binning on a set of morphometric parameters assessed in the image volumes (p < 0.01). The effect of frame averaging was not significant for any of the assessed parameters. Increased data binning led to larger trabecular thickness. In contrast, smaller bone volume fraction and bone volume were found as data binning increased. Trabeculae number and trabecular separation were not influenced by any of the parameters. In conclusion, the morphometric outcome of bone repair assessment in micro-CT demonstrated dependency upon data binning, but not frame averaging. Therefore, image acquisition of small anatomical structures (e.g., rat trabeculae) should be performed without data binning.
Morphometric analysis of the human common hepatic artery reveals a rich and accessible target for sympathetic liver denervation
Authors: Tzafriri Abraham Rami , Garcia-Polite Fernando , Keating John , Melidone Raffaele , Knutson Jennifer , Markham Peter , Edelman Elazer R. , Mahfoud Felix
Published: January 2022

This study quantified the distribution of nerves and adjacent anatomies surrounding human common hepatic artery (CHA) as guidance for catheter based denervation. CHA collected from cadaveric human donors (n = 20) were histologically evaluated and periarterial dimensions and distributions of nerves, lymph nodes, pancreas and blood vessels quantified by digital morphometry. Nerve abundance decreased significantly with distance from the aortic ostium (P < 0.0001) and was higher in the Superior/Inferior compared to the Anterior/Posterior quadrants (P = 0.014). In each locational group, nerves were absent from the artery wall, and starting 0.5–1.0 mm from the lumen exhibited a first order dependence on radial distance, fully defined by the median distance. Median subject-averaged nerve distance to the lumen was 2.75 mm, ranging from 2.1–3.1 mm in different arterial segments and quadrants and 2.0–3.5 mm in individuals. Inter-individual variance was high, with certain individuals exhibiting 50th and 75th nerve distances of, respectively, 3.5 and 6.5 mm The pancreas rarely approached within 4 mm of the lumen proximally and 2.5 mm more distally. The data indicate that the CHA is a rich and accessible target for sympathetic denervation regardless of sex and diabetes, with efficacy and safety most optimally balanced proximally.