bluuebunny/crossref_metadata_2025 huggingface dataset:
Intramedullary nail holes laser indicator, a non-invasive technique for interlocking of intramedullary nails
Authors: Maleki Mohammadreza , Tehrani Alireza Fadaei , Aray Ayda , Ranjbar Mehdi
Published: October 2021

Interlocking of intramedullary nails is a challenging procedure in orthopedic trauma surgery. Numerous methods have been described to facilitate this process. But they are exposed patient and surgical team to X-rays or involves trial and error. An accurate and non-invasive method has been provided to easily interlocking intramedullary nails. By transferring a safe visible light inside the nail, a drilling position appears which use to drilling bone toward the nail hole. The wavelength of this light was obtained from ex-vivo spectroscopy on biological tissues which has optimal transmission, reflectance, and absorption properties. Moreover, animal and human experiments were performed to evaluate performance of the proposed system. Ex-vivo performance experiments were performed successfully on two groups of cow and sheep samples. Output parameters were procedure time and drilling quality which there were significant differences between the two groups in procedure time (P < 0.05). But no significant differences were observed in drilling quality (P > 0.05). Moreover, an In-vivo performance experiment was performed successfully on a middle-aged man. To compare the provided method, targeting-arm, and free-hand techniques, two human experiments were performed on a middle-aged and a young man. The results indicate the advantage of the proposed technique in the procedure time (P < 0.05), while the drilling quality is equal to the free-hand technique (P = 0.05). Intramedullary nail holes laser indicator is a safe and accurate method that reduced surgical time and simplifies the process. This new technology makes it easier to interlocking the intramedullary nail which can have good clinical applications.
Apparatus design and behavioural testing protocol for the evaluation of spatial working memory in mice through the spontaneous alternation T-maze
Authors: d’Isa Raffaele , Comi Giancarlo , Leocani Letizia
Published: October 2021

Spatial working memory can be assessed in mice through the spontaneous alternation T-maze test. The T-maze is a T-shaped apparatus featuring a stem (start arm) and two lateral goal arms (left and right arms). The procedure is based on the natural tendency of rodents to prefer exploring a novel arm over a familiar one, which induces them to alternate the choice of the goal arm across repeated trials. During the task, in order to successfully alternate choices across trials, an animal has to remember which arm had been visited in the previous trial, which makes spontaneous alternation T-maze an optimal test for spatial working memory. As this test relies on a spontaneous behaviour and does not require rewards, punishments or pre-training, it represents a particularly useful tool for cognitive evaluation, both time-saving and animal-friendly. We describe here in detail the apparatus and the protocol, providing representative results on wild-type healthy mice.
Raptor breeding sites indicate high plant biodiversity in urban ecosystems
Authors: Natsukawa Haruki , Yuasa Hiroki , Komuro Shizuko , Sergio Fabrizio
Published: October 2021

Preserving biodiversity in urban ecosystems has become an urgent conservation priority, given the rapid upsurge in global urbanization. As woody plants play essential ecological roles and provide psychological benefits to human city dwellers, their preservation is of particular interest to conservation scientists. However, considering that extensive censuses of woody plants are resource-intensive, a key accomplishment is to find reliable conservation proxies that can be quickly used to locate biologically diverse areas. Here, we test the idea that sites occupied by apex predators can indicate high overall biodiversity, including high diversity of woody plants. To this end, we surveyed woody plant species within 500 m of Northern Goshawk (Accipiter gentilis) breeding sites in urban ecosystems of Japan and compared them with non-breeding control sites without goshawks. We found that goshawks successfully identified and signposted high levels of richness, abundance, and diversity of woody plants. Our findings show that sites occupied by top predatory species could be exploited as conservation proxies for high plant diversity. Due to their exigent ecological requirements, we would expect apex predators to be tied to high biodiversity levels in many other urban ecosystems worldwide.
Involvement of the habenula in the pathophysiology of autism spectrum disorder
Authors: Germann Jürgen , Gouveia Flavia Venetucci , Brentani Helena , Bedford Saashi A. , Tullo Stephanie , Chakravarty M. Mallar , Devenyi Gabriel A.
Published: October 2021

The habenula is a small epithalamic structure with widespread connections to multiple cortical, subcortical and brainstem regions. It has been identified as the central structure modulating the reward value of social interactions, behavioral adaptation, sensory integration and circadian rhythm. Autism spectrum disorder (ASD) is characterized by social communication deficits, restricted interests, repetitive behaviors, and is frequently associated with altered sensory perception and mood and sleep disorders. The habenula is implicated in all these behaviors and results of preclinical studies suggest a possible involvement of the habenula in the pathophysiology of this disorder. Using anatomical magnetic resonance imaging and automated segmentation we show that the habenula is significantly enlarged in ASD subjects compared to controls across the entire age range studied (6–30 years). No differences were observed between sexes. Furthermore, support-vector machine modeling classified ASD with 85% accuracy (model using habenula volume, age and sex) and 64% accuracy in cross validation. The Social Responsiveness Scale (SRS) significantly differed between groups, however, it was not related to individual habenula volume. The present study is the first to provide evidence in human subjects of an involvement of the habenula in the pathophysiology of ASD.
The effect of fatty diacid acylation of human PYY3-36 on Y2 receptor potency and half-life in minipigs
Authors: Østergaard Søren , Paulsson Johan F. , Kofoed Jacob , Zosel Franziska , Olsen Jørgen , Jeppesen Claus Bekker , Spetzler Jane , Ynddal Lars , Schleiss Luise Gram , Christoffersen Berit Østergaard , Raun Kirsten , Sensfuss Ulrich , Nielsen Flemming Seier , Jørgensen Rasmus , Wulff Birgitte S.
Published: October 2021

Peptides are notoriously known to display very short in vivo half-lives often measured in minutes which in many cases greatly reduces or eliminates sufficient in vivo efficacy. To obtain long half-lives allowing for up to once-weekly dosing regimen, fatty acid acylation (lipidation) have been used to non-covalently associate the peptide to serum albumin thus serving as a circulating depot. This approach is generally considered in the scientific and patent community as a standard approach to protract almost any given peptide. However, it is not trivial to prolong the half-life of peptides by lipidation and still maintain high potency and good formulation properties. Here we show that attaching a fatty acid to the obesity-drug relevant peptide PYY3-36 is not sufficient for long pharmacokinetics (PK), since the position in the backbone, but also type of fatty acid and linker strongly influences PK and potency. Furthermore, understanding the proteolytic stability of the backbone is key to obtain long half-lives by lipidation, since backbone cleavage still occurs while associated to albumin. Having identified a PYY analogue with a sufficient half-life, we show that in combination with a GLP-1 analogue, liraglutide, additional weight loss can be achieved in the obese minipig model.
The function of Scox in glial cells is essential for locomotive ability in Drosophila
Authors: Kowada Ryosuke , Kodani Atsushi , Ida Hiroyuki , Yamaguchi Masamitsu , Lee Im-Soon , Okada Yasushi , Yoshida Hideki
Published: October 2021

Synthesis of cytochrome c oxidase (Scox) is a Drosophila homolog of human SCO2 encoding a metallochaperone that transports copper to cytochrome c, and is an essential protein for the assembly of cytochrome c oxidase in the mitochondrial respiratory chain complex. SCO2 is highly conserved in a wide variety of species across prokaryotes and eukaryotes, and mutations in SCO2 are known to cause mitochondrial diseases such as fatal infantile cardioencephalomyopathy, Leigh syndrome, and Charcot-Marie-Tooth disease, a neurodegenerative disorder. These diseases have a common symptom of locomotive dysfunction. However, the mechanisms of their pathogenesis remain unknown, and no fundamental medications or therapies have been established for these diseases. In this study, we demonstrated that the glial cell-specific knockdown of Scox perturbs the mitochondrial morphology and function, and locomotive behavior in Drosophila. In addition, the morphology and function of synapses were impaired in the glial cell-specific Scox knockdown. Furthermore, Scox knockdown in ensheathing glia, one type of glial cell in Drosophila, resulted in larval and adult locomotive dysfunction. This study suggests that the impairment of Scox in glial cells in the Drosophila CNS mimics the pathological phenotypes observed by mutations in the SCO2 gene in humans.
Thickness-dependent in-plane anisotropy of GaTe phonons
Authors: Hoang Nguyen The , Lee Je-Ho , Vu Thi Hoa , Cho Sunglae , Seong Maeng-Je
Published: October 2021

Gallium Telluride (GaTe), a layered material with monoclinic crystal structure, has recently attracted a lot of attention due to its unique physical properties and potential applications for angle-resolved photonics and electronics, where optical anisotropies are important. Despite a few reports on the in-plane anisotropies of GaTe, a comprehensive understanding of them remained unsatisfactory to date. In this work, we investigated thickness-dependent in-plane anisotropies of the 13 Raman-active modes and one Raman-inactive mode of GaTe by using angle-resolved polarized Raman spectroscopy, under both parallel and perpendicular polarization configurations in the spectral range from 20 to 300 cm−1. Raman modes of GaTe revealed distinctly different thickness-dependent anisotropies in parallel polarization configuration while nearly unchanged for the perpendicular configuration. Especially, three Ag modes at 40.2 ($${\text{A}}_{\text{g}}^{1}$$

A

g

1

), 152.5 ($${\text{A}}_{\text{g}}^{7}$$

A

g

7

), and 283.8 ($${\text{A}}_{\text{g}}^{12}$$

A

g

12

) cm−1 exhibited an evident variation in anisotropic behavior as decreasing thickness down to 9 nm. The observed anisotropies were thoroughly explained by adopting the calculated interference effect and the semiclassical complex Raman tensor analysis.
Endocytic BDNF secretion regulated by Vamp3 in astrocytes
Authors: Han Jeongho , Yoon Sungryeong , Park Hyungju
Published: October 2021

Brain-derived neurotrophic factor (BDNF) regulates diverse brain functions via TrkB receptor signaling. Due to the expression of TrkB receptors, astrocytes can internalize extracellular BDNF proteins via receptor-mediated endocytosis. Endocytosed BDNF can be re-secreted upon stimulation, but the molecular mechanism underlying this phenomenon remains unrecognized. Our study reveals that vesicle-associated membrane protein 3 (Vamp3) selectively regulates the release of endocytic BDNF from astrocytes. By using quantum dot (QD)-conjugated mature BDNF (QD-BDNF) as a proxy for the extracellular BDNF protein, we monitored the uptake, transport, and secretion of BDNF from cultured cortical astrocytes. Our data showed that endocytic QD-BDNF particles were enriched in Vamp3-containing vesicles in astrocytes and that ATP treatment sufficiently triggered either the antero- or retrograde transport and exocytosis of QD-BDNF-containing vesicles. Downregulation of Vamp3 expression disrupted endocytic BDNF secretion from astrocytes but did not affect uptake or transport. Collectively, these results provide evidence of the selective ability of astrocytic Vamp3 to control endocytic BDNF secretion during BDNF recycling.
Symbiosis maintenance in the facultative coral, Oculina arbuscula, relies on nitrogen cycling, cell cycle modulation, and immunity
Authors: Rivera H. E. , Davies S. W.
Published: October 2021

Symbiosis with unicellular algae in the family Symbiodiniaceae is common across tropical marine invertebrates. Reef-building corals offer a clear example of cellular dysfunction leading to a dysbiosis that disrupts entire ecosystems in a process termed coral bleaching. Due to their obligate symbiotic relationship, understanding the molecular underpinnings that sustain this symbiosis in tropical reef-building corals is challenging, as any aposymbiotic state is inherently coupled with severe physiological stress. Here, we leverage the subtropical, facultatively symbiotic and calcifying coralOculina arbusculato investigate gene expression differences between aposymbiotic and symbiotic branches within the same colonies under baseline conditions. We further compare gene ontology (GO) and KOG enrichment in gene expression patterns fromO. arbusculawith prior work in the sea anemoneExaiptasia pallida(Aiptasia) and the salamanderAmbystoma maculatum—both of which exhibit endophotosymbiosis with unicellular algae. We identify nitrogen cycling, cell cycle control, and immune responses as key pathways involved in the maintenance of symbiosis under baseline conditions. Understanding the mechanisms that sustain a healthy symbiosis between corals and Symbiodiniaceae algae is of urgent importance given the vulnerability of these partnerships to changing environmental conditions and their role in the continued functioning of critical and highly diverse marine ecosystems.
IFNL4 genetic variant can predispose to COVID-19
Authors: Saponi-Cortes Jose Maria R. , Rivas Maria Dolores , Calle-Alonso Fernando , Sanchez Juan F. , Costo Alberto , Martin Carlos , Zamorano Jose
Published: October 2021

Interferon lambda 4 (IFNλ4) has shown antiviral activity against RNA viruses, including some coronaviruses. Besides, genetic variants of IFNL4 can be predictive of the clearance of RNA viruses. However, little is known about the effect of these genetic variants on SARS-CoV-2 infection. In this study, we investigated whether there was a relationship of the rs12979860 polymorphism of IFNL4 with COVID-19. We found that the T allele of rs12979860 was overexpressed in COVID-19 patients with regard to the general population without this disease (36.16% vs. 26.40%, p = 6.4 × 10–4; OR 0.633 C vs T; 95% CI 0.487, 0.824), suggesting that this allele could be a risk factor for COVID-19. Accordingly, the CC genotype was significantly lower in COVID-19 patients compared to controls (37.85% vs. 55.51%, p = 8 × 10–5; OR 0.488; 95% CI 0.342, 0.698). These results were not affected by sex, age, and disease severity in patients with COVID-19. Our findings suggest that, like other infectious diseases caused by RNA viruses, genetic variants of IFNL4 can predispose to COVID-19. Confirmation of our results may contribute to better understanding the mechanisms of this disease.
Approaching mercury distribution in burial environment using PLS-R modelling
Authors: Álvarez-Fernández Noemi , Martínez Cortizas Antonio , García-López Zaira , López-Costas Olalla
Published: October 2021

Mercury environmental cycle and toxicology have been widely researched. Given the long history of mercury pollution, researching mercury trends in the past can help to understand its behaviour in the present. Archaeological skeletons have been found to be useful sources of information regarding mercury loads in the past. In our study we applied a soil multi-sampling approach in two burials dated to the 5th to 6th centuries AD. PLRS modelling was used to elucidate the factors controlling mercury distribution. The model explains 72% of mercury variance and suggests that mercury accumulation in the burial soils is the result of complex interactions. The decomposition of the bodies not only was the primary source of mercury to the soil but also responsible for the pedogenetic transformation of the sediments and the formation of soil components with the ability to retain mercury. The amount of soft tissues and bone mass also resulted in differences between burials, indicating that the skeletons were a primary/secondary source of mercury to the soil (i.e. temporary sink). Within burial variability seems to depend on the proximity of the soil to the thoracic area, where the main mercury target organs were located. We also conclude that, in coarse textured soils, as the ones studied in this investigation, the finer fraction (i.e. silt + clay) should be analysed, as it is the most reactive and the one with the higher potential to provide information on metal cycling and incipient soil processes. Finally, our study stresses the need to characterise the burial soil environment in order to fully understand the role of the interactions between soil and skeleton in mercury cycling in burial contexts.
Establishment of novel in vitro culture system with the ability to reproduce oral biofilm formation on dental materials
Authors: Kohno Tomoki , Kitagawa Haruaki , Tsuboi Ririko , Nishimura Yuma , Imazato Satoshi
Published: October 2021

Intensive research has been conducted with the aim of developing dental restorative/prosthetic materials with antibacterial and anti-biofilm effects that contribute to controlling bacterial infection in the oral cavity. In situ evaluations were performed to assess the clinical efficacy of these materials by exposing them to oral environments. However, it is difficult to recruit many participants to collect sufficient amount of data for scientific analysis. This study aimed to assemble an original flow-cell type bioreactor equipped with two flow routes and assess its usefulness by evaluating the ability to reproduce in situ oral biofilms formed on restorative materials. A drop of bacterial suspension collected from human saliva and 0.2% sucrose solution was introduced into the assembled bioreactor while maintaining the incubation conditions. The bioreactor was able to mimic the number of bacterial cells, live/dead bacterial volume, and volume fraction of live bacteria in the in situ oral biofilm formed on the surface of restorative materials. The usefulness of the established culture system was further validated by a clear demonstration of the anti-biofilm effects of a glass-ionomer cement incorporating zinc-releasing glasses when evaluated by this system.
A data calibration method for micro air quality detectors based on a LASSO regression and NARX neural network combined model
Authors: Liu Bing , Jin Yueqiang , Xu Dezhi , Wang Yishu , Li Chaoyang
Published: October 2021

Studies have shown that there is a certain correlation between air pollution and various human diseases, especially lung diseases, so it is very meaningful to monitor the concentration of pollutants in the air. Compared with the national air quality monitoring station (national control point), the micro air quality detector has the advantage that it can monitor the concentration of pollutants in real time and grid, but its measurement accuracy needs to be improved. This paper proposes a model combining the least absolute selection and shrinkage operator (LASSO) regression and nonlinear autoregressive models with exogenous inputs (NARX) to calibrate the data measured by the micro air quality detector. Before establishing the LASSO-NARX model, correlation analysis is used to test whether the correlation between the concentration of air pollutants and its influencing factors is significant, and to find out the main factors that affect the concentration of pollutants. Due to the multicollinearity between various influencing factors, LASSO regression is used to further screen the influencing factors and give the quantitative relationship between the pollutant concentration and various influencing factors. In order to improve the prediction accuracy of pollutant concentration, the predicted value of each pollutant concentration in the LASSO regression model and the measurement data of the micro air quality detector are used as input variables, and the LASSO-NARX model is constructed using the NARX neural network. Several indicators such as goodness of fit, root mean square error, mean absolute error and relative mean absolute percent error are used to compare various air quality models. The results show that the prediction results of the LASSO-NARX model are not only better than the LASSO model alone and the NARX model alone, but also better than the commonly used multilayer perceptron and radial basis function neural network. Using this model to calibrate the measurement data of the micro air quality detector can increase the accuracy by 61.3–91.7%.
Profiling intestinal microbiota of Metaplax longipes and Helice japonica and their co-occurrence relationships with habitat microbes
Authors: Li Haidong , Li Shanshan , Fan Shiliang , Xu Yan , Tian Xiangli
Published: October 2021

Intestinal microbiota plays key roles in maintaining the health and homeostasis of the host. However, information about whether the formation of intestinal microbiota of wild aquatic animals is associated with habitat microbes is not fully understood. Here, intestine samples were collected from two wild crab species and sediment samples were collected from the habitat environment. The total DNA of each sample was extracted, and the V3–V4 regions of 16S rRNA were sequenced using the MiSeq platform. The purpose of this study was to investigate the composition and diversity of intestinal microbiota and habitat microbes, and bacterial community relationships between wild crab intestine and habitat sediment. In the present study, the composition and diversity of intestinal microbiota of the two crab species were different from the habitat microbes. In contrast, a similar composition and diversity of the intestinal microbiota were observed between two crab species. Moreover, the bacterial community relationships between crab intestine and habitat sediment were associated with intestinal regions. Further network analysis revealed that the network structure of the intestinal microbiota was not only associated with intestinal regions, but also with the crab species. Additionally, although the compositions of bacterial functions were similar between crab intestine and sediment, no significant correlation in bacterial functions was observed between crab intestine and sediment. The findings of the present study would contribute to understanding the relationship between intestinal microbiota of wild aquatic animal and habitat microbes, and providing new insights into the intestinal microbiota of wild aquatic animals.
Sham-derived effects and the minimal reliability of theta burst stimulation
Authors: Boucher P. O. , Ozdemir R. A. , Momi D. , Burke M. J. , Jannati A. , Fried P. J. , Pascual-Leone A. , Shafi M. M. , Santarnecchi Emiliano
Published: October 2021

Theta-burst stimulation (TBS) is a patterned form of repetitive transcranial magnetic stimulation (rTMS) that has been used to induce long-term modulation (plasticity) of corticospinal excitability in a drastically shorter duration protocol than conventional rTMS protocols. In this study we tested the reliability of the effects of two well defined TBS protocols, continuous TBS (cTBS) and intermittent TBS (iTBS), especially in relation to sham TBS, within and across the same 24 participants. All TBS protocols were repeated after approximately 1 month to assess the magnitude and reliability of the modulatory effects of each TBS protocol. Baseline and post-TBS changes in motor evoked potentials (MEP—measure of corticospinal excitability) amplitudes were compared across the cTBS, iTBS and sham TBS protocols and between the initial and retest visits. Overall, across participants, at the initial visit, iTBS facilitated MEPs as compared to baseline excitability, with sham eliciting the same effect. cTBS did not show a significant suppression of excitability compared to baseline MEPs at either visit, and even facilitated MEPs above baseline excitability at a single time point during the repeat visit. Otherwise, effects of TBS were generally diminished in the repeat visit, with iTBS and sham TBS replicating facilitation of MEPs above baseline excitability at similar time points. However, no protocol demonstrated consistent intra-individual modulation of corticospinal excitability upon retest. As the first study to test both iTBS and cTBS against sham TBS across repeat visits, our findings challenge the efficacy and reliability of TBS protocols and emphasize the importance of accounting for sham effects of TBS. Furthermore, given that therapeutic effects of TBS are hypothetically derived from consistent and repeated modulation of brain activity, the non-replicability of plasticity and sham effects call into question these basic mechanisms.
Antiviral activity of silymarin and baicalein against dengue virus
Authors: Low Zhao Xuan , OuYong Brian Ming , Hassandarvish Pouya , Poh Chit Laa , Ramanathan Babu
Published: October 2021

Dengue is an arthropod-borne viral disease that has become endemic and a global threat in many countries with no effective antiviral drug available currently. This study showed that flavonoids: silymarin and baicalein could inhibit the dengue virus in vitro and were well tolerated in Vero cells with a half-maximum cytotoxic concentration (CC50) of 749.70 µg/mL and 271.03 µg/mL, respectively. Silymarin and baicalein exerted virucidal effects against DENV-3, with a selective index (SI) of 10.87 and 21.34, respectively. Baicalein showed a better inhibition of intracellular DENV-3 progeny with a SI of 7.82 compared to silymarin. Baicalein effectively blocked DENV-3 attachment (95.59%) to the Vero cells, while silymarin prevented the viral entry (72.46%) into the cells, thus reducing viral infectivity. Both flavonoids showed promising antiviral activity against all four dengue serotypes. The in silico molecular docking showed that silymarin could bind to the viral envelope (E) protein with a binding affinity of − 8.5 kcal/mol and form hydrogen bonds with the amino acids GLN120, TRP229, ASN89, and THR223 of the E protein. Overall, this study showed that silymarin and baicalein exhibited potential anti-DENV activity and could serve as promising antiviral agents for further development against dengue infection.
Contrasting response of hydrological cycle over land and ocean to a changing CO2 pathway
Authors: Yeh Sang-Wook , Song Se-Yong , Allan Richard P. , An Soon-Il , Shin Jongsoo
Published: October 2021

The hydrological cycle has a significant impact on human activities and ecosystems, so understanding its mechanisms with respect to a changing climate is essential. In particular, a more detailed understanding of hydrological cycle response to transient climate change is required for successful adaptation and mitigation policies. In this study, we exploit large ensemble model experiments using the Community Earth System Model version 1.2.2 (CESM1) in which CO2 concentrations increase steadily and then decrease along the same path. Our results show that precipitation changes in the CO2 increasing and decreasing phases are nearly symmetrical over land but asymmetric over oceans. After CO2 concentrations peak, the ocean continues to uptake heat from the atmosphere, which is a key process leading the hydrological cycle’s contrasting response over land and ocean. The symmetrical hydrological cycle response over land involves a complex interplay between rapid responses to CO2 and slower responses to ensuing warming. Therefore, the surface energy constraints lead to the contrasting hydrological response over land and ocean to CO2 forcing that needs to be verified and considered in climate change mitigation and adaption actions.
An oceanic pathway for Madden–Julian Oscillation influence on Maritime Continent Tropical Cyclones
Authors: Balaguru Karthik , Leung L. Ruby , Hagos Samson M. , Krishnakumar Sujith
Published: October 2021

While the Madden–Julian Oscillation (MJO) has been shown to affect tropical cyclones (TCs) worldwide through its modulation of large-scale circulation in the atmosphere, little or no role for the ocean has been identified to date in this influence of MJO on TCs. Using observations and numerical model simulations, we demonstrate that MJO events substantially impact TCs over the Maritime Continent (MC) region through an oceanic pathway. While propagating across the MC region, MJO events cause significant sea surface cooling with an area-averaged value of about 0.35 ± 0.12 °C. Hence, TCs over the MC region immediately following the passage of MJO events encounter considerably cooler sea surface temperatures. Consequently, the enthalpy fluxes under the storms are reduced and the intensification rates decrease by more than 50% on average. These results highlight an important role played by the ocean in facilitating MJO-induced sub-seasonal variability in TC activity over the MC region.
Molecular differences between lymph nodes and distant metastases compared with primaries in colorectal cancer patients
Authors: Puccini Alberto , Seeber Andreas , Xiu Joanne , Goldberg Richard M. , Soldato Davide , Grothey Axel , Shields Anthony F. , Salem Mohamed E. , Battaglin Francesca , Berger Martin D. , El-Deiry Wafik S. , Tokunaga Ryuma , Naseem Madiha , Zhang Wu , Arora Sukeshi Patel , Khushman Moh’d M. , Hall Michael J. , Philip Philip A. , Marshall John L. , Korn W. Michael , Lenz Heinz-Josef
Published: October 2021

Lymph nodes (LNs) and distant metastases can arise from independent subclones of the primary tumor. Herein, we characterized the molecular landscape and the differences between LNs, distant metastases and primary colorectal cancers (CRCs). Samples were analyzed using next generation sequencing (NGS, MiSeq on 47 genes, NextSeq on 592 genes) and immunohistochemistry. Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous missense mutations, and microsatellite instability (MSI) was evaluated by NGS of known MSI loci. In total, 11,871 samples were examined, comprising primaries (N = 5862), distant (N = 5605) and LNs metastases (N = 404). The most frequently mutated genes in LNs were TP53 (72%), APC (61%), KRAS (39%), ARID1A (20%), PIK3CA (12%). LNs showed a higher mean TMB (13 mut/MB) vs distant metastases (9 mut/MB, p < 0.0001). TMB-high (≥17mut/MB) and MSI-H (8.8% and 6.9% vs 3.7%, p < 0.001 and p = 0.017, respectively) classifications were more frequent in primaries and LNs vs distant metastases (9.5% and 8.8% vs 4.2%, p < 0.001 and p = 0.001, respectively). TMB-high is significantly more common in LNs vs distant metastases and primaries (P < 0.0001), regardless MSI-H status. Overall, LNs showed significantly different rates of mutations in APC, KRAS, PI3KCA, KDM6A, and BRIP1 (p < 0.01) vs primaries, while presenting a distinct molecular profile compared to distant metastases. Our cohort of 30 paired samples confirmed the molecular heterogeneity between primaries, LNs, and distant metastases. Our data support the hypothesis that lymphatic and distant metastases harbor different mutational landscape. Our findings are hypothesis generating and need to be examined in prospective studies.
Clinical knowledge extraction via sparse embedding regression (KESER) with multi-center large scale electronic health record data
Authors: Hong Chuan , Rush Everett , Liu Molei , Zhou Doudou , Sun Jiehuan , Sonabend Aaron , Castro Victor M. , Schubert Petra , Panickan Vidul A. , Cai Tianrun , Costa Lauren , He Zeling , Link Nicholas , Hauser Ronald , Gaziano J. Michael , Murphy Shawn N. , Ostrouchov George , Ho Yuk-Lam , Begoli Edmon , Lu Junwei , Cho Kelly , Liao Katherine P. , Cai Tianxi ,   VA Million Veteran Program
Published: October 2021

The increasing availability of electronic health record (EHR) systems has created enormous potential for translational research. However, it is difficult to know all the relevant codes related to a phenotype due to the large number of codes available. Traditional data mining approaches often require the use of patient-level data, which hinders the ability to share data across institutions. In this project, we demonstrate that multi-center large-scale code embeddings can be used to efficiently identify relevant features related to a disease of interest. We constructed large-scale code embeddings for a wide range of codified concepts from EHRs from two large medical centers. We developed knowledge extraction via sparse embedding regression (KESER) for feature selection and integrative network analysis. We evaluated the quality of the code embeddings and assessed the performance of KESER in feature selection for eight diseases. Besides, we developed an integrated clinical knowledge map combining embedding data from both institutions. The features selected by KESER were comprehensive compared to lists of codified data generated by domain experts. Features identified via KESER resulted in comparable performance to those built upon features selected manually or with patient-level data. The knowledge map created using an integrative analysis identified disease-disease and disease-drug pairs more accurately compared to those identified using single institution data. Analysis of code embeddings via KESER can effectively reveal clinical knowledge and infer relatedness among codified concepts. KESER bypasses the need for patient-level data in individual analyses providing a significant advance in enabling multi-center studies using EHR data.
Characterizing the breast cancer lipidome and its interaction with the tissue microbiota
Authors: Giallourou Natasa , Urbaniak Camilla , Puebla-Barragan Scarlett , Vorkas Panagiotis A. , Swann Jonathan R. , Reid Gregor
Published: October 2021

Breast cancer is the most diagnosed cancer amongst women worldwide. We have previously shown that there is a breast microbiota which differs between women who have breast cancer and those who are disease-free. To better understand the local biochemical perturbations occurring with disease and the potential contribution of the breast microbiome, lipid profiling was performed on non-tumor breast tissue collected from 19 healthy women and 42 with breast cancer. Here we identified unique lipid signatures between the two groups with greater amounts of lysophosphatidylcholines and oxidized cholesteryl esters in the tissue from women with breast cancer and lower amounts of ceramides, diacylglycerols, phosphatidylcholines, and phosphatidylethanolamines. By integrating these lipid signatures with the breast bacterial profiles, we observed that Gammaproteobacteria and those from the class Bacillus, were negatively correlated with ceramides, lipids with antiproliferative properties. In the healthy tissues, diacylglyerols were positively associated with Acinetobacter, Lactococcus, Corynebacterium, Prevotella and Streptococcus. These bacterial groups were found to possess the genetic potential to synthesize these lipids. The cause-effect relationships of these observations and their contribution to disease patho-mechanisms warrants further investigation for a disease afflicting millions of women around the world.
Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study
Authors: Fendler Annika , Au Lewis , Shepherd Scott T. C. , Byrne Fiona , Cerrone Maddalena , Boos Laura Amanda , Rzeniewicz Karolina , Gordon William , Shum Benjamin , Gerard Camille L. , Ward Barry , Xie Wenyi , Schmitt Andreas M. , Joharatnam-Hogan Nalinie , Cornish Georgina H. , Pule Martin , Mekkaoui Leila , Ng Kevin W. , Carlyle Eleanor , Edmonds Kim , Rosario Lyra Del , Sarker Sarah , Lingard Karla , Mangwende Mary , Holt Lucy , Ahmod Hamid , Stone Richard , Gomes Camila , Flynn Helen R. , Agua-Doce Ana , Hobson Philip , Caidan Simon , Howell Michael , Wu Mary , Goldstone Robert , Crawford Margaret , Cubitt Laura , Patel Harshil , Gavrielides Mike , Nye Emma , Snijders Ambrosius P. , MacRae James I. , Nicod Jerome , Gronthoud Firza , Shea Robyn L. , Messiou Christina , Cunningham David , Chau Ian , Starling Naureen , Turner Nicholas , Welsh Liam , van As Nicholas , Jones Robin L. , Droney Joanne , Banerjee Susana , Tatham Kate C. , Jhanji Shaman , O’Brien Mary , Curtis Olivia , Harrington Kevin , Bhide Shreerang , Bazin Jessica , Robinson Anna , Stephenson Clemency , Slattery Tim , Khan Yasir , Tippu Zayd , Leslie Isla , Gennatas Spyridon , Okines Alicia , Reid Alison , Young Kate , Furness Andrew J. S. , Pickering Lisa , Gandhi Sonia , Gamblin Steve , Swanton Charles ,   The Crick COVID-19 Consortium, Nicholson Emma , Kumar Sacheen , Yousaf Nadia , Wilkinson Katalin A. , Swerdlow Anthony , Harvey Ruth , Kassiotis George , Larkin James , Wilkinson Robert J. , Turajlic Samra ,   The CAPTURE consortium
Published: October 2021

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer.
Lignin as a MALDI matrix for small molecules: a proof of concept
Authors: Zhao Xiaoyong , Wang Huiwen , Liu Yilong , Ou Ruohan , Liu Yaqin , Li Xian , Pan Yuanjiang
Published: October 2021

Natural lignin was firstly applied as a dual-ion-mode MALDI matrix for small molecules, which successfully identified over 30 different small molecules and six kinds of representative molecules were quantified with a good linear response.
A 3D pancreatic tumor model to study T cell infiltration
Authors: Mollica Hilaria , Teo Yi Juan , Tan Alrina Shin Min , Tan Damien Zhi Ming , Decuzzi Paolo , Pavesi Andrea , Adriani Giulia
Published: October 2021

Human T cell infiltration across the endothelium in a 3-dimensional pancreatic tumor model in relation to activation and cellular components.
Attempted reduction of a carbazolyl-diiodoalane
Authors: Hinz Alexander , Müller Maximilian P.
Published: October 2021

A carbazolyl-diiodoalane was prepared and subjected to reducing conditions with KC8, Mg(i) compounds, or Cp*2Co.
A Cd-MOF fluorescence sensor with dual functional sites for efficient detection of metal ions in multifarious water environments
Authors: Li Jing , Zhao Yun-Xiu , Wu Qian , Yang Hua , Lu Jing , Ma Hui-Yan , Wang Su-Na , Li Yun-Wu
Published: October 2021

A 2D MOF displays high performance luminescence quenching for detecting Fe3+ and Cu2+ in pure water, actual river water and simulated HEPES with superior low LODs. Multiple experiments and DFT calculations co-verify a weak interaction quenching mechanism.
Single non-noble metal atom doped C2N catalysts for chemoselective hydrogenation of 3-nitrostyrene
Authors: Huang Huaquan , Jian Changping , Zhu Yijia , Guo Rou , Chen Xujian , Wang Fang-Fang , Chen De-Li , Zhang Fumin , Zhu Weidong
Published: October 2021

A single non-noble metal atom doped Mn–C2N catalyst was theoretically screened to selectively transform 3-nitrostyrene into 3-vinylaniline.
Water/oil interfacial tension reduction – an interfacial entropy driven process
Authors: Bui Tai , Frampton Harry , Huang Shanshan , Collins Ian R. , Striolo Alberto , Michaelides Angelos
Published: October 2021

Interfacial disordering/interfacial entropy plays a critical role in determining the interfacial tension (IFT) of a fluid-fluid interface.
Critical conditions for whether two impacting nanodroplets can coalesce or not: a molecular simulation study
Authors: Li Tao
Published: October 2021

The coalescence dynamics of two impacting droplets is investigated and the critical conditions for them to coalesce are provided.
Kinetics of the oxidation of ammonia and amines with hydroxyl radicals in the aqueous phase
Authors: Yang Xiaoying , Tao Ye , Murphy Jennifer G.
Published: October 2021

The aqueous phase oxidation of ammonia and alkyl amines by OH is pH-dependent and can impact their atmospheric lifetime.
Amino-modified zirconia aerogels for the efficient filtration of NO2: effects of water on the removal mechanisms
Authors: Wang Xinbo , Li Kai , Liang Guojie , Zhao Yue , Su Ruyue , Luan Zhiqiang , Li Li , Xi Hailing
Published: October 2021

Nitramines/nitrosamines and nitrates separately become the dominant adsorption products under different RH conditions.
Enteromorpha prolifera polysaccharide–zinc complex modulates the immune response and alleviates LPS-induced intestinal inflammation via inhibiting the TLR4/NF-κB signaling pathway
Authors: Zhang Yumei , Duan Xinyi , Wassie Teketay , Wang Hai-hua , Li Tiejun , Xie Chunyan , Wu Xin
Published: October 2021

Enteromorpha prolifera polysaccharide–zinc (EP–Zn), a kind of polysaccharide–zinc complex, exerted immunomodulatory and anti-inflammatory activities under physiological and inflammatory conditions, respectively.
Dietary agents in mitigating chemotherapy-related cognitive impairment (chemobrain or chemofog): first review addressing the benefits, gaps, challenges and ways forward
Authors: Raghu Shamprasad Varija , Kudva Avinash Kundadka , Rao Suresh , Prasad Krishna , Mudgal Jayesh , Baliga Manjeshwar Shrinath
Published: October 2021

Chemobrain or chemofog is one of the important but less investigated side effects, where the cancer survivors treated with chemotherapy develop long-term cognitive impairments, affecting their quality of life.
Design and synthesis of a new series of 3,5-disubstituted-1,2,4-oxadiazoles as potential colchicine binding site inhibitors: antiproliferative activity, molecular docking, and SAR studies
Authors: Diab Rana T. , Abdel-Sami Zakaria K. , Abdel-Aal Eatedal H. , Al-Karmalawy Ahmed A. , Abo-Dya Nader E.
Published: October 2021

Novel oxadiazole candidates as potential colchicine binding site inhibitors: antiproliferative activity, molecular docking, and sar studie.
Organosulfur, organoselenium, and organotellurium ligands in the development of palladium, nickel, and copper-based catalytic systems for Heck coupling
Authors: Oswal Preeti , Arora Aayushi , Gairola Sakshi , Datta Anupama , Kumar Arun
Published: October 2021

Organosulfur, organoselenium, and organotellurium ligands in designing Pd, Ni, and Cu-based homogeneous, heterogeneous, and nanocatalytic systems for Heck coupling.
Amine-functionalized metal–organic framework integrated bismuth tungstate (Bi2WO6/NH2-UiO-66) composite for the enhanced solar-driven photocatalytic degradation of ciprofloxacin molecules
Authors: Karuppannan Rokesh , Mohan Sakar , Do Trong-On
Published: October 2021

The Bi2WO6/NH2-UiO-66 composite with Z-Scheme heterojunction formation offered efficient charge separation and strong redox property towards ciprofloxacin degradation under solar light irradiation.
Organic ammonium salt-assisted pinhole-free CuSCN films for carbon-based perovskite solar cells
Authors: He Zhen , Meng Fanning , Li Lianjie , Gao Liguo , Ma Tingli
Published: October 2021

Organic ammonium salt, PEAI, has been utilized as additive in CuSCN film of C-PSCs. It not only eliminated the pinhole, but also passivated the perovskite film and enhanced the interfacial connection, resulting in a 11% PCE improvement.
Synthesis of polysubstituted pyrrolesviaisocyanide-based multicomponent reactions as an efficient synthesis tool
Authors: Nazeri Mohammad Taghi , Shaabani Ahmad
Published: October 2021

The present review covers all synthetic methods based on isocyanide-based multicomponent reactions for the preparation of polysubstituted pyrroles as the parent cores of many essential drugs, biologically active compounds, and compounds with wide application in materials science.
A template oriented one-dimensional Schiff-base polymer: towards flexible nitrogen-enriched carbonaceous electrodes with ultrahigh electrochemical capacity
Authors: Xiao Zhichang , Han Junwei , He Haiyong , Zhang Xinghao , Xiao Jing , Han Daliang , Kong Debin , Wang Bin , Yang Quan-Hong , Zhi Linjie
Published: October 2021

Schiff-base-type polymer is successfully integrated into one-dimensional structure. The derived nitrogen-doped porous carbon nanofibers are proved to be ideal energy storage electrode materials in supercapacitor and lithium-ion capacitor.
Synthesis of tetracyclic spiroindolines by an interrupted Bischler–Napieralski reaction: total synthesis of akuammicine
Authors: Faltracco Matteo , Ruijter Eelco
Published: October 2021

The interrupted Bischler–Napieralski reaction of β,γ-unsaturated tryptamides affords tetracyclic spiro pyrroloindolines, which can be used in the total synthesis of the Strychnos alkaloid, akuammicine.
Extended anisotropic phonon dispersion and optical properties of two-dimensional ternary SnSSe
Authors: Usman Muhammad , Muhammad Zahir , Dastgeer Ghulam , Zawadzka Natalia , Niu Yijie , Imran Muhammad , Molas Maciej R. , Rui Hu
Published: October 2021

The phonon dispersion and optical properties of mechanically exfoliated SnSSe were investigated with the aid of high-resolution Raman scattering and photoluminescence (PL) spectroscopies along with first-principles calculations.
Sequence-sorted redox-switchable hetero[3]rotaxanes
Authors: Gaedke Marius , Hupatz Henrik , Witte Felix , Rupf Susanne M. , Douglas Clara , Schröder Hendrik V. , Fischer Lukas , Malischewski Moritz , Paulus Beate , Schalley Christoph A.
Published: October 2021

Programming the sequence of functional units in redox-switchable hetero[3]rotaxanes is achieved by integrative self-sorting for a library of five crown ethers.
Novel potentiometric sensors for determination of ondansetron hydrochloride in pure and dosage form
Authors: Abass Amina M. , Alabdullah Sahar S. M. , Hassan Omar Salih , Ahmed Ahmed
Published: October 2021

A new and sensitive potentiometric method has been developed and characterized for four novel sensors responsive to ondansetron hydrochloride.
A novel 3D terbium metal–organic framework as a heterogeneous Lewis acid catalyst for the cyanosilylation of aldehyde
Authors: Liu Yuqian , Zhao Peiran , Duan Chunying , He Cheng
Published: October 2021

A novel 3D lanthanide metal–organic framework synthesized from Tb ions and the rigid organic ligand H2sbdc could work as an efficient heterogeneous catalyst for the cyanosilylation of aromatic aldehydes.
Aggregation of retained helium and hydrogen in titanium beryllide Be12Ti: a first-principles study
Authors: Wang Yinlong , Wang Canglong , Meng Zhaocang , Liu Jitao , Li Yuhong , Yang Lei
Published: October 2021

The He bubble will initially nucleate around VBe2. Then the nucleation of the He bubble will occur around the divacancy of VBe2VBe1 and the trivacancy of VBe2VBe1VBe3. The presence of H atoms will significantly influence the nucleation of the He bubble.
In situ recalibration of ion selective electrodes
Authors: Sisodia Neel , McGuinness Kay L. , Wadhawan Jay D. , Lawrence Nathan S.
Published: October 2021

The ‘ref tracker’ electrode tracks any drift in the reference electrode. The user always knows that measured pH is real as any reference electrode drift is compensated for, in situ, with the ‘ref tracker’.
Methane pyrolysis in low-cost, alkali-halide molten salts at high temperatures
Authors: Palmer Clarke , Tarazkar Maryam , Gordon Michael J. , Metiu Horia , McFarland Eric W.
Published: October 2021

The scientific features and industrial implications of methane pyrolysis in molten salt reactors are evaluated including reaction rates, carbon morphologies, and post-reaction carbon-salt separations with process control knobs highlighted.