bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular cytopathology diagnosis of a lung neoplasm: Case report of an unusual non‐small cell carcinoma with MET exon 14 skipping mutation
Authors: Hosseini S. Mohsen , Khanafshar Elham , Seeley Eric J. , Ruiz‐Cordero Roberto 
Published: January 2021

AbstractHere we report the combined cytological and molecular diagnosis of a lung mass. The cytology and extensive immunohistochemistry on an endobronchial ultrasound‐guided fine needle aspiration biopsy were inconclusive. By genomic profiling of the cell block material, we identified a MET exon 14 skipping mutation that indicated a lung origin and made the patient eligible for the tyrosine kinase inhibitor, crizotinib. This case is a prime example of complementing adequate aspiration and cell block processing techniques with molecular testing. Such an approach would augment the usability of fine needle aspiration biopsy, both as a diagnostic modality and as the first line to find therapeutic targets in the era of precision medicine.
Early maternal and paternal caregiving moderates the links between preschoolers' reactivity and regulation and maturation of the HPA‐immune axis
Authors: Abraham Eyal , Zagoory‐Sharon Orna , Feldman Ruth 
Published: January 2021

AbstractWhile early caregiving and child's temperamental dispositions work in concert to shape social‐emotional outcomes, their unique and joint contribution to the maturation of the child's stress and immune systems remain unclear. We followed children longitudinally from infancy to preschool to address the buffering effect of early parenting on the link between temperamental dysregulation and hypothalamic–pituitary–adrenal (HPA)‐immune axis in preschool‐aged children. Participants included 47 typically developing children and their 94 parents in both mother‐father and two‐father families followed across the first 4‐years of family formation. In infancy, we observed parent‐infant synchrony and measured parental oxytocin; in preschool, we observed temperamental reactivity and self‐regulation and assessed children's cortisol and secretory Immunoglobulin A (s‐IgA), biomarkers of the stress and immune systems. Greater self‐regulation and lower negative emotionality were associated with lower baseline s‐IgA and cortisol, respectively. However, these links were defined by interactive effects so that preschoolers with low self‐regulation displayed higher s‐IgA levels only in cases of low parent‐infant synchrony and negative emotionality linked with greater baseline cortisol levels only when parental oxytocin levels were low. Results emphasize the long‐term stress‐buffering role of the neurobiology of parental care, demonstrate comparable developmental paths for mothers and fathers, and delineate the complex developmental cascades to the maturation of children's stress‐management systems.
Blastocyst complementation reveals that NKX2‐1 establishes the proximal‐peripheral boundary of the airway epithelium
Authors: Li Enhong , Ustiyan Vladimir , Wen Bingqiang , Kalin Gregory T. , Whitsett Jeffrey A. , Kalin Tanya V. , Kalinichenko Vladimir V. 
Published: January 2021

AbstractBackgroundDistinct boundaries between the proximal conducting airways and more peripheral‐bronchial regions of the lung are established early in foregut embryogenesis, demarcated in part by the distribution of SOX family and NKX2‐1 transcription factors along the cephalo‐caudal axis of the lung. We used blastocyst complementation to identify the role of NKX2‐1 in the formation of the proximal‐peripheral boundary of the airways in mouse chimeric embryos.ResultsWhile Nkx2‐1−/− mouse embryos form primordial tracheal cysts, peripheral pulmonary structures are entirely lacking in Nkx2‐1−/−mice. Complementation of Nkx2‐1−/− embryos with NKX2‐1‐sufficient embryonic stem cells (ESCs) enabled the formation of all tissue components of the peripheral lung but did not enhance ESC colonization of the most proximal regions of the airways. In chimeric mice, a precise boundary was formed between NKX2‐1‐deficient basal cells co‐expressing SOX2 and SOX9 in large airways and ESC‐derived NKX2‐1+SOX9+ epithelial cells of smaller airways. NKX2‐1‐sufficient ESCs were able to selectively complement peripheral, rather than most proximal regions of the airways. ESC complementation did not prevent ectopic expression of SOX9 but restored β‐catenin signaling in Nkx2‐1−/− basal cells of large airways.ConclusionsNKX2‐1 and β‐catenin function in an epithelial cell‐autonomous manner to establish the proximal‐peripheral boundary along developing airways.
Evaluating a trait‐based approach to compare natural enemy and pest communities in agroforestry vs. arable systems
Authors: Staton Tom , Walters Richard J. , Smith Jo , Breeze Tom D. , Girling Robbie D. 
Published: January 2021

AbstractDiversified farming systems, for example those that incorporate agroforestry elements, have been proposed as a solution that could maintain and improve multiple ecosystem services. However, habitat diversification in and around arable fields has complex and inconsistent effects on invertebrate crop pests and their natural enemies. This hinders the development of policy recommendations to promote the adoption of such management strategies for the provision of natural pest control services. Here, for the first time, we conducted a trait‐based approach to investigate the effect of farming system on plant, invertebrate herbivore, and invertebrate natural enemy communities. We then evaluated this approach by comparing the results to those generated using a traditional taxonomic approach. At each of three working farms, we sampled within an agroforestry field (a diverse farming system comprising alleys of arable crops separated by tree rows), and within a paired non‐diversified area of the farm (arable control field). Each of 96 sample points was sampled between 8 and 10 times, yielding 393,318 invertebrate specimens from 344 taxonomic groups. Diet specialization or granivory, lack of a pupal stage, and wing traits in invertebrates, along with late flowering, short flowering duration, creeping habit, and perenniality in plants, were traits more strongly associated with agroforestry crop alleys than the arable control fields. We hypothesize that this is a result of reduced habitat disturbance and increased habitat complexity in the agroforestry system. Taxonomic richness and diversity were higher in the agroforestry crop alleys compared to the arable control fields, but these effects were stronger at lower trophic levels. However, functional trait diversity of natural enemies was significantly higher in the agroforestry crop alleys than the arable control fields, suggesting an improved level of biocontrol, which was not detected by traditional diversity metrics. Of eight key pest taxa, three were significantly suppressed in the agroforestry system, while two were more abundant, compared to the arable control fields. Trait‐based approaches can provide a better mechanistic understanding of farming system effects on pests and their natural enemies, therefore we recommend their application and testing in future studies of diversified farming systems.
Functionally reversible impacts of disturbances on lake food webs linked to spatial and seasonal dependencies
Authors: Urrutia‐Cordero Pablo , Langenheder Silke , Striebel Maren , Eklöv Peter , Angeler David G. , Bertilsson Stefan , Csitári Bianka , Hansson Lars‐Anders , Kelpsiene Egle , Laudon Hjalmar , Lundgren Maria , Osman Omneya Ahmed , Parkefelt Linda , Hillebrand Helmut 
Published: January 2021

AbstractIncreasing human impact on the environment is causing drastic changes in disturbance regimes and how they prevail over time. Of increasing relevance is to further our understanding on biological responses to pulse disturbances (short duration) and how they interact with other ongoing press disturbances (constantly present). Because the temporal and spatial contexts of single experiments often limit our ability to generalize results across space and time, we conducted a modularized mesocosm experiment replicated in space (five lakes along a latitudinal gradient in Scandinavia) and time (two seasons, spring and summer) to generate general predictions on how the functioning and composition of multitrophic plankton communities (zoo‐, phyto‐ and bacterioplankton) respond to pulse disturbances acting either in isolation or combined with press disturbances. As pulse disturbance, we used short‐term changes in fish presence, and as press disturbance, we addressed the ongoing reduction in light availability caused by increased cloudiness and lake browning in many boreal and subarctic lakes. First, our results show that the top‐down pulse disturbance had the strongest effects on both functioning and composition of the three trophic levels across sites and seasons, with signs for interactive impacts with the bottom‐up press disturbance on phytoplankton communities. Second, community composition responses to disturbances were highly divergent between lakes and seasons: temporal accumulated community turnover of the same trophic level either increased (destabilization) or decreased (stabilization) in response to the disturbances compared to control conditions. Third, we found functional recovery from the pulse disturbances to be frequent at the end of most experiments. In a broader context, these results demonstrate that top‐down, pulse disturbances, either alone or with additional constant stress upon primary producers caused by bottom‐up disturbances, can induce profound but often functionally reversible changes across multiple trophic levels, which are strongly linked to spatial and temporal context dependencies. Furthermore, the identified dichotomy of disturbance effects on the turnover in community composition demonstrates the potential of disturbances to either stabilize or destabilize biodiversity patterns over time across a wide range of environmental conditions.
Bacteria and cancer cell pearl chain under dielectrophoresis
Authors: Kong Tian Fook , Tan Pei Yen , Tay Benjamin Zikai , Shen Xinhui , Marcos  
Published: January 2021

AbstractIn this work, we aim to observe and study the physics of bacteria and cancer cells pearl chain formation under dielectrophoresis (DEP). Experimentally, we visualized the formation of Bacillus subtilis bacterial pearl chain and human breast cancer cell (MCF‐7) chain under positive and negative dielectrophoretic force, respectively. Through a simple simulation with creeping flow, AC/DC electric fields, and particle tracing modules in COMSOL, we examined the mechanism by which bacteria self‐organize into a pearl chain across the gap between two electrodes via DEP. Our simulation results reveal that the region of greatest positive DEP force shifts from the electrode edge to the leading edge of the pearl chain, thus guiding the trajectories of free‐flowing particles toward the leading edge via positive DEP. Our findings additionally highlight the mechanism why the free‐flowing particles are more likely to join the existing pearl chain rather than starting a new pearl chain. This phenomenon is primarily due to the increase in magnitude of electric field gradient, and hence DEP force exerted, with the shortening gap between the pearl chain leading edge and the adjacent electrode. The findings shed light on the observed behavior of preferential pearl chain formation across electrode gaps.
A security‐driven network architecture for routing in industrial Internet of Things
Authors: Cao Jian , Wang Xingwei , Huang Min , Yi Bo , He Qiang 
Published: January 2021

AbstractIndustrial Internet of Things (IIoT), as the integration of industrial network and IoT, has attracted a lot of attention from both academia and industry. However, with such integration deepens, many issues suffered by the industrial networks are exposed and magnified. The secure routing is a key focus, since the industrial environment is extremely vulnerable and many potential threats (eg, distributed denial of service and selfish attacks) are introduced due to the connection to the Internet. In order to prevent the threats from the Internet and embrace the benefits of IIoT, a security‐driven network framework for routing is particularly designed. Specifically, we first leverage the technologies of software‐defined networking (SDN), network function virtualization (NFV), and blockchain to create the overall framework which is flexible, programmable, and secure. On one hand, the three‐level structure of SDN/NFV is applied to each domain, based on which we can flexibly control and program the underlying forwarding devices in this domain for the purpose of calculating the optimal routing policies. On the other hand, the blockchain is applied among different SDN controllers to create a trust and untamperable environment. Then, under this framework, a secure routing mechanism is proposed as well to prevent the attacks on the basis of node identity authentication and node behavior authentication. The simulation experiments are carried out on the OMNet++ platform and the experimental results indicate that the proposed mechanism outperforms the other state‐of‐the‐art methods in terms of scalability and robustness especially when encountering malicious attacks.
Convolution‐based filtering and forecasting: An application to WTI crude oil prices
Authors: Gourieroux Christian , Jasiak Joann , Tong Michelle 
Published: January 2021

AbstractWe introduce new methods of filtering and forecasting for the causal–noncausal convolution model. This model represents the dynamics of stationary processes with local explosions, such as spikes and bubbles, which characterize the time series of commodity prices, cryptocurrency exchange rates, and other financial and macroeconomic variables. The convolution model is a structural mixture of independent latent causal and noncausal component series. We propose an algorithm that recovers the latent components by evaluating the filtering density of one component, conditional on the observed past, present, and future values of the time series. Forecasts of the observed time series are obtained as a combination of filtered causal and noncausal component forecasts. The new filtering and forecasting methods are illustrated in a simulation study and compared with the results obtained from the mixed causal–noncausal autoregressive MAR model in application to WTI crude oil prices.
Efficacy of stinging nettle extract in combination with ε‐polylysine on the quality, safety, and shelf life of rainbow trout fillets
Authors: Alirezalu Kazem , Yaghoubi Milad , Nemati Zabihollah , Farmani Boukaga , Mousavi Khaneghah Amin 
Published: January 2021

AbstractThe effects of incorporation of stinging nettle extract (3% and 6%) and ɛ‐polylysine (0.1% and 0.2%) on chemical, microbial properties, and stability of rainbow trout fish fillets wrapped in polyethylene bags (in atmosphere condition) and refrigerated for 12 days at 4°C were evaluated. No remarkable differences regarding the chemical composition of rainbow trout fish (protein, moisture, fat, and ash content) resulting from the treatments were noted. The lowest TBARS (thiobarbituric acid reactive substance) and the highest phenolic compounds were noted in samples treated with 6% SNE + 0.2% ɛ‐PL on day 12, while the highest inhibitory effects against the growth of TVC, psychrotrophic bacteria, coliform, yeast, and molds corresponded to samples treated with 6% SNE (T4 and T5) at day 12. During the storage, the samples' TVB‐N (total volatile base nitrogen) increased, whereas the total phenolic content of the rainbow trout samples declined. The rainbow trout samples treated with 6% SNE + 0.2% ɛ‐PL had the highest amount of redness and the lowest TVB‐N values. Therefore, these natural ingredients could be used to maintain rainbow trout meat quality and shelf life.
Disrupted connectivity within visual, attentional and salience networks in the visual snow syndrome
Authors: Puledda Francesca , O'Daly Owen , Schankin Christoph , Ffytche Dominic , Williams Steven CR , Goadsby Peter J 
Published: January 2021

AbstractHere we investigate brain functional connectivity in patients with visual snow syndrome (VSS). Our main objective was to understand more about the underlying pathophysiology of this neurological syndrome. Twenty‐four patients with VSS and an equal number of gender and age‐matched healthy volunteers attended MRI sessions in which whole‐brain maps of functional connectivity were acquired under two conditions: at rest while watching a blank screen and during a visual paradigm consisting of a visual‐snow like stimulus. Eight unilateral seed regions were selected a priori based on previous observations and hypotheses; four seeds were placed in key anatomical areas of the visual pathways and the remaining were derived from a pre‐existing functional analysis. The between‐group analysis showed that patients with VSS had hyper and hypoconnectivity between key visual areas and the rest of the brain, both in the resting state and during a visual stimulation, compared with controls. We found altered connectivity internally within the visual network; between the thalamus/basal ganglia and the lingual gyrus; between the visual motion network and both the default mode and attentional networks. Further, patients with VSS presented decreased connectivity during external sensory input within the salience network, and between V5 and precuneus. Our results suggest that VSS is characterised by a widespread disturbance in the functional connectivity of several brain systems. This dysfunction involves the pre‐cortical and cortical visual pathways, the visual motion network, the attentional networks and finally the salience network; further, it represents evidence of ongoing alterations both at rest and during visual stimulus processing.
Middle turbinate mucosal flap: Low‐morbidity option in the management of skull base defects
Authors: Carnevale Claudio , Til‐Pérez Guillermo , Tomás‐Barberán Manuel , Ibañez‐Domínguez Javier , Arancibia‐Tagle Diego , Sarría‐Echegaray Pedro 
Published: January 2021

AbstractBackgroundTo describe the low morbidity of middle turbinate mucosal flap (MTMF) to repair anterior skull base defects.MethodsSkull base endonasal endoscopic surgeries performed at a tertiary hospital between 2015 and 2018 were analyzed. Patients were divided into two groups according the existence or not of a significant intraoperative cerebrospinal fluid (CSF) leak. In Group 1 (n = 28), gasket seal and a pedicled endonasal flap were used to repair the defect: 13 nasoseptal flaps (NSF), 8 inferolateral wall flaps (ILF), and 7 MTMF. In Group 2 only an endonasal flap was used: 9 NSF, 4 ILF, and 18 MTMF. Surgical and recovery time were analyzed (Student's t test). Our favorite surgical technique is described.ResultsFifty‐nine patients were included. Average surgical time was 27.7, 41.6, and 11.3 min for NSF, ILF, and MTMF, respectively. MTMF showed a faster recovery.ConclusionMTMF is a safe reconstructive option for anterior skull base defects.
Dual Agonist of Farnesoid X Receptor and Takeda G Protein‐Coupled Receptor 5 Inhibits Hepatitis B Virus Infection In Vitro and In Vivo
Authors: Ito Kiyoaki , Okumura Akinori , Takeuchi Junko S. , Watashi Koichi , Inoue Rieko , Yamauchi Taeko , Sakamoto Kazumasa , Yamashita Yukiko , Iguchi Yusuke , Une Mizuho , Wakita Takaji , Umezawa Kazuo , Yoneda Masashi 
Published: January 2021

Background and Aims
Chronic HBV infection is a major health problem worldwide. Currently, the first‐line treatment for HBV is nucleos(t)ide analogs or interferons; however, efficient therapeutic approaches that enable cure are lacking. Therefore, anti‐HBV agents with mechanisms distinct from those of current drugs are needed. Sodium taurocholate cotransporting polypeptide (NTCP) was previously identified as an HBV receptor that is inhibited by several compounds. Farnesoid X receptor (FXR) activation also inhibits NTCP function.

Approach and Results
In this study, we investigated the inhibitory effect of bile acid (BA) derivatives—namely obeticholic acid (OCA), 6α‐ethyl‐24‐nor‐5β‐cholane‐3α,7α,23‐triol‐23 sulfate sodium salt (INT‐767; a dual agonist of FXR and Takeda G protein‐coupled receptor [TGR5]), and 6α‐ethyl‐23(S)‐methyl‐cholic acid (INT‐777; a TGR5 agonist)—3‐(2,6‐dichlorophenyl)‐4‐(3′‐carboxy‐2‐chlorostilben‐4‐yl)oxymethyl‐5‐isopropylisoxazole (GW4064; a FXR agonist), cyclosporin A, and irbesartan. OCA and INT‐777 suppressed HBV infection in HepG2‐human NTCP‐C4 cells. Interestingly, INT‐767 showed potent inhibition by attaching to HBV particles rather than binding to NTCP. As an entry inhibitor, INT‐767 was stronger than various natural BAs. Furthermore, in chimeric mice with humanized liver, INT‐767 markedly delayed the initial rise of HBsAg, HBeAg, and HBV DNA and reduced covalently closed circular DNA. The strong inhibitory effect of INT‐767 may be due to the cumulative effect of its ability to inhibit the entry of HBV and to stimulate FXR downstream signaling, which affects the postentry step.

Conclusions
Our results suggest that BA derivatives, particularly INT‐767, are prospective candidate anti‐HBV agents. Clarifying the underlying mechanisms of BA derivatives would facilitate the development of anti‐HBV agents.
Clinical Presentation and Gene Expression of Acute Alcohol‐Induced Microvesicular Steatosis Mimicking Alcoholic Hepatitis
Authors: Spahr Laurent , Lanthier Nicolas , Tihy Mathieu , Frossard Jean‐Louis , Rubbia‐Brandt Laura , Goossens Nicolas 
Published: January 2021

Acute alcoholic microvesicular steatosis (MIC) may complicate heavy alcohol intake and present as alcoholic hepatitis (AH) syndrome. However, detailed clinical, biological, and histologic data associated with MIC are scarce. We compared the clinical presentation, histologic features, and hepatic transcriptomic of patients presenting with AH due to either MIC or severe alcoholic steatohepatitis (ASH). In this case‐control study, patients who drank heavily (>100 g/day) with the AH syndrome were included either in the MIC group (>50% severe microvesicular steatosis, no inflammation) or in the severe ASH group (polynuclear neutrophil infiltration, macrosteatosis, ballooned hepatocytes). All patients received standard supportive care plus steroids for those with severe ASH and were followed up for 3 months. Whole‐liver transcriptome profiling was performed on liver snap‐frozen biopsies. Compared to ASH (n = 24, mean age 49.3 years), patients in the MIC group (n = 12, mean age 49.1 years) had a higher reported alcohol intake (P < 0.01), lower Model for End‐Stage Liver Disease score (P < 0.05), lower hepatic venous pressure gradient (P < 0.01), higher alanine aminotransferase (P < 0.02) and gamma‐glutamyltransferase (P < 0.001), higher triglycerides (P < 0.001) and total cholesterol (P < 0.002), but similar bilirubin levels (P = 0.54). At histology, patients with MIC had a lower fibrotic stage compared to those with ASH (P < 0.001). A higher density of megamitochondria was seen in MIC compared to ASH (P < 0.05). During follow‐up, death or transplantation occurred in 4/12 (33%) patients with MIC and 7/24 (29%) patients with severe ASH. Differential hepatic gene expression in MIC compared to ASH included down‐regulation of genes related to inflammation and fibrosis and up‐regulation of genes involved in lipid metabolism and mitochondrial function. Conclusion: MIC is an acute, noninflammatory, potentially severe alcoholic liver injury mimicking ASH, is associated with a lower fibrosis stage, and has a distinct gene expression profile.