bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time fractional analysis of channel flow of couple stress Casson fluid using Fick’s and Fourier’s Laws
Authors: Ahmad Shafiq , Haq Sami Ul , Ali Farhad , Khan Ilyas , Nisar Kottakkaran Sooppy 
Published: February 2022

AbstractThis study aim to examine the channel flow of a couple stress Casson fluid. The flow is generated due to the motion of the plate at $$y=0$$

y
=
0

, while the plate at $$y=d$$

y
=
d

is at rest. This physical phenomenon is derived in terms of partial differential equations. The subjected governing PDE’s are non-dimensionalized with the help of dimensionless variables. The dimensionless classical model is generalized by transforming it to the time fractional model using Fick’s and Fourier’s Laws. The general fractional model is solved by applying the Laplace and Fourier integral transformation. Furthermore, the parametric influence of various physical parameters like Casson parameter, couple stress parameter, Grashof number, Schmidt number and Prandtl number on velocity, temperature, and concentration distributions is shown graphically and discussed. The heat transfer rate, skin friction, and Sherwood number are calculated and presented in tabular form. It is worth noting that the increasing values of the couple stress parameter $$\lambda$$
λ
deaccelerate the velocity of Couple stress Casson fluid.
Evaluation of Swab-Seq as a scalable, sensitive assay for community surveillance of SARS-CoV-2 infection
Authors: Kang HyunJin , Allison Sheilah , Spangenberg Amber , Carr Tara , Sprissler Ryan , Halonen Marilyn , Cusanovich Darren A. 
Published: February 2022

AbstractThe ongoing SARS-CoV-2 pandemic and subsequent demand for viral testing has led to issues in scaling diagnostic lab efforts and in securing basic supplies for collection and processing of samples. This has motivated efforts by the scientific community to establish improved protocols that are more scalable, less resource intensive, and less expensive. One such developmental effort has resulted in an assay called “Swab-Seq”, so named because it was originally developed to work with dry nasal swab samples. The existing gold standard test consists of RNA extracted from a nasopharyngeal (NP) swab that is subjected to quantitative reverse transcription polymerase chain reaction (qRT-PCR). Swab-Seq adapts this method to a next-generation sequencing readout. By pairing this modification with extraction-free sampling techniques, Swab-Seq achieves high scalability, low cost per sample, and a reasonable turnaround time. We evaluated the effectiveness of this assay in a community surveillance setting by testing samples collected from both symptomatic and asymptomatic individuals using the traditional NP swab. In addition, we evaluated extraction-free sampling techniques (both saliva and saline mouth gargle samples). We found the assay to be as clinically sensitive as the qRT-PCR assay, adaptable to multiple sample types, and able to easily accommodate hundreds of samples at a time. We thus provide independent validation of Swab-Seq and extend its utility regarding sample type and sample stability. Assays of this type greatly expand the possibility of routine, noninvasive, repeated testing of asymptomatic individuals suitable for current and potential future needs.
An ex vivo organ culture screening model revealed that low temperature conditions prevent side effects of anticancer drugs
Authors: Tian Tian , Miyazaki Kanako , Chiba Yuta , Funada Keita , Yuta Tomomi , Mizuta Kanji , Fu Yao , Kawahara Jumpei , Han Xue , Ando Yuna , Funada Ami , Yamada Aya , Iwamoto Tsutomu , Nakamura Seiji , Takahashi Ichiro , Fukumoto Satoshi , Yoshizaki Keigo 
Published: February 2022

AbstractDevelopment of chemotherapy has led to a high survival rate of cancer patients; however, the severe side effects of anticancer drugs, including organ hypoplasia, persist. To assume the side effect of anticancer drugs, we established a new ex vivo screening model and described a method for suppressing side effects. Cyclophosphamide (CPA) is a commonly used anticancer drug and causes severe side effects in developing organs with intensive proliferation, including the teeth and hair. Using the organ culture model, we found that treatment with CPA disturbed the growth of tooth germs by inducing DNA damage, apoptosis and suppressing cellular proliferation and differentiation. Furthermore, low temperature suppressed CPA-mediated inhibition of organ development. Our ex vivo and in vitro analysis revealed that low temperature impeded Rb phosphorylation and caused cell cycle arrest at the G1 phase during CPA treatment. This can prevent the CPA-mediated cell damage of DNA replication caused by the cross-linking reaction of CPA. Our findings suggest that the side effects of anticancer drugs on organ development can be avoided by maintaining the internal environment under low temperature.
Pneumococcal meningitis in adults in 2014–2018 after introduction of pediatric 13-valent pneumococcal conjugate vaccine in Japan
Authors: Chang Bin , Tamura Kosuke , Fujikura Hiroyuki , Watanabe Hiroshi , Tanabe Yoshinari , Kuronuma Koji , Fujita Jiro , Oshima Kengo , Maruyama Takaya , Abe Shuichi , Kasahara Kei , Nishi Junichiro , Kubota Tetsuya , Kinjo Yuki , Serizawa Yusuke , Shimbashi Reiko , Fukusumi Munehisa , Shimada Tomoe , Sunagawa Tomimasa , Suzuki Motoi , Oishi Kazunori ,   the Adult IPD Study Group, Chang Bin , Tamura Kosuke , Fujikura Hiroyuki , Watanabe Hiroshi , Tanabe Yoshinari , Kuronuma Koji , Fujita Jiro , Oshima Kengo , Maruyama Takaya , Abe Shuichi , Kasahara Kei , Nishi Junichiro , Kubota Tetsuya , Kinjo Yuki , Serizawa Yusuke , Shimbashi Reiko , Fukusumi Munehisa , Shimada Tomoe , Sunagawa Tomimasa , Suzuki Motoi , Oishi Kazunori , Gotoh Kenji , Tsubata Chikako , Takahashi Hiroki , Aoyagi Tetsuji , Nakamatsu Masashi , Imuta Naoko , Yokoyama Akihito , Takeda Hiroaki , Ishida Masayuki 
Published: February 2022

AbstractWe assessed the impact of the pediatric 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis in adults in Japan in 2014–2018 by comparing epidemiological characteristics of adults with invasive pneumococcal disease with (n = 222) and without (n = 1258) meningitis. The annual incidence of pneumococcal meningitis in 2016–2018 was 0.20–0.26 cases/100,000 population. Age (p < 0.001) and case fatality rate (p = 0.003) were significantly lower in patients with meningitis than in those without meningitis. The odds of developing meningitis were higher in asplenic/hyposplenic or splenectomized patients (adjusted odds ratio [aOR] 2.29, 95% CI 1.27–4.14), for serotypes 10A (aOR 3.26, 95% CI 2.10–5.06) or 23A (aOR 3.91, 95% CI 2.47–6.19), but lower for those aged ≥ 65 years (aOR 0.59, 95% CI 0.44–0.81). PCV13 had an indirect effect on nonmeningitis, but its impact on meningitis was limited because of an increase in non-PCV13 serotypes. Of meningitis isolates, 78 (35.1%) and 3 (1.4%) were penicillin G- or ceftriaxone-resistant, respectively. We also confirmed an association of the pbp1bA641C mutation with meningitis (aOR 2.92, 95% CI 1.51–5.65).
Microbotanical residues for the study of early hominin tools
Authors: Mercader Julio , Belev George , Bushozi Pastory , Clarke Siobhán , Favreau Julien , Itambu Makarius , Jianfeng Zhu , Koromo Samson , Larter Fergus , Lee Patrick , Maley Jason , Fernández-Marchena Juan Luis , Mohamed Abdallah , Mwambwiga Aloyce , Ngisaruni Benja , Kingi Meshack , Olesilau Lucas , Patalano Robert , Pedergnana Antonella , Sammynaiken Ramaswami , Siljedal Joakim , Soto María , Tucker Laura , Walde Dale , Ollé Andreu 
Published: February 2022

AbstractMore than 2 million years ago in East Africa, the earliest hominin stone tools evolved amidst changes in resource base, with pounding technology playing a key role in this adaptive process. Olduvai Gorge (now Oldupai) is a famed locality that remains paramount for the study of human evolution, also yielding some of the oldest battering tools in the world. However, direct evidence of the resources processed with these technologies is lacking entirely. One way to obtain this evidence is through the analysis of surviving residues. Yet, linking residues with past processing activities is not simple. In the case of plant exploitation, this link can only be established by assessing site-based reference collections inclusive of both anthropogenic and natural residues as a necessary first step and comparative starting point. In this paper, we assess microbotanical remains from rock clasts sourced at the same quarry utilized by Oldowan hominins at Oldupai Gorge. We mapped this signal and analysed it quantitatively to classify its spatial distribution objectively, extracting proxies for taxonomic identification and further comparison with freestanding soils. In addition, we used blanks to manufacture pounding tools for blind, controlled replication of plant processing. We discovered that stone blanks are in fact environmental reservoirs in which plant remains are trapped by lithobionts, preserved as hardened accretions. Tool use, on the other hand, creates residue clusters; however, their spatial distribution can be discriminated from purely natural assemblages by the georeferencing of residues and statistical analysis of resulting patterns. To conclude, we provide a protocol for best practice and a workflow that has the advantage of overcoming environmental noise, reducing the risk of false positive, delivering a firm understanding of residues as polygenic mixtures, a reliable use of controls, and most importantly, a stronger link between microbotanical remains and stone tool use.
KRAS gene mutation quantification in the resection or venous margins of pancreatic ductal adenocarcinoma is not predictive of disease recurrence
Authors: Amintas Samuel , Fernandez Benjamin , Chauvet Alexandre , Chiche Laurence , Laurent Christophe , Belleannée Geneviève , Marty Marion , Buscail Etienne , Dabernat Sandrine 
Published: February 2022

AbstractPancreatic ductal adenocarcinoma (PDAC) patients eligible for curative surgery undergo unpredictable disease relapse. Even patients with a good pathological response after neoadjuvant treatment (NAT) remain susceptible to recurrent PDAC. Molecular analysis of R0 margins may identify patients with a worse prognosis. The molecular status of mutant KRAS (exon 2, codon 12/13) was analysed retrospectively by digital droplet PCR in tumour areas, venous and resection margins of resected tumours, either undergoing up-front surgery (UFS) or after NAT with a good pathological response. Expectedly, tumour tissues or remnants from patients who underwent NAT presented lower KRAS mutant allele frequencies (MAF) than patients eligible for UFS. Similarly, ypT1 tumour MAFs were greater than the ypT0 tumour remnant MAFs in the NAT group. Mutant KRAS status in margins did not distinguish NAT subgroups. It was not predictive of shorter recurrence-free or overall survival within or between groups. KRAS-double negativity in both venous and resection margins did not identify patients with a better prognosis, regardless of the groups. The cohorts ‘sizes were small due to limited numbers of patients meeting the inclusion criteria, but KRAS-positivity or MAFs in resection and venous margins did not carry prognostic value. Comparison of margins from good versus bad responders receiving NAT may provide better clinical value.
Teriflunomide shifts the astrocytic bioenergetic profile from oxidative metabolism to glycolysis and attenuates TNFα-induced inflammatory responses
Authors: Kabiraj Parijat , Grund Ethan M. , Clarkson Benjamin D. S. , Johnson Renee K. , LaFrance-Corey Reghann G. , Lucchinetti Claudia F. , Howe Charles L. 
Published: February 2022

AbstractAstrocytes utilize both glycolytic and mitochondrial pathways to power cellular processes that are vital to maintaining normal CNS functions. These cells also mount inflammatory and acute phase reactive programs in response to diverse stimuli. While the metabolic functions of astrocytes under homeostatic conditions are well-studied, the role of cellular bioenergetics in astrocyte reactivity is poorly understood. Teriflunomide exerts immunomodulatory effects in diseases such as multiple sclerosis by metabolically reprogramming lymphocytes and myeloid cells. We hypothesized that teriflunomide would constrain astrocytic inflammatory responses. Purified murine astrocytes were grown under serum-free conditions to prevent acquisition of a spontaneous reactive state. Stimulation with TNFα activated NFκB and increased secretion of Lcn2. TNFα stimulation increased basal respiration, maximal respiration, and ATP production in astrocytes, as assessed by oxygen consumption rate. TNFα also increased glycolytic reserve and glycolytic capacity of astrocytes but did not change the basal glycolytic rate, as assessed by measuring the extracellular acidification rate. TNFα specifically increased mitochondrial ATP production and secretion of Lcn2 required ATP generated by oxidative phosphorylation. Inhibition of dihydroorotate dehydrogenase via teriflunomide transiently increased both oxidative phosphorylation and glycolysis in quiescent astrocytes, but only the increased glycolytic ATP production was sustained over time, resulting in a bias away from mitochondrial ATP production even at doses down to 1 μM. Preconditioning with teriflunomide prevented the TNFα-induced skew toward oxidative phosphorylation, reduced mitochondrial ATP production, and reduced astrocytic inflammatory responses, suggesting that this drug may limit neuroinflammation by acting as a metabolomodulator.
Internalization and trafficking of CSPG-bound recombinant VAR2CSA lectins in cancer cells
Authors: Wang Chris Kedong , Nelepcu Irina , Hui Desmond , Oo Htoo Zarni , Truong Sarah , Zhao Sarah , Tahiry Zakir , Esfandnia Shaghayegh , Ghaidi Fariba , Adomat Hans , Dagil Robert , Gustavsson Tobias , Choudhary Swati , Salanti Ali , Sorensen Poul H. , Al Nakouzi Nader , Daugaard Mads 
Published: February 2022

AbstractProteoglycans are proteins that are modified with glycosaminoglycan chains. Chondroitin sulfate proteoglycans (CSPGs) are currently being exploited as targets for drug-delivery in various cancer indications, however basic knowledge on how CSPGs are internalized in tumor cells is lacking. In this study we took advantage of a recombinant CSPG-binding lectin VAR2CSA (rVAR2) to track internalization and cell fate of CSPGs in tumor cells. We found that rVAR2 is internalized into cancer cells via multiple internalization mechanisms after initial docking on cell surface CSPGs. Regardless of the internalization pathway used, CSPG-bound rVAR2 was trafficked to the early endosomes in an energy-dependent manner but not further transported to the lysosomal compartment. Instead, internalized CSPG-bound rVAR2 proteins were secreted with exosomes to the extracellular environment in a strictly chondroitin sulfate-dependent manner. In summary, our work describes the cell fate of rVAR2 proteins in tumor cells after initial binding to CSPGs, which can be further used to inform development of rVAR2-drug conjugates and other therapeutics targeting CSPGs.
Prediction of lymph node metastasis in early colorectal cancer based on histologic images by artificial intelligence
Authors: Takamatsu Manabu , Yamamoto Noriko , Kawachi Hiroshi , Nakano Kaoru , Saito Shoichi , Fukunaga Yosuke , Takeuchi Kengo 
Published: February 2022

AbstractRisk evaluation of lymph node metastasis (LNM) for endoscopically resected submucosal invasive (T1) colorectal cancers (CRC) is critical for determining therapeutic strategies, but interobserver variability for histologic evaluation remains a major problem. To address this issue, we developed a machine-learning model for predicting LNM of T1 CRC without histologic assessment. A total of 783 consecutive T1 CRC cases were randomly split into 548 training and 235 validation cases. First, we trained convolutional neural networks (CNN) to extract cancer tile images from whole-slide images, then re-labeled these cancer tiles with LNM status for re-training. Statistical parameters of the tile images based on the probability of primary endpoints were assembled to predict LNM in cases with a random forest algorithm, and defined its predictive value as random forest score. We evaluated the performance of case-based prediction models for both training and validation datasets with area under the receiver operating characteristic curves (AUC). The accuracy for classifying cancer tiles was 0.980. Among cancer tiles, the accuracy for classifying tiles that were LNM-positive or LNM-negative was 0.740. The AUCs of the prediction models in the training and validation sets were 0.971 and 0.760, respectively. CNN judged the LNM probability by considering histologic tumor grade.
Simulating COVID19 transmission from observed movement
Authors: Zhang Yi , Tao Yudong , Shyu Mei-Ling , Perry Lynn K. , Warde Prem R. , Messinger Daniel S. , Song Chaoming 
Published: February 2022

AbstractCurrent models of COVID-19 transmission predict infection from reported or assumed interactions. Here we leverage high-resolution observations of interaction to simulate infectious processes. Ultra-Wide Radio Frequency Identification (RFID) systems were employed to track the real-time physical movements and directional orientation of children and their teachers in 4 preschool classes over a total of 34 observations. An agent-based transmission model combined observed interaction patterns (individual distance and orientation) with CDC-published risk guidelines to estimate the transmission impact of an infected patient zero attending class on the proportion of overall infections, the average transmission rate, and the time lag to the appearance of symptomatic individuals. These metrics highlighted the prophylactic role of decreased classroom density and teacher vaccinations. Reduction of classroom density to half capacity was associated with an 18.2% drop in overall infection proportion while teacher vaccination receipt was associated with a 25.3% drop. Simulation results of classroom transmission dynamics may inform public policy in the face of COVID-19 and similar infectious threats.
PD-L1 mediates lung fibroblast to myofibroblast transition through Smad3 and β-catenin signaling pathways
Authors: Guo Xia , Sunil Christudas , Adeyanju Oluwaseun , Parker Andrew , Huang Steven , Ikebe Mitsuo , Tucker Torry A. , Idell Steven , Qian Guoqing 
Published: February 2022

AbstractProgrammed death ligand-1 (PD-L1) is an immune checkpoint protein that has been linked with idiopathic pulmonary fibrosis (IPF) and fibroblast to myofibroblast transition (FMT). However, it remains largely unclear how PD-L1 mediates this process. We found significantly increased PD-L1 in the lungs of idiopathic pulmonary fibrosis patients and mice with pulmonary fibrosis induced by bleomycin and TGF-β. In primary human lung fibroblasts (HLFs), TGF-β induced PD-L1 expression that is dependent on both Smad3 and p38 pathways. PD-L1 knockdown using siRNA significantly attenuated TGF-β-induced expression of myofibroblast markers α-SMA, collagen-1, and fibronectin in normal and IPF HLFs. Further, we found that PD-L1 interacts with Smad3, and TGF-β induces their interaction. Interestingly, PD-L1 knockdown reduced α-SMA reporter activity induced by TGF-β in HLFs, suggesting that PD-L1 might act as a co-factor of Smad3 to promote target gene expression. TGF-β treatment also phosphorylates GSK3β and upregulates β-catenin protein levels. Inhibiting β-catenin signaling with the pharmaceutical inhibitor ICG001 significantly attenuated TGF-β-induced FMT. PD-L1 knockdown also attenuated TGF-β-induced GSK3β phosphorylation/inhibition and β-catenin upregulation, implicating GSK3β/β-catenin signaling in PD-L1-mediated FMT. Collectively, our findings demonstrate that fibroblast PD-L1 may promote pulmonary fibrosis through both Smad3 and β-catenin signaling and may represent a novel interventional target for IPF.
Towards optimal thermal distribution in magnetic hyperthermia
Authors: Rytov R. A. , Bautin V. A. , Usov N. A. 
Published: February 2022

AbstractA linear combination of spherically symmetric heat sources is shown to provide optimal stationary thermal distribution in magnetic hyperthermia. Furthermore, such spatial location of heat sources produces suitable temperature distribution in biological medium even for assemblies of magnetic nanoparticles with a moderate value of specific absorption rate (SAR), of the order of 100–150 W/g. We also demonstrate the advantage of using assemblies of spherical magnetic nanocapsules consisting of metallic iron nanoparticles covered with non magnetic shells of sufficient thickness in magnetic hyperthermia. Based on numerical simulation we optimize the size and geometric structure of biocompatible spherical capsules in order to minimize the influence of strong magneto-dipole interaction between closely spaced nanoparticles. It is shown that assembly of capsules can provide sufficiently high SAR values of the order of 250–400 W/g at moderate amplitudes H0 = 50–100 Oe and frequencies f = 100–200 kHz of alternating magnetic field, being appropriate for application in clinics.
Integrated bioinformatics analysis identifies established and novel TGFβ1-regulated genes modulated by anti-fibrotic drugs
Authors: Wilson Ava C. , Chiles Joe , Ashish Shah , Chanda Diptiman , Kumar Preeti L. , Mobley James A. , Neptune Enid R. , Thannickal Victor J. , McDonald Merry-Lynn N. 
Published: February 2022

AbstractFibrosis is a leading cause of morbidity and mortality worldwide. Although fibrosis may involve different organ systems, transforming growth factor-β (TGFβ) has been established as a master regulator of fibrosis across organs. Pirfenidone and Nintedanib are the only currently-approved drugs to treat fibrosis, specifically idiopathic pulmonary fibrosis, but their mechanisms of action remain poorly understood. To identify novel drug targets and uncover potential mechanisms by which these drugs attenuate fibrosis, we performed an integrative ‘omics analysis of transcriptomic and proteomic responses to TGFβ1-stimulated lung fibroblasts. Significant findings were annotated as associated with pirfenidone and nintedanib treatment in silico via Coremine. Integrative ‘omics identified a co-expressed transcriptomic and proteomic module significantly correlated with TGFβ1 treatment that was enriched (FDR-p = 0.04) with genes associated with pirfenidone and nintedanib treatment. While a subset of genes in this module have been implicated in fibrogenesis, several novel TGFβ1 signaling targets were identified. Specifically, four genes (BASP1, HSD17B6, CDH11, and TNS1) have been associated with pirfenidone, while five genes (CLINT1, CADM1, MTDH, SYDE1, and MCTS1) have been associated with nintedanib, and MYDGF has been implicated with treatment using both drugs. Using the Clue Drug Repurposing Hub, succinic acid was highlighted as a metabolite regulated by the protein encoded by HSD17B6. This study provides new insights into the anti-fibrotic actions of pirfenidone and nintedanib and identifies novel targets for future mechanistic studies.