bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling the first wave of Covid-19 pandemic in the Republic of Cyprus
Authors: Agapiou Sergios , Anastasiou Andreas , Baxevani Anastassia , Nicolaides Christos , Hadjigeorgiou Georgios , Christofides Tasos , Constantinou Elisavet , Nikolopoulos Georgios , Fokianos Konstantinos 
Published: April 2021

AbstractWe present different data analytic methodologies that have been applied in order to understand the evolution of the first wave of the Coronavirus disease 2019 in the Republic of Cyprus and the effect of different intervention measures that have been taken by the government. Change point detection has been used in order to estimate the number and locations of changes in the behaviour of the collected data. Count time series methods have been employed to provide short term projections and a number of various compartmental models have been fitted to the data providing with long term projections on the pandemic’s evolution and allowing for the estimation of the effective reproduction number.
Identification of novel inhibitors of Keap1/Nrf2 by a promising method combining protein–protein interaction-oriented library and machine learning
Authors: Shimizu Yugo , Yonezawa Tomoki , Sakamoto Junichi , Furuya Toshio , Osawa Masanori , Ikeda Kazuyoshi 
Published: April 2021

AbstractProtein–protein interactions (PPIs) are prospective but challenging targets for drug discovery, because screening using traditional small-molecule libraries often fails to identify hits. Recently, we developed a PPI-oriented library comprising 12,593 small-to-medium-sized newly synthesized molecules. This study validates a promising combined method using PPI-oriented library and ligand-based virtual screening (LBVS) to discover novel PPI inhibitory compounds for Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2). We performed LBVS with two random forest models against our PPI library and the following time-resolved fluorescence resonance energy transfer (TR-FRET) assays of 620 compounds identified 15 specific hit compounds. The high hit rates for the entire PPI library (estimated 0.56–1.3%) and the LBVS (maximum 5.4%) compared to a conventional screening library showed the utility of the library and the efficiency of LBVS. All the hit compounds possessed novel structures with Tanimoto similarity ≤ 0.26 to known Keap1/Nrf2 inhibitors and aqueous solubility (AlogP < 5). Reasonable binding modes were predicted using 3D alignment of five hit compounds and a Keap1/Nrf2 peptide crystal structure. Our results represent a new, efficient method combining the PPI library and LBVS to identify novel PPI inhibitory ligands with expanded chemical space.
A highly conserved mechanism for the detoxification and assimilation of the toxic phytoproduct L-azetidine-2-carboxylic acid in Aspergillus nidulans
Authors: Biratsi Ada , Athanasopoulos Alexandros , Kouvelis Vassili N. , Gournas Christos , Sophianopoulou Vicky 
Published: April 2021

AbstractPlants produce toxic secondary metabolites as defense mechanisms against phytopathogenic microorganisms and predators. L-azetidine-2-carboxylic acid (AZC), a toxic proline analogue produced by members of the Liliaceae and Agavaciae families, is part of such a mechanism. AZC causes a broad range of toxic, inflammatory and degenerative abnormalities in human and animal cells, while it is known that some microorganisms have evolved specialized strategies for AZC resistance. However, the mechanisms underlying these processes are poorly understood. Here, we identify a widespread mechanism for AZC resistance in fungi. We show that the filamentous ascomycete Aspergillus nidulans is able to not only resist AZC toxicity but also utilize it as a nitrogen source via GABA catabolism and the action of the AzhA hydrolase, a member of a large superfamily of detoxifying enzymes, the haloacid dehalogenase-like hydrolase (HAD) superfamily. This detoxification process is further assisted by the NgnA acetyltransferase, orthologue of Mpr1 of Saccharomyces cerevisiae. We additionally show that heterologous expression of AzhA protein can complement the AZC sensitivity of S. cerevisiae. Furthermore, a detailed phylogenetic analysis of AzhA homologues in Fungi, Archaea and Bacteria is provided. Overall, our results unravel a widespread mechanism for AZC resistance among microorganisms, including important human and plant pathogens.
Transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity
Authors: Mishra Bharat , Athar Mohammad , Mukhtar M. Shahid 
Published: April 2021

AbstractMacrophages are ubiquitous custodians of tissues, which play decisive role in maintaining cellular homeostasis through regulatory immune responses. Within tissues, macrophage exhibit extremely heterogeneous population with varying functions orchestrated through regulatory response, which can be further exacerbated in diverse genetic backgrounds. Gene regulatory networks (GRNs) offer comprehensive understanding of cellular regulatory behavior by unfolding the transcription factors (TFs) and regulated target genes. RNA-Seq coupled with ATAC-Seq has revolutionized the regulome landscape influenced by gene expression modeling. Here, we employ an integrative multi-omics systems biology-based analysis and generated GRNs derived from the unstimulated bone marrow-derived macrophages of five inbred genetically defined murine strains, which are reported to be linked with most of the population-wide human genetic variants. Our probabilistic modeling of a basal hemostasis pan regulatory repertoire in diverse macrophages discovered 96 TFs targeting 6279 genes representing 468,291 interactions across five inbred murine strains. Subsequently, we identify core and distinctive GRN sub-networks in unstimulated macrophages to describe the system-wide conservation and dissimilarities, respectively across five murine strains. Our study concludes that discrepancies in unstimulated macrophage-specific regulatory networks not only drives the basal functional plasticity within genetic backgrounds, additionally aid in understanding the complexity of racial disparity among the human population during stress.
Antibody–drug nanoparticle induces synergistic treatment efficacies in HER2 positive breast cancer cells
Authors: Abedin Muhammad Raisul , Powers Kaitlyne , Aiardo Rachel , Barua Dibbya , Barua Sutapa 
Published: April 2021

AbstractChemotherapeutic drugs suffer from non-specific binding, undesired toxicity, and poor blood circulation which contribute to poor therapeutic efficacy. In this study, antibody–drug nanoparticles (ADNs) are engineered by synthesizing pure anti-cancer drug nanorods (NRs) in the core of nanoparticles with a therapeutic monoclonal antibody, Trastuzumab on the surface of NRs for specific targeting and synergistic treatments of human epidermal growth factor receptor 2 (HER2) positive breast cancer cells. ADNs were designed by first synthesizing ~ 95 nm diameter × ~ 500 nm long paclitaxel (PTX) NRs using the nanoprecipitation method. The surface of PTXNRs was functionalized at 2′ OH nucleophilic site using carbonyldiimidazole and conjugated to TTZ through the lysine residue interaction forming PTXNR-TTZ conjugates (ADNs). The size, shape, and surface charge of ADNs were characterized using scanning electron microscopy (SEM), SEM, and zeta potential, respectively. Using fluorophore labeling and response surface analysis, the percentage conjugation efficiency was found > 95% with a PTX to TTZ mass ratio of 4 (molar ratio ≈ 682). In vitro therapeutic efficiency of PTXNR-TTZ was evaluated in two HER2 positive breast cancer cell lines: BT-474 and SK-BR-3, and a HER2 negative MDA-MB-231 breast cancer cell using MTT assay. PTXNR-TTZ inhibited > 80% of BT-474 and SK-BR-3 cells at a higher efficiency than individual PTX and TTZ treatments alone after 72 h. A combination index analysis indicated a synergistic combination of PTXNR-TTZ compared with the doses of single-drug treatment. Relatively lower cytotoxicity was observed in MCF-10A human breast epithelial cell control. The molecular mechanisms of PTXNR-TTZ were investigated using cell cycle and Western blot analyses. The cell cycle analysis showed PTXNR-TTZ arrested > 80% of BT-474 breast cancer cells in the G2/M phase, while > 70% of untreated cells were found in the G0/G1 phase indicating that G2/M arrest induced apoptosis. A similar percentage of G2/M arrested cells was found to induce caspase-dependent apoptosis in PTXNR-TTZ treated BT-474 cells as revealed using Western blot analysis. PTXNR-TTZ treated BT-474 cells showed ~ 1.3, 1.4, and 1.6-fold higher expressions of cleaved caspase-9, cytochrome C, and cleaved caspase-3, respectively than untreated cells, indicating up-regulation of caspase-dependent activation of apoptotic pathways. The PTXNR-TTZ ADN represents a novel nanoparticle design that holds promise for targeted and efficient anti-cancer therapy by selective targeting and cancer cell death via apoptosis and mitotic cell cycle arrest.
Incomplete footprint coverage under tension in repair of isolated supraspinatus full-thickness tear
Authors: Yoon Tae-Hwan , Kim Sung-Jae , Choi Yun-Rak , Kim Du-Seong , Chun Yong-Min 
Published: April 2021

AbstractAlthough it is well known that repairing large or massive tears under tension may have an adverse effect on healing of the repaired tendons, only few studies have addressed this issue in medium-sized isolated supraspinatus full-thickness tear. The purpose of this study was to compare the clinical outcomes and structural integrity of arthroscopic rotator cuff repair with tension versus without it. This study retrospectively investigated 90 patients who underwent arthroscopic repair in a single-row for medium-sized isolated supraspinatus full-thickness tear. The patients were assigned to either repaired under tension (Group A, n = 38) or repaired without tension (Group B, n = 52) groups. Functional outcomes were assessed using the patient reported subjective values and the active range of motion (ROM). Postoperative radiographic evaluation was performed 6 months after the surgery to assess the structural integrity of the repaired tendons. Changes in the subjective shoulder scores from initial to 2 years after surgery showed no statistical significance between the two groups. The ROMs measured at initial and 2 years after surgery also showed no statistical difference between the two groups. Postoperative radiological evaluations found a significantly higher re-tear rate in Group A (28.9%, 11/38) than in Group B (9.6%, 5/52). The torn cuff tendons that were repaired under tension as retraction with limited mobility had significantly higher re-tear rate despite having immobilized for 6 weeks after surgery, but their clinical outcomes showed no significant difference from the outcomes of repaired tendons without tension.
Structure–function engineering of novel fish gelatin-derived multifunctional peptides using high-resolution peptidomics and bioinformatics
Authors: Mirzapour-Kouhdasht Armin , Moosavi-Nasab Marzieh , Lee Chul Won , Yun Hyosuk , Eun Jong-Bang 
Published: April 2021

AbstractThe multifunctional properties of fish gelatin hydrolysates have not been completely elucidated. Here, the biological characterization of these peptides was performed to engineer multifunctional peptides. Bioactive peptides were produced from mackerel byproducts via successive enzymatic hydrolysis reactions using subtilisin A and actinidin as microbial and herbal proteases. The antibacterial activity against both gram-negative and -positive food-borne pathogens, includingEscherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, andKlebsiella pneumoniae, as well as the inhibitory potential of angiotensin-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV), was accessed in vitro. The synthesized peptides demonstrated multifunctional properties, which were further confirmed by in silico protocols. The ACE and DPP-IV inhibitory (IC50) values of P1, P2, and P3 were 0.92 and 0.87, 0.51 and 0.93, 0.78 and 1.16 mg mL−1, respectively. Moreover, the binding energy was sufficient for all three peptides to inhibit both ACE and DPP-IV enzymes with excellent three-dimensional conformation (RMSD = 0.000) for all six docking mechanisms.
Recent increase in the occurrences of Christmas typhoons in the Western North Pacific
Authors: Basconcillo Joseph , Moon Il-Ju 
Published: April 2021

AbstractTo imply the gravity of their impact on Christmas celebration, the term Christmas typhoon recently became more popular to refer to tropical cyclones (TC) in the Western North Pacific (WNP) during its less active season. The past 9 years from 2012 to 2020 saw more than 70% (210%) increases in Christmas typhoon occurrences in the WNP (Philippines). Furthermore, Mindanao Island, which is located in southern Philippines, has experienced an unprecedented 480% increase in TC passage in the same period. Here we show that the detected recent increase in Christmas typhoons are mainly associated with the shift of the Pacific Decadal Oscillation to its positive phase in early 2010s, which led to favorable changes in the large-scale environment for TC development such as higher relative vorticity, anomalous low-level westerlies, warmer sea surface temperatures in the central Pacific, and extended WNP subtropical high. We also found that the poleward shift of the Intertropical Convergence Zone and possibly, the recent recovery of the Siberian High contributed to such increased occurrences. As opposed to the more active TC season, there is a wide research gap during the less active season. We aim to fill in this knowledge gap to gain better insights on TC risk reduction.
Neurocysticercosis in patients with active epilepsy in the tea garden community of Assam, Northeast India
Authors: Devi K. Rekha , Borbora Debasish , Upadhyay Narayan , Goswami Dibyajyoti , Rajguru S. K. , Narain Kanwar 
Published: April 2021

AbstractNeurocysticercosis is a significant cause of epilepsy in the tropics. The present cross-sectional survey was conducted in the socioeconomically backward tea garden community of Assam to gauge the prevalence of neurocysticercosis in patients with active epilepsy and to determine the associated risk factors. In a door to door survey, a total of 1028 individuals from every fifth household of the study Teagarden were enrolled to identify self-reported seizure cases, followed by a neurological examination to confirm the diagnosis of active epilepsy. Patients with active epilepsy underwent clinical, epidemiological, neuroimaging (contrast-enhanced computerized tomography) and immunological evaluations to establish the diagnosis of neurocysticercosis. Clinically confirmed 53 (5.16%) active epilepsy were identified; 45 agreed to further assessment for neurocysticercosis and 19 (42.2%) cases fulfilled either definitive or probable diagnostic criteria for neurocysticercosis. Patients with epilepsy due to neurocysticercosis were more likely to suffer from taeniasis (20.0% vs 0.0%), rear pigs (57.9% vs 15.4%) or have pigs in their neighbourhood (78.9% vs 53.8%) relative to epileptic patients without neurocysticercosis. Rearing pigs (aOR 14.35, 95% CI: 3.98–51.75) or having pigs in the neighbourhood (aOR 12.34, 95% CI: 2.53–60.31) were independent risk factors of neurocysticercosis. In this community, the prevalence of taeniasis (adult worm infection) was 6.6% based on microscopy. The study reports a high prevalence of active epilepsy in the tea garden community of Assam and neurocysticercosis as its primary cause. The high prevalence of taeniasis is also a significant concern.
An opioid-sparing protocol with intravenous parecoxib can effectively reduce morphine consumption after simultaneous bilateral total knee arthroplasty
Authors: Ma Hsuan-Hsiao , Chou Te-Feng Arthur , Wang Hsin-Yi , Tsai Shang-Wen , Chen Cheng-Fong , Wu Po-Kuei , Chen Wei-Ming 
Published: April 2021

AbstractMultimodal pain management protocol effectively relieves pain following simultaneous bilateral total knee arthroplasty (SBTKA) but is associated with administration of large amounts of opioids in the perioperative period. In this prospective, randomized, assessor-blinded, single-surgeon clinical trial, the goal was to validate the efficacy of an opioid-sparing protocol for SBTKA with a reduced opioid dose, while achieving similar pain relief with few adverse events. Fifty-six patients who had undergone SBTKA were randomly allocated to receive either an opioid-sparing or opioid-based protocol. The primary outcome parameters were visual analogue scale (VAS) scores at rest, with movement, and cumulative morphine dose, through time. Secondary outcome parameters included drug-related adverse events and range of motion with continuous passive motion device, through time. In the opioid-sparing group, a lower VAS score with movement at postoperative 24 and 72 h was observed compared with the opioid-based group, but the difference did not reach the minimal clinically importance difference. A reduced cumulative morphine dose was noted in the opioid-sparing group at postoperative 24, 48 and 72 h. In conclusion, the opioid-sparing protocol may be used as an alternative modality for pain management following SBTKA. Similar pain relief effects may be achieved utilizing a reduced cumulative opioid dose, with few opioid related adverse events.
Tumor innervation and clinical outcome in pancreatic cancer
Authors: Ferdoushi Aysha , Griffin Nathan , Marsland Mark , Xu Xiaoyue , Faulkner Sam , Gao Fangfang , Liu Hui , King Simon J. , Denham James W. , van Helden Dirk F. , Jobling Phillip , Jiang Chen Chen , Hondermarck Hubert 
Published: April 2021

AbstractPancreatic cancer is a highly aggressive malignancy characterized by poor survival, recurrence after surgery and resistance to therapy. Nerves infiltrate the microenvironment of pancreatic cancers and contribute to tumor progression, however the clinicopathological significance of tumor innervation is unclear. In this study, the presence of nerves and their cross-sectional size were quantified by immunohistochemistry for the neuronal markers S-100, PGP9.5 and GAP-43 in a series of 99 pancreatic cancer cases versus 71 normal adjacent pancreatic tissues. A trend was observed between the presence of nerves in the tumor microenvironment of pancreatic cancer and worse overall patient survival (HR = 1.8, 95% CI 0.77–4.28, p = 0.08). The size of nerves, as measured by cross-sectional area, were significantly higher in pancreatic cancer than in the normal adjacent tissue (p = 0.002) and larger nerves were directly associated with worse patient survival (HR = 0.41, 95% CI 0.19–0.87, p = 0.04). In conclusion, this study suggests that the presence and size of nerves within the pancreatic cancer microenvironment are associated with tumor aggressiveness.
A cell-specific regulatory region of the human ABO blood group gene regulates the neighborhood gene encoding odorant binding protein 2B
Authors: Sano Rie , Takahashi Yoichiro , Fukuda Haruki , Harada Megumi , Hayakawa Akira , Okawa Takafumi , Kubo Rieko , Takeshita Haruo , Tsukada Junichi , Kominato Yoshihiko 
Published: April 2021

AbstractThe human ABO blood group system is of great importance in blood transfusion and organ transplantation.ABOtranscription is known to be regulated by a constitutive promoter in a CpG island and regions for regulation of cell-specific expression such as the downstream + 22.6-kb site for epithelial cells and a site in intron 1 for erythroid cells. Here we investigated whether the + 22.6-kb site might play a role in transcriptional regulation of the gene encoding odorant binding protein 2B (OBP2B), which is located on the centromere side 43.4 kb from the + 22.6-kb site. In the gastric cancer cell line KATOIII, quantitative PCR analysis demonstrated significantly reduced amounts ofOBP2BandABOtranscripts in mutant cells with biallelic deletions of the site created using the CRISPR/Cas9 system, relative to those in the wild-type cells, and Western blotting demonstrated a corresponding reduction of OBP2B protein in the mutant cells. Moreover, single-molecule fluorescence in situ hybridization assays indicated that the amounts of both transcripts were correlated in individual cells. These findings suggest thatOBP2Bcould be co-regulated by the + 22.6-kb site ofABO.
Intracranial failure after hippocampal-avoidance prophylactic cranial irradiation in limited-stage small-cell lung cancer patients
Authors: Cho Yeona , Lee Joongyo , Lee Ik Jae , Kim Jun Won , Baek Jong Geol , Jung Dong Min , Cho Byoung Chul , Hong Min Hee , Kim Hye Ryun , Lee Chang Geol , Yoon Hong In 
Published: April 2021

AbstractWe evaluated intracranial failure after hippocampus-avoidance-prophylactic cranial irradiation (HA-PCI) for limited-stage small-cell lung cancer (SCLC). Data of 106 patients who received PCI with 25 Gy were retrospectively reviewed. The patients were divided into two groups based on whether they underwent HA-PCI: the HA-PCI group (n = 48) and the conventional PCI (C-PCI) group (n = 58). Twenty-one patients experienced intracranial failure: 11 and 10 patients in the C-PCI and HA-PCI groups, respectively. Using the log-rank test, the intracranial failure rate was not significantly different between the groups (p = 0.215). No clinical factor was significantly associated with intracranial failure in multivariate Cox regression analysis, but HA-PCI tended to be associated with increased incidence of intracranial failure (HR 2.87, 95% CI 0.86–9.58, p = 0.087). Among patients who received HA-PCI, two developed peri-hippocampal recurrence. A higher thoracic radiotherapy dose (≥ 60 Gy) was significantly associated with DFS (HR 0.52, p = 0.048) and OS (HR 0.35, p = 0.003). However, HA-PCI was associated with neither DFS nor OS. Although HA-PCI may be associated with an increased risk of intracranial failure, HA-PCI did not impair disease control or survival. Future prospective randomized trials are needed to reach a definite conclusion.
Family-based gene-environment interaction using sequence kernel association test (FGE-SKAT) for complex quantitative traits
Authors: Guo Chao-Yu , Wang Reng-Hong , Yang Hsin-Chou 
Published: April 2021

AbstractAfter the genome-wide association studies (GWAS) era, whole-genome sequencing is highly engaged in identifying the association of complex traits with rare variations. A score-based variance-component test has been proposed to identify common and rare genetic variants associated with complex traits while quickly adjusting for covariates. Such kernel score statistic allows for familial dependencies and adjusts for random confounding effects. However, the etiology of complex traits may involve the effects of genetic and environmental factors and the complex interactions between genes and the environment. Therefore, in this research, a novel method is proposed to detect gene and gene-environment interactions in a complex family-based association study with various correlated structures. We also developed an R function for the Fast Gene-Environment Sequence Kernel Association Test (FGE-SKAT), which is freely available as supplementary material for easy GWAS implementation to unveil such family-based joint effects. Simulation studies confirmed the validity of the new strategy and the superior statistical power. The FGE-SKAT was applied to the whole genome sequence data provided by Genetic Analysis Workshop 18 (GAW18) and discovered concordant and discordant regions compared to the methods without considering gene by environment interactions.