bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses
Authors: Wahid Rahnuma , Mercer Laina , Macadam Andrew , Carlyle Sarah , Stephens Laura , Martin Javier , Chumakov Konstantin , Laassri Majid , Petrovskaya Svetlana , Smits Saskia L. , Stittelaar Koert J. , Gast Chris , Weldon William C. , Konopka-Anstadt Jennifer L. , Steven Oberste M. , Van Damme Pierre , De Coster Ilse , Rüttimann Ricardo , Bandyopadhyay Ananda , Konz John 
Published: July 2021

AbstractSabin-strain oral polio vaccines (OPV) can, in rare instances, cause disease in recipients and susceptible contacts or evolve to become circulating vaccine-derived strains with the potential to cause outbreaks. Two novel type 2 OPV (nOPV2) candidates were designed to stabilize the genome against the rapid reversion that is observed following vaccination with Sabin OPV type 2 (mOPV2). Next-generation sequencing and a modified transgenic mouse neurovirulence test were applied to shed nOPV2 viruses from phase 1 and 2 studies and shed mOPV2 from a phase 4 study. The shed mOPV2 rapidly reverted in the primary attenuation site (domain V) and increased in virulence. In contrast, the shed nOPV2 viruses showed no evidence of reversion in domain V and limited or no increase in neurovirulence in mice. Based on these results and prior published data on safety, immunogenicity, and shedding, the nOPV2 viruses are promising alternatives to mOPV2 for outbreak responses.
The beneficial effects of menopausal hormone therapy on renal survival in postmenopausal Korean women from a nationwide health survey
Authors: Ahn Shin Young , Choi Yoon Jin , Kim Jieun , Ko Gang Jee , Kwon Young Joo , Han Kyungdo 
Published: July 2021

AbstractSeveral studies have demonstrated the nephroprotective effects of estrogen on renal damage. In light of the inconsistent results of previous findings, this study aims to evaluate the in-depth role of menopausal hormone therapy (MHT) on the development of end stage renal disease (ESRD). 3,109,506 Korean adult women who had undergone a medical examination in 2009 (index year) were initially identified for inclusion in this study. We excluded subjects had not experienced menopause naturally, had data missing for at least one variable, and were diagnosed with ESRD within 1 year from the index year. MHT data was obtained from self-reporting questionnaires and the primary outcome was the development of ESRD from the index year until December 31, 2018. A final total of 1,460,311 subjects were included in this study. The participants were divided into four groups according to the duration of MHT; no history of MHT, MHT < 2 years, 2 ≤ MHT < 5 years, MHT ≥ 5 years. During the 9-year study period, a total of 4905 participants developed ESRD. The participants who had a history of MHT use were found to have a 30% reduced risk of developing ESRD. Results from the subgroup analyses were similar to that of the primary study. The findings in this study demonstrate the beneficial effects of MHT on the development of ESRD in postmenopausal women. Based on results, our study may offer suggestions for further studies to investigate the therapeutic options on kidney disease.
Larval cryopreservation as new management tool for threatened clam fisheries
Authors: Heres P. , Troncoso J. , Paredes E. 
Published: July 2021

AbstractCryopreservation is the only reliable method for long-term storage of biological material that guarantees genetic stability. This technique can be extremely useful for the conservation of endangered species and restock natural populations for declining species. Many factors have negatively affected the populations of high economical value shellfish in Spain and, as a result, many are declining or threatened nowadays. This study was focused on early-life stages of Venerupis corrugata, Ruditapes decussatus and Ruditapes philippinarum to develop successful protocols to enhance the conservation effort and sustainable shellfishery resources. Firstly, common cryoprotecting agents (CPAs) were tested to select the suitable permeable CPA attending to toxicity. Cryopreservation success using different combinations of CPA solutions, increasing equilibrium times and larval stages was evaluated attending to survival and shell growth at 2 days post-thawing. Older clam development stages were more tolerant to CPA toxicity, being ethylene-glycol (EG) and Propylene-glycol (PG) the least toxic CPAs. CPA solution containing EG yielded the highest post-thawing survival rate and the increase of equilibration time was not beneficial for clam larvae. Cryopreservation of trochophores yielded around 50% survivorship, whereas over 80% of cryopreserved D-larvae were able to recover after thawing.
Maternal biological age assessed in early pregnancy is associated with gestational age at birth
Authors: Lancaster Eva E. , Lapato Dana M. , Jackson-Cook Colleen , Strauss Jerome F. , Roberson-Nay Roxann , York Timothy P. 
Published: July 2021

AbstractMaternal age is an established predictor of preterm birth independent of other recognized risk factors. The use of chronological age makes the assumption that individuals age at a similar rate. Therefore, it does not capture interindividual differences that may exist due to genetic background and environmental exposures. As a result, there is a need to identify biomarkers that more closely index the rate of cellular aging. One potential candidate is biological age (BA) estimated by the DNA methylome. This study investigated whether maternal BA, estimated in either early and/or late pregnancy, predicts gestational age at birth. BA was estimated from a genome-wide DNA methylation platform using the Horvath algorithm. Linear regression methods assessed the relationship between BA and pregnancy outcomes, including gestational age at birth and prenatal perceived stress, in a primary and replication cohort. Prenatal BA estimates from early pregnancy explained variance in gestational age at birth above and beyond the influence of other recognized preterm birth risk factors. Sensitivity analyses indicated that this signal was driven primarily by self-identified African American participants. This predictive relationship was sensitive to small variations in the BA estimation algorithm. Benefits and limitations of using BA in translational research and clinical applications for preterm birth are considered.
Combined bioinformatics technology to explore pivot genes and related clinical prognosis in the development of gastric cancer
Authors: Xu Jiasheng , Wang Xinlu , Ke Qiwen , Liao Kaili , Wan Yanhua , Zhang Kaihua , Zhang Guanyu , Wang Xiaozhong 
Published: July 2021

AbstractTo screen the key genes in the development of gastric cancer and their influence on prognosis. The GEO database was used to screen gastric cancer-related gene chips as a training set, and the R packages limma tool was used to analyze the differential genes expressed in gastric cancer tissues compared to normal tissues, and then the selected genes were verified in the validation set. The String database was used to calculate their Protein–protein interaction (PPI) network, using Cytoscape software's Centiscape and other plug-ins to analyze key genes in the PPI network. The DAVID database was used to enrich and annotate gene functions of differential genes and PPI key module genes, and further explore correlation between expression level and clinical stage and prognosis. Based on clinical data and patient samples, differential expression of key node genes was verified by immunohistochemistry. The 63 characteristic differential genes screened had good discrimination between gastric cancer and normal tissues, and are mainly involved in regulating extracellular matrix receptor interactions and the PI3k-AKT signaling pathway. Key nodes in the PPI network regulate tumor proliferation and metastasis. Analysis of the expression levels of key node genes found that relative to normal tissues, the expression of ITGB1 and COL1A2 was significantly increased in gastric cancer tissues, and patients with late clinical stages of tumors had higher expression of ITGB1 and COL1A2 in tumor tissues, and their survival time was longer (P < 0.05). This study found that ITGB1 and COL1A2 are key genes in the development of gastric cancer and can be used as prognostic markers and potential new targets for gastric cancer.
Pseudoboehmite as a drug delivery system for acyclovir
Authors: Peres Renato Meneghetti , Sousa Jéssica Maiara Leme , de Oliveira Mariana Oliva , Rossi Maura Vincenza , de Oliveira Rene Ramos , de Lima Nelson Batista , Bernussi Ayrton , Warzywoda Juliusz , Sarmento Bruno , Munhoz Antonio Hortencio 
Published: July 2021

AbstractHerpes simplex virus is among the most prevalent sexually transmitted infections. Acyclovir is a potent, selective inhibitor of herpes viruses and it is indicated for the treatment and management of recurrent cold sores on the lips and face, genital herpes, among other diseases. The problem of the oral bioavailability of acyclovir is limited because of the low permeability across the gastrointestinal membrane. The use of nanoparticles of pseudoboehmite as a drug delivery system in vitro assays is a promising approach to further the permeability of acyclovir release. Here we report the synthesis of high purity pseudoboehmite from aluminium nitrate and ammonium hydroxide containing nanoparticles, using the sol–gel method, as a drug delivery system to improve the systemic bioavailability of acyclovir. The presence of pseudoboehmite nanoparticles were verified by infrared spectroscopy, transmission electron microscopy, and X-ray diffraction techniques. In vivo tests were performed with Wistar rats to compare the release of acyclovir, with and without the addition of pseudoboehmite. The administration of acyclovir with the addition of pseudoboehmite increased the drug content by 4.6 times in the plasma of Wistar rats after 4 h administration. We determined that the toxicity of pseudoboehmite is low up to 10 mg/mL, in gel and the dried pseudoboehmite nanoparticles.
Procedural outcomes in patients with dual versus single antiplatelet therapy prior to transcatheter aortic valve replacement
Authors: Seoudy Hatim , Thomann Maren , Frank Johanne , Lutz Matthias , Puehler Thomas , Lutter Georg , Müller Oliver J. , Frey Norbert , Saad Mohammed , Frank Derk 
Published: July 2021

AbstractThe impact of uninterrupted dual antiplatelet therapy (DAPT) on bleeding events among patients undergoing transcatheter aortic valve replacement (TAVR) has not been well studied. We conducted an analysis of 529 patients who underwent transfemoral TAVR in our centre and were receiving either DAPT or single antiplatelet therapy (SAPT) prior to the procedure. Accordingly, patients were grouped into a DAPT or SAPT group. Following current guidelines, patients in the SAPT group were switched to DAPT for 90 days after the procedure. The primary endpoint of our analysis was the incidence of bleeding events at 30 days according to the VARC-2 classification system. Any VARC-2 bleeding complications were found in 153 patients (28.9%), while major/life-threatening or disabling bleeding events occurred in 60 patients (11.3%). Our study revealed no significant difference between the DAPT vs. SAPT group regarding periprocedural bleeding complications. Based on multivariable analyses, major bleeding (HR 4.59, 95% CI 1.64–12.83, p = 0.004) and life-threatening/disabling bleeding (HR 8.66, 95% CI 3.31–22.65, p < 0.001) events were significantly associated with mortality at 90 days after TAVR. Both pre-existing DAPT and SAPT showed a comparable safety profile regarding periprocedural bleeding complications and mortality at 90 days. Thus, DAPT can be safely continued in patients undergoing transfemoral TAVR.
A bioimpedance-based monitor for real-time detection and identification of secondary brain injury
Authors: Everitt Alicia , Root Brandon , Calnan Daniel , Manwaring Preston , Bauer David , Halter Ryan 
Published: July 2021

AbstractSecondary brain injury impacts patient prognosis and can lead to long-term morbidity and mortality in cases of trauma. Continuous monitoring of secondary injury in acute clinical settings is primarily limited to intracranial pressure (ICP); however, ICP is unable to identify essential underlying etiologies of injury needed to guide treatment (e.g. immediate surgical intervention vs medical management). Here we show that a novel intracranial bioimpedance monitor (BIM) can detect onset of secondary injury, differentiate focal (e.g. hemorrhage) from global (e.g. edema) events, identify underlying etiology and provide localization of an intracranial mass effect. We found in an in vivo porcine model that the BIM detected changes in intracranial volume down to 0.38 mL, differentiated high impedance (e.g. ischemic) from low impedance (e.g. hemorrhagic) injuries (p < 0.001), separated focal from global events (p < 0.001) and provided coarse ‘imaging’ through localization of the mass effect. This work presents for the first time the full design, development, characterization and successful implementation of an intracranial bioimpedance monitor. This BIM technology could be further translated to clinical pathologies including but not limited to traumatic brain injury, intracerebral hemorrhage, stroke, hydrocephalus and post-surgical monitoring.
Cooperative roles of introns 1 and 2 of tobacco resistance gene N in enhanced N transcript expression and antiviral defense responses
Authors: Ikeda Chihiro , Taku Kazuo , Miyazaki Tsumugi , Shirai Rikako , Nelson Richard S. , Nyunoya Hiroshi , Matsushita Yasuhiko , Sasaki Nobumitsu 
Published: July 2021

AbstractThe tobacco virus resistance geneNcontains four introns. Transient expression of transcripts from anNtransgene containing these introns and driven by the native promoter in the presence of the elicitor of tobacco mosaic virus resulted in its increased expression. The requirement of the native promoter, the elicitor, or the individual introns for enhanced expression ofNhas not been fully studied. Here, we determined that 35S promoter-drivenNtranscript expression could be enhanced in the presence of the four introns regardless of the co-expression of the virus elicitor in tobacco. Function analyses using a series ofNtransgenes with different combination of introns revealed that the presence of intron 1 more so than intron 2 allowed higher accumulation of premature and matureNtranscripts; however, both introns were important for not only enhanced gene expression but also for induction of cell death in tobacco and induced local resistance to spread of virus inNicotiana benthamiana. Our findings indicate that introns 1 and 2 cooperatively contribute toNexpression and virus resistance.
Rapid statistical discrimination of fluorescence images of T cell receptors on immobilizing surfaces with different coating conditions
Authors: Saed Badeia , Munaweera Rangika , Anderson Jesse , O’Neill William D. , Hu Ying S. 
Published: July 2021

AbstractThe spatial organization of T cell receptors (TCRs) correlates with membrane-associated signal amplification, dispersion, and regulation during T cell activation. Despite its potential clinical importance, quantitative analysis of the spatial arrangement of TCRs from standard fluorescence images remains difficult. Here, we report Statistical Classification Analyses of Membrane Protein Images or SCAMPI as a technique capable of analyzing the spatial arrangement of TCRs on the plasma membrane of T cells. We leveraged medical image analysis techniques that utilize pixel-based values. We transformed grayscale pixel values from fluorescence images of TCRs into estimated model parameters of partial differential equations. The estimated model parameters enabled an accurate classification using linear discrimination techniques, including Fisher Linear Discriminant (FLD) and Logistic Regression (LR). In a proof-of-principle study, we modeled and discriminated images of fluorescently tagged TCRs from Jurkat T cells on uncoated cover glass surfaces (Null) or coated cover glass surfaces with either positively charged poly-L-lysine (PLL) or TCR cross-linking anti-CD3 antibodies (OKT3). Using 80 training images and 20 test images per class, our statistical technique achieved 85% discrimination accuracy for both OKT3 versus PLL and OKT3 versus Null conditions. The run time of image data download, model construction, and image discrimination was 21.89 s on a laptop computer, comprised of 20.43 s for image data download, 1.30 s on the FLD-SCAMPI analysis, and 0.16 s on the LR-SCAMPI analysis. SCAMPI represents an alternative approach to morphology-based qualifications for discriminating complex patterns of membrane proteins conditioned on a small sample size and fast runtime. The technique paves pathways to characterize various physiological and pathological conditions using the spatial organization of TCRs from patient T cells.
Interactions of platelets with circulating tumor cells contribute to cancer metastasis
Authors: Anvari Sina , Osei Ernest , Maftoon Nima 
Published: July 2021

AbstractRecent studies have suggested that platelets have a crucial role in enhancing the survival of circulating tumor cells in the bloodstream and aggravating cancer metastasis. The main function of platelets is to bind to the sites of the damaged vessels to stop bleeding. However, in cancer patients, activated platelets adhere to circulating tumor cells and exacerbate metastatic spreading. Several hypotheses have been proposed about the platelet–cancer cell interactions, but the underlying mechanisms of these interactions are not completely understood yet. In this work, we quantitatively investigated the interactions between circulating tumor cells, red blood cells, platelets, plasma flow and microvessel walls via computational modelling at the cellular scale. Our highly detailed computational model allowed us to understand and quantitatively explain the role of platelets in deformation, adhesion and survival of tumor cells in their active arrest to the endothelium.
CRISPR/Cas9-based genetic screen of SCNT-reprogramming resistant genes identifies critical genes for male germ cell development in mice
Authors: Akter Most Sumona , Hada Masashi , Shikata Daiki , Watanabe Gen , Ogura Atsuo , Matoba Shogo 
Published: July 2021

AbstractMale germ cells undergo complex developmental processes eventually producing spermatozoa through spermatogenesis, although the molecular mechanisms remain largely elusive. We have previously identified somatic cell nuclear transfer-reprogramming resistant genes (SRRGs) that are highly enriched for genes essential for spermatogenesis, although many of them remain uncharacterized in knockout (KO) mice. Here, we performed a CRISPR-based genetic screen using C57BL/6N mice for five uncharacterized SRRGs (Cox8c, Cox7b2, Tuba3a/3b, Faiml, and Gm773), together with meiosis essential gene Majin as a control. RT-qPCR analysis of mouse adult tissues revealed that the five selected SRRGs were exclusively expressed in testis. Analysis of single-cell RNA-seq datasets of adult testis revealed stage-specific expression (pre-, mid-, or post-meiotic expression) in testicular germ cells. Examination of testis morphology, histology, and sperm functions in CRISPR-injected KO adult males revealed that Cox7b2, Gm773, and Tuba3a/3b are required for the production of normal spermatozoa. Specifically, Cox7b2 KO mice produced poorly motile infertile spermatozoa, Gm773 KO mice produced motile spermatozoa with limited zona penetration abilities, and Tuba3a/3b KO mice completely lost germ cells at the early postnatal stages. Our genetic screen focusing on SRRGs efficiently identified critical genes for male germ cell development in mice, which also provides insights into human reproductive medicine.
Osseodensification enables bone healing chambers with improved low-density bone site primary stability: an in vivo study
Authors: Mello-Machado Rafael Coutinho , Sartoretto Suelen Cristina , Granjeiro Jose Mauro , Calasans-Maia José de Albuquerque , de Uzeda Marcelo Jose Pinheiro Guedes , Mourão Carlos Fernando de Almeida Barros , Ghiraldini Bruna , Bezerra Fabio Jose Barbosa , Senna Plinio Mendes , Calasans-Maia Mônica Diuana 
Published: July 2021

AbstractPrimary implant stability is a prerequisite for successful implant osseointegration. The osseodensification technique (OD) is a non-subtractive drilling technique that preserves the bone tissue, increases osteotomy wall density, and improves the primary stability. This study aimed to investigate the hypothesis that OD, through a wider osteotomy, produces healing chambers (HCs) at the implant-bone interface without impacting low-density bone primary stability. Twenty implants (3.5 × 10 mm) with a nanohydroxyapatite (nHA) surface were inserted in the ilium of ten sheep. Implant beds were prepared as follows: (i) 2.7-mm-wide using subtractive conventional drilling (SCD) technique (n = 10); (ii) 3.8-mm-wide using an OD bur system (n = 10). The sheep were randomized to two groups, with samples collected at either 14-(n = 5) or 28-days (n = 5) post-surgery and processed for histological and histomorphometric evaluation of bone-implant contact (BIC) and bone area fraction occupancy (BAFO). No significant group differences were found with respect to final insertion torque and implant stability quotient (p > 0.050). BIC values were higher for SCD after 14 and 28 days (p < 0.050); however, BAFO values were similar (p > 0.050). It was possible to conclude that the OD technique allowed a wider implant bed preparation without prejudice on primary stability and bone remodeling.
Eradicating mesothelin-positive human gastric and pancreatic tumors in xenograft models with optimized anti-mesothelin antibody–drug conjugates from synthetic antibody libraries
Authors: Hsu Hung-Ju , Tung Chao-Ping , Yu Chung-Ming , Chen Chi-Yung , Chen Hong-Sen , Huang Yu-Chuan , Tsai Pei-Hsun , Lin Su-I , Peng Hung-Pin , Chiu Yi-Kai , Tsou Yueh-Liang , Kuo Wei-Ying , Jian Jhih-Wei , Hung Fei-Hung , Hsieh Chiao-Yun , Hsiao Michael , Chuang Simon Shih-Hsien , Shen Chia-Ning , Wang Yong Alison , Yang An-Suei 
Published: July 2021

AbstractMesothelin (MSLN) is an attractive candidate of targeted therapy for several cancers, and hence there are increasing needs to develop MSLN-targeting strategies for cancer therapeutics. Antibody–drug conjugates (ADCs) targeting MSLN have been demonstrated to be a viable strategy in treating MSLN-positive cancers. However, developing antibodies as targeting modules in ADCs for toxic payload delivery to the tumor site but not to normal tissues is not a straightforward task with many potential hurdles. In this work, we established a high throughput engineering platform to develop and optimize anti-MSLN ADCs by characterizing more than 300 scFv CDR-variants and more than 50 IgG CDR-variants of a parent anti-MSLN antibody as candidates for ADCs. The results indicate that only a small portion of the complementarity determining region (CDR) residues are indispensable in the MSLN-specific targeting. Also, the enhancement of the hydrophilicity of the rest of the CDR residues could drastically increase the overall solubility of the optimized anti-MSLN antibodies, and thus substantially improve the efficacies of the ADCs in treating human gastric and pancreatic tumor xenograft models in mice. We demonstrated that the in vivo treatments with the optimized ADCs resulted in almost complete eradication of the xenograft tumors at the treatment endpoints, without detectable off-target toxicity because of the ADCs’ high specificity targeting the cell surface tumor-associated MSLN. The technological platform can be applied to optimize the antibody sequences for more effective targeting modules of ADCs, even when the candidate antibodies are not necessarily feasible for the ADC development due to the antibodies’ inferior solubility or affinity/specificity to the target antigen.