bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Perspectives on the Neurobiology of Sign Languages
Authors: Emmorey Karen 
Published: December 2021

The first 40 years of research on the neurobiology of sign languages (1960–2000) established that the same key left hemisphere brain regions support both signed and spoken languages, based primarily on evidence from signers with brain injury and at the end of the 20th century, based on evidence from emerging functional neuroimaging technologies (positron emission tomography and fMRI). Building on this earlier work, this review focuses on what we have learned about the neurobiology of sign languages in the last 15–20 years, what controversies remain unresolved, and directions for future research. Production and comprehension processes are addressed separately in order to capture whether and how output and input differences between sign and speech impact the neural substrates supporting language. In addition, the review includes aspects of language that are unique to sign languages, such as pervasive lexical iconicity, fingerspelling, linguistic facial expressions, and depictive classifier constructions. Summary sketches of the neural networks supporting sign language production and comprehension are provided with the hope that these will inspire future research as we begin to develop a more complete neurobiological model of sign language processing.
Effects of Clopidogrel, Prasugrel and Ticagrelor on Microvascular Function and Platelet Reactivity in Patients With Acute Coronary Syndrome Undergoing Coronary Artery Stenting. A Randomized, Blinded, Parallel Group Trial
Authors: Schnorbus Boris , Jurk Kerstin , Lackner Karl J. , Welk Caroline , Münzel Thomas , Gori Tommaso 
Published: December 2021

Aims: In this pre-specified analysis of the “endothelium, stent and antiplatelet therapy” study, we investigate the impact of antiplatelet therapies on microvascular function in patients undergoing stenting for an acute coronary syndrome.Methods and Results: Fifty-six patients [age: 63(55–67) years, males, 10 diabetics, 27 non-ST-elevation myocardial infarction] were randomized to receive clopidogrel, ticagrelor or prasugrel in form of oral loading 2 h before stenting followed by oral therapy. Investigators were blinded to the allocation. Laser-Doppler microvascular function and ADP-induced platelet aggregation capacity were measured at baseline, 2 h after oral antiplatelet loading, and 1 day, 1 week and 1 month after stenting during chronic therapy with the same antiplatelet agent. Platelet aggregation decreased in all groups 2 h after oral loading, with a significantly larger effect in the prasugrel group (P = 0.009). Similarly, prasugrel and ticagrelor loading was followed by an increase in microvascular reactive hyperemia (P = 0.007 and P = 0.042 compared to clopidogrel). This effect disappeared one day after coronary intervention, with a significant decrease in the prasugrel group (P = 0.026). Similarly, analysis of microvascular conductance showed a larger increase in the prasugrel group 2 h after loading (P = 0.022 among groups), and a decrease in all groups after stenting.Conclusions: Oral loading with prasugrel (and less consistently ticagrelor) is associated with improved microvascular function and stronger platelet inhibition in acute coronary syndrome patients. The microvascular effect was however lost 1 day after stenting and during subsequent follow-up. Further studies are necessary to clarify the the long-term effects and potential benefits of P2Y12 inhibitors on microvascular damage.ClINICALTRIALS.gov N°: NCT01700322EUDRACT-N°: 2011-005305-73.
The Role of ZnO as a Dopant and an Intergranular Phase in the Electrical Properties of Ca0.6Sr0.4TiO3 Ceramics
Authors: Zhang Lin , Wang Qian , Li Jie , Wang Chuanhui 
Published: December 2021

ZnO was introduced into Ca0.6Sr0.4TiO3ceramics as a dopant and an intergrangular phase in this research, followed by detailed structure characterization, energy storage performance analysis, and electrical behavior studies. The results revealed that the existence of ZnO as a dopant led to the decrease of conduction activation energy and the deterioration of energy storage behavior, while appropriate introduction of ZnO as an intergranular phase resulted in the increase of conduction activation energy and the optimization of energy storage performance. Additionally, the inverse relation between interfacial polarization and energy storage performance was observed in this study. Finally, an increased energy storage density of 1.16 J/cm3was achieved in 1 mol% ZnO-added Ca0.6Sr0.4TiO3ceramics.
BpOmpW Antigen Stimulates the Necessary Protective T-Cell Responses Against Melioidosis
Authors: Tomás-Cortázar Julen , Bossi Lorenzo , Quinn Conor , Reynolds Catherine J. , Butler David K. , Corcoran Niamh , Murchú Maitiú Ó , McMahon Eve , Singh Mahavir , Rongkard Patpong , Anguita Juan , Blanco Alfonso , Dunachie Susanna J. , Altmann Daniel , Boyton Rosemary J. , Arnold Johan , Giltaire Severine , McClean Siobhán 
Published: December 2021

Melioidosis is a potentially fatal bacterial disease caused by Burkholderia pseudomallei and is estimated to cause 89,000 deaths per year in endemic areas of Southeast Asia and Northern Australia. People with diabetes mellitus are most at risk of melioidosis, with a 12-fold increased susceptibility for severe disease. Interferon gamma (IFN-γ) responses from CD4 and CD8 T cells, but also from natural killer (NK) and natural killer T (NKT) cells, are necessary to eliminate the pathogen. We previously reported that immunization with B. pseudomallei OmpW (BpOmpW antigen) protected mice from lethal B. pseudomallei challenge for up to 81 days. Elucidating the immune correlates of protection of the protective BpOmpW vaccine is an essential step prior to clinical trials. Thus, we immunized either non-insulin-resistant C57BL/6J mice or an insulin-resistant C57BL/6J mouse model of type 2 diabetes (T2D) with a single dose of BpOmpW. BpOmpW induced strong antibody responses, stimulated effector CD4+ and CD8+ T cells and CD4+ CD25+ Foxp3+ regulatory T cells, and produced higher IFN-γ responses in CD4+, CD8+, NK, and NKT cells in non-insulin-resistant mice. The T-cell responses of insulin-resistant mice to BpOmpW were comparable to those of non-insulin-resistant mice. In addition, as a precursor to its evaluation in human studies, humanized HLA-DR and HLA-DQ (human leukocyte antigen DR and DQ isotypes, respectively) transgenic mice elicited IFN-γ recall responses in an enzyme-linked immune absorbent spot (ELISpot)-based study. Moreover, human donor peripheral blood mononuclear cells (PBMCs) exposed to BpOmpW for 7 days showed T-cell proliferation. Finally, plasma from melioidosis survivors with diabetes recognized our BpOmpW vaccine antigen. Overall, the range of approaches used strongly indicated that BpOmpW elicits the necessary immune responses to combat melioidosis and bring this vaccine closer to clinical trials.
Carbon Source Starvation of a Sulfate-Reducing Bacterium–Elevated MIC Deterioration of Tensile Strength and Strain of X80 Pipeline Steel
Authors: Li Zhong , Yang Jike , Guo Huihua , Kumseranee Sith , Punpruk Suchada , Mohamed Magdy E. , Saleh Mazen A. , Gu Tingyue 
Published: December 2021

It is known that starved sulfate-reducing bacterial biofilms corrode carbon steel more aggressively because they use electrons from elemental iron oxidation as an alternative source of energy. This work used carbon source starvation to vary MIC (microbiologically influenced corrosion) severity for studying subsequent MIC impacts on the degradation of X80 carbon steel mechanical properties. X80 square coupons and dogbone coupons were immersed in ATCC 1249 culture medium (200 ml in 450-ml anaerobic bottles) inoculated with Desulfovibrio vulgaris for 3-day pre-growth and then for an additional 14 days in fresh media with adjusted carbon source levels for starvation testing. After the starvation test, the sessile cell counts (cells/cm2) on the dogbone coupons in the bottles with carbon source levels of 0, 10, 50, and 100% (vs that in the full-strength medium) were 8.1 × 106, 3.2 × 107, 8.3 × 107, and 1.3 × 108, respectively. The pit depths from the X80 dogbone coupons were 1.9 μm (0%), 4.9 μm (10%), 9.1 μm (50%), and 6.4 μm (100%). The corresponding weight losses (mg/cm2) from the square coupons were 1.9 (0%), 3.3 (10%), 4.4 (50%), and 3.7 (100%). The 50% carbon source level had the combination of carbon starvation without suffering too much sessile cell loss. Thus, both its pit depth and weight loss were the highest. The electrochemical tests corroborated the pit depth and weight loss trends. The tensile tests of the dogbone coupons after the starvation incubation indicated that sulfate-reducing bacteria (SRB) made X80 more brittle and weaker. Compared with the fresh (no-SRB-exposure) X80 dogbone coupon’s ultimate tensile strain of 13.6% and ultimate tensile stress of 860 MPa, the 50% carbon source level led to the lowest ultimate tensile strain of 10.3% (24% loss when compared with the fresh dogbone) and ultimate tensile stress of 672 MPa (22% loss). The 100% carbon source level had a smaller loss in ultimate tensile strain than the 50% carbon source level, followed by 10% and then 0%. Moreover, the 100% carbon source level had a smaller loss in ultimate tensile strength than the 50%, followed by 10% and 0% in a tie. This outcome shows that even in the 17-day short-term test, significant degradation of the mechanical properties occurred and more severe MIC pitting caused more severe degradation.
A Case-Control Study for the Effectiveness of Oral Zinc in the Prevention and Mitigation of COVID-19
Authors: Gordon Antonio M. , Hardigan Patrick C. 
Published: December 2021

Background: The ongoing coronavirus disease-19 (COVID-19) pandemic (caused by an infection with severe acute respiratory syndrome (SARS)-coronavirus (CoV-2) has put a burden on the medical community and society at large. Efforts to reduce the disease burden and mortality over the course of the pandemic have focused on research to rapidly determine age-stratified seroepidemiologic surveys, a centralized research program to fast-track the most promising rapid diagnostics and serologic assays, and the testing of potential anti-viral agents, immunologic therapies, and vaccine candidates. Despite the lack of official recognition for the role of nutrition in the fight against COVID-19 infection, multiple groups proposed zinc supplementation as an adjuvant for the management of participants.Method: In an ambulatory, interventional, prospective, single-blind study, we evaluated the effectiveness of zinc supplementation in the prevention and mitigation of COVID-19 in two similar participant groups. In Clinic A (n = 104) participants were randomized to receive 10 mg, 25 mg, or 50 mg zinc picolinate daily, and Clinic B control participants paired according to their demographics and clinical parameters (n = 96). All participants were compared based on demographics, clinical comorbidities, blood counts, renal functions, vitamin D levels, and their development of symptomatic COVID-19 infection.Results: Symptomatic COVID-19 infection was significantly higher among the control group participants (N = 9, 10.4%) than the treatment participants (N = 2, 1.9%), p = 0.015. The unadjusted odds ratio indicates that symptomatic COVID-19 infection was 5.93 [95% CI: 1.51, 39.26] higher in the control group, p &lt; 0.01. Controlling for co-morbidities, individuals in the control group were 7.38 (95% CI: 1.80, 50.28) times more likely to develop symptomatic COVID-19 infection as compared with individuals in the treatment group (p &lt; 0.01). For every-one unit increase in the number of co-morbidities, the likelihood of developing symptomatic COVID-19 infection increased 1.57 (95% CI: 1.16, 2.19) (p = 0.01).Discussion: The findings from our study suggest that zinc supplementation in all three doses (10, 25, and 50 mg) may be an effective prophylaxis of symptomatic COVID-19 and may mitigate the severity of COVID-19 infection.Conclusion: Zinc is a relatively inexpensive mineral nutrient that is an effective prophylactic agent to prevent and mitigate the potentially deadly symptomatic SARS-CoV-2 infection. As the COVID-19 pandemic continues with a lag in vaccinations in some regions and the continued emergence of dangerously infectious variants of SARS-CoV-2, it is important to replicate our data in other populations and locations and to engage public health and nutrition services on the emergent need to use zinc supplantation or fortification of staple foods in the prevention and mitigation of COVID-19 infection severity.
Emergence of Multiple Novel Inter-Genotype Recombinant Strains of Human Astroviruses Detected in Pediatric Patients With Acute Gastroenteritis in Thailand
Authors: Wei Hongyu , Khamrin Pattara , Kumthip Kattareeya , Yodmeeklin Arpaporn , Maneekarn Niwat 
Published: December 2021

Objective: Human astrovirus (HAstV) is recognized as an important cause of acute gastroenteritis in children. Recombination between different genotypes of HAstV can contribute to diversity and evolution of the virus. This study aimed to investigate the emergence of HAstV recombinant strains in pediatric patients hospitalized with acute gastroenteritis in Chiang Mai, Thailand, spanning 2011–2020.Methods: A total of 92 archival HAstV strains collected from pediatric patients with acute gastroenteritis during 2011–2020 were further characterized to identify the recombinant strains. The ORF1b and ORF2 junction region of each strain was amplified and sequenced. The obtained sequences were analyzed in comparison with the reference sequences retrieved from GenBank database. Their genotypes were assigned using MEGA X software based on the partial ORF1b (RdRp) and ORF2 (capsid) regions, and the recombination breakpoints of recombinant strains were determined by SimPlot and RDP4 analyses.Results: Five inter-genotype recombinant strains with three recombination patterns of ORF1b/ORF2 of classic HAstV, HAstV8/HAstV1, HAstV8/HAstV3, and HAstV3/HAstV2, were detected. The recombination breakpoints of all strains were located at the 3′-end region of ORF1b close to the ORF1b/ORF2 junction.Conclusion: Several novel inter-genotype recombinant strains of classic HAstV genotypes were detected in pediatric patients with acute gastroenteritis in Chiang Mai, Thailand, during the period of 10 years from 2011 to 2020.
Adapted Physical Activity for Breast Cancer Patients Treated with Neoadjuvant Chemotherapy and Trastuzumab Against HER2 (APACAN2): A Protocol for a Feasibility Study
Authors: Ginzac Angeline , Bernadach Maureen , Molnar Ioana , Duclos Martine , Thivat Emilie , Durando Xavier 
Published: December 2021

BackgroundThe standard care for HER2-positive breast cancer is chemotherapy plus a HER2-directed therapy. This can lead to treatment-induced cardiotoxicity. On the other hand, the practice of physical activity is known to improve cardiac function; thus HER2-positive breast cancer patients could draw particular benefit from physical activity during treatment. However, at the time of diagnosis for breast cancer, the majority of patients are insufficiently active according to physical activity recommendations of World Health Organisation, and it is difficult to remain or become active during the treatment. There is a lack of data in the literature on the optimal program to propose to patients to encourage them to be active during treatment. The aim of our study is to assess the feasibility of a home-based physical activity program during neoadjuvant chemotherapy and trastuzumab for HER2-positive breast cancer.MethodsThe APACAN2 study is a single-centre, non-randomized interventional trial. Patients with HER2-positive breast cancer treated with anthracycline-based neoadjuvant chemotherapy and trastuzumab are eligible for enrolment. The supervised home-based physical activity program takes place during neoadjuvant chemotherapy (NACT). It combines aerobic and strengthening exercises. The primary endpoint is the proportion of patients reaching the international physical activity recommendations, i.e. 150 minutes of moderate-intensity activity per week at the end of NACT. The study started in April 2018 and seventy patients are expected to be recruited.DiscussionIn the literature, the majority of studies on practice of physical activity in breast cancer focus on adjuvant chemotherapy or on the period after the end of treatment. To the best of our knowledge, the APACAN2 study is the first to evaluate a home-based physical activity program during neoadjuvant chemotherapy for HER2-positive breast cancer.Trial Registration NumberClinicaltrials.gov: NCT02963363, registered on July 11, 2016. Identifier with the French National Agency for the Safety of Medicines and Health Products N°ID RCB 2016-A01344-47, registered in August 2016. Protocol: version 8, 24 February 2021.
A Continuous Correlation Between Residual Tumor Volume and Survival Recommends Maximal Safe Resection in Glioblastoma Patients: A Nomogram for Clinical Decision Making and Reference for Non-Randomized Trials
Authors: Skardelly Marco , Kaltenstadler Marlene , Behling Felix , Mäurer Irina , Schittenhelm Jens , Bender Benjamin , Paulsen Frank , Hedderich Jürgen , Renovanz Mirjam , Gempt Jens , Barz Melanie , Meyer Bernhard , Tabatabai Ghazaleh , Tatagiba Marcos Soares 
Published: December 2021

ObjectiveThe exact role of the extent of resection or residual tumor volume on overall survival in glioblastoma patients is still controversial. Our aim was to create a statistical model showing the association between resection extent/residual tumor volume and overall survival and to provide a nomogram that can assess the survival benefit of individual patients and serve as a reference for non-randomized studies.MethodsIn this retrospective multicenter cohort study, we used the non-parametric Cox regression and the parametric log-logistic accelerated failure time model in patients with glioblastoma. On 303 patients (training set), we developed a model to evaluate the effect of the extent of resection/residual tumor volume on overall survival and created a score to estimate individual overall survival. The stability of the model was validated by 20-fold cross-validation and predictive accuracy by an external cohort of 253 patients (validation set).ResultsWe found a continuous relationship between extent of resection or residual tumor volume and overall survival. Our final accelerated failure time model (pseudo R2 = 0.423; C-index = 0.749) included residual tumor volume, age, O6-methylguanine-DNA-methyltransferase methylation, therapy modality, resectability, and ventricular wall infiltration as independent predictors of overall survival. Based on these factors, we developed a nomogram for assessing the survival of individual patients that showed a median absolute predictive error of 2.78 (mean: 1.83) months, an improvement of about 40% compared with the most promising established models.ConclusionsA continuous relationship between residual tumor volume and overall survival supports the concept of maximum safe resection. Due to the low absolute predictive error and the consideration of uneven distributions of covariates, this model is suitable for clinical decision making and helps to evaluate the results of non-randomized studies.
Loss of Hyaluronan and Proteoglycan Link Protein-1 Induces Tumorigenesis in Colorectal Cancer
Authors: Wang Yao , Xu Xiaoyue , Marshall Jacqueline E. , Gong Muxue , Zhao Yang , Dua Kamal , Hansbro Philip M. , Xu Jincheng , Liu Gang 
Published: December 2021

Colorectal cancer (CRC) is the third most common diagnosed cancer worldwide, but there are no effective cures for it. Hyaluronan and proteoglycan link protein-1 (HAPLN1) is a component of the extracellular matrix (ECM) proteins and involved in the tumor environment in the colon. Transforming growth factor (TGF)-β is a key cytokine that regulates the deposition of ECM proteins in CRC. However, the role of HAPLN1 in TGF-β contributions to CRC remains unknown. We found that the mRNA expression of HAPLN1 was decreased in tumors from CRC patients compared with healthy controls and normal tissue adjacent to the tumor using two existing microarray datasets. This was validated at the protein level by tissue array from CRC patients (n = 59). HAPLN1 protein levels were also reduced in human CRC epithelial cells after 24 h of TGF-β stimulation, and its protein expression correlated with type I collagen alpha-1 (COL1A1) in CRC. Transfection of HAPLN1 overexpression plasmids into these cells increased protein levels but reduced COL1A1 protein, tumor growth, and cancer cell migration. TGF-β stimulation increased Smad2/3, p-Smad2/3, Smad4, and E-adhesion proteins; however, HAPLN1 overexpression restored these proteins to baseline levels in CRC epithelial cells after TGF-β stimulation. These findings suggest that HAPLN1 regulates the TGF-β signaling pathway to control collagen deposition via the TGF-β signaling pathway and mediates E-adhesion to control tumor growth. Thus, treatments that increase HAPLN1 levels may be a novel therapeutic option for CRC.
Locoregional Extension Patterns of Nasopharyngeal Carcinoma Detected by FDG PET/MR
Authors: Cao Caineng , Xu Yuanfan , Huang Shuang , Jiang Feng , Jin Ting , Jin Qifeng , Hua Yonghong , Hu Qiaoying , Chen Xiaozhong 
Published: December 2021

PurposeWe sought to define the locoregional extension patterns of nasopharyngeal carcinomas (NPCs) by positron emission tomography (PET)/magnetic resonance imaging (MRI) and to improve clinical target volume (CTV) delineation.MethodsBetween May 2017 and March 2021, 331 consecutive patients with nonmetastatic NPCs who underwent pretreatment, simultaneous whole-body PET/MRI for staging were included in this study.ResultsThe high-risk regions included the base of the sphenoid bone, the prestyloid compartment, prevertebral muscle, foramen lacerum, medial pterygoid plate, sphenoidal sinus, clivus, petrous apex, and foramen ovale. When the high-risk regions were invaded, the incidence rates of tumor invasion into the medium-risk regions increased. In contrast, when the high-risk regions were not involved, the incidence rates of tumor invasion into the medium-risk regions were mostly less than 10%, excluding the post-styloid compartment and oropharynx. According to the updated consensus guidelines of the neck node levels for head and neck tumors from 2013, level IIa (77.3%, 256/331), level IIb (75.8%, 251/331), and level VIIa (71.3%, 236/331) were the most frequently involved levels, followed by levels III (42.6%), Va (13.9%), IVa (8.8%), IVb (3.6%), Ib (3.6%), Vb (2.4%), VIIb (2.4%), VIII (1.8%), Vc (0.9%), and Xa (0.3%). Skip lymph node metastasis occurred in only 1.9% of patients.ConclusionsFor NPCs, primary disease and regional lymph node spread follow an orderly pattern, and a skip pattern of lymph node metastasis was unusual. Involved level radiotherapy might be feasible for cervical lymph node levels below the caudal border of cricoid cartilage and level VIIb.