bluuebunny/crossref_metadata_2025_split huggingface dataset:
No difference in cognitive task-related oscillations between human internal globus pallidus and subthalamic nucleus
Authors: Navid Muhammad Samran , Kammermeier Stefan , Niazi Imran K. , Sharma Vibhash D. , Vuong Shawn M. , Greenlee Jeremy D. W. , Singh Arun 
Published: May 2021

AbstractRecently it has been acknowledged that the basal ganglia nuclei play a major role in cognitive control; however, the contribution by their network remains unclear. Previous studies have demonstrated the role of the subthalamic nucleus (STN) in cognitive processing and suggested that its connections to cortical and other associated regions regulate response inhibition during conflict conditions. By contrast, the role of the internal globus pallidus (GPi) as the output nucleus before the thalamic relay has not yet been investigated during cognitive processing. We recorded local field potentials (LFPs) from externalized deep brain stimulation (DBS) electrodes implanted bilaterally in the GPi (n=9 participants with dystonia) and STN (n=8 participants with Parkinson’s disease (PD)) during a primed flanker task. Both dystonia (GPi group) and PD participants (STN group) responded faster to the congruent trials than the incongruent trials. Overall, the dystonic GPi group was significantly faster than the PD STN group. LFPs showed elevated cue-triggered theta (3-7 Hz) power in GPi and STN groups in a similar way. Response-triggered LFP beta power (13-25 Hz) was significantly increased in the GPi group compared to the STN group. Results demonstrate that GPi activity appears to be critical in the cognitive processing of action selection and response during the presence of conflict tasks similar to the STN group. As both GPi and STN nuclei are involved in cognitive processing; therefore, these nuclei may be targeted for neuromodulation to improve cognitive control via DBS.
ADVANCED AUTOLOGOUS LOWER DERMAL SLING TECHNIQUE FOR IMMEDIATE BREAST RECONSTRUCTION SURGERY IN SMALL AND NON-PTOTIC BREASTS
Authors: Koppiker Chaitanyanand B. , Noor Aijaz Ul , Dixit Santosh , Busheri Laleh , Sharan Gautam , Dhar Upendra , Allampati Hari Kiran , Nare Smeeta , Gangurde Nutan 
Published: May 2021

ABSTRACTBackgroundBreast reconstruction with an autologous lower dermal sling (ALDS) is an established one-stage procedure in patients with moderate to large ptotic breasts. However, this technique is difficult to perform in small and non/minimally ptotic breasts. We describe our experiences from a single institution about a novel Advanced Autologous Lower Dermal Sling (A-ALDS) technique for reconstruction in small breasts.MethodsWe performed one stage nipple/skin sparing mastectomies in 61 patients with immediate reconstruction either by conventional immediate breast reconstruction surgery or A-ALDS technique.ResultsMean age of study patients was 46.9 years. We observed significantly better cosmetic score and lower immediate complication rate vis-a-vis skin necrosis, implant loss with the A-ALDS technique (i.e., nil versus 3 in Conventional Immediate Breast Reconstruction Surgery - IBRS). 40 patients completed 12 months follow-up. The PROMs-Patient Reported Outcomes Measures (Breast-Q) revealed good to excellent scores for satisfaction with breast, cosmetic outcome and psychosocial well-being in patients operated with both these techniques. However, sexual well-being was significantly better in the A-ALDS group.ConclusionThe A-ALDS is a novel, cost-effective and safe technique for immediate one stage implant-based reconstruction for small breasts. It provides a dermal barrier flap and hence, ensures less complications, excellent cosmetic results and patient satisfaction.
Dual G9A and EZH2 inhibition stimulates an anti-tumour immune response in ovarian high-grade serous carcinoma
Authors: Spiliopoulou Pavlina , Spear Sarah , Mirza Hasan , Garner Ian , McGarry Lynn , Grundland-Freile Fabio , Cheng Zhao , Ennis Darren P. , McNamara Sophie , Natoli Marina , Mason Susan , Blyth Karen , Adams Peter D. , Roxburgh Patricia , Fuchter Matthew J. , Brown Bob , McNeish Iain A. 
Published: May 2021

AbstractOvarian high-grade serous carcinoma (HGSC) prognosis correlates directly with presence of intratumoral lymphocytes. However, cancer immunotherapy has yet to achieve meaningful survival benefit in patients with HGSC. Epigenetic silencing of immunostimulatory genes is implicated in immune evasion in HGSC and re-expression of these genes could promote tumour immune clearance. We discovered that simultaneous inhibition of the histone methyltransferases G9A and EZH2 activates the CXCL10-CXCR3 axis and increases homing of intratumoral effector lymphocytes and natural killer cells whilst suppressing tumour-promoting FoxP3+ CD4 T cells. The dual G9A/EZH2 inhibitor HKMTI-1-005 induced chromatin changes that resulted in the transcriptional activation of immunostimulatory gene networks, including the re-expression of elements of the ERV-K endogenous retroviral family. Importantly, treatment with HKMTI-1-005 improved the survival of mice bearing Trp53-/-null ID8 ovarian tumours and resulted in tumour burden reduction.These results indicate that inhibiting G9A and EZH2 in ovarian cancer alters the immune microenvironment and reduces tumour growth and therefore positions dual inhibition of G9A/EZH2 as a strategy for clinical development.Abstract Figure
Infection and vaccine-induced neutralizing antibody responses to the SARS-CoV-2 B.1.617.1 variant
Authors: Edara Venkata-Viswanadh , Lai Lilin , Sahoo Malaya K. , Floyd Katharine , Sibai Mamdouh , Solis Daniel , Flowers Maria W. , Hussaini Laila , Ciric Caroline Rose , Bechnack Sarah , Stephens Kathy , Mokhtari Elham Bayat , Mudvari Prakriti , Creanga Adrian , Pegu Amarendra , Derrien-Colemyn Alexandrine , Henry Amy R. , Gagne Matthew , Graham Barney S. , Wrammert Jens , Douek Daniel C. , Boritz Eli , Pinsky Benjamin A. , Suthar Mehul S. 
Published: May 2021

AbstractSARS-CoV-2 has caused a devastating global pandemic. The recent emergence of SARS-CoV-2 variants that are less sensitive to neutralization by convalescent sera or vaccine-induced neutralizing antibody responses has raised concerns. A second wave of SARS-CoV-2 infections in India is leading to the expansion of SARS-CoV-2 variants. The B.1.617.1 variant has rapidly spread throughout India and to several countries throughout the world. In this study, using a live virus assay, we describe the neutralizing antibody response to the B.1.617.1 variant in serum from infected and vaccinated individuals. We found that the B.1.617.1 variant is 6.8-fold more resistant to neutralization by sera from COVID-19 convalescent and Moderna and Pfizer vaccinated individuals. Despite this, a majority of the sera from convalescent individuals and all sera from vaccinated individuals were still able to neutralize the B.1.617.1 variant. This suggests that protective immunity by the mRNA vaccines tested here are likely retained against the B.1.617.1 variant. As the B.1.617.1 variant continues to evolve, it will be important to monitor how additional mutations within the spike impact antibody resistance, viral transmission and vaccine efficacy.
High Dose Convalescent Plasma in COVID-19: Results from the Randomized Trial CAPSID
Authors: Körper Sixten , Weiss Manfred , Zickler Daniel , Wiesmann Thomas , Zacharowski Kai , M.Corman Victor , Grüner Beate , Ernst Lucas , Spieth Peter , Lepper Philipp M. , Bentz Martin , Zinn Sebastian , Paul Gregor , Kalbhenn Johannes , Dollinger Matthias , Rosenberger Peter , Kirschning Thomas , Thiele Thomas , Appl Thomas , Mayer Benjamin , Schmidt Michael , Drosten Christian , Wulf Hinnerk , Kruse Jan Matthias , Jungwirth Bettina , Seifried Erhard , Schrezenmeier Hubert ,   for the CAPSID Clinical Trial Group
Published: May 2021

RationaleCOVID-19 convalescent plasma (CCP) has been considered a treatment option in COVID-19.ObjectivesTo assess the efficacy of neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment.MethodsPatients (n=105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone. Control group patients with progress on day 14 could cross over to the CCP group. Primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21. The trial is registered: clinicaltrials.gov #NCT04433910.Measurements and main resultsThe primary outcome occurred in 43.4% of patients in the CCP and 32.7% in the control group (p=0.32). The median time to clinical improvement was 26 days (IQR 15-not reached (n.r.)) in the CCP group and 66 days (IQR 13-n.r.) in the control group (p=0.27). Median time to discharge from hospital was 31 days (IQR 16-n.r.) in the CCP and 51 days (IQR 20–n.r.) in the control group (p=0.24). In the subgroup that received a higher cumulative amount of neutralizing antibodies the primary outcome occurred in 56.0% (versus 32.1%), with a shorter interval to clinical improvement, shorter time to hospital discharge and better survival compared to the control group.ConclusionCCP added to standard treatment did not result in a significant difference in the primary and secondary outcomes. A pre-defined subgroup analysis showed a significant benefit for CCP among those who received a larger amount of neutralizing antibodies.
Sex-Specific Function and Morphology of the Anterior Cruciate Ligament During Skeletal Growth in a Porcine Model
Authors: Howe Danielle , Cone Stephanie G. , Piedrahita Jorge A. , Collins Bruce , Fordham Lynn A. , Griffith Emily H. , Spang Jeffrey T. , Fisher Matthew B. 
Published: May 2021

AbstractPediatric anterior cruciate ligament (ACL) injuries are on the rise, and females experience higher ACL injury risk than males during adolescence. Studies in skeletally immature patients indicate differences in ACL size and joint laxity between males and females after the onset of adolescence. However, functional data regarding the ACL and its anteromedial and posterolateral bundles in the pediatric population remain rare. Therefore, this study uses a porcine model to investigate the sex-specific morphology and function of the ACL and its bundles throughout skeletal growth. Hind limbs from male and female Yorkshire pigs aged early youth to late adolescence were imaged using magnetic resonance imaging to measure the size and orientation of the ACL and its bundles, then biomechanically tested under anterior-posterior drawer using a robotic testing system. Joint laxity decreased (p<0.001) while joint stiffness increased (p<0.001) throughout skeletal growth in both sexes. The ACL was the primary stabilizer against anterior tibial loading in all specimens, while the functional role of the anteromedial bundle increased with age (p<0.001), with an earlier shift in males. ACL and posterolateral bundle cross-sectional area and ACL and anteromedial bundle length were larger in males than females during adolescence (p<0.01 for all), while ACL and bundle sagittal angle remained similar between sexes. Additionally, in situ ACL stiffness correlated with cross-sectional area across skeletal growth (r2=0.75, p<0.001 in males and r2=0.64, p<0.001 in females), but not within age groups. This study has implications for age and sex-specific surgical intervention strategies and suggests the need for human studies.
O-GlcNAc transferase regulates glioblastoma acetate metabolism via regulation of CDK5-dependent ACSS2 phosphorylation
Authors: Ciraku Lorela , Bacigalupa Zachary A. , Ju Jing , Moeller Rebecca A. , Lee Rusia H. , Smith Michael D. , Ferrer Christina M. , Trefely Sophie , Doan Mary T. , Gocal Wiktoria A. , D’Agostino Luca , Shi Wenyin , Jackson Joshua G. , Katsetos Christos D. , Snyder Nathaniel W. , Reginato Mauricio J. 
Published: May 2021

AbstractGlioblastomas (GBMs) preferentially generate acetyl-CoA from acetate as a fuel source to promote tumor growth. O-GlcNAcylation has been shown to be elevated by increasing O-GlcNAc transferase (OGT) in many cancers and reduced O-GlcNAcylation can block cancer growth. Here, we identify a novel mechanism whereby OGT regulates acetate-dependent acetyl-CoA production by regulating phosphorylation of acetyl-CoA synthetase 2 (ACSS2) by cyclin-dependent kinase 5 (CDK5). OGT is required and sufficient for GBM cell growth and regulates acetate conversion to acetyl-CoA. Elevating O-GlcNAcylation in GBM cells increases phosphorylation of ACSS2 on Ser-267 in a CDK5-dependent manner. Importantly, we show that ACSS2 Ser-267 phosphorylation regulates its stability by reducing polyubiquitination and degradation. ACSS2 Ser-267 is critical for OGT-mediated GBM growth as overexpression of ACSS2 Ser-267 phospho-mimetic rescues growth in vitro and in vivo. Importantly, we show that pharmacologically targeting OGT and CDK5 reduces GBM growth ex vivo. Thus, the OGT/CDK5/ACSS2 pathway may be a way to target altered metabolic dependencies in brain tumors.
A common SEC23B missense mutation in congenital dyserythropoietic anemia type II leads to growth restriction and symptoms of chronic pancreatitis in mice
Authors: Wei Wei , Liu Zhigang , Zhang Chao , Khoriaty Rami , Zhu Min , Zhang Bin 
Published: May 2021

AbstractHuman loss-of-function mutations in SEC23B result in congenital dyserythropoietic anemia type II (CDAII). Complete deficiency of SEC23B in mice leads to perinatal death caused by massive degeneration of professional secretory tissues. Functions of SEC23B in postnatal mice are unclear. In this study, we generated knockout (KO) mice with deletion of exons 5 and 6 of Sec23b and knockin (KI) mice with the E109K mutation, the most common CDAII missense mutation. Despite decreased SEC23B protein level, Sec23bki/ki mice showed no obvious abnormalities. Hemizygous (Sec23bki/ko) mice exhibit a partial lethal phenotype, with only half of expected mice survive past weaning. Sec23bki/ko pancreas had exocrine insufficiency and chronic pancreatitis histology, as well as increased ER stress and apoptosis. Moreover, Sec23bki/ko mice exhibited severe growth restriction accompanied by growth hormone (GH) insensitivity, reminiscent of the Laron syndrome. Growth restriction is not associated with hepatocyte-specific Sec23b deletion, suggesting non-liver origin of the phenotype. Inflammation associated with chronic pancreatic deficiency may explain GH insensitivity in Sec23bki/ko mice. Our results indicate that phenotype severities are linked to the residual functions of SEC23B, demonstrating the importance of SEC23B in pancreatic acinar function in adult mice. The Sec23bki/ko mice provide a novel model of chronic pancreatitis and growth retardation.
Convergent and divergent structural and functional brain abnormalities associated with developmental dyslexia: a cross-linguistic meta-analysis of neuroimaging studies
Authors: Yan Xiaohui , Jiang Ke , Li Hui , Wang Ziyi , Perkins Kyle , Cao Fan 
Published: May 2021

AbstractBrain abnormalities in the reading network have been repeatedly reported in individuals with developmental dyslexia (DD); however, it is still not totally understood where and why the structural and functional abnormalities are consistent/inconsistent across languages. In the current multimodal meta-analysis, we found convergent structural and functional alterations in the left superior temporal gyrus across languages, suggesting a neural signature of DD. We found greater reduction in grey matter volume and brain activation in the left inferior frontal gyrus in morpho-syllabic languages (e.g. Chinese) than in alphabetic languages, and greater reduction in brain activation in the left middle temporal gyrus and fusiform gyrus in alphabetic languages than in morpho-syllabic languages. These language differences are explained as consequences of being DD while learning a specific language. In addition, we also found brain regions that showed increased grey matter volume and brain activation, presumably suggesting compensations and brain regions that showed inconsistent alterations in brain structure and function. Our study provides important insights about the etiology of DD from a cross-linguistic perspective with considerations of consistency/inconsistency between structural and functional alterations.
Comparative transcriptome analysis of human and murine choroidal neovascularization identifies fibroblast growth factor inducible-14 as phylogenetically conserved mediator of neovascular age-related macular degeneration
Authors: Wolf Julian , Schlecht Anja , Rosmus Dennis-Dominik , Boneva Stefaniya , Agostini Hansjürgen , Schlunck Günther , Wieghofer Peter , Lange Clemens 
Published: May 2021

AbstractBackgroundVisual outcome of patients with neovascular age-related macular degeneration has significantly improved during the last years following the introduction of anti-vascular endothelial growth factor (VEGF) therapy. However, about one third of patients show persistent exudation and decreasing visual acuity despite recurrent anti-VEGF treatment, which implies a role of other, still unknown proangiogenic mediators.MethodsThe present study applied transcriptional profiling of human and mouse (C57BL/6J wildtype) choroidal neovascularization (CNV) membranes each with reference to healthy control tissue to identify yet unrecognized mediators of CNV formation. Key factors were further investigated by immunohistochemistry as well as by intravitreal inhibition experiments and multiplex protein assays in the laser-induced CNV mouse model.ResultsTranscriptional profiles of CNV membranes were characterized by enhanced activation of blood vessel development, cytoskeletal organization, and cytokine production, with angiogenesis and wound healing processes predominating in humans and activation of immune processes in mice. Besides several species-specific factors, 95 phylogenetically conserved CNV-associated genes were detected, among which fibroblast growth factor inducible-14 (FN14), a member of the tumor necrosis factor (TNF) receptor family, was identified as a key player of CNV formation. Blocking the pathway by intravitreal injection of a FN14 decoy receptor modulated the cytokine profile - most notably IL-6 - and led to a significant reduction of CNV size in vivo.ConclusionsThis study characterizes the transcriptome of human and mouse CNV membranes in an unprejudiced manner and identifies FN14 as a phylogenetically conserved mediator of CNV formation and a promising new therapeutic target for neovascular AMD.FundingThis study was funded by the Helmut-Ecker-Stiftung and the Volker-Homann-Stiftung.
ALKBH5 regulates somatic cell reprogramming in a phase specific manner
Authors: Khodeer Sherif , Klungland Arne , Dahl John Arne 
Published: May 2021

AbstractEstablishment of the pluripotency regulatory network in somatic cells by introducing four transcriptional factors, (Octamer binding transcription factor 4 (OCT4), SRY (sex determining region Y)-box 2 (SOX2), Kruppel - like factor 4 (KLF4), and cellular-Myelocytomatosis (c-MYC) provides a promising tool for cell-based therapies in regenerative medicine. Still, the mechanisms at play when generating induced pluripotent stem cells from somatic cells is only partly understood. Here we show that the RNA specific N6-methyladenosine (m6A) demethylase ALKBH5 regulates somatic cell reprogramming in a stage specific manner. Knockdown or knockout of Alkbh5 in the early reprogramming phase impairs the reprogramming efficiency by reducing the proliferation rate through arresting the cells at G2/M phase and decreasing the mesenchymal-to-epithelial transition (MET) rate. However, there is no significant change in reprogramming efficiency when Alkbh5 is depleted at the late phase of reprogramming. On the other hand, ALKBH5 overexpression at the earlyreprogramming phase has no significant impact on reprogramming efficiency, while overexpression at the late phase enhances the reprogramming by stabilizing Nanog transcripts resulting in upregulated Nanog expression. Our study provides mechanistic insight into the crucial dynamic role of ALKBH5 in regulating somatic cell reprogramming at the posttranscriptional level.
Quantitative monitoring of nucleotide sequence data from genetic resources in context of their citation in the scientific literature
Authors: Lange Matthias , Alako Blaise T.F. , Cochrane Guy , Ghaffar Mehmood , Mascher Martin , Habekost Pia-Katharina , Hillebrand Upneet , Scholz Uwe , Zunder Florian , Freitag Jens , Scholz Amber Hartman 
Published: May 2021

AbstractBackgroundLinking nucleotide sequence data (NSD) to scientific publication citations can enhance understanding of NSDs provenance, scientific use, and re-use in the community. By connecting publications with NSD records, NSD geographical provenance information, and author geographical information, it becomes possible to assess the contribution of NSD to infer trends in scientific knowledge gain at the global level.FindingsFor this data note, we extracted and linked records from the European Nucleotide Archive to citations in open-access publications aggregated at Europe PubMed Central. A total of 8,464,292 ENA accessions with geographical provenance information were associated with publications. We conducted a data quality review to uncover potential issues in publication citation information extraction and author affiliation tagging and developed and implemented best-practice recommendations for citation extraction. Flat data tables and an data warehouse with an interactive web application were constructed to enable ad hoc exploration of NSD use and summary statistics.ConclusionsThe extraction and linking of NSD with associated publication citations enables transparency. The quality review contributes to enhanced text mining methods for identifier extraction and use. Furthermore, the global provision and use of NSD enables scientists around the world to join literature and sequence databases in a multidimensional fashion. As a concrete use case, statistics of country clusters were visualized with respect to NSD access in the context of discussions around digital sequence information under the United Nations Convention on Biological Diversity.