bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gestational gigantomastia—a rare entity complicated by life-threatening haemorrhage
Authors: Neblett Carlos , Venugopal Rajeev , Johnson Miguel , Mitchell Derek , Kunc Vojtech 
Published: April 2021

Abstract
Gestational gigantomastia is a psychologically and physically debilitating disease of unknown aetiology. Underlying diseases that present as gigantomastia should be excluded by a thorough workup. Most cases respond to the preferred approach: conservative management, as foetal viability and well-being is of significant importance. However, in those cases where the maternal mortality is at risk, the surgical approach is preferred. Life-threatening haemorrhage may occur and early recognition and treatment is paramount to outcome. A case of gestational gigantomastia complicated by life-threatening haemorrhage is presented and discussed.
Large-Scale Phylogenomic Analyses Reveal the Monophyly of Bryophytes and Neoproterozoic Origin of Land Plants
Authors: Su Danyan , Yang Lingxiao , Shi Xuan , Ma Xiaoya , Zhou Xiaofan , Hedges S Blair , Zhong Bojian 
Published: April 2021

AbstractThe relationships among the four major embryophyte lineages (mosses, liverworts, hornworts, vascular plants) and the timing of the origin of land plants are enigmatic problems in plant evolution. Here, we resolve the monophyly of bryophytes by improving taxon sampling of hornworts and eliminating the effect of synonymous substitutions. We then estimate the divergence time of crown embryophytes based on three fossil calibration strategies, and reveal that maximum calibration constraints have a major effect on estimating the time of origin of land plants. Moreover, comparison of priors and posteriors provides a guide for evaluating the optimal calibration strategy. By considering the reliability of fossil calibrations and the influences of molecular data, we estimate that land plants originated in the Precambrian (980–682 Ma), much older than widely recognized. Our study highlights the important contribution of molecular data when faced with contentious fossil evidence, and that fossil calibrations used in estimating the timescale of plant evolution require critical scrutiny.
Genomic Basis of Striking Fin Shapes and Colors in the Fighting Fish
Authors: Wang Le , Sun Fei , Wan Zi Yi , Ye Baoqing , Wen Yanfei , Liu Huiming , Yang Zituo , Pang Hongyan , Meng Zining , Fan Bin , Alfiko Yuzer , Shen Yubang , Bai Bin , Lee May Shu Qing , Piferrer Francesc , Schartl Manfred , Meyer Axel , Yue Gen Hua 
Published: April 2021

Abstract
Resolving the genomic basis underlying phenotypic variations is a question of great importance in evolutionary biology. However, understanding how genotypes determine the phenotypes is still challenging. Centuries of artificial selective breeding for beauty and aggression resulted in a plethora of colors, long-fin varieties, and hyper-aggressive behavior in the air-breathing Siamese fighting fish (Betta splendens), supplying an excellent system for studying the genomic basis of phenotypic variations. Combining whole-genome sequencing, quantitative trait loci mapping, genome-wide association studies, and genome editing, we investigated the genomic basis of huge morphological variation in fins and striking differences in coloration in the fighting fish. Results revealed that the double tail, elephant ear, albino, and fin spot mutants each were determined by single major-effect loci. The elephant ear phenotype was likely related to differential expression of a potassium ion channel gene, kcnh8. The albinotic phenotype was likely linked to a cis-regulatory element acting on the mitfa gene and the double-tail mutant was suggested to be caused by a deletion in a zic1/zic4 coenhancer. Our data highlight that major loci and cis-regulatory elements play important roles in bringing about phenotypic innovations and establish Bettas as new powerful model to study the genomic basis of evolved changes.
PLIP 2021: expanding the scope of the protein–ligand interaction profiler to DNA and RNA
Authors: Adasme Melissa F , Linnemann Katja L , Bolz Sarah Naomi , Kaiser Florian , Salentin Sebastian , Haupt V Joachim , Schroeder Michael 
Published: April 2021

AbstractWith the growth of protein structure data, the analysis of molecular interactions between ligands and their target molecules is gaining importance. PLIP, the protein–ligand interaction profiler, detects and visualises these interactions and provides data in formats suitable for further processing. PLIP has proven very successful in applications ranging from the characterisation of docking experiments to the assessment of novel ligand–protein complexes. Besides ligand–protein interactions, interactions with DNA and RNA play a vital role in many applications, such as drugs targeting DNA or RNA-binding proteins. To date, over 7% of all 3D structures in the Protein Data Bank include DNA or RNA. Therefore, we extended PLIP to encompass these important molecules. We demonstrate the power of this extension with examples of a cancer drug binding to a DNA target, and an RNA–protein complex central to a neurological disease. PLIP is available online at https://plip-tool.biotec.tu-dresden.de and as open source code. So far, the engine has served over a million queries and the source code has been downloaded several thousand times.
Meclofenamate causes loss of cellular tethering and decoupling of functional networks in glioblastoma
Authors: Schneider Matthias , Vollmer Lea , Potthoff Anna-Laura , Ravi Vidhya M , Evert Bernd O , Rahman Mohummad A , Sarowar Shahin , Kueckelhaus Jan , Will Paulina , Zurhorst David , Joseph Kevin , Maier Julian P , Neidert Nicolas , d’Errico Paolo , Meyer-Luehmann Melanie , Hofmann Ulrich G , Dolf Andreas , Salomoni Paolo , Güresir Erdem , Enger Per Ø , Chekenya Martha , Pietsch Torsten , Schuss Patrick , Schnell Oliver , Westhoff Mike-Andrew , Beck Jürgen , Vatter Hartmut , Waha Andreas , Herrlinger Ulrich , Heiland Dieter H 
Published: April 2021

Abstract

Background
Glioblastoma cells assemble to a syncytial communicating network based on tumor microtubes (TMs) as ultra-long membrane protrusions. The relationship between network architecture and transcriptional profile remains poorly investigated. Drugs that interfere with this syncytial connectivity such as meclofenamate (MFA) may be highly attractive for glioblastoma therapy.

Methods
In a human neocortical slice model using glioblastoma cell populations of different transcriptional signatures, three-dimensional tumor networks were reconstructed, and TM-based intercellular connectivity was mapped on the basis of two-photon imaging data. MFA was used to modulate morphological and functional connectivity; downstream effects of MFA treatment were investigated by RNA sequencing and fluorescence-activated cell sorting (FACS) analysis.

Results
TM-based network morphology strongly differed between the transcriptional cellular subtypes of glioblastoma and was dependent on axon guidance molecule expression. MFA revealed both a functional and morphological demolishment of glioblastoma network architectures which was reflected by a reduction of TM-mediated intercellular cytosolic traffic as well as a breakdown of TM length. RNA sequencing confirmed a downregulation of NCAM and axon guidance molecule signaling upon MFA treatment. Loss of glioblastoma communicating networks was accompanied by a failure in the upregulation of genes that are required for DNA repair in response to temozolomide (TMZ) treatment and culminated in profound treatment response to TMZ-mediated toxicity.

Conclusion
The capacity of TM formation reflects transcriptional cellular heterogeneity. MFA effectively demolishes functional and morphological TM-based syncytial network architectures. These findings might pave the way to a clinical implementation of MFA as a TM-targeted therapeutic approach.
Tobacco transcription factor bHLH123 improves salt tolerance by activating NADPH oxidase NtRbohE expression
Authors: Liu Dan , Li Yang-Yang , Zhou Zhi-Cheng , Xiang Xiaohua , Liu Xin , Wang Jie , Hu Zheng-Rong , Xiang Shi-Peng , Li Wei , Xiao Qin-Zhi , Wang Yuanying , Hu Ri-Sheng , Zhao Qiang 
Published: April 2021

Abstract
In plants, reactive oxygen species (ROS) produced following the expression of the respiratory burst oxidase homolog (Rboh) gene are important regulators of stress responses. However, little is known about how plants acclimate to salt stress through the Rboh-derived ROS signaling pathway. Here, we showed that a 400-bp fragment of the tobacco (Nicotiana tabacum) NtRbohE promoter played a critical role in the salt response. Using yeast one-hybrid (Y1H) screens, NtbHLH123, a bHLH transcription factor, was identified as an upstream partner of the NtRbohE promoter. These interactions were confirmed by Y1H, electrophoretic mobility assay, and chromatin immunoprecipitation assays. Overexpression of NtbHLH123 resulted in greater resistance to salt stress, while NtbHLH123-silenced plants had reduced resistance to salt stress. We also found that NtbHLH123 positively regulates the expression of NtRbohE and ROS production soon after salt stress treatment. Moreover, knockout of NtRbohE in the 35S::NtbHLH123 background resulted in reduced expression of ROS-scavenging and salt stress-related genes and salt tolerance, suggesting that NtbHLH123-regulated salt tolerance is dependent on the NtbHLH123-NtRbohE signaling pathway. Our data show that NtbHLH123 is a positive regulator and acts as a molecular switch to control a Rboh-dependent mechanism in response to salt stress in plants.
Business sectors’ initiatives on health and safety protocols and vaccination program among employees during the COVID-19 pandemic
Authors: Yutuc Alma V , Olazo Danzen B , Sarmiento Philip Joseph D 
Published: April 2021

Abstract
In a recent correspondence, the author discussed the issues of ‘no-jab, no job’ policy, which is planned to be implemented by governments and companies in many countries. This paper highlights the business sectors’ initiatives in ensuring the implementation of health and safety protocols and vaccination program among employees during the COVID-19 pandemic.
Functional plasticity in lateral hypothalamus and its prediction of cognitive impairment in patients with diffuse axonal injury: evidence from a resting-state functional connectivity study
Authors: Wang Yao , Zhou Fuqing , Li Yan , Li Jian , Kuang Hongmei , Chen Qi , Hong Tao , Gong Honghan 
Published: April 2021

Objective
Diffuse axonal injury (DAI) is a common pathological process after traumatic brain injury, which may cause survivors severe functional disorders, including cognitive impairment and physical disability. Recent literature indicated lateral hypothalamus and medial hypothalamus damage during DAI. Thus, we aim to investigate whether there is imaging evidence of hypothalamic injury in patients with DAI and its clinical association.

Methods
Twenty-four patients with diagnosed DAI and 26 age and sex-matched healthy controls underwent resting-state functional MRI. We assessed the lateral hypothalamus and medial hypothalamus functional connectivity with seed-based analysis in DAI. Furthermore, a partial correlation was used to measure its clinical association. The prediction of the severity of DAI from the altered lateral hypothalamus and medial hypothalamus connectivity was conducted using a general linear model.

Results
Compared with healthy control, the DAI group showed significantly decreased lateral hypothalamus functional connectivity with the basal ganglia and cingulate gyrus, which was positively correlated with mini-mental state examination scores (Bonferroni correction at P < 0.0125). Importantly, this disrupted functional connectivity can be used to predict the patients’ cognitive state reliably (P = 0.006; P = 0.009, respectively) in DAI. Moreover, we also observed increased connectivity of medial hypothalamus with the superior temporal gyrus and the regions around the operculum. Furthermore, there was a trend of negative correlation between the medial hypothalamus functional connectivity changes to the right superior temporal gyrus and the disability rating scale scores in the DAI group.

Conclusion
Our results suggest that there are alterations of medial hypothalamus and lateral hypothalamus connectivity in DAI and further understand its clinical symptoms, including related cognitive impairment.
Detection of SARS-CoV-2 specific IgA in the human milk of COVID-19 vaccinated, lactating health care workers
Authors: Valcarce Vivian , Stafford Lauren S. , Neu Josef , Cacho Nicole , Parker Leslie , Mueller Martina , Burchfield David J , Li Nan , Larkin Joseph 
Published: April 2021

ABSTRACTImportanceIn 2019, a deadly virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for COVID-19, emerged. In December 2020, two mRNA-based COVID-19 vaccines were approved for use in the United States (US) which provide immunity to those receiving the vaccine. Maternally derived antibodies are a key element of infants’ immunity. Certain vaccines given to pregnant and lactating mothers provide immunity to infants through transmission across the placenta, umbilical cord (IgG) and human milk (IgA). Human milk produced by mothers with a history of COVID-19 infection contains SARS-CoV-2 IgA and IgG.ObjectiveTo determine whether SARS-CoV-2 specific immunoglobulins are found in human milk after the COVID-19 vaccination, and to characterize the types of immunoglobulins present.Design, setting, and participantsThis is a prospective observational study conducted at Shands Hospital, University of Florida from December 2020 to March 2021. Twenty-two lactating healthcare workers who received the SARS-CoV-2 mRNA vaccine (Pfizer/BioNtech or Moderna) made up the sample group. Plasma and human milk were collected at three-time points (pre-vaccination, post-first vaccine dose, and post-second vaccine dose). SARS-CoV-2 specific IgA and IgG in human milk and in plasma were measured by ELISA. Maternal demographics was compiled.ExposuresPfizer/BioNtech or Moderna vaccination.Main outcome and measureLevels of SARS-CoV-2 IgA and IgG in human milk and plasma.ResultsWe found significant secretion of SARS-CoV-2 specific IgA and IgG in human milk and plasma after SARS-CoV-2 vaccination.Conclusions and relevanceOur results show that the mRNA-based COVID-19 vaccines induce SARS-CoV-2 specific IgA and IgG secretion in human milk. Further studies are needed to determine the duration of this immune response, its capacity to neutralize the COVID-19 virus, the transfer of passive immunity to breastfeeding infants, and the potential therapeutic use of human milk IgA to combat SARS-CoV-2 infections and COVID-19.KEY POINTSQuestionIs there SARS-CoV-2 specific IgA in the human milk of lactating women after COVID-19 vaccination?FindingsIn this prospective observational study that included 22 lactating women, we found SARS-CoV-2 specific IgA in the human milk in response to the COVID-19 vaccination series. There is statistically significant secretion of SARS-CoV-2 IgA in human milk after mRNA COVID-19 vaccination series completion (p < 0.0001).MeaningNewborn immunologic defense is present but immature. SARS-CoV-2 IgA secreted in the human milk could potentially provide COVID-19 protection to nursing infants. These results could guide a strategy for SARS-CoV-2 vaccination among lactating women.
Detection of SARS-CoV-2 variant 501Y.V2 in Comoros Islands in January 2021
Authors: Agoti Charles N. , Githinji George , Mohammed Khadija S. , Lambisia Arnold L. , de Laurent Zaydah R. , Mburu Maureen W. , Ong’era Edidah M. , Morobe John M. , Otieno Edward , Azali Hamza Abdou , Abdallah Kamal Said , Diarra Abdoulaye , Yahaya Ali Ahmed , Athanasius Dratibi Fred , Moeletsi Nicksy Gumede , Tsofa Benjamin , Bejon Philip , Borus Peter , Nokes D. James , Ochola-Oyier Isabella 
Published: April 2021

AbstractPhylogenetic analysis of six SARS-CoV-2 genomes collected from the Comoros islands confirmed local circulation of the 501Y.V2 variant of concern during the country’s first major SARS-CoV-2 wave in January 2021. These findings demonstrate the importance of SARS-CoV-2 genomic surveillance and have implications for ongoing COVID-19 control strategies on the islands.Article summary lineCirculation of SARS-CoV-2 501Y.V2 variant of concern in the Comoros Islands during a major COVID-19 infection wave in January 2021
The emergence of SARS-CoV-2 variant(s) and its impact on the prevalence of COVID-19 cases in Nabatieh region, Lebanon
Authors: Noureddine Fatima Y. , Chakkour Mohamed , El Roz Ali , Reda Jana , Al Sahily Reem , Assi Ali , Joma Mohamed , Salami Hassan , Hashem Sadek J. , Harb Batoul , Salami Ali , Ghssein Ghassan 
Published: April 2021

AbstractBackgroundAn outbreak of an unknown respiratory illness caused by a novel corona-virus, SARS-CoV-2, emerged in the city of Wuhan in Hubei province, China, in December 2019 and was referred to as coronavirus disease-2019 (COVID-19). Soon after, it was declared as a global pandemic by the World Health Organization (WHO) in March 2020. SARS-CoV-2 mainly infects the respiratory tract with different outcomes ranging from asymptomatic infection to severe critical illness leading to death. Different SARS-CoV-2 variants are emerging of which three have raised concerns worldwide due to their high transmissibility among populations.ObjectiveTo study the prevalence of COVID-19 in the region of Nabatieh - South Lebanon during the past year and assess the presence of SARS-CoV-2 variants and their effect on the spread of infection during times of lock-down. Methods: In our study, 37,474 nasopharyngeal swab samples were collected and analyzed for the detection of SARS-CoV-2 virus in suspected patients attending a tertiary health care center in South Lebanon during the period between March 16, 2020 and February 21, 2021.ResultsResults demonstrated a variation in the prevalence rates ranging from less than 1% during full lockdown of the country to 8.4% upon easing lockdown restrictions and reaching 27.5% after the holidays and 2021 New Year celebrations. Interestingly, a new variant(s) appeared starting January 2021 with a significant positive association between the prevalence of positive tests and the percentage of the variant(s).ConclusionOur results indicate that the lockdown implemented by the Lebanese officials presented an effective intervention to contain COVID-19 spread. Our study also showed that lifting lockdown measures during the holidays, which allowed indoor crowded gatherings to occur, caused a surge in COVID-19 cases and rise in the mortality rates nationwide. More importantly, we confirmed the presence of a highly transmissible SARS-CoV-2 variant(s) circulating in the Lebanese community, at least since January 2021 onwards.
Growth charts for individualized evaluation of brain morphometry for preschool children
Authors: Zhang Hongxi , Li Jia , Su Xiaoli , Hu Yang , Liu Tianmei , Ni Shaoqing , Li Haifeng , Zuo Xi-Nian , Fu Junfen , Yuan Ti-Fei , Yang Zhi 
Published: April 2021

AbstractBrain development from 1 to 6 years-of-age anchors the rapid development of a wide range of functional capabilities. However, quantitative growth charts of typical development during this age period are lacking, preventing the identification of early brain abnormalities. Here we characterize the time-dependent individual differences of cortical thickness and subcortical volume in 340 typically developing children and construct regional growth curves for these brain morphological measures. The growth curves reflect four types of time-dependence for cortical thickness and subcortical volume metrics. At the individual level, the growth curve model provides percentiles for each brain region’s cortical thickness or volume during ages 1 to 6, allowing for individualized inferences of brain developmental status relative to the same-age population. The growth curves further demonstrate clinical utility potentials by identifying children with developmental speech and language disorders, achieving high accuracies on data collected on both 1.5T and 3T scanners. Our results fill the knowledge gap in brain morphometrics in a critical development period and provide an avenue for individualized brain developmental status evaluation, with demonstrated sensitivity and generalizability.
Volumetric lung cancer screening reduces unnecessary low-dose computed tomography scans: results from a single-centre prospective trial on 4,119 subjects
Authors: Milanese Gianluca , Sabia Federica , Ledda Roberta Eufrasia , Sestini Stefano , Marchianò Alfonso Vittorio , Sverzellati Nicola , Pastorino Ugo 
Published: April 2021

AbstractPurposeTo compare low-dose computed tomography (LDCT) outcome and volume-doubling time (VDT) derived from measured volume (MV) and estimated volume (EV) of pulmonary nodules (PN) detected in a single-centre lung cancer screening trial.Materials and MethodsMV, EV and VDT were obtained for prevalent pulmonary nodules detected at the baseline round of the bioMILD trial. LDCT outcome (based on bioMILD thresholds) and VDT categories were simulated on a PN- and a screenees-based analysis. Weighted Cohen’s kappa test was used to assess the agreement between diagnostic categories as per MV and EV.Results1,583 screenees displayed 2,715 pulmonary nodules. On a PN-based analysis 40.1% PNs would have been included in different LDCT categories if measured by MV or EV. Agreement between MV and EV was moderate (κ = 0.49) and fair (κ = 0.37) for LDCT outcome and VDT categories, respectively.On a screenees-based analysis, 46% pulmonary nodules would have been included in different LDCT categories if measured by MV or EV. Agreement between MV and EV was moderate (κ = 0.52) and fair (κ = 0.34) for LDCT outcome and VDT categories, respectively.ConclusionsWithin a simulated lung cancer screening based on recommendation by estimated volumetry, the number of LDCT performed for the evaluation of pulmonary nodules would be higher as compared to the prospective volumetric management.
The Impact of HPV DNA/p16 in Laryngeal/Hypopharyngeal Cancer: a Systematic Review and Meta-analysis
Authors: Van der Elst Sarah , Russo Daniel P. , Mumaw Derek , Wotman Michael , Tham Tristan 
Published: April 2021

AbstractBackgroundThis meta-analysis seeks to investigate the association between HPV and p16 status with overall survival in laryngeal and hypopharyngeal carcinoma.MethodsMedline, Scopus, EMBASE, and the Cochrane Library were used to identify studies for inclusion. Abstracts that discussed HPV/p16 status and prognosis in laryngeal or hypopharyngeal carcinoma were included. Next, full-text articles were screened and included based upon a checklist established a priori. Pooled hazard ratios for overall survival were generated using a random effects model. RevMan 5.3, Meta Essentials, and OpenMeta[Analyst] were used for statistical analysis.ResultsThirteen studies published between 2014 and 2019 with sample sizes ranging from 31 to 9,656 were selected for inclusion in this meta-analysis. The pooled data demonstrated that p16 status was not significantly associated with OS in either laryngeal or hypopharyngeal carcinoma with HRs of 1.03 (95% CI: 0.73–1.45; p = 0.88) and 1.02 (95% CI: 0.55–1.86; p = 0.96), respectively. The pooled data showed that HPV status was predictive of OS in laryngeal cancer with 0.63 (95% CI: 0.41–0.97; p = 0.03).ConclusionsOur results suggest that p16-positivity does not provide a survival benefit in LC and HPC. This is in contrast to studies in the oropharynx, where p16 status is a standard proxy for HPV infection and HPV infection is associated with improved prognosis.