bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experience With “Jaw in a Day” Technique
Authors: Sukato Daniel C. , Hammer Daniel , Wang Weitao , Shokri Tom , Williams Fayette , Ducic Yadranko 
Published: March 2020

AbstractThe “Jaw in a Day” (JIAD) technique, first described by Levine and colleagues, establishes immediate functional occlusion through a single-stage maxillomandibular reconstruction with concurrent implant placement and provisional prosthesis delivery. In this study, the authors describe 2 cases exemplifying the reconstructive principles of JIAD. One patient underwent mandibular reconstruction with the JIAD technique and another patient underwent JIAD with an optimized rapid sequence computer-aided design and computer-aided manufacturing (CAD-CAM) for composite maxillomandibular reconstruction. Immediate implant-borne prosthesis was fixated and all implants osseointegrated into the neomandible. Although the authors’ patient outcomes are consistent with the literature, the published reports of JIAD remain limited, and further studies are required to assess the long-term functional and aesthetic outcomes as well as cost-effectiveness of this approach.
Effect of Deviated Nasal Septum on Choriodal Thickness
Authors: Şahin Ender , Songur Murat Serkan , Kantekin Yunus , Bayhan Hasan Ali , Can Ilknur Haberal 
Published: March 2020

Introduction:
Nasal septal deviation (NSD) is one of the major causes of upper airway obstruction. Chronic hypoxia and hypercapnia due to NSD may affect the choroidal blood flow and may change the choroidal thickness (CT). In this study, the authors aimed to research the assessment of CT before and after septoplasty in patients with NSD.

Methods:
Ninety-two patients who underwent septoplasty surgery with the diagnose of nasal septum deviation and 58 patients for control group were enrolled to the study. CT values measured before and three months after septoplasty surgery.

Results:
CT values were subfoveal 272.51 ± 27.62, nasal 245.50 ± 21.22, temporal 248.35 ± 30.25 and subfoveal 232.09 ± 44.17, nasal 222.09 ± 38.82,temporal 227.12 ± 28.80 for the control and NSD groups, respectively (P < 0.001). Also choroid thickness values (subfoveal 232.09 ± 44.17, nasal 222.09 ± 38.82, temporal 227.12 ± 28.80; subfoveal 252 ± 18.90, nasal 228 ± 22.12, temporal 240 ± 25.80) were significantly different in patients with NSD, before and after septoplasty procedure, respectively (P < 0.001).

Conclusion:
To the authors’ knowledge this is the first study investigating choroid thickness measurements before and after septoplasty in patients with NSD. We found significant correlation between NSD and CT. After septoplasty surgery at 3rd month, CT increased significantly in comparision with the preoperative values.
Elevated Intracranial Pressure Associated With Exogenous Hormonal Therapy Used for Gender Affirmation
Authors: Nguyen Huy V. , Gilbert Aubrey L. , Fortin Elizabeth , Vodopivec Ivana , Torun Nurhan , Chwalisz Bart K. , Cestari Dean M. , Rizzo Joseph F. 
Published: April 2020

Background:
Addison disease, corticosteroid withdrawal, and taking synthetic growth hormone have been linked with development of intracranial hypertension, but there is still debate on whether administration of other exogenous hormones plays a role in precipitating elevated pressure. The growing use of hormonal therapy for gender affirmation provides an opportunity to explore this possibility.

Methods:
All transgender patients taking exogenous hormones for female-to-male (FTM) and male-to-female (MTF) transitions who were diagnosed with intracranial hypertension at Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital and Beth Israel Deaconess Medical Center between August 2014 and November 2018 were included in a retrospective review. Visual acuity, type, and dose of exogenous hormone, visual field testing, clinical exam, results of neuroimaging and lumbar puncture, and treatment modalities were catalogued and analyzed.

Results:
Six transgender individuals were identified. Five were FTM, with an average hormone treatment time of 18.4 months, and one was MTF who had been treated with hormones for 4 years. The average age of all patients was 23.5 years. The average time between onset of symptoms and presentation was 5 months. Fifty percent of the patients reported pulse-synchronous tinnitus, 83% reported positional headache, 33% reported transient visual obscurations, and 16% reported diplopia. Lumbar punctures performed on 4 of the patients revealed elevated opening pressures and normal cerebrospinal fluid constituents. MRI findings consistent with elevated intracranial pressure (ICP) were present in the other 2 patients in whom lumbar puncture was unsuccessful. Four patients were treated with acetazolamide and one was treated with topiramate, with an average follow-up time of 15.7 months. All patients demonstrated bilateral optic disc swelling, and all maintained normal acuity and color vision. Performance on visual field testing was not significantly affected in any patient.

Conclusions:
This is the largest reported series to date of gender-transitioning patients with intracranial hypertension, including one novel MTF conversion. These observations warrant further investigation into the possible link of exogenous hormonal therapy and elevated ICP and any mechanisms or confounders underlying this potential association.
A novel germline mutation in thePOT1gene predisposes to familial non-medullary thyroid cancer
Authors: Srivastava Aayushi , Miao Beiping , Skopelitou Diamanto , Kumar Varun , Kumar Abhishek , Paramasivam Nagarajan , Bonora Elena , Hemminki Kari , Försti Asta , Bandapalli Obul Reddy 
Published: March 2020

AbstractNon-medullary thyroid cancer (NMTC) is a common endocrine malignancy with a genetic basis that has yet to be unequivocally established. In a recent whole genome sequencing study of five families with recurrence of NMTCs, we shortlisted promising variants with the help of bioinformatics tools. Here, we reportin silicoanalyses andin vitroexperiments on a novel germline variant (p.V29L) in the highly conserved oligonucleotide/oligosaccharide binding domain of theProtection of Telomeres 1 (POT1)gene in one of the families. The results showed that the variant demonstrates a reduction in telomere-bound POT1 levels in the mutant protein as compared to its wild-type counterpart. HEK293Tcells carryingPOT1V29Lshowed increased telomere length in comparison to wild type cells, strongly suggesting that the mutation causes telomere dysfunction and may play a role in predisposition to NMTC in this family. This study reports the first germlinePOT1mutation in a family with a predominance of thyroid cancer, thereby expanding the spectrum of cancers associated with mutations in the shelterin complex.
Modeling of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Proteins by Machine Learning and Physics-Based Refinement
Authors: Heo Lim , Feig Michael 
Published: March 2020

ABSTRACTProtein structures are crucial for understanding their biological activities. Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent need to understand the biological behavior of the virus and provide a basis for developing effective therapies. Since the proteome of the virus was determined, some of the protein structures could be determined experimentally, and others were predicted via template-based modeling approaches. However, tertiary structures for several proteins are still not available from experiment nor they could be accurately predicted by template-based modeling because of lack of close homolog structures. Previous efforts to predict structures for these proteins include efforts by DeepMind and the Zhang group via machine learning-based structure prediction methods, i.e. AlphaFold and C-I-TASSER. However, the predicted models vary greatly and have not yet been subjected to refinement. Here, we are reporting new predictions from our in-house structure prediction pipeline. The pipeline takes advantage of inter-residue contact predictions from trRosetta, a machine learning-based method. The predicted models were further improved by applying molecular dynamics simulation-based refinement. We also took the AlphaFold models and refined them by applying the same refinement method. Models based on our structure prediction pipeline and the refined AlphaFold models were analyzed and compared with the C-I-TASSER models. All of our models are available athttps://github.com/feiglab/sars-cov-2-proteins.
Structure-Based Design, Synthesis and Biological Evaluation of Peptidomimetic Aldehydes as a Novel Series of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease
Authors: Dai Wenhao , Zhang Bing , Jiang Xia-Ming , Su Haixia , Li Jian , Zhao Yao , Xie Xiong , Jin Zhenming , Peng Jingjing , Liu Fengjiang , Li Chunpu , Li You , Bai Fang , Wang Haofeng , Chen Xi , Cen Xiaobo , Hu Shulei , Yang Xiuna , Wang Jiang , Liu Xiang , Xiao Gengfu , Jiang Hualiang , Rao Zihe , Zhang Lei-Ke , Xu Yechun , Yang Haitao , Liu Hong 
Published: March 2020

ABSTRACTSARS-CoV-2 is the etiological agent responsible for the COVID-19 outbreak in Wuhan. Specific antiviral drug are urgently needed to treat COVID-19 infections. The main protease (Mpro) of SARS-CoV-2 is a key CoV enzyme that plays a pivotal role in mediating viral replication and transcription, which makes it an attractive drug target. In an effort to rapidly discover lead compounds targeting Mpro, two compounds (11aand11b) were designed and synthesized, both of which exhibited excellent inhibitory activity with an IC50 value of 0.05 μM and 0.04 μM respectively. Significantly, both compounds exhibited potent anti-SARS-CoV-2 infection activity in a cell-based assay with an EC50 value of 0.42 μM and 0.33 μM, respectively. The X-ray crystal structures of SARS-CoV-2 Mproin complex with11aand11bwere determined at 1.5 Å resolution, respectively. The crystal structures showed that11aand11bare covalent inhibitors, the aldehyde groups of which are bound covalently to Cys145 of Mpro. Both compounds showed good PK properties invivo, and11aalso exhibited low toxicity which is promising drug leads with clinical potential that merits further studies.
Molecular and functional diversity of distinct subpopulations of extracellular vesicles from stressed pancreatic beta cells: implications for autoimmunity
Authors: Giri Khem Raj , de Beaurepaire Laurence , Jegou Dominique , Lavy Margot , Mosser Mathilde , Dupont Aurelien , Fleurisson Romain , Dubreil Laurence , Collot Mayeul , Van Endert Peter , Bach Jean-Marie , Mignot Gregoire , Bosch Steffi 
Published: March 2020

AbstractBeta cell failure and apoptosis following islet inflammation have been associated with autoimmune type 1 diabetes pathogenesis. As conveyors of biological active material, extracellular vesicles (EV) act as mediators in communication with immune effectors fostering the idea that EV from inflamed beta cells may contribute to autoimmunity. Evidence accumulates that beta exosomes promote diabetogenic responses, but relative contributions of larger vesicles as well as variations in the composition of the beta cell’s vesiculome due to environmental changes have not been explored yet. Here, we made side-by-side comparisons of the phenotype and function of apoptotic bodies (AB), microvesicles (MV) and small EV (sEV) isolated from an equal amount of MIN6 beta cells exposed to inflammatory, hypoxic or genotoxic stressors. Under normal conditions, large vesicles represent 93% of the volume, but only 2% of the number of the vesicles. Our data reveal a consistently higher release of AB and sEV and to a lesser extent of MV, exclusively under inflammatory conditions commensurate with a 4-fold increase in the total volume of the vesiculome and enhanced export of immune-stimulatory material including the autoantigen insulin, microRNA, and cytokines. Whilst inflammation does not change the concentration of insulin inside the EV, specific Toll-like receptor-binding microRNA sequences preferentially partition into sEV. Exposure to inflammatory stress engenders drastic increases in the expression of monocyte chemoattractant protein 1 in all EV and of interleukin-27 solely in AB suggesting selective sorting towards EV subspecies. Functional in vitro assays in mouse dendritic cells and macrophages reveal further differences in the aptitude of EV to modulate expression of cytokines and maturation markers. These findings highlight the different quantitative and qualitative imprints of environmental changes in subpopulations of beta EV that may contribute to the spread of inflammation and sustained immune cell recruitment at the inception of the (auto-) immune response.Graphical AbstractInflammation stimulates release of a heterogeneous population of beta EV with differential expression of immunogenic substances involved in immune cell recruitment and activation.HighlightsStress engenders an up to four-fold increase in the volume of the vesiculome and enhanced auto-antigen releaseCytokines are selectively sorted into EV subspeciesTLR-binding microRNAs are enriched in sEVEV from stressed beta cells promote dendritic and macrophage cell activation
Sensorimotor conflicts induce somatic passivity and louden quiet voices in healthy listeners
Authors: Orepic Pavo , Rognini Giulio , Kannape Oliver Alan , Faivre Nathan , Blanke Olaf 
Published: March 2020

AbstractSensorimotor conflicts are known to alter the perception of accompanying sensory signals and deficits in sensory attenuation have been observed in schizophrenia. In the auditory domain, self-generated tones or voices (compared to tones or voices presented passively or with sensorimotor delays) have been associated with changes in loudness perception and attenuated neural responses. It has been argued that for sensory signals to be attenuated, predicted and sensory consequences must have a consistent spatiotemporal relationship, between button presses and reafferent tactile signals, via predictive sensory signaling, a process altered in schizophrenia. Here, we investigated auditory sensory attenuation for a series of morphed voices while healthy participants applied sensorimotor stimulations that had no spatiotemporal relationship to the voice stimuli and that have been shown to induce mild psychosis-like phenomena. In two independent groups of participants, we report a loudening of silent voices and found this effect only during maximal sensorimotor conflicts (versus several control conditions). Importantly, conflicting sensorimotor stimulation also induced a mild psychosis-like state in the form of somatic passivity and participants who experienced stronger passivity lacked the sensorimotor loudening effect. We argue that this conflict-related sensorimotor loudness amplification may represent a reduction of auditory self-attenuation that is lacking in participants experiencing a concomitant mild psychosis-like state. We interpret our results within the framework of the comparator model of sensorimotor control, and discuss the implications of our findings regarding passivity experiences and hallucinations in schizophrenia.
Mps1 expression is critical for chromosome orientation and segregation in yeast with high ploidy
Authors: Sartin Ashlea , Gish Madeline , Harsha Jillian , Haworth Dawson , LaVictoire Rebecca , Meyer Régis E 
Published: March 2020

AbstractIn aneuploid cancer cells, the chromosome segregation apparatus is sensitive to increased chromosome number. The conserved protein kinase, Mps1, is a critical actor of this machinery, orienting the chromosomes properly on the spindle. Abnormally high levels of this kinase have been found in tumors with elevated chromosome number. However, it remains unclear, mechanistically, if and how cells with higher ploidy become dependent upon increased Mps1 levels. To answer these questions, we explored Mps1 dependence in yeast cells with increased sets of chromosomes. We discovered that having more chromosomes affects the ability of cells to orient chromosomes properly. The cells with increased numbers of chromosomes are particularly sensitive to the reduction of Mps1 activity. Inmps1loss of function mutants, cells display an extended prometaphase with a longer spindle and a delay in orienting properly the chromosomes. Altogether, our results suggest that increased numbers of chromosomes render cells more dependent on Mps1 for orienting chromosomes on the spindle. The phenomenon described here may be relevant in understanding why hyperdiploid cancer cells become excessively reliant on high Mps1 expression for successful chromosome segregation.Author summaryMost cells in solid tumors usually carry far more chromosomes than normal cells. Losing or gaining chromosomes during cell division can lead to aneuploidy (an abnormal number of chromosomes), cancer, and other diseases. Mps1 is a master regulator of cell division that is critical to keep the correct number chromosomes in each daughter cell. This master regulator has been shown to target and affect the function of various actors involved in cell division. Abnormally high levels of this master regulator are found in tumors with elevated chromosome numbers. The high levels of this regulator appear to be protecting these tumor cells. To answer if and how cells with higher ploidy become so dependent of Mps1, we generated yeast cells with increased set of chromosomes. Here, we report that cells with elevated chromosome number are particularly sensitive to the reduction of Mps1 level. In cells with higher ploidy and reduced level of Mps1, the progression during cell division is delayed. In the mutant cells, their ability to properly orient and segregate their chromosomes on the spindle is greatly reduced.
Behavioral, physiological, and neural signatures of surprise during naturalistic sports viewing
Authors: Antony James W. , Hartshorne Thomas H. , Pomeroy Ken , Gureckis Todd M. , Hasson Uri , McDougle Samuel D. , Norman Kenneth A. 
Published: March 2020

SummarySurprise signals a discrepancy between past and current beliefs. It is theorized to be linked to affective experiences, the creation of particularly resilient memories, and segmentation of the flow of experience into discrete perceived events. However, the ability to precisely measure naturalistic surprise has remained elusive. We used advanced basketball analytics to derive a quantitative measure of surprise and characterized its behavioral, physiological, and neural correlates in human subjects observing basketball games. We found that surprise was associated with segmentation of ongoing experiences, as reflected by subjectively perceived event boundaries and shifts in neocortical patterns underlying belief states. Interestingly, these effects differed by whether surprising moments contradicted or bolstered current predominant beliefs. Surprise also positively correlated with pupil dilation, activation in subcortical regions associated with dopamine, game enjoyment, and long-term memory. These investigations support key predictions from event segmentation theory and extend theoretical conceptualizations of surprise to real-world contexts.
Ultrasensitive small molecule fluorogenic probe for human heparanase
Authors: Liu Jun , Schleyer Kelton A. , Bryan Tyrel L. , Xie Changjian , Seabra Gustavo , Xu Yongmei , Kafle Arjun , Cui Chao , Wang Ying , Yin Kunlun , Fetrow Benjamin , Henderson Paul K. P. , Fatland Peter Z. , Liu Jian , Li Chenglong , Guo Hua , Cui Lina 
Published: March 2020

AbstractHeparanase is a critical enzyme involved in the remodeling of the extracellular matrix (ECM), and its elevated expression has been linked with diseases such as cancer and inflammation. The detection of heparanase enzymatic activity holds tremendous value in the study of the cellular microenvironment, and search of molecular therapeutics targeting heparanase, however, assays developed for this enzyme so far have suffered prohibitive drawbacks. Here we present an ultrasensitive fluorogenic small-molecule probe for heparanase enzymatic activity. The probe exhibits a 756-fold fluorescence turn-on response in the presence of human heparanase, allowing one-step detection of heparanase activity in real-time with a picomolar detection limit. The high sensitivity and robustness of the probe are exemplified in a high-throughput screening assay for heparanase inhibitors.
Design of potent membrane fusion inhibitors against SARS-CoV-2, an emerging coronavirus with high fusogenic activity
Authors: Zhu Yuanmei , Yu Danwei , Yan Hongxia , Chong Huihui , He Yuxian 
Published: March 2020

AbstractThe coronavirus disease COVID-19, caused by emerging SARS-CoV-2, has posed serious threats to global public health, economic and social stabilities, calling for the prompt development of therapeutics and prophylactics. In this study, we firstly verified that SARS-CoV-2 uses human ACE2 as a cell receptor and its spike (S) protein mediates high membrane fusion activity. Comparing to that of SARS-CoV, the heptad repeat 1 (HR1) sequence in the S2 fusion protein of SARS-CoV-2 possesses markedly increased α-helicity and thermostability, as well as a higher binding affinity with its corresponding heptad repeat 2 (HR1) site. Then, we designed a HR2 sequence-based lipopeptide fusion inhibitor, termed IPB02, which showed highly poent activities in inibibiting the SARS-CoV-2 S protein-mediated cell-cell fusion and pseudovirus infection. IPB02 also inhibited the SARS-CoV pseudovirus efficiently. Moreover, the strcuture and activity relationship (SAR) of IPB02 were characterzized with a panel of truncated lipopeptides, revealing the amino acid motifs critical for its binding and antiviral capacities. Therefore, the presented results have provided important information for understanding the entry pathway of SARS-CoV-2 and the design of antivirals that target the membrane fusion step.
The roles of online and offline replay in planning
Authors: Eldar Eran , Lièvre Gaëlle , Dayan Peter , Dolan Raymond J. 
Published: March 2020

AbstractAnimals and humans replay neural patterns encoding trajectories through their environment, both whilst they solve decision-making tasks and during rest. Both on-task and off-task replay are believed to contribute to flexible decision making, though how their relative contributions differ remains unclear. We investigated this question by using magnetoencephalography to study human subjects while they performed a decision-making task that was designed to reveal the decision algorithms employed. We characterized subjects in terms of how flexibly each adjusted their choices to changes in temporal, spatial and reward structure. The more flexible a subject, the more they replayed trajectories during task performance, and this replay was coupled with re-planning of the encoded trajectories. The less flexible a subject, the more they replayed previously and subsequently preferred trajectories during rest periods between task epochs. The data suggest that online and offline replay both participate in planning but support distinct decision strategies.