bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inverted Papilloma of the Orbit and Nasolacrimal System
Authors: Wang Jessie , Ford Joshua , Esmaeli Bita , Langer Paul , Esmaili Neda , Griepentrog Gregory J. , Couch Steven M. , Nguyen John , Gold Katherine G. , Duerksen Kathleen , Burkat Cat N. , Hartstein Morris E. , Gandhi Parag , Sobel Rachel K. , Moon Jee-Young , Barmettler Anne 
Published: June 2020

Purpose:
Periocular inverted papilloma (IP) is a rare, locally aggressive tumor with a propensity for recurrence and malignant transformation. Historically treated via wide excision, this study examines the characteristics and management of periocular IP, comparing those confined to the nasolacrimal system with those invading the orbit.

Methods:
An Institutional Review Board-approved, Health Insurance Portability and Accountability Act-compliant retrospective, comparative case series was conducted in patients with IP of the orbit or nasolacrimal system across 15 clinical sites.

Results:
Of 25 patients, 22 met inclusion criteria with 9 limited to the nasolacrimal system and 13 invading the orbit. Mean age was 60.4 years, 55% were women, all were unilateral. Mean follow-up was 48 months. Rates of smoking, dust and/or aerosol exposure, human papillomavirus (HPV) status, and inflammatory polyps were elevated compared to rates in the general population (45%, 18%, 18%, and 14%, respectively). Bony erosion on computed tomography scans was statistically significantly associated with orbit-invading IP (p = 0.002). Treatment involved all confined IP undergoing surgery alone while 39% of orbit-invading IP also received radiation therapy and/or chemotherapy (p = 0.054). Orbit-invading IP was more likely to be excised with wide margins than IP confined to the nasolacrimal system (85% vs. 22%, p = 0.007). Overall rates of malignancy, recurrence, and patient mortality from IP were found to be 27%, 23%, and 9%, respectively.

Conclusions:
IP invading the orbit typically requires aggressive therapy, while IP confined to the nasolacrimal system may be treated more conservatively. Using risk factors, characteristics, and outcomes, a treatment algorithm was created to guide management.
Age- and Sex-Related Development of the Normal Human Ear in a Child Population
Authors: Chunyang Xu , Lei Liu 
Published: June 2020

Background:
A large number of researches related to auricle development have been conducted in different countries, but there were few similar studies in China, especially in Chinese children. This study was designed to investigate the auricular development by measuring normal age- and sex-related dimensions of auricles in Chinese children.

Methods:
A total of 900 participants were evaluated according to their age and gender. From the landmarks, the dimensions of the and tragus including length and width, the relevant indices, inclination angles were measured. The average score of each item was calculated according to age and gender.

Results:
The dimensions of the and tragus including width and length showed certain developmental patterns respectively. No significantly difference was found for the inclination angles and relative indices between different age groups and different sides.

Conclusions:
The data indicated that there was a certain pattern of auricular development. There were also gender difference in the development of auricle. There were certain proportional relationships between different subunits of the auricle. These results may be useful for designing the plan of auricular reconstruction.
Three-Dimensional Evaluation on Cortical Bone During Orthodontic Surgical Treatment
Authors: Crimi Salvatore , Defila Luca , Nanni Martina , Cicciù Marco , Fiorillo Luca , Cervino Gabriele , Marchetti Claudio , Bianchi Alberto 
Published: June 2020

Abstract
Adult patients’ severe malocclusions, especially the skeletal ones, cannot be exclusively solved by the orthodontic treatment and therefore a combined orthodontic-surgical treatment is necessary. Today, numerous software allows to plane and to visualize the final treatment results simulating the best therapeutic option. This is a retrospective experimental study that aims to analyze the changes in the buccal cortical bone in patients undergoing orthodontics surgeries and to evaluate the correlation between the dental movement and the changes in the relative bone cortex. The study sample consists of 32 subjects. By applying the CBCT radiographic examinations, the measurements were made in well-defined points of reference. The 3D study of the dental changes of position and the cortical buccal bone related variation, suggests how the determined orthodontic movement of the dental element does not achieve an easily predictable bone variation. Therefore, it also suggests that there is no direct proportionality relationship between the extent of bone apposition/reabsorption and dental movement.
Fenestrated Falx Cerebri and Additional Sinuses in the Tentorium Cerebelli
Authors: Nayak Satheesha B. , Vasudeva Soumya K. 
Published: June 2020

Abstract
Morphological variations of falx cerebri and tentorium cerebelli are extremely rare. The authors report an extremely rare type of combined variation of falx cerebri and dural venous sinuses in the tentorium cerebelli. During the removal of the brain from cranial cavity, it was noted that the anterior part of the falx cerebri had fenestrations and it looked like a mesh. There was no associated variations of medial surface of cerebrum. Further, there were unusual sinuses within the tentorium cerebelli. Two of them were present in the right half of the tentorium cerebelli and one in the left half of the tentorium cerebelli. There variations could be of importance to radiologists and neurosurgeons. The fenestrations of falx cerebri might lead to misinterpretations in cases of head injuries and the additional sinuses in the tentorium cerebelli might cause unexpected bleeding during surgeries of posterior cranial fossa.
Tocilizumab for patients with COVID-19 pneumonia. The TOCIVID-19 prospective phase 2 trial
Authors: Perrone Francesco , Piccirillo Maria Carmela , Ascierto Paolo Antonio , Salvarani Carlo , Parrella Roberto , Marata Anna Maria , Popoli Patrizia , Ferraris Laurenzia , Marrocco-Trischitta Massimiliano M. , Ripamonti Diego , Binda Francesca , Bonfanti Paolo , Squillace Nicola , Castelli Francesco , Muiesan Maria Lorenza , Lichtner Miriam , Calzetti Carlo , Salerno Nicola Duccio , Atripaldi Luigi , Cascella Marco , Costantini Massimo , Dolci Giovanni , Facciolongo Nicola Cosimo , Fraganza Fiorentino , Massari Marco , Montesarchio Vincenzo , Mussini Cristina , Negri Emanuele Alberto , Botti Gerardo , Cardone Claudia , Gargiulo Piera , Gravina Adriano , Schettino Clorinda , Arenare Laura , Chiodini Paolo , Gallo Ciro 
Published: June 2020

AbstractBackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicentre, single-arm, hypothesis-driven phase 2 trial was planned to study the effect of Tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints). A cohort of patients consecutively enrolled after phase 2 was used as a validation dataset. A multivariable logistic regression was performed to generate hypotheses, while controlling for possible confounders.Resultsout of 301 patients in phase 2 intention-to-treat (ITT) analysis, 180 (59.8%) received tocilizumab. With 67 death events, lethality rates were 18.4% (97.5%CI: 13.6-24.0, P=0.52) and 22.4% (97.5%CI: 17.2-28.3, P<0.001) at 14 and 30 days. Lethality rates were lower in the validation dataset, including 920 patients. No signal of specific drug toxicity was reported. The multivariable logistic regression suggests tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Also, it supports a positive effect on lethality rate of the use of corticosteroids.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Such result support the use of tocilizumab while waiting for ongoing phase 3 trials.RegistrationEudraCT (2020-001110-38);clinicaltrials.gov(NCT04317092)
SARS-CoV-2 genomic and subgenomic RNAs in diagnostic samples are not an indicator of active replication
Authors: Alexandersen Soren , Chamings Anthony , Bhatta Tarka Raj 
Published: June 2020

AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in China in late December 2019 and has spread worldwide. Coronaviruses are enveloped, positive sense, single-stranded RNA viruses and employ a complicated pattern of virus genome length RNA replication as well as transcription of genome length and leader containing subgenomic RNAs. Although not fully understood, both replication and transcription are thought to take place in so-called double-membrane vesicles in the cytoplasm of infected cells. We here describe detection of SARS-CoV-2 subgenomic RNAs in diagnostic samples up to 17 days after initial detection of infection, provide evidence for their nuclease resistance and likely protection by cellular membranes consistent with being part of virus-induced replication organelles. Furthermore, we show that the ratios of genomic to subgenomic RNA as well as the ratios of plus to negative strand RNA of genomic and subgenomic RNA are consistent with what have been detected for other coronaviruses in cell culture; albeit with the caveat that in vivo diagnostic samples, even in relatively early infection, the ratios of these RNAs are most reminiscent of late culture, semi-purified virus preparations shown to have a relatively constant ratio of genomic to subgenomic RNAs of around 5-10 or higher, while the ratios of positive to negative strands are more than 100 for the genomic RNA and around 20 for the subgenomic RNAs. Overall, our results may help explain the extended PCR positivity of some samples, and may also, at least in part, help explain discrepancies in results of different diagnostic PCR methods described by others; in particular for samples with a low virus load or of poor quality. Overall, we present evidence that subgenomic RNAs may not be an indicator of active coronavirus replication/infection, but that these RNAs, similar to the virus genome RNA, may be rather stable, and thus detectable for an extended period, most likely due to their close association with cellular membranes.
Simultaneous classification of bilateral hand gestures using bilateral microelectrode recordings in a tetraplegic patient
Authors: Thomas Tessy M. , Nickl Robert W. , Thompson Margaret C. , Candrea Daniel N. , Fifer Matthew S. , McMullen David P. , Osborn Luke E. , Pohlmeyer Eric A. , Anaya Manuel , Anderson William S. , Wester Brock A. , Tenore Francesco V. , Cantarero Gabriela L. , Celnik Pablo A. , Crone Nathan E. 
Published: June 2020

ABSTRACTMost daily tasks require simultaneous control of both hands. Here we demonstrate simultaneous classification of gestures in both hands using multi-unit activity recorded from bilateral motor and somatosensory cortices of a tetraplegic participant. Attempted gestures were classified using hierarchical linear discriminant models trained separately for each hand. In an online experiment, gestures were continuously classified and used to control two robotic arms in a center-out movement task. Bimanual trials that required keeping one hand still resulted in the best performance (70.6%), followed by symmetric movement trials (50%) and asymmetric movement trials (22.7%). Our results indicate that gestures can be simultaneously decoded in both hands using two independently trained hand models concurrently, but online control using this approach becomes more difficult with increased complexity of bimanual gesture combinations. This study demonstrates the potential for restoring simultaneous control of both hands using a bilateral intracortical brain-machine interface.
Reconfiguration of Amplitude Driven Dominant Coupling Modes (DoCM) mediated by α-band in Adolescents with Schizophrenia Spectrum Disorders
Authors: Dimitriadis Stavros I. 
Published: June 2020

AbstractElectroencephalography (EEG) based biomarkers have been shown to correlated with the presence of psychotic disorders. Increased delta and decreased alpha power in psychosis indicate an abnormal arousal state. We investigated brain activity across the basic EEG frequencies and also dynamic functional connectivity of both intra and cross-frequency coupling that could reveal a neurophysiological biomarker linked to an aberrant modulating role of alpha frequency in adolescents with schizophrenia spectrum disorders (SSDs).A dynamic functional connectivity graph (DFCG) has been estimated using the imaginary part of phase lag value (iPLV) and correlation of the envelope (corrEnv). We analyzed DFCG profiles of electroencephalographic resting state (eyes closed) recordings of healthy controls (HC) (n=39) and SSDs subjects (n=45) in basic frequency bands {δ,θ,α1,α2,β1,β2,γ}. In our analysis, we incorporated both intra and cross-frequency coupling modes. Adopting our recent Dominant Coupling Mode (DoCM) model leads to the construction of an integrated DFCG (iDFCG) that encapsulates the functional strength and the DoCM of every pair of brain areas.We revealed significantly higher ratios of delta/alpha1,2 power spectrum in SSDs subjects versus HC. The probability distribution (PD) of amplitude driven DoCM mediated by alpha frequency differentiated SSDs from HC with absolute accuracy (100%). The network Flexibility Index (FI) was significantly lower for subjects with SSDs compared to the HC group.Our analysis supports a central role of alpha frequency alterations in the neurophysiological mechanisms of SSDs. Currents findings open up new diagnostic pathways to clinical detection of SSDs and supports the design of rational neurofeedback training.HighlightsRatios of delta/alpha1,2 relative power spectrum were significant higher in SSDs subjects compared to HCProbability distribution (PD) of amplitude driven DoCM mediated by alpha frequency differentiated SSDs from HC with 100%Network Flexibility index (FI) was significant lower for subjects with SSDs compared to HC group.
Varenicline rescues nicotine-induced decrease in motivation for sucrose reinforcement
Authors: Hart Erin , Hertia Daniel , Barrett Scott T , Charntikov Sergios 
Published: June 2020

AbstractVarenicline is one of the top medications used for smoking cessation and is often prescribed before termination of nicotine use. The effect of this combined nicotine and varenicline use on the reward system and motivation for primary reinforcement is underexplored. The goal of this study was to assess the effects of nicotine and varenicline on the consumption of sucrose. In Experiment 1, we first assessed the responding for sucrose after pretreatment with nicotine (0, 0.1, or 0.4 mg/kg) and varenicline (0.0, 0.1, 1.0 mg/kg) using a behavioral economics approach. The responding for sucrose was then assessed using a progressive ratio schedule of reinforcement after pretreatment with all possible combinations of nicotine and varenicline doses. In Experiment 2, rats were assessed for the consumption of sucrose in home cages after pretreatment with nicotine and varenicline. We found that a) nicotine decreased economic demand for sucrose, b) varenicline rescued nicotine-induced reduction in economic demand for sucrose, and c) history of varenicline treatment predicted responding for sucrose on a progressive ratio schedule of reinforcement where rats with a history of varenicline treatment responded significantly lower for sucrose across nicotine doses than rats that have not being exposed to varenicline. The results of Experiment 2 largely confirmed that nicotine decreases motivation for sucrose using a passive consumption protocol and that varenicline rescues this effect. Overall, these findings suggest that varenicline interacts with the effects of nicotine by restoring nicotine-induced reduction in motivation for appetitive rewards.
NMDA receptors control cortical axonal projections via EPHRIN-B/EPHB signaling
Authors: Zhou Jing , Lin Yong , Huynh Trung , Noguchi Hirofumi , Bush Jeffrey O. , Pleasure Samuel J. 
Published: June 2020

AbstractCallosal projections from primary somatosensory cortex (S1) are key for processing somatosensory inputs and integrating sensory-motor information. How the callosal innervation pattern in S1 is formed during early postnatal development is not clear. We found that the normal termination pattern of these callosal projections is disrupted in cortex specific NMDAR mutants. Rather than projecting selectively to the primary/secondary somatosensory cortex (S1/S2) border, axons were uniformly distributed throughout S1. In addition, the density of this projection increased over postnatal life until the mice died by P30. By combining genetic and antibody-mediated loss of function, we demonstrated that it is NR2B-containing NMDA receptors in target S1 that mediate this guidance phenotype, thus playing a central role in interhemispheric connectivity. Furthermore, we found that this function of NMDA receptors in callosal circuit formation is independent of ion channel function and instead depends on interactions with EPHRIN-B/EPHB. Thus, NMDAR cooperates with EPHRIN-B/EPHB in target S1 to control the formation callosal circuits by acting as an accessory axon guidance receptor modulating EPH-dependent repulsion.
Evolutionary genetics ofDrosophila melanogasterimmunity: role of the X chromosome and sex-specific dominance
Authors: Arun Manas Geeta , Agarwala Amisha , Jigisha  , Kashyap Mayank , Venkatesan Saudamini , Chechi Tejinder Singh , Syed Zeeshan Ali , Gupta Vanika , Prasad Nagaraj Guru 
Published: June 2020

AbstractIntralocus Sexual Conflict (IaSC) ensues when males and females of the same species experience divergent selection on shared traits. A large number of traits have been implicated in IaSC and there is growing evidence for sexual antagonism associated with immunity. X chromosomes are thought to be hotspots of sexually antagonistic genetic variation and have been shown to harbour substantial immunity-related genetic variation.Here, using interpopulation crosses and cytogenetic cloning, we investigated the role of the X chromosome in improved immune response of laboratory populations of the fruit-flyDrosophila melanogasterselected against systemic infection byPseudomonas entomophila.We could not detect any contribution of the X chromosome in the evolved immune response of our selected populations. However, we found strong evidence of sex-specific dominance related to immunity in our populations. Our results indicate that alleles that confer a superior immune response to the selected populations are, on average, partially dominant in females but partially recessive in males.We argue that sex-specific dominance over immunity evolved as a by-product of sexually antagonistic selection in the wild ancestors of our populations. We also highlight sex-specific dominance as a potential mechanism of sex differences in immunity, with population-level sex differences primarily driven by sex differences in heterozygotes.
Typical lipreading and audiovisual speech perception without motor simulation
Authors: Vannuscorps Gilles , Andres Michael , Carneiro Sarah , Rombaux Elise , Caramazza Alfonso 
Published: June 2020

ABSTRACTAll it takes is a face to face conversation in a noisy environment to realize that viewing a speaker’s lip movements contributes to speech comprehension. Following the finding that brain areas that control speech production are also recruited during lip reading, the received explanation is that lipreading operates through a covert unconscious imitation of the observed speech movements in the observer’s own speech motor system – a motor simulation. However, motor effects during lipreading do not necessarily imply simulation or a causal role in perception. In line with this alternative, we report here that some individuals born with lip paralysis, who are therefore unable to covertly imitate observed lip movements, have typical lipreading abilities and audiovisual speech perception. This constitutes existence proof that typically efficient lipreading abilities can be achieved without motor simulation. Although it remains an open question whether this conclusion generalizes to typically developed participants, these findings demonstrate that alternatives to motor simulation theories are plausible and invite the conclusion that lip-reading does not involve motor simulation. Beyond its theoretical significance in the field of speech perception, this finding also calls for a re-examination of the more general hypothesis that motor simulation underlies action perception and interpretation developed in the frameworks of the motor simulation and mirror neuron hypotheses.
UBR-Box containing protein, UBR5, is over-expressed in human lung adenocarcinoma and is a potential therapeutic target
Authors: Saurabh Kumar , Shah Parag P. , Doll Mark A. , Siskind Leah J. , Beverly Levi J. 
Published: June 2020

AbstractBackgroundN-end rule ubiquitination pathway is known to be disrupted in many diseases, including cancer. UBR5, an E3 ubiquitin ligase, is mutated and/or overexpressed in human lung cancer cells suggesting its pathological role in cancer.MethodsWe determined expression of UBR5 protein in multiple lung cancer cell lines and human patient samples. Using immunoprecipitation followed by mass spectrometry we determined the UBR5 interacting proteins. The impact of loss of UBR5 for lung adenocarcinoma cell lines was analyzed using cell viability, clonogenic assays andin vivoxenograft models in nude mice. Additional Western blot analysis was performed to assess the loss of UBR5 on downstream signaling. Statistical analysis was done by one-way ANOVA forin vitrostudies and Wilcoxon paired t-test for tumor volumesin vivo.ResultsWe show variability of UBR5 expression levels in lung adenocarcinoma cell lines and in primary human patient samples. To gain better insight into the role that UBR5 may play in lung cancer progression we performed unbiased interactome analyses for UBR5. Data indicate that UBR5 has a wide range of interacting protein partners that are known to be involved in critical cellular processes such as DNA damage, proliferation and cell cycle regulation. We have demonstrated that shRNA-mediated loss of UBR5 decreases cell viability and clonogenic potential of lung adenocarcinoma cell lines. In addition, we found decreased levels of activated AKT signaling after the loss of UBR5 in lung adenocarcinoma cell lines using multiple means of UBR5 knockdown/knockout. Furthermore, we demonstrated that loss of UBR5 in lung adenocarcinoma cells results in significant reduction of tumor volume in nude mice.ConclusionsThese findings demonstrate that deregulation of the N-end rule ubiquitination pathway plays a crucial role in the etiology of some human cancers, and blocking this pathway via UBR5-specific inhibitors, may represent a unique therapeutic target for human cancers.