bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laryngeal cancers in paediatric and young adult patients: epidemiology, biology and treatment
Authors: Lechien Jerome R. , Sadoughi Babak , Hans Stéphane 
Published: November 2021

Purpose of review
The aim of thi study was to review the recent literature on epidemiology, biology and treatment of laryngeal cancer in paediatric and young adult patients.

Recent findings
Epidemiological studies reported that 2–10% of patients with laryngeal cancer are younger than 40-year-old, while the prevalence of laryngeal cancer remains unknown in the paediatric population. The development of laryngeal cancer in young adults is multifactorial and may be linked to common carcinogens (tobacco and alcohol), occupational factors, laryngopharyngeal reflux, immunosuppression, human papillomavirus infection and genetic polymorphism. A substantial number of cohort studies reported a significant lower proportion of drinkers and smokers in young populations with laryngeal cancer, supporting the higher prevalence of chromosomal losses or abnormalities predisposing to cancer in this group. The development of laryngeal cancer in paediatric patients is strongly associated with genetic syndromes with DNA repair abnormalities. The pathological, clinical and survival outcome differences between young and old patient groups vary significantly between studies, depending on epidemiological, genetic features and therapeutic strategies used.

Summary
Paediatric and adult populations with laryngeal cancer present different clinical, pathological and survival outcomes. In the adult population, the patient age at the time of disease development underlies genetic and etiological differences with different mutation patterns between young and old patients, the latter being more frequently individuals with a history of tobacco and alcohol abuse. The differences between age groups regarding stage of cancer at initial presentation, as well as clinical and survival outcomes, are unclear, which may be due to demographic, ethnicity and population genetic differences.
Obligations and Behaviors That Impact Sleep in Prelicensure Baccalaureate Nursing Students
Authors: Blome Melissa , Johnson Michelle , Beck Mark , Jones Mark 
Published: November 2021

Background
Nursing students have obligations and behaviors that impact sleep.

Purpose
The purpose of this study was to investigate sleep among prelicensure baccalaureate nursing students and describe factors that impact their sleep quality and daytime sleepiness.

Methods
Prelicensure nursing students (n = 254) completed questionnaires that included demographics; obligations and behaviors that always, sometimes, or never caused sleep loss on a daily or weekly basis; the Pittsburgh Sleep Quality Index; the Epworth Sleepiness Scale; and the Sleep Hygiene Index.

Results
College classes were the most frequent reason why participants always lost sleep. Obligations of work, classes, and technology use into the night significantly predicted sleep hygiene; obligations of work, family, activity with friends, and classes significantly predicted sleep quality.

Conclusion
There is a need for education about behaviors and obligations that impact sleep in undergraduate nursing students, along with resources to assist in coping with external stressors.
A positively Tuned Voltage Indicator Reveals Electrical Correlates of Calcium Activity in the Brain
Authors: Evans S. Wenceslao , Shi Dongqing , Chavarha Mariya , Plitt Mark H. , Taxidis Jiannis , Madruga Blake , van Keulen Siri C. , Pang Michelle M. , Su Sharon , Hwang Fuu-Jiun , Zhang Guofeng , Reese Austin , Pradhan Lagnajeet , Fan Jiang Lan , Lee Sungmoo , Liu Yu , Suomivuori Carl-Mikael , Jiang Dongyun , Negrean Adrian , Wang Sui , Ji Na , Clandinin Thomas R. , Dror Ron O. , Bi Guoqiang , Makinson Christopher D. , Golshani Peyman , Giocomo Lisa M. , Losonczy Attila , Ding Jun B. , Lin Michael Z. 
Published: November 2021

AbstractNeuronal spiking activity is routinely recorded using genetically encoded calcium indicators (GECIs), but calcium imaging is limited in temporal resolution and does not report subthreshold voltage changes. Genetically encoded voltage indicators (GEVIs) offer better temporal resolution and subthreshold sensitivity, but spike detection with fast GEVIs has required specialized imaging equipment. Here, we report the ASAP4 subfamily of genetically encoded voltage indicators (GEVIs) that brighten in response to membrane depolarization, inverting the fluorescence-voltage relationship of previous ASAP GEVIs. Two variants, ASAP4b and ASAP4e, feature 128% and 178% fluorescence increases over 100-mV of depolarization, respectively, facilitating spike detection in single trials in vivo with standard 1 and 2-photon imaging systems. Simultaneous voltage and calcium imaging confirms improved temporal resolution and spike discernment by ASAP4 GEVIs. Thus, positively tuned ASAP4 voltage indicators enable recording of neuronal spiking activity using similar equipment as calcium imaging, while providing higher temporal resolution.One Sentence SummaryUpward ASAPs increase detection capability of GEVIs in vivo.
Machine Learning in the analysis of lethality and evolution of infection by the SARS-CoV-2 virus (COVID-19) in workers of the Mexico City Metro
Authors: García Islas Eréndira Itzel , de Anda Jáuregui Guillermo , Rodríguez Joaquín Salas , Soto Florencia Serranía 
Published: November 2021

AbstractIn terms of the number of fatalities, Mexico has been one of the countries most affected worldwide by the pandemic. Using different Machine Learning techniques, some of the first cases of the infection registered in Mexico City (CDMX), the geographical and political center of the country, are analyzed in order to determine the causes of lethality and evolution of infection by the SARS-CoV-2 virus, from April 1 to September 27, 2020 in workers of the Capital Metro.
Defining the architecture of cerebrospinal fluid cellular communities in neuroinflammatory diseases
Authors: Roostaei Tina , Diaconu Claudiu , Touil Hanane , Harbison Claire , Zhang Ya , Epstein Samantha , Tuddenham John , Thakur Kiran , Bryois Julien , Wiendl Heinz , Meyer Zu Hörste Gerd , Malhotra Dheeraj , Riley Claire , Menon Vilas , De Jager Philip L. 
Published: November 2021

AbstractCerebrospinal fluid (CSF) biomarkers are important for multiple sclerosis (MS) diagnosis. Moreover, absent of autopsy or biopsy tissue, CSF is the most relevant source for studying the immune cells involved in MS pathophysiology. Single-cell RNA sequencing (scRNA-seq) provides new opportunities to advance our understanding of disease-associated changes in CSF immune cells. Here, using scRNA-seq data generated from 58 CSF and 10 PBMC samples, we provide an updated atlas of the immune cells present in human CSF in MS and other neuroinflammatory conditions, including novel lymphoid and myeloid cell clusters. Our atlas can thus serve as a reference for future studies of immune cells in neuroinflammation. Our further characterization of CSF myeloid cells suggests that most CSF microglia-like cells resemble two of the previously-described brain microglia signatures. Additionally, our data from a sex-mismatched bone marrow transplant recipient suggest that CSF microglia-like cells are of peripheral origin. Our comparisons between MS and other neuroinflammatory disorders show a highly-specific increase in plasma cells, along with reductions in the proportion of microglia-like cells in MS CSF. Furthermore, our analyses on MS patients receiving anti-CD20 therapy ocrelizumab suggest that the treatment effects are not limited to B cell depletion, and ocrelizumab appears to reverse some MS-associated T and myeloid changes in CSF. Finally, we utilized our atlas to prioritize (1) CSF cell types expressing genes associated with MS susceptibility, and (2) ligand-receptor gene pairs that are differentially expressed in MS CSF, providing targets for further mechanistic and causal investigations in pathophysiology and treatment of MS.
Cohort profile: the Swiss Cerebral Palsy Registry (Swiss-CP-Reg) cohort study
Authors: Belle Fabiën N. , Hunziker Sandra M. , Fluss Joël , Grunt Sebastian , Juenemann Stephanie , Kuenzle Christoph , Meyer-Heim Andreas , Newman Christopher J. , Ramelli Gian Paolo , Weber Peter , Kuehni Claudia E. , Tscherter Anne 
Published: November 2021

SUMMARYBACKGROUNDCerebral Palsy (CP) is a group of permanent disorders of movement and posture that follows injuries to the developing brain. It results in motor dysfunction and a wide variety of comorbidities like epilepsy, pain, speech, hearing and vision disorders, cognitive dysfunction, and eating and digestive difficulties. Central data collection is essential to study the epidemiology, clinical presentations, care, and quality of life of patients affected by CP. CP specialists founded the Swiss Cerebral Palsy Registry (Swiss-CP-Reg) in 2017. This paper describes the design, structure, aims and achievements of the Swiss-CP-Reg and presents first results.METHODSSwiss-CP-Reg records patients of any age suffering from CP who are born, treated, or live in Switzerland. It collects data from medical records and reports, from questionnaires answered by patients and their families, and from data linkage with routine statistics and other registries. The registry contains information on diagnosis, clinical presentation, comorbidities, therapies, personal information, family history, and quality of life.ResultsFrom August 2017 to August 2021, 546 participants (55% males, mean age at registration 8 years (interquartile range [IQR]: 5-12) were enrolled in Swiss-CP-Reg. Most had been born at term (56%), were less than 2 years old at diagnosis (73%, median 9 months, IQR: 18-25), and were diagnosed with spastic CP (76%). Most (59%) live with a mild motor impairment (Gross Motor Function Classification System [GMFCS] level I or II), 12% with a moderate motor impairment (GMFCS level III), and 29% with a severe motor impairment (GMFCS level IV or V). In a subset of 170 participants, we measured intelligence quotient (IQ) and saw a reduced IQ by GMFCS scale increase. The Swiss-CP-Reg has a strong interest in research with currently 5 nested projects running, and many more planned.CONCLUSIONSSwiss-CP-Reg collects and exchanges national data on people living with CP to answer clinically relevant questions. Its structure enables retrospective and prospective data collection and knowledge exchange between experts to optimise and standardise treatment and improve the health and quality of life of those diagnosed with CP in Switzerland.ClinicalTrials.gov identifierNCT04992871
Comparing protein-protein interaction networks of SARS-CoV-2 and (H1N1) influenza using topological features
Authors: Khojasteh Hakimeh , Khanteymoori Alireza , Olyaee Mohammad Hossein 
Published: November 2021

AbstractBackgroundSARS-CoV-2 pandemic first emerged in late 2019 in China. It has since infected more than 183 million individuals and caused about 4 million deaths globally. A protein-protein interaction network (PPIN) and its analysis can provide insight into the behavior of cells and lead to advance the procedure of drug discovery. The identification of essential proteins is crucial to understand for cellular survival. There are many centrality measures to detect influential nodes in complex networks. Since SARS-CoV-2 and (H1N1) influenza PPINs pose 553 common proteins. Analyzing influential proteins and comparing these networks together can be an effective step helping biologists in drug design.ResultsWe used 21 centrality measures on SARS-CoV-2 and (H1N1) influenza PPINs to identify essential proteins. PCA-based dimensionality reduction was applied on normalized centrality values. Some measures demonstrated a high level of contribution in comparison to others in both PPINs, like Barycenter, Decay, Diffusion degree, Closeness (Freeman), Closeness (Latora), Lin, Radiality, and Residual. Using validation measures, the appropriate clustering method was chosen for centrality measures. We also investigated some graph theory-based properties like the power law, exponential distribution, and robustness.ConclusionsThrough analysis and comparison, both networks exhibited remarkable experimental results. The network diameters were equal and in terms of heterogeneity, SARS-CoV-2 PPIN tends to be more heterogeneous. Both networks under study display a typical power-law degree distribution. Dimensionality reduction and unsupervised learning methods were so effective to reveal appropriate centrality measures.
Ultrapotent and Broad Neutralization of SARS-CoV-2 Variants by Modular, Tetravalent, Bi-paratopic Antibodies
Authors: Miersch Shane , Saberianfar Reza , Chen Chao , Sharma Nitin , Amarasinghe Gaya K. , Caccuri Francesca , Zani Alberto , Caruso Arnaldo , Novelli Giuseppe , Sidhu Sachdev S 
Published: November 2021

SummaryNeutralizing antibodies (nAbs) that target the SARS-CoV-2 spike protein are approved for treatment of COVID-19. However, with the emergence of variants of concern, there is a need for new treatment options. We report a novel format that enables modular assembly of bi-paratopic, tetravalent nAbs with antigen-binding sites from two distinct nAbs. The tetravalent nAb was purified in high yield, and it exhibited biophysical characteristics that were comparable to those of approved therapeutic antibodies. The tetravalent nAb bound to the spike protein trimer at least 100-fold more tightly than bivalent IgGs (apparent KD < 1 pM), and it exhibited extremely high potencies against a broad array of pseudoviruses, chimeric viruses, and authentic virus variants. Together, these results establish the tetravalent diabody-Fc-Fab as a robust, modular platform for rapid production of drug-grade nAbs with potencies and breadth of coverage that greatly exceed those of conventional bivalent IgGs.
Influence of heterogeneous age-group contact patterns on critical vaccination rates for herd immunity to SARS-CoV-2
Authors: Saldaña Joan , Scoglio Caterina 
Published: November 2021

ABSTRACTCurrently, several western countries have more than half of their population fully vaccinated against COVID-19. At the same time, some of them are experiencing a fourth or even a fifth wave of cases, most of them concentrated in sectors of the populations whose vaccination coverage is lower than the average. So, the initial scenario of vaccine prioritization has given way to a new one where achieving herd immunity is the primary concern. Using an age-structured vaccination model with waning immunity, we show that, under a limited supply of vaccines, a vaccination strategy based on minimizing the basic reproduction number allows for the deployment of a number of vaccine doses lower than the one required for maximizing the vaccination coverage. Such minimization is achieved by giving greater protection to those age groups that, for a given social contact pattern, have smaller fractions of susceptible individuals at the endemic equilibrium without vaccination, that is, to those groups that are more vulnerable to infection.
Candidate gene modifiers of dystrophinopathy identified by the uniform application of genome-wide datasets to novel GWAS-identified loci
Authors: Flanigan Kevin M. , Waldrop Megan A. , Martin Paul T. , Alles Roxane , Dunn Diane M. , Alfano Lindsay N. , Simmons Tabatha R. , Moore-Clingenpeel Melissa , Burian John , Seok Sang-Cheol , Vieland Veronica J. , Weiss Robert B. 
Published: November 2021

AbstractAlthough the major determinant of disease severity in patients with severe Duchenne muscular dystrophy (DMD) or milder Becker muscular dystrophy (BMD) is whether their dystrophin gene (DMD) mutation disrupts the mRNA reading frame or allows expression of a partially functional protein, other genes have been proposed or demonstrated to modify the severity of disease progression. In a companion paper to this one, we describe our novel approaches to genome-wide association study (GWAS) of loss of ambulation (LOA) in the largest genome-wide search to date for loci influencing disease severity in DMD patients. Candidate regulatory SNPs that modify disease progression were identified using an evidential statistical paradigm and here we present a uniform application of recent functional genomic datasets to explore the potential functional impact of the top six candidate regions with PPLD scores of ≥0.4. The results of this analysis of the largest DMD GWAS survey to date elucidate recurrent and potentially new pathways for intervention in the dystrophinopathies.
Long-term Pannexin 1 ablation promotes structural and functional modifications in hippocampal neurons through the regulation of actin cytoskeleton and Rho GTPases activity
Authors: Flores-Muñoz Carolina , García-Rojas Francisca , Perez Miguel A. , Santander Odra , Mery Elena , Lopez-Espíndola Daniela , Gonzalez-Jamett Arlek M. , Fuenzalida Marco , Martinez Agustín D. , Ardiles Álvaro O. 
Published: November 2021

AbstractEnhanced activity and overexpression of Pannexin 1 (PANX1) channels contribute to neuronal pathologies, such as epilepsy and Alzheimer’s disease (AD). In the hippocampus, the PANX1 channels ablation alters glutamatergic neurotransmission, synaptic plasticity, and memory flexibility. Nevertheless, PANX1-knockout (KO) mice still preserve the ability to learn, suggesting that compensatory mechanisms work to stabilize neuronal activity. Here, we show that the absence of PANX1 in the adult brain promotes a series of structural and functional modifications in KO hippocampal synapses, preserving spontaneous activity. Adult CA1 neurons of KO mice exhibit enhanced excitability, complex dendritic branching, spine maturation, and multiple synaptic contacts compared to the WT condition. These modifications seem to rely on the actin-cytoskeleton dynamics as an increase in actin polymerization and an imbalance between Rac1 and RhoA GTPase activity is observed in the absence of PANX1. Our findings highlight a novel interaction between PANX1, actin, and small Rho GTPases that appear to be relevant for synapse maintenance as a long-term compensatory mechanism for PANX1 deficiency.
A trimeric NTD and RBD SARS-CoV-2 subunit vaccine induced protective immunity in CAG-hACE2 transgenic mice and rhesus macaques
Authors: Yu Jiaping , Yao Wenrong , Hu Yingsong , Wu Shuang , Li Jiao , Zhou Hongjun , Hong Kunxue , Chen Jianping , Liu Longding , Lan Ke , Zhu Feng-Cai , Liu Yong 
Published: November 2021

AbstractThe coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to significant public health, economic and social problems. Development of effective vaccines is still a priority to contain the virus and end the global pandemic. In this study, we reported that ReCOV, a recombinant trimeric NTD and RBD two-component SARS-CoV-2 subunit vaccine adjuvanted with BFA03 (an AS03-like squalene adjuvant), induced high levels of neutralizing antibodies against SARS-CoV-2 and the circulating variants in mice, rabbits and rhesus macaques. Notably, two-dose immunizations of ReCOV provided complete protection against challenge with SARS-CoV-2 in hACE2 transgenic mice and rhesus macaques, without observable antibody-dependent enhancement of infection. These results support further clinical development of ReCOV and the vaccine is currently being evaluated in a phase I clinical trial in New Zealand (NCT04818801).
The United States COVID-19 Forecast Hub dataset
Authors: Cramer Estee Y , Huang Yuxin , Wang Yijin , Ray Evan L , Cornell Matthew , Bracher Johannes , Brennen Andrea , Castero Rivadeneira Alvaro J , Gerding Aaron , House Katie , Jayawardena Dasuni , Kanji Abdul H , Khandelwal Ayush , Le Khoa , Niemi Jarad , Stark Ariane , Shah Apurv , Wattanchit Nutcha , Zorn Martha W , Reich Nicholas G 
Published: November 2021

AbstractAcademic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident hospitalizations, incident cases, incident deaths, and cumulative deaths due to COVID-19 at national, state, and county levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages.
Whole Exome Sequencing in dense families suggests genetic pleiotropy amongst Mendelian and complex neuropsychiatric syndromes
Authors: Ganesh Suhas , Vemula Alekhya , Bhattacharjee Samsiddhi , Mathew Kezia , Ithal Dhruva , Navin Karthick , Nadella Ravi Kumar , Viswanath Biju , Sullivan Patrick F ,   The ADBS consortium, Jain Sanjeev , Purushottam Meera 
Published: November 2021

AbstractWhole Exome Sequencing (WES) studies provide important insights into the genetic architecture of serious mental illness (SMI). Genes that are central to the shared biology of SMIs may be identified by WES in families with multiple affected individuals with diverse SMI (F-SMI). We performed WES in 220 individuals from 75 F-SMI families and 60 unrelated controls. Within pedigree prioritization employed criteria of rarity, functional consequence, and sharing by ≥3 affected members. Across the sample, gene and gene-set-wide case-control association analysis was performed with Sequence Kernel Association Test, accounting for kinship.In 14/16 families with ≥3 affected individuals, we identified a total of 79 rare predicted deleterious variants in 79 unique genes shared by ≥3 members with SMI and absent in 60 unrelated controls. Twenty (25%) genes were implicated in monogenic neurodevelopmental syndromes in OMIM, a fraction that is a significant overrepresentation (Fisher’s Exact test OR = 2.47, p = 0.001). In gene-set wise SKAT, statistically significant association was noted for genes related to synaptic function (SKAT-p = 0.014). In this WES study in F-SMI, we identify private, rare, protein altering variants in genes previously implicated in Mendelian neuropsychiatric syndromes; suggesting pleiotropic influences in neurodevelopment between complex and Mendelian syndromes.