bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetics of antibody responses dictate COVID-19 outcome
Authors: Lucas Carolina , Klein Jon , Sundaram Maria , Liu Feimei , Wong Patrick , Silva Julio , Mao Tianyang , Oh Ji Eun , Tokuyama Maria , Lu Peiwen , Venkataraman Arvind , Park Annsea , Israelow Benjamin , Wyllie Anne L. , Vogels Chantal B. F. , Muenker M. Catherine , Casanovas-Massana Arnau , Schulz Wade L. , Zell Joseph , Campbell Melissa , Fournier John B. ,   Yale IMPACT Research Team, Grubaugh Nathan D. , Farhadian Shelli , Wisnewski Adam V. , Cruz Charles Dela , Omer Saad , Ko Albert I. , Ring Aaron , Iwasaki Akiko 
Published: December 2020

SummaryRecent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). Yet, the exact feature of antibody responses that governs COVID-19 disease outcomes remain unclear. Here, we analysed humoral immune responses in 209 asymptomatic, mild, moderate and severe COVID-19 patients over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-Spike (S) IgG levels, length of hospitalization and clinical parameters associated with worse clinical progression. While high anti-S IgG levels correlated with worse disease severity, such correlation was time-dependent. Deceased patients did not have higher overall humoral response than live discharged patients. However, they mounted a robust, yet delayed response, measured by anti-S, anti-RBD IgG, and neutralizing antibody (NAb) levels, compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, while sera from 89% of patients displayed some neutralization capacity during their disease course, NAb generation prior to 14 days of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levelsper se, but rather with the delayed kinetics of NAb production.
Further development of spinal cord retreatment dose estimation: including radiotherapy with protons and light ions
Authors: Moore Joshua W. , Woolley Thomas E. , Hopewell John W. , Jones Bleddyn 
Published: December 2020

AbstractA new graphical user interface (GUI) was developed to aid in the assessment of changes in the radiation tolerance of spinal cord/similar central nervous system tissues with time between two treatment courses. The GUI allows any combination of photons, protons (or ions) to be used as the initial, or retreatment, course. Allowances for clinical circumstances, of reduced tolerance, can also be made. The radiobiological model was published previously and has been incorporated with additional checks and safety features, to be as conservative as possible. The proton option includes use of a fixed RBE of 1.1 (set as the default), or a variable RBE, the latter depending on the proton linear energy transfer (LET) for organs at risk. This second LET-based approach can also be used for ions, by changing the LET parameters. GUI screenshots are used to show the input and output parameters for clinical situations used in worked examples from previous publications, where the proton and ion treatments required additional ‘longhand’ calculations. The results from the GUI are in agreement with previously published calculations, but the results are now rapidly available without tedious and error-prone manual computations. The software outputs provide a maximum dose limit boundary, which should not be exceeded. Clinicians may also choose a lower number of treatment fractions, whilst using the same dose per fraction (or conversely a lower dose per fraction but with the same number of fractions) in order to achieve the intended clinical benefit. The new GUI will allow rational estimations of time related radiation tolerance changes in the spinal cord and similar central nervous tissues (optic chiasm, brainstem), which can be used to guide the choice of retreatment dose fractionation schedules.
Is the brain macroscopically linear? A system identification of resting state dynamics
Authors: Nozari Erfan , Bertolero Maxwell A. , Stiso Jennifer , Caciagli Lorenzo , Cornblath Eli J. , He Xiaosong , Mahadevan Arun S. , Pappas George J. , Bassett Dani Smith 
Published: December 2020

AbstractA central challenge in the computational modeling of neural dynamics is the trade-off between accuracy and simplicity. At the level of individual neurons, nonlinear dynamics are both experimentally established and essential for neuronal functioning. One may therefore expect the collective dynamics of massive networks of such neurons to exhibit an even larger repertoire of nonlinear behaviors. An implicit assumption has thus formed that an “accurate” computational model of whole-brain dynamics must inevitably be non-linear whereas linear models may provide a first-order approximation. To what extent this assumption holds, however, has remained an open question. Here, we provide new evidence that challenges this assumption at the level of whole-brain blood-oxygen-level-dependent (BOLD) and macroscopic field potential dynamics by leveraging the theory of system identification. Using functional magnetic resonance imaging (fMRI) and intracranial electroencephalography (iEEG), we model the spontaneous, resting state activity of 700 subjects in the Human Connectome Project (HCP) and 122 subjects from the Restoring Active Memory (RAM) project using state-of-the-art linear and nonlinear model families. We assess relative model fit using predictive power, computational complexity, and the extent of residual dynamics unexplained by the model. Contrary to our expectations, linear auto-regressive models achieve the best measures across all three metrics. To understand and explain this linearity, we highlight four properties of macroscopic neurodynamics which can counteract or mask microscopic nonlinear dynamics: averaging over space, averaging over time, observation noise, and limited data samples. Whereas the latter two are technological limitations and can improve in the future, the former two are inherent to aggregated macroscopic brain activity. Our results demonstrate the discounted potential of linear models in accurately capturing macroscopic brain dynamics. This, together with the unparalleled interpretability of linear models, can greatly facilitate our understanding of macroscopic neural dynamics, which in turn may facilitate the principled design of model-based interventions for the treatment of neuropsychiatric disorders.
Feasibility of next‐generation sequencing test for patients with advanced NSCLC in clinical practice
Authors: Ariyasu Ryo , Uchibori Ken , Ninomiya Hironori , Ogusu Shinsuke , Tsugitomi Ryosuke , Manabe Ryo , Sakamaoto Hiroaki , Tozuka Takehiro , Yoshida Hiroshi , Amino Yoshiaki , Kitazono Satoru , Yanagitani Noriko , Takeuchi Kengo , Nishio Makoto 
Published: December 2020

AbstractBackgroundThe usefulness of the Oncomine Dx Target test (Oncomine Dx), a next‐generation sequencing (NGS) test, has already been proven in clinical trials. However, NGS requires high‐quality tumor samples and takes a long time to generate results. The feasibility of NGS for use in advanced non‐small cell lung cancer (NSCLC) patients in clinical practice has not yet been determined.MethodsPatients serially diagnosed with advanced NSCLC were evaluated in our hospital. The Oncomine Dx, Cobas EGFR mutation test (Cobas EGFR), and ALK‐IHC were performed. The patients were divided into four sets: the full analysis set (FAS) that referred to patients diagnosed with NSCLC, the intent to perform companion diagnostics (CDx) set (IPS) that referred to patients in which CDx had been ordered regardless of sample quality, the per‐performed CDx set (PPS) that referred to patients who could undergo CDx regardless of the results, and the per‐completed CDx set (CCS) that referred to patients in which informative results were received from the CDx.ResultsThe total number of patients analyzed in the study was 167. The IPS/FAS of Oncomine Dx (80.2%) was lower than that of the ALK‐IHC (85.0%) and Cobas EGFR (92.8%). The CCS/FAS of Oncomine Dx (65.9%) was lower than that of the ALK‐IHC (82.0%) and Cobas EGFR (92.2%). PPS/IPS and CCS/PPS of the Oncomine Dx with nonsurgical biopsy ranged between 78.6% and 90.9%, which was lower than those patients who underwent surgical resection (95.0% and 100%).ConclusionsThe feasibility of Oncomine Dx in clinical practice was lower than the other CDx. The feasibility of Oncomine Dx will increase by improving the biopsy procedure.Key pointsSignificant study findings
The usefulness of a next‐generation sequencing (NGS) test has been proven in clinical trials.
The feasibility of NGS is lower than other diagnostics in clinical practice especially with regard to nonsurgical biopsy.
What this study adds
It is necessary to improve the feasibility of NGS in clinical practice.
To improve NGS feasibility, turnaround time must be shortened, and larger samples must be obtained during surgical procedures.
Toothbrushing frequency and gastric and upper aerodigestive tract cancer risk: A meta‐analysis
Authors: Wu Huadong , Zhang Jinjia , Zhou Baojun 
Published: December 2020

AbstractObjectiveResults of epidemiological studies evaluating the association between toothbrushing and gastric and upper aerodigestive tract (UADT) cancer risk showed inconsistent results. The purpose of this study was to evaluate the association between toothbrushing and gastric and UADT cancer risk and quantify the dose‐response association between them.MethodsWe searched the PubMed, EMBASE and Cochrane Library databases to identify relevant studies on toothbrushing and gastric and UADT cancer risk. Statistical analyses were performed using STATA 12.0 software.ResultsA total of 30 studies of involving 1 194 017 participants met eligibility criteria and were included in the meta‐analysis. Meta‐analysis using a random‐effect model showed that the high frequency of toothbrushing was associated with significantly reduced risk of gastric and UADT cancers (OR: 0.55, 95% CI 0.46‐0.64, P < .05). Our dose‐response analysis presented that every increased toothbrushing per day might reduce oral cavity cancer risk by 6%, pharyngeal cancer risk by 11%, laryngeal cancer risk by 3%, oesophageal cancer risk by 6% and gastric cancer risk by 4%.ConclusionsThis meta‐analysis suggested the negative relationship between frequency of toothbrushing and risk of gastric and UADT cancers. Toothbrushing may be a protective factor for gastric and UADT cancers. However, this association must be further validated through large prospective studies.
How does the environment influence consumers' perceptions of safety in acute mental health units? A qualitative study
Authors: Cutler Natalie Ann , Halcomb Elizabeth , Sim Jenny , Stephens Moira , Moxham Lorna 
Published: December 2020

ABSTRACTAims and objectivesTo explore how the physical and social environment of acute mental health units influences consumers' perception and experience of safety.BackgroundAcute mental health units are places in which consumers should feel safe. Not all consumers, however, feel safe in this environment. Little is known about what contributes to consumers' feelings of safety in this setting.DesignThe study used a qualitative descriptive design, influenced by naturalistic enquiry. Data were analysed using thematic analysis and are reported according to the COREQ checklist.MethodsFifteen people who had experienced admission to an acute mental health unit were individually interviewed.ResultsHaving a supportive environment enhanced consumers' perception and experience of safety. A supportive environment was experienced when consumers had privacy, felt safe from other consumers and had meaningful activities to participate in within the acute mental health unit. In contrast, having their privacy breached by other consumers made participants feel unsafe. Many participants were fearful of other consumers, and felt unsafe and unable to protect themselves. Lack of meaningful activities led to boredom and contributed to consumers feeling unsafe.ConclusionsPersonal spaces should address consumers' privacy needs without compromising staff access. Staff presence enhances consumers' feelings of safety, but this need can be heightened when consumers are unable to alert staff when they feel unsafe. Meaningful activities link consumers to their lives outside of the hospital and can enhance recovery.Relevance to clinical practiceUnderstanding how the acute unit environment is perceived by consumers can assist nurses and managers to promote feelings of safety among consumers. Feeling safe can, in turn, optimise recovery.
Shadow of a disformal Kerr black hole in quadratic degenerate higher-order scalar–tensor theories
Authors: Long Fen , Chen Songbai , Wang Mingzhi , Jing Jiliang 
Published: December 2020

AbstractWe have studied the shadow of a disformal Kerr black hole with an extra deformation parameter, which belongs to non-stealth rotating solutions in quadratic degenerate higher-order scalar–tensor (DHOST) theory. Our result show that the size of the shadow increases with the deformation parameter for the black hole with arbitrary spin parameter. However, the effect of the deformation parameter on the shadow shape depends heavily on the spin parameter of black hole and the sign of the deformation parameter. The change of the shadow shape becomes more distinct for the black hole with the more quickly rotation and the more negative deformation parameter. Especially, for the near-extreme black hole with negative deformation parameter, there exist a “pedicel”-like structure appeared in the shadow, which increases with the absolute value of deformation parameter. The eyebrow-like shadow and the self-similar fractal structures also appear in the shadow for the disformal Kerr black hole in DHOST theory. These features in the black hole shadow originating from the scalar field could help us to understand the non-stealth disformal Kerr black hole and quadratic DHOST theory.
Enhanced Mesenchymal Stromal Cells or Erythropoietin Provide Long-Term Functional Benefit After Neonatal Stroke
Authors: Larpthaveesarp Amara , Pathipati Praneeti , Ostrin Samuel , Rajah Anthony , Ferriero Donna , Gonzalez Fernando F. 
Published: December 2020

Background and Purpose:
Perinatal stroke is a common cause of life-long neurobehavioral compromise. Mesenchymal stromal cells (MSCs) and EPO (erythropoietin) have each demonstrated short-term benefit with delayed administration after stroke, and combination therapy may provide the most benefit. The purpose of this study is to determine the long-term histological and functional efficacy of enhanced, intranasal stem cell therapy (MSC preexposed to EPO) compared with standard MSC or multidose systemic EPO.

Methods:
Transient middle cerebral artery occlusion or sham surgery was performed in postnatal day (P) 10 Sprague-Dawley rats, who were treated with single-dose intranasal MSC, MSC preexposed to EPO (MSC/EPO), multidose systemic EPO (EPO3; 1000 u/kg per dose×3 every 72 hours), or cell-conditioned media on P13 (day 3 [P13–P19] for EPO), or on P17 (day 7 [P17–P23] for EPO). At 2 months of age, animals underwent novel object recognition, cylinder rearing, and open field testing to assess recognition memory, sensorimotor function, and anxiety in adulthood.

Results:
MSC, MSC/EPO, and EPO3 improved brain volume when administered at 3 or 7 days after middle cerebral artery occlusion. MSC/EPO also enhanced long-term recognition memory with either day 3 or day 7 treatment, but EPO3 had the most long-term benefit, improving recognition memory and exploratory behavior and reducing anxiety.

Conclusions:
These data suggest that single-dose MSC/EPO and multidose systemic EPO improve long-term neurobehavioral outcomes even when administration is delayed, although EPO was the most effective treatment overall. It is possible that EPO represents a final common pathway for improved long-term repair, although the specific mechanisms remain to be determined.
The Principle of Exclusive Flag State Jurisdiction
Authors: Whomersley Chris 
Published: December 2020

Abstract
The principle that a ship is subject to the exclusive jurisdiction of the flag State on the high seas is firmly established. But given the prevalence of open registries and the multiple challenges in the maritime sphere, such as maritime safety, the popularity of cruise holidays, the promotion of human rights for those working at sea, and the need to combat iuu fishing, is it any longer tenable to slavishly follow the principle? International instruments and judicial decisions have emphasised the responsibilities of flag States. But States have also increasingly turned to other mechanisms, especially port State control, to deal with the various problems.
Indicators of Secretory Activation in Mothers of Preterm Very Low Birth Weight Infants
Authors: Parker Leslie A. , Sullivan Sandra , Cacho Nicole , Engelmann Clara , Krueger Charlene , Mueller Martina 
Published: December 2020

Background Inconsistent information exists regarding indicators of secretory activation in mothers delivering very low birth weight infants. Research aims To compare time to the onset of secretory activation using three separate indicators. A secondary aim examined the association between indicators of secretory activation and milk production. Methods Indicators of secretory activation included maternal perception, volume attainment (production of ≥ 20 mL in two consecutive expression sessions) and biomarkers (sodium and lactose) obtained at volume attainment. Milk production was measured on Days 1–7 and then weekly for 6 weeks. Results In 69 mothers of infants born ≤ 32 weeks’ gestation and < 1500 g, we found no correlation in time to secretory activation between indicators. Earlier volume attainment was associated with increased milk production on Days 1–7, 14, 21, and 28 (all p < .007). Participants who exhibited both normal lactose and sodium levels produced more milk on Days 28 and 42 ( p = .028 and .011), those with only normal lactose levels produced more on Day 42 ( p = .026) and those with only normal sodium levels on Day 28 ( p = .036). Earlier secretory activation by volume attainment was associated with increased expression frequency during Days 2–5 (all p < .014) and participants with normal biomarkers expressed more frequently during Days 2–5 (all p < .020). Conclusion Mothers of very low birth weight infants are at risk for delayed secretory activation, which may decrease their milk production. Frequent expression during the first 5 days postpartum may promote earlier secretory activation. Valid methods of determining secretory activation are necessary to develop interventions promoting earlier secretory activation.
New findings associated with presumptive systemic lupus erythematosus in a kitten
Authors: Huvé Romain , Fontaine Pascal , Blais Marie-Claude , Conversy Bérénice 
Published: December 2020

Case summary An 8-month-old neutered male domestic shorthair kitten was examined for anorexia, lethargy and palatine ulcers. Systemic lupus erythematosus (SLE) was suspected based on a positive antinuclear antibody (ANA) titer and six manifestations of autoimmunity: fever, paronychia, oral ulcers, proteinuria, thrombocytopenia and leukopenia. Mastocytemia was observed on the blood smear. Although the clinical presentation of this case meets the classification criteria for SLE in humans, tick-borne disease and histopathology evaluation of the oral and cutaneous lesions would have been necessary to support a definite diagnosis of SLE. Baseline ANA titration was performed in two laboratories with conflicting results, which may reflect substrate differences used for the titration, but a false-positive result cannot be excluded. The cat received prednisolone and all clinical and laboratory abnormalities resolved after two months of treatment. Subsequent ANA titers remained positive and were not correlated to the patient’s clinical progression. Relevance and novel information This report describes new findings associated with a presumptive diagnosis of SLE in a kitten, highlighting that SLE may not be ruled out even in young cats and may be associated with mastocytemia. ANA titration is part of the initial diagnostic work-up of SLE but is a non-specific test and discrepancies can be observed between laboratories. The titration of more specific antibodies such as those used in humans would be helpful to diagnose SLE. ANA titration may not correlate with clinical activity of SLE; hence, the interest of an ANA titer follow-up to establish disease control warrants further investigation.
Analysis of Annual Costs of Mobile Clinics in the Southern United States
Authors: Attipoe-Dorcoo Sharon , Delgado Rigoberto , Lai Dejian , Gupta Aditi , Linder Stephen 
Published: December 2020

Introduction Mobile clinics provide an efficient manner for delivering healthcare services to at-risk populations, and there is a need to understand their economics. This study analyzes the costs of operating selected mobile clinic programs representing service categories in dental, dental/preventive, preventive care, primary care/preventive, and mammography/primary care/preventive. Methods The methodology included a self-reported survey of 96 mobile clinic programs operating in Texas, North Carolina, Georgia, and Florida; these states did not expand Medicaid and have a large proportion of uninsured individuals. Data were collected over an 8-month period from November 2016 to July 2017. The cost analyses were conducted in 2018, and were analyzed from the provider perspective. The average annual estimated costs; as well the costs per patient in each mobile clinic program within different service delivery types were assessed. Costs reported in the study survey were classified into recurrent direct costs and capital costs. Results Results indicate that mean operating costs range from about $300 000 to $2.5 million with costs increasing from mammography/primary care/preventive delivery to dental/preventive. The majority of mobile clinics provided dental care followed by dental/preventive. The cost per patient visit for all mobile clinic service types ranged from $65 to $529, and appears to be considerably less than those reported in the literature for fixed clinic services. Conclusion The overall costs of all delivery types in mobile clinics were lower than the costs of providing care to Medicare beneficiaries in federally funded health centers, making mobile clinics a sound economic complement to stationary healthcare facilities.