bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nf2 fine-tunes proliferation and tissue alignment during closure of the optic fissure in the embryonic mouse eye
Authors: Sun Wesley R , Ramirez Sara , Spiller Kelly E , Zhao Yan , Fuhrmann Sabine 
Published: October 2020

AbstractUveal coloboma represents one of the most common congenital ocular malformations accounting for up to 10% of childhood blindness (~1 in 5000 live birth). Coloboma originates from defective fusion of the optic fissure (OF), a transient gap that forms during eye morphogenesis by asymmetric, ventral invagination. Genetic heterogeneity combined with the activity of developmentally regulated genes suggests multiple mechanisms regulating OF closure. The tumor suppressor and FERM domain protein Neurofibromin 2 (NF2) controls diverse processes in cancer, development and regeneration, via Hippo pathway and cytoskeleton regulation. In humans, NF2 mutations can cause ocular abnormalities, including coloboma, however, its actual role in OF closure is unknown. Using conditional inactivation in the embryonic mouse eye, our data indicate that loss of Nf2 function results in a novel underlying cause for coloboma. In particular, mutant eyes show substantially increased retinal pigmented epithelium (RPE) proliferation in the fissure region with concomitant acquisition of RPE cell fate. Cells lining the OF margin can maintain RPE fate ectopically and fail to transition from neuroepithelial to cuboidal shape. In the dorsal RPE of the optic cup, Nf2 inactivation leads to a robust increase in cell number, with local disorganization of the cytoskeleton components F-actin and pMLC2. We propose that RPE hyperproliferation is the primary cause for the observed defects causing insufficient alignment of the OF margins in Nf2 mutants and failure to fuse properly, resulting in persistent coloboma. Our findings indicate that limiting proliferation particularly in the RPE layer is a critical mechanism during OF closure.
R&D collaborations along the industry life cycle: the case of German photovoltaics manufacturer
Authors: Hipp Ann 
Published: October 2020

Abstract
Industrial evolution prompts firms to enter into R&D collaborations to ensure competitiveness and substantial growth. This study expands the industry life cycle concept to include the extent and types of R&D collaborations. I analyze 6581 R&D collaborations by 60 manufacturers in the German photovoltaics (PV) industry from 1980 to 2016 using a negative binomial regression model. The results indicate that the number of R&D collaborations is higher in the post-shakeout than in the pre-shakeout period of an industry. While this is particularly true for science-based R&D collaborations with universities and public research organizations, market-based R&D collaborations evolve from predominantly competitors before an industry’s shakeout to suppliers and customers after a shakeout has occurred.
Optimal shape of the harvest control rule for different fishery management objectives
Authors: Yagi Tatsunori , Yamakawa Takashi 
Published: October 2020

Abstract
To determine the optimal shape of the harvest control rule (HCR) achieving common fisheries management objectives (maximizing the average catch, reducing the deviation of yields, and avoiding stock collapse) and ensure robustness to observation errors, we estimate the optimal values of biological reference points (BRPs) composing the HCR. While traditional HCRs usually consist of three BRPs based on the fishing mortality coefficient (F3-HCR), we introduce an alternative HCR defined by 21 BRPs based on the catch levels (C21-HCR) to cover various possible shapes of HCR including smooth ones. We compare the shape and the performance between the optimal C21-HCR and the optimal F3-HCR and conclude that the optimal HCR can be composed of the gradual combination of the basic strategies: the constant escapement strategy, the constant harvest rate (CHR) strategy, and the constant catch strategy. However, the current F3-HCR does not necessarily allow this combination and generally returns lower performance levels than the optimal C21-HCR (since the basic strategy is confined to CHR) excluding the range of low biomass. This result will provide a clear perspective to improve HCR according to the magnitude of assessment errors and to compromise multiple fisheries management objectives when various stakeholders are involved.
Convective and absolute instability of falling viscoelastic liquid jets surrounded by a gas
Authors: Alhushaybari A , Uddin J 
Published: October 2020

Abstract
We examine the convective and absolute instability of a 2D axisymmetric viscoelastic liquid jet falling vertically in a medium of an inviscid gas under the influence of gravity. We use the upper-convected Maxwell model to describe the viscoelastic liquid jet and together with an asymptotic approach, based on the slenderness of the jet, we obtain steady-state solutions. By considering travelling wave modes, and using linear instability analysis, the dispersion relation, relating the frequency to wavenumber of disturbances, is derived. We solve this dispersion relation numerically using the Newton–Raphson method and explore regions of instability in parameter space. In particular, we investigate the influence of gravity, the effect of changing the gas-to-liquid density ratio, the Weber number and the Deborah number on convective and absolute instability. In this paper, we utilize a mapping technique developed by Afzaal (2014, Breakup and instability analysis of compound liquid jets. Doctoral Dissertation, University of Birmingham) to find the cusp point in the complex frequency plane and its corresponding first-order saddle point (the pinch point) in the complex wavenumber plane for absolute instability. The convective/absolute instability boundary is identified for various parameter regimes along the axial length of the jet.
Analytic Sensitivity of 3 Nucleic Acid Detection Assays in Diagnosis of SARS-CoV-2 Infection
Authors: Sieker Jakob T , Horowitz Coby , Hu Cheng-Tsung K , Lacombe-Daphnis Meriane , Chirokas Bernadette , Pina Coteia , Heger Nicholas E , Rabson Arthur R , Zhou Ming , Bogen Steven A , Horowitz Gary L 
Published: October 2020

Abstract

Background
Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription PCR is the primary method to diagnose coronavirus disease 2019 (COVID-19). However, the analytic sensitivity required is not well defined and it is unclear how available assays compare.

Methods
For the Abbott RealTime SARS-CoV-2 assay (m2000; Abbott Molecular), we determined that it could detect viral concentrations as low as 26 copies/mL, we defined the relationship between cycle number and viral concentrations, and we tested naso- and oropharyngeal swab specimens from 8538 consecutive individuals. Using the m2000 as a reference assay method, we described the distribution of viral concentrations in these patients. We then used selected clinical specimens to determine the positive percent agreement of 2 other assays with more rapid turnaround times [Cepheid Xpert Xpress (GeneXpert; Cepheid); n = 27] and a laboratory developed test on the Luminex ARIES system [ARIES LDT (Luminex); n = 50] as a function of virus concentrations, from which we projected their false-negative rates in our patient population.

Results
SARS-CoV-2 was detected in 27% (95% CI: 26%–28%) of all specimens. Estimated viral concentrations were widely distributed, and 17% (95% CI: 16%–19%) of positive individuals had viral concentrations &lt;845 copies/mL. Positive percent agreement was strongly related to viral concentration, and reliable detection (i.e., ≥95%) was observed at concentrations &gt;100 copies/mL for the GeneXpert but not the ARIES LDT, corresponding to projected false-negative rates of 4% (95% CI: 0%–21%) and 27% (95% CI: 11%–46%), respectively.

Conclusions
Substantial proportions of clinical specimens have low to moderate viral concentrations and may be missed by methods with less analytic sensitivity.
Orofacial dyskinesia post resection of pineal gland tumor
Authors: Yazbeck Mohamad , Dabboucy Baraa , Comair Youssef 
Published: October 2020

Abstract
We reported a case of a 33-year-old lady who was diagnosed with a Pineal tumor and underwent craniotomy and gross total surgical resection of the mass through a right occipital transtentorial approach. Immediately upon extubation, the patient started to have persistent chewing-like movements typical of orofacial dyskinesia that resulted later in buccal mucosal injury and swelling of the lips. The movements spontaneously resolved after 3 days. The patient was not taking any medications that were known to induce such movements. Literature review showed that one of the possible mechanisms could be that the suddenly reduced melatonin level in the acute postoperative period leads to dysregulation of dopamine secretion in the nigrostriatal and limbic system causing these abnormal movements. To the best of our knowledge, this is the first such reported complication of orofacial dyskinesia post craniotomy for resection of the pineal tumor in humans.
Samurai and Southern Belles: Interracial Romance, Southern Morality, and the 1860 Japanese Embassy
Authors: Doan Natalia 
Published: October 2020

Abstract
The 1860 Japanese Embassy to the United States was the first diplomatic encounter between Japanese and American people on American soil, and sparked a whirlwind of national optimism and cultural fantasy that challenged the linked conceptions of race, masculinity, and power. In a time when interracial relationships were prohibited in much of the United States, seventeen-year-old samurai Tateishi Onojirō, nicknamed “Tommy,” and his rising count of love letters made headlines across America. This article argues that, in 1860, representations of the 1860 Japanese Embassy and Tateishi in daily Southern newspapers were used to further complicate the concept of Japanese masculinity and dramatize the differences between the American North and South. The perceived desirability of American women became a source of pride at the same time interracial encounters between American women and the Japanese embassy threatened American racial hierarchies. Examining how interactions between samurai diplomats and transnational actors challenged antebellum hierarchies of race, masculinity, and power expands the significance of the 1860 embassy to the study of gender and interracial romantic relations, the production of regional identity, and the influence of Tokugawa Japan on antebellum American identity formation.
Coordinated homeostasis of essential mineral nutrients: a focus on iron
Authors: Hanikenne Marc , Esteves Sara M , Fanara Steven , Rouached Hatem 
Published: October 2020

Abstract
In plants, iron (Fe) transport and homeostasis are highly regulated processes. Fe deficiency or excess dramatically limits plant and algal productivity. Interestingly, complex and unexpected interconnections between Fe and various macro- and micronutrient homeostatic networks, supposedly maintaining general ionic equilibrium and balanced nutrition, are currently being uncovered. Although these interactions have profound consequences for our understanding of Fe homeostasis and its regulation, their molecular bases and biological significance remain poorly understood. Here, we review recent knowledge gained on how Fe interacts with micronutrient (e.g. zinc, manganese) and macronutrient (e.g. sulfur, phosphate) homeostasis, and on how these interactions affect Fe uptake and trafficking. Finally, we highlight the importance of developing an improved model of how Fe signaling pathways are integrated into functional networks to control plant growth and development in response to fluctuating environments.
Low-Dose Activated Protein C Suppresses the Development of Cerebral Infarction and Neurological Deficits in Mice
Authors: Yamato Keiko , Nakajo Yukako , Yamamoto-Imoto Hitomi , Kokame Koichi , Miyata Toshiyuki , Takahashi Jun C , Kataoka Hiroharu , Yanamoto Hiroji 
Published: October 2020

Abstract

BACKGROUND
A large prospective study previously reported that a higher plasma level of protein C (PC) was associated with a lower incidence of ischemic stroke.

OBJECTIVE
To investigate the neuroprotective properties of activated PC (APC) against acute ischemic stroke using the 3-vessel occlusion model.

METHODS
Male C57BL/6J mice received APC (human APC) at 0.25, 0.5, or 1.0 (low dose) or 2.0, 4.0, or 8.0 mg/kg (high dose). Edaravone (Eda) (1.0, 3.0, or 10 mg/kg, a neuroprotectant approved for use in Japan), albumin (2.0 mg/kg), heparin (100 or 600 U/kg), or saline was used as the control. The drug or control was administered intravenously twice in the initial 24 h or 5 times in 3 d, starting 5 min after the induction of ischemia.

RESULTS
Low-dose APC significantly reduced lesion volumes, not affecting the depth of ischemia. High-dose APC did not significantly reduce lesion volumes, causing hemorrhagic transformation in some cases. In the chronic phase, lesion volumes were significantly suppressed in the APC or Eda group, and only the APC group showed a significant attenuation of neurological deficits. The protease-activated receptor (PAR)-1 antagonist SCH79797, administered during preischemia, completely abolished APC-induced neuroprotection. The overshoot-like abrupt recovery in regional cerebral blood flow observed in the control in the initial reperfusion phase was significantly suppressed by the APC treatment, indicating that the cerebral autoregulation system, consisting of endothelial cells and blood-brain barrier functions, was preserved.

CONCLUSION
Low-dose APC, potentially via the PAR-1-dependent anti-inflammatory cascade, protects the brain against ischemic stroke without increasing the risk of hemorrhagic transformation or death.
Optimizing Hepatitis C Virus (HCV) Treatment in a US Colocated HCV/Opioid Agonist Therapy Program
Authors: Habchi Jackie , Thomas Aurielle M , Sprecht-Walsh Sophie , Arias Elenita , Bratberg Jeffrey , Hurley Linda , Hart Susan , Taylor Lynn E 
Published: October 2020

Abstract

Background
A minority of patients with opioid use disorder are treated for hepatitis C virus infection (HCV). While colocated HCV and opioid agonist therapy (OAT) along with harm reduction can facilitate prevention and cascade to cure, there are few real-world examples of such embedded care models in the United States in the direct-acting antiviral (DAA) era.

Methods
We conducted a retrospective chart review to determine sustained virologic response (SVR) and reinfection rates during the first 5-year period of DAA availability among individuals tested and treated on-site at Rhode Island’s only nonprofit methadone maintenance program.

Results
Of 275 who initiated DAAs, the mean age (range) was 43 (22–71) years, 34.5% were female, 57.5% had genotype 1a, 23.3% had cirrhosis, and 92% were Medicaid recipients. SVR was 85.0% (232/273), while modified intent-to-treat SVR was 93.2% (232/249); 17 patients did not achieve SVR, 2 awaited SVR 12 weeks post-end-of-treatment, and 24 were lost to follow-up. Thirty reinfections were identified over 375.5 person-years of follow-up (rate, 7.99/100 person-years). The median time to first reinfection (interquartile range) was 128 (85.25–202.5) days. Before July 1, 2018, 72 patients accessed DAAs over 3.7 years; after Medicaid DAA restrictions were lifted, 109 patients accessed DAAs over 1.3 years. The Prior Authorization (PA) process requires many steps, differing across 11 RI insurers, taking 45–120 minutes per patient.

Conclusions
DAA treatment was effective among a marginalized population in an urban colocated OAT/HCV program. Removing DAA restrictions facilitates treatment initiation. The PA process remains a modifiable barrier to expanding capacity in the United States.
Remdesivir Use in Patients Requiring Mechanical Ventilation due to COVID-19
Authors: Lapadula Giuseppe , Bernasconi Davide Paolo , Bellani Giacomo , Soria Alessandro , Rona Roberto , Bombino Michela , Avalli Leonello , Rondelli Egle , Cortinovis Barbara , Colombo Enrico , Valsecchi Maria Grazia , Migliorino Guglielmo Marco , Bonfanti Paolo , Foti Giuseppe ,   Remdesivir-Ria Study Group, Gambaro Alessandra , Spolti Anna , Beretta Ilaria , Bisi Luca , Cappelletti Anna , Chiesa Elisabetta , Cogliandro Viola , Columpsi Paola , Foresti Sergio , Gustinetti Giulia , Iannuzzi Francesca , Pollastri Ester , Rossi Marianna , Sabbatini Francesca , Squillace Nicola , Ferlicca Daniela , Mauri Fabrizia , Giani Marco , Pozzi Matteo , Russotto Vincenzo , Gambaro Alessandra , Spolti Anna , Beretta Ilaria , Bisi Luca , Cappelletti Anna , Chiesa Elisabetta , Cogliandro Viola , Columpsi Paola , Foresti Sergio , Gustinetti Giulia , Iannuzzi Francesca , Pollastri Ester , Rossi Marianna , Sabbatini Francesca , Squillace Nicola , Ferlicca Daniela , Mauri Fabrizia , Giani Marco , Pozzi Matteo , Russotto Vincenzo 
Published: October 2020

Abstract

Background
Remdesivir has been associated with accelerated recovery of severe coronavirus disease 2019 (COVID-19). However, whether it is also beneficial in patients requiring mechanical ventilation is uncertain.

Methods
All consecutive intensive care unit (ICU) patients requiring mechanical ventilation due to COVID-19 were enrolled. Univariate and multivariable Cox models were used to explore the possible association between in-hospital death or hospital discharge, considered competing-risk events, and baseline or treatment-related factors, including the use of remdesivir. The rate of extubation and the number of ventilator-free days were also calculated and compared between treatment groups.

Results
One hundred thirteen patients requiring mechanical ventilation were observed for a median of 31 days of follow-up; 32% died, 69% were extubated, and 66% were discharged alive from the hospital. Among 33 treated with remdesivir (RDV), lower mortality (15.2% vs 38.8%) and higher rates of extubation (88% vs 60%), ventilator-free days (median [interquartile range], 11 [0–16] vs 5 [0–14.5]), and hospital discharge (85% vs 59%) were observed. Using multivariable analysis, RDV was significantly associated with hospital discharge (hazard ratio [HR], 2.25; 95% CI, 1.27–3.97; P = .005) and with a nonsignificantly lower mortality (HR, 0.73; 95% CI, 0.26–2.1; P = .560). RDV was also independently associated with extubation (HR, 2.10; 95% CI, 1.19–3.73; P = .011), which was considered a competing risk to death in the ICU in an additional survival model.

Conclusions
In our cohort of mechanically ventilated patients, RDV was not associated with a significant reduction of mortality, but it was consistently associated with shorter duration of mechanical ventilation and higher probability of hospital discharge, independent of other risk factors.
Demographic and occupational determinants of anti-SARS-CoV-2 IgG seropositivity in hospital staff
Authors: Martin Christopher A , Patel Prashanth , Goss Charles , Jenkins David R , Price Arthur , Barton Linda , Gupta Pankaj , Zaccardi Francesco , Jerina Helen , Duraisingham Sai , Brunskill Nigel J , Khunti Kamlesh , Pareek Manish 
Published: October 2020

Abstract

Background
Although evidence suggests that demographic characteristics including minority ethnicity increase the risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), it is unclear whether these characteristics, together with occupational factors, influence anti-SARS-CoV-2 IgG seroprevalence in hospital staff.

Methods
We conducted cross-sectional surveillance examining seroprevalence of anti-SARS-CoV-2 IgG amongst staff at University Hospitals of Leicester (UHL) NHS Trust. We quantified seroprevalence stratified by ethnicity, occupation and seniority of practitioner and used logistic regression to examine demographic and occupational factors associated with seropositivity.

Results
A total of 1148/10662 (10.8%) hospital staff members were seropositive. Compared to White staff (seroprevalence 9.1%), seroprevalence was higher in South Asian (12.3%) and Black (21.2%) staff. The occupations and department with the highest seroprevalence were nurses/healthcare assistants (13.7%) and the Emergency Department (ED)/Acute Medicine (17.5%), respectively. Seroprevalence decreased with seniority in medical/nursing practitioners. Minority ethnicity was associated with seropositivity on an adjusted analysis (South Asian: aOR 1.26; 95%CI: 1.07–1.49 and Black: 2.42; 1.90–3.09). Anaesthetics/ICU staff members were less likely to be seropositive than ED/Acute medicine staff (0.41; 0.27–0.61).

Conclusions
Ethnicity and occupational factors, including specialty and seniority, are associated with seropositivity for anti-SARS-Cov-2 IgG. These findings could be used to inform occupational risk assessments for front-line healthcare workers.
Endotypes of primary osteoarthritis identified by plasma metabolomics analysis
Authors: Werdyani Salem , Liu Ming , Zhang Hongwei , Sun Guang , Furey Andrew , Randell Edward W , Rahman Proton , Zhai Guangju 
Published: October 2020

Abstract

Objective
To identify endotypes of osteoarthritis (OA) by a metabolomics analysis.

Methods
Study participants included hip/knee OA patients and controls. Fasting plasma samples were metabolomically profiled. Common factor analysis and K-means clustering were applied to the metabolomics data to identify the endotypes of OA patients. Logistic regression was utilized to identify the most significant metabolites contributing to the endotypes. Clinical and epidemiological factors were examined in relation to the identified OA endotypes.

Results
Six hundred and fifteen primary OA patients and 237 controls were included. Among the 186 metabolites measured, 162 passed the quality control analysis. The 615 OA patients were classified in three clusters (A, 66; B, 200; and C, 349). Patients in cluster A had a significantly higher concentration of butyrylcarnitine (C4) than other clusters and controls (all P &lt; 0.0002). Elevated C4 is thought to be related to muscle weakness and wasting. Patients in cluster B had a significantly lower arginine concentration than other clusters and controls (all P &lt; 7.98 × 10−11). Cluster C patients had a significantly lower concentration of lysophosphatidylcholine (with palmitic acid), which is a pro-inflammatory bioactive compound, than other clusters and controls (P &lt; 3.79 × 10−6). Further, cluster A had a higher BMI and prevalence of diabetes than other clusters (all P ≤ 0.0009), and also a higher prevalence of coronary heart disease than cluster C (P = 0.04). Cluster B had a higher prevalence of coronary heart disease than cluster C (P = 0.003) whereas cluster C had a higher prevalence of osteoporosis (P = 0.009).

Conclusion
Our data suggest three possible clinically actionable endotypes in primary OA: muscle weakness, arginine deficit and low inflammatory OA.