bluuebunny/crossref_metadata_2025 huggingface dataset:
Static to inducibly dynamic stereocontrol: The convergent use of racemic β-substituted ketones
Authors: DeHovitz Jacob S. , Loh Yong Yao , Kautzky Jacob A. , Nagao Kazunori , Meichan Andrew J. , Yamauchi Motoshi , MacMillan David W. C. , Hyster Todd K.
Published: October 2020

Expanding the kinetic resolution purview

Dynamic kinetic resolution (DKR) is a powerful method to transform a pair of mirror-image reactants into just one of the two possible mirror-image products. The key is to find a means of rapidly interconverting the reactants while one of them is being more efficiently funneled to product. DeHovitz
et al.
report cooperative application of organocatalysis, photoredox catalysis, and enzymatic catalysis to achieve DKR of β-substituted ketones into chiral alcohols. This β position has typically been considered too configurationally stable for a DKR approach.

Science
, this issue p.
1113
Moving beyond buzzwords
How Innovation Works
Matt Ridley
HarperCollins, 2020. 416 pp.
The Innovation Delusion
Lee Vinsel and Andrew L. Russell
Currency, 2020. 272 pp.
Authors: Greenbaum Dov , Gerstein Mark
Published: October 2020

Rejecting conventional connotations, two books urge readers to rethink innovation
Plotting a path to a more sustainable future
The Ministry for the Future
Kim Stanley Robinson
Orbit, 2020. 576 pp.
Authors: Abbott Carl
Published: October 2020

Persistent political pressure staves off global warming in a new climate allegory
Zena Werb (1945–2020)
Authors: Boudreau Nancy , Bissell Mina
Published: October 2020

Pioneering cancer biologist and beloved mentor
Making a bed for viral infections
Authors: Mirchandani Ananda S. , Walmsley Sarah R.
Published: October 2020

An inflamed mucosal niche is permissive for symptomatic respiratory syncytial virus infection
Novel communities are a risky business
Authors: Dornelas Maria , Madin Joshua S.
Published: October 2020

High turnover leads to novel combinations of species and involves high extinction
A discrete subset of epigenetically primed human NK cells mediates antigen-specific immune responses
Authors: Stary Victoria , Pandey Ram Vinay , Strobl Johanna , Kleissl Lisa , Starlinger Patrick , Pereyra David , Weninger Wolfgang , Fischer Gottfried F. , Bock Christoph , Farlik Matthias , Stary Georg
Published: October 2020

CD49a
+
CD16
−
NK cells from the liver and contact dermatitis lesions specifically recognize antigens and contribute to adaptive immunity.
In Vitro
Activity Analysis of a New Polymyxin, SPR741, Tested in Combination with Antimicrobial Agents against a Challenge Set of
Enterobacteriaceae
, Including Molecularly Characterized Strains
Authors: Mendes Rodrigo E. , Rhomberg Paul R. , Lister Troy , Cotroneo Nicole , Parr Thomas R. , Castanheira Mariana
Published: October 2020

The activities of azithromycin, fusidic acid, vancomycin, doxycycline, and minocycline were evaluated alone and in combination with SPR741. A total of 202
Escherichia coli
and 221
Klebsiella pneumoniae
isolates were selected, and they included a genome-sequenced subset (
n
= 267), which was screened
in silico
for β-lactamase, macrolide-lincosamide-streptogramin (MLS), and tetracycline (
tet
) genes. Azithromycin (>16 mg/liter), fusidic acid (>64 mg/liter), vancomycin (>16 mg/liter), and SPR741 (>8 mg/liter) showed off-scale MICs when each was tested alone against all isolates.
Mutations in
fbiD
(
Rv2983
) as a Novel Determinant of Resistance to Pretomanid and Delamanid in Mycobacterium tuberculosis
Authors: Rifat Dalin , Li Si-Yang , Ioerger Thomas , Shah Keshav , Lanoix Jean-Philippe , Lee Jin , Bashiri Ghader , Sacchettini James , Nuermberger Eric
Published: October 2020

The nitroimidazole prodrugs delamanid and pretomanid comprise one of only two new antimicrobial classes approved to treat tuberculosis (TB) in 50 years. Prior
in vitro
studies suggest a relatively low barrier to nitroimidazole resistance in
Mycobacterium tuberculosis
, but clinical evidence is limited to date. We selected pretomanid-resistant
M. tuberculosis
mutants in two mouse models of TB using a range of pretomanid doses. The frequency of spontaneous resistance was approximately 10
−5
CFU.
Comparative Peptidomic and Metatranscriptomic Analyses Reveal Improved Gamma-Amino Butyric Acid Production Machinery in Levilactobacillus brevis Strain NPS-QW 145 Cocultured with Streptococcus thermophilus Strain ASCC1275 during Milk Fermentation
Authors: Xiao Tingting , Yan Aixin , Huang Jian-Dong , Jorgensen Erik M. , Shah Nagendra P.
Published: October 2020

The high-gamma-amino butyric acid (GABA)-producing bacterium
Levilactobacillus brevis
strain NPS-QW 145, along with
Streptococcus thermophilus
(one of the two starter bacteria used to make yogurt for its proteolytic activity), enhances GABA production in milk. However, a mechanistic understanding of how
Levilactobacillus brevis
cooperates with
S. thermophilus
to stimulate GABA production has been lacking. Comparative peptidomic and metatranscriptomic analyses were carried out to unravel the casein and lactose utilization patterns during milk fermentation with the coculture.
Regulation of Pulmonary Bacterial Immunity by Follistatin-Like Protein 1
Authors: Henkel Matthew , Dutta Justin A. , Partyka Jessica , Eddens Taylor , Hirsch Raphael , Kolls Jay K. , Campfield Brian T.
Published: October 2020

Klebsiella pneumoniae
is a common cause of antibiotic-resistant pneumonia. Follistatin-like protein 1 (FSTL-1) is highly expressed in the lung and is critical for lung homeostasis. The role of FSTL-1 in immunity to bacterial pneumonia is unknown. Wild-type (WT) and FSTL-1 hypomorphic (Hypo) mice were infected with
Klebsiella pneumoniae
to determine infectious burden, immune cell abundance, and cytokine production. FSTL-1 Hypo/TCRδ
−/−
and FSTL-1 Hypo/IL17ra
−/−
were also generated to assess the role of γδT17 cells in this model.
Impact of oral corticosteroids on respiratory outcomes in acute preschool wheeze: a randomised clinical trial
Authors: Wallace Alexandra , Sinclair Owen , Shepherd Michael , Neutze Jocelyn , Trenholme Adrian , Tan Eunicia , Brabyn Christine , Bonisch Megan , Grey Naomi , Johnson David W , McNamara David , Thompson John M D , Asher Innes , Dalziel Stuart R
Published: October 2020

Objective

To determine if administration of oral prednisolone to preschool children with acute wheeze alters respiratory outcomes.

Design

Double-blind, randomised, placebo-controlled equivalence trial.

Setting

Three hospitals in New Zealand.

Patients

477 children aged 24–59 months with acute wheeze associated with respiratory illness.

Interventions

2 mg/kg (maximum 40 mg) oral prednisolone or similar placebo, once daily for 3 days.

Main outcome measures

Primary outcome was change in Preschool Respiratory Assessment Measure (PRAM) score 24 hours after intervention. Secondary outcomes included PRAM score at 4 hours, length of emergency department and inpatient stays, admission and representation rates, time to return to normal activities and use of additional oral prednisolone or intravenous medications. Analysis was by intention-to-treat.

Results

There was no difference between groups for change in PRAM score at 24 hours (difference between means −0.39, 95% CI −0.84 to 0.06, p=0.09). Absolute PRAM score was lower in the prednisolone group at 4 hours (median (IQR) 1 (0–2) vs 2 (0–3), p=0.01) and 24 hours (0 (0–1) vs 0 (0–1), p=0.01), when symptoms had resolved for most children regardless of initial treatment. Admission rate, requirement for additional oral prednisolone and use of intravenous medication were lower in the prednisolone group, although there were no differences between groups for time taken to return to normal activities or rates of representation within 7 days.

Conclusion

Oral prednisolone does not alter respiratory outcomes at 24 hours or beyond in preschool children presenting with acute wheeze.
Correlation of histopathology of trabecular meshwork with clinical features in primary congenital glaucoma
Authors: Agarwal Rinky , Sen Seema , Kashyap Seema , Dada Tanuj , Nag Tapas Chandra , Gupta Viney , Sihota Ramanjit
Published: October 2020

Purpose

To correlate histopathological changes of trabecular meshwork (TM) with clinical features in primary congenital glaucoma (PCG).

Methods

This was a prospective interventional study including 66 eyes of 39 PCG children aged ≤12 months at diagnosis. Corneal clarity, corneal diameter (CD), intraocular pressure (IOP) and cup disc ratio (C:D ratio) were assessed at baseline and at 1-year follow-up. The trabecular meshwork (TM) specimens obtained during primary combined trabeculectomy and trabeculotomy augmented with Mitomycin-C were evaluated on light microscopy to look for eosinophilic membrane (EM), status of trabecular beams and trabecular endothelial cells (TEC), presence of intervening spaces, TM thickness and TEC count which were then correlated with clinical features.

Results

At 1-year follow-up, IOP reduced from 27.96±10.2 to 11.88±5.63 mm Hg, p<0.001, C:D ratio decreased from 0.65±0.34 to 0.49±0.06, p=0.036, and the bleb had a significant tendency to change from well formed (59–46) to flat type (3–6) or thin, cystic type (4–14) (p=0.014). Presence of EM on the cameral surface was associated with a lower baseline IOP. Fused trabecular beams were associated with higher baseline IOP. The TM was significantly thicker in eyes with IOP >20 mm Hg at presentation (1.86±0.7 mm vs 1.3±0.47 mm, p=0.0356). Eyes with IOP ≤14 mm Hg at final follow-up had lower TEC count than eyes with IOP >14 mm Hg (0.92±0.45 cells/mm2 vs 1.00±0.74 cells/mm2, p=0.0028).

Conclusion

A light microscopic analysis of surgical specimens may guide prognosis of PCG. However, larger studies are required to validate these results.
Overcoming barriers of retinal care delivery during a pandemic—attitudes and drivers for the implementation of digital health: a global expert survey
Authors: Faes Livia , Rosenblatt Amir , Schwartz Roy , Touhami Sara , Ventura Camila V , Chatziralli Irini P , Ruiz-Medrano Jorge , Vogt Denise , Savastano Alfonso , Ruiz-Garcia Humberto , Pohlmann Dominika , Loewenstein Anat
Published: October 2020

Background/Aims

The SARS-CoV-2 pandemic has imposed barriers to retinal care delivery worldwide. In this context, retinal services are exploring novel ways to ensure access to healthcare.

Methods

We conducted a worldwide survey among retinal specialists between March 31, 2020 and April 12, 2020. The expert survey was developed on the basis of focus group discussions involving retinal specialists and literature searches. It included 44 questions on alternative ways of care provision including digital health domains such as teleophthalmology, home monitoring or decentralised patient care.

Results

214 retinal experts participated in the survey, of which 120 (56.1%) had more than 15 years of experience in ophthalmology. Most participants were clinicians (n=158, 73.9%) practising in Western Europe (n=159, 74%). In the majority of institutions, teleophthalmology, home monitoring and decentralised patient care have not been implemented before the pandemic (n=46, 21.8.1%; n=64, 29.9%; n=38, 19.1%). During the pandemic, the use of teleophthalmology and home monitoring increased significantly (n=105, p<0.001; n=90, p<0.001). In the subgroup of institutions reporting no teleophthalmology service before and implementing a service during the pandemic (34/70, 48.6%), reimbursement was the sole significant parameter (OR 9.62 (95% CI 2.42 to 38.16); p<0.001).

Conclusion

Digital health is taking the centre stage tackling unpreceded challenges of retinal care delivery during the SARS-CoV-2 pandemic and may sustainably change the way we practice ophthalmology.
Retinal findings in hospitalised patients with severe COVID-19
Authors: Pereira Leonardo Amarante , Soares Larissa Caroline Mansano , Nascimento Priscila Alves , Cirillo Luciano Rabello Netto , Sakuma Hebert Toshiaki , Veiga Glaucia Luciano da , Fonseca Fernando Luiz Afonso , Lima Vagner Loduca , Abucham-Neto Julio Zaki
Published: October 2020

Aim

To identify retinal findings using dilated eye examination, which are possibly related to SARS-CoV-2 infection in hospitalised patients with confirmed severe COVID-19.

Methods

In this cross-sectional study, hospitalised patients with confirmed severe COVID-19 in a single referral centre for the treatment of COVID-19, in Santo André, São Paulo Metropolitan Area, Brazil, underwent dilated eye examination of both eyes performed by a retina specialist. Findings were recorded using a portable digital fundus camera. Retinographies were analysed by two retina specialists. Medical records were reviewed for assessment of patient demographics, baseline comorbidities and clinical data.

Results

There were a total of 18 patients, nine (50%) male, median IQR age of 62.5 (12) years. Ten of the 18 patients (55.6%; 95% CI 33.7 to 75.4) had abnormalities on dilated eye examination. The main findings were flame-shaped haemorrhages (N=4; 22.2%; 95% CI 9.0 to 45.2) and ischaemic pattern lesions (cotton wool spots and retinal sectorial pallor) (N=4; 22.2%; 95% CI 9.0 to 45.2), with one patient having both cotton wool spots and flame-shaped haemorrhages.

Conclusion

These findings suggest that patients with severe COVID-19 have acute vascular lesions of the inner retina including flame-shaped haemorrhages and cotton wool spots. Further studies controlling for confounding factors are necessary to properly assess these findings so as to increase the understanding of COVID-19 pathophysiology and to identify new therapies.
Guidelines on the management of ascites in cirrhosis
Authors: Aithal Guruprasad P , Palaniyappan Naaventhan , China Louise , Härmälä Suvi , Macken Lucia , Ryan Jennifer M , Wilkes Emilie A , Moore Kevin , Leithead Joanna A , Hayes Peter C , O"Brien Alastair J , Verma Sumita
Published: October 2020

The British Society of Gastroenterology in collaboration with British Association for the Study of the Liver has prepared this document. The aim of this guideline is to review and summarise the evidence that guides clinical diagnosis and management of ascites in patients with cirrhosis. Substantial advances have been made in this area since the publication of the last guideline in 2007. These guidelines are based on a comprehensive literature search and comprise systematic reviews in the key areas, including the diagnostic tests, diuretic use, therapeutic paracentesis, use of albumin, transjugular intrahepatic portosystemic stent shunt, spontaneous bacterial peritonitis and beta-blockers in patients with ascites. Where recent systematic reviews and meta-analysis are available, these have been updated with additional studies. In addition, the results of prospective and retrospective studies, evidence obtained from expert committee reports and, in some instances, reports from case series have been included. Where possible, judgement has been made on the quality of information used to generate the guidelines and the specific recommendations have been made according to the ‘Grading of Recommendations Assessment, Development and Evaluation (GRADE)’ system. These guidelines are intended to inform practising clinicians, and it is expected that these guidelines will be revised in 3 years’ time.
Platelet aggregates, a marker of severe COVID-19 disease
Authors: Rampotas Alexandros , Pavord Sue
Published: October 2020

Thrombocytopenia is common in an intensive care unit (ICU) setting due to endogenous and iatrogenic factors. Despite that, thrombocytopenia in patients with severe COVID-19 infections is surprisingly uncommon. By examining the blood film of 20 ICU patients with COVID-19, we observed the presence of platelet aggregates and macrothrombocytes indicating increased platelet activity. We compared these findings with 20 blood films of non-severe COVID-19 cases where these findings were absent. These morphology features could be consistent with severe COVID-19 infection and is further evidence of the important role that platelets play when COVID-19 manifests with thrombotic complications or respiratory failure.
It depends on how you ask: measuring bias in population surveys of compliance with COVID-19 public health guidance
Authors: Timmons Shane , McGinnity Frances , Belton Cameron , Barjaková Martina , Lunn Peter
Published: October 2020

Objective

Accurate measurement of compliance with COVID-19 guidance is important for public health policy and communications. Responses to surveys, however, are susceptible to psychological biases, including framing effects and social desirability. Our aim was to measure the effects of these biases on estimates of compliance with public health guidance (eg, hand-washing, social distancing).

Design

We conducted two online experiments (n=1800) and varied whether questions were framed positively or negatively (eg, ‘I always wash my hands…’ vs ‘I don’t always wash my hands…’). We also varied the degree to which anonymity was assured, via a ‘list’ experiment.

Results

Reported compliance, despite being generally high, was reduced by negatively framing questions and increasing anonymity using a list experiment technique. Effect sizes were large: compliance estimates diminished by up to 17% points and 10% points, respectively.

Conclusion

Estimates of compliance with COVID-19 guidance vary substantially with how the question is asked. Standard tracking surveys tend to pose questions in ways that lead to higher estimates than alternative approaches. Experimental tests of these surveys offer public health officials greater insight into the range of likely compliance estimates to better inform policy and communications.
Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions
Authors: Russick Jules , Joubert Pierre-Emmanuel , Gillard-Bocquet Mélanie , Torset Carine , Meylan Maxime , Petitprez Florent , Dragon-Durey Marie-Agnes , Marmier Solenne , Varthaman Aditi , Josseaume Nathalie , Germain Claire , Goc Jérémy , Dieu-Nosjean Marie-Caroline , Validire Pierre , Fournel Ludovic , Zitvogel Laurence , Bindea Gabriela , Lupo Audrey , Damotte Diane , Alifano Marco , Cremer Isabelle
Published: October 2020

Background

Natural killer (NK) cells play a crucial role in tumor immunosurveillance through their cytotoxic effector functions and their capacity to interact with other immune cells to build a coordinated antitumor immune response. Emerging data reveal NK cell dysfunction within the tumor microenvironment (TME) through checkpoint inhibitory molecules associated with a regulatory phenotype.

Objective

We aimed at analyzing the gene expression profile of intratumoral NK cells compared with non-tumorous NK cells, and to characterize their inhibitory function in the TME.

Methods

NK cells were sorted from human lung tumor tissue and compared with non- tumoral distant lungs.

Results

In the current study, we identify a unique gene signature of NK cell dysfunction in human non-small cell lung carcinoma (NSCLC). First, transcriptomic analysis reveals significant changes related to migratory pattern with a downregulation of sphingosine-1-phosphate receptor 1 (S1PR1) and CX3C chemokine receptor 1 (CX3CR1) and overexpression of C-X-C chemokine receptor type 5 (CXCR5) and C-X-C chemokine receptor type 6 (CXCR6). Second, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and killer cell lectin like receptor (KLRC1) inhibitory molecules were increased in intratumoral NK cells, and CTLA-4 blockade could partially restore MHC class II level on dendritic cell (DC) that was impaired during the DCs/NK cell cross talk. Finally, NK cell density impacts the positive prognostic value of CD8+ T cells in NSCLC.

Conclusions

These findings demonstrate novel molecular cues associated with NK cell inhibitory functions in NSCLC.
Triage and justice in an unjust pandemic: ethical allocation of scarce medical resources in the setting of racial and socioeconomic disparities
Authors: Tolchin Benjamin , Hull Sarah C , Kraschel Katherine
Published: October 2020

Shortages of life-saving medical resources caused by COVID-19 have prompted hospitals, healthcare systems, and governmentsto develop crisis standards of care, including 'triage protocols' to potentially ration medical supplies during the public health emergency. At the same time, the pandemic has highlighted and exacerbated racial, ethnic, and socioeconomic health disparities that together constitute a form of structural racism. These disparities pose a critical ethical challenge in developing fair triage systems that will maximize lives saved without perpetuating systemic inequities. Here we review alternatives to 'utilitarian' triage, including first-come first-served, egalitarian, and prioritarian systems of allocating scarce medical resources. We assess the comparative advantages and disadvantages of these allocation schemes. Ultimately, we argue that while triage protocols should not exacerbate disparities, they are not an adequate mechanism for redressing systemic health inequities. Entrenched health disparities must be addressed through broader social change.
Enigmatic role of coagulopathy among sepsis survivors: a review of coagulation abnormalities and their possible link to chronic critical illness
Authors: Winer Leah K , Salyer Christen , Beckmann Nadine , Caldwell Charles C , Nomellini Vanessa
Published: October 2020

There are sparse clinical data addressing the persistence of disordered coagulation in sepsis and its role in chronic critical illness. Coagulopathy in the absence of anticoagulant therapy and/or liver disease can be highly variable in sepsis, but it tends to be prolonged in patients in the intensive care unit with a length of stay greater than 14 days. These coagulation abnormalities tend to precede multisystem organ failure and persistence of these coagulation derangements can predict 28-day mortality. The studies evaluated in this review consistently link sepsis-associated coagulopathy to poor long-term outcomes and indicate that disordered coagulation is associated with unfavorable outcomes in chronic critical illness. However, the causative mechanism and the definitive link remain unclear. Longer follow-up and more granular data will be required to fully understand coagulopathy in the context of chronic critical illness.
Time-focusing time-of-flight, a new method to turn a MAC-E-filter into a quasi-differential spectrometer
Authors: Fulst A. , Lokhov A. , Fedkevych M. , Steinbrink N. , Weinheimer C.
Published: October 2020

Spectrometers based on the magnetic adiabatic collimation followed by an electrostatic filter (MAC-E-filter) principle combine high angular acceptance with an excellent energy resolution. These features make MAC-E-filters very valuable for experiments where the kinetic energy of ions or electrons from rare processes has to be measured with utmost sensitivity and precision. Examples are direct neutrino mass experiments like KATRIN which investigate the energy of electrons in the endpoint region of the tritium $$\beta $$
β
-spectrum. However, the MAC-E-filter is a very sharp energy high-pass filter but not a differential spectrometer. To determine a spectral shape of a charged particle source, different electric retarding potentials have to be used sequentially, reducing the statistics. In a previous work we have shown that the advantages of the standard MAC-E-filter can be combined with a measurement of the time-of-flight (TOF), allowing to determine spectral information over a certain energy range with one retarding potential only, with the corresponding gain in statistics. This TOF method requires one to know the start time of the charged particles, which is not always possible. Therefore, we propose a new method which does not require the determination of the start time and which we call “time-focusing time-of-flight” (tfTOF): by applying a time dependent acceleration and deceleration potential at a subsequent MAC-E-filter, an energy dependent post-bunching of the charged particles is achieved.
CRITICAL SUCCESS FACTORS IN THE FRONT END OF INNOVATION: RESULTS FROM AN EMPIRICAL STUDY
Authors: WAGNER SIMON , BICAN PETER M. , BREM ALEXANDER
Published: October 2020

This study empirically analyses the effects of five critical success factors on the front end of innovation and new product development success. Data from a self-developed questionnaire on a cross-industry sample of 77 German-based small- and medium-sized firms were collected through an online survey. Accouting for factors not included in previous studies, the results indicate that strategic alignment, creative encouragement, and external collaboration are the key predictors of front-end success. Surprisingly, the impact of process formalisation and the importance of cross-functional collaboration for front-end success could not be supported. We conject that collaboration in the front end of innovation must exceed simple communication and information exchange to significantly effect front-end success. Managerial implications of this study include the need for an internal search for ideas by fostering employees’ creative abilities while simultaneously remaining open to external input. Also, activities in the front end of innovation should be aligned with the organisation’s overall business strategy to promote successful ideation.
Foraminifers in upper Viséan–lower Serpukhovian limestones (Mississippian) from South Wales: regional correlation and implications for British foraminiferal zonal schemes
Authors: Cózar Pedro , Somerville Ian D.
Published: October 2020

Foraminiferal assemblages have been recorded in sections from the Gower Peninsula and North Crop in South Wales, of Holkerian (Stormy Limestone Formation), late Asbian to lower late Brigantian (Oxwich Head Limestone Formation) and late Brigantian (Oystermouth Formation) age. The absence of lower Asbian foraminifers in the studied successions is confirmed. These formations and biostratigraphic boundaries are correlated with those in northern England, where similar foraminiferal assemblages are recorded.

It is considered that
Loeblichia paraammonoides
does not occur in Wales. Its record is based on a misidentification of
L
.
ammonoides
and its presence in Britain is questioned. The distribution of
Bibradya
in Britain seems to be restricted to the late Asbian.
Archaediscus
at angulatus stage and ancestral forms of
Palaeotextularia
are confirmed in the uppermost Holkerian. Ancestral forms of
Koskinobigenerina
and
Climacammina
recorded below the upper Asbian and lower Brigantian, respectively, are considered to be misidentifications.
Archaediscus
at tenuis stage recorded from the Oystermouth Formation can form a plausible marker for the equivalent Three Yard Limestone and Four Fathom Limestone members in northern England. The acme of discoidal archaediscids is equivalent to the Four Fathom Limestone Member. In contrast to a ready comparison with foraminiferal microfaunas from northern England, comparison with North Wales is problematic. Nevertheless, it would appear that most assemblages previously cited as early Asbian, would now likely be reassigned to the late Asbian, similar to the observations in South Wales.
New Numerical Algorithm for Deflation of Infinite and Zero Eigenvalues and Full Solution of Quadratic Eigenvalue Problems
Authors: Drmač Zlatko , Glibić Ivana Šain
Published: October 2020

This article presents a new method for computing all eigenvalues and eigenvectors of quadratic matrix pencil
Q
(λ)=λ
2
M
+ λ
C
+
K
. It is an upgrade of the quadeig algorithm by Hammarlinget al., which attempts to reveal and remove by deflation a certain number of zero and infinite eigenvalues before QZ iterations. Proposed modifications of the quadeig framework are designed to enhance backward stability and to make the process of deflating infinite and zero eigenvalues more numerically robust. In particular, careful preprocessing allows scaling invariant/component-wise backward error and thus a better condition number. Further, using an upper triangular version of the Kronecker canonical form enables deflating additional infinite eigenvalues, in addition to those inferred from the rank of
M
. Theoretical analysis and empirical evidence from thorough testing of the software implementation confirm superior numerical performances of the proposed method.
Modular Neural Networks for Low-Power Image Classification on Embedded Devices
Authors: Goel Abhinav , Aghajanzadeh Sara , Tung Caleb , Chen Shuo-Han , Thiruvathukal George K. , Lu Yung-Hsiang
Published: October 2020

Embedded devices are generally small, battery-powered computers with limited hardware resources. It is difficult to run deep neural networks (DNNs) on these devices, because DNNs perform millions of operations and consume significant amounts of energy. Prior research has shown that a considerable number of a DNN’s memory accesses and computation are redundant when performing tasks like image classification. To reduce this redundancy and thereby reduce the energy consumption of DNNs, we introduce the Modular Neural Network Tree architecture. Instead of using one large DNN for the classifier, this architecture uses multiple smaller DNNs (called
modules
) to progressively classify images into groups of categories based on a novel visual similarity metric. Once a group of categories is selected by a module, another module then continues to distinguish among the similar categories within the selected group. This process is repeated over multiple modules until we are left with a single category. The computation needed to distinguish dissimilar groups is avoided, thus reducing redundant operations, memory accesses, and energy. Experimental results using several image datasets reveal the effectiveness of our proposed solution to reduce memory requirements by 50% to 99%, inference time by 55% to 95%, energy consumption by 52% to 94%, and the number of operations by 15% to 99% when compared with existing DNN architectures, running on two different embedded systems: Raspberry Pi 3 and Raspberry Pi Zero.
Variable Step-Size Control Based on Two-Steps for Radau IIA Methods
Authors: Pinto Severiano González , Abreu Domingo Hernández , Montijano Juan Ignacio
Published: October 2020

Two-step embedded methods of order
s
based on
s
-stage Radau IIA formulas are considered for the variable step-size integration of stiff differential equations. These embedded methods are aimed at local error control and are computed through a linear combination of the internal stages of the underlying method in the last two steps. Particular embedded methods for 2 ≤
s
≤ 7 internal stages with good stability properties and damping for the stiff components are constructed. Furthermore, a new formula for step-size change is proposed, having the advantage that it can be applied to any
s
-stage Radau IIA method. It is shown through numerical testing on some representative stiff problems that the RADAU5 code by Hairer and Wanner with the new strategy performs as well or even better as with the standard one, which is only feasible for an odd number of stages. Numerical experiments support the efficiency and flexibility of the new step-size change strategy.
Data Profiling in Property Graph Databases
Authors: Maiolo Sofía , Etcheverry Lorena , Marotta Adriana
Published: October 2020

Property Graph databases are being increasingly used within the industry as a powerful and flexible way to model real-world scenarios. With this flexibility, a great challenge appears regarding profiling tasks due to the need of adapting them to these new models while taking advantage of the Property Graphs’ particularities. This article proposes a set of data profiling tasks by integrating existing methods and techniques and an taxonomy to classify them. In addition, an application pipeline is provided while a formal specification of some tasks is defined.
Creating Accessible Online Floor Plans for Visually Impaired Readers
Authors: Madugalla Anuradha , Marriott Kim , Marinai Simone , Capobianco Samuele , Goncu Cagatay
Published: October 2020

We present a generic model for providing blind and severely vision-impaired readers with access to online information graphics. The model supports fully and semi-automatic transcription and allows the reader a choice of presentation mediums. We evaluate the model through a case study: online house floor plans. To do so, we conducted a formative user study with severely vision impaired users to determine what information they would like from an online floor plan and how to present the floor plan as a text-only description, tactile graphic, and on a touchscreen with audio feedback. We then built an automatic transcription tool using specialized graphics recognition algorithms. Finally, we measured the quality of system recognition as well as conducted a second user study to evaluate the usefulness of the accessible graphics produced by the tool for each of the three formats. The results generally support the design of the generic model and the usefulness of the tool we have produced. However, they also reveal the inability of current graphics recognition algorithms to handle unforeseen graphical conventions. This highlights the need for automatic transcription systems to return a level of confidence in the recognized components and to present this to the end-user so they can have an appropriate level of trust.
Polygenic Scores in Developmental Psychology: Invite Genetics In, Leave Biodeterminism Behind
Authors: Raffington Laurel , Mallard Travis , Harden K. Paige
Published: October 2020

Polygenic scores offer developmental psychologists new methods for integrating genetic information into research on how people change and develop across the life span. Indeed, polygenic scores have correlations with developmental outcomes that rival correlations with traditional developmental psychology variables, such as family income. Yet linking people's genetics with differences between them in socially valued developmental outcomes, such as educational attainment, has historically been used to justify acts of state-sponsored violence. In this review, we emphasize that an interdisciplinary understanding of the environmental and structural determinants of social inequality, in conjunction with a transactional developmental perspective on how people interact with their environments, is critical to interpreting associations between polygenic measures and phenotypes. While there is a risk of misuse, early applications of polygenic scores to developmental psychology have already provided novel findings that identify environmental mechanisms of life course processes that can be used to diagnose inequalities in social opportunity.
Subduction-Driven Volatile Recycling: A Global Mass Balance
Authors: Bekaert D.V. , Turner S.J. , Broadley M.W. , Barnes J.D. , Halldórsson S.A. , Labidi J. , Wade J. , Walowski K.J. , Barry P.H.
Published: October 2020

Volatile elements (water, carbon, nitrogen, sulfur, halogens, and noble gases) played an essential role in the secular evolution of the solid Earth and emergence of life. Here we provide an overview of Earth's volatile inventories and describe the mechanisms by which volatiles are conveyed between Earth's surface and mantle reservoirs, via subduction and volcanism. Using literature data, we compute volatile concentration and flux estimates for Earth's major volatile reservoirs and provide an internally balanced assessment of modern global volatile recycling. Using a nitrogen isotope box model, we show that recycling of N (and possibly C and S) likely began before 2 Ga and that ingassing fluxes have remained roughly constant since this time. In contrast, our model indicates recycling of H2O(and most likely noble gases) was less efficient in the past. This suggests a decoupling of major volatile species during subduction through time, which we attribute to the evolving thermal regime of subduction zones and the different stabilities of the carrier phases hosting each volatile. ▪  This review provides an overview of Earth's volatile inventory and the mechanisms by which volatiles are transferred between Earth reservoirs via subduction. ▪  The review frames the current thinking regarding how Earth acquired its original volatile inventory and subsequently evolved through subduction processes and volcanism.
Defining and Classifying New Subgroups of Diabetes
Authors: Balasubramanyam Ashok
Published: October 2020

An etiologically based classification of diabetes is needed to account for the heterogeneity of type 1 and type 2 diabetes (T1D and T2D) and emerging forms of diabetes worldwide. It may be productive for both classification and clinical discovery to consider variant forms of diabetes as a spectrum. Maturity onset diabetes of youth and neonatal diabetes serve as models for etiologically defined, rare forms of diabetes in the spectrum. Ketosis-prone diabetes is a model for more complex forms, amenable to phenotypic dissection. Bioinformatic approaches such as clustering analyses of large datasets and multi-omics investigations of rare and atypical phenotypes are promising avenues to explore and define new subgroups of diabetes.
Dynamics of Atrial Fibrillation Mechanisms and Comorbidities
Authors: Heijman Jordi , Linz Dominik , Schotten Ulrich
Published: October 2020

Atrial fibrillation (AF) contributes to morbidity and mortality of millions of individuals. Its molecular, cellular, neurohumoral, and hemodynamic pathophysiological mechanisms are complex, and there is increasing awareness that a wide range of comorbidities can contribute to AF-promoting atrial remodeling. Moreover, recent research has highlighted that AF risk is not constant and that the temporal variation in concomitant conditions contributes to the complexity of AF dynamics. In this review, we provide an overview of fundamental AF mechanisms related to established and emerging comorbidities or risk factors and their role in the AF-promoting effects. We focus on the accumulating evidence for the relevance of temporally dynamic changes in these risk factors and the consequence for AF initiation and maintenance. Finally, we highlight the important implications for future research and clinical practice resulting from the dynamic interaction between AF risk factors and mechanisms.
MMP9 inhibition increases autophagic flux in chronic heart failure
Authors: Nandi Shyam S. , Katsurada Kenichi , Sharma Neeru M. , Anderson Daniel R. , Mahata Sushil K. , Patel Kaushik P.
Published: October 2020

This study elucidates that the improved cardiac extracellular matrix (ECM) remodeling and cardioprotective effect of matrix metalloprotease 9 (MMP9) inhibition in chronic heart failure (CHF) are via increased autophagic flux. Autophagy is cardioprotective; however, the mechanism of autophagy suppression in CHF is unknown. We for the first time demonstrated here that increased MMP9 suppressed cardiac autophagy and ablation of MMP9 increased cardiac autophagic flux in CHF rats. Restoring the physiological level of autophagy in the failing heart is a challenge, and our study addressed this challenge. The novelty and highlights of this report are as follows: 1) MMP9 regulates cardiomyocyte and fibroblast autophagy, 2) MMP9 inhibition protects CHF after myocardial infarction (MI) via increased cardiac autophagic flux, and 3) MMP9 inhibition increased cardiac autophagy via activation of AMP-activated protein kinase (AMPK)α, Beclin-1, Atg7 pathway and suppressed mechanistic target of rapamycin (mTOR) pathway.
Estrogen receptor-α prevents right ventricular diastolic dysfunction and fibrosis in female rats
Authors: Cheng Tik-Chee , Philip Jennifer L. , Tabima Diana M. , Kumari Santosh , Yakubov Bakhtiyor , Frump Andrea L. , Hacker Timothy A. , Bellofiore Alessandro , Li Rongbo , Sun Xin , Goss Kara N. , Lahm Tim , Chesler Naomi C.
Published: October 2020

Using a novel loss-of-function mutation in estrogen receptor-α (ERα), we demonstrate that female, but not male, ERα mutant rats display right ventricular (RV)-vascular uncoupling, diastolic dysfunction, and fibrosis following pressure overload, indicating a sex-dependent role of ERα in protecting against adverse RV remodeling. TIMP metallopeptidase inhibitor 1 (Timp1), matrix metalloproteinase 9 (Mmp9), kallikrein-related peptidase 10 ( Klk10), and Jun Proto-Oncogene ( Jun) were identified as potential mediators in ERα-regulated pathways in RV pressure overload.
Sleep deprivation and endothelial function: reconciling seminal evidence with recent perspectives
Authors: Cherubini Joshua M. , Cheng Jem L. , Williams Jennifer S. , MacDonald Maureen J.
Published: October 2020

Sleep is critical for the maintenance of physiological homeostasis and, as such, inadequate sleep beckons a myriad of pathologies. Sleep deprivation is a growing health concern in contemporary society since short sleep durations are associated with increased cardiovascular disease risk and atherosclerotic plaque development. Vascular endothelial dysfunction is an antecedent to atherosclerosis and cardiovascular disease. Herein, we review seminal literature indicating that short sleep durations attenuate endothelial function and explore more recent evidence indicating that sleep deprivation perturbs autonomic balance and the circadian rhythmicity of peripheral vascular clock components. We further examine literature that indicates a mechanistic link between short sleep duration and endothelial dysfunction and subsequent morbidity. Understanding the mechanisms that regulate endothelial function in the context of sleep deprivation facilitates the development and optimization of interventions, such as exercise, that mitigate the ramifications of inadequate sleep on vascular function and cardiovascular health.

Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/sleep-deprivation-and-endothelial-function/
A Systematic Review and Meta-analysis on the Prevalence of Low Birth Weight Infants in Iran
Authors: Sabbaghchi Maryam , Jalali Rostam , Mohammadi Masoud
Published: October 2020

Background. Low birth weight is a significant index for survival, intrauterine growth, and mortality in infants. Thus, this study is aimed at determining the prevalence of low birth weight in Iranian infants through a systematic review and meta-analysis. Methods. This study was performed by meta-analysis from January 2000 to December 2019. The studies relevant to the topic have been obtained through search in databases of Scopus, ScienceDirect, SID, Magiran, Barakat Knowledge Network System, Medline (PubMed), and Google Scholar. Heterogeneity of the studies has been assessed by theI2index, and data analysis was done using Comprehensive Meta-Analysis software. Results. By investigating 14 articles and 93924 infants, the total prevalence of low birth weight in infants in Iran was achieved at 8.5% (95% CI: 7.3-9.9%) according to the meta-analysis; the most prevalence of low birth weight was in infants in Hamedan at 19.1% (95% CI: 21.2-17.2%) in 2007, and the lowest prevalence of low birth weight was in infants in Tonekabon at 4.2% (95% CI: 3.4-5.2%) in 2005, and also, by increasing the sample size, the prevalence of low birth weight increases, by which the difference is statistically significant (P<0.05). Conclusion. Due to the high prevalence of low birth weight in infants in Iran, health policy-makers must take effective attempts in order to reduce it in infants.
The Efficacy and Safety of Ureteric Stent Removal with Strings versus No Strings: Which Is Better?
Authors: Luo Zhenkai , Jiao Binbin , Zhao Hang , Huang Tao , Geng Lin , Zhang Guan
Published: October 2020

Objective. To evaluate the current evidence on the effectiveness and safety of ureteric stent removal using strings compared to conventional methods. Materials and Methods. The electronic databases PubMed, Embase, China National Knowledge Infrastructure (CNKI), and the Cochrane Library were systematically searched up to March 2020. Two reviewers searched the literature, independently extracted the data, and evaluated the quality of the studies according to the inclusion and exclusion criteria. The data analysis was performed with the software program Review Manager 5.3. Results. Eleven studies with a total of 1809 patients were included in the analysis based on the inclusion criteria. Our meta‐analysis showed that visual analogue scale (VAS) scores were significantly lower in the string group than in the conventional group (weighted mean difference (WMD) ‐2.63; 95% confidence interval (CI) ‐3.68, ‐1.58; P < 0.00001). In terms of stent dwell time, the string group had an advantage (WMD ‐9.53; 95% CI ‐14.20, ‐4.86; P < 0.0001). In addition, no significant differences in the occurrence of urinary tract infection (UTI) (odds ratio (OR) 1.03; 95% CI 0.62, 1.72; P = 0.92), emergency room visits (OR 0.99; 95% CI 0.59, 1.67; P = 0.97), or other complications (P > 0.05) were observed between the two groups. Conclusion. Our findings suggest that an extraction string is an effective and safe method for the removal of ureteric stents. This method gives patients the benefits of reduced pain and shortened stent dwell time without increasing the risk of UTI. Nevertheless, these findings should be further confirmed through large‐volume, well‐designed prospective randomized controlled trials (RCTs).
Saponin from Periploca forrestii Schltr Mitigates Oxazolone-Induced Atopic Dermatitis via Modulating Macrophage Activation
Authors: Zeng Luting , Liu Yingqin , Xing Congcong , Huang Yijie , Sun Xin , Sun Guangchen
Published: October 2020

Atopic dermatitis (AD) is a relapsing, acute, and chronic skin disease featured by intractable itching, eczematous skin. Conventional therapies based on immunosuppression such as corticosteroids are associated with multiple adverse reactions. Periploca forrestii Schltr saponin (PFS) was shown to potently inhibit murine arthritis by protecting bone and cartilage injury and suppressing NF-κB activation. However, its therapeutic effect on oxazolone-induced atopic dermatitis (AD) and the underlying mechanisms on macrophage are still unclear. The AD-like dermatitis was induced by repeated oxazolone challenge to the skin of BALB/c mice in vivo. Blood and ears were biochemically or histologically processed. RT-PCR, western blotting, and ELISA were conducted to evaluate the expression of macrophage factors. Mouse bone marrow-derived macrophages (BMDMs) stimulated with lipopolysaccharide (LPS) were used as a model in vitro. PFS treatment inhibited AD-like dermatitis development. PFS downregulated epidermis thickness and cell infiltration, with histological analysis of the skin lesion. PFS alleviated plasma immunoglobulin (Ig) E, IgG2a, and IgG1 levels. PFS downregulated the expression of M1 macrophage factors, tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, monocyte chemotactic protein-1 (MCP-1), and nitric oxide synthase2 (NOS2), and M2 macrophage factors, IL-4, arginase1 (Arg1) and CD163 in AD-like skin, which were confirmed by western blot and ELISA analysis. In addition, PFS inhibited LPS-induced macrophage polarization via the inhibition of the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and nuclear translocation of NF-κB p65. These results suggest that PFS exerted an antidermatitis effect against oxazolone by modulating macrophage activation. PFS administration might be useful in the treatment of AD and inflammatory skin diseases.
Monotone Iterative Technique for Conformable Fractional Differential Equations with Deviating Arguments
Authors: Chen Huiling , Meng Shuman , Cui Yujun
Published: October 2020

This paper is concerned with the existence of extremal solutions for periodic boundary value problems for conformable fractional differential equations with deviating arguments. We first build two comparison principles for the corresponding linear equation with deviating arguments. With the help of new comparison principles, some sufficient conditions for the existence of extremal solutions are established by combining the method of lower and upper solutions and the monotone iterative technique. As an application, an example is presented to enrich the main results of this article.