bluuebunny/crossref_metadata_2025 huggingface dataset:
Green roofs: trends and concepts of landscaping
Authors: Novgorodskaya Natalya Olegovna , Granitsa Yuliya Vladimirovna
Published: June 2020

The research object is a green roof. The author reviews the modern tendencies and approaches to using accessible roofs which are developing concomitantly. The first approach focuses on studying the constructive peculiarities, organizational innovations, the existing systems, schemes and ways of arranging an accessible roof, as well as the problems caused by incorrect projecting and errors of construction. The second approach considers green roofs in terms of their possible good influence on the ecological situation in cities and notes their advantages both for people and the environment. This approach prioritizes not over technical arrangement but planting - the intensive one (the creation of landscaped recreational objects which involves significant financial expenses), or the extensive one (green planting). The research methods include the analysis of scientific works, generalization of data on green roofs, its analysis, detection of common tendencies, strengths and weaknesses. The author formulates the following conclusions: Nowadays, there are two types of accessible roofs usage: the traditional one and the inversive one; They differ in the order of layering: in the traditional organization of a green roof the heat-insulating layer is mounted under the water-insulating one, while in the inversive one - above; An inversive roof has several advantages including lifetime extension and the reduction of costs associated with its creation and maintenance; The problem of water collection organization can be solved by means of an external or internal downpipe, or a water collector with separate flowcups; Green roofs help mitigate unfavourable ecological situation in cities. The article describes the concept of a rooftop cafe developed within the project on the discipline “Ecological projecting in an urbanized environment” and the principles of landscaping elements selection.   
Eit skilt som prøver å vera eit skilt
Authors: Jonvik Merete
Published: June 2020

I kunst- og forskingsprosjektet Samarbeid mellom små og store vesen samarbeida ei gruppe born og ein kunstnar om å skapa eit kunstverk. Intensjonen med prosjektet var å utforska om likeverd og horisontalitet i kunstproduksjon beståande av asymmetriske relasjonar er mogleg. Med bakgrunn i deltakande observasjon, intervju og fotodokumentasjon drøfter artikkelen ulike former for samarbeid som viste seg i kunstproduksjonsprosessen, og kunstverket som kom ut av samarbeidet. Utforskinga av om likeverd og horisontalitet er mogleg i samarbeid mellom store og små i kunstproduksjon syner at forsøka enda nettopp som forsøk på horisontalitet, snarare enn faktisk horisontalitet. Artikkelen diskuterer vidare korleis prosess og resultat kan vurderast i deltakarbaserte kunstprosjekt generelt, og i dette prosjektet spesielt. Erfaringar frå Samarbeid mellom små og store vesen indikerer ei gjensidig avhengigheit mellom estetiske og sosiale aspekt. Artikkelen problematiserer difor om det estetiske let seg skilja frå det sosiale i kvalitetsvurderingar, mellom anna med referanse til Claire Bishop, Grant Kester og David Bell.
A proopiomelanocortin‐derived peptide sequence enhances plasma stability of peptide drugs
Authors: Löw Karin , Roulin Alexandre , Kunz Stefan
Published: June 2020

Bioactive peptide drugs hold promise for therapeutic application due to their high potency and selectivity but display short plasma half‐life. Examination of selected naturally occurring peptide hormones derived from proteolytic cleavage of the proopiomelanocortin (POMC) precursor lead to the identification of significant plasma‐stabilizing properties of a 12‐amino acid serine‐rich orphan sequence NSSSSGSSGAGQ in human γ3‐melanocyte‐stimulating hormone (MSH) that is homologous to previously discovered NSnGGH (n = 4–24) sequences in owls. Notably, transfer of this sequence to des‐acetyl‐α‐MSH and the therapeutically relevant peptide hormones neurotensin and glucagon‐like peptide‐1 likewise enhance their plasma stability without affecting receptor signaling. The stabilizing effect of the sequence module is independent of plasma components, suggesting a direct effect in cis. This natural sequence module may provide a possible strategy to enhance plasma stability, complementing existing methods of chemical modification.
The imitation game: a viral strategy to subvert the complement system
Authors: Agrawal Palak , Sharma Samriddhi , Pal Pradipta , Ojha Hina , Mullick Jayati , Sahu Arvind
Published: June 2020

Viruses are obligate parasites of cellular hosts and therefore are constantly confronted with the host immune system. Evasion of innate immunity mechanisms by viruses is paramount for the establishment of their infection. The complement system can directly neutralize viruses and also augments adaptive immune responses against them. This system, therefore, is central to host innate immune surveillance, and viruses have evolved a multitude of ways to escape its assault. A major strategy employed by viruses is the molecular mimicry of human complement regulators, namely regulators of complement activation (RCA) proteins and CD59. Herein, we outline up‐to‐date information on the structure, function and role of viral homologs of the human complement regulators in viral pathogenesis.
Blood‐derived DNA methylation predictors of mortality discriminate tumor and healthy tissue in multiple organs
Authors: Zhang Yan , Bewerunge‐Hudler Melanie , Schick Matthias , Burwinkel Barbara , Herpel Esther , Hoffmeister Michael , Brenner Hermann
Published: June 2020

Evidence has shown that certain methylation markers derived from blood can mirror corresponding methylation signatures in internal tissues. In the current study, we aimed to investigate two strong epigenetic predictors for life span, derived from blood DNA methylation data, in tissue samples of solid cancer patients. Using data from the Cancer Genome Atlas (TCGA) and the German DACHS study, we compared a mortality risk score (MRscore) and DNAmPhenoAge in paired tumor and adjacent normal tissue samples of patients with lung (N = 69), colorectal (n = 299), breast (n = 90), head/neck (n = 50), prostate (n = 50), and liver (n = 50) cancer. To explore the concordance across tissue and blood, we additionally assessed the two markers in blood samples of colorectal cancer (CRC) cases and matched controls (n = 93) in the DACHS+ study. The MRscore was significantly elevated in tumor tissues compared to normal tissues of all cancers except prostate cancer, for which an opposite pattern was observed. DNAmPhenoAge was consistently higher in all tumor tissues. The MRscore discriminated lung, colorectal, and prostate tumor tissues from normal tissues with very high accuracy [AUCs of 0.87, 0.99 (TCGA) /0.94 (DACHS), and 0.92, respectively]. DNAmPhenoAge accurately discriminated five types of tumor tissues from normal tissues (except prostate cancer), with AUCs of 0.82–0.93. The MRscore was also significantly higher in blood samples of CRC cases than in controls, with areas under the curve (AUC) of 0.74, whereas DNAmPhenoAge did not distinguish cases from controls, with AUC of 0.54. This study provides compelling evidence that blood‐derived DNAm markers could reflect methylation changes in less accessible tissues. Further research should explore the potential use of these findings for cancer diagnosis and early detection.
Neuroendocrine subtypes of small cell lung cancer differ in terms of immune microenvironment and checkpoint molecule distribution
Authors: Dora David , Rivard Christopher , Yu Hui , Bunn Paul , Suda Kenichi , Ren Shengxiang , Lueke Pickard Shivaun , Laszlo Viktoria , Harko Tunde , Megyesfalvi Zsolt , Moldvay Judit , Hirsch Fred R. , Dome Balazs , Lohinai Zoltan
Published: June 2020

Small cell lung cancer (SCLC) has recently been subcategorized into neuroendocrine (NE)‐high and NE‐low subtypes showing ‘immune desert’ and ‘immune oasis’ phenotypes, respectively. Here, we aimed to characterize the tumor microenvironment according to immune checkpoints and NE subtypes in human SCLC tissue samples at the protein level. In this cross‐sectional study, we included 32 primary tumors and matched lymph node (LN) metastases of resected early‐stage, histologically confirmed SCLC patients, which were previously clustered into NE subtypes using NE‐associated key RNA genes. Immunohistochemistry (IHC) was performed on formalin‐fixed paraffin‐embedded TMAs with antibodies against CD45, CD3, CD8, MHCII, TIM3, immune checkpoint poliovirus receptor (PVR), and indoleamine 2,3‐dioxygenase (IDO). The stroma was significantly more infiltrated by immune cells both in primary tumors and in LN metastases compared to tumor nests. Immune cell (CD45+ cell) density was significantly higher in tumor nests (P = 0.019), with increased CD8+ effector T‐cell infiltration (P = 0.003) in NE‐low vs NE‐high tumors. The expression of IDO was confirmed on stromal and endothelial cells and was positively correlated with higher immune cell density both in primary tumors and in LN metastases, regardless of the NE pattern. Expression of IDO and PVR in tumor nests was significantly higher in NE‐low primary tumors (vs NE‐high, P < 0.05). We also found significantly higher MHC II expression by malignant cells in NE‐low (vs NE‐high, P = 0.004) tumors. TIM3 expression was significantly increased in NE‐low (vs NE‐high, P < 0.05) tumors and in LN metastases (vs primary tumors, P < 0.05). To our knowledge, this is the first human study that demonstrates in situ that NE‐low SCLCs are associated with increased immune cell infiltration compared to NE‐high tumors. PVR, IDO, MHCII, and TIM3 are emerging checkpoints in SCLC, with increased expression in the NE‐low subtype, providing key insight for further prospective studies on potential biomarkers and targets for SCLC immunotherapies.
The Efficacy of Geraniol and ß-Citronellol against Freshwater and Marine Monogeneans
Authors: Morales-Serna Francisco N. , Martínez-Brown Juan M. , Avalos-Soriano Anaguiven , Sarmiento-Vázquez Sara , Hernández-Inda Zaira L. , Medina-Guerrero Rosa M. , Fajer-Ávila Emma J. , Ibarra-Castro Leonardo
Published: June 2020

Monogeneans are parasitic flatworms that may be a threat for finfish aquaculture. In this study, the anthelmintic activity of two terpenes, geraniol and β-citronellol, was tested in vitro against ancyrocephalin and diplectanid monogeneans. Experiments were performed in both water and a culture medium. We observed that monogeneans in culture medium may be more tolerant to treatments compared with bioassays performed only in water. Concentrations of 300 mg/L of both compounds were required to kill 100% of monogeneans at 1 h postexposure. The toxicity of β-citronellol to fish was not evaluated. However, geraniol at 300 mg/L and 150 mg/L killed juvenile Nile Tilapia Oreochromis niloticus and White Snook Centropomus viridis, respectively, after a few minutes. Therefore, the present work suggests that other alternatives should be studied for use against monogeneans in aquaculture.
An open‐source software for monitoring intrafraction motion during external beam radiation therapy based on superimposition of contours of projected ROIs on cine‐MV images
Authors: Lessard Rémi , Tremblay Nicolas M. , Plourde Marc‐Émile , Guillot Mathieu
Published: June 2020

Purpose

To present an open‐source software (https://github.com/CHUSRadOncPhys/FluoMV) for monitoring intrafraction motion that is based on the visualization of superimposed contours of projected region‐of‐interests from DICOM RTSTRUCT files on cine‐MV images acquired and displayed in real‐time during radiation therapy delivery. Clinical use with prostate gold fiducial markers is presented.

Methods

Projections of regions of interest (ROI) in the reference frame of the electronic portal imaging device are computed offline for different gantry angles before the first treatment fraction. During treatment delivery, the contrast of portal images is automatically adjusted using a histogram equalization algorithm. The projections associated with the current gantry angle are then superimposed on the images in real time. This allows the therapist to evaluate if the imaged structures of interest remain within their respective contours during treatment delivery and to potentially interrupt the treatment if deemed necessary. The spatial accuracy of the method was evaluated by imaging a ball bearing phantom in a set‐up where the position of the projected ROI is highly sensitive to gantry angle errors. The visibility of fiducial markers during one fraction of seven different volumetric modulated arc therapy (VMAT) prostate treatments is characterized.

Results

The geometric validation showed a negligible systematic error μ < 0.1 mm for the position of the projections. The random errors associated with the time accuracy of the gantry angle readout were characterized by standard deviations σ ≤ 0.6 mm. The VMAT clinical treatments showed that the fiducial markers were frequently visible, allowing for a meaningful clinical use.

Conclusions

The results demonstrate that the method presented is sufficiently accurate to be used for intrafraction monitoring of patients. The fact that this method could be implemented on many modern linacs at little to no cost and with no additional dose delivered to the patients makes this solution very attractive for improving patient care and safety in radiation therapy.
The Synthesis of Chiral Allyl Carbamates via Merger of Photoredox and Nickel Catalysis
Authors: Garbacz Mateusz , Stecko Sebastian
Published: June 2020

A mild, and versatile, organophotoredox/Ni‐mediated protocol was developed for the direct preparation of diverse, enantioenriched allyl carbamates. The reported approach represents a significant departure from classical step‐by‐step synthesis of allyl carbamates. This dual photoredox/Ni based strategy offers unrivalled capacity for convergent unification of readily available alkyl halides and chiral carbamates derived from 1‐bromo‐alken‐3‐ols with high chemoselectivity and efficiency. The reported photoredox/Ni catalyzed cross‐coupling reaction is not limited to carbamates, but also to other O‐derivatives such as esters, ethers, acetals, carbonates or silyl ethers. To demonstrate the utility of the reported protocol, the resulting allyl carbamates were transformed into functionalized non‐racemic allylamines through a sigmatropic rearrangement reaction in enantiospecific manner. This approach allowed for synthesis of enantiomeric allylamines by a simple control of the geometry of a double bond of allyl carbamates.

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Zinc/Indium Bimetallic Lewis Acid Relay Catalysis for Dehydrogenative Silylation/Hydrosilylation Reaction of Terminal Alkynes with Bis(hydrosilane)s
Authors: Tani Tomohiro , Sohma Yudai , Tsuchimoto Teruhisa
Published: June 2020

When mixed with two different Lewis acid catalysts of zinc and indium, terminal alkynes were found to react with bis(hydrosilane)s to selectively provide 1,1‐disilylalkenes from among several possible products, by way of a sequential dehydrogenative silylation/intramolecular hydrosilylation reaction. Adding a pyridine base is crucial in this reaction; a switch as a catalyst of the zinc Lewis acid is turned on by forming a zinc−pyridine‐base complex. A range of the 1,1‐disilylalkenes can be obtained by a combination of aryl and aliphatic terminal alkynes plus aryl‐, heteroaryl‐, and naphthyl‐tethered bis(hydrosilane)s. The 1,1‐disilylalkene prepared here is available as a reagent for further transformations by utilizing its C−Si or C=C bond. The former includes Hiyama cross‐coupling, bismuth‐catalyzed ether formation, and iododesilylation; the latter includes double alkylation and epoxidation. Mechanistic studies clarified the role of the two Lewis acids: the zinc–pyridine‐base complex catalyzes the dehydrogenative silylation as a first stage, and, following on this, the indium Lewis acid catalyzes the ring‐closing hydrosilylation as a second stage, thus leading to the 1,1‐disilylalkene.

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Empowering Clinician Education With Patient‐outcome Feedback
Authors: Iserson Kenneth V.
Published: June 2020

Emergency physicians (EPs) often lack the information they need about their patients’ outcomes so that they can both optimally adjust and refine their diagnostic and treatment processes and recognize their clinical errors. Patient‐outcome feedback (POF) provides that information by informing clinicians about a patient’s clinical course after that clinician’s evaluation and treatment. This feedback may encompass the period after the EP has transferred a patient’s care to another EP or after the patient has left the ED or hospital. EPs obtain POF through various active and passive methods, depending on their institutional and medical record systems. Active methods require that clinicians or others spend time and effort acquiring the information; passive methods deliver it automatically. POF is an excellent performance‐based measurement that helps clinicians to stimulate their learning and to build their own validated mental library of outcomes with which to make clinical decisions, i.e., heuristics and System 1 thinking. POF offers especially useful feedback about patients who have been admitted, were referred to specialists, had major interventions, had potentially significant tests pending on discharge, or were handed off to another EP. The current health care system makes it difficult for EPs to discover their patients’ outcomes, squandering significant educational opportunities. Three stimuli to improve this situation would be to require EPs to receive passive POF as part of hospital accreditation, for reviewing POF to be classified as a Category 1 Continuing Medical Education activity, and to reimburse clinicians for learning activities related to POF. Research indicates that our health care institutions and systems would be well served to provide clinicians with ongoing automatic information about their patients’ outcomes.
Emergency Department Well‐being Initiatives During the COVID‐19 Pandemic: An After‐action Review
Authors: Zaidi Sara R. , Sharma Vineet K. , Tsai Shiu‐Lin , Flores Stefan , Lema Penelope C. , Castillo Jenny
Published: June 2020

The COVID‐19 pandemic has significantly impacted the well‐being of our health care professionals, particularly frontline providers in the emergency department (ED). Our ED, located in New York City, was severely affected, exposing the staff to a combination of unique stressors. Our ED Wellness Committee responded by implementing various initiatives focusing on the physical, mental, and social needs of our providers to support them through this difficult time. The initiatives we describe offer a framework that may help other departments understand the importance of provider well‐being during a pandemic.
Malignant asbestos‐related disease in a population exposed to asbestos
Authors: Orriols Ramon , Tarrés Josep , Albertí‐Casas Constança , Rosell‐Murphy Magdalena , Abós‐Herràndiz Rafael , Canela‐Soler Jaume
Published: June 2020

Objectives

The first asbestos fiber cement plant in Spain operated in Cerdanyola, in the Barcelona metropolitan area, between 1907 and 1997. We describe clinical and epidemiological characteristics of patients diagnosed with the malignant asbestos‐related disease (ARD) in the area of the plant between 2007 and 2016.

Methods

A prospective, descriptive study was undertaken in the 12 municipalities of the county of Barcelona most proximate to the plant. We describe malignant ARD cases by time of diagnosis, source of exposure, periods of exposure and latency, and distribution by sex. Cumulative incidence and age‐standardized incidence rates (ASIR) are calculated.

Results

Of 477 patients diagnosed with ARD between 2007 and 2016, 128 (26%) presented with asbestos‐associated malignancy. Pleural mesothelioma was noted in 105 patients (82.0%) with a linear trend Z‐score of −0.2 (NS) in men and 2.7 (P < .01) in women. The highest ASIRs for malignant ARD (6.1/100 000 residents/year; 95% confidence interval [CI], 2.2‐13.3) and pleural mesothelioma (4.8/100 000 residents/year; 95% CI, 1.5‐11.6) occurred in municipalities closest to the focal point of contamination. The origin of malignant ARD was nonoccupational in 32.2% of men and 81.6% of women (P < .001).

Conclusions

More than 20 years after the closure of the fiber cement plant, the grave consequences of exposure to asbestos remain. The detection of cases of pleural mesothelioma in men seems to have plateaued whereas in women an ascending trend continues, which principally has its origin in nonoccupational exposures.
Baraitser–Winter cerebrofrontofacial syndrome: Report of two adult siblings
Authors: Hampshire Karly , Martin Pierre‐Marie , Carlston Colleen , Slavotinek Anne
Published: June 2020

Baraitser–Winter cerebrofrontofacial syndrome (BWCS) is a rare, autosomal dominant condition that is characterized by intellectual disability, distinctive craniofacial features, structural brain abnormalities, seizures, microcephaly, hearing loss, and ocular colobomas. The first three cases were described in 1988 by Baraitser and Winter and included two siblings and an unrelated third patient. Subsequently, causative missense variants in the ACTB and ACTG1 genes were identified, with de novo occurrence in patients with the condition. Herein, we describe two adult siblings who were born to unaffected parents and who were diagnosed with BWCS in their fourth and sixth decade of life following exome sequencing performed for intellectual disability. We review the literature reports of adult patients with BWCS to document the clinical features and phenotypic variability that can occur later in life. This is the first molecularly confirmed report of germline mosaicism in BWCS and one of only a few reports to describe two BWCS patients belonging to the same family.
Characterization of sleep habits and medication outcomes for sleep disturbance in children and adults with Angelman syndrome
Authors: Pereira Joseph A. , Ravichandran Caitlin T. , Mullett Jennifer , McDougle Christopher J. , Keary Christopher J.
Published: June 2020

The objectives of this study were to characterize the sleep habits of 50 clinically referred individuals with Angelman syndrome (AS) and to retrospectively compare the effectiveness/tolerability of the three most commonly prescribed sleep medications in the sample. An experienced physician assigned a Clinical Global Impressions‐Severity scale (CGI‐S) score for each subject's AS‐specific symptoms. Caregivers completed the Child Sleep Habits Questionnaire (CSHQ; screen for sleep problems in school‐aged [4–10 years] children), a screening assessment for sleep problems. Caregivers provided information about medication trials targeting disturbed sleep, with the physician assigning a CGI‐Improvement scale (CGI‐I) score for each trial. Linear regression showed significant negative association between age and CSHQ score. In their lifetime, 72% of participants had taken a medication for sleep, most commonly melatonin, clonidine and trazodone. The majority continued these for 6 months or longer. With these medications, many demonstrated significant improvement in sleep disturbances, with no difference in odds of improvement between medications. Disturbed sleep was common in this cohort and significantly worse in younger‐aged participants. The majority received at least one medication trial for disturbed sleep and each of the most commonly prescribed medication was effective for a substantial percentage of participants. Most participants remained on medication for at least 6 months, suggesting favorable tolerability.
The epidemiology of sex chromosome abnormalities
Authors: Berglund Agnethe , Stochholm Kirstine , Gravholt Claus Højbjerg
Published: June 2020

Sex chromosome abnormalities (SCAs) are characterized by gain or loss of entire sex chromosomes or parts of sex chromosomes with the best‐known syndromes being Turner syndrome, Klinefelter syndrome, 47,XXX syndrome, and 47,XYY syndrome. Since these syndromes were first described more than 60 years ago, several papers have reported on diseases and health related problems, neurocognitive deficits, and social challenges among affected persons. However, the generally increased comorbidity burden with specific comorbidity patterns within and across syndromes as well as early death of affected persons was not recognized until the last couple of decades, where population‐based epidemiological studies were undertaken. Moreover, these epidemiological studies provided knowledge of an association between SCAs and a negatively reduced socioeconomic status in terms of education, income, retirement, cohabitation with a partner and parenthood. This review is on the aspects of epidemiology in Turner, Klinefelter, 47,XXX and 47,XYY syndrome.
Habitat use by a primate community in a lowland dipterocarp forest in Danum Valley, Borneo
Authors: Hanya Goro , Kanamori Tomoko , Kuze Noko , Wong Siew Te , Bernard Henry
Published: June 2020

Knowledge of niche partitioning with respect to habitat is indispensable to understand the mechanism of coexistence of multiple species. Among primates, however, data are still deficient because repeated survey for a sufficiently long time, covering seasonal changes over a large area, is the only way to clarify habitat segregation within a seasonally fluctuating environment. Southeast Asia is particularly interesting because of the supra‐annual, highly unpredictable seasonality in fruiting known as mast fruiting. We conducted repeated route census, habitat monitoring, and group tracking for 25 months in two study sites (ca. 10 km apart) in the largely primary lowland dipterocarp forest of the Danum Valley Conservation Area, eastern Sabah, northern Borneo, Malaysia. The five species of diurnal primates (Bornean orangutan Pongo pygmaeus, Müeller's gibbon Hylobates muelleri, red leaf monkey Presbytis rubicunda, long‐tailed macaque Macaca fascicularis, and southern pig‐tailed macaque M. nemestrina) did not show horizontal spatial segregation. Red leaf monkeys showed preferences for places with short tree height, but their distribution was not confined to such places. In response to the fruiting peak observed once during the study period, orangutans increased their numbers simultaneously in the two study sites. The average tree height used by the five species was different, but their range overlapped substantially. Compared with other primate communities, the lack of horizontal spatial segregation and the suggested long‐distance movement of orangutans seem to be unique characteristics in Borneo, although the use of different forest strata is a widespread phenomenon among primate communities throughout the world.
Staphylococcus aureusbiofilm exoproteins are cytotoxic to human nasal epithelial barrier in chronic rhinosinusitis
Authors: Panchatcharam Beula Subashini , Cooksley Clare M. , Ramezanpour Mahnaz , Vediappan Rajan Sundaresan , Bassiouni Ahmed , Wormald Peter J. , Psaltis Alkis J. , Vreugde Sarah
Published: June 2020

Background

Chronic rhinosinusitis patients (CRS) suffer from chronic inflammation of the sinus mucosa associated with chronic relapsing infections. Mucosal biofilms, associated withStaphylococcus aureus, have been implicated as a cause. We compared the effect of exoproteins secreted from clinical isolates ofS aureusfrom CRS patients in planktonic and biofilm form on the nasal epithelial barrier.

Methods

ClinicalS aureusisolates from 39 CRS patients were grown in planktonic and biofilm forms and their exoproteins concentrated. These were applied to primary human nasal epithelial cells grown at the air‐liquid interface. Transepithelial electrical resistance, permeability of flourescein isothiocyanate‐dextrans, and cytotoxicity were measured. Structure and expression of tight junctions zona occludens‐1, and claudin‐1 proteins were assessed by electron microscopy and immunofluorescence. The Wilcoxon signed rank test was used for statistical analyses.

Results

S aureusbiofilm exoproteins showed dose‐ and time‐dependent reduction of transepithelial electrical resistance, increased cell toxicity, and increased permeability (p< 0.001) compared with equal concentrations of planktonic cultures. Discontinuity in zona occludens‐1 and claudin‐1 immunofluorescence was confirmed as disrupted tight junctions on electron microscopy.

Conclusion

S aureusbiofilm exoproteins disrupt the mucosal barrier structure in a time‐ and dose‐dependent manner and are toxic. Damage to the mucosal barrier byS aureusbiofilm exoproteins may play a major role in CRS etiopathogenesis.
Management of odontogenic sinusitis: multidisciplinary consensus statement
Authors: Craig John R. , Tataryn Roderick W. , Aghaloo Tara L. , Pokorny Alan T. , Gray Stacey T. , Mattos Jose L. , Poetker David M.
Published: June 2020

Background

Odontogenic sinusitis (ODS) can present a therapeutic dilemma because multiple treatment strategies have been reported. ODS review articles have been published, but they have lacked multidisciplinary collaboration and an evidence‐based methodology. The purpose of this article was to perform an evidence‐based review of ODS management options, and develop a multidisciplinary consensus statement on ODS management options.

Methods

An evidence‐based review of dental and medical literature on ODS management was performed using PubMed, EMBASE, and Cochrane Review Databases up to December 2019. Exclusion criteria included non‐English‐language articles, case series with fewer than 10 patients, fungal sinusitis, and studies that did not report treatment success rates. Because aggregate levels of evidence for recommendations were no higher than level C, a clinical consensus statement was conducted using a modified Delphi method.

Results

Sixteen articles met inclusion criteria for the evidence‐based review on the following ODS management options: dental treatment alone or combined with ESS for various dental pathologies, and endoscopic sinus surgery (ESS) alone for dental implant‐related ODS. Strong consensus was achieved for 9 of the 10 clinical statements, the strongest being the use of shared decision‐making for selecting management strategies. No consensus was reached for determining the extent of ESS necessary for uncomplicated ODS.

Conclusion

Strong consensus was reached that ODS management should involve shared decision‐making between the otolaryngologist, dental provider, and patient, where the benefits and risks of dental treatment and ESS are discussed. Higher‐quality studies are necessary to develop evidence‐based treatment recommendations for ODS.
Chronic rhinosinusitis: assessment of changes in nociceptive neurons
Authors: Bogaert Stijn , Van Crombruggen Koen , Holtappels Gabriele , De Ruyck Natalie , Suchonos Nicole , Park Jonas Jae‐Hyun , Bachert Claus
Published: June 2020

Background

Pain is a major symptom of chronic rhinosinusitis (CRS). It is mainly associated with CRS without nasal polyps (CRSsNP) and has a major impact in the decision to move on to surgery. Patients with CRS with nasal polyps (CRSwNP) are characterized by trigeminal hypoesthesia and suffer from less pain. The aim of this study was to investigate whether CRS induces alterations in the peripheral nociceptive neurons, mainly focusing on quantitative changes.

Methods

Sinus mucosa and inferior turbinate (IT) samples were obtained from patients with CRS, and IT tissue of healthy patients served as controls. Reverse transcription quantitative polymerase chain reaction (RT‐qPCR) was performed for neuronal markers including CNTNAP2, FAM19A1, GFRA2, NEFH, NTRK1, PLXNC1, RET, SCN10A, SCN11A, TRPV1, and PGP 9.5; enzyme‐linked immunosorbent assay (ELISA) was performed for KCNK18, SCN10A, MRGPRD, and MAP2. For PGP 9.5, immunohistochemistry was additionally used to analyze tissue slides.

Results

We included 35 patients with CRSsNP, 47 patients with CRSwNP, and 18 control patients. No differences in expression of the neuronal markers were observed between CRSsNP, CRSwNP, and controls. SCN10A was the only marker exclusively expressed on nociceptive neurons in sinus tissue. No histological difference in nerve fibers was observed between sinus mucosa of both phenotypes.

Conclusion

Our results indicate that the nociceptive nerve density in CRSwNP is not lower than in CRSsNP, as was assumed previously. The nociceptive neurons in sinonasal mucosa cannot be classified into subtypes due to the lack of specificity of the respective marker genes. Our findings question the generally accepted claim that nasal polyp tissue does not contain any nerves.
Repetitive negative thinking is associated with amyloid, tau, and cognitive decline
Authors: Marchant Natalie L. , Lovland Lise R. , Jones Rebecca , Pichet Binette Alexa , Gonneaud Julie , Arenaza‐Urquijo Eider M. , Chételat Gael , Villeneuve Sylvia ,   for the PREVENT‐AD Research Group
Published: June 2020

Introduction

The Cognitive Debt hypothesis proposes that repetitive negative thinking (RNT), a modifiable process common to many psychological risk factors for Alzheimer's disease (AD) may itself increase risk. We sought to empirically examine relationships between RNT and markers of AD, compared with anxiety and depression symptoms.

Methods

Two hundred and ninety‐two older adults with longitudinal cognitive assessments, including 113 with amyloid‐positron emission tomography (PET) and tau‐PET scans, from the PREVENT‐AD cohort and 68 adults with amyloid‐PET scans from the IMAP+ cohort were included. All participants completed RNT, anxiety, and depression questionnaires.

Results

RNT was associated with decline in global cognition (P = .02); immediate (P = .03) and delayed memory (P = .04); and global amyloid (PREVENT‐AD: P = .01; IMAP+: P = .03) and entorhinal tau (P = .02) deposition. Relationships remained after adjusting for potential confounders.

Discussion

RNT was associated with decline in cognitive domains affected early in AD and with neuroimaging AD biomarkers. Future research could investigate whether modifying RNT reduces AD risk.
COVID‐19: A Global Threat to the Nervous System
Authors: Koralnik Igor J. , Tyler Kenneth L.
Published: June 2020

In less than 6 months, the severe acute respiratory syndrome‐coronavirus type 2 (SARS‐CoV‐2) has spread worldwide infecting nearly 6 million people and killing over 350,000. Initially thought to be restricted to the respiratory system, we now understand that coronavirus disease 2019 (COVID‐19) also involves multiple other organs, including the central and peripheral nervous system. The number of recognized neurologic manifestations of SARS‐CoV‐2 infection is rapidly accumulating. These may result from a variety of mechanisms, including virus‐induced hyperinflammatory and hypercoagulable states, direct virus infection of the central nervous system (CNS), and postinfectious immune mediated processes. Example of COVID‐19 CNS disease include encephalopathy, encephalitis, acute disseminated encephalomyelitis, meningitis, ischemic and hemorrhagic stroke, venous sinus thrombosis, and endothelialitis. In the peripheral nervous system, COVID‐19 is associated with dysfunction of smell and taste, muscle injury, the Guillain‐Barre syndrome, and its variants. Due to its worldwide distribution and multifactorial pathogenic mechanisms, COVID‐19 poses a global threat to the entire nervous system. Although our understanding of SARS‐CoV‐2 neuropathogenesis is still incomplete and our knowledge is evolving rapidly, we hope that this review will provide a useful framework and help neurologists in understanding the many neurologic facets of COVID‐19. ANN NEUROL 2020;88:1–11 ANN NEUROL 2020;88:1–11
Identifying Progression in Multiple Sclerosis: New Perspectives
Authors: Filippi Massimo , Preziosa Paolo , Langdon Dawn , Lassmann Hans , Paul Friedemann , Rovira Àlex , Schoonheim Menno M. , Solari Alessandra , Stankoff Bruno , Rocca Maria A.
Published: June 2020

The identification of progression in multiple sclerosis is typically retrospective. Given the profound burden of progressive multiple sclerosis, and the recent development of effective treatments for these patients, there is a need to establish measures capable of identifying progressive multiple sclerosis early in the disease course. Starting from recent pathological findings, this review assesses the state of the art of potential measures able to predict progressive multiple sclerosis. Future promising biomarkers that might shed light on mechanisms of progression are also discussed. Finally, expansion of the concept of progressive multiple sclerosis, by including an assessment of cognition, patient‐reported outcomes, and comorbidities, is considered. ANN NEUROL 2020;88:438–452
Cyclopropenylmethylkation – Ein verborgenes Intermediat in Gold(I)‐katalysierten Reaktionen
Authors: Kreuzahler Mathis , Haberhauer Gebhard
Published: June 2020

In den letzten Jahren konnte eine Vielzahl an Gold‐katalysierten Reaktionen von Alkinen beschrieben werden. Eine der bekanntesten Spezies der Reaktion von zwei Alkineinheiten ist das Vinyl‐substituierte Goldvinyliden‐Intermediat. In dieser Arbeit können wir zeigen, dass die Reaktion eines Halogenacetylens und eines Alkins über das bisher übersehene Cyclopropenylmethylkation als Intermediat abläuft. Die Existenz und die relative Stabilität dieses verborgenen Intermediats wird durch quantenchemische Rechnungen und 13C‐Markierungsexperimente belegt. Ein Vergleich des Cyclopropenylmethylkations und des bereits bekannten Vinyliden‐Intermediats zeigt, dass dieses nur im Fall von kleinen Cyclen stabiler ist. Diese Stabilität dreht sich in größeren Cyclen allerdings um. Im Fall des kleinsten Vertreters beider Spezies stellt das Vinylidenkation den Übergangszustand zum Cyclopropenylmethylkation dar. Die Aufdeckung dieses Intermediats sollte dabei helfen ein tieferes Verständnis für Gold‐katalysierte C‐C‐Verknüpfungsreaktionen von Alkinen zu erlangen. Da Enine aus dem Cyclopropenylmethylkation gebildet werden können, schafft die Einbeziehung dieses Intermediats die Grundlage für die Entwicklung neuer synthetischer Methoden zum Aufbau von großen cyclischen halogenierten und nicht‐halogenierten konjugierten Enin‐Systemen.
Graphene Oxide as a Mediator in Organic Synthesis: a Mechanistic Focus
Authors: Lombardi Lorenzo , Bandini Marco
Published: June 2020

Graphene oxide (GO) is experiencing growing interest by synthetic organic chemists as a promoter of chemical transformations. The synergistic role of the multiple functionalities featuring the nanostructured carbon materials and their π‐domains enables the interplay of specific activation modes towards organic compounds that can explore unprecedented chemical modifications. A detailed comprehension of the mechanistic details that govern the transformations guided by GO is a not fully solved task in the field. In this direction, more sophisticated and diversified techniques are employed, providing insights towards intriguing activation modes exerted by the π‐matrix and the oxygenated/sulfonate groups decorating the functionalized nano‐carbon material. The present Minireview accounts for a critical survey of the most recent developments in the area of GO‐mediated organic transformations with a specific focus on mechanist aspects.
Electro‐Mechanochemical Atom Transfer Radical Cyclizations using Piezoelectric BaTiO3
Authors: Schumacher Christian , Hernández José G. , Bolm Carsten
Published: June 2020

The formation and regeneration of active CuI species is a fundamental mechanistic step in copper‐catalyzed atom transfer radical cyclizations (ATRC). Typically, the presence of the catalytically active CuI species in the reaction mixture is secured by using high CuI catalyst loadings or the addition of complementary reducing agents. In this study it is demonstrated how the piezoelectric properties of barium titanate (BaTiO3) can be harnessed by mechanical ball milling to induce electrical polarization in the strained piezomaterial. This strategy enables the conversion of mechanical energy into electrical energy, leading to the reduction of a CuII precatalyst into the active CuI species in copper‐catalyzed mechanochemical solvent‐free ATRC reactions.
CO2 Methanation via Amino Alcohol Relay Molecules Employing a Ruthenium Nanoparticle/Metal Organic Framework Catalyst
Authors: Cui Xinjiang , Shyshkanov Serhii , Nguyen Tu N. , Chidambaram Arunraj , Fei Zhaofu , Stylianou Kyriakos C. , Dyson Paul J.
Published: June 2020

Methanation of carbon dioxide (CO2) is attractive within the context of a renewable energy refinery. Herein, we report an indirect methanation method that harnesses amino alcohols as relay molecules in combination with a catalyst comprising ruthenium nanoparticles (NPs) immobilized on a Lewis acidic and robust metal–organic framework (MOF). The Ru NPs are well dispersed on the surface of the MOF crystals and have a narrow size distribution. The catalyst efficiently transforms amino alcohols to oxazolidinones (upon reaction with CO2) and then to methane (upon reaction with hydrogen), simultaneously regenerating the amino alcohol relay molecule. This protocol provides a sustainable, indirect way for CO2 methanation as the process can be repeated multiple times.
Graphene‐Like Covalent Organic Framework with a Wide Band Gap Synthesized On Surface via Stepwise Reactions
Authors: Shi Guoqiang , Zhou Junfeng , Li Zhuo , Sun Ye , Kantorovich Lev N. , Fang Qiang , Besenbacher Flemming , Yu Miao
Published: June 2020

Developing graphene‐like two‐dimensional materials naturally possessing a band gap has sparked enormous interest. Thanks to the inherent wide band gap and high mobility in the 2D plane, covalent organic frameworks containing triazine rings (t‐COFs) hold great promise in this regard, whilst the synthesis of single‐layer t‐COFs remains highly challenging. Herein, we present the fabrication of a well‐defined graphene‐like t‐COF on Au(111). Instead of single/multiple‐step single‐type reactions commonly applied for on‐surface synthesis, distinct stepwise on‐surface reactions, including alkynyl cyclotrimerization, C−O bond cleavage, and C−H bond activation, are triggered on demand, leading to product evolution in a controlled step‐by‐step manner. Aside from the precise control in sophisticated on‐surface synthesis, this work proposes a single‐atomic‐layer organic semiconductor with a wide band gap of 3.41 eV.
Eggshell membrane reinforced polypropylene biocomposite and its tactile assessment
Authors: Na Woo Seok , Sinha Tridib Kumar , Lee Jinho , Oh Jeong Seok
Published: June 2020

Considering the better tactile performance (pleasantness) of different materials for example, leather, fur, feather, and so on, which are known to be the tribopositive materials, herein, the tribo‐positive eggshell membrane (ESM) powders derived from waste eggshell were melt‐mixed with polypropylene (PP) to prepare a low‐cost ESM/PP biocomposite of enhanced tactile property. In this regard, in‐plane coefficient of friction (COF) has been examined and found a decreasing trend with increasing the ESM content which may consider towards improving the pleasantness of the composite, and which is due to the increase of surface smoothness and adhesion property laid by incorporation of polar ESM within the nonpolar PP matrix. However, the decrease of COF was not spontaneous. Alternatively, the increase of tribopositive character of the composite due to addition of tribopositive ESM within the tribonegative PP, as investigated by fabricating a single electrode triboelectric nanogenerator (STENG)‐like device made of the ESM/PP composite may be considered potential to realize the enhancement of touch‐feeling performance. The triboelectric results showed well‐correlation not only with the COF, but also with the thermal and mechanical properties of the composite. It is thus, prejudiced that triboelectric investigation can be used as a potential tool to realize/manage the touch‐feeling properties of different products.
Functional identification of Bombyx mori Atg13 in autophagy
Authors: Li Shuyan , Xu Jing , Xu Xianying , Ma Weiyuan , Tian Ling , Li Kang
Published: June 2020

The autophagy process involves a series of autophagy‐related (Atg) proteins, which are conserved in eukaryotes. ULK1/Atg1‐ATG13/Atg13 is the core protein complex for autophagy initiation in response to nutrient and hormone signaling. However, how Atg13 is regulated to participate in autophagy is unclear in insects. Here in Bombyx mori, the variation of BmAtg13 was correlated with autophagy induced by steroid hormone 20‐hydroxyecdysone (20E) or starvation. Developmental profiles from feeding to prepupal stage revealed that there were two bands of BmAtg13 protein detected by western blot analysis, therein the upper band was intensively decreased, while the lower band was significantly increased which was in accordance with its mRNA variation; and immunofluorescent staining indicated that BmAtg13 was nucleocytoplasmic translocated during larval‐pupal metamorphosis when autophagy was dramatically induced. BmAtg13 knockdown and overexpression both inhibits autophagy. Besides, 20E treatment‐induced BmAtg13 gene expression, while blocking 20E signaling transduction by knockdown of BmUsp reduced both gene expression and protein level of BmAtg13. These results reveal that BmAtg13 is required for 20E‐ and starvation‐induced autophagy in B. mori, which provides the foundation for further related studies.
5‐(4‐Methoxybenzylidene)thiazolidine‐2,4‐dione‐derived VEGFR‐2 inhibitors: Design, synthesis, molecular docking, and anticancer evaluations
Authors: El‐Adl Khaled , Sakr Helmy , Nasser Mohamed , Alswah Mohamed , Shoman Fatma M. A.
Published: June 2020

A novel series of 5‐(4‐methoxybenzylidene)thiazolidine‐2,4‐dione derivatives, 5a–g and 7a–f, was designed, synthesized, and evaluated for their anticancer activity against HepG2, HCT116, and MCF‐7 cells. HepG2 and HCT116 were the most sensitive cell lines to the influence of the new derivatives. In particular, compounds 7f, 7e, 7d, and 7c were found to be the most potent derivatives of all the tested compounds against the HepG2, HCT116, and MCF‐7 cancer cell lines. Compound 7f (IC50 = 6.19 ± 0.5, 5.47 ± 0.3, and 7.26 ± 0.3 µM, respectively) exhibited a higher activity than sorafenib (IC50 = 9.18 ± 0.6, 8.37 ± 0.7, and 5.10 ± 0.4 µM, respectively) against HepG2 and MCF‐7, cells but a lower activity against HCT116 cancer cells, respectively. Also, this compound displayed a higher activity than doxorubicin (IC50 = 7.94 ± 0.6, 8.07 ± 0.8, and 6.75 ± 0.4 µM, respectively) against HepG2 and MCF‐7 cells, but nearly the same activity against HCT116 cells, respectively. All derivatives, 5a–g and 7a–f, were evaluated for their inhibitory activities against vascular endothelial growth factor receptor‐2 (VEGFR‐2). Among them, compound 7f was found to be the most potent derivative that inhibited VEGFR‐2 at an IC50 value of 0.12 ± 0.02 µM, which is nearly the same as that of sorafenib (IC50 = 0.10 ± 0.02 µM). Compounds 7e, 7d, 7c, and 7b exhibited the highest activity, with IC50 values of 0.13 ± 0.02, 0.14 ± 0.02, 0.14 ± 0.02, and 0.18 ± 0.03 µM, respectively, which are more than the half of that of sorafenib. Furthermore, molecular docking was performed to investigate their binding mode and affinities toward the VEGFR‐2 receptor. The data obtained from the docking studies highly correlated with those obtained from the biological screening.
Functional Zwitterionic Polymers on Surface: Structures and Applications
Authors: Li Minglun , Zhuang Bilin , Yu Jing
Published: June 2020

Zwitterionic polymers are important in a wide range of industrial, biological and medical fields. Their chemical structures include an equal amount of anion and cation groups, and such structures give rise to many unique functionalities, such as temperature response, anti‐polyelectrolyte effect, and strong hydration properties. In this review, we focus on the structures and applications of functional zwitterionic polymers on surfaces. We review three areas of applications according to the architecture of the polymeric systems: surface coating, complex solutions, and hydrogel. We review the simulation and theory work and highlight some outlooks for further development.