bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic surveillance of COVID-19 cases in Beijing
Authors: Du Pengcheng , Ding Nan , Li Jiarui , Zhang Fujie , Wang Qi , Chen Zhihai , Song Chuan , Han Kai , Xie Wen , Liu Jingyuan , Wang Linghang , Wei Lirong , Ma Shanfang , Hua Mingxi , Yu Fengting , Wang Lin , Wang Wei , An Kang , Chen Jianjun , Liu Haizhou , Gao Guiju , Wang Sa , Huang Yanyi , Wu Angela R. , Wang Jianbin , Liu Di , Zeng Hui , Chen Chen
Published: October 2020

The spread of SARS-CoV-2 in Beijing before May, 2020 resulted from transmission following both domestic and global importation of cases. Here we present genomic surveillance data on 102 imported cases, which account for 17.2% of the total cases in Beijing. Our data suggest that all of the cases in Beijing can be broadly classified into one of three groups: Wuhan exposure, local transmission and overseas imports. We classify all sequenced genomes into seven clusters based on representative high-frequency single nucleotide polymorphisms (SNPs). Genomic comparisons reveal higher genomic diversity in the imported group compared to both the Wuhan exposure and local transmission groups, indicating continuous genomic evolution during global transmission. The imported group show region-specific SNPs, while the intra-host single nucleotide variations present as random features, and show no significant differences among groups. Epidemiological data suggest that detection of cases at immigration with mandatory quarantine may be an effective way to prevent recurring outbreaks triggered by imported cases. Notably, we also identify a set of novel indels. Our data imply that SARS-CoV-2 genomes may have high mutational tolerance.
A medicare-based comparative mortality analysis of active surveillance in older women with DCIS
Authors: Akushevich Igor , Yashkin Arseniy P. , Greenup Rachel A. , Hwang E. Shelley
Published: October 2020

Over 97% of individuals diagnosed with ductal carcinoma in situ (DCIS) will choose to receive guideline concordant care (GCC), which was originally designed to treat invasive cancers and is associated with treatment related morbidity. An alternative to GCC is active surveillance (AS) where therapy is delayed until medically necessary. Differences in mortality risk between the two approaches in women age 65+ are analyzed in this study. SEER and Medicare information on treatment during the first year after diagnosis was used to identify three cohorts based on treatment type and timing: GCC (N = 21,772; immediate consent for treatment), AS1 (N = 431; delayed treatment within 365 days), and AS2 (N = 205; no treatment/ongoing AS). A propensity score-based approach provided pseudorandomization between GCC and AS groups and survival was then compared. Strong influence of comorbidities on the treatment received was observed for all age-groups, with the greatest burden observed in the AS2 group. All-cause and breast-cancer-specific mortality hazard ratios (HR) for AS1 were not statistically different from the GCC group; AS2 was associated with notably higher risk for both all-cause (HR:3.54; CI:3.29, 3.82) and breast-cancer-specific (HR:10.73; CI:8.63,13.35) mortality. Cumulative mortality was substantially higher from other causes than from breast cancer, regardless of treatment group. Women managed with AS for DCIS had higher all-cause and breast-cancer-specific mortality. This effect declined after accounting for baseline comorbidities. Delays of up to 12 months in initiation of GCC did not underperform immediate surgery.
Prevalence and types of inconsistencies in clinical pharmacogenetic recommendations among major U.S. sources
Authors: Shugg Tyler , Pasternak Amy L. , London Bianca , Luzum Jasmine A.
Published: October 2020

Clinical implementation of pharmacogenomics (PGx) is slow. Previous studies have identified some inconsistencies among clinical PGx recommendations, but the prevalence and types of inconsistencies have not been comprehensively analyzed among major PGx guidance sources in the U.S. PGx recommendations from the Clinical Pharmacogenetics Implementation Consortium, U.S. Food and Drug Administration drug labels, and major U.S. professional medical organizations were analyzed through May 24, 2019. Inconsistencies were analyzed within the following elements: recommendation category; whether routine screening was recommended; and the specific biomarkers, variants, and patient groups involved. We identified 606 total clinical PGx recommendations, which contained 267 unique drugs. Composite inconsistencies occurred in 48.1% of clinical PGx recommendations overall, and in 93.3% of recommendations from three sources. Inconsistencies occurred in the recommendation category (29.8%), the patient group (35.4%), and routine screening (15.2%). In conclusion, almost one-half of clinical PGx recommendations from prominent U.S. guidance sources contain inconsistencies, which can potentially slow clinical implementation.
Contribution of sex on the underlying mechanism of the gambling disorder severity
Authors: Jiménez-Murcia Susana , Granero Roser , Giménez Mónica , del Pino-Gutiérrez Amparo , Mestre-Bach Gemma , Mena-Moreno Teresa , Moragas Laura , Baño Marta , Sánchez-González Jéssica , de Gracia Marta , Baenas-Soto Isabel , Contaldo S. Fabrizio , Valenciano-Mendoza Eduardo , Mora-Maltas Bernat , López-González Hibai , Menchón José M. , Fernández-Aranda Fernando
Published: October 2020

Significant increasing prevalences have been observed in gambling disorder (GD) in the last decades. This study analyzed the underlying mechanisms of the gambling severity with path analysis (implemented through Structural Equation Modeling, SEM), and assessed the potential moderator effect of the patients’ sex. A sample of n = 512 treatment-seeking patients was assessed for sociodemographics and clinical state previously to the treatment. Results obtained in two separate SEM (for men and women) revealed differences in the direct effects and the mediational links. Among the male subsample, higher GD severity was directly related to the higher cognitive bias and the younger age of onset of the problematic gambling, while impulsivity levels and age of onset achieved an indirect effect on the disordered gambling mediated by the cognitive bias. Among females, GD severity was directly increased by younger age of onset, higher cognitive bias and lower self-directedness, while lower socioeconomic positions, and higher levels in harm avoidance achieved an indirect effect on the gambling severity mediated also by the distortions related to the gambling activity. These results provide new empirical evidence for a better understanding of the GD etiology, suggesting that the underlying complex links mediating the GD severity are strongly related to the patients’ sex. The results can also contribute to design more effectiveness and precise therapy programs of patient-centered care.
Visual word form processing deficits driven by severity of reading impairments in children with developmental dyslexia
Authors: Brem S. , Maurer U. , Kronbichler M. , Schurz M. , Richlan F. , Blau V. , Reithler J. , van der Mark S. , Schulz E. , Bucher K. , Moll K. , Landerl K. , Martin E. , Goebel R. , Schulte-Körne G. , Blomert L. , Wimmer H. , Brandeis D.
Published: October 2020

The visual word form area (VWFA) in the left ventral occipito-temporal (vOT) cortex is key to fluent reading in children and adults. Diminished VWFA activation during print processing tasks is a common finding in subjects with severe reading problems. Here, we report fMRI data from a multicentre study with 140 children in primary school (7.9–12.2 years; 55 children with dyslexia, 73 typical readers, 12 intermediate readers). All performed a semantic task on visually presented words and a matched control task on symbol strings. With this large group of children, including the entire spectrum from severely impaired to highly fluent readers, we aimed to clarify the association of reading fluency and left vOT activation during visual word processing. The results of this study confirm reduced word-sensitive activation within the left vOT in children with dyslexia. Interestingly, the association of reading skills and left vOT activation was especially strong and spatially extended in children with dyslexia. Thus, deficits in basic visual word form processing increase with the severity of reading disability but seem only weakly associated with fluency within the typical reading range suggesting a linear dependence of reading scores with VFWA activation only in the poorest readers.
Decrease in social cohesion in a colonial seabird under a perturbation regime
Authors: Genovart M. , Gimenez O. , Bertolero A. , Choquet R. , Oro D. , Pradel R.
Published: October 2020

Social interactions, through influence on behavioural processes, can play an important role in populations’ resilience (i.e. ability to cope with perturbations). However little is known about the effects of perturbations on the strength of social cohesion in wild populations. Long-term associations between individuals may reflect the existence of social cohesion for seizing the evolutionary advantages of social living. We explore the existence of social cohesion and its dynamics under perturbations by analysing long-term social associations, in a colonial seabird, the Audouin’s gull Larus audouinii, living in a site experiencing a shift to a perturbed regime. Our goals were namely (1) to uncover the occurrence of long-term social ties (i.e. associations) between individuals and (2) to examine whether the perturbation regime affected this form of social cohesion. We analysed a dataset of more than 3500 individuals from 25 years of monitoring by means of contingency tables and within the Social Network Analysis framework. We showed that associations between individuals are not only due to philopatry or random gregariousness but that there are social ties between individuals over the years. Furthermore, social cohesion decreased under the perturbation regime. We sustain that perturbations may lead not only to changes in individuals’ behaviour and fitness but also to a change in populations’ social cohesion. The consequences of decreasing social cohesion are still not well understood, but they can be critical for the population dynamics of social species.
HIV- and HCV-specific markers and echocardiographic pulmonary artery systolic pressure among United States veterans
Authors: Zola Courtney E. , Duncan Meredith S. , So-Armah Kaku , Crothers Kristina A. , Butt Adeel A. , Gibert Cynthia L. , Kim Joon Woo W. , Lim Joseph K. , Re Vincent Lo , Tindle Hilary A. , Freiberg Matthew S. , Brittain Evan L.
Published: October 2020

Hepatitis C virus (HCV) may increase pulmonary hypertension (PH) risk among people living with HIV (PLWH). Prior studies on this topic have been relatively small and examined selected populations. We determine whether HIV/HCV coinfection is associated with higher pulmonary artery systolic pressure (PASP) and prevalent echocardiographic PH. We performed a cross-sectional analysis of 6032 (16% HIV/HCV coinfected) Veterans Aging Cohort Study participants enrolled 4/1/2003–9/30/2012 with echocardiographic PASP measures. We performed multiple linear and logistic regression analyses to determine whether HIV/HCV mono- or co-infection were associated with PASP and PH compared to uninfected individuals. Individuals with HIV/HCV coinfection displayed a higher PASP than uninfected individuals ($$\widehat{\beta }$$

β
^

=1.10, 95% CI 0.01, 2.20) but there was no association between HIV/HCV coinfection and prevalent PH. Subset analyses examined HIV and HCV disease severity markers separately and jointly. Among PLWH, HCV coinfection ($$\widehat{\beta }$$

β
^

=1.47, 95% CI 0.26, 2.67) and CD4 + cell count ($$\widehat{\beta }$$

β
^

= − 0.68, 95% CI − 1.10, − 0.27), but not HIV viral load nor ART regimen, were associated with PASP. Among people with HCV, neither HIV coinfection nor HCV biomarkers were associated with PASP. Among US veterans referred for echocardiography, HIV/HCV coinfection was not associated with a clinically significant elevation in pulmonary pressure. Lower absolute CD4 + T-cell count was inversely associated with PASP which warrants further investigation in prospective studies.
The HIF1α/JMY pathway promotes glioblastoma stem-like cell invasiveness after irradiation
Authors: Gauthier Laurent R. , Saati Mahasen , Bensalah-Pigeon Hayet , Ben M’Barek Karim , Gitton-Quent Oscar , Bertrand Romane , Busso Didier , Mouthon Marc-André , Collura Ada , Junier Marie-Pierre , Chneiweiss Hervé , Pineda José R. , Boussin François D.
Published: October 2020

Human glioblastoma (GBM) is the most common primary malignant brain tumor. A minor subpopulation of cancer cells, known as glioma stem-like cells (GSCs), are thought to play a major role in tumor relapse due to their stem cell-like properties, their high resistance to conventional treatments and their high invasion capacity. We show that ionizing radiation specifically enhances the motility and invasiveness of human GSCs through the stabilization and nuclear accumulation of the hypoxia-inducible factor 1α (HIF1α), which in turn transcriptionally activates the Junction-mediating and regulatory protein (JMY). Finally, JMY accumulates in the cytoplasm where it stimulates GSC migration via its actin nucleation-promoting activity. Targeting JMY could thus open the way to the development of new therapeutic strategies to improve the efficacy of radiotherapy and prevent glioma recurrence.
Stress-sensing in the human greying hair follicle: Ataxia Telangiectasia Mutated (ATM) depletion in hair bulb melanocytes in canities-prone scalp
Authors: Sikkink Stephen K. , Mine Solene , Freis Olga , Danoux Louis , Tobin Desmond J.
Published: October 2020

Canities (or hair greying) is an age-linked loss of the natural pigment called melanin from hair. While the specific cause(s) underlying the loss of melanogenically-active melanocytes from the anagen hair bulbs of affected human scalp remains unclear, oxidative stress sensing appears to be a key factor involved. In this study, we examined the follicular melanin unit in variably pigmented follicles from the aging human scalp of healthy individuals (22–70 years). Over 20 markers were selected within the following categories: melanocyte-specific, apoptosis, cell cycle, DNA repair/damage, senescence and oxidative stress. As expected, a reduction in melanocyte-specific markers in proportion to the extent of canities was observed. A major finding of our study was the intense and highly specific nuclear expression of Ataxia Telangiectasia Mutated (ATM) protein within melanocytes in anagen hair follicle bulbs. ATM is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks and functions as an important sensor of reactive oxygen species (ROS) in human cells. The incidence and expression level of ATM correlated with pigmentary status in canities-affected hair follicles. Moreover, increased staining of the redox-associated markers 8-OHdG, GADD45 and GP-1 were also detected within isolated bulbar melanocytes, although this change was not clearly associated with donor age or canities extent. Surprisingly, we were unable to detect any specific change in the expression of other markers of oxidative stress, senescence or DNA damage/repair in the canities-affected melanocytes compared to surrounding bulbar keratinocytes. By contrast, several markers showed distinct expression of markers for oxidative stress and apoptosis/differentiation in the inner root sheath (IRS) as well as other parts of the hair follicle. Using our in vitro model of primary human scalp hair follicle melanocytes, we showed that ATM expression increased after incubation with the pro-oxidant hydrogen peroxide (H2O2). In addition, this ATM increase was prevented by pre-incubation of cells with antioxidants. The relationship between ATM and redox stress sensing was further evidenced as we observed that the inhibition of ATM expression by chemical inhibition promoted the loss of melanocyte viability induced by oxidative stress. Taken together these new findings illustrate the key role of ATM in the protection of human hair follicle melanocytes from oxidative stress/damage within the human scalp hair bulb. In conclusion, these results highlight the remarkable complexity and role of redox sensing in the status of human hair follicle growth, differentiation and pigmentation.
Assessment of the WAP-Myc mouse mammary tumor model for spontaneous metastasis
Authors: Utz Begüm , Turpin Rita , Lampe Johanna , Pouwels Jeroen , Klefström Juha
Published: October 2020

Breast cancer is the most common form of cancer in women. Despite significant therapeutic advances in recent years, breast cancer also still causes the greatest number of cancer-related deaths in women, the vast majority of which (> 90%) are caused by metastases. However, very few mouse mammary cancer models exist that faithfully recapitulate the multistep metastatic process in human patients. Here we assessed the suitability of a syngrafting protocol for a Myc-driven mammary tumor model (WAP-Myc) to study autochthonous metastasis. A moderate but robust spontaneous lung metastasis rate of around 25% was attained. In addition, increased T cell infiltration was observed in metastatic tumors compared to donor and syngrafted primary tumors. Thus, the WAP-Myc syngrafting protocol is a suitable tool to study the mechanisms of metastasis in MYC-driven breast cancer.
Publisher Correction: Non-cuttable material created through local resonance and strain rate effects
Authors: Szyniszewski Stefan , Vogel Rene , Bittner Florian , Jakubczyk Ewa , Anderson Miranda , Pelacci Manuel , Chinedu Ajoku , Endres Hans-Josef , Hipke Thomas
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
When a foreign gene meets its native counterpart: computational biophysics analysis of two PgiC loci in the grass Festuca ovina
Authors: Li Yuan , Mohanty Sandipan , Nilsson Daniel , Hansson Bengt , Mao Kangshan , Irbäck Anders
Published: October 2020

Duplicative horizontal gene transfer may bring two previously separated homologous genes together, which may raise questions about the interplay between the gene products. One such gene pair is the “native” PgiC1 and “foreign” PgiC2 in the perennial grass Festuca ovina. Both PgiC1 and PgiC2 encode cytosolic phosphoglucose isomerase, a dimeric enzyme whose proper binding is functionally essential. Here, we use biophysical simulations to explore the inter-monomer binding of the two homodimers and the heterodimer that can be produced by PgiC1 and PgiC2 in F. ovina. Using simulated native-state ensembles, we examine the structural properties and binding tightness of the dimers. In addition, we investigate their ability to withstand dissociation when pulled by a force. Our results suggest that the inter-monomer binding is tighter in the PgiC2 than the PgiC1 homodimer, which could explain the more frequent occurrence of the foreign PgiC2 homodimer in dry habitats. We further find that the PgiC1 and PgiC2 monomers are compatible with heterodimer formation; the computed binding tightness is comparable to that of the PgiC1 homodimer. Enhanced homodimer stability and capability of heterodimer formation with PgiC1 are properties of PgiC2 that may contribute to the retaining of the otherwise redundant PgiC2 gene.
Risk of higher dose methotrexate for renal impairment in patients with rheumatoid arthritis
Authors: Hayashi Keigo , Sada Ken-Ei , Asano Yosuke , Asano Sumie Hiramatsu , Yamamura Yuriko , Ohashi Keiji , Morishita Michiko , Watanabe Haruki , Narazaki Mariko , Matsumoto Yoshinori , Wada Jun
Published: October 2020

Renal impairment is a major concern in patients taking high-dose methotrexate (MTX) for malignancy, but it has not been fully explored in rheumatoid arthritis (RA) patients taking low-dose MTX. This study aimed to elucidate the dose-dependent effects of MTX on the renal function of patients with RA. We retrospectively reviewed 502 consecutive RA patients who were prescribed MTX for ≥ 1 year at Okayama University Hospital between 2006 and 2018. The primary outcome was the change in estimated glomerular filtration rate (eGFR) over 1 year. The association between MTX dosage (< 8, 8–12, and ≥ 12 mg/week) and the change in eGFR was evaluated using multiple linear regression analysis with adjustment for possible confounding factors including age, sex, disease duration, body weight, comorbidity, baseline eGFR, concomitant treatment, and disease activity. Mean patient age was 63 years; 394 (78%) were female. Median disease duration was 77 months, while mean MTX dosage was 8.6 mg/week. The last 1-year change of eGFR (mean ± SD) in patients treated with MTX < 8 (n = 186), 8–12 (n = 219), ≥ 12 mg/week (n = 97) decreased by 0.2 ± 7.3, 0.6 ± 8.6, and 4.5 ± 7.9 mL/min/1.73 m2/year, respectively (p < 0.0001). After adjustment for the confounding factors, MTX ≥ 12 mg/week was still correlated with a decrease in 1-year eGFR (beta-coefficient: − 2.5; 95% confidence interval, − 4.3 to − 0.6; p = 0.0089) in contrast to MTX 8–12 mg/week. Careful monitoring of renal function is required in patients with MTX ≥ 12 mg/week over the course of RA treatment regardless of disease duration.
Histological evidence for secretory bioluminescence from pectoral pockets of the American Pocket Shark (Mollisquama mississippiensis)
Authors: Claes Julien M. , Delroisse Jérôme , Grace Mark A. , Doosey Michael H. , Duchatelet Laurent , Mallefet Jérôme
Published: October 2020

The function of pocket shark pectoral pockets has puzzled scientists over decades. Here, we show that the pockets of the American Pocket Shark (Mollisquama mississippiensis) contain a brightly fluorescent stratified cubic epithelium enclosed in a pigmented sheath and in close contact with the basal cartilage of the pectoral fins; cells of this epithelium display a centripetal gradient in size and a centrifuge gradient in fluorescence. These results strongly support the idea that pocket shark’s pockets are exocrine holocrine glands capable of discharging a bioluminescent fluid, potentially upon a given movement of the pectoral fin. Such capability has been reported in many other marine organisms and is typically used as a close-range defensive trick. In situ observations would be required to confirm this hypothesis.
ViceCT and whiceCT for simultaneous high-resolution visualization of craniofacial, brain and ventricular anatomy from micro-computed tomography
Authors: Llambrich Sergi , Wouters Jens , Himmelreich Uwe , Dierssen Mara , Sharpe James , Gsell Willy , Martínez-Abadías Neus , Vande Velde Greetje
Published: October 2020

Up to 40% of congenital diseases present disturbances of brain and craniofacial development resulting in simultaneous alterations of both systems. Currently, the best available method to preclinically visualize the brain and the bones simultaneously is to co-register micro-magnetic resonance (µMR) and micro-computed tomography (µCT) scans of the same specimen. However, this requires expertise and access to both imaging techniques, dedicated software and post-processing knowhow. To provide a more affordable, reliable and accessible alternative, recent research has focused on optimizing a contrast-enhanced µCT protocol using iodine as contrast agent that delivers brain and bone images from a single scan. However, the available methods still cannot provide the complete visualization of both the brain and whole craniofacial complex. In this study, we have established an optimized protocol to diffuse the contrast into the brain that allows visualizing the brain parenchyma and the complete craniofacial structure in a single ex vivo µCT scan (whiceCT). In addition, we have developed a new technique that allows visualizing the brain ventricles using a bilateral stereotactic injection of iodine-based contrast (viceCT). Finally, we have tested both techniques in a mouse model of Down syndrome, as it is a neurodevelopmental disorder with craniofacial, brain and ventricle defects. The combined use of viceCT and whiceCT provides a complete visualization of the brain and bones with intact craniofacial structure of an adult mouse ex vivo using a single imaging modality.
How the incentive to contribute affects contributions in the one-shot public goods game
Authors: van den Berg Pieter , Dewitte Peter , Aertgeerts Ine , Wenseleers Tom
Published: October 2020

Enmeshed in various social structures, humans must often weigh their own interest against the interest of others—including the common interest of groups they belong to. The Public Goods Game (PGG), which succinctly pits individual interest against group interest, has been a staple of research into how people make such decisions. It has been studied in many variations, in the laboratory and (increasingly) online. One of the defining parameters of the PGG is the marginal per capita return of the group project (MPCR), which determines the incentive for contributing to the group project relative to the incentive of keeping points in the personal account. The effect of MPCR on contributions has been investigated before, but its effects have never been characterised with high resolution. Here, we present a systematic and high-resolution investigation of the effect of MPCR in groups of three. We do this in a large-scale online decision making experiment recruiting participants from Amazon Mechanical Turk. Our results provide a fine-grained account of the relationship between incentive to cooperate on the one hand and cooperation on the other, and can help to provide a basis for choosing MPCR magnitudes for future research endeavours using online PGG studies.
Temporal trends of care practices, morbidity, and mortality of extremely preterm infants over 10-years in South Wales, UK
Authors: Boel Lieve , Banerjee Sujoy , Clark Megan , Greenwood Annabel , Sharma Alok , Goel Nitin , Bagga Gautam , Poon Chuen , Odd David , Chakraborty Mallinath
Published: October 2020

Contemporary outcome data of preterm infants are essential to commission, evaluate and improve healthcare resources and outcomes while also assisting professionals and families in counselling and decision making. We analysed trends in clinical practice, morbidity, and mortality of extremely preterm infants over 10 years in South Wales, UK. This population-based study included live born infants < 28 weeks of gestation in tertiary neonatal units between 01/01/2007 and 31/12/2016. Patient characteristics, clinical practices, mortality, and morbidity were studied until death or discharge home. Temporal trends were examined by adjusted multivariable logistic regression models and expressed as adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). A sensitivity analysis was conducted after excluding infants born at < 24 weeks of gestation. In this population, overall mortality for infants after live birth was 28.2% (267/948). The odds of mortality (aOR 0.93, 95% CI [0.88, 0.99]) and admission to the neonatal unit (0.93 [0.87, 0.98]) significantly decreased over time. Non-invasive ventilation support during stabilisation at birth increased significantly (1.26 [1.15, 1.38]) with corresponding decrease in mechanical ventilation at birth (0.89 [0.81, 0.97]) and following admission (0.80 [0.68–0.96]). Medical treatment for patent ductus arteriosus significantly decreased over the study period (0.90 [0.85, 0.96]). The incidence of major neonatal morbidities remained stable, except for a reduction in late-onset sepsis (0.94 [0.89, 0.99]). Gestation and centre of birth were significant independent factors for several outcomes. The results from our sensitivity analysis were compatible with our main results with the notable exception of death after admission to NICU (0.95 [0.89, 1.01]). There were significant improvements in survival and reduction of late-onset sepsis of extreme preterm infants in South Wales between 2007 and 2016. The sensitivity analysis suggests that some of the temporal changes observed were driven by improved outcomes in the most preterm of infants. Clinical practices related to respiratory support have changed but significant variations in clinical practices and outcomes between centres remain unexplained. The adoption of regional evidence-based clinical guidelines is likely to improve outcomes and reduce variation.
Assessment of the direct quantitation of SARS-CoV-2 by droplet digital PCR
Authors: Deiana Michela , Mori Antonio , Piubelli Chiara , Scarso Salvatore , Favarato Mosè , Pomari Elena
Published: October 2020

Droplet digital PCR (ddPCR) is a sensitive and reproducible technology widely used for quantitation of several viruses. The aim of this study was to evaluate the 2019-nCoV CDC ddPCR Triplex Probe Assay (BioRad) performance, comparing the direct quantitation of SARS-CoV-2 on nasopharyngeal swab with the procedure applied to the extracted RNA. Moreover, two widely used swab types were compared (UTM 3 mL and ESwab 1 mL, COPAN). A total of 50 nasopharyngeal swabs (n = 25 UTM 3 mL and n = 25 ESwab 1 mL) from SARS-CoV-2 patients, collected during the pandemic at IRCCS Sacro Cuore Don Calabria Hospital (Veneto Region, North-East Italy), were used for our purpose. After heat inactivation, an aliquot of swab medium was used for the direct quantitation. Then, we compared the direct method with the quantitation performed on the RNA purified from nasopharyngeal swab by automated extraction. We observed that the direct approach achieved generally equal RNA copies compared to the extracted RNA. The results with the direct quantitation were more accurate on ESwab with a sensitivity of 93.33% [95% CI, 68.05 to 99.83] and specificity of 100.00% for both N1 and N2. On the other hand, on UTM we observed a higher rate of discordant results for N1 and N2. The human internal amplification control (RPP30) showed 100% of both sensitivity and specificity independent of swabs and approaches. In conclusion, we described a direct quantitation of SARS-CoV-2 in nasopharyngeal swab. Our approach resulted in an efficient quantitation, without automated RNA extraction and purification. However, special care needs to be taken on the potential bias due to the conservation of samples and to the heating treatment, as we used thawed and heat inactivated material. Further studies on a larger cohort of samples are warranted to evaluate the clinical value of this direct approach.
Histological changes in human skin 32 days after death and the potential forensic significance
Authors: Wei Wang , Michu Qi , Wenjuan Dong , Jianrong Wen , Zhibing Han , Ming Yang , Bo Jin , Xia Lin
Published: October 2020

To observe the histological changes in human skin within 32 days after death to explore its potential significance in forensic practice. The intact full-thickness skin and subcutaneous tissue from the sternum of eight corpses were placed in an environment of 4–6 °C for 4 h, 6 h, 12 h, 18 h, 24 h, 36 h, 48 h, 60 h, 72 h, 84 h, 96 h, 6 d, 8 d, 10 d, 12 d, 16 d, 20 d, 24 d, 28 d, and 32 d. Then, the whole layer of the skin was stained with haematoxylin & eosin. The histological morphology of the epidermis, dermis and appendages (sweat glands, hair follicles, and sebaceous glands) was observed under an light microscope. The epithelial nucleus condensed at 24 h after death, and cell lysis was exhausted after 20 days. The post-mortem changes in the dermis occurred later than that of the epidermis (72 h), but after epidermal changes started, the change was more rapid. At 16 d, the layers had become homogenized. The epidermis and dermis had completely separated 24 d after death. The changes in the sweat glands appeared earlier (24 h) and disappeared later (32 days); the sebaceous glands and hair follicles began to undergo degenerative changes at 96 h after death, and at approximately 20 d, only their contour remained. There were individual and structural differences in the post-mortem histological changes in the skin. At 4–6 °C ambient temperature, some structures of the human skin still exist for a long time after death, and these structures can be used to identify the source of the tissue; post-mortem histological changes in the skin occur at specific times, which can be used to help infer the time of death. A comprehensive observation of changes in the skin composition/structure is required to comprehensively analyse possible death times.
Author Correction: Synthesis of nickel nanoparticles by a green and convenient method as a magnetic mirror with antibacterial activities
Authors: Ahghari Mohammad Reza , Soltaninejad Vahhab , Maleki Ali
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Performance and clinical utility of supervised machine-learning approaches in detecting familial hypercholesterolaemia in primary care
Authors: Akyea Ralph K. , Qureshi Nadeem , Kai Joe , Weng Stephen F.
Published: October 2020

Familial hypercholesterolaemia (FH) is a common inherited disorder, causing lifelong elevated low-density lipoprotein cholesterol (LDL-C). Most individuals with FH remain undiagnosed, precluding opportunities to prevent premature heart disease and death. Some machine-learning approaches improve detection of FH in electronic health records, though clinical impact is under-explored. We assessed performance of an array of machine-learning approaches for enhancing detection of FH, and their clinical utility, within a large primary care population. A retrospective cohort study was done using routine primary care clinical records of 4,027,775 individuals from the United Kingdom with total cholesterol measured from 1 January 1999 to 25 June 2019. Predictive accuracy of five common machine-learning algorithms (logistic regression, random forest, gradient boosting machines, neural networks and ensemble learning) were assessed for detecting FH. Predictive accuracy was assessed by area under the receiver operating curves (AUC) and expected vs observed calibration slope; with clinical utility assessed by expected case-review workload and likelihood ratios. There were 7928 incident diagnoses of FH. In addition to known clinical features of FH (raised total cholesterol or LDL-C and family history of premature coronary heart disease), machine-learning (ML) algorithms identified features such as raised triglycerides which reduced the likelihood of FH. Apart from logistic regression (AUC, 0.81), all four other ML approaches had similarly high predictive accuracy (AUC > 0.89). Calibration slope ranged from 0.997 for gradient boosting machines to 1.857 for logistic regression. Among those screened, high probability cases requiring clinical review varied from 0.73% using ensemble learning to 10.16% using deep learning, but with positive predictive values of 15.5% and 2.8% respectively. Ensemble learning exhibited a dominant positive likelihood ratio (45.5) compared to all other ML models (7.0–14.4). Machine-learning models show similar high accuracy in detecting FH, offering opportunities to increase diagnosis. However, the clinical case-finding workload required for yield of cases will differ substantially between models.
Fatty-acid-induced FABP5/HIF-1 reprograms lipid metabolism and enhances the proliferation of liver cancer cells
Authors: Seo Jieun , Jeong Do-Won , Park Jong-Wan , Lee Kwang-Woong , Fukuda Junji , Chun Yang-Sook
Published: October 2020

Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor essential for cancer cell survival. The reprogramming of lipid metabolism has emerged as a hallmark of cancer, yet the relevance of HIF-1α to this process remains elusive. In this study, we profile HIF-1α-interacting proteins using proteomics analysis and identify fatty acid-binding protein 5 (FABP5) as a critical HIF-1α-binding partner. In hepatocellular carcinoma (HCC) tissues, both FABP5 and HIF-1α are upregulated, and their expression levels are associated with poor prognosis. FABP5 enhances HIF-1α activity by promoting HIF-1α synthesis while disrupting FIH/HIF-1α interaction at the same time. Oleic-acid treatment activates the FABP5/HIF-1α axis, thereby promoting lipid accumulation and cell proliferation in HCC cells. Our results indicate that fatty-acid-induced FABP5 upregulation drives HCC progression through HIF-1-driven lipid metabolism reprogramming.
Large electromechanical strain and unconventional domain switching near phase convergence in a Pb-free ferroelectric
Authors: Venkateshwarlu Sarangi , Venkataraman Lalitha K. , Segouin Valentin , Marlton Frederick P. , Hin Ho Chin , Chernyshov Dmitry , Ren Yang , Jørgensen Mads R. V. , Nayak Sanjib , Rödel Jürgen , Daniel Laurent , Pramanick Abhijit
Published: October 2020

In many ferroelectrics, large electromechanical strains are observed near regions of composition- or temperature- driven phase coexistence. Phenomenologically, this is attributed to easy re-orientation of the polarization vector and/or phase transition, although their effects are highly convoluted and difficult to distinguish experimentally. Here, we used synchrotron X-ray scattering and digital image correlation to differentiate between the microscopic mechanisms leading to large electrostrains in an exemplary Pb-free piezoceramic Sn-doped barium calcium zirconate titanate. Large electrostrains of ~0.2% measured at room-temperature are attributed to an unconventional effect, wherein polarization switching is aided by a reversible phase transition near the tetragonal-orthorhombic phase boundary. Additionally, electrostrains of ~0.1% or more could be maintained from room temperature to 140 °C due to a succession of different microscopic mechanisms. In situ X-ray diffraction elucidates that while 90° domain reorientation is pertinent below the Curie temperature (TC), isotropic distortion of polar clusters is the dominant mechanism above TC.
A conformational tweak for enhanced cellular internalization, photobleaching resistance and prolonged imaging efficacy
Authors: Meher Niranjan , Bidkar Anil Parsram , Barman Debasish , Ghosh Siddhartha Sankar , Iyer Parameswar Krishnan
Published: October 2020

A simple strategy of conformational manipulation has been unveiled to fine-tune the photophysical and supramolecular self-assembly properties of small molecular systems, which subsequently regulates their biological activities.
Bridging and axial carbene binding modes in cobalt corrole complexes: effect on carbene transfer
Authors: Musselman Bradley W. , Lehnert Nicolai
Published: October 2020

Two different types of carbene intermediates are observed in the reaction of ethyl diazoacetate (EDA) with different Co corrole complexes, and their properties and reactivities are reported.
Investigating the solid-state assembly of pharmaceutically-relevant N,N-dimethyl-O-thiocarbamates in the absence of labile hydrogen bonds
Authors: Tan Davin , Ng Zi Xuan , Ganguly Rakesh , Li Yongxin , Soo Han Sen , Mohamed Sharmarke , García Felipe
Published: October 2020

There are many active pharmaceutical ingredients that lack N–H, O–H and S–H hydrogen-bond donor functional groups.
Theoretical insights on acceptor–donor dyads for organic photovoltaics
Authors: Turelli Michele , Alberga Domenico , Lattanzi Gianluca , Ciofini Ilaria , Adamo Carlo
Published: October 2020

Transport mechanisms in a set of crystal polymorphs of a donor–acceptor dyad used in a SMOSC, are revealed through the comparison of polymorphs’ transport efficiencies. The findings offer hints on how to improve the design of better performing dyads.
Electro- and photoelectro-catalysts derived from bimetallic amorphous metal–organic frameworks
Authors: Fonseca Javier , Choi Sunho
Published: October 2020

It is developed a synthesis method for the design of new bimetallic amorphous MOFs. Such frameworks serve as precursors to prepare high-performance electro- and photoelectro-catalysts for ORR, OER and HER in both acidic and alkaline media.
Direct design of active catalysts for low temperature oxidative coupling of methane via machine learning and data mining
Authors: Ohyama Junya , Kinoshita Takaaki , Funada Eri , Yoshida Hiroshi , Machida Masato , Nishimura Shun , Uno Takeaki , Fujima Jun , Miyazato Itsuki , Takahashi Lauren , Takahashi Keisuke
Published: October 2020

Direct design of low temperature oxidative coupling of methane catalysts is proposed via machine learning and data mining.
Vapochromic luminescence of a spin-coated copper(i) complex thin film by the direct coordination of vapour molecules
Authors: Kondo Sae , Yoshimura Nobutaka , Yoshida Masaki , Kobayashi Atsushi , Kato Masako
Published: October 2020

The spin-coated thin film fabricated with a simple Cu(i) complex exhibits luminescence colour changes in response to N-heteroaromatic vapours reversibly.
Transition metal chemistry of heavier group 14 congener triple-bonded complexes: syntheses and reactivity
Authors: Saini Suresh , Agarwal Abhishek , Bose Shubhankar Kumar
Published: October 2020

The intriguing class of metal–ylidyne ME (E = Si–Pb) complexes has received widespread interest in recent years due to their exceptional structure and reactivity features. In this report we summarize the recent developments and their reactivity studies.
Solid state mononuclear divalent nickel spin crossover complexes
Authors: Qamar Obaid Ali , Cong Cong , Ma Huaibo
Published: October 2020

As a unique 3d8spin crossover phenomenon, diverse electron configurations provide more options and strategies for selection.
Effect of dynamic correlation on the ultrafast relaxation of uracil in the gas phase
Authors: Chakraborty Pratip , Liu Yusong , Weinacht Thomas , Matsika Spiridoula
Published: October 2020

High level multi-reference non-adiabatic dynamics simulations reveal that uracil’s photoexcited S2 state decays very quickly without any significant trapping.
An investigation of the photovoltaic parameters of ZnS grown on ZnO(101̄1)
Authors: Fernandes Cristian Dias , Ferrer Mateus Meneghetti , Raubach Cristiane Wienke , Moreira Eduardo Ceretta , Gularte Luciano Timm , Cava Sergio , Piotrowski Maurício Jeomar , Jardim Pedro Lovato Gomes , Carvalho Ramon Dadalto , Moreira Mario Lucio
Published: October 2020

The selective growth of ZnS on ZnO (zinc nitrateversusacetate precursors) affects the photovoltaic parameters when the material is used as a photoanode in solar cells.
Utilizing host–guest interaction enables the simultaneous enhancement of the quantum yield and Stokes shift in organosilane-functionalized, nitrogen-containing carbon dots for laminated luminescent solar concentrators
Authors: Huang Hsiu-Ying , Talite Maria Jessabel , Cai Kun-Bin , Soebroto Ruth Jeane , Chang Sheng-Hsiung , Liu Wei-Ren , Chou Wu-Ching , Yuan Chi-Tsu
Published: October 2020

Solar energy can be harvested using luminescent solar concentrators (LSCs) incorporated with edge-mounted solar cells without sacrificing their see-through visibility, thus facilitating the development of solar windows.
Lewis acid-mediated synthesis of mono- and tris-indole adducts from chiral aziridines
Authors: Macha Lingamurthy , Singh Deepak , Rhee Hyong-Jin , Ha Hyun-Joon
Published: October 2020

Lewis acid-mediated regio- and stereoselective nucleophilic addition of 2- (or) 3-substituted indoles to non-activated aziridine 2-carboxaldehydes afforded mono- and tris-indole adducts.
Ultrasmall SnO2 nanocrystals sandwiched into polypyrrole and Ti3C2Tx MXene for highly effective sodium storage
Authors: Ding Jianfeng , Tang Cheng , Zhu Guanjia , He Fengyi , Du Aijun , Wu Minghong , Zhang Haijiao
Published: October 2020

A novel sandwich-type P-SnO2/Ti3C2 composite with superior sodium storage capability has been fabricated, where polypyrrole (PPy) layer modified SnO2 nanocrystals are strongly coupled with Ti3C2Tx Mxene nanosheets through Sn–O–Ti chemical bonds.
A sodium alginate-based sustained-release IPN hydrogel and its applications
Authors: Zou Zuhao , Zhang Bijun , Nie Xiaoqin , Cheng Yu , Hu Zhang , Liao Mingneng , Li Sidong
Published: October 2020

Interpenetrating polymer network (IPN) hydrogels are crosslinked by two or more polymer networks, providing free volume space in the three-dimensional network structure, and providing conditions for the sustained and controlled release of drugs.
Design and fabrication of a microfluidic chip to detect tumor markers
Authors: Sun Cuimin , You Hui , Gao Nailong , Chang Jianguo , Gao Qingxue , Xie Yang , Xie Yao , Xu Ronald X.
Published: October 2020

A microfluidic chip for detecting tumor markers integrated functions including blood plasma separation, microvalve operation, and antibody immobilization.
Effects of synthesised polyaniline (PAni) contents on the anti-static properties of PAni-based polylactic acid (PLA) films
Authors: Wong Pei-Yi , Phang Sook-Wai , Baharum Azizah
Published: October 2020

An anti-static polymer film was prepared using biodegradable poly(lactic acid) as a matrix and polyaniline (PAni) as an anti-static agent to eliminate accumulated static charges.
Preparation and properties of aramid pulp/acrylonitrile-butadiene rubber composites
Authors: Zhang Rui , Li Yingzhe , Du Zhongjin , Li Zhuo , Wan Sheng , Yuan Xinna , Wang Yuping
Published: October 2020

Aramid pulp (AP) was introduced into acrylonitrile-butadiene rubber (NBR)-based composites in various amounts by two different introduction methods. The predispersion of AP in the NBR increased the tensile strength of the composites with a relatively high AP content.
Formulation and characterization of oil-in-water nanoemulsions stabilized by crude saponins isolated from onion skin waste
Authors: Dahlawi Saad M. , Nazir Wahab , Iqbal Rashid , Asghar Waqas , Khalid Nauman
Published: October 2020

Crude saponins isolated from onion skin waste were studied to minimize the interfacial tension at oil–water interfaces, and to evaluate important factors on the formulation and characterization of nanoemulsions stabilized by these saponins as a new natural emulsifier.
Signal-enhanced real-time magnetic resonance of enzymatic reactions at millitesla fields
Authors: Korchak Sergey , Jagtap Anil P. , Glöggler Stefan
Published: October 2020

We demonstrate that metabolism can be monitored in real-time with magnetic resonance at milli-tesla fields that are 1000 fold lower than state-of-the-art high field spectrometers.
Bridging photochemistry and photomechanics with NMR crystallography: the molecular basis for the macroscopic expansion of an anthracene ester nanorod
Authors: Chalek Kevin R. , Dong Xinning , Tong Fei , Kudla Ryan A. , Zhu Lingyan , Gill Adam D. , Xu Wenwen , Yang Chen , Hartman Joshua D. , Magalhães Alviclér , Al-Kaysi Rabih O. , Hayward Ryan C. , Hooley Richard J. , Beran Gregory J. O. , Bardeen Christopher J. , Mueller Leonard J.
Published: October 2020

NMR crystallography establishes absolute unit-cell orientations relative to the shape change, revealing the atomic-resolution mechanism for the nanorod's photomechanical response.
Implanting an electrolyte additive on a single crystal Ni-rich cathode surface for improved cycleability and safety
Authors: Han Yongkang , Xu Jinmei , Wang Wei , Long Fu , Qu Qunting , Wang Yan , Zheng Honghe
Published: October 2020

Interfacial modification is one of the most important technologies to improve the overall electrochemical properties of Ni-rich cathodes.
Expediting polysulfide catalytic conversion for lithium–sulfur batteries via in situ implanted ultrafine Fe3O4 nanocrystals in carbon nanospheres
Authors: Su Zhe , Chen Mingqi , Pan Yankai , Liu Yajing , Xu Hai , Zhang Yayun , Long Donghui
Published: October 2020

The sluggish reaction kinetics and notorious polysulfide shuttling arising from the multistep solid/liquid conversion are the significant obstacles to practical applications of lithium–sulfur (Li–S) batteries.