bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Prehospital Crushed Prasugrel Tablets in Patients With ST-Segment–Elevation Myocardial Infarction Planned for Primary Percutaneous Coronary Intervention
Authors: Vlachojannis Georgios J. , Wilschut Jeroen M. , Vogel Rosanne F. , Lemmert Miguel E. , Delewi Ronak , Diletti Roberto , van der Waarden Nancy W.P.L. , Nuis Rutger-Jan , Paradies Valeria , Alexopoulos Dimitrios , Zijlstra Felix , Montalescot Gilles , Angiolillo Dominick J. , Krucoff Mitchell W. , Van Mieghem Nicolas M. , Smits Pieter C.
Published: October 2020

Background:

Early treatment with a potent oral platelet P2Y
12
inhibitor is recommended in patients presenting with ST-segment–elevation myocardial infarction scheduled to undergo primary percutaneous coronary intervention (pPCI). The impact on coronary reperfusion of crushed P2Y
12
inhibitor tablets, which lead to more prompt and potent platelet inhibition, is unknown.

Methods:

We conducted a randomized controlled, multicenter trial in the Netherlands, enrolling patients with ST-segment–elevation myocardial infarction scheduled to undergo pPCI. Patients were randomly allocated to receive in the ambulance, before transfer, a 60-mg loading dose of prasugrel either as crushed or integral tablets. The independent primary end points were thrombolysis in myocardial infarction (TIMI) 3 flow in the infarct-related artery at initial coronary angiography, and complete (≥70%) ST-segment resolution 1 hour after pPCI. The safety end points were TIMI major and Bleeding Academic Research Consortium ≥3 bleedings. Secondary end points included platelet reactivity and ischemic outcomes.

Results:

A total of 727 patients were assigned to either crushed or integral tablets of prasugrel loading dose. The median time from study treatment to wire-crossing during pPCI was 57 (47–70) minutes. The primary end point TIMI 3 flow in the infarct-related artery before pPCI occurred in 31.0% in the crushed group versus 32.7% in the integral group (odds ratio, 0.92 [95% CI, 0.65–1.30],
P
=0.64). Complete ST-segment resolution 1 hour after pPCI was present in 59.9% in the crushed group versus 57.3% in the integral group (odds ratio, 1.11 [95% CI, 0.78–1.58],
P
=0.55). Platelet reactivity at the beginning of pPCI, measured as P2Y
12
reactivity unit, differed significantly between groups (crushed, 192 [132–245] versus integral, 227 [184–254],
P
≤0.01). TIMI major and Bleeding Academic Research Consortium ≥3 bleeding occurred in 0% in the crushed group versus 0.8% in the integral group, and in 0.3% in the crushed group versus 1.1% in the integral group, respectively. There were no differences observed between groups regarding ischemic events at 30 days.

Conclusions:

Prehospital administration of crushed prasugrel tablets does not improve TIMI 3 flow in the infarct-related artery before pPCI or complete ST-segment resolution 1 h after pPCI in patients presenting with ST-segment–elevation myocardial infarction scheduled for pPCI.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03296540.
Thinking Beyond the Lockdown: On the Possibility of a Democratic Biopolitics
Authors: Sotiris Panagiotis
Published: October 2020

COVID-19 is not only a health emergency but also a strategic challenge for any politics of resistance, struggle and transformation. Understanding the social and political dynamics associated with morbidity and mortality and the many ‘ecologies of disease’ associated with the pandemic is necessary if we want to think beyond the limits of the lockdown strategy. It is here that the possibility of a democratic biopolitics emerges as part of a broader strategy for communism.
Global Governance and the Double Movement
Authors: Mendly Dorottya
Published: October 2020

This article reconstructs the evolution of global governance through time, in a perspective organized around Karl Polanyi’s double movement. Starting from present-day global governance, the article reaches back in time to understand the different socially and historically contingent layers that have constituted it as a discourse and a set of practices. It argues based on the notion that global governance is a hegemonic discourse of world politics, and claims that it is so because it has become inclusive enough to accommodate both the “movement” and the “countermovement” in its cognitive and material structures. In this order of knowledge, the “healthy functioning” of the global economy always precedes the existence of prosperous societies, and comes before maintaining harmony in the ecosystem. This order sustains the active-reactive dynamics of the double movement and limits the possibilities of change in global governance.
An annotated key to the Bovista (Lycoperdaceae, Basidiomycota) species in Russia

Authors: REBRIEV YURY A. , GE ZAI-WEI , VORONINA ELENA Y. , FOMINA ELENA S. , NAZARENKO ALEXANDER V.
Published: October 2020

The present paper deals with Bovista species diversity in Russia. Morphological features of the genus are presented as well as geographical distribution in Russia and globally. We present a phylogenetic tree and the correlation of molecular data and morphology is discussed. An identification key for 16 species known in Russia from herbarium collections is provided as well as SEM and LM images of basidiospores and capillitium of these species. According to morphological and genetic data three taxa are probably undescribed. We need additional collections for these species in order to describe them as new. The variability of the polymorphic Bovista aestivalis and some other species is discussed too.
Taxonomic Studies of the genus Decticus Serville, 1831 from China (Orthoptera: Tettigoniidae: Tettigoniinae), based on Morphology and Songs
Authors: LIU FEI , CHEN LIUSHENG , LIU CHUNXIANG
Published: October 2020

The genus Decticus Serville contains sixteen known species and subspecies, those widely distributed in the Palaearctic, among which three species and subspecies have been recorded in China. Morphological features in specimens of Decticus are variable. Stable characteristics and reliable methods for distict the species and subspcies are required. The geometric morphometrics was conducted to explore morphological variance on structure of right tegmen of Decticus specimens based on 30 landmarks, as well as qualitative analysis on variances of body size, male stridualtory apparatus and genital characters. The male calling songs structures, if available, can be compared and identified species usefully. The results indicate that the analyzed samples suggest two species, D. albifrons (Fabricius, 1775) and D. verrucivorus (Linnaeus, 1758). D. verrucivorus includes four subspecies, D. v. verrucivorus (Linnaeus, 1758), D. v. crassus Götz, 1970 (a newly recorded subspecies from China), and two new subspecies, D. v. latipennis ssp. n. and D. v. sayram ssp. n.. The songs of D. albifrons and D. v. verrucivorus, D. v. crassus are composed of numerous single chirps. One chirp of D. albifrons consists of one low-amplitude and short-duration syllable, and one high-amplitude and long-duration syllable. One chirp of D. v. verrucivorus consists of five syllables with different amplitudes. One chirp of D. v. crassus consists of five or six syllables with different amplitudes. Illustrations of necessary morphological and bioacoustical characters are presented.
Evapotranspiration Climatology of Indiana Using In Situ and Remotely Sensed Products
Authors: Niyogi Dev , Jamshidi Sajad , Smith David , Kellner Olivia
Published: October 2020

An intercomparison of multiresolution evapotranspiration (ET) datasets with reference to ground-based measurements for the development of regional reference (ETref) and actual (ETa) evapotranspiration maps over Indiana is presented. A representative ETref equation for the state is identified by evaluating 10 years of in situ measurements (2009–19). A statewide ETref climatology is developed using the ETref equation and high-resolution surface meteorological data from the gridded surface meteorological dataset (gridMET). For ETa analyses, MODIS, Simplified Surface Energy Balance Operational dataset (SSEBop), Global Land Evaporation Amsterdam Model (GLEAM) (versions 3.3a and 3.3b), and NLDAS (Noah and VIC) datasets are evaluated using AmeriFlux data. Thirty years of rainfall data from Climate Hazards Group Infrared Precipitation with Station Data Rainfall (CHIRPS) are used with the ET datasets to develop effective precipitation fields. Results show that the standardized Penman–Monteith equation performs as the best ETref equation with median symmetric accuracy (MSA) of 0.37, Taylor’s skill score (TSC) of 0.89, and r2 = 0.83. The analysis shows that the gridMET dataset overestimates wind speed and requires adjustment before a series of statewide ETref climatology maps are generated (1990–2020). For ETa, the MODIS and GLEAM (3.3b) datasets outperform the rest, with MSA = 0.5, TSC = 0.8, and r2 = 0.8. The state ETa dataset is generated using all MODIS data from 2003 and blending the MODIS data with GLEAM (3.3b) to cover data unavailability. Using the top-performing datasets, annual ETref for Indiana is computed as 1110 mm, ETa as 708 mm, and precipitation as 1091 mm. A marginal increasing climatological trend is found for Indiana’s ETref (0.013 mm yr−1) while ETa is found to be relatively stable. The state’s water availability, defined as rainfall minus ETa, has remained positive and stable at 0.99 mm day−1 (annual magnitude of +3820 mm).
Preference Dynamics in Sequential Consumer Choice with Defaults
Authors: Donkers Bas , Dellaert Benedict G.C. , Waisman Rory M. , Häubl Gerald
Published: October 2020

This research examines the impact of defaults on product choice in sequential-decision settings. Whereas prior research has shown that a default can affect what consumers purchase by promoting choice of the preselected option, the influence of defaults is more nuanced when consumers make a series of related choices. In such a setting, consumer preferences may evolve across choices due to “spillover” effects from one choice to subsequent choices. The authors hypothesize that defaults systematically attenuate choice spillover effects because accepting a default is a more passive process than either choosing a nondefault option in the presence of a default or making a choice in the absence of a default. Three experiments and a field study provide compelling evidence for such default-induced changes in choice spillover effects. The findings show that firms’ setting of high-price defaults with the aim of influencing consumers to choose more expensive products can backfire through the attenuation of spillover. In addition to advancing the understanding of the interplay between defaults and preference dynamics, insights from this research have important practical implications for firms applying defaults in sequential choices.
Clinical outcomes of posterior laminectomy and pedicle screw fixation for upper cervical intraspinal tumors: a case series
Authors: Chen Zhida , Yu Hui , Song Chao , Zhang Li , Wu Jin , Xiao Lili , Lin Bin
Published: October 2020

Objective

This study was performed to introduce posterior laminectomy and pedicle screw fixation for the treatment of upper cervical spinal cord tumors and investigate the curative effects.

Methods

Eighteen patients (11 men, 7 women) who underwent surgical treatment of an upper cervical intraspinal tumor from January 2008 to June 2013 were reviewed. Clinical parameters including age, sex, affected spinal levels, lesion location, duration and type of symptoms, and pathological features were retrospectively investigated.

Results

The mean operation time was 181.9 ± 25.5 minutes (range, 135–240 minutes), and the mean blood loss volume was 1038.9 ± 284.2 mL (range, 750–1530 mL). The Frankel grade, Japanese Orthopaedic Association score, and Karnofsky performance status score were significantly better postoperatively than preoperatively. The radiographic examination revealed good bone graft fusion. Two patients developed tumor recurrence, while four patients developed intraoperative or postoperative complications.

Conclusions

Management of upper cervical intraspinal tumors by posterior laminectomy and pedicle screw fixation can relieve compression of the cervical cord and nerve root, thoroughly remove the tumor lesion, reconstruct the stability of the upper cervical spine, and improve patients’ quality of life.
Unexpected sequelae of the COVID-19 pandemic: A strange case of myoclonus in the Tasmanian winter
Authors: Dang Minh Huan , Rodman Bodie , Raj Rajesh
Published: October 2020

Peritoneal dialysis treatment generates significant amounts of waste for disposal from patients’ homes. In Australia, in the days after the onset of the COVID-19 pandemic, waste collection from homes was temporarily stopped. Our patient tried to dispose of his waste by burning the used bags and tubing, using paint thinner as an accelerant. We present a case report of the unusual neurological complication he developed.
Improved damping and mechanical properties of carbon fibrous laminates with tailored carbon nanotube/polyurethane hybrid membranes
Authors: Ouyang Qin , Wang Xiaohong , Yao Yongtao , Liu Ling
Published: October 2020

This paper design two kinds of damping interleaves, traditional thermoplastic polyurethane (TPU) and novel carbon nanotube (CNT) modified TPU porous membranes are designed and respectively interleaved into the interfaces of a carbon fiber-reinforced plastic (CFRP). How the interleaves affect the damping behaviors and quasi-static mechanical properties of the CFRP is comparatively investigated. Results show that both TPU and CNT/TPU interleaved CFRPs possess good damping behaviors within a wide temperature range of 50∼150°C as well as a wide frequency band from 0.1 to 30 Hz, where, the former is a little better. But, storage modulus of the CNT/TPU interleaved CFRP is always higher than that of the TPU interleaved CFRP at different temperatures and frequencies. Moreover, the flexural strength and interlaminar shear strength are both decreased by 36.0% and 24.0% for the TPU interleaved CFRP, and 20.0% and 17.8% for the CNT/TPU interleaved CFRP, respectively, when compared to the baseline CFRP, suggesting the CNT/TPU interleaf brings less negative effect on the mechanical properties of CFRP. Comparatively, CNT/TPU interleaved CFRP is more multifunctional, possessing good damping feature and reasonable mechanical properties, which is maybe more potential in the structural-functional field, especially where needs shock absorption and noise reduction.
Correlation Between N-Terminal Pro-Brain Natriuretic Peptide Levels and Cardiopulmonary Exercise Testing in Patients With Pre-Capillary Pulmonary Hypertension: A Pilot Study
Authors: Aueyingsak Sahachat , Khrisanapant Wilaiwan , Kukongviriyapun Upa , Pasurivong Orapin , Ratanawatkul Pailin , Wanitpongpan Chinadol , Pussadhamma Burabha
Published: October 2020

Background:

N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiopulmonary exercise testing (CPET) are useful for severity assessment in patients with pulmonary hypertension (PH). Correlations between these tests in pre-capillary PH patients is less well studied.

Methods:

We studied 23 patients with pre-capillary PH: 8 with idiopathic pulmonary arterial hypertension (IPAH), 6 with systemic sclerosis-associated PAH (SSc-PAH), and 9 with chronic thromboembolic pulmonary hypertension (CTEPH). Clinical evaluation, NT-proBNP levels, six-minute walking test (6MWT), spirometry, and CPET were evaluated on the same day. Correlation between NT-proBNP levels and CPET parameters were investigated.

Results:

In all patients, NT-proBNP levels were significantly correlated with peak oxygen uptake (VO2) ( r = −0.47), peak oxygen pulse ( r = −0.43), peak cardiac output (CO) ( r = −0.57), peak end-tidal partial pressure of carbon dioxide (PETCO2) ( r = −0.74), ventilatory equivalent to carbon dioxide (VE/VCO2) at anaerobic threshold (AT) ( r = 0.73), and VE/VCO2slope ( r = 0.64). Significant correlations between NT-proBNP levels and peak PETCO2and VE/VCO2were found in IPAH and CTEPH subgroups, and a significant correlation between NT-proBNP levels and VO2at AT was found in the CTEPH subgroup. No significant correlation was found in the SSc-PAH subgroup.

Conclusion:

NT-proBNP levels were significantly correlated with CPET parameters in patients with IPAH and CTEPH subgroups, but not in SSc-PAH subgroup. A further study with larger population is required to confirm these preliminary findings.
Hanging, blowing, slamming and playing: Erotic control and overflow in a digital chemsex scene
Authors: Møller Kristian
Published: October 2020

Based on participant observation, this article details the use of methamphetamine (crystal meth) in a social scene mediated by a video conferencing service similar to Zoom. Taking an affective-materialist approach and applying concepts from play theory, it describes the visual erotic culture that emerges in the 100 simultaneous videos of drug-using people, mostly men. It details the scene’s modulation of temporality, how drug use is performed in relationship to numerous screens and the way ceremonialization counters the platformed deintensification. Finally, it discusses how digital chemsex encounters might overflow categories of gender and sexuality, and how the article may enrich the study of drugged sexual play.
Older-age onset of Kimura’s disease
Authors: Kakehi Eiichi , Kotani Kazuhiko , Yoshida Tsubasa , Nakai Tsubasa , Sakurai Shigehisa , Hirotani Akane , Simizu Kaduyo , Nozaki Takafumi , Shoji Keisuke , Adachi Seiji , Matsumura Masami
Published: October 2020

A 60-year-old man was admitted to our hospital with bilateral post auricular masses, first noticed 1 year earlier. Blood tests showed eosinophilia and high immunoglobulin E (IgE) levels, and cervical computed tomography showed 10-mm soft tissue masses with scattered lymphadenopathy. The tumors showed intermediate and high signal intensity on T1- and T2-weighted cervical magnetic resonance imaging, respectively. After mass resection, the tumors were diagnosed as Kimura’s disease (KD). Generally, KD affects young men; however, even in older patients, KD should be included as a differential diagnosis for head and neck tumors in patients with eosinophilia and high IgE.
Holistic Patient Assessment: Dermatology in Dental Practice
Authors: Chapireau David , Bashir Saqib J. , Fan Kathleen
Published: October 2020

As part of the holistic approach to their patients, General Dental Practitioners are well placed to identify common skin lesions. Awareness and recognition of worrying lesions allow timely and appropriate referrals for further investigation and treatment. In this paper, we review benign, premalignant and malignant skin lesions, as well as genetic skin conditions. Past medical, family and social history (including sun exposure and previous cutaneous malignancy) is important. Examination includes the lesion, the skin type and the regional lymph nodes. The different common lesions are described, and the epidemiology, clinical features and treatment are discussed.

Screening for skin lesions on the head and neck may be undertaken as part of overall dental care as part of the holistic examination of patients. Particularly with precancerous lesions and skin cancer, an early detection and referral from a dentist can expedite treatment and improve prognosis.
Maintaining Resident Social Connections During COVID-19: Considerations for Long-Term Care
Authors: Ickert Carla , Rozak Heather , Masek Jennifer , Eigner Keeley , Schaefer Sherry
Published: October 2020

Worldwide, long-term care (LTC) homes have been heavily impacted by the coronavirus disease 2019 (COVID-19) pandemic. The significant risk of COVID-19 to LTC residents has resulted in major public health restrictions placed on LTC visitation. This article describes the important considerations for the facilitation of social connections between LTC residents and their loved ones during the COVID-19 pandemic, based on the experiences of 10 continuing care homes in Alberta, Canada. Important considerations include: technology, physical space, human resource requirements, scheduling and organization, and infection prevention and control. We describe some of the challenges encountered when implementing alternative visit approaches such as video and phone visits, window visits and outdoor in-person visits, and share several strategies and approaches to managing this new process within LTC.
Next-generation sequencing of 35 RHD variants in 16 253 serologically D− pregnant women in the Finnish population
Authors: Tammi Silja M. , Tounsi Wajnat A. , Sainio Susanna , Kiernan Michele , Avent Neil D. , Madgett Tracey E. , Haimila Katri
Published: October 2020

Fetal RHD screening for targeted routine antenatal anti-D prophylaxis has been implemented in many countries, including Finland, since the 2010s. Comprehensive knowledge of the RHD polymorphism in the population is essential for the performance and safety of the anti-D prophylaxis program. During the first 3 years of the national screening program in Finland, over 16 000 samples from RhD− women were screened for fetal RHD; among them, 79 samples (0.5%) containing a maternal variant allele were detected. Of the detected maternal variants, 35 cases remained inconclusive using the traditional genotyping methods and required further analysis by next-generation sequencing (NGS) of the whole RHD gene to uncover the variant allele. In addition to the 13 RHD variants that have been previously reported in different populations, 8 novel variants were also detected, indicating that there is more variation of RHD in the RhD− Finnish population than has been previously known. Three of the novel alleles were identified in multiple samples; thus, they are likely specific to the original Finnish population. National screening has thus provided new information about the diversity of RHD variants in the Finnish population. The results show that NGS is a powerful method for genotyping the highly polymorphic RHD gene compared with traditional methods that rely on the detection of specific nucleotides by polymerase chain reaction amplification.
The association of ABO blood group with indices of disease severity and multiorgan dysfunction in COVID-19
Authors: Hoiland Ryan L. , Fergusson Nicholas A. , Mitra Anish R. , Griesdale Donald E. G. , Devine Dana V. , Stukas Sophie , Cooper Jennifer , Thiara Sonny , Foster Denise , Chen Luke Y. C. , Lee Agnes Y. Y. , Conway Edward M. , Wellington Cheryl L. , Sekhon Mypinder S.
Published: October 2020

Studies on severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) suggest a protective effect of anti-A antibodies against viral cell entry that may hold relevance for SARS-CoV-2 infection. Therefore, we aimed to determine whether ABO blood groups are associated with different severities of COVID-19. We conducted a multicenter retrospective analysis and nested prospective observational substudy of critically ill patients with COVID-19. We collected data pertaining to age, sex, comorbidities, dates of symptom onset, hospital admission, intensive care unit (ICU) admission, mechanical ventilation, continuous renal replacement therapy (CRRT), standard laboratory parameters, and serum inflammatory cytokines. National (N = 398 671; P = .38) and provincial (n = 62 246; P = .60) ABO blood group distributions did not differ from our cohort (n = 95). A higher proportion of COVID-19 patients with blood group A or AB required mechanical ventilation (P = .02) and CRRT (P = .004) and had a longer ICU stay (P = .03) compared with patients with blood group O or B. Blood group A or AB also had an increased probability of requiring mechanical ventilation and CRRT after adjusting for age, sex, and presence of ≥1 comorbidity. Inflammatory cytokines did not differ between patients with blood group A or AB (n = 11) vs O or B (n = 14; P > .10 for all cytokines). Collectively, our data indicate that critically ill COVID-19 patients with blood group A or AB are at increased risk for requiring mechanical ventilation, CRRT, and prolonged ICU admission compared with patients with blood group O or B. Further work is needed to understand the underlying mechanisms.
Algae-meditated route to cuprous oxide (Cu2O) nanoparticle: differential expression profile of MALAT1 and GAS5 LncRNAs and cytotoxic effect in human breast cancer
Authors: Taherzadeh-Soureshjani Parisa , Chehelgerdi Mohammad
Published: October 2020

Background

Breast cancer (BC), as the most widely recognized disease in women worldwide, represents about 30% of all cancers impacting women. This study was aimed to synthesize Cu2O nanoparticles from the cystoseira myrica algae (CM-Cu2O NPs) assess their antimicrobial activity against pathogenic bacteria and fungi. We evaluated the expression levels of lncRNAs (MALAT1 and GAS5) and apoptosis genes (p53, p27, bax, bcl2 and caspase3), their prognostic roles.

Methods

In this study, CM-Cu2O NPs synthesized by cystoseira myrica algae extraction used to evaluate its cytotoxicity and apoptotic properties on MDA-MB-231, SKBR3 and T-47D BC cell lines compared to HDF control cell line. The CM-Cu2O NPs was characterized by UV–Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Transmission electron microscopy (TEM) and Scanning electron microscopy (SEM). The antimicrobial activity of CM-Cu2O NPs was assessed against pathogenic bacteria, staphylococcus aureus (S. aureus) PTCC 1112 bacteria as a standard gram-positive bacteria and pseudomonas aeruginosa (P. aeruginosa) PTCC 1310 as a standard gram-negative bacterium. Expression profile of MALAT1 and GAS5 lncRNAs and apoptosis genes, i.e., p27, bax, bcl2 and caspase3 genes, were calculated utilizing qRT-PCR. The changes in the expression levels were determined using the DDCT method.

Results

MALAT1 was upregulated in MDA-MB-231, SKBR3 and T-47D BC (p < 0.01), while GAS5 was downregulated in SKBR3 and T-47D cell lines tested compared with HDF control cell line (p < 0.05) was found. The results revealed that, p27, bax and caspase3 were significantly upregulated in BC cell lines as compared with normal cell line. Bcl2 expression was also significantly increased in MDA-MB-231 and T47D cell lines compared with normal cell line, but bcl2 levels were downregulated in SKBR3 cell line.

Conclusions

Our results confirm the beneficial cytotoxic effects of green-synthesized CM-Cu2O NPs on BC cell lines. This nanoparticle decreased angiogenesis and induces apoptosis, so we conclude that CM-Cu2O NPs can be used as a supplemental drug in cancer treatments. Significantly, elevated circulating lncRNAs were demonstrated to be BC specific and could differentiate BC cell lines from the normal cell lines. It was demonstrated that lncRNAs used in this study and their expression profiles can be created as biomarkers for early diagnosis and prognosis of BC. Further studies utilizing patients would give recognizable identification of lncRNAs as key players in intercellular interactions.
Genomic diversity and population structure of the Leonberger dog breed
Authors: Letko Anna , Minor Katie M. , Jagannathan Vidhya , Seefried Franz R. , Mickelson James R. , Oliehoek Pieter , Drögemüller Cord
Published: October 2020

Background

Leonberger is a giant dog breed formed in the 1850s in Germany. Its post-World War II popularity has resulted in a current global population of ~ 30,000 dogs. The breed has predispositions to neurodegenerative disorders and cancer, which is likely due in large part to limited genetic diversity. However, to date there is no scientific literature on the overall demography and genomic architecture of this breed.

Results

We assessed extensive pedigree records, SNP array genotype data, and whole-genome sequences (WGS) on 142,072, 1203 and 39 Leonberger dogs, respectively. Pedigree analyses identified 22 founder animals and revealed an apparent popular sire effect. The average pedigree-based inbreeding coefficient of 0.29 and average kinship of 0.31 show a dramatic loss of genetic diversity. The observed average life span decreased over time from 9.4 years in 1989 to 7.7 years in 2004. A global health survey confirmed a high prevalence of cancer and neurological disorders. Analysis of SNP-based runs of homozygosity (ROH) identified 125,653 ROH with an average length of 5.88 Mb, and confirmed an average inbreeding coefficient of 0.28. Genome-wide filtering of the WGS data revealed 28 non-protein-changing variants that were present in all Leonberger individuals and a list of 22 potentially pathogenic variants for neurological disorders of which 50% occurred only in Leonbergers and 50% occurred rarely in other breeds. Furthermore, one of the two mtDNA haplogroups detected was present in one dog only.

Conclusions

The increasing size of the Leonberger population has been accompanied by a considerable loss of genetic diversity after the bottleneck that occurred in the 1940s due to the intensive use of popular sires resulting in high levels of inbreeding. This might explain the high prevalence of certain disorders; however, genomic data provide no evidence for fixed coding variants that explain these predispositions. The list of candidate causative variants for polyneuropathy needs to be further evaluated. Preserving the current genetic diversity is possible by increasing the number of individuals for breeding while restricting the number of litters per sire/dam. In addition, outcrossing would help optimize long-term genetic diversity and contribute to the sustainability and health of the population.
Spatial and temporal modulation of enterotoxigenic E. coli H10407 pathogenesis and interplay with microbiota in human gut models
Authors: Roussel Charlène , De Paepe Kim , Galia Wessam , De Bodt Jana , Chalancon Sandrine , Leriche Françoise , Ballet Nathalie , Denis Sylvain , Alric Monique , Van de Wiele Tom , Blanquet-Diot Stéphanie
Published: October 2020

Background

EnterotoxigenicEscherichia coli(ETEC) substantially contributes to the burden of diarrheal illnesses in developing countries. With the use of complementary in vitro models of the human digestive environment, TNO gastrointestinal model (TIM-1), and Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME), we provided the first detailed report on the spatial-temporal modulation of ETEC H10407 survival, virulence, and its interplay with gut microbiota. These systems integrate the main physicochemical parameters of the human upper digestion (TIM-1) and simulate the ileumvsascending colon microbial communities and luminalvsmucosal microenvironments, captured from six fecal donors (M-SHIME).

Results

A loss of ETEC viability was noticed upon gastric digestion, while a growth renewal was found at the end of jejunal and ileal digestion. The remarkable ETEC mucosal attachment helped to maintain luminal concentrations above 6 log10 mL−1in the ileum and ascending colon up to 5 days post-infection. Seven ETEC virulence genes were monitored. Most of them were switched on in the stomach and switched off in the TIM-1 ileal effluents and in a late post-infectious stage in the M-SHIME ascending colon. No heat-labile enterotoxin production was measured in the stomach in contrast to the ileum and ascending colon. Using16SrRNA gene-based amplicon sequencing, ETEC infection modulated the microbial community structure of the ileum mucus and ascending colon lumen.

Conclusions

This study provides a better understanding of the interplay between ETEC and gastrointestinal cues and may serve to complete knowledge on ETEC pathogenesis and inspire novel prophylactic strategies for diarrheal diseases.
Platelet-to-lymphocyte ratio is correlated with a delay in feeding resumption following a transhiatal esophagectomy with cervical anastomosis
Authors: El Asmar Antoine , Ghabi Elie , Saber Toufic , Abou-Malhab Christina , Akl Bernard , El Rassi Ziad
Published: October 2020

Introduction

The lymphocytic population, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are prognostic tools predictive of adverse outcomes for several solid tumors and oncologic surgeries, one of which is esophageal adenocarcinoma. Furthermore, delayed resumption of oral feeding postoperatively is associated with significant morbidity. Given the controversies regarding post-op nutritional support in these patients, this study investigates the prognostic role of the lymphocytic percentage, the NLR, and the PLR in predicting prolonged length of hospital stay (LOHS) and ICU stay (LOICUS) as well as delayed oral feeding following transhiatal esophagectomy (THE) for adenocarcinoma of the esophagogastric junction (AEG).

Methods

Forty consecutive patients who underwent transhiatal esophagectomy performed by a single surgeon for Siewert type II and type III adenocarcinoma of the esophagogastric junction at a tertiary referral center were selected. Retrospective data collection was performed from the patients’ medical records, and statistical analysis was performed using Pearson correlation and Student’s t test and Chi-square testing.

Results

An increased LOHS was correlated with a lower preoperative lymphocyte percentage (p = 0.043), higher NLR (p = 0.010) and PLR (p = 0.015), and an increased number of packed red blood cell (PRBC) transfusions perioperatively (p = 0.030). An increased LOICUS was correlated with a lower preoperative lymphocyte percentage (p = 0.033), higher NLR (p = 0.018) and PLR (p = 0.044), an increased number of PRBC transfusions (p = 0.001), and patients’ comorbidities (p < 0.05). A delay in feeding resumption was correlated with a lower preoperative lymphocyte percentage (p = 0.022), higher NLR (p = 0.004) and PLR (p = 0.001), an increased PRBC transfusions (p = 0.001), and diabetes mellitus (p = 0.033). Multivariate analysis with automatic linear modeling showed that only the preoperative PLR was a powerful predictor for the delay of feeding resumption (p < 0.01).

Conclusion

The lymphocyte percentage, PLR, and NLR are found to be associated with prolonged hospitalization and ICU stay and delayed oral feeding following THE for Siewert types II and III AEG. We hope by this series, to have set, at least one preliminary cornerstone, in the creation of a prognostic model, capable of assessing the need for an intraoperative jejunostomy placement, in patients undergoing esophagectomy for distal esophageal carcinoma.
Human pegivirus (HPgV, GBV-C) RNA in volunteer blood donors from a public hemotherapy service in Northern Brazil
Authors: Silva Aniel de Sarom Negrão , Silva Clayton Pereira , Barata Rafael Ribeiro , da Silva Pedro Victor Reis , Monteiro Patrícia Danin Jordão , Lamarão Letícia , Burbano Rommel Mário Rodríguez , Nunes Márcio Roberto Teixeira , de Lima Patrícia Danielle Lima
Published: October 2020

Background

Human pegivirus (HPgV)—formerly known as GBV-C—is a member of the Flaviviridae family and belongs to the species Pegivirus C. It is a non-pathogenic virus and is transmitted among humans mainly through the exposure to contaminated blood and is often associated with human immunodeficiency virus (HIV) infection, among other viruses. This study aimed to determine the prevalence of HPgV viremia, its association with HIV and clinical epidemiological factors, as well as the full-length sequencing and genome characterization of HPgV recovered from blood donors of the HEMOPA Foundation in Belém-PA-Brazil.

Methods

Plasma samples were obtained from 459 donors, tested for the presence of HPgV RNA by the RT-qPCR. From these, a total of 26 RT-qPCR positive samples were submitted to the NGS sequencing approach in order to obtain the full genome. Genome characterization and phylogenetic analysis were conducted.

Results

The prevalence of HPgV was 12.42%. We observed the highest prevalences among donors aged between 18 and 30 years old (16.5%), with brown skin color (13.2%) and men (15.8%). The newly diagnosed HIV-1 prevalence was 26.67%. The HPgV genotype 2 (2a and 2b) was identified. No data on viral load value was found to corroborate the protective effect of HPgV on HIV evolution.

Conclusions

This study provided information regarding the HPgV infection among blood donors from HEMOPA Foundation. Furthermore, we genetically characterized the HPgV circulating strains and described by the first time nearly complete genomes of genotype 2 in Brazilian Amazon.
Diagnostic value of clusterin immunostaining in hepatocellular carcinoma
Authors: Li Yuan , Liu Fangfang , Zhou Wendi , Zhang Sharon , Chu Peiguo , Lin Fan , Wang Hanlin L.
Published: October 2020

Background

Histologic distinction between well differentiated hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions is a known challenge. Existing biomarkers are of limited diagnostic value. Our previous studies observed an enhanced canalicular expression pattern of clusterin (CLU) in HCC, which was not observed in benign hepatocellular mass lesions such as hepatocellular adenoma. The aim of this study was to further investigate its diagnostic value for HCC by examining the expression pattern of CLU in a large number of non-hepatocellular tumors, and by comparing it with two other commonly used hepatocellular markers pCEA and CD10 that also show a canalicular staining pattern in HCC.

Methods

Enhanced canalicular staining patterns of CLU, pCEA and CD10 were analyzed on 54 surgically resected well to moderately differentiated HCCs on whole tissue sections, of which 37 had surrounding regenerative nodules while the remaining 17 had a non-cirrhotic background. CLU immunostaining was also performed on tissue microarray sections that contained 74 HCCs (40 of which were also stained for pCEA and CD10), 55 normal liver tissue samples, and 1305 non-hepatocellular tumors from multiple organs.

Results

Enhanced CLU canalicular staining was observed in 70% (89/128) HCCs but not in regenerative nodules, normal liver tissues or any non-hepatocellular tumors. The sensitivity and specificity for enhanced canalicular staining pattern of CLU in HCCs were 0.70 and 1.00. This enhanced canalicular pattern was observed in only 26 and 23% HCCs for CD10 and pCEA, respectively. These results further demonstrate that the distinctive enhanced canalicular pattern of CLU is unique to HCC.

Conclusions

CLU is superior to pCEA and CD10 as a diagnostic immunomarker in that it can help distinguish well to moderately differentiated HCC not only from non-HCC malignancies but also from benign hepatocellular mass lesions.
Leaf open time sinogram (LOTS): a novel approach for patient specific quality assurance of total marrow irradiation
Authors: Thiyagarajan Rajesh , Sharma Dayananda Shamurailatpam , Kaushik Suryakant , Sawant Mayur , Ganapathy K. , Nambi Raj N. Arunai , Chilukuri Srinivas , Sundar Sham C. , Patro Kartikeswar Ch. , Manikandan Arjunan , Noufal M. P. , Sivaraman Rangasamy , Easow Jose , Jalali Rakesh
Published: October 2020

There is no ideal detector-phantom combination to perform patient specific quality assurance (PSQA) for Total Marrow (TMI) and Lymphoid (TMLI) Irradiation plan. In this study, 3D dose reconstruction using mega voltage computed tomography detectors measured Leaf Open Time Sinogram (LOTS) was investigated for PSQA of TMI/TMLI patients in helical tomotherapy. The feasibility of this method was first validated for ten non-TMI/TMLI patients, by comparing reconstructed dose with (a) ion-chamber (IC) and helical detector array (ArcCheck) measurement and (b) planned dose distribution using 3Dγ analysis for 3%@3mm and dose to 98% (D98%) and 2% (D2%) of PTVs. Same comparison was extended for ten treatment plans from five TMI/TMLI patients. In all non-TMI/TMLI patients, reconstructed absolute dose was within ± 1.80% of planned and IC measurement. The planned dose distribution agreed with reconstructed and ArcCheck measured dose with mean (SD) 3Dγ of 98.70% (1.57%) and 2Dγ of 99.48% (0.81%). The deviation in D98% and D2% were within 1.71% and 4.10% respectively. In all 25 measurement locations from TMI/TMLI patients, planned and IC measured absolute dose agreed within ± 1.20%. Although sectorial fluence verification using ArcCHECK measurement for PTVs chest from the five upper body TMI/TMLI plans showed mean ± SD 2Dγ of 97.82% ± 1.27%, the reconstruction method resulted poor mean (SD) 3Dγ of 92.00% (± 5.83%), 64.80% (± 28.28%), 69.20% (± 30.46%), 60.80% (± 19.37%) and 73.2% (± 20.36%) for PTVs brain, chest, torso, limb and upper body respectively. The corresponding deviation in median D98% and D2% of all PTVs were < 3.80% and 9.50%. Re-optimization of all upper body TMI/TMLI plans with new pitch and modulation factor of 0.3 and 3 leads significant improvement with 3Dγ of 100% for all PTVs and median D98% and D2% < 1.6%. LOTS based PSQA for TMI/TMLI is accurate, robust and efficient. A field width, pitch and modulation factor of 5 cm, 0.3 and 3 for upper body TMI/TMLI plan is suggested for better dosimetric outcome and PSQA results.
The prognostic value of the lymph node ratio for local advanced gastric cancer patients with intensity-modulated radiation therapy and concurrent chemotherapy after radical gastrectomy in China
Authors: Yang Yongqiang , Ma Yifu , Xiang Xiaoyong , Xing Pengfei , Wu Yongyou , Zhang Liyuan , Tian Ye
Published: October 2020

Background

Nearly 50% of new gastric cancer cases and gastric cancer-related deaths worldwide occur in China. No global consensus has been reached about the optimal management of locally advanced gastric cancer. Although the Guidelines for the Diagnosis and Treatment of Gastric Cancer from the National Health Commission of China, which has been updated three times since 2010, explicitly emphasize the necessity of adjuvant chemoradiation, few clinical institutions in China routinely adhere to the recommended radiotherapy guidelines. This study aimed to examine the efficacy, in terms of locoregional control and long-term survival, and the safety of adjuvant radiotherapy using intensity-modulated radiation therapy (IMRT) with concurrent and adjuvant fluoropyrimidine-based chemotherapy for gastric cancer.

Methods

This was a retrospective evaluation of 156 patients with high-risk gastric cancer who underwent adjuvant chemoradiotherapy between September 2008 and May 2019. The prescribed planning target volume median dose was 45 Gy in 1.8 Gy daily fractions, and all patients received concurrent and adjuvant fluoropyrimidine-based chemotherapy. Locoregional control, distant metastasis, and overall survival rates were estimated. Clinicopathological characteristics and patterns of failure were retrospectively reviewed to identify factors associated with survival and recurrence.

Results

The median follow-up duration was 56 months (range 3–130 months) for all patients. Of the patients, 11 (7.1%) were lost to follow-up, and 49 (31.4%) and 104 (66.7%) had stage II or III disease according to the eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging criteria. The frequencies of acute grade 3 or 4 gastrointestinal and hematological toxicity were 9.6% and 10.9%, respectively. In total, 152 patients (97.4%) completed the entire chemoradiation regimen. No toxicity-related deaths occurred. Nineteen patients (12.2%) had locoregional recurrence, 26 (16.7%) had distant metastases, and 12 (7.7%) had peritoneal metastasis. The overall survival (OS) rates were 83.5%, 65.0%, and 59.5%, while the disease-free survival rates were 75.1%, 61.0%, and 55.6% at 1, 3, and 5 years, respectively. In the multivariate analysis, age, pathological T stage and lymph node ratio (LNR) were found to be independent predictors of OS.

Conclusion

Postoperative concomitant IMRT and chemotherapy were well tolerated, with acceptable toxicities and encouraging locoregional tumor control and long-term survival. The LNR can be used as an important prognostic indicator for OS. Adjuvant chemoradiotherapy should be considered for all patients with a high risk of locoregional recurrence, especially in China.
Long-term results of endoclamping in patients undergoing minimally invasive mitral valve surgery where external aortic clamping cannot be used – a propensity matched analysis
Authors: Cetinkaya Ayse , Ebraheem Emad , Bramlage Karin , Hein Stefan , Bramlage Peter , Choi Yeong-Hoon , Schönburg Markus , Richter Manfred
Published: October 2020

Background

Minimally invasive mitral valve surgery is standard of care in many centres and it is commonly associated with the need for cardiopulmonary bypass. Conventional external aortic clamping (exoclamping) is not always feasible, so endoaortic clamping (endoclamping) has evolved as a viable alternative. The aim of this study is to compare endoclamping (Intraclude™, Edwards Lifesciences) with exoclamping (Chitwood) during minimally invasive mitral valve procedures.

Methods

This single-centre study included 822 consecutive patients undergoing minimally invasive mitral valve procedures. The endoclamp was used in 64 patients and the exoclamp in 758. Propensity-score (PS) matching was performed resulting in 63 patients per group. Outcome measures included procedural variables, length of intensive care unit (ICU) and hospital stay, major adverse cardiac and cerebrovascular events (MACCE) and repeat surgery.

Results

The mean age was similar in the two group (62.2 [endoclamp] vs. 63.5 [exoclamp] years; p = 0.554), as were the cardiopulmonary bypass (145 vs. 156 min; p = 0.707) and the procedure time (203 vs. 211 min; p = 0.648). The X-clamp time was significantly shorter in the endoclamp group (88 vs. 99 min; p = 0.042). Length of ICU stay (25.0 vs. 23.0 h) and length of hospital stay (10.0 vs. 9.0 days) were slightly longer in the endoclamp group, but without statistical significance. There were nominal but no statistically significant differences between the groups in the rates of stroke, vascular complications, myocardial infarction or repeat mitral valve surgery. The conversion rate to open sternotomy approach was 2.4% without difference between groups. The estimated 7-year survival rate was similar for both groups (89.9% [endoclamp]; 84.0% [exoclamp]) with a hazard ratio of 1.291 (95% CI 0.453–3.680).

Conclusions

Endoaortic clamping is an appropriate and reasonably safe alternative to the conventional Chitwood exoclamp for patients in which the exoclamp cannot be used because the ascending aorta cannot be safely mobilised.
Phenotypic and genetic spectrum of isolated macrodactyly: somatic mosaicism of PIK3CA and AKT1 oncogenic variants
Authors: Tian Wen , Huang Yingzhao , Sun Liying , Guo Yang , Zhao Sen , Lin Mao , Dong Xiying , Zhong Wenyao , Yin Yuehan , Chen Zefu , Zhang Nan , Zhang Yuanqiang , Wang Lianlei , Lin Jiachen , Yan Zihui , Yang Xinzhuang , Zhao Junhui , Qiu Guixing , Zhang Jianguo , Wu Zhihong , Wu Nan ,   (Deciphering Disorders Involving Scoliosis, COmorbidities) study group
Published: October 2020

Background

Isolated macrodactyly is a severe congenital hand anomaly with functional and physiological impact. Known causative genes include PIK3CA, AKT1 and PTEN. The aim of this study is to gain insights into the genetics basis of isolated macrodactyly.

Results

We enrolled 24 patients with isolated macrodactyly. Four of them were diagnosed with Proteus syndrome based on skin presentations characteristic to this disease.
Targeted next-generation sequencing was performed using patients’ blood and affected tissues. Overall, 20 patients carry mosaic PIK3CA pathogenic variants, i.e. p.His1047Arg (N = 7), p.Glu542Lys (N = 6), p.Glu545Lys (N = 2), p.His1047Leu (N = 2), p.Glu453Lys (N = 1), p.Gln546Lys (N = 1) and p.His1047Tyr (N = 1). Four patients who met the diagnostic criteria of Proteus syndrome carry mosaic AKT1 p.Glu17Lys variant. Variant allele frequencies of these mosaic variants obtained through next-generation sequencing range from 10 to 33%. In genotype–phenotype correlation analysis of patients with PIK3CA variant, we found that patients with the macrodactyly of the lower limbs tend to carry PIK3CA variants located in the helical domain (P = 0.005).

Conclusions

Mosaic PIK3CA and AKT1 variants can be found in all of our samples with isolated macrodactyly. Insights into phenotypic and genetic spectrum of isolated macrodactyly may be helpful in perusing a more precise and effective management of isolated macrodactyly.