bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of Cretaceous high-silica granite by complementary crystal accumulation and silicic melt extraction in the coastal region of southeastern China
Authors: Chen Jing-Yuan , Yang Jin-Hui , Zhang Ji-Heng , Sun Jin-Feng , Zhu Yu-Sheng , Hartung Eva
Published: April 2021

It is generally hypothesized that high-silica (SiO2 > 75 wt%) granite (HSG) originates from crystal fractionation in the shallow crust. Yet, identifying the complementary cumulate residue of HSG within plutons remains difficult. In this work, we examine the genetic links between the porphyritic monzogranite and HSG (including porphyritic granite, monzogranite, and alkali feldspar granite) from the coastal area of southeastern China using detailed zircon U-Pb ages, trace elements, Hf-O isotopes, and whole-rock geochemistry and Nd-Hf isotopic compositions. Zircon U-Pb ages indicate that the porphyritic monzogranite and HSG are coeval (ca. 96–99 Ma). The HSG and porphyritic monzogranite have similar formation ages within analytic error, identical mineral assemblages, similar Nd-Hf isotopic compositions, and consistent variations in their zircon compositions (i.e., Eu/Eu*, Zr/Hf, and Sm/Yb), which suggests that their parental magma came from a common silicic magma reservoir and that the lithological differences are the result of melt extraction processes. The porphyritic monzogranite has relatively high SiO2 (70.0–73.4 wt%), Ba (718–1070 ppm), and Sr (493–657 ppm) contents, low K2O and Rb concentrations and low Rb/Sr ratios (0.1–0.2), and it displays weak Eu anomalies (Eu/Eu* = 0.57–0.90). Together with the petrographic features of the porphyritic monzogranite, these geochemical variations indicate that the porphyritic monzongranite is the residual silicic cumulate of the crystal mush column. The HSG (SiO2 = 75.0–78.4) has variable Rb/Sr ratios (2–490) and very low Sr (1–109 ppm) and Ba (9–323 ppm) contents. Zircon from the HSG and porphyritic monzogranite overlap in Eu/Eu*, Zr/Hf, and Sm/Yb ratios and Hf contents; however, some zircon from the HSG show very low Eu/Eu* (<0.1) and Zr/Hf ratios. These features suggest that the HSG represents the high-silica melt that was extracted from a crystal-rich mush. The injection of mantle-derived hotter mafic magma into the mush column and the exsolution of F/Cl−-enriched volatiles (or fluids) from the interstitial melt rejuvenated the pre-existing highly crystalline mush. Subsequent extraction and upward migration of silicic melt resulting from compaction of the mush column formed the HSG at shallow crustal levels, which left the complementary crystal residue solidified as porphyritic monzogranite at the bottom.
Associations between attainment of incentivized primary care indicators and incident lower limb amputation among those with type 2 diabetes: a population-based historical cohort study
Authors: Gunn Laura H , Vamos Eszter P , Majeed Azeem , Normahani Pasha , Jaffer Usman , Molina German , Valabhji Jonathan , McKay Ailsa J
Published: April 2021

Introduction

England has invested considerably in diabetes care through such programs as the Quality and Outcomes Framework (QOF) and National Diabetes Audit (NDA). Associations between program indicators and clinical endpoints, such as amputation, remain unclear. We examined associations between primary care indicators and incident lower limb amputation.

Research design and methods

This population-based retrospective cohort study, spanning 2010–2017, was comprised of adults in England with type 2 diabetes and no history of lower limb amputation. Exposures at baseline (2010–2011) were attainment of QOF glycated hemoglobin (HbA1c), blood pressure and total cholesterol indicators, and number of NDA processes completed. Propensity score matching was performed and multivariable Cox proportional hazards models, adjusting for disease-related, comorbidity, lifestyle, and sociodemographic factors, were fitted using matched samples for each exposure.

Results

83 688 individuals from 330 English primary care practices were included. Mean follow-up was 3.9 (SD 2.0) years, and 521 (0.6%) minor or major amputations were observed (1.62 per 1000 person-years). HbA1c and cholesterol indicator attainment were associated with considerably lower risks of minor or major amputation (adjusted HRs; 95% CIs) 0.61 (0.49 to 0.74; p<0.0001) and 0.67 (0.53 to 0.86; p=0.0017), respectively). No evidence of association between blood pressure indicator attainment and amputation was observed (adjusted HR 0.88 (0.73 to 1.06; p=0.1891)). Substantially lower amputation rates were observed among those completing a greater number of NDA care processes (adjusted HRs 0.45 (0.24 to 0.83; p=0.0106), 0.67 (0.47 to 0.97; p=0.0319), and 0.38 (0.20 to 0.70; p=0.0022) for comparisons of 4–6 vs 0–3, 7–9 vs 0–3, and 7–9 vs 4–6 processes, respectively). Results for major-only amputations were similar for HbA1c and blood pressure, though cholesterol indicator attainment was non-significant.

Conclusions

Comprehensive primary care-based secondary prevention may offer considerable protection against diabetes-related amputation. This has important implications for diabetes management and medical decision-making for patients, as well as type 2 diabetes quality improvement programs.
Exploring the GLP-1–GLP-1R axis in porcine pancreas and gastrointestinal tract in vivo by ex vivo autoradiography
Authors: Manell Elin , Puuvuori Emmi , Svensson Anna , Velikyan Irina , Hulsart-Billström Gry , Hedenqvist Patricia , Holst Jens Juul , Jensen Waern Marianne , Eriksson Olof
Published: April 2021

Introduction

Glucagon-like peptide-1 (GLP-1) increases insulin secretion from pancreatic beta-cells and GLP-1 receptor (GLP-1R) agonists are widely used as treatment for type 2 diabetes mellitus. Studying occupancy of the GLP-1R in various tissues is challenging due to lack of quantitative, repeatable assessments of GLP-1R density. The present study aimed to describe the quantitative distribution of GLP-1Rs and occupancy by endogenous GLP-1 during oral glucose tolerance test (OGTT) in pigs, a species that is used in biomedical research to model humans.

Research design and methods

GLP-1R distribution and occupancy were measured in pancreas and gastrointestinal tract by ex vivo autoradiography using the GLP-1R-specific radioligand177Lu-exendin-4 in two groups of pigs, control or bottle-fed an oral glucose load. Positron emission tomography (PET) data from pigs injected with68Ga-exendin-4 in a previous study were used to retrieve data on biodistribution of GLP-1R in the gastrointestinal tract.

Results

High homogenous uptake of177Lu-exendin-4 was found in pancreas, and even higher uptake in areas of duodenum. Low uptake of177Lu-exendin-4 was found in stomach, jejunum, ileum and colon. During OGTT, there was no increase in plasma GLP-1 concentrations and occupancy of GLP-1Rs was low. The ex vivo autoradiography results were highly consistent with to the biodistribution of68Ga-exendin-4 in pigs scanned by PET.

Conclusion

We identified areas with similarities as well as important differences regarding GLP-1R distribution and occupancy in pigs compared with humans. First, there was strong ligand binding in the exocrine pancreas in islets. Second, GLP-1 secretion during OGTT is minimal and GLP-1 might not be an important incretin in pigs under physiological conditions. These findings offer new insights on the relevance of porcine diabetes models.
Quality of life support in advanced cancer—web and technological interventions: systematic review and narrative synthesis
Authors: Kane Kathleen , Kennedy Fiona , Absolom Kate L , Harley Clare , Velikova Galina
Published: April 2021

Background

As treatments continue to progress, patients with advanced cancer are living longer. However, ongoing physical side-effects and psychosocial concerns can compromise quality of life (QoL). Patients and physicians increasingly look to the internet and other technologies to address diverse supportive needs encountered across this evolving cancer trajectory.

Objectives

1. To examine the features and delivery of web and technological interventions supporting patients with advanced cancer. 2. To explore their efficacy relating to QoL and psychosocial well-being.

Methods

Relevant studies were identified through electronic database searches (MEDLINE, PsychINFO, Embase, CINAHL, CENTRAL, Web of Science and ProQuest) and handsearching. Findings were collated and explored through narrative synthesis.

Results

Of 5274 identified records, 37 articles were included. Interventions were evaluated within studies targeting advanced cancer (13) or encompassing all stages (24). Five subtypes emerged: Interactive Health Communication Applications (n=12), virtual programmes of support (n=11), symptom monitoring tools (n=8), communication conduits (n=3) and information websites (n=3). Modes of delivery ranged from self-management to clinically integrated. Support largely targeted psychosocial well-being, alongside symptom management and healthy living. Most studies (78%) evidenced varying degrees of efficacy through QoL and psychosocial measures. Intervention complexity made it challenging to distinguish the most effective components. Incomplete reporting limited risk of bias assessment.

Conclusion

While complex and varied in their content, features and delivery, most interventions led to improvements in QoL or psychosocial well-being across the cancer trajectory. Ongoing development and evaluation of such innovations should specifically target patients requiring longer-term support for later-stage cancer.

PROSPERO registration number

CRD42018089153.
State of the science: cannabis and cannabinoids in palliative medicine—the potential
Authors: Roychoudhury Priodarshi , Kapoor Astha Koolwal , Walsh Declan , Cortes Henry , Clarke Hance
Published: April 2021

Cannabinoids are chemicals derived naturally from the cannabis plant or are synthetically manufactured. They interact directly with cannabinoid receptors or share chemical similarity with endocannabinoids (or both). Within palliative medicine, cannabinoid receptors (CB1 and CB2) may modulate some cancer symptoms: appetite, chemotherapy-induced nausea and vomiting, and mood, pain and sleep disorders. Opioid and cannabinoid receptors have overlapping neuroanatomical receptor distribution, particularly at the dorsal horn, dorsal striatum and locus coeruleus. They have a favourable safety profile compared with opioids, and cannabis-based medicines help chronic pain. While cannabidiol (CBD) has anti-inflammatory properties, tetrahydrocannabinol (THC) is the psychoactive substance for issues such as mood and sleep. Nabiximols (Sativex), a CBD:THC combination, is Food and Drug Administration approved for some multiple sclerosis symptoms and epilepsy. There has been a swift societal evolution in attitudes about use of cannabis and cannabinoid medicines for chronic pain. In the USA, 33 states have now legalised prescription-based medical cannabis for several medical conditions; Canada has had legislation since 2001 authorising medical use. The European Union (EU) recently declared all EU citizens must have access to medical cannabis over the next 4 years. The integration into medicine and routine clinical use of cannabis is fraught with information gaps, regulatory issues and scarcity of research. Each patient should have a comprehensive assessment and risk–benefit discussion before any cannabis-based intervention to avoid possible complications such as hallucinations, psychosis and potential cardiac harm.
Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target
Authors: Smati Sarra , Polizzi Arnaud , Fougerat Anne , Ellero-Simatos Sandrine , Blum Yuna , Lippi Yannick , Régnier Marion , Laroyenne Alexia , Huillet Marine , Arif Muhammad , Zhang Cheng , Lasserre Frederic , Marrot Alain , Al Saati Talal , Wan JingHong , Sommer Caroline , Naylies Claire , Batut Aurelie , Lukowicz Celine , Fougeray Tiffany , Tramunt Blandine , Dubot Patricia , Smith Lorraine , Bertrand-Michel Justine , Hennuyer Nathalie , Pradere Jean-Philippe , Staels Bart , Burcelin Remy , Lenfant Françoise , Arnal Jean-François , Levade Thierry , Gamet-Payrastre Laurence , Lagarrigue Sandrine , Loiseau Nicolas , Lotersztajn Sophie , Postic Catherine , Wahli Walter , Bureau Christophe , Guillaume Maeva , Mardinoglu Adil , Montagner Alexandra , Gourdy Pierre , Guillou Hervé
Published: April 2021

Objective

We evaluated the influence of sex on the pathophysiology of non-alcoholic fatty liver disease (NAFLD). We investigated diet-induced phenotypic responses to define sex-specific regulation between healthy liver and NAFLD to identify influential pathways in different preclinical murine models and their relevance in humans.

Design

Different models of diet-induced NAFLD (high-fat diet, choline-deficient high-fat diet, Western diet or Western diet supplemented with fructose and glucose in drinking water) were compared with a control diet in male and female mice. We performed metabolic phenotyping, including plasma biochemistry and liver histology, untargeted large-scale approaches (liver metabolome, lipidome and transcriptome), gene expression profiling and network analysis to identify sex-specific pathways in the mouse liver.

Results

The different diets induced sex-specific responses that illustrated an increased susceptibility to NAFLD in male mice. The most severe lipid accumulation and inflammation/fibrosis occurred in males receiving the high-fat diet and Western diet, respectively. Sex-biased hepatic gene signatures were identified for these different dietary challenges. The peroxisome proliferator-activated receptor α (PPARα) co-expression network was identified as sexually dimorphic, and in vivo experiments in mice demonstrated that hepatocyte PPARα determines a sex-specific response to fasting and treatment with pemafibrate, a selective PPARα agonist. Liver molecular signatures in humans also provided evidence of sexually dimorphic gene expression profiles and the sex-specific co-expression network for PPARα.

Conclusions

These findings underscore the sex specificity of NAFLD pathophysiology in preclinical studies and identify PPARα as a pivotal, sexually dimorphic, pharmacological target.

Trial registration number

NCT02390232.
Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies
Authors: Balestrini Simona , Chiarello Daniela , Gogou Maria , Silvennoinen Katri , Puvirajasinghe Clinda , Jones Wendy D , Reif Philipp , Klein Karl Martin , Rosenow Felix , Weber Yvonne G , Lerche Holger , Schubert-Bast Susanne , Borggraefe Ingo , Coppola Antonietta , Troisi Serena , Møller Rikke S , Riva Antonella , Striano Pasquale , Zara Federico , Hemingway Cheryl , Marini Carla , Rosati Anna , Mei Davide , Montomoli Martino , Guerrini Renzo , Cross J Helen , Sisodiya Sanjay M
Published: April 2021

Objective

The term ‘precision medicine’ describes a rational treatment strategy tailored to one person that reverses or modifies the disease pathophysiology. In epilepsy, single case and small cohort reports document nascent precision medicine strategies in specific genetic epilepsies. The aim of this multicentre observational study was to investigate the deeper complexity of precision medicine in epilepsy.

Methods

A systematic survey of patients with epilepsy with a molecular genetic diagnosis was conducted in six tertiary epilepsy centres including children and adults. A standardised questionnaire was used for data collection, including genetic findings and impact on clinical and therapeutic management.

Results

We included 293 patients with genetic epilepsies, 137 children and 156 adults, 162 females and 131 males. Treatment changes were undertaken because of the genetic findings in 94 patients (32%), including rational precision medicine treatment and/or a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms. There was a rational precision medicine treatment for 56 patients (19%), and this was tried in 33/56 (59%) and was successful (ie, >50% seizure reduction) in 10/33 (30%) patients. In 73/293 (25%) patients there was a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms, and this was successful in 24/73 (33%).

Significance

Our survey of clinical practice in specialised epilepsy centres shows high variability of clinical outcomes following the identification of a genetic cause for an epilepsy. Meaningful change in the treatment paradigm after genetic testing is not yet possible for many people with epilepsy. This systematic survey provides an overview of the current application of precision medicine in the epilepsies, and suggests the adoption of a more considered approach.
Ischaemic stroke on anticoagulation therapy and early recurrence in acute cardioembolic stroke: the IAC study
Authors: Yaghi Shadi , Henninger Nils , Giles James A , Leon Guerrero Christopher , Mistry Eva , Liberman Ava L , Asad Daniyal , Liu Angela , Nagy Muhammad , Kaushal Ashutosh , Azher Idrees , Mac Grory Brian , Fakhri Hiba , Brown Espaillat Kiersten , Pasupuleti Hemanth , Martin Heather , Tan Jose , Veerasamy Manivannan , Esenwa Charles , Cheng Natalie , Moncrieffe Khadean , Moeini-Naghani Iman , Siddu Mithilesh , Scher Erica , Trivedi Tushar , Furie Karen L , Keyrouz Salah G , Nouh Amre , de Havenon Adam , Khan Muhib , Smith Eric E , Gurol M Edip
Published: April 2021

Background and purpose

A subset of ischaemic stroke patients with atrial fibrillation (AF) have ischaemic stroke despite anticoagulation. We sought to determine the association between prestroke anticoagulant therapy and recurrent ischaemic events and symptomatic intracranial haemorrhage (sICH).

Methods

We included consecutive patients with acute ischaemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from eight comprehensive stroke centres in the USA. We compared recurrent ischaemic events and delayed sICH risk using adjusted Cox regression analyses between patients who were prescribed anticoagulation (ACp) versus patients who were naïve to anticoagulation therapy prior to the ischaemic stroke (anticoagulation naïve).

Results

Among 2084 patients in IAC, 1518 had prior anticoagulation status recorded and were followed for 90 days. In adjusted Cox hazard models, ACp was associated with some evidence of a higher risk higher risk of 90-day recurrent ischaemic events only in the fully adjusted model (adjusted HR 1.50, 95% CI 0.99 to 2.28, p=0.058) but not increased risk of 90-day sICH (adjusted HR 1.08, 95% CI 0.46 to 2.51, p=0.862). In addition, switching anticoagulation class was not associated with reduced risk of recurrent ischaemic events (adjusted HR 0.41, 95% CI 0.12 to 1.33, p=0.136) nor sICH (adjusted HR 1.47, 95% CI 0.29 to 7.50, p=0.641).

Conclusion

AF patients with ischaemic stroke despite anticoagulation may have higher recurrent ischaemic event risk compared with anticoagulation-naïve patients. This suggests differing underlying pathomechanisms requiring different stroke prevention measures and identifying these mechanisms may improve secondary prevention strategies.
Evaluation of structured data from electronic health records to identify clinical classification criteria attributes for systemic lupus erythematosus
Authors: Walunas Theresa L , Ghosh Anika S , Pacheco Jennifer A , Mitrovic Vesna , Wu Andy , Jackson Kathryn L , Schusler Ryan , Chung Anh , Erickson Daniel , Mancera-Cuevas Karen , Luo Yuan , Kho Abel N , Ramsey-Goldman Rosalind
Published: April 2021

Objective

Our objective was to develop algorithms to identify lupus clinical classification criteria attributes using structured data found in the electronic health record (EHR) and determine whether they could be used to describe a cohort of people with lupus and discriminate them from a defined healthy control cohort.

Methods

We created gold standard lupus and healthy patient cohorts that were fully adjudicated for the American College of Rheumatology (ACR), Systemic Lupus International Collaborating Clinics (SLICC) and European League Against Rheumatism/ACR (EULAR/ACR) classification criteria and had matched EHR data. We implemented rule-based algorithms using structured data within the EHR system for each attribute of the three classification criteria. Individual criteria attribute and classification criteria algorithms as a whole were assessed over our combined cohorts and the overall performance of the algorithms was measured through sensitivity and specificity.

Results

Individual classification criteria attributes had a wide range of sensitivities, 7% (oral ulcers) to 97% (haematological disorders) and specificities, 56% (haematological disorders) to 98% (photosensitivity), but all could be identified in EHR data. In general, algorithms based on laboratory results performed better than those primarily based on diagnosis codes. All three classification criteria systems effectively distinguished members of our case and control cohorts, but the SLICC criteria-based algorithm had the highest overall performance (76% sensitivity, 99% specificity).

Conclusions

It is possible to characterise disease manifestations in people with lupus using classification criteria-based algorithms that assess structured EHR data. These algorithms may reduce chart review burden and are a foundation for identifying subpopulations of patients with lupus based on disease presentation to support precision medicine applications.
Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) common language definition of gout
Authors: Murdoch Rachel , Barry Michael J , Choi Hyon K , Hernandez Daniel , Johnsen Brianne , Labrador Manuel , Reid Susan , Singh Jasvinder A , Terkeltaub Robert , Vázquez Mellado Janitzia , Dalbeth Nicola
Published: April 2021

Objective

To develop a Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) common language definition of gout, with the goal of increasing public understanding and awareness, and ensure consistent and understandable messages about gout.

Methods

A G-CAN working group that included patients, physicians and nongovernmental organisation (NGO) representatives was formed to develop a common language definition of gout for use with the public, media, healthcare providers and stakeholders. A literature search and interviews with patients, healthcare workers and stakeholders informed development of the definition. Following consultation with G-CAN members and partners, the definition was endorsed by the G-CAN board.

Results

The G-CAN common language definition of gout describes the epidemiology, pathophysiology, symptoms and impact, risk factors, comorbidities, management and healthcare and workforce considerations. Detailed information is provided to support the content of the definition. After the publication of the English-language version, the definition will be available for translation into other languages by G-CAN members.

Conclusion

G-CAN has developed a concise and easily understandable statement describing gout in language that can be used in conversations with the lay public, media, NGOs, funders, healthcare providers and other stakeholders.
The effect of perturbations of the glycocalyx on microvascular perfusion in the obese trauma population: an in vitro study
Authors: Diebel Lawrence N , Marinica Alexander Liviu , Edelman David , Liberati David
Published: April 2021

Objectives

Patients with morbid obesity have impaired responses to resuscitation following severe injury, which may contribute to adverse outcomes. Obesity is associated with microvascular dysfunction and metabolic changes associated with altered hemorheological profiles. These include decreased red blood cell (RBC) deformity associated with increased aggregation and adhesion. These RBC changes may be impacted by the glycocalyx layer of the endothelial cell (EC) and RBC. Degradation of either or both glycocalyx layers may impair microvascular perfusion. This was studied from blood obtained from patients with obesity and in an in vitro microfluidic device to mimic the microvascular environment.

Methods

RBCs were obtained from fresh whole blood from normal controls and patients with obesity (body mass index 37.6–60.0). RBC glycocalyx was indexed by fluorescent intensity and shedding of EC glycocalyx components into the serum was determined by measurement of syndecan-1 and hyaluronic acid. In a second set of experiments, human umbilical vein endothelial cell monolayers (HUVEC) were perfused with RBC suspensions from control and patients with obesity using a microfluidic device and RBC adherence under normoxic or shock conditions (hypoxia+epinephrine) was determined using confocal microscopy. HUVEC glycocalyx thickness and shedding were also measured.

Results

Microfluidic studies demonstrated that RBC obtained from subjects with obesity had increased adhesion to the endothelial layer, which was more profound under shock conditions versus normal subjects. This appeared to be related to increased shedding of the endothelial glycocalyx following shock as well as a diminished RBC glycocalyx layer in the obese population.

Conclusion

Blood from patients with obesity have decreased RBC glycocalyx thickness accompanied by evidence of increased EC glycocalyx shedding. In vitro adhesion to the endothelium was more pronounced with RBC from patients with obesity and was significantly greater under ‘shock conditions’. Hemorheological properties of RBC from patients with obesity may account for failure of standard resuscitation procedures in the trauma patient.

Level of evidence
Experimental determination of the residual compressive strength of fire-damaged concrete columns retrofitted using CFRP wrapping
Authors: Koppula Ravali , Salem Osama (Sam) , Elshaer Ahmed
Published: April 2021

The study presented in this paper aimed to experimentally investigate the residual compressive strength of fire-damaged concrete columns retrofitted using carbon fibre-reinforced polymer (CFRP) wrapping sheets. The experimental program involved testing ten column specimens (200 mm × 200 mm × 1500 mm) that were previously exposed to standard fire before being retrofitted using CFRP wrapping sheets. The study imitated a real-life scenario in which concrete columns previously exposed to one- and two-hour standard fire while being subjected to service loads (20% and 40% of the column’s ultimate design capacity) were retrofitted using one and two layers of CFRP wrapping sheets. The test results showed that the effect of increasing the applied load ratio in reducing the post-fire residual compressive strength was more pronounced in the columns wrapped with two layers of CFRP sheets and exposed to a longer fire duration (2 h).
Introgression of Thinopyrum elongatum DNA fragments carrying resistance to fusarium head blight into Triticum aestivum cultivar Chinese Spring is associated with alteration of gene expression
Authors: Haldar Aparna , Tekieh Farideh , Balcerzak Margaret , Wolfe Danielle , Lim DaEun , Joustra Kelsey , Konkin David , Han Fangpu , Fedak George , Ouellet Thérèse
Published: April 2021

The tall wheatgrass species Thinopyrum elongatum carries on the long arm of chromosome 7E, a locus that contributes strongly to resistance to fusarium head blight (FHB), a devastating fungal disease affecting wheat crops in all temperate areas of the world. Introgression of Th. elongatum 7E chromatin into chromosome 7D of wheat was induced by the ph1b mutant of CS. Recombinants between chromosome 7E and wheat chromosome 7D, induced by the ph1b mutation, were monitored by a combination of molecular markers and phenotyping for FHB resistance. Progeny of up to five subsequent generations derived from two lineages, 64-8 and 32-5, were phenotyped for FHB symptoms and genotyped using published and novel 7D- and 7E-specific markers. Fragments from the distal end of 7EL, still carrying FHB resistance and estimated to be less than 114 and 66 Mbp, were identified as introgressed into wheat chromosome arm 7DL of progeny derived from 64-8 and 32-5, respectively. Gene expression analysis revealed variation in the expression levels of genes from the distal ends of 7EL and 7DL in the introgressed progeny. The 7EL introgressed material will facilitate the use of the 7EL FHB resistance locus in wheat breeding programs.
Spectral characterization of SPDC-based single-photon sources for quantum key distribution
Authors: Euler Sabine , Fitzke Erik , Nikiforov Oleg , Hofmann Daniel , Dolejsky Till , Walther Thomas
Published: April 2021

In our laboratory, we employ two biphoton sources for quantum key distribution. The first is based on cw parametric down-conversion of photons at 404 nm in PPKTP waveguide chips, while the second is based on the pulsed parametric down-conversion of 775 nm photons in PPLN waveguides. The spectral characterization is important for the determination of certain side-channel attacks. A Hong-Ou-Mandel experiment employing the first photon source revealed a complex structure of the common Hong-Ou-Mandel dip. By measuring the spectra of the single photons at 808 nm, we were able to associate these structures to the superposition of different transverse modes of the pump photons in our waveguide chips. The pulsed source was characterized by means of single-photon spectra measured by a sensitive spectrum analyzer as well as dispersion-based measurements. Finally, we also describe Hong-Ou-Mandel experiments using the photons from the second source.
A minimal nonlinearity logarithmic potential: Kinks with super-exponential profiles
Authors: Kumar Pradeep , Khare Avinash , Saxena Avadh
Published: April 2021

We study a [Formula: see text]-dimensional field theory based on the [Formula: see text] potential which represents minimal nonlinearity in the context of phase transitions. There are three degenerate minima at [Formula: see text] and [Formula: see text]. There are novel, asymmetric kink solutions of the form [Formula: see text] connecting the minima at [Formula: see text] and [Formula: see text]. The domains with [Formula: see text] repel the linear excitations, the waves (e.g., phonons). Topology restricts the domain sequences and therefore the ordering of the domain walls. Collisions between domain walls are rich for properties such as transmission of kinks and particle conversion, etc. For illustrative purposes we provide a comparison of these results with the [Formula: see text] model and its half-kink solution, which has an exponential tail in contrast to the super-exponential tail for the [Formula: see text] potential. Finally, we place the results in the context of other logarithmic models.
From Knowledge-Pools to Activated Networks: A Conceptual Approach to Absorptive-Capacities in a Rural Destination of Azerbaijan
Authors: Schuhbert Arne
Published: April 2021

The conception of tourist destinations as knowledge-creating systems still shows substantial gaps, especially when it comes to destinations in Developing Countries. Building upon a theoretical enhancement of the concept of absorptive-capacity and backed by empirical findings from a rural destination of Azerbaijan, this paper presents a conceptual approach to model the activation of inter-organisational linkages as an ability of individual companies to recognise and valorise product-potentials in their destinations’ ecosystem. Using a triangulated methodology to analyse procedural, cultural and structural determinants for the absorption of innovation-knowledge, potentials for the creation of knowledge-networks are presented from the perspective of the Azerbaijani accommodation business.
The Factors that Affect Healthcare Workers’ Intention to Use of E-Finance Applications in Turkey
Authors: Baki Rahmi , Bağcı Haşim
Published: April 2021

E-finance applications, being the significant outcome of the rapid developments in information technologies in the finance sector, have grown to be increasingly significant and beneficial. Time-saving e-finance applications are more important for healthcare professionals as they have an intensive work schedule. In this research, the healthcare professionals working in Turkey, the factors influencing their intention to use the e-finance application is intended to be examined. Data collected from a sample of 517 people, including doctors, nurses, and other healthcare professionals, were analysed through Structural Equation Modelling. As a result of the analysis, it was seen that the Trust variable has a major effect on healthcare workers’ intention to use e-finance. This research also finds that Personal Initiatives, Ease of Use and Usefulness have a positive and significant impact on the aforementioned dependent variable, respectively. As a result, findings that will increase the use of e-finance applications by healthcare professionals are presented in the study.
Entropy inequality and energy dissipation of inertial Qian–Sheng model for nematic liquid crystals
Authors: Jiang Ning , Luo Yi-Long , Ma Yangjun , Tang Shaojun
Published: April 2021

For the inertial Qian–Sheng model of nematic liquid crystals in the [Formula: see text]-tensor framework, we illustrate the roles played by the entropy inequality and energy dissipation in the well-posedness of smooth solutions when we employ energy method. We first derive the coefficients requirements from the entropy inequality, and point out the entropy inequality is insufficient to guarantee energy dissipation. We then introduce a novel Condition (H) which ensures the energy dissipation. We prove that when both the entropy inequality and Condition (H) are obeyed, the local in time smooth solutions exist for large initial data. Otherwise, we can only obtain small data local solutions. Furthermore, to extend the solutions globally in time and obtain the decay of solutions, we require at least one of the two conditions: entropy inequality, or [Formula: see text], which significantly enlarge the range of the coefficients in previous works.
Environmental Performance of Firms and Access to Bank Loans
Authors: Shen Hongtao , Wu Huiying , Long Wenbin , Luo Le
Published: April 2021

This study examines whether better environmental performance of a firm facilitates its access to bank loans in China and how state ownership and regional environmental pollution moderate this relationship. Using a sample of Chinese firms listed on the Shanghai or Shenzhen stock exchanges from 2007 to 2015, we find that better environmental performance is associated with greater access to bank loans, which is consistent with the predictions of risk-management theory. Furthermore, we find that the relationship between environmental performance and access to bank loans is weakened for state-owned firms and strengthened for firms operating in the regions with higher environmental pollution, suggesting that institutional factors play an important role when banks make lending decisions. Our results have implications for managers, policymakers, and banks in the transition to a green economy.
Discussion on 'Ordovician and Silurian changes in sea level'
Authors: Bassett M. G.
Published: April 2021

D
r
M. G. B
assett
writes: I am pleased that Dr McKerrow has drawn attention to the
differences in scale at which ancient sea level changes can be recognized, both in a vertical and lateral
distributional sense. In particular he has pointed out in a number of cases the important role that local
tectonism can play in causing changes, and that in some cases these may be imposed on or intercalated with
eustatic and/or other regional movements. In recent years ‘recognition’ of eustatic
changes in various parts of the geological column has become quite fashionable, but in many cases
such ‘events’ are based on widely scattered evidence with little accurate control on
correlation between different areas. Such correlation is imperative if eustatic movements are to be
invoked.

I find that many of the Ordovician–Silurian sea level changes described by Dr McKerrow could be
interpreted in one or more ways, but in most cases it is a question of degree or scale. However, I would
like to question his interpretation at the Wenlock-Ludlow boundary, where his diagram would suggest
deepening over a fairly wide area. I have elsewhere (Bassett 1976) drawn attention to the fact that
many sequences in the Anglo-Baltic area suggest widespread regression and not transgression at this
level (e.g. Pembrokeshire, Norway, Estonia), and in most cases correlation is considered to be accurate
to at least within a graptolite zone. In this respect I consider the deepening situation in southern Wales
and the Welsh Borderland to be an effect of fairly local tectonic warping, whereas Dr McKerrow presumably
sees it as part of a broader pattern.
Scale effect on the anisotropy characteristics of rock joint roughness
Authors: Du Shi-Gui , Du Kai-Qian , Yong Rui , Ye Jun , Luo Zhan-You
Published: April 2021

Accurate assessment of anisotropy and scale effect of rock joint roughness is essential for evaluating the mechanical behaviour of rock joints. However, in previous studies, how to quantify roughness anisotropy of rock joints remained largely unsolved, and the research on the scale effect on roughness anisotropy is not conclusive. A statistical analysis on the joint roughness coefficient of different sized profiles was implemented to investigate the scale dependence of joint roughness. The scale effect on the roughness anisotropy was investigated based on the class ratio transform approach. The roughness anisotropy was characterized by local anisotropy and global anisotropy. The global anisotropy tends to be almost constant when the sample size exceeds the stationarity threshold length of 70 cm. The result shows that the global anisotropy is scale dependent. However, the scale effect on local anisotropy is less apparent. The case study indicates that the class ratio transform approach is of value in roughness anisotropy investigation.
On Steady-State Evolutionary Algorithms and Selective Pressure: Why Inverse Rank-Based Allocation of Reproductive Trials Is Best
Authors: Corus Dogan , Lissovoi Andrei , Oliveto Pietro S. , Witt Carsten
Published: April 2021

We analyse the impact of the selective pressure for the global optimisation capabilities of steady-state evolutionary algorithms (EAs). For the standard bimodal benchmark function
TwoMax
, we rigorously prove that using uniform parent selection leads to exponential runtimes with high probability to locate both optima for the standard (

+1) EA and (

+1) RLS with any polynomial population sizes. However, we prove that selecting the worst individual as parent leads to efficient global optimisation with overwhelming probability for reasonable population sizes. Since always selecting the worst individual may have detrimental effects for escaping from local optima, we consider the performance of stochastic parent selection operators with low selective pressure for a function class called
TruncatedTwoMax,
where one slope is shorter than the other. An experimental analysis shows that the EAs equipped with inverse tournament selection, where the loser is selected for reproduction and small tournament sizes, globally optimise
TwoMax
efficiently and effectively escape from local optima of
TruncatedTwoMax
with high probability. Thus, they identify both optima efficiently while uniform (or stronger) selection fails in theory and in practice. We then show the power of inverse selection on function classes from the literature where populations are essential by providing rigorous proofs or experimental evidence that it outperforms uniform selection equipped with or without a restart strategy. We conclude the article by confirming our theoretical insights with an empirical analysis of the different selective pressures on standard benchmarks of the classical MaxSat and multidimensional knapsack problems.
Behold the Ch!Ld
Authors: P-Ray
Published: April 2021

From the intersection of computational science and technological speculation, with boundaries limited only by our ability to imagine what could be.

Opportunity can come calling when you least expect it.
Robustness meets algorithms
Authors: Diakonikolas Ilias , Kamath Gautam , Kane Daniel M. , Li Jerry , Moitra Ankur , Stewart Alistair
Published: April 2021

In every corner of machine learning and statistics, there is a need for estimators that work not just in an idealized model, but even when their assumptions are violated. Unfortunately, in high dimensions, being provably robust and being efficiently computable are often at odds with each other.

We give the first efficient algorithm for estimating the parameters of a high-dimensional Gaussian that is able to tolerate a constant fraction of corruptions that is independent of the dimension. Prior to our work, all known estimators either needed time exponential in the dimension to compute or could tolerate only an inverse-polynomial fraction of corruptions. Not only does our algorithm bridge the gap between robustness and algorithms, but also it turns out to be highly practical in a variety of settings.
Isomorphism, canonization, and definability for graphs of bounded rank width
Authors: Grohe Martin , Neuen Daniel
Published: April 2021

We investigate the interplay between the graph isomorphism problem, logical definability, and structural graph theory on a rich family of dense graph classes: graph classes of bounded rank width. We prove that the combinatorial Weisfeiler-Leman algorithm of dimension (3
k
+ 4) is a complete isomorphism test for the class of all graphs of rank width at most
k.
A consequence of our result is the first polynomial time canonization algorithm for graphs of bounded rank width.

Our second main result addresses an open problem in descriptive complexity theory: we show that fixed-point logic with counting expresses precisely the polynomial time properties of graphs of bounded rank width.
Software professionals, malpractice law, and codes of ethics
Authors: Choi Bryan H.
Published: April 2021

In pursuit of professional status for computing professionals.
AI in Measurement Science
Authors: Liu Chao , Sun Jiashu
Published: April 2021

Measurement of biological systems containing biomolecules and bioparticles is a key task in the fields of analytical chemistry, biology, and medicine. Driven by the complex nature of biological systems and unprecedented amounts of measurement data, artificial intelligence (AI) in measurement science has rapidly advanced from the use of silicon-based machine learning (ML) for data mining to the development of molecular computing with improved sensitivity and accuracy. This review presents an overview of fundamental ML methodologies and discusses their applications in disease diagnostics, biomarker discovery, and imaging analysis. We next provide the working principles of molecular computing using logic gates and arithmetical devices, which can be employed for in situ detection, computation, and signal transduction for biological systems. This review concludes by summarizing the strengths and limitations of AI-involved biological measurement in fundamental and applied research.
The Science and Art of Clinical Genetic Variant Classification and Its Impact on Test Accuracy
Authors: Giles Hunter H. , Hegde Madhuri R. , Lyon Elaine , Stanley Christine M. , Kerr Iain D. , Garlapow Megan E. , Eggington Julie M.
Published: April 2021

Clinical genetic variant classification science is a growing subspecialty of clinical genetics and genomics. The field's continued improvement is essential for the success of precision medicine in both germline (hereditary) and somatic (oncology) contexts. This review focuses on variant classification for DNA next-generation sequencing tests. We first summarize current limitations in variant discovery and definition, and then describe the current five- and four-tier classification systems outlined in dominant standards and guideline publications for germline and somatic tests, respectively. We then discuss measures of variant classification discordance and the field's bias for positive results, as well as considerations for panel size and population screening in the context of estimates of positive predictive value thatincorporate estimated variant classification imperfections. Finally, we share opinions on the current state of variant classification from some of the authors of the most widely used standards and guideline publications and from other domain experts.
Damage-Associated Molecular Patterns (DAMPs) in Plant Innate Immunity: Applying the Danger Model and Evolutionary Perspectives
Authors: Tanaka Kiwamu , Heil Martin
Published: April 2021

Danger signals trigger immune responses upon perception by a complex surveillance system. Such signals can originate from the infectious nonself or the damaged self, the latter termed damage-associated molecular patterns (DAMPs). Here, we apply Matzinger's danger model to plant innate immunity to discuss the adaptive advantages of DAMPs and their integration into preexisting signaling pathways. Constitutive DAMPs (cDAMPs), e.g., extracellular ATP, histones, and self-DNA, fulfill primary, conserved functions and adopt a signaling role only when cellular damage causes their fragmentation or localization to aberrant compartments. By contrast, immunomodulatory peptides (also known as phytocytokines) exclusively function as signals and, upon damage, are activated as inducible DAMPs (iDAMPs). Dynamic coevolutionary processes between the signals and their emerging receptors and shared co-receptors have likely linked danger recognition to preexisting, conserved downstream pathways.
Influence of innate immune activation on endocrine and metabolic pathways in infancy
Authors: O’Connor K. M. , Ashoori M. , Dias M. L. , Dempsey E. M. , O’Halloran K. D. , McDonald F. B.
Published: April 2021

Prematurity is the leading cause of neonatal morbidity and mortality worldwide. Premature infants often require extended hospital stays, with increased risk of developing infection compared with term infants. A picture is emerging of wide-ranging deleterious consequences resulting from innate immune system activation in the newborn infant. Those who survive infection have been exposed to a stimulus that can impose long-lasting alterations into later life. In this review, we discuss sepsis-driven alterations in integrated neuroendocrine and metabolic pathways and highlight current knowledge gaps in respect of neonatal sepsis. We review established biomarkers for sepsis and extend the discussion to examine emerging findings from human and animal models of neonatal sepsis that propose novel biomarkers for early identification of sepsis. Future research in this area is required to establish a greater understanding of the distinct neonatal signature of early and late-stage infection, to improve diagnosis, curtail inappropriate antibiotic use, and promote precision medicine through a biomarker-guided empirical and adjunctive treatment approach for neonatal sepsis. There is an unmet clinical need to decrease sepsis-induced morbidity in neonates, to limit and prevent adverse consequences in later life and decrease mortality.
Heterogeneity and neurovascular integration of intraportally transplanted islets revealed by 3-D mouse liver histology
Authors: Chen Chien-Chia , Peng Shih-Jung , Wu Pei-Yu , Chien Hung-Jen , Lee Chih-Yuan , Chung Mei-Hsin , Tang Shiue-Cheng
Published: April 2021

Modern 3-D histology identifies the clot- and plaque-like islet grafts in the mouse liver, which otherwise cannot be distinguished with the standard microtome-based histology. The two types of grafts are similar in blood microvessel density and sympathetic reinnervation. Their differences, however, are their locations, severity of associated liver injury, and access to lymphatic vessels. Our work provides the technical and morphological foundation for future high-definitional 3-D tissue/cellular analyses of human islet grafts in the liver.
Deletion of Kir5.1 abolishes the effect of high Na+ intake on Kir4.1 and Na+-Cl− cotransporter
Authors: Duan Xin-Peng , Wu Peng , Zhang Dan-Dan , Gao Zhong-Xiuzi , Xiao Yu , Ray Evan C. , Wang Wen-Hui , Lin Dao-Hong
Published: April 2021

Kir5.1 plays an important role in mediating the effect of high sodium intake on basolateral K+ channels in the distal convoluted tubule and Na+-Cl− cotransporter activity/expression.