bluuebunny/crossref_metadata_2025 huggingface dataset:
RETRACTED: Multi‐Stimuli Nanocomposite Therapeutic: Docetaxel Targeted Delivery and Synergies in Treatment of Human Breast Cancer Tumor
Authors: Taheri‐Ledari Reza , Zhang Wenjie , Radmanesh Maral , Mirmohammadi Seyedeh Shadi , Maleki Ali , Cathcart Nicole , Kitaev Vladimir
Published: September 2020

A versatile breast cancer‐targeting nanocomposite therapeutic combining docetaxel (DXL), polyvinyl alcohol (PVA) network for controlled release, and silica‐protected magnetic iron oxide nanoparticles (Fe3O4 NPs) for targeted delivery and gold nanoparticles (AuNPs) for plasmonic photothermal therapy (PPTT) is presented in this work. First, the designed nanocomposite is magnetically directed for cancer‐targeted therapy confirmed by computerized tomography (CT) scans. Second, 10% DXL by mass is loaded into PVA, a pH and temperature responsive gel, for controlled release. Third, PPTT is confirmed with Au/Fe3O4/PVA‐10%DXL using a prototype circulation system and then for tumor treatment in vivo; Au/Fe3O4/PVA‐10%DXL is conveniently directed and the entrapped DXL is selectively released (≈96%) via the interaction of green and near‐infrared (NIR) light with the localized surface plasmon resonance of AuNPs. A 75% cell death is reported from in vitro studies with DXL doses as low as 20 µg mL−1 of Au/Fe3O4/PVA‐10%DXL, and a 70% tumor growth inhibition is demonstrated by in vivo experiments with the biosafety studies confirming minimal side effects to other organs. Overall, the developed Au/Fe3O4/PVA‐10%DXL has a strong potential to simultaneously enhance CT imaging contrast together with the targeted delivery of DXL.
Evolution of SHORT VEGETATIVE PHASE (SVP) genes in Rosaceae: Implications of lineage‐specific gene duplication events and function diversifications with respect to their roles in processes other than bud dormancy
Authors: Liu Jinyi , Ren Min , Chen Hui , Wu Silin , Yan Huijun , Jalal Abdul , Wang Changquan
Published: September 2020

MADS‐box genes that are homologous to Arabidopsis SHORT VEGETATIVE PHASE (SVP) have been shown to play key roles in the regulation of bud dormancy in perennial species, particularly in the deciduous fruit trees of Rosaceae. However, their evolutionary profiles in Rosaceae have not yet been analyzed systematically. Here, The SVP genes were found to be significantly expanded in Rosaceae when compared with annual species from Brassicaceae. Phylogenetic analysis showed that Rosaceae SVP genes could be classified into five clades, namely, SVP1, SVP2‐R1, SVP2‐R2, SVP2‐R3 and SVP3. The SVP1 clade genes were retained in most of the species, whereas the SVP2‐R2 and SVP2‐R3 clades were found to be Maleae‐ and Amygdaleae‐specific (Both of the lineages belong to Amygdaloideae), respectively, and SVP2‐R1 was Rosoideae‐specific in Rosaceae. Furthermore, 10 lineage‐specific gene duplication (GD) events (GD1–10) were proposed for the expansion of SVP genes, suggesting that the expansion and divergence of Rosaceae SVP genes were mainly derived by lineage‐specific manner during evolution. Moreover, tandem and segmental duplications were the major reasons for the expansion of SVP genes, and interestingly, tandem duplications, a well‐known evolutionary feature of SVP genes, were found to be mainly Amygdaloideae‐specific. Sequence alignment, selection pressure, and cis‐acting element analysis suggested large functional innovations and diversification of SVP genes in different lineages of Rosaceae. Finally, the different growth cycle of Rosa multiflora and their novel expression patterns of RmSVP genes provided new insights into the functional diversification of SVP genes in terms of their roles in processes other than bud dormancy.
The O(N ) model with ϕ6 potential in ℝ2 × ℝ+
Authors: Herzog Christopher P. , Kobayashi Nozomu
Published: September 2020

Abstract

We study the large N limit of O(N ) scalar field theory with classically marginal ϕ6 interaction in three dimensions in the presence of a planar boundary. This theory has an approximate conformal invariance at large N . We find different phases of the theory corresponding to different boundary conditions for the scalar field. Computing a one loop effective potential, we examine the stability of these different phases. The potential also allows us to determine a boundary anomaly coefficient in the trace of the stress tensor. We further compute the current and stress-tensor two point functions for the Dirichlet case and decompose them into boundary and bulk conformal blocks. The boundary limit of the stress tensor two point function allows us to compute the other boundary anomaly coefficient. Both anomaly coefficients depend on the approximately marginal ϕ6 coupling.
Evaluation einer Therapieanpassung bei ASS-Low-Response in der Gefäßchirurgie
Authors: Hummel T , Meves S. H. , Breuer-Kaiser A. , Düsterwald J. O. , Mühlberger D. , Mumme A. , Neubauer H.
Published: September 2020

Hintergrund

Eine verminderte antithrombozytäre Prophylaxe („Low-Response [LR]“/„high on-treatment platelet reactivity [HPR]“) mit Acetylsalicylsäure (ASS) ist mit einem erhöhten Risiko für thrombembolische Ereignisse assoziiert. Die Prävalenz einer Low-Response ist mit ca. 20 % häufig und ein Therapieregime wurde bisher noch nicht etabliert. Das Ziel dieser prospektiven Studie war es, die Effektivität eines Therapieschemas zur Therapieanpassung bei detektierter LR/HPR bei gefäßchirurgischen Patienten zu evaluieren.

Methodik

Insgesamt wurden 36 gefäßchirurgischen Patienten mit einer antithrombozytären Dauermedikation mit ASS 100 mg/Tag und einer nachgewiesenen ASS-Low-Response (ALR) in die Studie eingeschlossen. Entsprechend dem festgelegten Therapieplan wurde bei diesen Patienten eine Therapieanpassung durchgeführt und eine Kontrollaggregometrie zur Erfolgskontrolle durchgeführt. Das verwendete Therapieschema folgte dem Test-and-treat-Prinzip. Zur Beurteilung der Wirkung von ASS diente die Impedanzaggregometrie mittels Mehrelektrodenaggregometer (Multiplate).

Ergebnisse

Insgesamt konnten alle 36 Patienten erfolgreich in eine Response überführt werden. Bei 32 (88,89 %) Patienten erfolgte eine Dosiserhöhung auf 300 mg ASS, 2 (5,56 %) Patienten wurden von ASS auf Clopidogrel umgestellt. Bei weiteren 2 (5,56 %) Patienten wurde auf eine orale Antikoagulation mit Phenprocoumon aufgrund anderer Indikationen umgestellt. Blutungskomplikationen oder Nebenwirkungen traten nicht auf.

Schlussfolgerung

Das gewählte Therapieschema zur Behandlung einer Low-Response erwies sich als effektiv und sicher bei gefäßchirurgischen Patienten. Überwiegend führte eine leitliniengerechte Dosiserhöhung der Prophylaxe von 100 mg auf 300 mg ASS zu einer effektiven Thrombozytenaggregationshemmung in der Aggregometrie.
Is the productivity premium of internationalized firms technology-driven?
Authors: Battisti Michele , Belloc Filippo , Del Gatto Massimo
Published: September 2020

We ask whether the productivity advantage of internationalized firms documented by the international trade literature can be interpreted most accurately in terms of proximity to the “technological frontier”. We answer in the affirmative using a methodology (based on mixture models) of unbundling technology and total factor productivity (TFP) by estimating “technology-specific” production function parameters. Exploiting detailed data provided by the EFIGE database (a sample of firms distributed across Austria, France, Germany, Hungary, Italy, Spain, and the UK), we find technology gaps (with respect to the frontier) more than three times larger than the TFP gaps on average. We also find sizable technology advantages for firms undertaking foreign direct investment and/or exporting to other European Union countries or to China, for importers of materials, and for firms with competitors in China and the USA. Medium and large firms feature a higher technology premium, which is even higher for firms operating in country-sectors that are more exposed to import competition from China. Younger firms use better technologies but less effectively.
Imaging-based patient-reported outcomes (PROs) database: How we do it
Authors: Gyftopoulos Soterios , Jacobs Adam , Samim Mohammad
Published: September 2020

Patient-reported outcomes (PROs) provide an essential understanding of the impact a condition or treatment has on a patient, while complementing other, more traditional outcomes information like survival and time to symptom resolution. PROs have become increasingly important in medicine with the push toward patient-centered care. The creation of a PROs database within an institution or practice provides a way to collect, understand, and use this kind of patient feedback to inform quality improvement and develop the evidence base for medical decision-making and on a larger scale could potentially help determine national standards of care and treatment guidelines. This paper provides a first-hand account of our experience setting up an imaging-based PROs database at our institution and is organized into steps the reader can follow for creating a PROs database of their own. Given the limited use of PROs within both diagnostic and interventional radiology, we hope our paper stimulates a new interest among radiologists who may have never considered outcomes work in the past.
Very long-term follow-up of aplastic anemia treated with immunosuppressive therapy or allogeneic hematopoietic cell transplantation
Authors: Drexler Beatrice , Zurbriggen Felicitas , Diesch Tamara , Viollier Romaine , Halter Joerg P. , Heim Dominik , Holbro Andreas , Infanti Laura , Buser Andreas , Gerull Sabine , Medinger Michael , Tichelli André , Passweg Jakob R.
Published: September 2020

Introduction

Since the 1970s outcome of aplastic anemia (AA) patients has improved significantly due to the introduction of immunosuppressive therapy (IST) and allogeneic hematopoietic transplantation (HCT). However, patients may suffer from persistent disease, relapse, clonal evolution, graft-versus-host disease and other late effects. Here, we analyse very long-term outcome of all AA patients at our institution comparing not only survival, but also response status and complications.

Methods

Patient charts of all 302 AA patients treated between 1973 and 2017 at the University Hospital Basel, Switzerland, were retrospectively analysed.

Results

First line treatment was IST in 226 (75%) and HCT in 76 (25%) patients. Overall survival at 30 years was similar in patients treated initially by HCT and IST (44% (±14%), and 40% (± 9%) respectively, with better results in more recent years. Partial and no response occurred more frequently after IST, relapse incidence after IST was 24 %, whereas non-engraftment and graft failure was documented in 15 patients (19 %) after HCT. Clonal evolution to myelodysplastic syndrome / acute myeloid leukemia was 16 % at 25 years in IST patients, 1.3 % in HCT patients, iron overload (18 versus 4 %, p = 0.002) and cardiovascular events (11 versus 1 %, p=0.011) occured significantly more often in IST than HCT treated patients. The majority of long-term survivors, 96% of those alive at 25 years, were in complete remission at last follow up, irrespective of the initial treatment modality.

Conclusion

Very long term survivors after AA are those with stable hematopoietic recovery.
Initial chest radiographs and artificial intelligence (AI) predict clinical outcomes in COVID-19 patients: analysis of 697 Italian patients
Authors: Mushtaq Junaid , Pennella Renato , Lavalle Salvatore , Colarieti Anna , Steidler Stephanie , Martinenghi Carlo M. A. , Palumbo Diego , Esposito Antonio , Rovere-Querini Patrizia , Tresoldi Moreno , Landoni Giovanni , Ciceri Fabio , Zangrillo Alberto , De Cobelli Francesco
Published: September 2020

Objective

To evaluate whether the initial chest X-ray (CXR) severity assessed by an AI system may have prognostic utility in patients with COVID-19.

Methods

This retrospective single-center study included adult patients presenting to the emergency department (ED) between February 25 and April 9, 2020, with SARS-CoV-2 infection confirmed on real-time reverse transcriptase polymerase chain reaction (RT-PCR). Initial CXRs obtained on ED presentation were evaluated by a deep learning artificial intelligence (AI) system and compared with the Radiographic Assessment of Lung Edema (RALE) score, calculated by two experienced radiologists. Death and critical COVID-19 (admission to intensive care unit (ICU) or deaths occurring before ICU admission) were identified as clinical outcomes. Independent predictors of adverse outcomes were evaluated by multivariate analyses.

Results

Six hundred ninety-seven 697 patients were included in the study: 465 males (66.7%), median age of 62 years (IQR 52–75). Multivariate analyses adjusting for demographics and comorbidities showed that an AI system-based score ≥ 30 on the initial CXR was an independent predictor both for mortality (HR 2.60 (95% CI 1.69 − 3.99; p < 0.001)) and critical COVID-19 (HR 3.40 (95% CI 2.35–4.94; p < 0.001)). Other independent predictors were RALE score, older age, male sex, coronary artery disease, COPD, and neurodegenerative disease.

Conclusion

AI- and radiologist-assessed disease severity scores on CXRs obtained on ED presentation were independent and comparable predictors of adverse outcomes in patients with COVID-19.

Trial registration

ClinicalTrials.gov NCT04318366 (https://clinicaltrials.gov/ct2/show/NCT04318366).

Key Points

• AI system–based score ≥ 30 and a RALE score ≥ 12 at CXRs performed at ED presentation are independent and comparable predictors of death and/or ICU admission in COVID-19 patients.

• Other independent predictors are older age, male sex, coronary artery disease, COPD, and neurodegenerative disease.

• The comparable performance of the AI system in relation to a radiologist-assessed score in predicting adverse outcomes may represent a game-changer in resource-constrained settings.
Low-dose MDCT: evaluation of the impact of systematic tube current reduction and sparse sampling on the detection of degenerative spine diseases
Authors: Sollmann Nico , Mei Kai , Riederer Isabelle , Probst Monika , Löffler Maximilian T. , Kirschke Jan S. , Noël Peter B. , Baum Thomas
Published: September 2020

Objectives

To investigate potential radiation dose reduction for multi-detector computed tomography (MDCT) exams of the spine by using sparse sampling and virtually lowered tube currents combined with statistical iterative reconstruction (SIR).

Methods

MDCT data of 26 patients (68.9 ± 11.7 years, 42.3% males) were retrospectively simulated as if the scans were acquired at 50%, 10%, 5%, and 3% of the original X-ray tube current or number of projections, using SIR for image reconstructions. Two readers performed qualitative image evaluation considering overall image quality, artifacts, and contrast and determined the number and type of degenerative changes. Scoring was compared between readers and virtual low-dose and sparse-sampled MDCT, respectively.

Results

Image quality and contrast decreased with virtual lowering of tube current and sparse sampling, but all degenerative changes were correctly detected in MDCT with 50% of tube current as well as MDCT with 50% of projections. Sparse-sampled MDCT with only 10% of initial projections still enabled correct identification of all degenerative changes, in contrast to MDCT with virtual tube current reduction by 90% where non-calcified disc herniations were frequently missed (R1: 23.1%, R2: 21.2% non-diagnosed herniations). The average volumetric CT dose index (CTDIvol) was 1.4 mGy for MDCT with 10% of initial projections, compared with 13.8 mGy for standard-dose imaging.

Conclusions

MDCT with 50% of original tube current or projections using SIR still allowed for accurate diagnosis of degenerative changes. Sparse sampling may be more promising for further radiation dose reductions since no degenerative changes were missed with 10% of initial projections.

Key Points

• Most common degenerative changes of the spine can be diagnosed in multi-detector CT with 50% of tube current or number of projections.

• Sparse-sampled multi-detector CT with only 10% of initial projections still enables correct identification of degenerative changes, in contrast to imaging with 10% of original tube current.

• Sparse sampling may be a promising option for distinct lowering of radiation dose, reducing the CTDIvolfrom 13.8 to 1.4 mGy in the study cohort.
Choroidal thickness in lamellar macular holes
Authors: Kal Magdalena , Winiarczyk Mateusz , Głuszek Stanisław , Mackiewicz Jerzy
Published: September 2020

Purpose

(1) To assess the thickness of the central choroid (BM-CSI) in swept-source optical coherence tomography (SS-OCT) examination of lamellar macular holes (LMHs). (2) To establish correlations between the thickness of the central choroid (BM-CSI) in the LHM and the parameters of best-corrected visual acuity and reading vision in patients with LMH.

Methods

This prospective case-control study assessed a group of 30 patients (30 eyes) with LMHs and a control group of 45 patients (90 eyes). The thickness of the central choroid (BM-CSI) was measured with an SS-OCT device. The average choroidal thickness in the fovea was defined as average thickness in the central area of 1000 μm in diameter, according to the Early Treatment Diabetic Retinopathy Study (ETDRS). The results were correlated with best-corrected visual acuity (BCVA), and reading vision.

Results

The average choroidal thickness in the study group (SG) with LMH was 160.34 μm (SD = 77.1), whereas in the control group (CG), it was 225.11 μm (SD = 93.8). The difference of 64.77 μm was statistically significant (p < 0.05). The BCVA was within the range between 0.7 (logMAR) and 0.1 (logMAR), with an average of 0.36 (logMAR) (SD = 0.23). Reading vision was within the range between − 0.2 (logMAR) and 0.3 (logMAR), with an average of 0.27 (logMAR) (SD = 0.12). A significant correlation between BCVA and the choroid (BM-CSI) was found. The correlation coefficient is average (r = 0.44) and positive. With better BCVA, a significantly thicker choroid (BM-CSI) can be observed. No significant correlation between BM-CSI and reading vision was found. The correlation coefficient value is minor (r = − 0.289), whereas lower values of BM-CSI can be observed with worse reading vision.

Conclusion

We suggest that the choroid may take part in the pathogenesis of LMH development. Its significant thinning may be responsible for the ischemic degenerative mechanism degenerating outer layers of retina, apart from tractional mechanism.
The physiology of regulated BDNF release
Authors: Brigadski Tanja , Leßmann Volkmar
Published: September 2020

The neurotrophic factor BDNF is an important regulator for the development of brain circuits, for synaptic and neuronal network plasticity, as well as for neuroregeneration and neuroprotection. Up- and downregulations of BDNF levels in human blood and tissue are associated with, e.g., neurodegenerative, neurological, or even cardiovascular diseases. The changes in BDNF concentration are caused by altered dynamics in BDNF expression and release. To understand the relevance of major variations of BDNF levels, detailed knowledge regarding physiological and pathophysiological stimuli affecting intra- and extracellular BDNF concentration is important. Most work addressing the molecular and cellular regulation of BDNF expression and release have been performed in neuronal preparations. Therefore, this review will summarize the stimuli inducing release of BDNF, as well as molecular mechanisms regulating the efficacy of BDNF release, with a focus on cells originating from the brain. Further, we will discuss the current knowledge about the distinct stimuli eliciting regulated release of BDNF under physiological conditions.
Semi-supervised deep learning based named entity recognition model to parse education section of resumes
Authors: Gaur Bodhvi , Saluja Gurpreet Singh , Sivakumar Hamsa Bharathi , Singh Sanjay
Published: September 2020

A job seeker’s resume contains several sections, including educational qualifications. Educational qualifications capture the knowledge and skills relevant to the job. Machine processing of the education sections of resumes has been a difficult task. In this paper, we attempt to identify educational institutions’ names and degrees from a resume’s education section. Usually, a significant amount of annotated data is required for neural network-based named entity recognition techniques. A semi-supervised approach is used to overcome the lack of large annotated data. We trained a deep neural network model on an initial (seed) set of resume education sections. This model is used to predict entities of unlabeled education sections and is rectified using a correction module. The education sections containing the rectified entities are augmented to the seed set. The updated seed set is used for retraining, leading to better accuracy than the previously trained model. This way, it can provide a high overall accuracy without the need of large annotated data. Our model has achieved an accuracy of 92.06% on the named entity recognition task.
The importance of timely treatment for quality of life and survival in patients with symptomatic spinal metastases
Authors: van Tol Floris R. , Suijkerbuijk Karijn P. M. , Choi David , Verkooijen Helena M. , Oner F. Cumhur , Verlaan Jorrit-Jan
Published: September 2020

Purpose

A major challenge in metastatic spinal disease is timely identification of patients. Left untreated, spinal metastases may lead to gross mechanical instability and/or neurological deficits, often requiring extensive invasive surgical treatment. The aim of this cohort study was to assess the correlation between delayed treatment of patients with spinal metastases and functional performance, quality of life and survival.

Methods

All patients surgically treated for metastatic spinal disease at a tertiary care facility were included for analysis. Patients who underwent elective surgery were considered as timely treated, whereas patients requiring emergency surgery were considered to be treated in a delayed fashion. EQ-5D scores, KPS scores and mortality rates were compared between the two groups.

Results

A total of 317 patients (215 timely treated, 102 delayed) had survivorship data available and 202 patients (147 timely treated, 55 delayed) had clinical data available. Multivariate analyses showed delayed treatment was associated with lower EQ-5D and KPS scores and higher mortality rates, independent of confounders such as baseline EQ-5D/KPS scores, neurological status, tumor prognosis and patient age.

Conclusions

The results from the present study show delayed treatment of patients with symptomatic spinal metastases has both direct and indirect adverse consequences for functional performance status, quality of life and survival. Optimization of referral pattern may accelerate the time to surgical treatment, potentially leading to better quality of life and survival.
Surgery for diaphragma sellae meningioma: how I do it
Authors: Belouaer Amani , Starnoni Daniele , Daniel Roy Thomas
Published: September 2020

Background

Surgery for diaphragma sellae meningiomas (DSM) remains challenging due to the intimate neurovascular relationships of the tumor. Excision of DSM along with a decompression of the optic apparatus requires a good knowledge of the skull base anatomy and a precise preoperative evaluation of the tumor extensions.

Method

We describe the key steps of transcranial approach for DSM with a video illustration. The surgical anatomy is described along with the advantages and limitations of this approach.

Conclusions

The transcranial approach allows a safe tumor excision with an early and adequate control of the neurovascular structures, while minimizing postoperative CSF rhinorrhea.
Intra-brand competition in a differentiated oligopoly
Authors: Breton Michèle , Sbragia Lucia
Published: September 2020

In this paper we consider a differentiated oligopoly with two product varieties that are supplied by two groups of firms. After computing the Cournot solution of the game, we study its sensitivity to different sources of competition, namely the degree of product substitutability and market composition. Market composition can change either via new firms entering one industry or via firms switching production techniques, thus modifying the intensity of intra-brand competition. After studying the welfare consequences of an intensification of competition, we identify the equilibrium market composition when firms are driven by profit considerations. All the results are expressed in terms of the degree of product substitutability and of what we define “weighted relative efficiency” (WRE), which is a parameter combining both firm characteristics and market conditions.
Impact of non-proteinogenic amino acids in the discovery and development of peptide therapeutics
Authors: Ding Yun , Ting Joey Paolo , Liu Jinsha , Al-Azzam Shams , Pandya Priyanka , Afshar Sepideh
Published: September 2020

With the development of modern chemistry and biology, non-proteinogenic amino acids (NPAAs) have become a powerful tool for developing peptide-based drug candidates. Drug-like properties of peptidic medicines, due to the smaller size and simpler structure compared to large proteins, can be changed fundamentally by introducing NPAAs in its sequence. While peptides composed of natural amino acids can be used as drug candidates, the majority have shown to be less stable in biological conditions. The impact of NPAA incorporation can be extremely beneficial in improving the stability, potency, permeability, and bioavailability of peptide-based therapies. Conversely, undesired effects such as toxicity or immunogenicity should also be considered. The impact of NPAAs in the development of peptide-based therapeutics is reviewed in this article. Further, numerous examples of peptides containing NPAAs are presented to highlight the ongoing development in peptide-based therapeutics.
Anti-inflammatory activities of puerarin in high-fat diet-fed rats with streptozotocin-induced gestational diabetes mellitus
Authors: Xu Wenting , Tang Mengyu , Wang Jiahui , Wang Lihong
Published: September 2020

To investigate the effect of puerarin on insulin resistance and inflammation in rats with gestational diabetes mellitus (GDM). Gestational diabetic model rats were established by intraperitoneal injection of streptozotocin (25 mg/kg) combined with high-fat feeding and were randomly assigned to three groups: the control group, the GDM group, and the puerarin-treated group. Puerarin was intragastrically administered to rats daily until the offspring were born. The rats in both the GDM group and control group were administered the same volume of normal saline. Serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in all groups of rats were measured. Haematoxylin and eosin staining was used to evaluate morphological changes in the liver, pancreas, and adipose tissues around the reproductive organs. Western blotting was carried out to measure the protein expression of IRS-1 and inflammatory factors, including TNF-α, TLR4, MyD88 and phosphorylated NF-κB, in the adipose tissues around the reproductive organs. Puerarin had preventive effects on GDM-induced pathological changes and ameliorated glucose and lipid metabolism disorders in GDM rats. Puerarin upregulated IRS-1 expression and decreased the protein expression of TNF-α, TLR4, and MyD88 as well as the levels of phosphorylated NF-κB in adipose tissues around the reproductive organs in GDM rats. This study indicated that puerarin exerts anti-inflammatory effects by downregulating the important TLR4/MyD88/NF-κB inflammatory signalling pathway. Therefore, puerarin can decrease the expression of TNF-α and ameliorate insulin resistance in GDM rats, suggesting the potential efficacy of puerarin in GDM treatment.
Experimental and Theoretical Studies of Cu-Sn Intermetallic Phase Growth During High-Temperature Storage of Eutectic SnAg Interconnects
Authors: Morozov A. , Freidin A. B. , Klinkov V. A. , Semencha A. V. , Müller W. H. , Hauck T.
Published: September 2020

In this paper, the growth of intermetallic compound (IMC) layers is considered. After soldering, an IMC layer appears and establishes a mechanical contact between eutectic tin-silver solder bumps and Cu interconnects in microelectronic components. Intermetallics are relatively brittle in comparison with copper and tin. In addition, IMC formation is typically based on multi-component diffusion, which may include vacancy migration leading to Kirkendall voiding. Consequently, the rate of IMC growth has a strong implication on solder joint reliability. Experiments show that the intermetallic layers grow considerably when the structure is exposed to heat. Mechanical stresses may also affect intermetallic growth behavior. These stresses arise not only from external loadings but also from thermal mismatch of the materials constituting the joint, and from the mismatch produced by the change in shape and volume due to the chemical reactions of IMC formation. This explains why in this paper special attention is being paid to the influence of stresses on the kinetics of the IMC growth. We develop an approach that couples mechanics with the chemical reactions leading to the formation of IMC, based on the thermodynamically sound concept of the chemical affinity tensor, which was recently used in general statements and solutions of mechanochemistry problems. We start with a report of experimental findings regarding the IMC growth at the interface between copper pads and tin based solder alloys in different microchips during a high temperature storage test. Then we analyze the growth kinetics by means of a continuum model. By combining experiment, theory, and a comparison of experimental data and theoretical predictions we finally find the values of the diffusion coefficient and an estimate for the chemical reaction constant. A comparison with literature data is also performed.
Konstruktion und Validierung eines multidimensionalen Beobachtungsinstruments zur Erfassung der klassenführungsbezogenen Performanzen von sportunterrichtenden Lehrkräften (KlaPe-Sport)
Authors: Baumgartner Matthias , Oesterhelt Verena , Reuker Sabine
Published: September 2020

Obschon die Klassenführung von sportunterrichtenden Lehrkräften ein bedeutsamer Faktor eines guten Sportunterrichts darstellt, liegen keine Beobachtungsinstrumente vor, um die Qualität der klassenführungsbezogenen Performanzen bei sportunterrichtenden Lehrkräften valide, reliabel und objektiv erheben zu können. Derartige Instrumente erscheinen jedoch als wünschenswert, weil damit die Qualität der Klassenführung von sportunterrichtenden Lehrkräften ökologisch valide, situiert und verhaltensnah erfasst werden kann. In vorliegender Studie wurde dementsprechend die Fragestellung bearbeitet, durch welche Qualitätskriterien sich die klassenführungsbezogenen Performanzen bei sportunterrichtenden Lehrkräften erfassen lassen. In einem ersten Schritt wurde dazu eine Literaturanalyse realisiert und ein provisorisches Beobachtungsinstrument entwickelt. In einem zweiten Schritt wurde das Instrument im Rahmen einer Delphi-Runde und im Sinne einer inhaltlichen Validierung Sportdidaktikerinnen und Sportdidaktikern (n = 8) vorgelegt. Latente und manifeste Variablen wurden dabei verändert, ausgeschlossen und neue Variablen generiert. Zur empirischen Validierung wurde in einem dritten Schritt ein Beurteilungsverfahren durchgeführt. Raterinnen und Rater (n = 6) absolvierten dazu ein Training. Im Anschluss wurde die Qualität der klassenführungsbezogenen Performanzen anhand von 166 Unterrichtsstunden bei angehenden und tätigen sportunterrichtenden Lehrkräften beurteilt. Zur Überprüfung der Güte des Instruments wurden Faktorenanalysen durchgeführt und die Interraterreliabilität berechnet. Aus der empirischen Überprüfung geht ein 9‑faktorielles Modell hervor, welches aus 27 manifesten Variablen besteht. Die empirische Lösung weist auf einen ausreichenden bis guten Modell-Fit, die Interraterreliabilität zeigt gute bis exzellente Kennwerte. Mit der Studie wurde ein multidimensionales Beobachtungsinstrument entwickelt, mit dem die klassenführungsbezogenen Performanzen von sportunterrichtenden Lehrkräften valide, reliabel und objektiv erfasst werden können.
Botrops derived hemocoagulase formulation a probable agent for diabetic wound healing
Authors: Keni Raghuvir , Gourishetti Karthik , Kinra Manas , Nayak Pawan G. , Shenoy Rekha , Nandakumar Krishnadas , Jagdale Rajesh N. , Raghavendra K. V. , Ahmed Syed Mushtaq
Published: September 2020

Botroclot is a marketed preparation containing hemocoagulase, which is an enzyme having coagulant activity, isolated from the snake Botrops atrox. This formulation is used in dental surgeries and other minor surgical wounds. However, the formulation remains untested in diabetic wounds. Hence, we proposed a study for the topical application of Botroclot in high-fat diet (HFD) + Streptozotocin (STZ) induced diabetic rats. HFD was fed initially to rats which facilitates the development of insulin resistance. Thereafter, an injection of STZ (40 mg/kg, i.p.) was given. This resulted in the development of diabetes with elevated fasting glucose and impaired glucose tolerance. After stabilization of blood glucose values, wounds were created by punch biopsy on the dorsal side of the palm of the rat to mimic the diabetic wounds frequently seen in the case of humans. Later, the application of Botroclot on these wounds was carried out for 15 days. Topical application of hemocoagulase improved the wound closure and there was a gradual decrease in inflammatory markers and a substantial increase in collagen deposition occurred. Histopathological findings indicated the same, with an increase in granulation tissue suggesting that the topical application moderately improves the wound healing in diabetic rats. We conclude that Botroclot can have a mild to moderate effect in improving collagen deposition and thus wound contraction, improving wound closure in diabetic wounds in rats. This study also establishes the basis for exploration of agents from venom-based sources in diabetic wound healing.
Reasonable accommodation in Irish equality law: an incomplete transformation
Authors: Buckley Lucy-Ann , Quinlivan Shivaun
Published: September 2020

The UN Convention on the Rights of Persons with Disabilities is the first international human rights convention to state expressly that discrimination includes the failure to provide reasonable accommodation. The duty has been described as transformative but has also been critiqued for its lack of structural impact. This paper evaluates the transformative potential of the reasonable accommodation duty encompassed by the Convention, and considers how its potential can be realised. It argues that the duty is transformative because of the substantive equality it provides for individuals, and because it requires both active engagement with persons with disabilities and proactive consideration of barriers to inclusion, in multiple contexts. However, it contends that full realisation of the duty's transformative potential depends on appropriate legislative formulation. This may be a problem in dualist states where application of the Convention is not automatic and pre-existing legislation may be perceived as satisfying the obligation. The paper supports this contention with an analysis of Irish law, arguing that the full transformative potential of the reasonable accommodation duty has not yet been achieved in Ireland, and identifying the reasons for this. The paper examines the practical consequences of inadequate implementation and highlights pitfalls and best practice.
Maternal antioxidant intake during pregnancy and the development of cows’ milk allergy in the offspring
Authors: Tuokkola Jetta , Lamminsalo Anni , Metsälä Johanna , Takkinen Hanna-Mari , Tapanainen Heli , Åkerlund Mari , Niinistö Sari , Toppari Jorma , Ilonen Jorma , Veijola Riitta , Knip Mikael , Kaila Minna , Virtanen Suvi M.
Published: September 2020

Cows’ milk allergy (CMA) is the most common food allergy in young children, and it is often the first manifestation of atopic diseases. Accordingly, very early environmental factors, such as maternal diet during pregnancy, may play a role in the development of CMA, but the evidence is limited. The aim of this study was to investigate the association between maternal intake of antioxidant nutrients during pregnancy and the subsequent development of CMA in the offspring in a prospective, population-based birth cohort within the Finnish Type 1 Diabetes Prediction and Prevention Study. Maternal dietary information during pregnancy was collected with a detailed, validated FFQ. The maternal dietary information and the information on putative confounding factors were available for 4403 children. Information on diagnosed CMA (n 448) was obtained from a medical registry and queried from the parents up to child’s age of 3 years. The Finnish food composition database was used to calculate the average daily intake of nutrients. Logistic regression was applied for statistical analyses, and the nutrient intakes were adjusted for energy intake. OR are presented per 1 sd increment of the particular nutrient intake. Maternal total and dietary intake of β-carotene was associated with an increased risk of CMA in the offspring when adjusted for the putative confounding factors (total OR 1·10, 95 % CI 1·02, 1·20; dietary OR 1·10; 95 % CI 1·01, 1·19). Using dietary supplements containing antioxidants in addition to a balanced diet may not confer any additional benefits.
Domain formation via phase separation for spherical biomembranes with small deformations
Authors: ELLIOTT C. M. , HATCHER L.
Published: September 2020

We derive and analyse an energy to model lipid raft formation on biological membranes involving a coupling between the local mean curvature and the local composition. We apply a perturbation method recently introduced by Fritz, Hobbs and the first author to describe the geometry of the surface as a graph over an undeformed Helfrich energy minimising surface. The result is a surface Cahn–Hilliard functional coupled with a small deformation energy. We show that suitable minimisers of this energy exist and consider a gradient flow with conserved Allen–Cahn dynamics, for which existence and uniqueness results are proven. Finally, numerical simulations show that for the long-time behaviour raft-like structures can emerge and stabilise, and their parameter dependence is further explored.
Increasing dietary fibre intake in healthy adults using personalised dietary advice compared with general advice: a single-blind randomised controlled trial
Authors: Rijnaarts Iris , de Roos Nicole M , Wang Taojun , Zoetendal Erwin G , Top Jan , Timmer Marielle , Bouwman Emily P , Hogenelst Koen , Witteman Ben , de Wit Nicole
Published: September 2020

Objective:

A high-fibre diet is associated with a lower risk for diseases. However, few adults meet the dietary fibre recommendation. Therefore, the effects and acceptance of an algorithm-generated personalised dietary advice (PDA) compared with general advice (GA) on fibre intake were investigated.

Design:

A 6-week, single-blind randomised controlled trial with a 3-month follow-up.

Setting:

PDA was based on habitual intake and provided fibre-rich alternatives using a website; GA contained brochures. Dietary intake was assessed at baseline, week 1, week 6 and 3-month follow-up. Both groups evaluated their advice at week 6. All participants had access to PDA from week 7 until 3-month follow-up.

Participants:

Two groups of healthy adults: PDA (n 34) and GA (n 47). For 3-month follow-up analysis, participants were re-divided into visitors (n 52) and non-visitors (n 26) of the PDA.

Results:

At week 6, energy intake remained stable in both groups, but fibre intake per 1000 kcal increased non-significantly in both groups (PDA = Δ0·5 ± 2·8; GA = Δ0·8 ± 3·1, P = 0·128). Importantly, a significantly higher percentage of PDA participants adhered to the recommendation compared with week 1 (PDA = 21 % increase; GA = 4 % increase, P ≤ 0·001). PDA participants evaluated the advice significantly better compared with GA participants. At 3-month follow-up, fibre intake increased compared with baseline (visitors = Δ2·2 ± 2·6, P < 0·001; non-visitors = Δ1·5 ± 1·9, P = 0·001), but was insignificantly different between groups. Visitors had a decrease and non-visitors had an increase in energy intake (visitors =Δ − 132 ± 525; non-visitors = Δ109 ± 507, P = 0·055).

Conclusions:

The algorithm-generated PDA was well accepted and stimulated adherence to the recommendations more than GA, indicating to be a suitable and cost-efficient method for improving dietary fibre intake in healthy adults.
Deep Water Cycling and the Multi‐Stage Cooling of the Earth
Authors: Seales J. , Lenardic A.
Published: September 2020

Paleo‐temperature data indicates that the Earth's mantle has not cooled at a constant rate. The data show slow cooling from 3.8 to 2.5 Ga followed by more rapid cooling until the present. This has been argued to indicate a transition from a single plate mode to a plate tectonics. However, a tectonic change may not be necessary. Multistage cooling can result from deep water cycling coupled to mantle convection. Melting and volcanism removes water from the mantle (degassing). Dehydration tends to stiffen the mantle, which slows convective vigor and plate velocities causing mantle heating. Higher mantle temperature tends to lower mantle viscosity and increase plate velocities. If these two tendencies are in balance, then mantle cooling can be weak. Breaking this balance, via a switch to net mantle rehydration, can cool the mantle more rapidly. We use coupled water cycling and mantle convection models to test the viability of this hypothesis. Within model and data uncertainty, the hypothesis that deep water cycling can lead to a multi‐stage Earth cooling is consistent with data constraints. Probability distributions, for successful models, indicate that plate and plate margin strength play a minor role for resisting plate motions relative to the resistance from interior mantle viscosity.
A Jovian Magnetodisc Model for the Juno Era
Authors: Connerney J. E. P. , Timmins S. , Herceg M. , Joergensen J. L.
Published: September 2020

The Jovian magnetosphere assumes a disc‐like geometrical configuration (“magnetodisc”) owing to the persistent presence of a system of azimuthal currents circulating in a washer‐shaped volume aligned with, or near, the magnetic equatorial plane. A Voyager era empirical model of the magnetodisc is fitted to vector magnetic field measurements obtained during the Juno spacecraft's first 24 orbits. The best fitting (within 30 Jovian radii) magnetodisc model is characterized by an inner and outer radius of 7.8 and 51.4 Jovian radii, a half‐thickness of 3.6 Jovian radii, with a surface normal at 9.3° from the Jovigraphic pole and 204.2° System 3 west longitude. We supplement the magnetodisc model with a second current system, also confined to the magnetic equatorial plane, consisting of outward radial currents that presumably effect the transfer of angular momentum to outward flowing plasma. Allowing for variation of the magnetodisc's azimuthal and radial current systems from one 53‐day orbit to the next, we develop an index of magnetospheric activity that may be useful in interpretation of variations in auroral observations.
Converting lateral scanning into axial focusing to speed up three-dimensional microscopy
Authors: Chakraborty Tonmoy , Chen Bingying , Daetwyler Stephan , Chang Bo-Jui , Vanderpoorten Oliver , Sapoznik Etai , Kaminski Clemens F. , Knowles Tuomas P. J. , Dean Kevin M. , Fiolka Reto
Published: September 2020

In optical microscopy, the slow axial scanning rate of the objective or the sample has traditionally limited the speed of volumetric imaging. Recently, by conjugating either a movable mirror to the image plane in a remote-focusing geometry or an electrically tuneable lens (ETL) to the back focal plane, rapid axial scanning has been achieved. However, mechanical actuation of a mirror limits the axial scanning rate (usually only 10–100 Hz for piezoelectric or voice coil-based actuators), while ETLs introduce spherical and higher-order aberrations that prevent high-resolution imaging. In an effort to overcome these limitations, we introduce a novel optical design that transforms a lateral-scan motion into a spherical aberration-free axial scan that can be used for high-resolution imaging. Using a galvanometric mirror, we scan a laser beam laterally in a remote-focusing arm, which is then back-reflected from different heights of a mirror in the image space. We characterize the optical performance of this remote-focusing technique and use it to accelerate axially swept light-sheet microscopy by an order of magnitude, allowing the quantification of rapid vesicular dynamics in three dimensions. We also demonstrate resonant remote focusing at 12 kHz with a two-photon raster-scanning microscope, which allows rapid imaging of brain tissues and zebrafish cardiac dynamics with diffraction-limited resolution.
Dissecting clinical heterogeneity of bipolar disorder using multiple polygenic risk scores
Authors: Coombes Brandon J. , Markota Matej , Mann J. John , Colby Colin , Stahl Eli , Talati Ardesheer , Pathak Jyotishman , Weissman Myrna M. , McElroy Susan L. , Frye Mark A. , Biernacka Joanna M.
Published: September 2020

Bipolar disorder (BD) has high clinical heterogeneity, frequent psychiatric comorbidities, and elevated suicide risk. To determine genetic differences between common clinical sub-phenotypes of BD, we performed a systematic polygenic risk score (PRS) analysis using multiple PRSs from a range of psychiatric, personality, and lifestyle traits to dissect differences in BD sub-phenotypes in two BD cohorts: the Mayo Clinic BD Biobank (N = 968) and Genetic Association Information Network (N = 1001). Participants were assessed for history of psychosis, early-onset BD, rapid cycling (defined as four or more episodes in a year), and suicide attempts using questionnaires and the Structured Clinical Interview for DSM-IV. In a combined sample of 1969 bipolar cases (45.5% male), those with psychosis had higher PRS for SCZ (OR = 1.3 per S.D.; p = 3e-5) but lower PRSs for anhedonia (OR = 0.87; p = 0.003) and BMI (OR = 0.87; p = 0.003). Rapid cycling cases had higher PRS for ADHD (OR = 1.23; p = 7e-5) and MDD (OR = 1.23; p = 4e-5) and lower BD PRS (OR = 0.8; p = 0.004). Cases with a suicide attempt had higher PRS for MDD (OR = 1.26; p = 1e-6) and anhedonia (OR = 1.22; p = 2e-5) as well as lower PRS for educational attainment (OR = 0.87; p = 0.003). The observed novel PRS associations with sub-phenotypes align with clinical observations such as rapid cycling BD patients having a greater lifetime prevalence of ADHD. Our findings confirm that genetic heterogeneity contributes to clinical heterogeneity of BD and consideration of genetic contribution to psychopathologic components of psychiatric disorders may improve genetic prediction of complex psychiatric disorders.