bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreatic resection with perioperative drug repurposing of propranolol and etodolac: trial protocol of the phase-II randomised placebo controlled PROSPER trial
Authors: Hüttner Felix J , Rooman Ilse , Bouche Gauthier , Knebel Phillip , Hüsing Johannes , Mihaljevic André L , Hackert Thilo , Strobel Oliver , Büchler Markus W , Diener Markus K
Published: September 2020

Introduction

Pancreatic cancer is the fourth-leading cause of cancer-related death in developed countries. Despite advances in systemic chemotherapy, the mainstay of curative therapy for non-metastatic disease is surgical resection. However, the perioperative period is characterised by stress and inflammatory reactions that can contribute to metastatic spread and disease recurrence. Catecholamines and prostaglandins play a crucial role in these reactions. Therefore, a drug repurposing of betablockers and cyclooxygenase inhibitors seems reasonable to attenuate tumour-associated inflammation by inhibiting psychological, surgical and inflammatory stress responses. This may cause a relevant antitumourigenic and antimetastatic effect during the perioperative period, a window for cancer-directed therapy that is currently largely unexploited.

Methods and analysis

This is a prospective, single-centre, two-arm randomised, patient and observer blinded, placebo-controlled, phase-II trial evaluating safety and feasibility of combined perioperative treatment with propranolol and etodolac in adult patients with non-metastatic cancer of the pancreatic head undergoing elective pancreatoduodenectomy. 100 patients fulfilling the eligibility criteria will be randomised to perioperative treatment for 25 days perioperatively with a combination of propranolol and etodolac or placebo. Primary outcome of interest will be safety in terms of serious adverse events and reactions within 3 months. Furthermore, adherence to trial medication will be assessed as feasibility outcomes. Preliminary efficacy data will be evaluated for the purpose of power calculation for a potential subsequent phase-III trial. The clinical trial is accompanied by a translational study investigating the mechanisms of action of the combined therapy on a molecular basis.

Ethics and dissemination

The PROSPER-trial has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4042875) and the Ethics Committee of the Medical Faculty of the University of Heidelberg (reference number AFmo-385/2018). The final trial results will be published in a peer-reviewed journal and will be presented at appropriate national and international conferences.

Trial registration numbers

DRKS00014054; EudraCT number: 2018-000415-25.
Addressing the high-f problem in pseudo-Nambu–Goldstone boson dark energy models with dark matter–dark energy interaction
Authors: Mukhopadhyay Upala , Paul Avik , Majumdar Debasish
Published: September 2020

We consider a dark energy scenario driven by a scalar field $$\phi $$
ϕ
with a pseudo-Nambu–Goldstone boson (pNGB) type potential $$V(\phi )=\mu ^4 \left( 1+ \mathrm{cos}(\phi /f) \right) $$

V

(
ϕ
)

=

μ
4

1
+
cos
(
ϕ
/
f
)

. The pNGB originates out of breaking of spontaneous symmetry at a scale f close to Planck mass $$M_\mathrm{{pl}}$$

M
pl

. We consider two cases namely the quintessence dark energy model with pNGB potential and the other, where the standard pNGB action is modified by the terms related to Slotheon cosmology. We demonstrate that for this pNGB potential, high-f problem is better addressed when the interaction between dark matter and dark energy is taken into account and that Slotheon dark energy scenario works even better over quintessence in this respect. To this end, a mass limit for dark matter is also estimated.
Fermi motion and medium effects on reaction cross sections of 13,14,15B + C, Al at intermediate and high energies
Authors: Rashdan M. , Abdel-Karim T. A.
Published: September 2020

Analysis of reaction cross sections of [Formula: see text] are performed with Glauber model (GM) including medium modifications arising from Fermi motion and in-medium nucleon–nucleon (NN) total reaction cross section. The density distributions of Boron isotopes are described by a deformed-average Fermi shape, whose proton and neutron radii and deformation parameters are derived from relativistic mean field (RMF), harmonic oscillator (HO) and two-parameter Fermi (2pF). These densities can describe the reaction cross section of Boron isotopes except for [Formula: see text] which is better described by an HO core plus extended Gaussian (HOG) or HO plus a modified Yukawa (HOMY) tail, which depends on the 1n separation energy. It is found that Fermi motion effects dominated at intermediate energy, and they are important to describe the data in addition to in-medium effects. In-medium effects, which are incorporated locally, reduced the reaction cross section by about 3–5% at all energies. [Formula: see text] is confirmed as a one-neutron halo nucleus, where a large extended tail is observed in the extracted HOMY and HOG model densities as well as in the extracted radii, where the matter radius of [Formula: see text] is found to be about 2.92 fm, which is larger than that of [Formula: see text] (2.5 fm) and [Formula: see text] (2.82 fm) predicted using the GM model including Fermi motion and in-medium effects.
Nonlinear vacuum electrodynamics and spontaneous breaking of Lorentz symmetry
Authors: Escobar C. A. , Potting R.
Published: September 2020

We study spontaneous breaking of Lorentz symmetry in nonlinear vacuum electrodynamics. Using a first-order formulation of the latter proposed by Plebański, we apply a Dirac constraint analysis and derive an effective Hamiltonian. We show that there exists a large class of potentials for which the effective Hamiltonian is bounded from below, while at the same time possessing local minima in which the field strength acquires a nonzero vacuum expectation value, thereby breaking Lorentz invariance spontaneously. These possible vacua can be classified in four classes, depending on the way Lorentz symmetry is broken. We show that the small field fluctuations around these vacua involve modes for which the dynamics can develop degeneracies, resulting in shock-wave-like and/or superluminal motion. Finally, we study the physical applicability of these models, and show how the Lorentz breaking vacua might in principle be detected by coupling the model to a suitable external current, or to gravity.
Optimization of Aluminium Doping Concentration in Titanium Dioxide Nanoparticles Photo Anode for Enhancing Efficiency of Dye-Sensitized Solar Cell
Authors: Kulkarni Swati S. , Bodkhe Gajanan A. , Sayyad Pasha W. , Deshmukh Megha A. , Hussaini S. S. , Shirsat Mahendra D.
Published: September 2020

Well crystallized Aluminium (Al) doped Titanium dioxide (TiO2) nanoparticles with various doping concentration (0, 0.05[Formula: see text]M, 0.07[Formula: see text]M, 0.09[Formula: see text]M and 0.11[Formula: see text]M) were synthesized successfully by sol–gel route to develop the photo anode of Dye Sensitized Solar Cell (DSSC). Anatase crystalline nature of TiO2 nanoparticles was confirmed using X-ray diffraction (XRD) and Raman spectrophotometer. The Atomic Force Microscopy (AFM) was used to investigate the morphology of the photo anode (Al-doped TiO2 nanoparticles). The photovoltaic performance of the DSSC in terms of Current, Voltage and efficiency was investigated with a standard illumination of AM1.5G having an irradiance 100[Formula: see text]mW/cm2. Optimized values of Short Circuit Current density ([Formula: see text]), Open Circuit Voltage ([Formula: see text]) and efficiency ([Formula: see text]) obtained was 247.62[Formula: see text][Formula: see text]A/cm2, 359[Formula: see text]mV and 0.02456%, respectively for 0.07[Formula: see text]M Al doping concentration. Eco-friendly Eosin Y dye was used for sensitization of the photo anode. The optimized photovoltaic cell exhibits very good efficiency (80.05% more than the earlier reported work).
Optimal Control of Fractional Order COVID-19 Epidemic Spreading in Japan and India 2020
Authors: Das Meghadri , Samanta G. P.
Published: September 2020

In Japan, the first case of Coronavirus disease 2019 (COVID-19) was reported on 15th January 2020. In India, on 30th January 2020, the first case of COVID-19 in India was reported in Kerala and the number of reported cases has increased rapidly. The main purpose of this work is to study numerically the epidemic peak for COVID-19 disease along with transmission dynamics of COVID-19 in Japan and India 2020. Taking into account the uncertainty due to the incomplete information about the coronavirus (COVID-19), we have taken the Susceptible-Asymptomatic-Infectious-Recovered (SAIR) compartmental model under fractional order framework for our study. We have also studied the effects of fractional order along with other parameters in transfer dynamics and epidemic peak control for both the countries. An optimal control problem has been studied by controlling social distancing parameter.
MEG
Authors: Zhang Jialiang , Zha Yue , Beckwith Nicholas , Liu Bangya , Li Jing
Published: September 2020

Emerging three-dimensional (3D) memory technologies, such as the Hybrid Memory Cube (HMC) and High Bandwidth Memory (HBM), provide high-bandwidth and massive memory-level parallelism. With the growing heterogeneity and complexity of computer systems (CPU cores and accelerators, etc.), efficiently integrating emerging memories into existing systems poses new challenges and requires detailed evaluation in a realistic computing environment. In this article, we propose MEG, an open source, configurable, cycle-exact, and RISC-V-based full-system emulation infrastructure using FPGA and HBM. MEG provides a highly modular hardware design and includes a bootable Linux image for a realistic software flow, so that users can perform cross-layer software-hardware co-optimization in a full-system environment. To improve the observability and debuggability of the system, MEG also provides a flexible performance monitoring scheme to guide the performance optimization. The proposed MEG infrastructure can potentially benefit broad communities across computer architecture, system software, and application software. Leveraging MEG, we present two cross-layer system optimizations as illustrative cases to demonstrate the usability of MEG. In the first case study, we present a reconfigurable memory controller to improve the address mapping of standard memory controller. This reconfigurable memory controller along with its OS support allows us to optimize the address mapping scheme to fully exploit the massive parallelism provided by the emerging three-dimensional (3D) memories. In the second case study, we present a lightweight IOMMU design to tackle the unique challenges brought by 3D memory in providing virtual memory support for near-memory accelerators. We provide a prototype implementation of MEG on a Xilinx VU37P FPGA and demonstrate its capability, fidelity, and flexibility on real-world benchmark applications. We hope MEG fills a gap in the space of publicly available FPGA-based full-system emulation infrastructures, specifically targeting memory systems, and inspires further collaborative software/hardware innovations.
Computing Autotopism Groups of Partial Latin Rectangles
Authors: Stones Rebecca J. , Falcón Raúl M. , Kotlar Daniel , Marbach Trent G.
Published: September 2020

Computing the autotopism group of a partial Latin rectangle (PLR) can be performed in multiple ways. This study has two aims: comparing some of these methods experimentally to identify those that are competitive; and identifying design goals for developing practical software. We compare six families of algorithms (two backtracking and four graph-theoretic methods), with and without using entry invariants (EIs), in a range of settings. Two EIs are considered: frequencies of row, column, and symbol representatives; and 2 × 2 submatrices. The best approach to computing autotopism groups varies.

When PLRs have many autotopisms (such as having very few entries or being a group table), the McKay, Meynert, and Myrvold (MMM) method computes generators for the autotopism group efficiently. (The MMM method is the standard way to compute autotopisms.) Otherwise, PLRs ordinarily have trivial or small autotopism groups, and the task is to verify this. The so-called PLR graph method is slightly more efficient in this setting than the MMM method (in some circumstances, around twice as fast).

With an intermediate number of entries, the quick-to-compute strong EIs are effective at reducing the need for computation without introducing significant overhead. With a full or almost-full PLR, a more sophisticated EI is needed to reduce down-the-line computation.

These results suggest a hybrid approach to computing autotopism groups: The software decides on suitable EIs based on the input; and the user chooses between the MMM or the PLR graph methods, depending on their dataset.

This article expands the authors’ previous article
Computing autotopism groups of PLRs: a pilot study
.
Notary
Authors: Athalye Anish , Belay Adam , Kaashoek M. Frans , Morris Robert , Zeldovich Nickolai
Published: September 2020

Notary is a new design for a hardware wallet, a device that is used to perform sensitive transactional operations like cryptocurrency transfers. Notary aims to be more secure than past hardware wallets by eliminating classes of bugs by design and by formally proving the correctness of the key operation used in its implementation. We built a physical prototype of Notary and showed that it achieves functionality similar to existing hardware wallets while avoiding many bugs that affect them.
Sputtered Nickel Oxide Thin Films on n-Si(100)/SiO2 Surfaces for Photo-Electrochemical Oxygen Evolution Reaction (OER): Impact of Deposition Temperature on OER Performance and on Composition before and after OER
Authors: Fingerle M. , Tengeler S. , Calvet W. , Jaegermann W. , Mayer T.
Published: September 2020

Magnetron sputtered nickel oxide thin films deposited on the native oxide of crystalline n-Si(100) wafers are studied in dependence of the substrate deposition temperature (600 °C, 400 °C, 200 °C, and room temperature) using X-ray and synchrotron excited photoemission spectroscopy as well as cyclic-voltammetry under illumination. We show that the substrate temperature during nickel oxide sputtering governs the composition of the pristine NiOx film and the OER performance. Two dedicated nickel oxide species are found with Ni2+ corresponding to stoichiometric NiO while Ni3+ indicates an oxygen rich NiOx (x > 1) phase. With decreasing deposition temperature, the ratio of Ni3+/Ni2+ in the pristine NiOx film increases. Information depth dependent synchrotron related photoemission spectroscopy further suggests that oxygen rich NiOx is found on top of the surface and at the grain boundaries. The OER onset potential improves from 1.55 V to 1.1 V in correlation to an increasing Ni3+/Ni2+ ratio in the pristine NiOx film and an increasing emission from a nickel oxyhydroxide phase (h-NiOx) after photo-assisted cyclic-voltammetry in alkaline solution. Upon electrochemical treatment, a reconditioning process is observed with the formation of h-NiOx that consists of Ni(OH)2 and NiOOH, while NiOx disappears.
Vitamin D supplementation as a rational pharmacological approach in the COVID-19 pandemic
Authors: Ferder León , Martín Giménez Virna Margarita , Inserra Felipe , Tajer Carlos , Antonietti Laura , Mariani Javier , Manucha Walter
Published: September 2020

The COVID-19 pandemic has reached most of the countries worldwide causing death, which often results from an inflammatory storm associated with severe acute respiratory syndrome (SARS). This has prompted researchers to seek specific novel and definitive treatments urgently. In this context, it is interesting to evaluate the preventive and therapeutic effects of existing pharmacological agents that could be useful. In this regard, vitamin D supplementation, particularly in individuals likely to be deficient, may be a promising option. Vitamin D is a hormone that modulates many of the same inflammatory and oxidative signaling pathways triggered during COVID-19. For example, vitamin D suppresses the actions of the renin-angiotensin system, which has a determining role in the pathophysiology of the inflammatory response related to COVID-19. This paper analyzes the evidence that vitamin D supplementation might be a valuable preventive/therapeutic measure in groups at risk for or infected with COVID-19. It also discusses how clinical studies could be best designed to evaluate the possible advantages of vitamin D supplementation for the benefit of public health during the pandemic.
Sex steroids skew ACE2 expression in human airway: a contributing factor to sex differences in COVID-19?
Authors: Kalidhindi Rama Satyanarayana Raju , Borkar Niyati A. , Ambhore Nilesh Sudhakar , Pabelick Christina M. , Prakash Y. S. , Sathish Venkatachalem
Published: September 2020

The incidence, severity, and mortality of ongoing coronavirus infectious disease 19 (COVID-19) is greater in men compared with women, but the underlying factors contributing to this sex difference are still being explored. In the current study, using primary isolated human airway smooth muscle (ASM) cells from normal males versus females as a model, we explored the effect of estrogen versus testosterone in modulating the expression of angiotensin converting enzyme 2 (ACE2), a cell entry point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using confocal imaging, we found that ACE2 is expressed in human ASM. Furthermore, Western analysis of ASM cell lysates showed significantly lower ACE2 expression in females compared with males at baseline. In addition, ASM cells exposed to estrogen and testosterone for 24 h showed that testosterone significantly upregulates ACE2 expression in both males and females, whereas estrogen downregulates ACE2, albeit not significant compared with vehicle. These intrinsic and sex steroids induced differences may help explain sex differences in COVID-19.
On the origin of finger enslaving: control with referent coordinates and effects of visual feedback
Authors: Abolins Valters , Stremoukhov Alex , Walter Caroline , Latash Mark L.
Published: September 2020

We report a consistent slow increase in finger enslaving (force production by noninstructed fingers) when visual feedback was presented on the force produced by either two instructed fingers or two noninstructed fingers of the hand. In contrast, force drifts could be in opposite directions depending on the visual feedback. We interpret enslaving and its drifts at the level of control with referent coordinates for the involved muscles, possibly reflecting spread of cortical excitation.
Minimally invasive neural stimulation with a novel ultra-sensitive step function opsin: implications and future directions
Authors: Lawrence Aamna , Chang Hui Ho Vanessa
Published: September 2020

Optogenetics has become a popular tool to probe the link between neural circuits and behavior, since the technique was first introduced in 2005. Recently, Gong et al. (Gong X, Mendoza-Halliday D, Ting JT, Kaiser T, Sun X, Bastos AM, Wimmer RD, Guo B, Chen Q, Zhou Y, Pruner M, Wu CWH, Park D, Deisseroth K, Barak B, Boyden ES, Miller EK, Halassa MM, Fu Z, Bi G, Desimone R, Feng G. Neuron 107: 38–51, 2020) developed an ultra-sensitive step-function opsin capable of activating any region of the mouse brain and cortical areas in macaques with external illumination, thus aiming toward minimally invasive light delivery. In this article, we highlight and discuss the new opsin's potential in nonhuman primate research.
Wild Bitter Melon Exerts Anti-Inflammatory Effects by Upregulating Injury-Attenuated CISD2 Expression following Spinal Cord Injury
Authors: Kung Woon-Man , Lin Chai-Ching , Kuo Chan-Yen , Juin Yu-Ching , Wu Po-Ching , Lin Muh-Shi , Klivényi Péter
Published: September 2020

Background. Spinal cord injuries (SCIs) induce secondary neuroinflammation through astrocyte reactivation, which adversely affects neuronal survival and eventually causes long-term disability. CDGSH iron sulfur domain 2 (CISD2), which has been reported to be involved in mediating the anti-inflammatory responses, can serve as a target in SCI therapy. Wild bitter melon (WBM; Momordica charantia Linn. var. abbreviata Ser.) contains an anti-inflammatory agent called alpha-eleostearic acid (α-ESA), a peroxisome proliferator-activated receptor-β (PPAR-β) ligand. Activated PPAR-β inhibits the nuclear factor κB (NF-κB) signaling pathway via the inhibition of IκB (inhibitor of NF-κB) degradation. The role of astrocyte deactivation and CISD2 in anti-inflammatory mechanisms of WBM in acute SCIs is unknown. Materials and Methods. A mouse model of SCI was generated via spinal cord hemisection. The SCI mice were administered WBM intraperitoneally (500 mg/kg bodyweight). Lipopolysaccharide- (LPS-) stimulated ALT cells (astrocytes) were used as an in vitro model for studying astrocyte-mediated inflammation post-SCI. The roles of CISD2 and PPAR-β in inflammatory signaling were examined using LPS-stimulated SH-SY5Y cells transfected with si-CISD2 or scramble RNA. Results. WBM mitigated the SCI-induced downregulation of CISD2, PPAR-β, and IκB and upregulation of glial fibrillary acidic protein (GFAP; marker of astrocyte reactivation) in the spinal cord of SCI mice. Additionally, WBM (1 μg/mL) mitigated LPS-induced CISD2 downregulation. Furthermore, SH-SY5Y neural cells with CISD2 knockdown exhibited decreased PPAR-β expression and augmented NF-κB signaling. Conclusion. To the best of our knowledge, this is the first study to report that CISD2 is an upstream modulator of the PPAR-β/NF-κB proinflammatory signaling pathway in neural cells, and that WBM can mitigate the injury-induced downregulation of CISD2 in SCI mice and LPS-stimulated ALT astrocytes.
Laboratory Study of Flocculation and Pressure Filtration Dewatering of Waste Slurry
Authors: Min Fanlu , Wang Dengfeng , Du Jiarui , Song Hangbiao , Wang Yucheng , Lv Huanjie , Ma Jiawei
Published: September 2020

In the process of large‐scale urban construction, large amounts of waste slurry are produced. The slurry has a high water content and is difficult to precipitate naturally, resulting in low treatment efficiency. To improve the treatment efficiency of slurry, a variety of inorganic and organic polymer flocculants were used to carry out flocculation settlement tests on the slurry. The changes in the slurry properties and the filtration dewatering effect after flocculation were tested. The results show that the addition of flocculant makes the slurry particles form aggregates, which leads to rapid precipitation of the slurry. The use of an inorganic flocculant significantly reduced the zeta potential of the slurry. Organic polymer flocculant, however, had little effect on the slurry potential, but did cause the slurry to produce larger size aggregates, resulting in a better flocculation effect than inorganic flocculant. Inorganic flocculants and organic flocculants can improve the pressure filtration dewatering performance of slurry. CPAM12 (cationic polyacrylamide, with a relative molecular weight of 12 million Daltons) had the best overall effect. The formation of aggregates after flocculation and the change in the nonuniformity coefficient (Cu) were the main cause of improvement of pressure filtration dewatering performance of the slurry. When Cu decreases from 11.85 to 8.75, the time required for pressure filtration stabilization is shortened by 70%. The nonuniformity coefficient of flocculated slurry can be used to evaluate flocculants, determine the optimal dosage, and predict the dewatering effect.
Control of Coexisting Attractors with Preselection of the Survived Attractor in Multistable Chua’s System: A Case Study
Authors: Njitacke Zeric Tabekoueng , Fozin Theophile Fonzin , Tchapga Christian Tchito , Leutcho Gervais Dolvis , Wouapi K. Marcel , Kengne Jacques , Loredo-Villalobos Carlos-Arturo
Published: September 2020

Although the control of multistability has already been reported, the one with preselection of the desired attractor is still uncovered in systems with more than two coexisting attractors. This work reports the control of coexisting attractors with preselection of the survived attractors in paradigmatic Chua’s system with smooth cubic nonlinearity. Techniques of linear augmentation combined to system invariant parameters like equilibrium points are used to choose the desired surviving attractors among the coexisting ones. Nonlinear dynamical tools including bifurcation diagrams, standard Lyapunov exponents, phase portraits, and cross section of initial conditions are exploited to reveal the selection scenarios of the survived attractor in the multistability control process of Chua’s system. The main crisis towards annihilation of multistability in Chua’s system when varying the coupling strength is interior crisis and border collision. Theoretical and numerical results obtained are further validated with PSpice analysis.
Radiation Induces Pulmonary Fibrosis by Promoting the Fibrogenic Differentiation of Alveolar Stem Cells
Authors: Wang Lu-Kai , Wu Tsai-Jung , Hong Ji-Hong , Chen Fang-Hsin , Yu John , Wang Chun-Chieh , Ballini Andrea
Published: September 2020

The lung is a radiosensitive organ, which imposes limits on the therapeutic dose in thoracic radiotherapy. Irradiated alveolar epithelial cells promote radiation-related pneumonitis and fibrosis. However, the role of lung stem cells (LSCs) in the development of radiation-induced lung injury is still unclear. In this study, we found that both LSCs and LSC-derived type II alveolar epithelial cells (AECII) can repair radiation-induced DNA double-strand breaks, but the irradiated LSCs underwent growth arrest and cell differentiation faster than the irradiated AECII cells. Moreover, radiation drove LSCs to fibrosis as shown with the elevated levels of markers for epithelial-mesenchymal transition and myofibroblast (α-smooth muscle actin (α-SMA)) differentiation in in vitro and ex vivo studies. Increased gene expressions of connective tissue growth factor and α-SMA were found in both irradiated LSCs and alveolar cells, suggesting that radiation could induce the fibrogenic differentiation of LSCs. Irradiated LSCs showed an increase in the expression of surfactant protein C (SP-C), the AECII cell marker, and α-SMA, and irradiated AECII cells expressed SP-C and α-SMA. These results indicated that radiation induced LSCs to differentiate into myofibroblasts and AECII cells; then, AECII cells differentiated further into either myofibroblasts or type I alveolar epithelial cells (AECI). In conclusion, our results revealed that LSCs are sensitive to radiation-induced cell damage and may be involved in radiation-induced lung fibrosis.
Effectiveness of the Healthy Lifestyle Promotion Program for Yaquis with Obesity and Risk of Diabetes in the Short and Medium Term: A Translational Study
Authors: Castro-Juarez Alejandro Arturo , Serna-Gutiérrez Araceli , Dórame-López Norma Alicia , Solano-Morales Mariela , Gallegos-Aguilar Ana Cristina , Díaz-Zavala Rolando Giovanni , Alemán-Mateo Heliodoro , Urquidez-Romero Rene , Campa-Quijada Fernanda , Valenzuela-Guzmán Diana Marcela , Esparza-Romero Julián , Cardoso Claudia
Published: September 2020

Type 2 diabetes (T2D) is a public health problem worldwide, and the main risk factor for its development is obesity. The Yaqui ethnic group of Sonora has serious obesity problems, resulting in an increased risk of T2D in its inhabitants. The objective of this study was to evaluate the effectiveness of a health promotion program on obesity parameters and cardiovascular risk factors in short- (6 months) and medium-term periods (12 months) in indigenous Yaquis of Sonora. The design is a translational clinical study of a single cohort with prepost intervention measurements in a sample of 93 subjects. The effectiveness of the program was evaluated by comparing obesity parameters, metabolic markers, and physical activity 6 and 12 months with those measured under basal conditions using a paired

t

-test or Wilcoxon rank-sum test. The short-term retention percentage was 58.0%. There was a decrease in body weight (

Δ
=
−
3.9
 
kg

,

p
≤
0.05

) and other obesity parameters, and an increase in physical activity and improvements in metabolic markers (

p
≤
0.05

) was observed. Similar findings were obtained for the medium-term period; body weight loss was also -3.9 kg (

p
≤
0.05

). The short and medium-term results of the program showed improvements in the obesity parameters and other cardiovascular risk factors of the participants. These results support the effectiveness of the program and its translation in this ethnic group.
A Novel Variant in the Calcium-Sensing Receptor Associated with Familial Hypocalciuric Hypercalcemia and Low-to-Normal PTH
Authors: Majumdar Sachin K. , Jacob Tess , Bale Allen , Bailey Allison , Kwon Jeffrey , Hughes Terence , Barbieri Andrea L. , Laskin William , Cohen Paul , Carling Tobias John Eric
Published: September 2020

Familial hypocalciuric hypercalcemia (FHH) is considered a relatively benign condition characterized by mild elevations in serum calcium and relatively low urinary calcium excretion. It results from an elevated set point in serum calcium arising from variants in the calcium-sensing receptor (CaSR) gene but also AP2S1 and GNA11 genes, which encode for adaptor-related protein complex 2 and G11 proteins, respectively. The manifestations of FHH can vary and sometimes overlap with primary hyperparathyroidism making the diagnosis challenging. Case Presentations. We report a mother and daughter with a novel heterozygous variant in the CaSR gene resulting in a serine to leucine substitution at position 147 (S147L) of the CaSR. Both patients had mild hypercalcemia, relatively low urinary calcium excretion, elevated calcitriol, and low-to-normal intact PTH. The proband (daughter) presented with symptoms associated with hypercalcemia and was incidentally found to have a bony lesion suspicious for osteitis fibrosa cystica, and she was also diagnosed with sarcoidosis. Subtotal parathyroidectomy revealed normal-weight parathyroid glands comprised of 50–80% parathyroid epithelial cells, which has been documented as within the spectrum of normal. Her mother had no symptoms, and no intervention was pursued. Conclusion. We report a novel variant in the CaSR associated with FHH in two patients with similar biochemical features yet differing clinical manifestations. While the relationship of the bony findings and parathyroid histology with this variant remains unclear, these cases enrich our knowledge of CaSR physiology and provide further examples of how varied the manifestations of FHH can be.
Typhoon Vulnerability Analysis in South Korea Utilizing Damage Record of Typhoon Maemi
Authors: Kim Ji-Myong , Son Kiyoung , Yum Sang-Guk , Ahn Sungjin
Published: September 2020

The purpose of this research is to identify the indicators of typhoon damage and develop a metric for typhoon vulnerability functions employing the losses associated with Typhoon Maemi. Typhoons cause significant financial damages worldwide every year. Federal and local governments, insurance companies, and construction companies strive to develop typhoon risk assessment models and use them to quantify the risks so that they can avoid, mitigate, or transfer the financial risks. Therefore, typhoon risk assessment modeling is becoming increasingly important, and in order to achieve a sophisticated evaluation, it is also important to reflect more specified and local vulnerabilities. Although several previous studies on economic loss associated with natural catastrophe have identified essential risk indicators, there has been a shortage of more specific research studies focusing on the correlation between vulnerability and economic loss caused by typhoons. In order to fill this gap, this study collected and analyzed the actual loss record of Typhoon Maemi collected and accumulated by a major insurance company in Korea. In order to create the vulnerability functions and to identify the natural hazard indicators and basic building information indicators, information from the insurance record was used in the analysis. The results and metric of this research provide a pragmatic approach that helps create vulnerability functions for abovementioned sectors and like estimating local vulnerabilities and predicting and coping with the possible damage and loss from typhoons.
Isolation and Characterization of Multipotent Canine Urine-Derived Stem Cells
Authors: Xu Yan , Zhang Tao , Chen Yang , Shi Qiang , Li Muzhi , Qin Tian , Hu Jianzhong , Lu Hongbin , Liu Jun , Chen Can
Published: September 2020

Current cell-based therapies on musculoskeletal tissue regeneration were mostly determined in rodent models. However, a direct translation of those promising cell-based therapies to humans exists a significant hurdle. For solving this problem, canine has been developed as a new large animal model to bridge the gap from rodents to humans. In this study, we reported the isolation and characterization of urine-derived stem cells (USCs) from mature healthy beagle dogs. The isolated cells showed fibroblast-like morphology and had good clonogenicity and proliferation. Meanwhile, these cells positively expressed multiple markers of MSCs (CD29, CD44, CD90, and CD73), but negatively expressed for hematopoietic antigens (CD11b, CD34, and CD45). Additionally, after induction culturing, the isolated cells can be differentiated into osteogenic, adipogenic, chondrogenic, and tenogenic lineages. The successful isolation and verification of USCs from canine were useful for studying cell-based therapies and developing new treatments for musculoskeletal injuries using the preclinical canine model.
Specific Mechanisms of Chromosomal Instability Indicate Therapeutic Sensitivities in High-Grade Serous Ovarian Carcinoma
Authors: Tamura Naoka , Shaikh Nadeem , Muliaditan Daniel , Soliman Tanya N. , McGuinness Jennifer R. , Maniati Eleni , Moralli Daniela , Durin Mary-Anne , Green Catherine M. , Balkwill Frances R. , Wang Jun , Curtius Kit , McClelland Sarah E.
Published: September 2020

Chromosomal instability (CIN) comprises continual gain and loss of chromosomes or parts of chromosomes and occurs in the majority of cancers, often conferring poor prognosis. Because of a scarcity of functional studies and poor understanding of how genetic or gene expression landscapes connect to specific CIN mechanisms, causes of CIN in most cancer types remain unknown. High-grade serous ovarian carcinoma (HGSC), the most common subtype of ovarian cancer, is the major cause of death due to gynecologic malignancy in the Western world, with chemotherapy resistance developing in almost all patients. HGSC exhibits high rates of chromosomal aberrations and knowledge of causative mechanisms would represent an important step toward combating this disease. Here we perform the first in-depth functional characterization of mechanisms driving CIN in HGSC in seven cell lines that accurately recapitulate HGSC genetics. Multiple mechanisms coexisted to drive CIN in HGSC, including elevated microtubule dynamics and DNA replication stress that can be partially rescued to reduce CIN by low doses of paclitaxel and nucleoside supplementation, respectively. Distinct CIN mechanisms indicated relationships with HGSC-relevant therapy including PARP inhibition and microtubule-targeting agents. Comprehensive genomic and transcriptomic profiling revealed deregulation of various genes involved in genome stability but were not directly predictive of specific CIN mechanisms, underscoring the importance of functional characterization to identify causes of CIN. Overall, we show that HGSC CIN is complex and suggest that specific CIN mechanisms could be used as functional biomarkers to indicate appropriate therapy.

Significance:

These findings characterize multiple deregulated mechanisms of genome stability that lead to CIN in ovarian cancer and demonstrate the benefit of integrating analysis of said mechanisms into predictions of therapy response.
Is There Any Correlation between Spread of Excitation Width and the Refractory Properties of the Auditory Nerve in Cochlear Implant Users?
Authors: Coutinho da Silva Juliana , Schmidt Goffi-Gomez Maria Valéria , Tsuji Robinson Koji , Bento Ricardo , Brito Neto Rubens
Published: September 2020

Background: The spread of excitation (SOE) and auditory nerve recovery function (REC) are objective measures recorded by neural response telemetry and may interfere in cochlear implant (CI) stimulation. Objective: To analyze and correlate SOE with the refractory periods in subjects with pre- and postlingual deafness implanted with different electrode arrays. Methods: This was a retrospective study of 323 ears separated by perimodiolar or straight arrays and by pre- or postlingually deaf recipients. Measures were collected intraoperatively on electrode 11. The SOE width was measured in millimeters at the 0.75 point of the curve, and the relative (tau) and absolute (t0) refractory periods were measured in microseconds. Results: There was a statistical correlation between the SOE and the t0 in the patients with postlingual deafness implanted with the perimodiolar array. The SOE width was statistically different between the straight and perimodiolar arrays and between the pre- and postlingual groups in the perimodiolar array. Tau was statistically different between the pre- and postlingual groups with the straight array and the t0, between the pre- and postlingual groups with the perimodiolar array. Neural response threshold and amplitude of the neural response were not statistically different among groups. Conclusion: There was a correlation between SOE width and t0 only in patients with acquired deafness. The findings suggest that different factors influence SOE and REC, considering SOE is different according to the electrode array and REC being different according the onset of deafness.
Prevalence and Treatment Outcomes of Marine-Lenhart Syndrome in Japan
Authors: Danno Hirosuke , Nishihara Eijun , Kousaka Kazuyoshi , Nakamura Tomohiko , Kasahara Toshihiko , Kudo Takumi , Ito Mitsuru , Fukata Shuji , Nishikawa Mitsushige , Miyauchi Akira
Published: September 2020

Introduction: Marine-Lenhart syndrome (MLS) is now understood to be a combination of Graves’ disease and autonomously functioning thyroid nodule(s) (AFTNs). The prevalence of the syndrome and suitable treatments for those living in iodine-sufficient areas are uncertain. Objectives: We aimed to investigate the prevalence, treatment, and prognosis of MLS in Japan, an iodine-sufficient area. Methods: This study involved patients who visited our hospital between February 2005 and August 2019. Among patients with both thyrotoxicosis and thyroid nodule(s) larger than 10 mm, MLS and isolated AFTNs were diagnosed based on serum thyroid-stimulating hormone receptor antibody levels and scintigraphy using radioiodine or technetium-99m and thyroid uptake. Results: Twenty-two patients were found to have MLS, compared to 372 with isolated AFTNs and 8,343 with Graves’ disease, during the period. Therefore, the rate of MLS cases was 0.26% among all patients with Graves’ disease (22/8,343). Treatments and outcomes were assessed for cases of MLS (n = 18) and isolated AFTNs (n = 269). Antithyroid drugs (ATDs) were withdrawn in 27.8% of cases in the MLS group and 10.3% in the isolated AFTN group. There was no significant difference in the clinical outcome after ATD withdrawal between the 2 groups. However, the rate of hypothyroidism after radioactive iodine (RAI) administration was significantly higher in the MLS group than in the isolated AFTN group (42.9 vs. 9.0%, p = 0.005) despite similar doses of RAI. Conclusions: The prevalence of MLS among patients with Graves’ disease was 0.26% in Japan. RAI therapy induces hypothyroidism more frequently than in those with AFTNs probably because RAI is taken up in the surrounding Graves’ tissues.
Hypercalcemia Associated with Extramammary Paget’s Disease
Authors: Sato Tetsuko , Wada Yoshihisa , Kamitani Nobuhiko , Yamamoto Takenobu , Aoyama Yumi , Fujimoto Wataru , Tanaka Ryo
Published: September 2020

Hypercalcemia of malignancy occurs in up to one third of patients at some point during the course of their advanced stage. The majority of them is caused by humoral hypercalcemia of malignancy due to systemic secretion of parathyroid hormone–related protein (PTHrP) by tumor cells. Extramammary Paget’s disease is a slow-growing cutaneous malignancy commonly limited to the epidermis of the anogenital region, but rarely becomes invasive and metastatic to distant sites. Herein, we report a 70-year-old male patient with metastatic extramammary Paget’s disease. He consulted our hospital with altered consciousness and tumor in his genital area. Physical examination revealed erythematous plaque with a tumor on the scrotum and perineum. It was diagnosed as extramammary Paget’s disease (multiple liver metastases and multiple lymph node metastases by skin biopsy and image examination). Increases in serum-corrected calcium and PTHrP-intact levels (15.3 mg/dL and 66.1 pg/L, respectively) were confirmed. PTHrP immunohistochemistry showed positive staining in the tumor cells. We diagnosed humoral hypercalcemia of malignancy. We treated hypercalcemia with saline, furosemide, zoledronic acid, and elcatonin. Regarding the local control of the tumor, 30 Gy/10 Fr electron beam therapy was performed. However, treatment with zoledronic acid was only temporally effective to correct hypercalcemia, and an increased serum calcium level developed again. Concurrently, the liver metastases were rapidly enlarged, and his general condition gradually deteriorated. The patient died on day 55. When patients with extramammary Paget’s disease show unconsciousness, serum calcium level should be measured and PTHrP-producing tumor distinguished.
Diffuse Neuromatosis of Intrahepatic and Extrahepatic Bile Ducts as a Rare Cause of Jaundice
Authors: Vassos Nikolaos , Perrakis Aristotelis , Schmid Axel , Croner Roland S. , Gruetzmann Robert , Agaimy Abbas
Published: September 2020

Background: Neuroma of the biliary tree is extremely rare with no more than 100 cases reported so far. They mostly present with obstructive jaundice and have been commonly described after surgery or abdominal trauma. Although involvement of the extrahepatic bile duct is far more common, occurrence in the intrahepatic ducts has not so far been reported. Case Report: We describe 3 cases of diffuse biliary tree neuroma affecting 3 females aged 53–68 years. None had a history of neurofibromatosis type1. All presented with progressive obstructive jaundice with no evidence of gallstones. A history of previous surgery was noted in 2 patients. Initial impression on clinical and imaging examination was highly suspicious for bile duct carcinoma in 2 patients. Histology showed diffuse neuromatous proliferation replacing and thickening the bile duct walls. The third patient had concurrent neuroma and recurrent cholangiocarcinoma causing great clinical confusion as initial biopsy showed only benign neuroma, but CA 19-9 was steadily increasing, necessitating a second biopsy which then confirmed recurrent carcinoma. Conclusion: This uncommon cause of long-distance bile duct stenosis and progressive jaundice should be included in the differential diagnosis of bile duct neoplasms, in particular when there is a previous surgical history in this abdominal region.
Early Selective C-Reactive Protein Apheresis in a Patient with Acute ST Segment Elevation Myocardial Reinfarction
Authors: Milosevic Maja , Balint Bela , Boskovic Srdjan , Bojic Milovan , Nikolic Aleksandra , Otasevic Petar
Published: September 2020

The patient was admitted for urgent coronary angiography following an acute anterior ST segment elevation myocardial reinfarction (STEMI) caused by acute stent thrombosis. A stent had been implanted 10 days prior to the reinfarction for an acute anterior STEMI. However, the patient had stopped taking ticagrelor post-discharge. Primary percutaneous coronary intervention of the left anterior descending artery was performed. Subsequently, due to a high C-reactive protein (CRP) level, 3 CRP apheresis sessions were performed, with the first session starting 12 h after the onset of symptoms. A significant drop in CRP was noted after each apheresis. The post-procedural course was uneventful.
Eye injuries due to private fireworks and firecrackers
Authors: Gabel-Pfisterer Ameli , Böhringer Daniel , Agostini Hansjuergen
Published: September 2020

Background: On festive days worldwide eyes are severely injured by fireworks. The data on the number and severity are to date not registered in Germany. Objective: How frequent are firework-induced injuries in Germany, who are the affected, how serious are the injuries, which forms of treatment are necessary and how frequent are accompanying injuries? Method: A German nationwide online-based survey was carried out in all inpatient eye departments and data over the last 3 consecutive years were descriptively analyzed. Results: From New Years Eve 2016/2017, when 41 eye departments sent in data, the participation could be increased to 51 eye departments in 2018/2019. More than one third (33–39%) of all 1356 patients over 3 years were minors, 60% were younger than 25 years old and roughly 60% of patients were injured as bystanders or in an unclear situation. In total 25% of all eye injuries were considered severe and required inpatient treatment. Accompanying injuries of the other eye, the face and hands were more frequent in minors than in adults. Eyeball ruptures were reported in 10 minors and 38 adults over the 3 years. Summary: Particularly minors and bystanders need better protection.
Unifocal versus Multiple Ileal Neuroendocrine Tumors Location: An Embryological Origin
Authors: Kalifi Maroin , Walter Thomas , Milot Laurent , Hervieu Valérie , Millot Ingrid , Gibert Benjamin , Roche Colette , Forestier Julien , Lombard-Bohas Catherine , Pasquer Arnaud , Poncet Gilles
Published: September 2020

Introduction: Small-intestinal neuroendocrine tumors (SI-NET) are situated preferentially within the ileum. The aim was to describe a potential difference in location between unifocal and multiple ileal-NET. Patients and Methods: Between December 2010 and December 2019, all consecutive patients who underwent resection in our European Neuroendocrine Tumor Society Center of Excellence, of at least 1 non-duodenal SI-NET, were retrospectively included. The main objective was to prove that multiple ileal-NET were mostly located on the left side of the superior mesenteric artery (SMA) axis (defined as 40 cm from the ileocecal valve), and unifocal ones on the right side. Results: Ninety-four patients were included, 6 with unifocal jejunal-NET located 35 cm (range, 10–60) from the duodenojejunal angle (DJA), 44 (47%) with unifocal ileal-NET and 44 (47%) with multiple ileal-NET. The median number of tumors in multiple ileal-NET was 7 (range, 2–95), within a median small bowel segment of 105 cm (10–240). The median length between the proximal tumor and the DJA was 428 cm (300–635) and 540 cm (350–725) for the distal one; 40 (91%) of them were located on the left side of the SMA axis. In contrast, unifocal ileal-NET were located at a median distance of 577 cm (305–820) from the DJA (p < 0.001, compared to multiple ileal-NET); 30 (68%) of them were on the right side of the SMA axis (p < 0.001). Conclusion: Multiple ileal-NET are mostly located on the left side of the SMA axis. Further studies are warranted to explore the embryological origin of unifocal versus multiple ileal-NET.