bluuebunny/crossref_metadata_2025 huggingface dataset:
Extended-spectrum β-lactamase-producingEscherichia colirib osteomyelitis with debridement and vacuum-assisted closure
Authors: Mitsui Suguru , Tauchi Shunsuke , Mizuki Shinpei , Tobe Satoshi
Published: January 2021

Rib osteomyelitis is a rare disease, comprising 1% or less of all osteomyelitis. Treatment of rib osteomyelitis includes prolonged antibiotic therapy and surgical intervention. Indications for surgical treatment of rib osteomyelitis remain unclear, however, because of few reported cases. We report the first known case of extended-spectrum β-lactamase-producingEscherichia colirib osteomyelitis caused by urosepsis. The 69-year-old male patient remains free of recurrence and symptoms after rib resection and vacuum-assisted closure treatment with antibiotic therapy. Rib osteomyelitis should be considered as differential diagnosis when patients report chest pain after bacteraemic infection. We recommend surgical treatment for patients with drug-resistant bacterial rib osteomyelitis.
Migration of PFO closure device and entrapment within tricuspid valve leading to tricuspid regurgitation: surgical correction of an extremely rare complication after transcutaneous PFO closure
Authors: Thet Myat Soe , Sepehripour Amir , Atieh Abed Elfattah F A , Di Salvo Carmelo
Published: January 2021

A 41-year-old woman was referred to tertiary cardiothoracic surgery centre following embolisation of the Amplatzer patent foramen ovale (PFO) closure device to septal leaflet of tricuspid valve with reopening of PFO. Two years earlier, she presented with thalamic stroke, and she was found to have a PFO following investigations. The following year she underwent transcatheter closure. Six months after the percutaneous closure, she presented again with significant periods of shortness of breath. Imaging studies revealed the migration and embolisation of PFO closure device to the septal leaflet of tricuspid valve with reopening of the foramen and significant tricuspid valve regurgitation. She underwent open heart surgery using cardiopulmonary bypass for retrieval of the device, closure of the foramen and repair of the tricuspid valve. The patient recovered well without any significant issues following surgery.
Fusobacterium nucleatumcausing a pyogenic liver abscess: a rare complication of periodontal disease that occurred during the COVID-19 pandemic
Authors: Collins Laurence , Diamond Tom
Published: January 2021

Fusobacterium nucleatumis a periodontal commensal and pathogen. In rare cases, these anaerobic gram-negative bacilli have been reported to cause pyogenic liver abscesses (PLAs). We describe a patient who developed a periodontal abscess during the COVID-19 pandemic and was unable to access the restricted General Dental Services at this time. She subsequently developed aF. nucleatumbacteraemia and liver abscess. The non-specific signs and symptoms experienced meant the patient self-isolated due to suspected COVID-19 infection and presentation to hospital was delayed. We also include the results of a literature search of other cases of PLAs attributed toF. nucleatum. PLAs often develop insidiously. They require percutaneous drainage and prolonged antimicrobial therapy. Clinicians should be aware of this rare complication of a dentoalveolar infection in a patient who is systemically unwell.
Axillary artery thrombosis resulting in upper limb amputation as a COVID-19 sequela
Authors: Ramachandran Riju , Vasudevan Pillai Anoop , Raja Suyambu , Sailesh Sailakshmi
Published: January 2021

Novel COVID-19 continues to intrigue medical professionals with its varied presentations. Though it affects the respiratory tract primarily, thrombogenesis has been the Achilles’ heel. A 44-year-old man diagnosed with COVID-19 presented with upper limb pain at a local hospital and was found to have thrombosis of the right axillary artery. Despite a successful embolectomy at the local hospital, there was re-occlusion of the axillary artery and the limb became ischaemic. He was referred to our institution by which time the limb became gangrenous above the elbow and had to be amputated. Extensive sloughing of the nerves was also seen in the local area. Hypercoagulability presenting with various manifestations is common in COVID-19 and needs early anticoagulation. We present this asymptomatic patient who lost a limb to this COVID-19 sequelae.
How to combat efforts to overturn bans on electronic nicotine delivery systems: lessons from tobacco industry efforts during the 1980s to open closed cigarette markets in Thailand
Authors: Patanavanich Roengrudee , Glantz Stanton A
Published: January 2021

Until 1990, it was illegal for transnational tobacco companies (TTCs) to sell cigarettes in Thailand. We reviewed and analysed internal tobacco industry documents relevant to the Thai market during the 1980s. TTCs’ attempts to access the Thai cigarette market during the 1980s concentrated on political lobbying, advertising and promotion of the foreign brands that were illegal to sell in Thailand at the time. They sought to take advantage of the Thai Tobacco Monopoly’s (TTM) inefficiency to propose licencing agreements and joint ventures with TTM and took advantages of unclear regulations about cigarette marketing to promote their products through advertising and sponsorship activities. After their initial efforts failed, they successfully lobbied the US to impose trade sanctions to liberalise Thailand’s market. Similar to the situation for cigarettes in the 1980s, since 2017, Philip Morris International has worked in parallel with a pro-e-cigarette group to pressure Thailand’s government to allow sales of electronic nicotine delivery systems (ENDS; including e-cigarettes and heated tobacco products), knowing the products were illegal under Thai law. Health advocates and government authorities should be aware of past TTCs’ tactics for cigarettes and anticipate that TTCs will attempt to use international trade law to force markets open for ENDS if their domestic efforts fail.
Mentoring as an intervention to promote gender equality in academic medicine: a systematic review
Authors: House Allan , Dracup Naila , Burkinshaw Paula , Ward Vicky , Bryant Louise D
Published: January 2021

Background

Mentoring is frequently suggested as an intervention to address gender inequalities in the workplace.

Objectives

To systematically review evidence published since a definitive review in 2006 on the effectiveness of mentoring interventions aimed at achieving gender equality in academic medicine.

Design

Systematic Review, using the Template for Intervention Description and Replication as a template for data extraction and synthesis.

Sample

Studies were included if they described a specific mentoring intervention in a medical school or analogous academic healthcare organisation and included results from an evaluation of the intervention.

Eligibility criteria

Mentoring was defined as (1) a formally organised intervention entailing a supportive relationship between a mentor, defined as a more senior/experienced person and a mentee defined as a more junior/inexperienced person; (2) mentoring intervention involved academic career support (3) the mentoring relationship was outside line management or supervision of performance and was defined by contact over an extended period of time.

Outcomes

The impact of mentoring was usually reported at the level of individual participants, for example, satisfaction and well-being or self-reported career progression. We sought evidence of impact on gender equality via reports of organisation-level effectiveness, of promotion or retention, pay and academic performance of female staff.

Results

We identified 32 publications: 8 review articles, 20 primary observational studies and 4 randomised controlled trials. A further 19 discussed mentoring in relation to gender but did not meet our eligibility criteria. The terminology used, and the structures and processes reported as constituting mentoring, varied greatly. We identified that mentoring is popular with many who receive it; however, we found no robust evidence of effectiveness in reducing gender inequalities. Primary research used weak evaluation designs.

Conclusions

Mentoring is a complex intervention. Future evaluations should adopt standardised approaches used in applied health research to the design and evaluation of effectiveness and cost-effectiveness.
Evaluation of patient characteristics, management and outcomes for COVID-19 at district hospitals in the Western Cape, South Africa: descriptive observational study
Authors: Mash Robert James , Presence-Vollenhoven Mellisa , Adeniji Adeloye , Christoffels Renaldo , Doubell Karlien , Eksteen Lawson , Hendrikse Amee , Hutton Lauren , Jenkins Louis , Kapp Paul , Lombard Annie , Marais Heleen , Rossouw Liezel , Stuve Katrin , Ugoagwu Abi , Williams Beverley
Published: January 2021

Objectives

To describe the characteristics, clinical management and outcomes of patients with COVID-19 at district hospitals.

Design

A descriptive observational cross-sectional study.

Setting

District hospitals (4 in metro and 4 in rural health services) in the Western Cape, South Africa. District hospitals were small (<150 beds) and led by family physicians.

Participants

All patients who presented to the hospitals’ emergency centre and who tested positive for COVID-19 between March and June 2020.

Primary and secondary outcome measures

Source of referral, presenting symptoms, demographics, comorbidities, clinical assessment and management, laboratory turnaround time, clinical outcomes, factors related to mortality, length of stay and location.

Results

1376 patients (73.9% metro, 26.1% rural). Mean age 46.3 years (SD 16.3), 58.5% females. The majority were self-referred (71%) and had comorbidities (67%): hypertension (41%), type 2 diabetes (25%), HIV (14%) and overweight/obesity (19%). Assessment of COVID-19 was mild (49%), moderate (18%) and severe (24%). Test turnaround time (median 3.0 days (IQR 2.0–5.0 days)) was longer than length of stay (median 2.0 day (IQR 2.0–3.0)). The most common treatment was oxygen (41%) and only 0.8% were intubated and ventilated. Overall mortality was 11%. Most were discharged home (60%) and only 9% transferred to higher levels of care. Increasing age (OR 1.06 (95% CI 1.04 to 1.07)), male (OR 2.02 (95% CI 1.37 to 2.98)), overweight/obesity (OR 1.58 (95% CI 1.02 to 2.46)), type 2 diabetes (OR 1.84 (95% CI 1.24 to 2.73)), HIV (OR 3.41 (95% CI 2.06 to 5.65)), chronic kidney disease (OR 5.16 (95% CI 2.82 to 9.43)) were significantly linked with mortality (p<0.05). Pulmonary diseases (tuberculosis (TB), asthma, chronic obstructive pulmonary disease, post-TB structural lung disease) were not associated with increased mortality.

Conclusion

District hospitals supported primary care and shielded tertiary hospitals. Patients had high levels of comorbidities and similar clinical pictures to that reported elsewhere. Most patients were treated as people under investigation. Mortality was comparable to similar settings and risk factors identified.
Anticancer immunity induced by a synthetic tumor-targeted CD137 agonist
Authors: Upadhyaya Punit , Lahdenranta Johanna , Hurov Kristen , Battula Sailaja , Dods Rachel , Haines Eric , Kleyman Marianna , Kristensson Julia , Kublin Jessica , Lani Rachid , Ma Jun , Mudd Gemma , Repash Elizabeth , Van Rietschoten Katerine , Stephen Tom , You Fanglei , Harrison Helen , Chen Liuhong , McDonnell Kevin , Brandish Philip , Keen Nicholas
Published: January 2021

Background

In contrast to immune checkpoint inhibitors, the use of antibodies as agonists of immune costimulatory receptors as cancer therapeutics has largely failed. We sought to address this problem using a new class of modular synthetic drugs, termed tumor-targeted immune cell agonists (TICAs), based on constrained bicyclic peptides (Bicycles).

Methods

Phage libraries displayingBicycleswere panned for binders against tumor necrosis factor (TNF) superfamily receptors CD137 and OX40, and tumor antigens EphA2, Nectin-4 and programmed death ligand 1. The CD137 and OX40Bicycleswere chemically conjugated to tumor antigenBicycleswith different linkers and stoichiometric ratios of binders to obtain a library of low molecular weight TICAs (MW <8 kDa). The TICAs were evaluated in a suite ofin vitroandin vivoassays to characterize their pharmacology and mechanism of action.

Results

LinkingBicyclesagainst costimulatory receptors (e.g., CD137) toBicyclesagainst tumor antigens (e.g., EphA2) created potent agonists that activated the receptors selectively in the presence of tumor cells expressing these antigens. An EphA2/CD137 TICA (BCY12491) efficiently costimulated human peripheral blood mononuclear cellsin vitroin the presence of EphA2 expressing tumor cell lines as measured by the increased secretion of interferon γ and interleukin-2. Treatment of C57/Bl6 mice transgenic for the human CD137 extracellular domain (huCD137) bearing EphA2-expressing MC38 tumors with BCY12491 resulted in the infiltration of CD8+ T cells, elimination of tumors and generation of immunological memory. BCY12491 was cleared quickly from the circulation (plasma t1/2in mice of 1–2 hr), yet intermittent dosing proved effective.

Conclusion

Tumor target-dependent CD137 agonism using a novel chemical approach (TICAs) afforded elimination of tumors with only intermittent dosing suggesting potential for a wide therapeutic index in humans. This work unlocks a new path to effective cancer immunotherapy via agonism of TNF superfamily receptors.
Mandibular force profiles and tooth morphology in growth series of Albertosaurus sarcophagus and Gorgosaurus libratus (Tyrannosauridae: Albertosaurinae) provide evidence for an ontogenetic dietary shift in tyrannosaurids1
Authors: Therrien François , Zelenitsky Darla K. , Voris Jared T. , Tanaka Kohei
Published: January 2021

The albertosaurines Albertosaurus sarcophagus and Gorgosaurus libratus are among the best represented tyrannosaurids, known from nearly complete growth series. These specimens provide an opportunity to study mandibular biomechanical properties and tooth morphology to infer changes in feeding behaviour and bite force through ontogeny in tyrannosaurids. Mandibular force profiles reveal that the symphyseal region of albertosaurines is consistently stronger in bending than the mid-dentary region, indicating that the anterior extremity of the jaws played an important role in prey capture and handling through ontogeny. The symphyseal region was better adapted to withstand torsional stresses than in most non-avian theropods, but not to the extent seen in Tyrannosaurus rex, suggesting that albertosaurine feeding behaviour may have involved less bone crushing or perhaps relatively smaller prey than in Tyrannosaurus rex. The constancy of these biomechanical properties at all known growth stages indicates that although albertosaurines maintained a similar feeding strategy through ontogeny, prey size/type had to change between juvenile and mature individuals. This ontogenetic dietary shift likely happened when individuals reached a mandibular length of ∼58 cm, a size at which teeth shift from ziphodont to incrassate in shape and bite force begins to increase exponentially. The fact that large albertosaurines were capable of generating bite forces equivalent to similar-sized tyrannosaurines suggests that no significant differences in jaw-closing musculature existed between the two clades and that the powerful bite of Tyrannosaurus rex is the result of its large body size rather than of unique adaptations related to a specialized ecology.
Potential for individual tree monitoring in ponderosa pine dominated forests using unmanned aerial system structure from motion point clouds
Authors: Creasy Matthew B. , Tinkham Wade T. , Hoffman Chad M. , Vogeler Jody C.
Published: January 2021

Characterization of forest structure is important for management-related decision making, monitoring, and adaptive management. Increasingly, observations of forest structure are needed at both finer resolutions and across greater extents to support spatially explicit management planning. Unmanned aerial system (UAS) based photogrammetry provides an airborne method of forest structure data acquisition at a significantly lower cost and time commitment than existing methods such as airborne laser scanning (LiDAR). This study utilizes nearly 5000 stem-mapped trees in ponderosa pine (Pinus ponderosa Lawson & C. Lawson) dominated forests to evaluate several algorithms for detecting individual tree locations and characterizing crown area across tree sizes. Our results indicate that adaptive variable window detection methods with UAS-based canopy height models have greater tree detection rates compared with fixed window analysis across a range of tree sizes. Using the UAS approach, probability of detecting individual trees decreases from 97% for dominant overstory to 67% for suppressed understory trees. Additionally, crown radii were correctly determined within 0.5 m for approximately two-thirds of sampled trees. These findings highlight the potential for UAS photogrammetry to characterize forest structure through the detection of trees and tree groups in open-canopy ponderosa pine forests. Further work should investigate how these methods transfer to more diverse species compositions and forest structures.
Spatiotemporal Complexity Analysis for a Space-Time Discrete Generalized Toxic-Phytoplankton-Zooplankton Model with Self-Diffusion and Cross-Diffusion
Authors: Zhong Shihong , Wang Jinliang , Bao Junhua , Li You , Jiang Nan
Published: January 2021

In this paper, a couple map lattice (CML) model is used to study the spatiotemporal dynamics and Turing patterns for a space-time discrete generalized toxic-phytoplankton-zooplankton system with self-diffusion and cross-diffusion. First, the existence and stability conditions for fixed points are obtained by using linear stability analysis. Second, the conditions for the occurrence of flip bifurcation, Neimark–Sacker bifurcation and Turing bifurcation are obtained by using the center manifold reduction theorem and bifurcation theory. The results show that there exist two nonlinear mechanisms, flip-Turing instability and Neimark–Sacker–Turing instability. Moreover, some numerical simulations are used to illustrate the theoretical results. Interestingly, rich dynamical behaviors, such as periodic points, periodic or quasi-periodic orbits, chaos and interesting patterns (plaques, curls, spirals, circles and other intermediate patterns) are found. The results obtained in the CML model contribute to comprehending the complex pattern formation of spatially extended discrete generalized toxic-phytoplankton-zooplankton system.
On the joint continuity of topological pressures for sub-additive singular-valued potentials
Authors: Qu Congcong , Xu Lan
Published: January 2021

Given a non-conformal repeller [Formula: see text] of a [Formula: see text] map [Formula: see text], we give a variational principle of a dimensional upper bound of the non-conformal repellers. If [Formula: see text] is [Formula: see text] then we prove the joint continuity of topological pressure for sub-additive singular-valued potentials on maps and parameters.
Significance of fault seal in assessing CO
2
storage capacity and containment risks – an example from the Horda Platform, northern North Sea
Authors: Wu Long , Thorsen Rune , Ottesen Signe , Meneguolo Renata , Hartvedt Kristin , Ringrose Philip , Nazarian Bamshad
Published: January 2021

An understanding of fault seal is crucial for assessing the storage capacity and containment risks of CO
2
storage sites, as it can significantly affect the projects on across-fault and along-fault migration/leakage risk, as well as reservoir pressure predictions. We present a study from the Smeaheia area in the northern Horda Platform offshore Norway, focusing on two fault-bounded structural closures, namely the Alpha and Beta structures. We aim to use this study to improve the geological understanding of the northern Horda Platform for CO
2
storage scale-up potentials and illustrate the importance of fault seal analysis in containment risk assessment and storage capacity evaluation of a CO
2
storage project. Our containment risk assessment shows that the Alpha structure has low fault-related containment risks; thus, it has a potential value to be an additional storage target. The Beta structure shows larger fault-related containment risks due to juxtaposition of the prospective storage aquifer with the basement across the Øygarden Fault System. The storage capacity of Smeaheia will be determined by the long-term dynamic interplay between pressure depletion and recharging. Our study shows that across-fault pressure communication between Smeaheia and the depleting Troll reservoir is likely to be through several relay ramps of the Vette Fault System. However, Smeaheia also shows pressure-recharging potentials, such as through the subcropping areas at the Base Nordland Unconformity. The depletion observed in the newly drilled well 32/4-3S gives a good validation point for our fault seal predictions and provides valuable insights for future dynamic simulations.

Thematic collection:
This article is part of the Geoscience for CO
2
storage collection available at:
https://www.lyellcollection.org/cc/geoscience-for-co2-storage
Petrology and Nd–Sr isotopic composition of alkaline lamprophyres from the Early to Late Cretaceous Mundwara Alkaline Complex, NW India: evidence of crystal fractionation, accumulation and corrosion in a complex magma chamber plumbing system
Authors: Sharma Abhinay , Sahoo Samarendra , Rao N. V. Chalapathi , Belyatsky Boris , Dhote Prashant , Lehmann Bernd
Published: January 2021

The Early to Late Cretaceous Mundwara alkaline complex (comprising the Musala, Mer and Toa plugs) displays a broad spectrum of alkaline rocks closely associated in space and time with the Deccan large igneous province in NW India. Petrology and Nd–Sr isotopic data on the two youngest and altogether compositionally different lamprophyre dykes of the Mundwara alkaline complex are presented in this paper to understand their petrogenesis and also to constrain the magmatic processes responsible for generation of the rock spectrum in the complex (pyroxenite, picrite ankaramite, carbonatite, shonkinite, olivine gabbro, feldspathoidal and foid-free syenite). The two lamprophyre dykes occurring in the Mer and the Musala hills are referred to as basaltic camptonite I and camptonite II, respectively. The basaltic camptonite I is highly porphyritic and contains olivine, clinopyroxene and magnetite macrocrysts embedded within the groundmass of microphenocyrsts composed of clinopyroxene, phlogopite, magnetite and feldspar. Camptonite II, however, with a more or less similar texture, contains amphibole, biotite, magnetite and clinopyroxene within the microphenocrystic groundmass of amphibole, biotite, apatite and feldspar. Pyroxenes are chemically zoned and display corrosion of the cores, revealing that they are antecrysts developed during the early stages of magma evolution and later on inherited by more evolved magmas. The mineral chemistry and trace element composition of the lamprophyres reveal that fractional crystallization was a dominant process. Early segregation of olivine + Cr-rich clinopyroxene + Cr-spinel from a primary hydrous alkali basalt within a magmatic plumbing system is inferred, which led to the generation of basaltic camptonitic magma (M1) forming the Mer hill lamprophyre. Subsequently, progressive fractionation of pyroxene and Fe–Ti oxides from the basaltic camptonitic (M1) magma generated camptonitic (M2) magma forming the Musala hill lamprophyre. Both lamprophyre dykes on the Sr–Nd isotopic array reflect plume-type asthenospheric derivation, which largely corresponds to the Réunion plume and other alkaline rocks of the Deccan large igneous province. Our study brings out a complex sequence of processes such as crystal fractionation, accumulation and corrosion in the magmatic plumbing system involved in the generation of the Mundwara alkaline complex.
Study on Permeability of Deep‐Buried Sandstone under Triaxial Cyclic Loads
Authors: Sheng Mingqiang , Mabi Awei , Lu Xigen
Published: January 2021

The triaxial cyclic loading and unloading test was carried out on a TAW‐2000 rock mechanics to study the permeability characteristics of deep‐buried sandstone. This paper analyzed the evolution laws of permeability, elastic modulus, rock damage, dissipated energy, and acoustic emission events of sandstone under different confining pressures. It also introduced the concept of relative strain and further discussed the relationship between relative strain and permeability. The test results showed that the permeability of sandstone under cyclic loading and unloading obviously experienced three stages. At a low strain level, the damage degree of sandstone was low. As a result, both the number of acoustic emission events and the proportion of the dissipated energy density were small. In this stage, with increasing the stress, the permeability decreased. With the increase of the relative strain, the propagation of fissure increased through rock interior and the damage of rock was accumulated. Consequently, the number of acoustic emission events grew slowly, and the proportion of dissipated energy density and the damage variable (D) increased gradually. In this stage, the permeability increases. As the axial strain reached the peak strain, the fissures developed into cracks and the rock failure happened. The number of acoustic emission events increased rapidly; both the proportion of the dissipated energy density and the damage variable (D) obtain the maximum value. In this stage, the permeability increased greatly. In this study, the point of fissure propagation of rock specimens was used as the point of demarcation. Before the fissures propagated, the permeability increased slowly and it was in accordance with a linear function. After the fissures propagated, the degree of rock damage increased, and the permeability increased in the form of an exponential function. The larger the confining pressure was, the smaller the relative strain corresponding to the point of fissure propagation was.
Study on Anchor Cable instead of Single Hydraulic Prop Support in Advance Support of Deep Roadway
Authors: Su Wenpeng , Zheng Boyang , Jiang Pengfei
Published: January 2021

In order to solve the problems of complicated advanced support process, high labor intensity, affecting the rapid advance of working face and the destruction of roof bolt (cable) by advance single hydraulic prop in ultra kilometer deep mine roadway, the deformation characteristics of roadway surrounding rock is analyzed. Taking the 27304 working face of Wanglou coal mine as the engineering background, numerical simulation, field monitoring, and theoretical calculation were used to analyze the deformation characteristics of roadway surrounding rock within the advanced influence range of 27304 working face. This paper puts forward the active advance support technology scheme, in which grouting anchor cable replaces the existing single hydraulic prop in the advance influence range of the working face in the ultra‐kilometer deep mine, and observes and analyzes the deformation and failure characteristics of the surrounding rock of the working face advance roadway. The numerical simulation results show that in the advanced influence range of deep roadway, grouting anchor cable was used to replace the previous single hydraulic prop, and the vertical stress at both ends of the working face decreased by 15 MPa, with a decrease rate of 33.3%; the displacement of roadway roof, floor, and two sides decreased by 10 mm, 55 mm, and 20 mm, with a decrease rate of 40%, 68.75%, and 47.6%, respectively. The field monitoring results show that the roof separation is obviously improved after using grouting anchor cable as the active advance support scheme. It solves the problem of safe and efficient production faced by the ultra‐kilometer deep shaft in Wanglou coal mine and provides theoretical and technical support for unmanned double roadway advance support under the condition of safe and efficient mining.
A Bilevel Programming Location Approach to Regional Waste Electric and Electronic Equipment Collection Centers: A Study in China
Authors: Li Honglei , Lu Yi
Published: January 2021

As one of the largest markets of electronic and electric equipment, China has not completely established the formal recycling system of WEEE compared with the developed countries. As a result, China is facing the huge challenge of resource waste and water/soil environmental pollution. In this paper, according to the current regulations on WEEE recycling and disposal issued by Chinese government, the business model of the Chinese WEEE recycling system was designed, and a bilevel programming-based model was proposed to help the disposal factories to establish the regional efficient and economical WEEE recycling network. This model addressed the optimization of bilateral benefits of disposal factories and the third-party recycling agencies/stations. An experiment based on a regional WEEE recycling business data was solved by the NSGA algorithm to validate the proposed model. With the result, the proposed model was compared with the related studies on Chinese WEEE recycling network planning. With the comparison and the analysis on the experiment result, it was found that the proposed model had considerably stable convergence and optimization performance, which proved that this model can be regarded as a useful tool to the planning of the Chinese regional WEEE recycling network. In the last part, the future improvement of the proposed model was also discussed.
An Improved Triggering Updating Method of Interest Message with Adaptive Threshold Determination for Directed Diffusion Routing Protocol
Authors: Wang Jun , Liu Xiaohang , He Zhitao , Zhang Yadan , Gao Song
Published: January 2021

Although some progress has been made in studying the triggering updating methods of interest message for reducing node energy consumption in directed diffusion routing protocols, they do not consider the anisotropy of sensing areas of nodes and the requirement of diversity of interest message exchange rates within real‐time performance, which makes these studies unable to accurately adapt to the characteristics of interest message update. In this work, we proposed an improved triggering updating method (ITUM) consisted of adaptive threshold determination based on the analytic hierarchy process and update judgement by similarity comparison of interest messages. Meanwhile, the network model and the sensing model are presented to describe actual network scenarios. We analyze the impact of critical parameters and evaluate the performance of ITUM with several interest message updating methods from the aspect of lowering the number of information exchanges. The simulation results prove that ITUM can improve the adaptability to scene changes while decreasing the number of information exchanges compared with the existing methods. Furthermore, it is shown that ITUM is a highly effective solution for determining the triggering updating conditions of various information exchange rates in directed diffusion routing protocol.
Analysis of the Physical Behavior of the Periodic Mixed-Convection Flow around a Nonconducting Horizontal Circular Cylinder Embedded in a Porous Medium
Authors: Ashraf Muhammad , Ullah Zia , Zia Saqib , Alharbi Sayer O. , Baleanu Dumitru , Khan Ilyas
Published: January 2021

An oscillatory mixed-convection fluid flow mechanism across a nonconducting horizontal circular cylinder embedded in a porous medium has been computed. For this purpose, a model in the form of partial differential equations is formulated, and then, the governing equations of the dimensionless model are transformed into the primitive form for integration by using primitive variable formulation. The impact of emerging parameters such as porous medium parameter

Ω

, Richardson number

λ

, magnetic force parameter

ξ

, and Prandtl number Pr on skin friction, heat transfer, and current density is interpreted graphically. It is demonstrated that accurate numerical results can be obtained by the present method by treating nonoscillating and oscillating parts of coupled partial differential equations simultaneously. In this study, it is well established that the transient convective heat transfer, skin friction, and current density depend on amplitude and phase angle. One of the objects of the present study is to predict the mechanism of heat and fluid flow around different angles of a nonconducting horizontal circular cylinder embedded in a porous medium.
Osthole‐Loaded Nanoemulsion Enhances Brain Target in the Treatment of Alzheimer’s Disease via Intranasal Administration
Authors: Song Yilei , Wang Xiangyu , Wang Xingrong , Wang Jianze , Hao Qiulian , Hao Jifu , Hou Xueqin
Published: January 2021

Osthole (OST) is a natural coumarin compound that exerts multiple pharmacologic effects. However, the poor water solubility and the low oral absorption of OST limit its clinical application for the treatment of neurologic diseases. A suitable preparation needs to be tailored to evade these unfavourable properties of OST. In this study, an OST nanoemulsion (OST‐NE) was fabricated according to the pseudoternary phase diagram method, which was generally used to optimize the prescription in light of the solubility of OST in surfactants and cosurfactants. The final composition of OST‐NE was 3.6% of ethyl oleate as oil phase, 11.4% of the surfactant (polyethylene glycol ester of 15‐hydroxystearic acid: polyoxyethylene 35 castor oil = 1 : 1), 3% of polyethylene glycol 400 as cosurfactant, and 82% of the aqueous phase. The pharmacokinetic study of OST‐NE showed that the brain‐targeting coefficient of OST was larger by the nasal route than that by the intravenous route. Moreover, OST‐NE inhibited cell death, decreased the apoptosis‐related proteins (Bax and caspase‐3), and enhanced the activity of antioxidant enzymes (superoxide dismutase and glutathione) in L‐glutamate‐induced SH‐SY5Y cells. OST‐NE improved the spatial memory ability, increased the acetylcholine content in the cerebral cortex, and decreased the activity of acetylcholinesterase in the hippocampus of Alzheimer’s disease model mice. In conclusion, this study indicates that the bioavailability of OST was improved by using the OST‐NE via the nasal route. A low dose of OST‐NE maintained the neuroprotective effects of OST, such as inhibiting apoptosis and oxidative stress and regulating the cholinergic system. Therefore, OST‐NE can be used as a possible alternative to improve its bioavailability in the prevention and treatment of Alzheimer’s disease.
Osimertinib plus Ramucirumab: The Best of Both Worlds?
Authors: Garon Edward B.
Published: January 2021

Both osimertinib and the combination of erlotinib plus ramucirumab are approved for initial therapy of advanced EGFR mutation–positive non–small cell lung cancer. Osimertinib is also approved in previously treated T790M mutation–positive patients. The accompanying article reports on a study combining osimertinib with ramucirumab.

See related article by Yu et al., p. 992
Arginase Therapy Combines Effectively with Immune Checkpoint Blockade or Agonist Anti-OX40 Immunotherapy to Control Tumor Growth
Authors: Badeaux Mark D. , Rolig Annah S. , Agnello Giulia , Enzler Danlee , Kasiewicz Melissa J. , Priddy Leslie , Wiggins Jason F. , Muir Alexander , Sullivan Mark R. , Van Cleef Jessica , Daige Christopher , Vander Heiden Matthew G. , Rajamanickam Venkatesh , Wooldridge James E. , Redmond William L. , Rowlinson Scott W.
Published: January 2021

Metabolic dysregulation is a hallmark of cancer. Many tumors exhibit auxotrophy for various amino acids, such as arginine, because they are unable to meet the demand for these amino acids through endogenous production. This vulnerability can be exploited by employing therapeutic strategies that deplete systemic arginine in order to limit the growth and survival of arginine auxotrophic tumors. Pegzilarginase, a human arginase-1 enzyme engineered to have superior stability and enzymatic activity relative to the native human arginase-1 enzyme, depletes systemic arginine by converting it to ornithine and urea. Therapeutic administration of pegzilarginase in the setting of arginine auxotrophic tumors exerts direct antitumor activity by starving the tumor of exogenous arginine. We hypothesized that in addition to this direct effect, pegzilarginase treatment indirectly augments antitumor immunity through increased antigen presentation, thus making pegzilarginase a prime candidate for combination therapy with immuno-oncology (I-O) agents. Tumor-bearing mice (CT26, MC38, and MCA-205) receiving pegzilarginase in combination with anti–PD-L1 or agonist anti-OX40 experienced significantly increased survival relative to animals receiving I-O monotherapy. Combination pegzilarginase/immunotherapy induced robust antitumor immunity characterized by increased intratumoral effector CD8+ T cells and M1 polarization of tumor-associated macrophages. Our data suggest potential mechanisms of synergy between pegzilarginase and I-O agents that include increased intratumoral MHC expression on both antigen-presenting cells and tumor cells, and increased presence of M1-like antitumor macrophages. These data support the clinical evaluation of I-O agents in conjunction with pegzilarginase for the treatment of patients with cancer.
Clinical Characteristics, Molecular Features, and Long-Term Follow-Up of 15 Patients with Neonatal Diabetes: A Single-Centre Experience
Authors: Abali Zehra Yavas , De Franco Elisa , Karakilic Ozturan Esin , Poyrazoglu Sukran , Bundak Ruveyde , Bas Firdevs , Flanagan Sarah E. , Darendeliler Feyza
Published: January 2021

Background: Diabetes diagnosed within the first 6 months of life is defined as neonatal diabetes mellitus (NDM). Mutations in the KCNJ11, ABCC8, and INS genes are the most common cause of permanent NDM. In populations with a high rate of consanguinity, Wolcott-Rallison syndrome caused by biallelic EIF2AK3 mutations is common. Methods: We studied the clinical characteristics and underlying genetic cause of disease in 15 individuals with diabetes onset before 6 months of age as defined by sustained hyperglycaemia requiring insulin treatment. Patients who had a remission of the diabetes, defined by a normal blood glucose and HbA1c value without insulin or sulphonylurea (SU) treatment, within the first 18 months of life were classified as having transient NDM (TNDM). Results: We report 15 patients with NDM from 14 unrelated families, including 10 with reported parental consanguinity. 1/15 patients had a remission of diabetes, leading to a diagnosis of TNDM. Mutations were detected in 80% (n = 12/15) of the cohort (ABCC8 [n = 4], PTF1A-distal enhancer [n = 3], KCNJ11 [n = 2], EIF2AK3 [n = 1], INS [n = 1], and SLC19A2 [n = 1]). All cases were initially treated with multiple dose insulin injections. One patient with an ABCC8 mutation transitioned from insulin to SU resulting in improved metabolic control at the age of 20 years. Conclusion: Although the number of individuals born to consanguineous parents was considerably high in this cohort, KATP channel mutations (ABCC8/KCNJ11) were more common than EIF2AK3 mutations (n = 6 vs. n = 1). Genetic analyses should be performed in all NDM cases due to the potential impact on treatment and prognosis.
Gorilla Abundance Estimations within North-East Moukalaba-Doudou National Park, Gabon
Authors: Ismaila Nana , Maloueki Ulrich
Published: January 2021

Accurate measures of animal population densities are essential to evaluate conservation status and implement action plans to ensure species survival. Gorilla numbers were assessed using the recce survey method within Moukalaba-Doudou National Park (MDNP) in Gabon using fresh nest counts of up to 1 week old. We walked 3,592 km within a 23.01-km2 study site totalling a sampling effort of 297 days. Encounter rate was 0.12 fresh nests per kilometre, and gorilla density estimates generated by home range sizes (by minimal convex polygon) ranged between 1.14 and 1.48 gorillas/km2. Gorillas preferred mixed forest for nesting over other habitats (Cheason index value 1.31). Results showed that gorilla density values within the study area concurred with previous studies that used line transect methodologies. We conclude that the choice of sampling design is dependent on environmental conditions characterised by each habitat type and target species.
In the Mood for a Blood Donation? Pilot Study about Momentary Mood, Satisfaction, and Return Behavior in Deferred First-Time Donors
Authors: Greffin Klara , Muehlan Holger , Tomczyk Samuel , Suemnig Ariane , Schmidt Silke , Greinacher Andreas
Published: January 2021

Introduction: To maintain a sufficient donor pool, deferred first-time donors (FTD) should be motivated to return for blood donation. This pilot study investigates how deferral affects momentary mood, satisfaction with the donation process, and subsequent return behavior to examine their potential for motivating (deferred) FTD. Methods: All of the subjects (n = 96) completed a first questionnaire (A1) before pre-donation assessment. Deferred FTD (n = 22) were asked to complete a second questionnaire (A2) immediately after deferral, while non-deferred FTD (n = 74) filled in the second questionnaire (A3) after blood donation. The impact of deferral, momentary mood, and satisfaction with the donation process on return behavior within 12 months was tested by calculating two path analyses, controlling for sex and age. Results: Mood (p < 0.001) and satisfaction with social aspects of the donation process (p = 0.01) were decreased after deferral. Deferred FTD were less likely than non-deferred FTD to return to the blood donation center within 12 months (60.8 vs. 36.4%; p = 0.043). However, path analyses revealed that deferral effects on mood and satisfaction were not connected to return behavior. Instead, age had a significant influence on return behavior (p < 0.05) such that, overall, non-returning FTD were older than returning FTD, regardless of their deferral status. Conclusion: Our findings suggest that mood and satisfaction with the donation process are directly affected by deferral but not clearly responsible for low return rates. It seems promising to embed these variables in established health behavior models in further studies to increase the return rates of deferred FTD.
Predictors for 2-Year Functional and Morphological Outcomes of a Treat-and-Extend Regimen with Ranibizumab in Patients with Diabetic Macular Edema
Authors: Giannakaki-Zimmermann Helena , Behrndt Alexandra , Hoffmann Laura , Guichard Maria-Magdalena , Türksever Cengiz , Prünte Christian , Hatz Katja
Published: January 2021

Purpose: The purpose of the study was to investigate longer term functional and morphological outcomes and their predictors in diabetic macular edema (DME) following a treat-and-extend regimen (TER) without loading dose under ranibizumab. Methods: Patient data were reviewed and analyzed retrospectively over a period of 24 months after initiation of TER. Best-corrected visual acuity (BCVA), treatment frequency, and quantitative and qualitative spectral-domain optical coherence tomography parameters were assessed. Results: 118 eyes of 87 patients were included. A mean of 9.74 ± 2.13 injections in the first and 7.63 ± 2.29 in the second year were applied. There were significant gains of BCVA and reductions in central retinal thickness from baseline to 12 and 24 months (all p < 0.001). Percentage of eyes with an intact inner segment/outer segment (IS/OS) junction increased from 15.3% at baseline to 42.1% at 24 months (p < 0.001). An intact IS/OS junction at baseline increased the probability of having a dry retina after 12 months by 79.3% (p = 0.017) and after 24 months by 88.1% (p = 0.040). Less IS/OS disruption at baseline predicted longer maximum recurrence-free treatment intervals at 2 years (r = −0.345, p < 0.001) and better BCVA at 1 year (r = −0.347, p < 0.001). Baseline bigger intraretinal cysts were associated with more IS/OS disruption at 24 months (r = 0.305, p = 0.007). Younger age and lower BCVA at baseline were predictive for a higher BCVA gain at 24 months (p = 0.046, p < 0.001). Conclusion: Ranibizumab applied in a TER without loading dose in DME significantly improves visual acuity and retinal anatomical structure throughout 2 years. The evaluated predictors might help guide routine clinical treatment in DME.
Role of Oxidative Stress and Severity of Diabetic Retinopathy in Type 1 and Type 2 Diabetes
Authors: Bokhary Kholoud , Aljaser Feda , Abudawood Manal , Tabassum Hajera , Bakhsh Afnan , Alhammad Shatha , Aleyadhi Rawan , Almajed Faisal , Alsubki Roua
Published: January 2021

Background: Diabetic retinopathy (DR) is a sight-threatening complication of diabetes mellitus (DM). Oxidative stress generated on account of hyperglycemic state may lead to retinal abnormalities including DR. Objectives: The aim of the study was to evaluate the status of antioxidant enzymes; superoxide dismutase (SOD), and catalase (CAT), in different stages of DR severity in subjects with type 1 DM (T1DM) and type 2 DM (T2DM). Methods: The cross-sectional study enrolled 148 subjects with T1DM (n = 17), T2DM (n = 96), and nondiabetic controls (n = 35). Subjects with DM were divided into 2 subgroups based on DR severity (mild-to-severe nonproliferative DR [NPDR] and proliferative DR [PDR]), and serum glycated hemoglobin (HbA1c), lipid profile, SOD, and CAT were estimated. Results: Both SOD and CAT levels were lower in diabetic subjects than nondiabetic controls. A significant positive correlation was found between HbA1C level and severity of DR (p < 0.0001). Levels of SOD and CAT varied significantly with DR severity in both diabetic groups at p < 0.05. Furthermore, levels of SOD and CAT were found to decrease significantly (p < 0.001) in DR (+) compared to DR (−) patients. Also, increased levels of HbA1c were significantly associated (p < 0.001) with decreased SOD in both subgroups (NPDR and PDR). DR severity was significantly associated with SOD and CAT in the NPDR and PDR subgroups (p < 0.05). Conclusion: Oxidative stress and decreased antioxidant defenses are associated with DR progression to its PDR stage.