bluuebunny/crossref_metadata_2025 huggingface dataset:
A Microfluidic Platform for On-Chip Analysis of Circulating Tumor Cells
Authors: Darabi Jeff , Schober Joseph
Published: October 2021

Studies have shown that primary tumor sites begin shedding cancerous cells into peripheral blood at early stages of cancer, and the presence and frequency of circulating tumor cells (CTCs) in blood is directly proportional to disease progression. The challenge is that the concentration of the CTCs in peripheral blood may be extremely low. In the past few years, several microfluidic-based concepts have been investigated to isolate CTCs from whole blood. However, these devices are generally hampered by complex fabrication processes and very low volumetric throughputs, which may not be practical for rapid clinical applications. This paper presents a high-performance yet simple magnetophoretic microfluidic chip for the enrichment and on-chip analysis of rare CTCs from blood. Microscopic and flow cytometric assays developed for selection of cancer cell lines, selection of monoclonal antibodies, and optimization of bead coupling are discussed. Additionally, on-chip characterization of rare cancer cells using high resolution immunofluorescence microscopy and modeling results for prediction of CTC capture length are presented. The device has the ability to interface directly with on-chip pre and post processing modules such as mixing, incubation, and automated image analysis systems. These features will enable us to isolate rare cancer cells from whole blood and detect them on the chip with subcellular resolution.
Performing Fourier Transform on a Velocity Profile From Atmospheric Turbulence Studies
Authors: Adansi Richard , Terrazas Jose , Rodriguez Arturo , Kotteda V. M. Krushnarao , Kumar Vinod , Rubio Aldo , Avalos Edgar
Published: October 2021

Atmospheric Turbulence poses a challenge to land-based observatories operated by the United States Air Force (USAF) tasked with space situational awareness. By developing new methods for quantifying Turbulence, we intend to provide increased USAF capability in this domain. Current models for quantifying atmospheric Turbulence include Kolmogorov and Non-Kolmogorov methods. Through the nature of Fourier Transform, sinusoidal function, it is possible to determine the frequency at which velocities occur in a specified vertical distance and eventually determine eddy size in a control volume. First, an ANSYS Computational Fluid Dynamics (CFD) model will be created to simulate atmospheric Turbulence in a defined control volume. The simulation will include a one-dimensional flow over a flat plate. The data we acquired from the simulation were used to derive an equation relating the velocity to the vertical distance (velocity profile). We will perform a regression analysis to fit data from Large-Eddy Simulations (LES) and apply Fourier transformation from a time domain to a frequency domain. The objective is to use Fourier transform analysis to determine eddy size distribution and turbulent cascade dissipation in a control volume by analyzing the frequency of velocities. By calculating such eddy size distribution, we may quantify Turbulence in said control volume and compare results with the traditional Kolmogorov method.
Investigation of Proppant Distributions in Rock Fractures With Applications to Hydraulic Fracturing
Authors: Mofakham Amir A. , Rousta Farid , Crandall Dustin M. , Ahmadi Goodarz
Published: October 2021

Hydraulic fracturing or fracking is a procedure used extensively by oil and gas companies to extract natural gas or petroleum from unconventional sources. During this process, a pressurized liquid is injected into wellbores to generate fractures in rock formations to create more permeable pathways in low permeability rocks that hold the oil. To keep the rock fractures open after removing the high pressure, proppant, which typically are sands with different shapes and sizes, are injected simultaneously with the fracking fluid to spread them throughout rock fractures. The extraction productivity from shale reservoirs is significantly affected by the performance and quality of the proppant injection process. Since these processes occur under the ground and in the rock fractures, using experimental investigations to examine the process is challenging, if not impossible. Therefore, employing numerical tools for analyzing the process could provide significant insights leading to the fracking process improvement. Accordingly, in this investigation, a 4-way coupled Computational Fluid Dynamic and Discrete Element Method (CFD-DEM) code was used to simulate proppant transport into a numerically generated realistic rock fracture geometry. The simulations were carried out for a sufficiently long period to reach the fractures’ steady coverage by proppant. The proppant fracture coverage is a distinguishing factor that can be used to assess the proppant injection process quality. A series of simulations with different proppant sizes as well as various fracking fluid flow rates, were performed. The corresponding estimated fracture coverages for different cases were compared. The importance of proppant size as well as the fluid flow rate on the efficiency of the proppant injection process, were evaluated and discussed.
Dispersion of Particles Coming Out of the Mouth While Speaking in a Ventilated Indoor Environment
Authors: Ali Masoomi Morteza , Salmanzadeh Mazyar , Ahmadi Goodarz
Published: October 2021

Breathing air that contains virus-infected droplets is the leading cause of Covid-19 transmission. Sneezing, coughing, breathing, and talking of an infected person would generate aerosolized droplets that carry the coronavirus. Earlier research efforts have focused on sneezing and coughing as the primary transmission sources. New experiments and field studies have shown that breathing and talking are also effective mechanisms in spreading viruses. In this article, the dispersion of particles/droplets during speaking is studied. COVID-19 virus is about 120 nanometers and is suspended in saliva or mucus droplets emitted by an injected person. These droplets evaporate in a fraction of a second as they enter the environment and reduce in size. However, the droplets’ viral content remains the same as they move by the room’s airflow. The particles from sneezing and coughing are larger than those released by speaking. As the particles/droplets are small, the effect of gravity is small, and they remain suspended in the air for a long time. Also, being small makes them more easily penetrate the respiratory passages.

Using the computational fluid dynamics method in conjunction with the ANSYS-Fluent software, the particle transport and dispersion were simulated. The Eulerian approach modeled the airflow (continuous phase), and the Lagrangian approach modeled the particle (discrete phase) movements. This study also investigated the ventilation system’s effects on the distribution of particles in the indoor environment. The displacement and mixing air distribution systems were considered. Simulation results showed that droplets remain suspended in the room for a relatively long time after evaporation. Large particles were deposited quickly, and a significant percentage of smaller particles were removed by the ventilation system. The concentration of particles in the upper half of the room was also quite low for the mixing ventilation system. This was due to the fact that the room air mixing system is relatively uniform; this uniformity of airflow caused the particles to get trapped quickly. Also, for the displacement system, the room airflow was not uniform; these particles were then dispersed in the room and spent more time in the indoor environment.
Shape Reconstruction of Liquid Ligaments and Droplets Model via Multi-View Digital Inline Holography
Authors: Shang Weixiao , Gomez Mateo , Meyer Terrence R. , Chen Jun
Published: October 2021

Digital inline holography (DIH), as a three-dimensional (3D) measurement technique, is widely used in characterizations of the particles, droplets or bubbles under different multi-phase flow circumstances. By analyzing the phase information carried by the interference pattern, the reconstruction of shape and the location of a test target is then achieved. However, such reconstruction mechanism produces different levels of uncertainty between the in-plane (the plane parallel to the hologram plane) direction and out-of-plane (the plane normal to the hologram plane) direction, and the uncertainty of the latter is larger than the former. Also, the reconstruction algorithm fails when the interference patterns of some sections of the target are overlapped on the hologram since the overlapped patterns are merged into a pure shadow which doesn’t carry any phase information. This paper tested a method, the Multi-view Digital Inline Holography (MvDIH), that combines the holograms recorded from multiple views to overcome the addressed defects of the single view DIH. This technique uses the similar setup as the DIH but applies a different post-process method to implement the reconstruction. As the DIH is applied to each view, one can not only acquire the cross-section of the target in the hologram plane but also the outline of such cross-section in the space. Then, two reconstruction methods with different ideologies are developed as, the one based on the outline and the one based on the cross-section. A post-process algorithm is developed to realize these two reconstruction methods with the holograms recorded from different views. To evaluate the performance of the Multi-view DIH, a test model which imitates the droplet and liquid ligament structure is 3D printed and measured by the proposed method. The results demonstrate that, with only three view, both method provides limited reconstruction result. When comparing to the true test model, for the outline based method, some parts of the reconstructed model are missing and some details are merged into one piece with simple geometry. Yet, for the cross-section based method, the reconstructed model contains redundant parts which also make such result unsatisfied. As the used holograms are increased to six views, the reconstructed result for cross-section based method is approaching to the true model, but still some sections are reconstructed with certain level of ambiguity.
Fluid Flow and Heat Transfer of Liquid Sodium in Small-Scale Heat Sinks With Different Geometries
Authors: Pourghasemi Mahyar , Fathi Nima
Published: October 2021

3-D numerical simulations are performed to investigate liquid sodium (Na) flow and the heat transfer within miniature heat sinks with different geometries and hydraulic diameters of less than 5 mm. Two different straight small-scale heat sinks with rectangular and triangular cross-sections are studied in the laminar flow with the Reynolds number up to 1900. The local and average Nusselt numbers are obtained and compared against eachother. At the same surface area to volume ratio, rectangular minichannel heat sink leads to almost 280% higher convective heat transfer rate in comparison with triangular heat sink. It is observed that the difference between thermal efficiencies of rectangular and triangular minichannel heat sinks was independent of flow Reynolds number.
Progress in Analytical Modeling of Water Hammer
Authors: Urbanowicz Kamil , Jing Haixiao , Bergant Anton , Stosiak Michał , Lubecki Marek
Published: October 2021

In this paper analytical formulas of water hammer known from the literature are simplified to the shortest possible mathematical form based on dimensionless parameters: dimensionless time, water hammer number, etc. Novel formulas are determined, for example for the flow velocity and wall shear stress in the Muto and Takahashi solution. A complete solution in the Laplace domain is presented and the problem of its inverse transformation is discussed. A series of comparative studies of analytical solutions with numerical solutions and the results of experimental research were carried out. The compared analytical solutions, taking into account the frequency-dependent nature of the hydraulic resistances, show very good agreement with the experimental results in a wide range of water hammer numbers, in particular when Wh ≤ 0.1. On the other hand, it turned out that the analytical model based on the quasi-steady friction in great detail simulates dynamic pressure response in systems characterized by a high value of the water hammer number Wh ≥ 0.5.
Numerical Simulations and Data Analyses to Identify Aerodynamic Noise Sources Emitted From Small Axial Fan
Authors: Obayashi Wataru , Aono Hikaru , Tatsukawa Tomoaki , Fujii Kozo , Takeda Koichi , Takemi Kazutoshi , Murakami Naoya
Published: October 2021

The aerodynamic noise from fan motors is main noise source of domestic electric appliances and office automation equipment. Reduction of the fan motor noise emission is important to construct comfortable living and working environment. In this study, we investigate aerodynamic noise generation mechanisms associated with a rotating small axial fan using high-resolution large-eddy simulation. The computed results present the first mode of blade passing frequency and its harmonics although there is slight difference in the frequency. Using the data obtained, data analyses are carried out by using snapshot proper orthogonal decomposition and dynamic mode decomposition. The results indicate and suggest possible three sources of noise: variation of the flows over the impellers, complex flows near the boss of the fan, and separated flows in a narrow region between the impeller tips and the casing.
Research on the Performance of a Passive Gas-Liquid Separator Used in Space
Authors: Wu Chengshuo , Wu Peng , Huang Bin , Wu Dazhuan
Published: October 2021

Gas-liquid separation technology is one of the key technologies of environmental control and life support in manned spaceflight. In order to realize gas-liquid separation under microgravity, a prototype of a gas-liquid separator based on passive static separation technology was designed, manufactured, and studied by both ground experimental tests and computational fluid dynamics (CFD). Results show that the experimental results on earth are in good agreement with the simulation results and the internal fluid distribution directly determines the separation rate of the separator. The separation rate and internal flow field of the separator were also investigated under various flow rate conditions and gravity levels. Results show that higher liquid flow rate and lower gravity level can improve gas-liquid separation rate which attributes to the formation of a complete liquid film at the bottom of the collector. The separation rate can reach 100% within the specific ratio range, and the structure of the equipment is simple, without any power components, meeting the requirements of long life and high reliability of space equipment. It can provide a reference for gas-liquid separation in space under the microgravity environment.
The Effects of an Associative, Dissociative, Internal, and External Focus of Attention on Running Economy
Authors: Aghdaei Mahin , Farsi Alireza , Khalaji Maryam , Porter Jared
Published: October 2021

Much research has been executed to investigate how altering focus of attention impacts performance and feelings of fatigue. Using a within-participant design, the present study examined how an associative and dissociative attentional in addition to an internal and external attentional dimension influenced the running economy of nonprofessional runners. Twelve women (aged 18–30 years old) ran on a treadmill at 70% of their predetermined maximum velocity. Participants ran in four counterbalanced conditions (dissociative-external, dissociative-internal, associative-external, and associative-internal). Average oxygen volume, respiration volume and breathing frequency, heart rate, blood lactate level, and Borg rating of perceived exertion were measured. Our findings revealed when participants adopted a dissociative-external focus of attention, they consumed less oxygen, had lower blood lactate, and a lower rating of perceived exertion compared with trials completed using an associative attention strategy. The findings of this study demonstrate that running economy is improved and feelings of fatigue are lowest when using a combination of a dissociative-external focus of attention.
Student Voice in Primary Physical Education: A 30-Year Scoping Review of Literature
Authors: Iannucci Cassandra , Parker Melissa
Published: October 2021

The past decade has seen an increased focus on student voice in physical education; yet, the majority reflects the thoughts, feelings, and experiences of agency of secondary-level students. It has been suggested that the perspectives and experiences of students in primary physical education remain largely absent from the literature. Therefore, the purpose of this review was to answer the question “what peer-reviewed data on student voice in primary physical education was published between January 1990 and March 2020?” This article provides a map of 89 articles that accessed student voice in primary physical education. Conclusions highlight a need for democratic possibilities for primary students to engage and contribute to their physical education learning experiences as well as a continued exploration of the implementation and impact of authentic methods of accessing and responding to student voice in primary physical education.
Opportunities Denied: The Divergent Resonance of Opportunity for Indigenous and Non-Indigenous Hockey Players With the Now-Disbanded Beardy’s Blackhawks
Authors: Rathwell Mika , Henry Robert , McKegney Sam
Published: October 2021

For 25 years, the Beardy’s Blackhawks were Canada’s only U18 AAA hockey team located on and operated by a First Nation. The team encouraged young, Indigenous athletes to take pride in their cultural heritage and offered a sense of belonging and acceptance while also providing an opportunity for non-Indigenous players to play in such an environment. In 2019, the Saskatchewan Hockey Association made the decision to eliminate the Blackhawks from the league, describing their removal as a need to address “league concerns” related to billeting and younger player development. The purpose of this article is to analyze differences in how opportunity is understood and experienced by final-roster players (2019/2020 hockey season) and past alumni and, particularly, how it diverged across racial and cultural axes. What is found through semistructured interviews is that the concept of opportunity shifts between Indigenous and non-Indigenous players: Whereas Indigenous players tend to view opportunity in relation to cultural pride, non-Indigenous players view opportunity primarily in relation to future hockey opportunities. We argue that specific elite sporting opportunities that are characterized by Indigenous values are needed for a greater and more diverse range of Indigenous athletes to succeed in elite sport.
2D macro-XRF to reveal redacted sections of French queen Marie-Antoinette secret correspondence with Swedish count Axel von Fersen
Authors: Michelin Anne , Pottier Fabien , Andraud Christine
Published: October 2021

MA-XRF data processing helps to uncover hidden writings, shedding new light on Queen Marie-Antoinette and Fersen’s relationship.
Timing of charge migration in betaine by impact of fast atomic ions
Authors: Rousseau Patrick , González-Vázquez Jesús , Piekarski Dariusz G. , Kopyra Janina , Domaracka Alicja , Alcamí Manuel , Adoui Lamri , Huber Bernd A. , Díaz-Tendero Sergio , Martín Fernando
Published: October 2021

Intramolecular charge migration induced by fast highly charged atomic ions in the betaine zwitterion is ultrafast and adiabatic.
Liquid crystal–based open surface microfluidics manipulate liquid mobility and chemical composition on demand
Authors: Xu Yang , Rather Adil M. , Yao Yuxing , Fang Jen-Chun , Mamtani Rajdeep S. , Bennett Robert K. A. , Atta Richard G. , Adera Solomon , Tkalec Uroš , Wang Xiaoguang
Published: October 2021

Liquid crystal surfaces enable manipulation of liquid mobility and cargo release via temperature, electrolytes, and light.
GABARAP sequesters the FLCN-FNIP tumor suppressor complex to couple autophagy with lysosomal biogenesis
Authors: Goodwin Jonathan M. , Walkup Ward G. , Hooper Kirsty , Li Taoyingnan , Kishi-Itakura Chieko , Ng Aylwin , Lehmberg Timothy , Jha Archana , Kommineni Sravya , Fletcher Katherine , Garcia-Fortanet Jorge , Fan Yaya , Tang Qing , Wei Menghao , Agrawal Asmita , Budhe Sagar R. , Rouduri Sreekanth R. , Baird Dan , Saunders Jeff , Kiselar Janna , Chance Mark R. , Ballabio Andrea , Appleton Brent A. , Brumell John H. , Florey Oliver , Murphy Leon O.
Published: October 2021

Membrane conjugation of GABARAP sequesters the FLCN-FNIP complex to coordinate activation of MiT/TFE family transcription factors.
Can we teach a tired cell new tricks?
Authors: Henrickson Sarah E.
Published: October 2021

PD-1
+
viral specific CD8 T cells with proliferative capacity are identified in human head and neck squamous cell carcinoma.
Candida tropicaliscellulitis in a patient with cirrhosis, well-controlled HIV and diabetes
Authors: Gutiérrez Villanueva Andrea , Díaz de Santiago Alberto , Martínez Vera Fernanado , De la Fuente Moral Sara
Published: October 2021

We present the case of a patient with multiple comorbidities, including cirrhosis, poorly controlled diabetes mellitus and HIV infection, who was diagnosed with skin and soft-tissue infection of right lower limb. Outcome was poor after prescribing standard antibiotic therapy, and we finally obtained isolation ofCandida tropicalisin cultures of infected tissue. The patient’s condition improved after antifungal treatment was started, and he could be discharged with oral therapy. Here, we report the literature’s first case of cellulitis provoked byC. tropicalisin a patient with cirrhosis.
Adult presentation of multisystem inflammatory syndrome (MIS) associated with recent COVID-19 infection: lessons learnt in timely diagnosis and management
Authors: Yao Qiang , Waley Laura , Liou Natasha
Published: October 2021

Multisystem inflammatory syndrome in adults (MIS-A) is an uncommon and under-recognised postinfectious manifestation that presents 4–6 weeks after COVID-19 infection. Patients affected tend to be young or middle-aged, from ethnic minority backgrounds and previously healthy. In addition to high fever and myalgia, there are a myriad of extrapulmonary symptoms and signs, including cardiac, gastrointestinal, neurological and dermatological involvement. Cardiovascular shock and markedly raised inflammatory markers are prominent features, while significant hypoxia is uncommon. Patients respond well to corticosteroid therapy, but failure of clinicians to recognise this recently identified phenomenon, which can mimic common conditions including sepsis, could delay diagnosis and treatment. Here we present a case of MIS-A in an adult woman, compare her presentation and management with other similar case reports, and reflect on how clinicians can learn from our experiences.
Subacute thyroiditis after inactive SARS-CoV-2 vaccine
Authors: Saygılı Emre Sedar , Karakilic Ersen
Published: October 2021

Viral infections have often been associated with subacute (De Quervain) thyroiditis. Rare cases of subacute thyroiditis have been reported after vaccines. Various vaccines have been developed with different techniques against SARS-CoV-2. This case report presents a rare case of subacute thyroiditis after the inactive SARS-CoV-2 virus vaccine, CoronaVac.
Placenta percreta presenting as uterine rupture following previous B-Lynch suture
Authors: Saha Shubhashis , Abraham Anuja , Raja Navaneethan Preethi , Abraham Kavitha
Published: October 2021

Placenta accreta spectrum disorder varies from minimally adherent placenta to deeply invasive placenta. Placenta percreta is a rare cause for uterine rupture and the incidence of morbidly adherent placenta is on the rise due to increase in the rates of caesarean section. We report a case of a 32-year-old, G2P1L1 who presented to us at 27 weeks in a state of haemodynamic shock with intrauterine fetal death. She had a history of prior caesarean section complicated by postpartum haemorrhage requiring B-Lynch suturing. With an initial diagnosis of caesarean scar rupture, she underwent an emergency laparotomy. Intraoperatively, the caesarean scar was found to be intact and uterine fundal rupture with placental protrusion identified. She underwent caesarean hysterectomy and was discharged in a stable condition. The histopathology report confirmed the diagnosis of placenta percreta.
Posterior interosseous neuropathy: distinguishing from a proximal radial neuropathy
Authors: McKenna Mary Clare , Woods Jack , Dolan Róisín , Connolly Seán
Published: October 2021

The posterior interosseous nerve is the terminal motor branch of the radial nerve that innervates the extensor carpi ulnaris and the extensors of the thumb and fingers. We describe a case of a posterior interosseous neuropathy presenting with the typical ‘finger drop’ and partial ‘wrist drop’. We focus on the clinical signs that distinguish it from a more proximal radial neuropathy, clarified by nerve conduction studies and needle electromyography. Multimodal imaging of the forearm did not identify a compressive lesion. Persistent symptoms prompted surgical exploration 5 years after initial onset. It identified compression of the posterior interosseous nerve in the region of the arcade of Frohse and leash of Henry. The sites were decompressed and concurrent salvage secondary reconstructive tendon transfers were required in view of the severe axonal loss with minimal chance of functional reinnervation.
Effectiveness of a lifestyle weight-loss intervention targeting inactive former elite athletes: the Champ4Life randomised controlled trial
Authors: Silva Analiza M , Nunes Catarina L , Jesus Filipe , Francisco Ruben , Matias Catarina N , Cardoso Miguel , Santos Inês , Carraça Eliana V , Finlayson Graham , Silva Marlene Nunes , Dickinson Stephanie , Allison David , Minderico Cláudia S , Martins Paulo , Sardinha Luis B
Published: October 2021

Objectives

Many athletes struggle in managing the end of their career, often gaining weight and adopting unhealthy lifestyles. Lifestyle programmes targeting former athletes who have gained substantial fat mass (FM) postsports career are lacking. We studied the effects of the Champ4Life programme on body composition and other health-related outcomes in former elite athletes with overweight or obesity.

Methods

Ninety-four former athletes(42.4±7.3 y, 34.0% female) were recruited and randomly assigned to either an intervention group (IG; n=49) or a control group (CG; n=45). The IG attended 12 educational sessions addressing physical activity, weight management and nutrition. They also had a nutrition appointment aimed to prescribe a moderate caloric deficit(~300–500 kcal/day). Dual-energy X-ray absorptiometry was used to assess body composition. The Short-Form Health Survey-36 questionnaire was used to measure general health-related quality of life. Blood samples were collected to assess cardiometabolic health parameters.

Results

At 12 months, the IG lost more weight (estimated difference (ED)=−5.3 kg; −6.9 to −3.8), total FM (ED=−4.1 kg; −5.4 to −2.8) and abdominal FM (ED=−0.49 kg; −0.64 to −0.33) than did the CG (p’s<0.001). Cardiometabolic health markers also improved significantly (p<0.05) more in the IG at 12 months (insulin (ED=−4.9 μU/mL;−8.0 to −1.8); homoeostatic model assessment (ED=−1.2; −2.1 to −0.4); total cholesterol (ED=−21.8 mg/dL; -35.4 to −8.2); low-density lipoprotein (ED=18.2 mg/dL;−29.2 to −7.1)), as did quality-of-life dimensions (physical functioning (ED=11.7; 6.5 to 16.9); physical role (ED=17.6; 2.1 to 33.0); general health (ED=19.4; 11.4 to 27.4); vitality (ED=13.3; 5.3 to 21.3) and mental health (ED=12.3; 4.1 to 20.6)).

Conclusions

The Champ4Life programme was effective in substantially reducing total and abdominal FM while preserving fat-free mass and improving health-related markers. These findings will enable evidence-based decisions when implementing lifestyle interventions targeting retired elite athletes.

Trial registeration number

NCT03031951.
Clinical value of laboratory indicators for predicting disease progression and death in patients with COVID-19: a retrospective cohort study
Authors: Wang Qian , Cheng Jie , Shang Jian , Wang Ying , Wan Jing , Yan You-qin , Liu Wen-bin , Zhang Hai-Ping , Wang Jian-ping , Wang Xiao-yue , Li Zi-ang , Lin Jun
Published: October 2021

Objectives

As early prediction of severe illness and death for patients with coronavirus disease 2019 (COVID-19) is important, we aim to explore the clinical value of laboratory indicators in evaluating the progression and prognosis of patients with COVID-19.

Design

Retrospective cohort study.

Setting

Hospital-based study in China.

Participants

Adult patients with COVID-19 from December 15, 2019 to March 15, 2020.

End point

Disease severity and mortality.

Methods

Clinical data of 638 patients with COVID-19 were collected and compared between severe and non-severe groups. The predictive ability of laboratory indicators in disease progression and prognosis of COVID-19 was analysed using the receiver operating characteristic curve. The survival differences of COVID-19 patients with different levels of laboratory indicators were analysed utilising Kaplan-Meier analysis.

Results

29.8% (190/638) of patients with COVID-19 progressed to severe. Compared with patients with no adverse events, C reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and D-dimer were significantly higher in severe patients with adverse events, such as acute myocardial injury, respiratory failure, acute kidney injury, mechanical ventilation, intensive care unit admission, multiple organ dysfunction syndromes and death (all p<0.05). The multivariate logistic analysis suggested that CRP, NLR and D-dimer were independent risk factors for the disease progression of COVID-19 (all p<0.05). The model combining all of them owned the highest area under the receiver operating characteristic curve (AUC) predicting disease progression and death of COVID-19, with AUC of 0.894 (95% CI 0.857 to 0.931) and 0.918 (95% CI 0.873 to 0.962), respectively. Survival analysis suggested that the patients with a high level of CRP, NLR or D-dimer performed shorter overall survival time (all p<0.05).

Conclusions

The combination of CRP, NLR and D-dimer could be an effective predictor for the aggravation and death in patients with COVID-19. The abnormal expression of these indicators might suggest a strong inflammatory response and multiple adverse events in patients with severe COVID-19.
Population heterogeneity in associations between hormonal contraception and antidepressant use in Sweden: a prospective cohort study applying intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA)
Authors: Zettermark Sofia , Khalaf Kani , Perez-Vicente Raquel , Leckie George , Mulinari Diana , Merlo Juan
Published: October 2021

Objectives

From a reproductive justice framework, we aimed to investigate how a possible association between hormonal contraceptive (HC) and antidepressants use (as a proxy for depression) is distributed across intersectional strata in the population. We aimed to visualise how intersecting power dynamics may operate in combination with HC use to increase or decrease subsequent use of antidepressants. Our main hypothesis was that the previously observed association between HC and antidepressants use would vary between strata, being more pronounced in more oppressed intersectional contexts. For this purpose, we applied an intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy approach.

Design

Observational prospective cohort study using record linkage of national Swedish registers.

Setting

The population of Sweden.

Participants

All 915 954 women aged 12–30 residing in Sweden 2010, without a recent pregnancy and alive during the individual 1-year follow-up.

Primary outcome measure

Use of any antidepressant, meaning being dispensed at least one antidepressant (ATC: N06A) during follow-up.

Results

Previously mentally healthy HC users had an OR of 1.79 for use of antidepressants compared with non-users, whereas this number was 1.28 for women with previous mental health issues. The highest antidepressant use were uniformly found in strata with previous mental health issues, with highest usage in women aged 24–30 with no immigrant background, low income and HC use (51.4%). The largest difference in antidepressant use between HC users and non-users was found in teenagers, and in adult women of immigrant background with low income. Of the total individual variance in the latent propensity of using antidepressant 9.01% (healthy) and 8.16% (with previous mental health issues) was found at the intersectional stratum level.

Conclusions

Our study suggests teenagers and women with immigrant background and low income could be more sensitive to mood effects of HC, a heterogeneity important to consider moving forward.
Qualitative exploration of lesbian parents’ experiences of accessing healthcare for their adopted children in England
Authors: Kelsall-Knight Lucille
Published: October 2021

Objective

To explore the experiences of lesbian parents accessing healthcare for their adopted children in England.

Design

A qualitative inductive design, using narrative inquiry with a critical incident recall interview approach. Interviews were analysed using merged tools of critical event analysis and broadening, burrowing, storying and restorying.

Setting

Participants were recruited from a British lesbian, gay, bisexual and transgender fostering and adoption charity.

Participants

Six lesbian adoptive parents with experience of accessing healthcare for their adopted children in England.

Results

Following data analysis, five themes were identified: navigating heteronormativity, navigating healthcare settings and professionals and having an ‘adopted’ status, intersectional identity of lesbian-parented adoptive families accessing healthcare, reflective imagery of lesbian parents and adoptive families and professional expectations. Self-imposed strategies instigated by the parents to strengthen and protect their familial identities were also discovered.

Conclusions

The needs and challenges of lesbian adoptive families may be different to those of heterosexual and biological families when accessing healthcare. There was an undercurrent of discriminatory practice, shown by various healthcare professionals, and a lack of understanding of the adoption process, knowledge surrounding the child’s history and legal stance with regards to parental responsibility. Further training is needed for healthcare professionals.
Development and psychometric validation for evaluating written medicine information in Thailand: The Consumer Information Rating Form
Authors: Wongtaweepkij Kamonphat , Krska Janet , Pongwecharak Juraporn , Pongpunna Supawinee , Jarernsiripornkul Narumol
Published: October 2021

Objective

To translate and validate the consumer information rating form (CIRF) for use in Thai populations.

Design

The development of the CIRF was carried out in two phases: translation process and cognitive interview, and psychometric testing.

Setting

A university hospital and a tertiary hospital in northeast Thailand.

Participants

150 outpatients from medicine department: 30 for phase 1 and 120 patients for phase 2 study.

Methods

The CIRF was translated with cultural adaptation into Thai using cognitive interview technique in a sample of outpatients. A larger sample of outpatients then completed the CIRF in relation to either a package insert (PI) or a patient information leaflet (PIL) for one of three medicines: atorvastatin, celecoxib and metformin. Construct validity was assessed using principal component analysis (PCA) and internal consistency using Cronbach’s α coefficient. Known group validity was assessed by comparing mean consumers’ ratings for PIs and PILs.

Results

Thirty participants engaged in the cognitive interview and 120 participants completed the CIRF. The PCA found the 17 items of the CIRF were extracted into three factors: comprehensibility, utility and design quality scales, mirroring the original. Cronbach’s α for the overall scale (0.904) indicated good internal consistency. Known-group validity demonstrated significant differences in consumers’ rating between PIs and PILs for almost all items (p<0.001).

Conclusion

Thai version of CIRF had acceptable validity and reliability for Thai consumers’ ratings of written medicine information. The CIRF could be of practical use in the process of developing medicine information to ensure consumers’ comprehension and their usefulness.
Psychosocial impacts on the Christchurch Muslim community following the 15 March terrorist attacks: a mixed-methods study protocol
Authors: Sulaiman-Hill Ruqayya C. , Porter Richard , Tanveer Sandila , Boden Joseph , Beaglehole Ben , Schluter Philip J , Dean Shaystah , Bell Caroline
Published: October 2021

Introduction

On 15 March 2019, a white supremacist gunman opened fire in two mosques in Christchurch, New Zealand, during Friday prayers, killing 51 people and injuring 40. The event was witnessed by at least 250 survivors and also live streamed on social media, leading to widespread and repeated exposure within the community. It is expected that survivors, families and community members will be at increased risk of developing mental disorders due to the scale and violence of these attacks.

This protocol describes the first phase of a proposed longitudinal study to screen and assess the long-term impacts of the terrorist attack on members of the Christchurch Muslim community, to determine clinical need and facilitate access to appropriate interventions and to gain insights into working with such a traumatised, ethnically diverse population. It has been developed in close collaboration with members of that community.

Methods and analysis

A mixed-method design is described, combining self-report measures with a clinician-administered diagnostic interview. Participants include Christchurch Muslims aged 18 years and over, with a target sample size of n=200. Analyses will determine prevalence of major mental disorders, while regression analyses will model the relationship between pre-event features, trauma exposure and mental disorders. A small number of participants, stratified by exposure type, will also take part in a qualitative interview in English. All study information and self-report measures are provided in translations based on the ethnolinguistic composition of the group and are available in paper and online versions.

Ethics and dissemination

Ethical approval was granted by the New Zealand Health and Disability Ethics Committee 19/NTA/147. All participants provide informed consent, either written or online via REDCap software. Findings will be disseminated initially to the impacted community, then by publication in scientific journals, presentations and to government agencies.

Trial registration number

The study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12620000909921.
Multiomics reveal unique signatures of human epiploic adipose tissue related to systemic insulin resistance
Authors: Krieg Laura , Didt Konrad , Karkossa Isabel , Bernhart Stephan H , Kehr Stephanie , Subramanian Narmadha , Lindhorst Andreas , Schaudinn Alexander , Tabei Shirin , Keller Maria , Stumvoll Michael , Dietrich Arne , von Bergen Martin , Stadler Peter F , Laurencikiene Jurga , Krüger Martin , Blüher Matthias , Gericke Martin , Schubert Kristin , Kovacs Peter , Chakaroun Rima , Massier Lucas
Published: October 2021

Objective

Human white adipose tissue (AT) is a metabolically active organ with distinct depot-specific functions. Despite their locations close to the gastrointestinal tract, mesenteric AT and epiploic AT (epiAT) have only scarcely been investigated. Here, we aim to characterise these ATs in-depth and estimate their contribution to alterations in whole-body metabolism.

Design

Mesenteric, epiploic, omental and abdominal subcutaneous ATs were collected from 70 patients with obesity undergoing Roux-en-Y gastric bypass surgery. The metabolically well-characterised cohort included nine subjects with insulin sensitive (IS) obesity, whose AT samples were analysed in a multiomics approach, including methylome, transcriptome and proteome along with samples from subjects with insulin resistance (IR) matched for age, sex and body mass index (n=9). Findings implying differences between AT depots in these subgroups were validated in the entire cohort (n=70) by quantitative real-time PCR.

Results

While mesenteric AT exhibited signatures similar to those found in the omental depot, epiAT was distinct from all other studied fat depots. Multiomics allowed clear discrimination between the IS and IR states in all tissues. The highest discriminatory power between IS and IR was seen in epiAT, where profound differences in the regulation of developmental, metabolic and inflammatory pathways were observed. Gene expression levels of key molecules involved in AT function, metabolic homeostasis and inflammation revealed significant depot-specific differences with epiAT showing the highest expression levels.

Conclusion

Multi-omics epiAT signatures reflect systemic IR and obesity subphenotypes distinct from other fat depots. Our data suggest a previously unrecognised role of human epiploic fat in the context of obesity, impaired insulin sensitivity and related diseases.
Activation of GM-CSF and TLR2 signaling synergistically enhances antigen-specific antitumor immunity and modulates the tumor microenvironment
Authors: Yan Wan-Lun , Wu Chiao-Chieh , Shen Kuan-Yin , Liu Shih-Jen
Published: October 2021

Background

The major challenge of antitumor immunotherapy is dealing with the immunosuppressive tumor microenvironment, which involves immature myeloid cell accumulation that results in T cell dysfunction. Myeloid cell activation is induced by Toll-like receptor agonists. Additionally, granulocyte/macrophage colony stimulating factor (GM-CSF) promotes myelopoiesis and recruits myeloid cells. Here, we combined the Toll-like receptor 2 (TLR2) agonist lipoprotein and GM-CSF to assess whether this bifunctional immunotherapy has synergistic effects on myeloid cells and could be further developed as a therapeutic intervention that enhances the antitumor response.

Methods

We investigated the synergistic effects of biadjuvanted tumor antigen on antigen-presenting cell (APC) activation in bone marrow-derived dendritic cells. Furthermore, therapeutic efficacy was monitored in different tumor models treated via intratumoral or subcutaneous administration routes. The immune effects of the bifunctional fusion protein on myeloid cells in the tumor mass and draining lymph nodes were analyzed by flow cytometry. The induction of cytotoxic T lymphocytes was evaluated via intracellular cytokine levels, perforin/granzyme B staining and an in vivo killing assay.

Results

The TLR2 agonist lipoprotein combined with GM-CSF synergistically induced DC maturation, which subsequently enhanced antitumor immunity. In addition, rlipoE7m-MoGM modulated tumor-infiltrating myeloid cell populations. Vaccination with rlipoE7m-MoGM therapy increased the number of CCR7+CD103+ cDC1s, whereas the number of suppressive tumor-associated macrophages was reduced in the tumor lesions. Consistent with this observation, proliferating antigen-specific CD8+ T cells are highly infiltrated within the tumor, and the expression of IFN-r and perforin was most pronounced within antigen-specific CD8+ T cells in mice administered rlipoE7m-MoGM therapy. This finding corresponded with observation that the combination of a TLR2 agonist and GM-CSF provides increased antitumor activity by inhibiting established tumor outgrowth and protecting against metastatic cancer compared with a TLR2 agonist alone. Importantly, tumor growth inhibition was not due to the direct effects of the TLR2 agonist or GM-CSF but was instead due to the induction of antigen-specific immunity.

Conclusions

The combination of a TLR2 agonist and GM-CSF has synergistic effects that inhibit tumor growth and modulate tumor-infiltrating APCs. This therapeutic approach could be applied to other tumor antigens to treat different cancers.
Eliciting an immune-mediated antitumor response through oncolytic herpes simplex virus-based shared antigen expression in tumors resistant to viroimmunotherapy
Authors: Ghonime Mohammed G , Saini Uksha , Kelly Michael C , Roth Justin C , Wang Pin-Yi , Chen Chun-Yu , Miller Katherine , Hernandez-Aguirre Ilse , Kim Yeaseul , Mo Xiaokui , Stanek Joseph R , Cripe Tim , Mardis Elaine , Cassady Kevin A
Published: October 2021

Background

Oncolytic virotherapy (OV) is an immunotherapy that incorporates viral cancer cell lysis with engagement of the recruited immune response against cancer cells. Pediatric solid tumors are challenging targets because they contain both an inert immune environment and a quiet antigenic landscape, making them more resistant to conventional OV approaches. Further complicating this, herpes simplex virus suppresses host gene expression during virotherapy infection.

Methods

We therefore developed a multimodal oncolytic herpes simplex virus (oHSV) that expresses ephrin A2 (EphA2), a shared tumor-associated antigen (TAA) expressed by many tumors to improve immune-mediated antitumor activity. We verified the virus genotypically and phenotypically and then tested it in an oHSV-resistant orthotopic model (including immunophenotypic analysis), in flank and in T cell-deficient mouse models. We then assessed the antigen-expressing virus in an unrelated peripheral tumor model that also expresses the shared tumor antigen and evaluated functional T-cell response from the treated mice.

Results

Virus-based EphA2 expression induces a robust acquired antitumor immune responses in both an oHSV-resistant murine brain and peripheral tumor model. Our new multimodal oncolytic virus (1) improves survival in viroimmunotherapy resistant tumors, (2) alters both the infiltrating and peripheral T-cell populations capable of suppressing tumor growth on rechallenge, and (3) produces EphA2-specific CD8 effector-like populations.

Conclusions

Our results suggest that this flexible viral-based platform enables immune recognition of the shared TAA and improves the immune-therapeutic response, thus making it well suited for low-mutational load tumors.