bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the transit time spread characteristic of 20-in. hybrid photomultiplier tube used for high-energy particle detection
Authors: Xin Liwei , Shen Tao , Tian Jinshou , Guo Lehui , Liu Hulin , Chen Ping , Xue Yanhua , Ji Chao , Wang Xing , Gao Guilong , He Kai
Published: April 2022

According to the requirements of high-energy particle detection for a large photocathode detection surface, low transit time spread (TTS), and low-cost photomultiplier tube (PMT), a kind of 20-in. hybrid large-area PMT based on the silicon (Si) electron multiplier array was designed and optimized. This study tracked the trajectories of photoelectrons from the photocathode to the silicon electron multiplier array based on the Monte Carlo and finite-integral method. The critical effects on the TTS characteristic of the large-area PMT, including the focusing electrode structure, glass shell structure, different potential differences, and relative distance from the photocathode vertex to the silicon electron multiplier array, were studied in detail. After optimizing the structure of the glass shell, the 20-in. hybrid PMT based on the ultra-small Si electron multiplier array with 40 mm collection diameter can achieve an excellent TTS of about 1.87 ns from the photocathode to the Si electron multiplier array at a collection potential difference of 2000 V.
Interaction between solitary waves and a combined structure of two concentric asymmetric porous arc walls
Authors: Zhai Zhenfeng , Zheng Siming , Wan Decheng
Published: April 2022

An analytical model based on the linear potential flow theory is developed to study the diffraction problem of solitary wave interaction with a combined structure of two thin concentric asymmetric porous arc walls. The two closed virtual circles, where the two arc walls are located, are used to partition the entire fluid region into three sub-regions; the velocity potentials associated with each region are expanded in terms of a series of appropriate eigenfunctions. Furthermore, a series of simultaneous equations are used to determine the unknown coefficients in the expressions of the velocity potentials. The accuracy of the present model is verified by comparing its output with published results. Meanwhile, the impact of various important parameters (i.e., annular spacing, incident angle, the orientation of two arc walls, and porosity of walls) with respect to wave forces and relative wave height is examined. Numerical results reveal that dual-arc walls provide more significant protection for the interior cylinder than single walls. The two cross-placed arc walls provide excellent protection for the interior cylinder with their sheltered area extended. This research is anticipated to provide useful theoretical guidance for nearshore engineering design.
Strain-modulated electronic transport in two-dimensional carbon allotropes
Authors: Yang Ningjing , Chen Qingyuan , Xu Yafang , Luo Jinlong , Yang Hai , Jin Guojun
Published: April 2022

Carbon has various allotropes showing rich physical properties. Here, we take net C and net W as the research objects. They are all composed of carbonic squares C4, hexagons C6, and octagons C8, but with different compositions. Using the combination of density functional theory calculations and non-equilibrium Green’s function method, we study the significant changes in electronic structures and transport behaviors in response to external strain. For net C, tunable negative differential resistance (NDR) is observed. The NDR bias region can be moved and widened, while its peak-to-valley ratio can be increased from the original 1.14 to largest 2.67. The electrical conductivity of net W exhibits a very good linear relationship within a large strain range from −4% to +4%, and it can be increased to 219.9%. By analyzing their band structures, the effective regulations of strain on both the NDR and linear conductivity are explained. These results show not only the differences from deformation for various carbon rings under strain but also a certain guiding significance for applications in electronic devices.
Unveiling exozodiacal light
Authors: Spalding Eckhart , Defrère Denis , Ertel Steve
Published: April 2022

Nulling interferometry draws aside bright stellar glare to probe fine dust in extrasolar systems that may hamper future searches for Earthlike worlds.
Impact of oxidative stress SNPs on sperm DNA damage and male infertility in a south-east Iranian population
Authors: Karam Zahra Miri , Baba Salari Milad , Anjom Shoaa Ahmad , Dehghan Kouhestani Somaye , Bahram Nejad Asma , Ashourzadeh Sareh , Zangouyee Moahammad Reza , Bazrafshani Mohammad Reza
Published: April 2022

Aim We examined four single nucleotide polymorphisms in four antioxidant genes (PON1, CAT, GPx1 and SOD2) in 100 infertility cases and 100 controls from an Iranian population-based case–control study to confirm the assumption that polymorphisms in oxidative stress genes increase the risk of sperm DNA damage and idiopathic male infertility. Methods Restriction fragment length polymorphism and tetra-primer amplification refractory mutation system PCR were used to identify genotypes. Sperm DNA damage was assessed using the Sperm Chromatin Dispersion test (Halo Sperm), and the total antioxidant capacity of seminal fluid was determined using the FRAP assay. Key results Our findings demonstrated that alleles Arg-PON1 (rs662) and Ala-MnSOD (rs4880) variant genotypes were considerably linked with a higher risk of male infertility. Conclusions Linear regression analysis revealed that those with the PON1 Gln192Arg or SOD2 Val16Ala variants have significantly higher levels of sperm DNA fragmentation and lower levels of the total antioxidant capacity in seminal fluid. Implications These findings suggest that genetic differences in antioxidant genes may be linked to oxidative stress, sperm DNA damage, and idiopathic male infertility.
Layered evolution of gene expression in “superfast” muscles for courtship
Authors: Pease James B. , Driver Robert J. , de la Cerda David A. , Day Lainy B. , Lindsay Willow R. , Schlinger Barney A. , Schuppe Eric R. , Balakrishnan Christopher N. , Fuxjager Matthew J.
Published: April 2022

Significance

The process by which new complex traits evolve has been a persistent conundrum throughout the history of evolutionary inquiry. How multiple physiological changes at the organism level and genetic changes at the molecular level combine is still unclear for many traits. Here, we studied the displays of manakins, who beat their wings together at nearly twice the speed of other songbirds to produce a loud “snap” that attracts mates. We simultaneously analyzed evolution of gene expression levels and gene sequences to identify key genes related to muscle contractions and tissue regeneration after stress. Our results show how innovative behavioral traits evolve as a layered process where recent molecular shifts build on ancestral genetic evolutionary changes.
Intermittent prednisone treatment in mice promotes exercise tolerance in obesity through adiponectin
Authors: Quattrocelli Mattia , Wintzinger Michelle , Miz Karen , Panta Manoj , Prabakaran Ashok D. , Barish Grant D. , Chandel Navdeep S. , McNally Elizabeth M.
Published: April 2022

The fat–muscle communication regulates metabolism and involves circulating signals like adiponectin. Modulation of this cross-talk could benefit muscle bioenergetics and exercise tolerance in conditions like obesity. Chronic daily intake of exogenous glucocorticoids produces or exacerbates metabolic stress, often leading to obesity. In stark contrast to the daily intake, we discovered that intermittent pulses of glucocorticoids improve dystrophic muscle metabolism. However, the underlying mechanisms, particularly in the context of obesity, are still largely unknown. Here we report that in mice with diet-induced obesity, intermittent once-weekly prednisone increased total and high-molecular weight adiponectin levels and improved exercise tolerance and energy expenditure. These effects were dependent upon adiponectin, as shown by genetic ablation of the adipokine. Upregulation of Adipoq occurred through the glucocorticoid receptor (GR), as this effect was blocked by inducible GR ablation in adipocytes. The treatment increased the muscle metabolic response of adiponectin through the CAMKK2–AMPK cascade. Our study demonstrates that intermittent glucocorticoids produce healthful metabolic remodeling in diet-induced obesity.
Influence of temperature on magnetorheological fluid properties and damping performance
Authors: Kumar Kariganaur Ashok , Kumar Hemantha , Arun M
Published: April 2022

The magnetorheological (MR) system’s performance depends on the MR fluid’s temperature in operation. This study aims to evaluate the temperature effect of MR fluid on performance while the damper is working. Before synthesizing MR fluid, scanning electron microscopy, x-ray diffraction, and particle size analysis verifies for the synthesis of MR fluid in-house. Characterization of the MR fluid at different temperatures and magnetic fields was carried out. The Herschel–Bulkley model is used to analyse the nonlinearity in the fluid by incorporating the temperature effect. The range of critical parameters used to fabricate the MR damper is selected using the Technique for Order of Preference by Similarity to Ideal Solution performance score. The temperature of the MR fluid is measured using an embedded thermocouple while the damper is operating at different loading parameters. The results reveal that the fluid temperature rises significantly from atmospheric to 125.39 °C with decrease in damping force by 66.32% at higher loading parameters. The theoretical model predicts the increase in temperature similar to that of the experimental values with an average error of 10.24% in the on-state condition. Particle characterization after dynamic testing reveals particle morphology has not changed but the saturation magnetization of the particles reduced by 57% at higher temperatures (127 °C). It is observed through thermogravimetric analysis that, the life of the fluid is reduced by 0.25%, which is negligible after dynamic testing of the fluid for approximately 85000 cycles. Finally, to imitate the temperature effect on the particle, particles were heat-treated at 200 °C, 400 °C, and 600 °C, and through scanning electron microscope image it is confirmed that deterioration of the particle starts after 200°C, if the fluid is operated for a prolonged amount of time.
Possibility for Using Biochar for Sustainable Agriculture: a Case Study in Bulgaria
Authors: Velichkova Rositsa , Zheng Wandong , Markov Detelin , Simova Iskra , Ivanov Ivan , Denev Ivan , Pushkarov Martin
Published: April 2022

In both industrialized and developing countries, soil loss and degradation are observed at unprecedented rates and profound implications for soil ecosystem properties. In many regions, loss of soil productivity occurs despite the intensive use of agrochemicals, in parallel with the adverse environmental impact of soil and water resources. The soil types and the agro-ecological areas in Bulgaria are presented. Four samples of chernozem soil were collected and were investigated with and without biochar. The results obtained show the effect of adding biochar to the change of the pH of the soil
A Meritocratic Origin of Egalitarian Behaviour
Authors: Cappelen Alexander W , Mollerstrom Johanna , Reme Bjørn-Atle , Tungodden Bertil
Published: April 2022

We report from a study of how uncertainty about whether a given inequality reflects performance or luck shapes distributive behaviour. We show theoretically that the reaction to uncertainty depends on how people trade-off the probability of making a mistake when redistributing, and the size of this mistake. We show experimentally that uncertainty causes a strong egalitarian pull among a majority of meritocratic individuals. The theoretical framework and the experimental results are supported in general population surveys in the United States and Norway. Our findings suggest that how people handle uncertainty about the source of inequality may be of great importance for understanding distributive conflicts in society.
Traumatic Brain Injury-Related Optic Nerve Damage
Authors: Qiu Jianhua , Boucher Masen , Conley Grace , Li Yue , Zhang Jingdong , Morriss Nicholas , Meehan III William P , Mannix Rebekah
Published: April 2022

Vision disorders are associated with traumatic brain injury (TBI) in 20%–40% of clinical cases and involve a diverse set of potential symptoms that can present acutely or chronically. Due to its structure and position, the optic nerve is vulnerable to multiple forms of primary injury, which can result in traumatic optic neuropathy (TON). Multiple studies have shown that the optic tract may also be injured during TBI, though data regarding the temporospatial resolution of injury to the optic nerve are sparse. We evaluated the time course of optic nerve injury and visual impairments in our closed head impact acceleration mouse model of mild TBI (mTBI) designed to mimic repetitive injuries experienced in the context of sport. Our results show that inflammation and gliosis occur acutely in response to injury. Additionally, indications of optic nerve degeneration and functional loss of vision beginning at 1-month postinjury, and retinal ganglion cell loss at 7 months, revealed that the degeneration is continuous and permanent. Together, this study demonstrated that the optic nerve is vulnerable to damage during mTBI, which can cause TON and vision loss. These findings will be important for clinicians to consider to determine whether optic nerve is injured in the TBI patients with vision problems.
Uruguay
Authors: Bardazano Gianella
Published: April 2022

According to dogmatic literature on Uruguayan Constitutional history, one of its main characteristics is the link between the successive reforms of the Constitution and the corresponding agreements between the main political parties. This is confirmed by an analysis of the Uruguayan constitutional processes from the perspective of the theory of law and political science. This central feature, at the same time, relates to the institutional significance—manifest in reform processes—that political agreements between parties have had. The constitutional reforms of 1917, 1934, 1942, 1952, and 1966 were total reforms, each of which completely replaced the text of the previous constitution in place. The reforms approved in 1912, 1932, 1936–1938, 1942, 1989, 1994, 1996, and 2004, were, instead, partial in nature. As Uruguayan scholars correctly point out, all those reforms were supported by broad agreements among the main political parties. However, the facet I would like to stress is the specific power-sharing purpose of those agreements—that is, the agreements that motivated and guided reforms were directed to the quite express goal of co-participation of the main political parties in government. This is a descriptive chapter that addresses, in the first place, the Uruguayan constitutional evolution on the basis of the aforementioned central characteristic of that process (i.e. successive adjustments to the political parties’ power-sharing mechanisms) to, then, expose the central elements of the current Constitution under the same light.
Authoritarian Constitutionalism
Authors: Pozas-Loyo Andrea , Ríos-Figueroa Julio
Published: April 2022

Authoritarian constitutionalism is a distinct phenomenon that involves an intriguing mixture of a regime type commonly known for its tendency to abuse power with a centuries-old lineage of theories and practices seeking precisely to place limits on how it be used. This chapter provides a conceptual and analytical framework that addresses both dimensions of authoritarian constitutionalism, and in so doing, it discusses the theoretical and empirical advantages and disadvantages of distinct conceptualizations of this term. It then illustrates the different categories in a conceptual map with examples drawn from Latin American countries. The chapter concludes with some promising avenues for research in this interesting and vibrant area.
Constitutions and Foreign Affairs
Authors: Lopes Dawisson Belém , Valente Mario Schettino
Published: April 2022

This chapter focuses on the Constitutions of twenty-two countries from Latin America and the Caribbean to analyse their foreign policy cycles by identifying the constitutional distribution of legal prerogative, and assessing alternatives for participation as well as opposition through institutional design. The results display a variety of constitutional patterns on foreign policy-making in the region, and, despite the changing nature of this subject matter, aim to represent an important heuristic resource for the development of future investigations on the external affairs of Latin American and Caribbean countries. Three specific goals will guide this chapter: (i) mapping out the distribution of prerogatives among Latin American states’ branches through procedural regulation; (ii) identifying non-procedural regulation mechanisms, i.e. normative principles which underpin foreign policy making, as clearly seen in the Brazilian case; and (iii) organizing sets of countries by comparing their constitutional designs.
Costa Rica
Authors: Wilson Bruce M. , Rodriguez Loaiza Olman
Published: April 2022

Costa Rica’s political and geographic remoteness from the Capitanía General de Guatemala (the political and economic administrative centre for Spain’s Central American colonies) allowed the province a great deal of administrative freedom that benefited the country in the independence period. A widely held view of Costa Rica’s democratic origins was based on the country’s geopolitical detachment and general poverty of the settlers. However, this view has been largely debunked and replaced by evidence that suggests that the province was neither egalitarian nor particularly democratic in its early years. This chapter demonstrates that Costa Rica’s rise as one of Latin America’s most accomplished constitutional democracies was neither immediate nor complete at the time of independence, but came about through numerous political struggles, constitutional documents, and several non-democratic governments before the country became a fully-fledged democracy, marked by the first post-Civil War election in 1953.
The Constitutional History of Ecuador
Authors: Salazar Daniela
Published: April 2022

This chapter provides an overview of the constitutional history of Ecuador as well as some details on the current structure of the country’s 2008 Constitution. The fact that Ecuador has associated political change with constituent movements has translated into twenty constitutions with one common characteristic: their inability to fulfil the transformations promised. The chapter begins by reviewing the constitutional history of Ecuador, from before its independence to the present. It then turns to the current Ecuadorian Constitution, approved in Montecristi, Ecuador, in 2008, which has been the subject of praise and criticism by scholars studying neo-constitutionalism and Andean constitutionalism. Focusing on what makes this Constitution distinct, the chapter describes its main provisions regarding rights, the separation of powers, territorial distribution of power, and constitutional reform. It concludes by examining the characteristics of constitutional review by the judiciary and constitutional scholarship in Ecuador.
Use of Health Information Exchange in the Continuity of Care as Viewed by Patients and Nurses
Authors: Itzhaki Michal , Koren Ella , Abu Hussein Khaled , Levy Liron , Gantz Irit , Barnoy Sivia
Published: April 2022

Patients' attitudes toward sharing their personal health information are critical for implementation of health information exchange. Nurses contribute significantly to information sharing within the care continuum in hospitals and community. This study aimed to examine the awareness and readiness of patients with chronic illness and nurses to the use health information exchange. A cross-sectional study was conducted among 314 inpatients with a chronic illness, 110 nurses working in internal wards, and 55 contact nurses working in a large health maintenance organization. The findings showed that the mean level of awareness was low across all three groups. Contact nurses expressed more positive attitudes than internal ward nurses or patients and were more willing than patients to share information with healthcare workers. Knowledge, attitudes, and being a nurse predicted the intention to share information with medical healthcare providers and with agents not involved in direct care. Before implementation of a health information exchange system, it is important to raise awareness, readiness, and intention to use it among the public, nurses, and other medical staff. Policy makers should organize national campaigns under the auspices of the Ministry of Health to present the advantages and provide detailed information about the system.
Divergent Perspectives of Filipino PLWH, Their Partners, and Care Providers on Sexuality After an HIV Diagnosis: A Q-Methodological Analysis
Authors: Calaguas Noriel P.
Published: April 2022

This study explores the perspectives that Filipinos with professional and personal experience with people living with HIV hold about sexuality after an HIV diagnosis. Twenty people living with HIV (PLWH), 11 partners of PLWH, and 10 HIV care professionals in the Philippines were asked to rank-order 54 statements about sexuality post-HIV diagnosis. They shared the reasoning behind their rankings on an online survey platform. By-person factor analysis was done, with factors extracted based on principal component analysis followed by varimax rotation. The analysis yielded six factors with 22 males' and 3 females' Q-sorts exemplifying the views regarding sexuality post-HIV diagnosis: to be human, is to be sexual; information is power; fear of being othered; partnership for enhanced sexuality; disclosure and trust; and communication is foundational. This study revealed diverse viewpoints about sexuality after an HIV diagnosis. HIV care professionals play a decisive role in addressing concerns relating to the sexual health and well-being of newly diagnosed PLWH.
Genomics update 2022: Clinician and patient hot topics
Authors: Wysocki Kenneth , Seibert Diane
Published: April 2022

Advances in genomics research and clinical applications continue to accelerate. Coupled with the availability of direct-to-consumer (DTC) marketing of genetic testing and new discoveries, patients are increasingly coming into primary care with genomic questions. This article offers a snapshot of the kinds of questions patients are asking and that providers should be prepared to discuss such as what to do with DTC results or whether pharmacogenetics testing would help make sure “the right” medication is prescribed. Clinicians should understand the value of clinical guidelines (and where to find them), how to find a genetic specialist, what's happening with gene editing (to include gene sequencing), what's on the horizon in cancer care, and what the future might hold.
The Utility of the Ultrasonographic Characteristics in Differentiating Between Malignant and Tuberculous Mediastinal Lymphadenopathy During EBUS-TBNA
Authors: Madan Karan , Madan Manu , Mittal Saurabh , Tiwari Pavan , Hadda Vijay , Mohan Anant , Pandey Ravindra M. , Guleria Randeep
Published: April 2022

Background:

Ultrasonographic characteristics may help differentiate between benign and malignant lymph nodes during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). There is limited data on the utility of various ultrasonographic lymph node features to differentiate between malignant and tuberculous mediastinal lymphadenopathy.

Methods:

We studied the various EBUS ultrasonographic lymph node characteristics (size, shape, margins, heterogeneous echotexture, calcification, central hilar structure, lymph node conglomeration, central intranodal vessel, and coagulation necrosis sign) from our available EBUS-TBNA database.

Results:

We extracted 1086 subjects [547 with tuberculosis (TB) and 539 with malignant diagnosis]. Comparing the 2 groups (multivariate analysis), presence of central hilar structure (8.2% vs. 2.6%), coagulation necrosis sign (37.5% vs. 13.7%), lymph node conglomeration (30.5% vs. 7.2%), calcification (5.1% vs. 1.5%), and distinct margins (83.5% vs. 69.8%), were significantly more common in TB (P<0.05). On the other hand, malignant lymph nodes were larger and more likely to show the presence of a central intranodal vessel (20% vs. 15.8%, P=0.04, multivariate analysis). The absence of lymph node conglomeration had the highest overall diagnostic accuracy (0.61) for the differentiation between malignant and tuberculous lymph nodes.

Conclusion:

Sonographic lymph node characteristics may help differentiate malignant and tuberculous mediastinal lymphadenopathy. Contrary to previously published literature, we observed coagulation necrosis sign, heterogeneous echotexture and absent central intranodal vessel, more commonly in TB than malignant nodes. These findings from a TB endemic setting are different from other settings, where the prevalence of lung cancer is high in patients undergoing EBUS-TBNA.
Biomechanically Compliant Gynecologic Training Simulator
Authors: Nadhif Muhammad Hanif , Irsyad Muhammad , Ocviyanti Dwiana
Published: April 2022

Introduction

Pap smear training is commonly conducted using simulators before practicing with humans. Unfortunately, existing simulators do not well simulate the biomechanical properties of pelvic tissues, and this may negatively impact the training outcome. In this study, we used finite element analysis (FEA) to identify a material that most accurately simulates pelvic tissues in terms of biomechanical properties for fabricating gynecologic training simulators. The selected material was then used to fabricate a vagina and cervix model using a hybrid technique of fused deposition modeling and molding to qualitatively confirm the structural integrity of the simulator.

Methods

The vagina and cervix were reconstructed in a 3-dimensional feature according to geometrical parameters reported in the literature. The biomechanical compliance of the simulators was investigated by comparing 5 materials—RTV615, Dragon Skin 10, Dragon Skin 30, Dragon Skin FX-Pro, and Ecoflex 00-30—and a pelvic tissue model (control) using 2 FEA modules. The structural mechanics module simulated the insertion and opening of a vaginal speculum, and the (1) horizontal opening of the vagina and peak von Mises stress at the anterior and (2) posterior walls of the vagina were obtained. The explicit dynamics module estimated (1) the fracture stress during punch biopsies and (2) maximum perpendicular deformation of the cervix before break. The most biomechanically compliant material was subsequently used to fabricate the simulator using the hybrid technique.

Results

From the FEA, the horizontal opening of the vagina, peak von Mises stress at the anterior wall of the vagina, peak von Mises stress at the posterior wall of the vagina fracture stress, and maximum perpendicular deformation of the cervix before break were obtained; the results of Dragon Skin 10 and the control were most similar. Therefore, the simulator was fabricated using the material. A qualitative evaluation of the simulator by the naked eye verified its structural integrity.

Conclusions

Of the materials studied, the FEA results showed that Dragon Skin 10 was the most accurate material for simulating pelvic tissues in terms of the biomechanical properties in a gynecologic training simulator. The simulator was also successfully fabricated using the hybrid technique. Further studies may also involve experimental testing to support the simulation results.
Changing characteristics over time of individuals receiving COVID-19 vaccines in Denmark: A population-based descriptive study of vaccine uptake
Authors: Reilev Mette , Olesen Morten , Kildegaard Helene , Støvring Henrik , Andersen Jacob H. , Hallas Jesper , Lund Lars C. , Ladebo Louise , Ernst Martin T. , Damkier Per , Jensen Peter B. , Pottegård Anton , Rasmussen Lotte
Published: April 2022

Aims

The Danish authorities implemented a differential rollout of the COVID-19 vaccines where individuals at high risk of COVID-19 were prioritized. We describe the temporal uptake of COVID-19 vaccines and changing characteristics of vaccine recipients in Denmark.

Methods

Using the Danish national health care registries, we identified all Danish residents ≥5 years of age who received at least one dose of a COVID-19 vaccine from December 27th, 2020, to January 29th, 2022. We charted the daily number of newly vaccinated individuals and the cumulative vaccine coverage over time, stratified by vaccine type, age groups, and vaccination priority groups. In addition, we described characteristics of vaccine recipients during 2-months-intervals and in vaccination priority groups.

Results

By January 29th, 2022, 86%, 84% and 63% of Danish residents ≥5 years had received a first, second, and third dose, respectively, of a COVID-19 vaccine, most commonly the BNT162b2 vaccine (84% of vaccinated individuals). Vaccine uptake ranged from 48% in 5-11-year-olds up to 98% in 65-74-year-olds. Individuals vaccinated before June 2021 were older (median age 61-70 years vs. 10-35 years in later periods) and had more comorbidities such as hypertension (22-28% vs. 0.77-2.8% in later periods), chronic lung disease (9.4-15% vs. 3.7-4.6% in later periods), and diabetes (9.3-12% vs. 0.91-2.4% in later periods).

Conclusions

The uptake of the COVID-19 vaccines is high in Denmark. We document substantial changes over time in characteristics of vaccine recipients which should be considered when designing and interpreting studies on the effectiveness and safety of COVID-19 vaccines.
No magic bullet: limiting in-school transmission in the face of variable SARS-CoV-2 viral loads
Authors: Van Egeren Debra , Stoddard Madison , Malakar Abir , Ghosh Debayan , Acharya Antu , Mainuddin Sk , Majumdar Biswajit , Luo Deborah , Nolan Ryan , Joseph-McCarthy Diane , White Laura F. , Hochberg Natasha S. , Basu Saikat , Chakravarty Arijit
Published: April 2022

In the face of a long-running pandemic, understanding the drivers of ongoing SARS-CoV-2 transmission is crucial for the rational management of COVID-19 disease burden. Keeping schools open has emerged as a vital societal imperative during the pandemic, but in-school transmission of SARS-CoV-2 can contribute to further prolonging the pandemic. In this context, the role of schools in driving SARS-CoV-2 transmission acquires critical importance. Here we model in-school transmission from first principles to investigate the effectiveness of layered mitigation strategies on limiting in-school spread. We examine the effect of masks and air quality (ventilation, filtration and ionizers) on steady-state viral load in classrooms, as well as on the number of particles inhaled by an uninfected person. The effectiveness of these measures in limiting viral transmission is assessed for variants with different levels of mean viral load (Wuhan, Delta, Omicron). Our results suggest that a layered mitigation strategy can be used effectively to limit in-school transmission, with certain limitations. First, poorly designed strategies (insufficient ventilation, no masks, staying open under high levels of community transmission) will permit in-school spread even if some level of mitigation is ostensibly present. Second, for viral variants that are sufficiently contagious, it may be difficult to construct any set of interventions capable of blocking transmission once an infected individual is present, underscoring the importance of other measures. Our findings provide several practical recommendations: the use of a layered mitigation strategy that is designed to limit transmission, with other measures such as frequent surveillance testing and smaller class sizes (such as by offering remote schooling options to those who prefer it) as needed.
Identification of Global DNA Methylation Signatures in Patients of High Altitude Induced Venous Thrombo-Embolism (HA-VTE)
Authors: Srivastava Swati , Garg Iti , Kumari Babita , Yanamandra Uday , Singh Jasjit , Ganju Lilly , Varshney Rajeev
Published: April 2022

Background

Pathophysiology of venous thrombo-embolism (VTE) depends upon several acquired, inherited and environmental risk factors, including high altitude (HA) exposure. The present study aims to gain insights into pathophysiological mechanism(s) of high altitude induced VTE (HA-VTE) by studying global methylation signatures.

Methodology

Blood samples were collected from Indian Army volunteers divided into four study groups; sea level control (SLC), sea level VTE patients (SL-VTE), high altitude control (HAC) and high altitude VTE patients (HA-VTE). Methylation patterns were studied using whole genome bisulfate sequencing. Differentially methylated genes and pathways were identified by comparing percentage methylation.

Results

Highest DM was observed in SL-VTE (1162 gene) compared to SLC where in hyper methylation was predominant (62.9%) compared to hypo methylation (37.05%). A reverse trend was observed in HA-VTE, where hypo methylation (61.69%) was predominant over hyper methylation (38.30%) in a total of 296 DM genes. Differential hypomethylation of genes involved in cell adhesion/platelet activity (CADM1, PTPRK, PDGFA) and immune response (CXCL12, IL4, IRF4, NLRP1) was observed in HA-VTE whereas genes encoding transcription factors (GSC, RPSKA1), trans membrane receptor (NOTCH2) and growth factor (TGFB2) were hypermethylated in comparison to SL-VTE. Methylation pattern of HA-VTE compared to HAC showed hypomethylation in genes involved in oxidative phosphorylation (CPOX), immune response and stress response (NDRG1), while those involved in signaling mechanisms (KALRN), neurotransmitter release (TMPRSS2) and transcription factor (ELF1) were hyper-methylated.

Conclusions

Our study for the first time reveals genome wide methylation pattern in HA-VTE group where in differential hypo methylation in cell adhesion and inflammation genes was observed.
The Application of Data Science Techniques and Algorithms in Women’s Health Studies
Authors: Akpan Ikpe Justice , Aguolu Obianuju Genevieve
Published: April 2022

Objective

Evaluate and map data science methods employed to solve health conditions of women, examine the problems tackled and the effectiveness.

Research Method

Text analytics, science mapping, and descriptive evaluation of data science methods utilized in women-related health research.

Findings

(i). The trends in scholarships using data science methods indicate gaps between women and men relating to health burden and access to health. (ii). The coronavirus (SARS-CoV-2) outbreak and the ongoing COVID-19 pandemic tend to widen the identified health gaps, increasing the disease burden for women, while reducing access to health. There are noticeable additional health burdens on pregnant women and those with several health conditions (breast cancer, gynecologic oncology, cardiovascular disease, and more). (iii). Over 95% of studies using data science methods (artificial intelligence, machine learning, novel algorithms, predictive, big data, visual analytics, clinical decision support systems, or a combination of the methods) indicate significant effectiveness. (iv). Mapping of the scientific literature to authors, sources, and countries show an upward trend; 997 (16%), 113 (1.33%), and 57 (2.63%) per article, respectively. About 95% of research utilizing data science methods in women’s health studies occurred within the last four (4) years.

Conclusions

The application of data science methods in tackling different health problems of women is effective and growing, and capable of easing the burden of health in women. The ongoing COVID-19 pandemic tends to compound the health burden for women more than men. Policymakers must do more to improve access to health for women.
Detection of mosaic chromosomal alterations in children with severe developmental disorders recruited to the DDD study
Authors: Eberhardt Ruth Y. , Wright Caroline F. , FitzPatrick David R. , Hurles Matthew E. , Firth Helen V.
Published: April 2022

Purpose

Structural mosaicism has been previously implicated in developmental disorders. We aim to identify rare mosaic chromosomal alterations (MCAs) in probands with severe undiagnosed developmental disorders.

Methods

We identified MCAs in SNP array data from 12,530 probands in the Deciphering Developmental Disorders (DDD) study using MoChA.

Results

We found 61 MCAs in 57 probands, many of these were tissue specific. In 23/26 (88.5%) cases for which the MCA was detected in saliva where blood was also available for analysis, the MCA could not be detected in blood. The MCAs included 20 polysomies, comprising either one arm of a chromosome or a whole chromosome, for which we were able to show the timing of the error (25% mitosis, 40% meiosis I, 35% meiosis II). Only 2/57 (3.5%) of the probands in whom we found MCAs had another likely genetic diagnosis identified by whole exome sequencing, despite an overall diagnostic yield of ∼40% across the cohort.

Conclusion

Our results show that identification of MCAs provides candidate diagnoses for previously undiagnosed patients with developmental disorders, potentially explaining ∼0.45% of cases in the DDD study. Nearly 90% of these MCAs would have remained undetected by analysing DNA from blood and no other tissue.
Effectiveness of Typhoid Conjugate Vaccine in Zimbabwe used in response to an outbreak among children and young adults: a matched case control study
Authors: Lightowler Maria S. , Manangazira Portia , Nackers Fabienne , Van Herp Michel , Phiri Isaac , Kuwenyi Kuziwa , Panunzi Isabella , Garone Daniela , Marume Farayi , Tarupiwa Andrew , Ferreras Eva , Duri Clemence , Luquero Francisco J.
Published: April 2022

Background

Zimbabwe suffers from regular outbreaks of typhoid fever (TF), worse since 2017. Most cases were in Harare and a vaccination campaign with Typhoid Conjugate Vaccine (TCV) was conducted in March 2019. The vaccine effectiveness (VE) was assessed against culture-confirmed S. Typhi in children six months to 15 years and in individuals six months to 45 years in Harare.

Methods

A matched case-control study was conducted in three urban suburbs of Harare targeted by the TCV vaccination campaign. Suspected TF cases were enrolled prospectively in four health facilities and were matched to facility (1:1) and community (1:5) controls.

Findings

Of 504 suspected cases from July 2019 to March 2020, 148 laboratory-confirmed TF cases and 153 controls confirmed-negative were identified. One hundred and five (47 aged six months to 15 years) cases were age, sex, and residence matched with 105 facility-based controls while 96 cases were matched 1:5 by age, sex, and immediate-neighbour with 229 community controls.

The adjusted VE against confirmed TF was 75% (95%CI: 1–94, p=0.049) compared to facility controls, and 84% (95%CI: 57–94, p<0.001) compared to community controls in individuals six months to 15 years. The adjusted VE against confirmed TF was 46% (95%CI: 26–77, p=0.153) compared to facility controls, and 67% (95%CI: 35–83, p=0.002) compared to community controls six months to 45 years old.

Interpretation

This study confirms that one vaccine dose of TCV is effective to control TF in children between six months and 15 years old in an African setting.
Human Papillomavirus (HPV) self-testing among un- and under-screened Māori, Pasifika, and Asian women in Aotearoa New Zealand: a preference survey among responders and interviews with clinical-trial non-responders
Authors: Sherman Susan M. , Bartholomew Karen , Brewer Naomi , Bromhead Collette , Crengle Sue , Cunningham Chris , Douwes Jeroen , Foliaki Sunia , Grant Jane , Maxwell Anna , McPherson Georgina , Potter John D. , Scott Nina , Wihongi Helen
Published: April 2022

Aim

Māori, Pasifika, and Asian women are less likely to attend cervical screening and Māori and Pasifika women are more likely to be diagnosed with later-stage cervical cancer than other women in Aotearoa New Zealand. This study – with under-screened women taking part in a randomised controlled trial comparing self-testing and standard screening – explored the acceptability of an HPV self-test kit and the preferred method for receiving it.

Methods

Māori, Pasifika, and Asian women (N=376) completed a postal questionnaire. Twenty-six women who had not accepted the trial invitation were interviewed to understand their reasons for non-participation.

Results

Most women found the self-test kit easy and convenient to use and reported that they did not find it painful, uncomfortable, or embarrassing. This was reflected in the preference for a self-test over a future smear test on the same grounds. Most women preferred to receive the kit by mail and take the test themselves, rather than having it done by a doctor or nurse. There was a range of preferences relating to how to return the kit. Phone calls with non-responders revealed that, although most had received the test kit, the reasons for not choosing to be involved included not wanting to, being too busy, or forgetting.

Conclusions

HPV self-testing was acceptable for Māori, Pasifika, and Asian women in Aotearoa New Zealand. HPV self-testing has considerable potential to reduce the inequities in the current screening programme and should be made available with appropriate delivery options as soon as possible.
A recurrent network architecture explains tectal activity dynamics and experience-dependent behaviour
Authors: Zylbertal Asaph , Bianco Isaac H.
Published: April 2022

The ongoing activity of neuronal populations represents an internal brain state that influences how sensory information is processed to control behaviour. Conversely, external sensory inputs perturb network dynamics, resulting in lasting effects that persist beyond the duration of the stimulus. However, the relationship between these dynamics and circuit architecture and their impact on sensory processing, cognition and behaviour are poorly understood. By combining cellular-resolution calcium imaging with mechanistic network modelling, we aimed to infer the spatial and temporal network interactions in the zebrafish optic tectum that shape its ongoing activity and state-dependent responses to visual input. We showed that a simple recurrent network architecture, wherein tectal dynamics are dominated by fast, short range, excitation countered by long-lasting, activity-dependent suppression, was sufficient to explain multiple facets of population activity including intermittent bursting, trial-to-trial sensory response variability and spatially-selective response adaptation. Moreover, these dynamics also predicted behavioural trends such as selective habituation of visually evoked prey-catching responses. Overall, we demonstrate that a mechanistic circuit model, built upon a uniform recurrent connectivity motif, can estimate the incidental state of a dynamic neural network and account for experience-dependent effects on sensory encoding and visually guided behaviour.
Gradient-k: Improving the Performance of K-Means Using the Density Gradient
Authors: Ciuparu Andrei , Mureșan Raul C.
Published: April 2022

We introduce Gradient-k, an upgrade of the k-means algorithm that improves clustering accuracy and reduces the number of iterations required for convergence. This is achieved by correcting the distance used in the k-means algorithm by a factor based on the angle between the density gradient and the direction to the cluster center. We show that this correction allows the algorithm to go beyond the traditional tessellation obtained by k-means, enabling the creation of nonlinear separation boundaries. The correction also provides the ability to distinguish clusters having non-normal shapes and of varying densities. Furthermore, Gradient-k has a lower computational complexity for datasets with many samples. We compare the performance of Gradient-k with that of k-means and of DBSCAN on several benchmark datasets, as well as on a more realistic dataset in the context of neural spike sorting.
Performance and limitations of linkage-disequilibrium-based methods for inferring the genomic landscape of recombination and detecting hotspots: a simulation study
Authors: Raynaud Marie , Gagnaire Pierre-Alexandre , Galtier Nicolas
Published: April 2022

Knowledge of recombination rate variation along the genome provides important insights into genome and phenotypic evolution. Population genomic approaches offer an attractive way to infer the population-scaled recombination rate ρ=4Nerusing the linkage disequilibrium information contained in DNA sequence polymorphism data. Such methods have been used in a broad range of plant and animal species to build genome-wide recombination maps. However, the reliability of these inferences has only been assessed under a restrictive set of conditions. Here, we evaluate the ability of one of the most widely used coalescent-based programs,LDhelmet, to infer a genomic landscape of recombination with the biological characteristics of a human-like landscape including hotspots. Using simulations, we specifically assessed the impact of methodological (sample size, phasing errors, block penalty) and evolutionary parameters (effective population size (Ne), demographic history, mutation to recombination rate ratio) on inferred map quality. We report reasonably good correlations between simulated and inferred landscapes, but point to limitations when it comes to detecting recombination hotspots. False positive and false negative hotspots considerably confound fine-scale patterns of inferred recombination under a wide range of conditions, particularly whenNeis small and the mutation/recombination rate ratio is low, to the extent that maps inferred from populations sharing the same recombination landscape appear uncorrelated. We thus address a message of caution for the users of these approaches, at least for genomes with complex recombination landscapes such as in humans.
The dynamical Matryoshka model: 2. Modeling of local lipid dynamics at the sub-nanosecond timescale in phospholipid membranes
Authors: Cisse Aline , Matsuo Tatsuhito , Plazanet Marie , Natali Francesca , Koza Michael Marek , Ollivier Jacques , Bicout Dominique J. , Peters Judith
Published: April 2022

Biological membranes are generally formed by lipids and proteins. Often, the membrane properties are studied through model membranes formed by phospholipids only. They are molecules composed by a hydrophilic head group and hydrophobic tails, which can present a panoply of various motions, including small localized movements of a few atoms up to the diffusion of the whole lipid or collective motions of many of them. In the past, efforts were made to measure these motions experimentally by incoherent neutron scattering and to quantify them, but with upcoming modern neutron sources and instruments, such models can now be improved. In the present work, we expose a quantitative and exhaustive study of lipid dynamics on DMPC and DMPG membranes, using the Matryoshka model recently developed by our group. The model is confronted here to experimental data collected on two different membrane samples, at three temperatures and two instruments. Despite such complexity, the model describes reliably the data and permits to extract a series of parameters. The results compare also very well to other values found in the literature.

Abstract Figure

Figure 1:

Graphical abstract.

Highlights

- The Matryoshka model brings a new general description of local lipid dynamics.

- Phospholipid membranes on various conditions are compared in this novel framework.

- Effects of main phase transition, membrane geometry or motion direction are probed.

- Despite high number of parameters, overfitting is avoided by a global fit strategy.