bluuebunny/crossref_metadata_2025 huggingface dataset:
Disease-associated mutations in WDR34 lead to diverse impacts on the assembly and function of dynein-2
Authors: Shak Caroline , Vuolo Laura , Uddin Borhan , Katoh Yohei , Brown Tom , Mukhopadhyay Aakash G. , Heesom Kate , Roberts Anthony J. , Stevenson Nicola , Nakayama Kazuhisa , Stephens David J.
Published: October 2022

The primary cilium is a sensory organelle, receiving signals from the external environment and relaying them into the cell. Mutations in proteins required for transport in the primary cilium result in ciliopathies, a group of genetic disorders that commonly lead to the malformation of organs such as the kidney, liver and eyes and skeletal dysplasias. The motor proteins dynein-2 and kinesin-2 mediate retrograde and anterograde transport, respectively, in the cilium. WDR34 (also known as DYNC2I2), a dynein-2 intermediate chain, is required for the maintenance of cilia function. Here, we investigated WDR34 mutations identified in Jeune syndrome, short-rib polydactyly syndrome and asphyxiating thoracic dysplasia patients. There is a poor correlation between genotype and phenotype in these cases, making diagnosis and treatment highly complex. We set out to define the biological impacts on cilia formation and function of WDR34 mutations by stably expressing the mutant proteins in WDR34-knockout cells. WDR34 mutations led to different spectrums of phenotypes. Quantitative proteomics demonstrated changes in dynein-2 assembly, whereas initiation and extension of the axoneme, localization of intraflagellar transport complex-B proteins, transition zone integrity and Hedgehog signalling were also affected.
Automated segmentation of endometriosis using transfer learning technique
Authors: Visalaxi S. , Sudalaimuthu T.
Published: October 2022

Background: This paper focuses on segmenting the exact location of endometriosis using the state-of-art technique known as U-Net. Endometriosis is a progressive disorder that has a significant impact on women. The lesion-like appearance that grows inside the uterus and sheds for every periodical cycle is known as endometriosis. If the lesion exists and is transferred to other locations in the women’s reproductive system, it may lead to a serious problem. Besides radiologists deep learning techniques exist for recognizing the presence and aggravation of endometriosis.

Methods: The proposed method known as structural similarity analysis of endometriosis (SSAE) identifies the similarity between pathologically identified and annotated images obtained from standardized dataset known as GLENDA v1.5 by implementing two systematic approaches. The first approach is based on semantic segmentation and the second approach uses statistical analysis. Semantic segmentation is a cutting-edge technology for identifying exact locations by performing pixel-level classification. In semantic segmentation, U-Net is a transfer-learning architecture that works effectively for biomedical image classification. The SSAE implements the U-Net architecture for segmenting endometriosis based on the region of occurrence. The second approach proves the similarity between pathologically identified images and the corresponding annotated images using a statistical evaluation. Statistical analysis was performed using calculation of both the mean and standard deviation of all four regions by implementing systematic sampling procedure.

Results: The SSAE obtains the intersection over union value of 0.72 and the F1 score of 0.74 for the trained dataset. The means of both the laparoscopic and annotated images for all regions were similar. Consequently, the SSAE facilitated the presence of abnormalities in a specific region.

Conclusions: The proposed SSAE approach identifies the affected region using U-Net architecture and systematic sampling procedure.
Surgical residents’ approach to training: are elements of deliberate practice observed?
Authors: Nelson Ferguson Kendra , Paradis Josée
Published: October 2022

Background: Research in the area of deliberate practice has consistently shown that intense, concentrated, goal-oriented practice in a focused domain, such as medicine, can improve both skill development and performance to attain a progressively higher standard of excellence. In theory, utilizing deliberate practice in a medical context could result in improved surgical training and in turn better patient outcomes. Therefore, the purpose of this study was to gain a better understanding of how surgical residents approach their training from the perspective of the surgical residents themselves and to explore if elements of deliberate practice are observed.

Methods: Eight surgical trainees participated in one of two focus groups depending on their training level (five junior residents; three senior residents). With the exploratory nature of this research, a focus group methodology was utilized.

Results: By employing both deductive and inductive thematic analysis techniques, three themes were extracted from the data: learning resources and strategies, role of a junior/senior, and approaching weaknesses.

Conclusions: Although elements of deliberate practice were discussed, higher functioning is necessary to achieve performance excellence, leading to improved patient outcomes.
Treatment of patients with ventral hernia and obesity
Authors: Belokonev Vladimir , Pushkin Sergey , Zaharov Valeriy , Kovaleva Zinaida , Grachev Dmitriy , Vol'gov Lev , Larina Tat'yana , Parshikov Vladimir , Samarcev Vladimir
Published: October 2022

The monograph is devoted to the pathogenesis, clinic and treatment of patients with ventral hernia and obesity up to grade II. The features of the development of the disease, accompanied by the development of a cutaneous-subcutaneous apron — panniculus, which significantly affects the dynamics of hernia enlargement and the quality of life of the patient, are described. The classification of the panniculus, developed on the basis of the proposed mathematical model of the development of the pathological process in the abdominal wall, and the justification of indications for its removal are presented. The technique of performing operations in patients with hernias and obesity is described, including the features of processing the remaining edges of the cutaneous-subcutaneous apron, which is aimed at preventing the formation of subcutaneous tissue infarction and seroma in the postoperative period. An algorithm for the treatment of patients with hernias and obesity is proposed, including indications for the volume of surgery depending on the size of the hernia and the skin-subcutaneous apron. Possible complications of operations, methods of their prevention and immediate results are described.
Designed for surgeons, students, residents, postgraduates and researchers engaged in the study of problems of experimental and clinical herniology.
Methods of financial planning and evaluation of the effectiveness of management of production and financial activities of the enterprise
Authors: Mischenko Aleksandr , Pilyugina Anna , Abdikeev Niyaz , Omel'chenko Irina
Published: October 2022

The monograph considers a set of models of financial planning and evaluation of the effectiveness of management of production and financial activities of the enterprise, which allows to obtain modeling results in conditions of various initial data. Methodological approaches to the construction of performance management systems on key aspects of the operational, financial and investment activities of the enterprise are presented. The possibility of applying in practice models of production and economic optimization in conditions of increasing credit and investment activity is shown.
It is designed for students, postgraduates and teachers of economic training areas, as well as for economists, managers and managers of enterprises.
Scientific and applied tasks of technosphere safety
Authors: Esipov Yuriy , Meshi Besik , Dzhilyadzhi Mustafa , Hazov Aleksandr
Published: October 2022

The monograph sets and solves the following tasks in a complex: systematization of types of safety; formalization of the structure and models of accidents; unification of the concepts of "safety" and "risk", primarily in relation to technical systems "protection - object - subject - environment"; as well as the tasks of combining and (or) generalization of algorithms for calculating safety indicators and the risk of systems based on probabilistic and possibilistic (fuzzy) measures of occurrence of accidents and the establishment of application boundaries for "objective" and (or) "subjective" indicators of safety and risk of technical systems. Using typical examples, the methods and results of solving the stated tasks are considered.
For students, postgraduates and teachers of technical and technological universities and faculties, as well as for a wide range of readers interested in technosphere security issues.
Information and Communication Policy in Wartime: the Case of Ukraine
Authors: Karpchuk Natalia
Published: October 2022

Information and communication policy aims to build effective, harmonious communication between all actors of the democratic process with extensive use of ICTs and direct communication. The war creates an aggressive environment, which also affects the communication processes in the information sphere of the state, in particular, there is more emphasis on information, less – on deliberation. The article examines the tools used by Ukraine’s state and non-state structures to: 1) objectively inform the citizens and avoid panic, 2) inform the world community about the war and intensify international support for Ukraine, 3) fight Kremlin fakes and convey reality to the RF citizens. The specifics of TV broadcasting in Ukraine during the war, media activity of officials, social pages and Telegram channels of ministries, the Armed Forces, the Office of the President, the Verkhovna Rada of Ukraine, public organizations fighting against disinformation and fakes are analyzed. It is found out that the chosen information and communication policy is efficient at the national level (mobilized citizens to fight for victory, reduced panic, increased awareness and criticism of fakes) and at the “western” level (international moral, financial and military support to Ukraine, sanctions against Russia). However, the work in the information space of the Russian Federation is problematic because it is exposed to fierce opposition by the objects of Russian propaganda.
El comercio de salazones de pescado lusitanas: una lectura desde los pecios romanos del Mediterráneo.
Authors: Bombico Sonia
Published: October 2022

Los pecios son esenciales para el estudio de las economías antiguas. Este artículo se centra en el estudio de los pecios romanos del Mediterráneo Occidental cargados de ánforas lusitanas para el transporte de salazones de pescado. A pesar de su reducido número, estos pecios ofrecen pruebas de la evolución general del comercio de mercancías lusitanas, en particular de las salazones y salsas de pescado, y ayudan a identificar las principales rutas comerciales de exportación para todo el Imperio Romano.
Impact of Immigration Act 2014
Authors: Hurrell Anita
Published: October 2022

The coalition's first piece of immigration legislation makes changes to the immigration system that will affect children, explains Anita Hurrell, legal and policy officer at Coram Children's Legal Centre
Experts come together to forge early intervention momentum
Authors: Puffett Neil
Published: October 2022

CYP Now's Early Intervention conference brought together some of England's leading advocates and practitioners in early intervention to discuss the way ahead for policy and practice
Children hit by legal aid cuts
Authors: Hurrell Anita
Published: October 2022

Eighteen months on from drastic cuts to civil legal aid, evidence is showing the detrimental impact on children's rights, explains Anita Hurrell, legal and policy officer at Coram Children's Legal Centre
Councils identify elements of ‘gold standard’ in leaving care services
Authors: Hayes Derren
Published: October 2022

The New Belongings programme has seen councils devise improvements for young people leaving care, with senior buy-in and care leaver involvement critical to making positive changes as they make the move to independent living
Time to end cycle of offending
Authors: Puffett Neil
Published: October 2022

Better support for the children of prisoners could make it less likely they offend themselves, say campaigners
Government rights failings exposed
Authors: Hurrell Anita
Published: October 2022

Children's charities have launched a damning report highlighting the government's failure to prioritise children, reports Anita Hurrell, legal and policy officer at Coram Children's Legal Centre
When are Two Hats Better than One?
Authors: Lepper Joe
Published: October 2022

Some local authorities have combined the functions of director of children's services with those of other top-tier managers. Joe Lepper explores the benefits and potential pitfalls of different approaches
Councils lead efforts to prevent young people being radicalised
Authors: Brown Jess
Published: October 2022

Councils are central to government efforts to protect vulnerable children from being exploited by radical religious groups, and inner city authorities, such as Tower Hamlets, are at the forefront of developing new ways to do this
CSE action plan: the key elements
Authors: Puffett Neil
Published: October 2022

After recent child sexual abuse revelations, the government has developed a national response strategy
Protecting the vulnerable online
Authors: Coleman John
Published: October 2022

Children's professionals must help vulnerable young people stay safe online, says John Coleman
Tackling discrimination in schools
Authors: Offord Adam
Published: October 2022

Councils should insist schools record and report incidents of racism and religious hatred, youth leaders say
Your guide to the Children and Social Work Act
Authors: Hayes Derren
Published: October 2022

What the act means for everyday practice across the children's workforce
Youth mental health champions
Authors: Hayes Derren
Published: October 2022

Teachers are to be trained how to respond to pupils in mental distress under a government initiative
Goodwill unfazed by big brief
Authors: Puffett Neil
Published: October 2022

Children's minister offers councils more improvement support, but warns doing more with less will continue
Concerns over family court deal
Authors: Hayes Derren
Published: October 2022

Children's advocates claim agreement could see Cafcass and social workers “collude” in care cases
Government turns to innovation programme to address care rise
Authors: Puffett Neil
Published: October 2022

Three projects aimed at preventing children coming into care and helping those already in the system to leave are to be expanded to 20 councils. Experts call for greater emphasis on supporting families to stay together
Predictive analytics
Authors: Selwyn Richard
Published: October 2022

Commissioners are grasping the potential of data analytics to predict demand for children's services, says Richard Selwyn
Merits of Labour youth plans
Authors: Cook Bren
Published: October 2022

Youth work academic assesses if Labour's Youth Strategy could regenerate the sector following deep cuts
VOLUNTEERS HELP CHILDREN IN CARE
Authors: Pestano Catherine
Published: October 2022

Independent visitors provide vital support to children in care. Catherine Pestano, who helps co-ordinate a network of nearly 80 volunteers in Croydon, south London, describes a typical week for the service
Study links trauma to offending
Authors: Hayes Derren
Published: October 2022

Study of young offenders in West Midlands prompts plans to redesign youth justice and support systems
THE LANGUAGE OF CHILDREN'S SERVICES
Authors: Goddard Charlotte
Published: October 2022

Like many other sectors, children's services use a lot of jargon but there is concern some common terms risk stigmatising children, young people and families. Charlotte Goddard investigates
Questions on revamped national child asylum transfer scheme
Authors: Simpson Fiona
Published: October 2022

Amid the recent surge of migrants across the Channel, the government has made compulsory a scheme to disperse unaccompanied asylum-seeking children across the UK after some South East councils were struggling to cope
Learning and reflections from the iHV Emotional Wellbeing at Work Champions Programme
Authors: Baldwin Sharin , Stephen Rachel , Kelly Patricia , Bishop Philippa
Published: October 2022

The health visiting workforce, along with healthcare staff from other sectors, have reported increased rates of stress, anxiety and burnout following the COVID-19 pandemic. In response, the Institute of Health Visiting developed an Emotional Wellbeing at Work (EWW) programme in 2020. Following the successful implementation and evaluation of the original programme, a Champions cascade delivery model was adopted to increase the reach of the programme and build greater capacity to enhance the emotional wellbeing of the health visiting workforce. This article discusses the evaluation, learning and reflections from the EWW programme, developed specifically for the health visiting workforce in the UK.
managing equality and diversity, part 9: poverty: Poor chance
Authors: Jozwiak Gabriella
Published: October 2022

How are some settings providing the extra support that disadvantaged children need, asks Gabriella Jozwiak
childcare counsel
Authors: Robins Caroline
Published: October 2022

Our resident employment lawyer Caroline Robins, Eversheds principal associate, answers your questions
Interview
Authors: Bollington Andrew
Published: October 2022

Launched in September, Squirrel Scouts will be rolled out in the communities hardest hit by the pandemic. Children will be encouraged to get active and explore nature, earning them badges like other Scouts. It is the first time in 35 years the Scouts have launched a new programme.
education for sustainability: All equal
Authors: Boyd Diane
Published: October 2022

Continuing her series on introducing the Sustainable Development Goals, Diane Boyd examines how to promote gender equality and the empowerment of women and girls
Measuring near stereopsis
Authors: Vancleef Kathleen , Reed Jenny
Published: October 2022

Dr Kathleen Vancleef and Professor Jenny Read discuss stereopsis and how it is best assessed clinically.
Binocular vision: Correcting disparity
Authors: Schroth Volkhard , Prenat Olga , Vlasak Natalia , Crelier Roger
Published: October 2022

Volkhard Schroth, Olga Prenat, Dr Natalia Vlasak and Professor Roger Crelier introduce the Hoya EyeGenius, a new method for measuring and correcting fixation disparity
Lifting the lid on dry eye practice – part 5: quantity, quality or both?
Authors: McArthur Craig
Published: October 2022

In the latest in our series aimed at those thinking about a specialised dry eye clinical service, Craig McArthur looks at the nature and aetiology of aqueous deficiency dry eye disease.
TFOS Dry Eye WorkShop II – part one
Authors: Farrant Sarah
Published: October 2022

In the first of a three-part discussion of the key points from the recently published second TFOS Dry Eye Workshop, Sarah Farrant describes the latest definition and classification of dry eye disease.
New insights into the long-term success of etafilcon A daily disposable contact lenses
Authors: Brennan Noel , Ruston David
Published: October 2022

Dr Noel Brennan and David Ruston discuss the latest findings with etafilcon A daily disposable contact lenses which support the significant role for hydrogel daily disposables in contemporary contact lens practice.
The evolution of clinical vision assessment 1
Authors: Thomson David
Published: October 2022

In the first of a two-part discussion of the various ways of assessing vision and visual acuity, Professor David Thomson focuses on distance charts of both high and variable contrast (C78864, one distance learning CET point suitable for optometrists and dispensing opticians)
The Rosenberg Self-esteem Scale: A Confirmatory Factor Analysis Study
Authors: Bouih Abdelouahed , Benattabou Driss , Nadif Bendaoud , Benhima Mohamed , Benfilali Ismail
Published: October 2022

The aim of the present study is to conduct a confirmatory factor analysis (CFA) of the Rosenberg Self-esteem Scale (RSES) as part of the study of affective variables using a sample of English as a foreign language (EFL) university students in Morocco. Two hundred and six (N = 206) participants of undergraduate, graduate, and post-graduate levels completed the self-esteem (SE) questionnaire. Using classical methods of factor extraction before employing more robust techniques comprising minimum average partial (MAP) and parallel analysis (PA) to perform preliminary factor analysis (FA) using principal axis factoring (PAF), results conclusively and parsimoniously yielded a one-factor solution with acceptable construct reliability (Composite Reliability). CFA results, including goodness-of-fit indexes, confirmed that the one-factor model was better fitting compared to its competing independent two-factor counterpart, but marginally less so compared to the correlated version of the latter. Two out of the three constructed models showed good fit indexes, thus demonstrating the conformity of two measurement models with their respective hypothesized structural models. Furthermore, using the heterotrait-monotrait (HTMT) ratio, both two-factor models showed acceptable discriminant validity. The obtained results further corroborate both the one-factor and two-factor solutions reported in previous works for which we present new evidence from a Moroccan EFL context.
Simulating random optical fields: tutorial
Authors: Hyde Milo Wilt
Published: October 2022

Numerous applications—including optical communications, directed energy, remote sensing, and optical tweezing—utilize the principles of statistical optics and optical coherence theory. Simulation of these phenomena is, therefore, critical in the design of new technologies for these and other such applications. For this reason, this tutorial describes how to generate random electromagnetic field instances or realizations consistent with a given or desired cross-spectral density matrix for use in wave optics simulations. This tutorial assumes that the reader has knowledge of the fundamental principles of statistical optics and optical coherence theory. An extensive reference list is provided where the necessary background information can be found. We begin this tutorial with a brief summary of the coherent-mode representation and the superposition rule of stochastic electromagnetic fields as these foundational ideas form the basis of all known synthesis techniques. We then present optical field expressions that apply these concepts before discussing proper sampling and discretization. We finally compare and contrast coherent-mode- and superposition-rule-based synthesis approaches, discussing the pros and cons of each. As an example, we simulate the synthesis and propagation of an electromagnetic partially coherent field from the literature. We compare simulated or sample statistics to theory to verify that we have successfully produced the desired field and are capturing its propagation behaviors. All computer programs, including detailed explanations of the source code, are provided with this tutorial. We conclude with a brief summary.
Polarization-independent and ultra-sensitive biosensor with a one-dimensional topological photonic crystal
Authors: Su Mingyang , Wang Chaofeng , Li Kangsen , Wu Leiming , Lin Qiawu , Zhou Renlong , Yang Sa
Published: October 2022

Optical biosensor, which perceptively captures the variety of refractive index (RI) of the surrounding environment, has great potential applications in detecting property changes and types of analytes. However, the disequilibrium of light-matter interaction in different polarizations lead to the polarization-dependence and low sensitivity. Here, we propose a polarization-independent and ultrasensitive biosensor by introducing a one-dimensional topological photonic crystal (1D TPhC), where two N-period 1D photonic crystals (PhC1 and PhC2) with different topological invariants are designed for compressing the interaction region of the optical fields, and enhancing the interaction between the light and analyte. Since the strong light-matter interaction caused by the band-inversion is polarization-independent, the biosensor can obtain superior sensing performance both for TE and TM polarization modes. The sensitivity and Figure of Merit (FOM) of the designed biosensor are 1.5677×106 RIU−1 (1.3497 × 106 RIU−1) and 7.8387×1010 RIU−1deg−1 (4.4990×1010 RIU−1deg−1) for TM (TE) polarization mode, which performs two orders of magnitude enhancement compared with the reported biosensors. With the protection of the topological edge state, this biosensor has high tolerance to the thickness deviations and refractive index (RI) variations of the component materials, which can reduce the requirements on fabrication and working environment. It is anticipated that the proposed biosensor possesses excellent sensing performances, may have great potentials in environmental monitoring, medical detection, etc.
Carrier-envelope-phase and helicity control of electron vortices and spirals in photodetachment
Authors: Majczak M. M. , Cajiao Vélez F. , Kamiński J. Z. , Krajewska K.
Published: October 2022

Formation of electron vortices and spirals in photodetachment from the H− anion driven by isolated ultrashort laser pulses of circular polarization or by pairs of such pulses (of either co-rotating or counter-rotating polarizations) are analyzed under the scope of the strong-field approximation. It is demonstrated that the carrier-envelope phase (CEP) and helicity of each individual pulse can be used to actively manipulate and control the vortical and spiral patterns in the probability amplitude of photodetachment. Specifically, we show that the vortical patterns can be rotated in momentum space by the CEP of the driving pulse (or, of two identical pulses); thus, offering a tool of pulse characterization. For co-rotating pulses of arbitrary CEPs, a novel type of structured vortices is discovered. Also, we demonstrate that the momentum spirals are formed when photodetachment is driven by two pulses of time-reversal symmetry, which is accompanied by absolute disappearance of vortical structures. Hence, we attribute the spiral formation to annihilation of vortices with antivortices, which are generated by time-reversed pulses comprising the train. Finally, the CEP and helicity control of spiral structures is demonstrated, leading to their rotation in momentum space.
High temperature infrared-radar compatible stealthy metamaterial based on an ultrathin high-entropy alloy
Authors: Gui Boheng , Wang Jun , Zhu Ying , Zhang Lei , Feng Mingde , Wang Jiafu , Ma Hua , Qu Shaobo
Published: October 2022

In this work, a high temperature infrared (IR) and radar compatible stealthy metamaterial based on ultrathin high-entropy alloy are proposed. From room temperature to 600°C, the fabricated radar absorption layer (RAL) can have wideband absorption in X-band (8.2-12.4 GHz) with average absorption 78% owing to magnetic resonance and ohmic loss. The ultrathin high-entropy alloy film is further design as infrared shielding layer (ISL) due to low-emissivity property. The ISL and RAL consist of the IR-microwave compatible stealth metamaterial. It can give rise to the strong reduction of both radar wave reflection and infrared thermal emission. Its bandwidth (absorption over 90%) is 2.15 GHz. In the infrared atmosphere window, it can suppress a half of thermal radiation. This is realized by the subtle combination between the RAL and specifically designed ISL that control the infrared emission and microwave absorption. These results show that they are practically very promising for the application of a radar-infrared bi-stealth technology in high temperature environment.
Single-pixel imaging interferometer based on the synthesis of spatial coherence
Authors: Imbe Masatoshi
Published: October 2022

In this study, an interferometric method with conventional optical components without pixelated devices for the single-pixel imaging of a spatially incoherent light source is proposed. The tilting mirror performs linear phase modulation to extract each spatial frequency component from the object wave. The intensity at each modulation is detected sequentially to synthesize the spatial coherence such that the Fourier transform computation reconstructs the object image. Experimental results are provided to confirm that interferometric single-pixel imaging enables reconstruction with spatial resolution determined by the relation between the spatial frequency and tilt of the mirrors.
Phosphoinositide species and filamentous actin formation mediate engulfment by senescent tumor cells
Authors: Frey Wesley D. , Anderson Ashlyn Y. , Lee Hyemin , Nguyen Julie B. , Cowles Emma L. , Lu Hua , Jackson James G.
Published: October 2022

Cancer cells survive chemotherapy and cause lethal relapse by entering a senescent state that facilitates expression of many phagocytosis/macrophage-related genes that engender a novel cannibalism phenotype. We used biosensors and live-cell imaging to reveal the basic steps and mechanisms of engulfment by senescent human and mouse tumor cells. We show filamentous actin in predator cells was localized to the prey cell throughout the process of engulfment. Biosensors to various phosphoinositide (PI) species revealed increased concentration and distinct localization of predator PI(4) P and PI(4,5)P2 at the prey cell during early stages of engulfment, followed by a transient burst of PI(3) P before and following internalization. PIK3C2B, the kinase responsible for generating PI(3)P, was required for complete engulfment. Inhibition or knockdown of Clathrin, known to associate with PIK3C2B and PI(4,5)P2, severely impaired engulfment. In sum, our data reveal the most fundamental cellular processes of senescent cell engulfment, including the precise localizations and dynamics of actin and PI species throughout the entire process.
Modelling the first wave of COVID-19 in India
Authors: Hazra Dhiraj Kumar , Pujari Bhalchandra S. , Shekatkar Snehal M. , Mozaffer Farhina , Sinha Sitabhra , Guttal Vishwesha , Chaudhuri Pinaki , Menon Gautam I.
Published: October 2022

Estimating the burden of COVID-19 in India is difficult because the extent to which cases and deaths have been undercounted is hard to assess. Here, we use a 9-component, age-stratified, contact-structured epidemiological compartmental model, which we call the INDSCI-SIM model, to analyse the first wave of COVID-19 spread in India. We use INDSCI-SIM, together with Bayesian methods, to obtain optimal fits to daily reported cases and deaths across the span of the first wave of the Indian pandemic, over the period Jan 30, 2020 to Feb 15, 2021. We account for lock-downs and other non-pharmaceutical interventions (NPIs), an overall increase in testing as a function of time, the under-counting of cases and deaths, and a range of age-specific infection-fatality ratios. We first use our model to describe data from all individual districts of the state of Karnataka, benchmarking our calculations using data from serological surveys. We then extend this approach to aggregated data for Karnataka state. We model the progress of the pandemic across the cities of Delhi, Mumbai, Pune, Bengaluru and Chennai, and then for India as a whole. We estimate that deaths were undercounted by a factor between 2 and 5 across the span of the first wave, converging on 2.2 as a representative multiplier that accounts for the urban-rural gradient. We also estimate an overall under-counting of cases by a factor of between 20 and 25 towards the end of the first wave. Our estimates of the infection fatality ratio (IFR) are in the range 0.05—0.15, broadly consistent with previous estimates but substantially lower than values that have been estimated for other LMIC countries. We find that approximately 35% of India had been infected overall by the end of the first wave, results broadly consistent with those from serosurveys. These results contribute to the understanding of the long-term trajectory of COVID-19 in India.
Effectiveness of tailored digital health interventions for mental health at the workplace: A systematic review of randomised controlled trials
Authors: Moe-Byrne Thirimon , Shepherd Jessie , Merecz-Kot Dorota , Sinokki Marjo , Naumanen Päivi , Hakkaart-van Roijen Leona , Van Der Feltz-Cornelis Christina
Published: October 2022

Mental health problems in the workplace are common and have a considerable impact on employee wellbeing and productivity. Mental ill-health costs employers between £33 billion and £42 billion a year. According to a 2020 HSE report, roughly 2,440 per 100,000 workers in the UK were affected by work-related stress, depression, or anxiety, resulting in an estimated 17.9 million working days lost. We performed a systematic review of randomised controlled trials (RCTs) to assess the effect of tailored digital health interventions provided in the workplace aiming to improve mental health, presenteeism and absenteeism of employees. We searched several databases for RCTs published from 2000 onwards. Data were extracted into a standardised data extraction form. The quality of the included studies was assessed using the Cochrane Risk of Bias tool. Due to the heterogeneity of outcome measures, narrative synthesis was used to summarise the findings. Seven RCTs (eight publications) were included that evaluated tailored digital interventions versus waiting list control or usual care to improve physical and mental health outcomes and work productivity. The results are promising to the advantage of tailored digital interventions regarding presenteeism, sleep, stress levels, and physical symptoms related to somatisation; but less for addressing depression, anxiety, and absenteeism. Even though tailored digital interventions did not reduce anxiety and depression in the general working population, they significantly reduced depression and anxiety in employees with higher levels of psychological distress. Tailored digital interventions seem more effective in employees with higher levels of distress, presenteeism or absenteeism than in the general working population. There was high heterogeneity in outcome measures, especially for work productivity; this should be a focus of attention in future studies.
CASK and FARP localize two classes of post-synaptic ACh receptors thereby promoting cholinergic transmission
Authors: Li Lei , Liu Haowen , Qian Kang-Ying , Nurrish Stephen , Zeng Xian-Ting , Zeng Wan-Xin , Wang Jiafan , Kaplan Joshua M. , Tong Xia-Jing , Hu Zhitao
Published: October 2022

Changes in neurotransmitter receptor abundance at post-synaptic elements play a pivotal role in regulating synaptic strength. For this reason, there is significant interest in identifying and characterizing the scaffolds required for receptor localization at different synapses. Here we analyze the role of two C. elegans post-synaptic scaffolding proteins (LIN-2/CASK and FRM-3/FARP) at cholinergic neuromuscular junctions. Constitutive knockouts or muscle specific inactivation of lin-2 and frm-3 dramatically reduced spontaneous and evoked post-synaptic currents. These synaptic defects resulted from the decreased abundance of two classes of post-synaptic ionotropic acetylcholine receptors (ACR-16/CHRNA7 and levamisole-activated AChRs). LIN-2’s AChR scaffolding function is mediated by its SH3 and PDZ domains, which interact with AChRs and FRM-3/FARP, respectively. Thus, our findings show that post-synaptic LIN-2/FRM-3 complexes promote cholinergic synaptic transmission by recruiting AChRs to post-synaptic elements.
Activation of the integrative and conjugative element Tn916 causes growth arrest and death of host bacteria
Authors: Bean Emily L. , McLellan Lisa K. , Grossman Alan D.
Published: October 2022

Integrative and conjugative elements (ICEs) serve as major drivers of bacterial evolution. These elements often confer some benefit to host cells, including antibiotic resistance, metabolic capabilities, or pathogenic determinants. ICEs can also have negative effects on host cells. Here, we investigated the effects of the ICE (conjugative transposon) Tn916on host cells. Because Tn916is active in a relatively small subpopulation of host cells, we developed a fluorescent reporter system for monitoring activation of Tn916in single cells. Using this reporter, we found that cell division was arrested in cells ofBacillus subtilisandEnterococcus faecalis(a natural host for Tn916) that contained an activated (excised) Tn916. Furthermore, most of the cells with the activated Tn916subsequently died. We also observed these phenotypes on the population level inB.subtilisutilizing a modified version of Tn916that can be activated in the majority of cells. We identified two genes (orf17andorf16) in Tn916that were sufficient to cause growth defects inB.subtilisand identified a single gene,yqaR, that is in a defective phage (skin) in theB.subtilischromosome that was required for this phenotype. These three genes were only partially responsible for the growth defect caused by Tn916, indicating that Tn916possesses multiple mechanisms to affect growth and viability of host cells. These results highlight the complex relationships that conjugative elements have with their host cells and the interplay between mobile genetic elements.
The global trends and regional differences in incidence of Zika virus infection and implications for Zika virus infection prevention
Authors: Guo Zirui , Jing Wenzhan , Liu Jue , Liu Min
Published: October 2022

Background

Zika virus (ZIKV) infection has potential result in severe birth effects. An improved understanding of global trend and regional differences is needed.

Methods

Annual ZIKV infection episodes and incidence rates were collected from Global Burden of Disease Study 2019. Episodes changes and estimated annual percentage changes (EAPCs) of age-standardized incidence rate (ASR) were calculated. Top passenger airport-pairs were obtained from the International Air Transport Association to understand places susceptible to imported ZIKV cases.

Results

Globally, the ASR increased by an average of 72.85% (95%CI: 16.47% to 156.53%) per year from 2011 to 2015 and subsequently decreased from 20.25 per 100,000 in 2015 to 3.44 per 100,000 in 2019. Most of ZIKV infections clustered in Latin America. The proportion of episodes in Central and Tropical Latin America decreased in 2019 with sporadic episodes elsewhere. High Socio-Demographic Index (SDI) regions had more episodes in 2019 than in 2015. Additionally, 15–49 years group had the largest proportion of episodes, females had a higher number of episodes, and a higher incidence rate of 70 plus group was observed in males than females. Certain cities in Europe, North America and Latin America/Caribbean had a high population mobility in ZIKV outbreak areas considered a high risk of imported cases.

Conclusions

ZIKV infection is still a public health threat in Latin America and Caribbean and high SDI regions suffered an increasing trend of ZIKV infection. Interventions such as development of surveillance networks and vector-control should be attached to ZIKV control in these key regions. Reproductive suggestions should be taken to reduce ZIKV-related birth defects for the people of reproductive age who are facing a higher threat of ZIKV infection, especially females. Moreover, surveillance of travellers is needed to reverse the uptrends of travel-related imported ZIKV infection. More studies focusing on ZIKV should be performed to make targeted and effective prevention strategies in the future.
TLR7 controls myeloid-derived suppressor cells expansion and function in the lung of C57BL6 mice infected with Schistosoma japonicum
Authors: Zhou Lu , Zhu Yiqiang , Mo lengshan , Wang Mei , Lin Jie , Zhao Yi , Feng Yuanfa , Xie Anqi , Wei Haixia , Qiu Huaina , Huang Jun , Yang Quan
Published: October 2022

Toll-like receptors (TLRs) play an important role in the induction of innate and adaptive immune responses against Schistosoma japonicum (S. japonicum) infection. However, the role of Toll-like receptor 7 (TLR7) in the mouse lung during S. japonicum infection and the myeloid-derived suppressor cells (MDSCs) affected by the absence of TLR7 are not clearly understood. In this study, the results indicated that the MDSCs were accumulated and the proportion and activation of CD4+ and CD8+ T cells were decreased in the lung of mice at 6–7 weeks after S. japonicum infection. Then, the expression of TLR7 was detected in isolated pulmonary MDSCs and the results showed that the expression of TLR7 in MDSCs was increased after infection. Furthermore, TLR7 agonist R848 could down-regulate the induction effect of the soluble egg antigen (SEA) on pulmonary MDSCs in vitro. Meanwhile, TLR7 deficiency could promote the pulmonary MDSCs expansion and function by up-regulating the expression of PD-L1/2 and secreting of IL-10 in the mice infected with S. japonicum. Mechanistic studies revealed that S. japonicum infection and the antigen effects are mediated by NF-κB signaling. Moreover, TLR7 deficiency aggravates S. japonicum infection-induced damage in the lung, with more inflammatory cells infiltration, interstitial dilatation and granuloma in the tissue. In summary, this study indicated that TLR7 signaling inhibits the accumulation and function of MDSCs in S. japonicum infected mouse lung by down-regulating the expression of PD-L1/2 and secreting of IL-10, via NF-κB signaling.
The gut microbial metabolic capacity of microbiome-humanized vs. wild type rodents reveals a likely dual role of intestinal bacteria in hepato-intestinal schistosomiasis
Authors: Cortés Alba , Martin John , Rosa Bruce A. , Stark Klara A. , Clare Simon , McCarthy Catherine , Harcourt Katherine , Brandt Cordelia , Tolley Charlotte , Lawley Trevor D. , Mitreva Makedonka , Berriman Matthew , Rinaldi Gabriel , Cantacessi Cinzia
Published: October 2022

Increasing evidence shows that the host gut microbiota might be involved in the immunological cascade that culminates with the formation of tissue granulomas underlying the pathophysiology of hepato-intestinal schistosomiasis. In this study, we investigated the impact ofSchistosoma mansoniinfection on the gut microbial composition and functional potential of both wild type and microbiome-humanized mice. In spite of substantial differences in microbiome composition at baseline, selected pathways were consistently affected by parasite infection. The gut microbiomes of infected mice of both lines displayed, amongst other features, enhanced capacity for tryptophan and butyrate production, which might be linked to the activation of mechanisms aimed to prevent excessive injuries caused by migrating parasite eggs. Complementing data from previous studies, our findings suggest that the host gut microbiome might play a dual role in the pathophysiology of schistosomiasis, where intestinal bacteria may contribute to egg-associated pathology while, in turn, protect the host from uncontrolled tissue damage.
Rule-based habitat suitability modelling for the reintroduction of the grey wolf (Canis lupus) in Scotland
Authors: Gwynn Vashti , Symeonakis Elias
Published: October 2022

Though native to Scotland, the grey wolf (Canis lupus) was extirpated c.250 years ago as part of a global eradication drive. The global population has recently expanded, now occupying 67% of its former range. Evidence is growing that apex predators provide a range of ecological benefits, most stemming from the reduction of overgrazing by deer–something from which Scotland suffers. In this study, we build a rule-based habitat suitability model for wolves on the Scottish mainland. From existing literature, we identify the most important variables as land cover, prey density, road density and human density, and establish thresholds of suitability for each. Fuzzy membership functions are used to assign suitability values to each variable, followed by fuzzy overlay to combine all four: a novel approach to habitat suitability modelling for terrestrial mammals. Model sensitivity is tested for land cover and prey density, as these variables constitute a knowledge gap and an incomplete dataset, respectively. The Highlands and Grampian mountains emerge strongly and consistently as the most suitable areas, largely due to high negative covariance between prey density and road/human density. Sensitivity testing reveals the models are fairly robust to changes in prey density, but less robust to changes in the scoring of land cover, with the latter altering the distribution of land mainly through the 70–100% suitability range. However, in statistical significance tests, only the least and most generous versions of the model emerge as giving significantly different results. Depending on the version of the model, a contiguous area of between 10,139km2 and 18,857km2 is shown to be 80 to 100% suitable. This could be sufficient to support between 50 and 94 packs of four wolves, if the average pack range size is taken to be 200km2. We conclude that in terms of habitat availability, reintroduction should be feasible.
Discussion of costs and financial burden in clinical practice: A survey of medical oncologists in Australia
Authors: Agarwal Anupriya , Karikios Deme J. , Stockler Martin R. , Morton Rachael L.
Published: October 2022

Background

A diagnosis of cancer is associated with significant physical, psychological and financial burden. Including costs of cancer is an important component of shared decision making. Doctors bear a responsibility towards educating patients about the financial aspects of care. Multiple organisations have advocated for price transparency and implementing Informed Financial Consent in the clinic. However, few studies have evaluated the perspectives of oncologists on the current state of this discussion.

Aims

The aim of this study is to determine the views and perspectives of medical oncologists regarding communication of costs and financial burden in patients with cancer.

Methods

We conducted a prospective cross-sectional online survey via REDCap. The survey was distributed to medical oncologists and advanced trainees currently registered with Medical Oncology Group of Australia (MOGA). Data was collected using the online survey comprising socio-demographic characteristics, discussion of costs and financial burden, and facilitators and barriers to these discussions.

Results

547 members of MOGA were invited to participate in the study, and 106 of 547 MOGA members (19%) completed the survey. Most oncologists (66%) felt that it was their responsibility to discuss costs of care, however a majority of oncologists (59.3%) reported discussing costs with less than half of their patients. Only 25% of oncologists discussed financial concerns with more than half of their patients, and most oncologists were unfamiliar with cancer-related financial burden. Most Oncologists with greater clinical experience and those working in private practice were more likely to discuss costs with a majority of their patients.

Conclusions

Certain characteristics of medical oncologists and their practices were associated with reported prevalence of discussing costs of care and financial burden with their patients. In the context of rising costs of cancer care, interventions targeting modifiable factors such as raising oncologist awareness of costs of care and financial burden, screening for financial toxicity and availability of costs information in an easily accessible manner, may help increase the frequency of patient-doctor discussions about costs of care, contributing to informed decision-making and higher-quality cancer care.