bluuebunny/crossref_metadata_2025 huggingface dataset:
Grupos de interesse importam: reflexões sobre a atuação em audiências públicas
Authors: Troiano Mariele
Published: October 2022

O objetivo deste capítulo é apresentar algumas características dos grupos de interesse apontadas pela literatura, problematizando as assimetrias de acesso e de influência, sobretudo em arenas decisórias. Por meio da análise das audiências públicas, apresenta-se a discussão sobre o ingresso institucional desses grupos.
De Vargas a Bolsonaro: continuidades e descontinuidades da burocracia no Brasil
Authors: Nogueira Johnny Daniel Matias , de Miranda Daniel Estevão Ramos
Published: October 2022

A trajetória da moderna burocracia pública brasileira encontra seu marco inaugural na década de 1930. Até aquele momento histórico, a organização e o funcionamento de órgãos públicos pelos princípios do “universalismo de procedimentos” (Nunes, 1997) eram muito limitados, sendo as Forças Armadas um dos poucos exemplos dessa lógica. Daquele marco inaugural até as duas primeiras décadas do século XXI, é possível distinguir dois grandes períodos do ponto de vista das relações entre o regime político e os empreendimentos de (re)construção do Estado e de seu aparelho burocrático no Brasil.
A trajetória recente da construção do serviço civil na administração pública federal brasileira: dilemas e perspectivas
Authors: Fernandes Ciro Campos Christo , Palotti Pedro Lucas de Moura , Souza Pedro Masson Sesconetto
Published: October 2022

O presente capítulo apresenta a trajetória recente da construção do serviço civil na administração federal, contextualizando os fatores políticos e institucionais que influenciaram a expansão do contingente de servidores, sua qualificação e distribuição por carreiras, órgãos e setores.
Defesa de quem? Criação de uma burocracia de defesa como alternativa à militarização da burocracia e seus desdobramentos
Authors: Toledo José Paulo , dos Santos José Carlos , Cardoso Jr. José Celso
Published: October 2022

Inicialmente, o capítulo explora as capacidades que um burocrata da área possui quando do surgimento dessa especialidade de atuação. Em um segundo momento, aprofunda a discussão sobre a importância desse ator para o contexto sociopolítico brasileiro, analisando as implicações econômicas e políticas ligadas a essa iniciativa. O capítulo conclui que, na construção desse corpo burocrático, há a possibilidade de materializar grandes reestruturações: econômicas, por meio da industrialização coordenada demandando mão de obra qualificada, por um lado, e política, reconstruindo as relações civil-militares de forma a sedimentar o controle civil sobre as Forças Armadas.
“Que seja eterno enquanto dure”: ambição política, coalizões e accountability como determinantes da rotatividade ministerial no sistema presidencial multipartidário brasileiro
Authors: Palotti Pedro Lucas de Moura , Cavalcante Pedro Luiz Costa , Gomes Juliana Betini Fachini
Published: October 2022

Este capítulo tem como objetivo compreender os determinantes da rotatividade ministerial em sistemas presidencialistas multipartidários. Elementos como a estrutura do partido a que pertence o presidente, características institucionais do sistema eleitoral e partidário, existência de grupos de apoio político e social, além de questões regionais, étnicas e religiosas, bem como variáveis relacionadas às capacidades e interesses individuais de ministros, em conjunto, contribuem para o caráter multivariado, dinamismo e elevada complexidade das nomeações ministeriais e renúncias.
À GUISA DE CONCLUSÃO: Avançar é preciso: consolidando uma agenda de pesquisa sobre burocracia, sociedade e políticas públicas
Authors: Ribeiro Pedro Floriano , Troiano Mariele , Albrecht Nayara
Published: October 2022

A relação entre burocracia e política não é um tema trivial. Como bem demonstrou a literatura recente, Estado e sociedade não são atores monolíticos e suas relações são marcadas por uma heterogeneidade de repertórios de interação (Abers et al., 2014). Entretanto, os trabalhos sobre burocracia pública, por um determinado período, não consideraram essa complexidade ao oscilar entre uma rígida dicotomia entre política e administração e a perspectiva de que o Estado é um mero instrumento das classes dominantes.
The diagnosis and management of acute hyponatraemia in critical care
Authors: Campbell Karen , Mortimore Gerri
Published: October 2022

Nurses working in critical care, consisting of the intensive care and high dependency units, will encounter a broad range of diseases and conditions. Therefore, a comprehensive knowledge and understanding of common presentations is required, especially for advanced clinical practitioners (ACPs). One of the most common electrolyte disturbances seen within these areas is hyponatraemia, affecting around 40% of patients in critical care and 30% of inpatients. It is important that ACPs working in this area are aware of the symptoms and recommended diagnosis and management.
Should our PCN adopt the John Lewis model?
Authors: Cumberlege Justin
Published: October 2022

Justin Cumberlege, a Partner in the healthcare law firm Hempsons, provides advice to practice managers on a popular request to model using the John Lewis structure for the primary care network
Changemakers: Influences on Engagement in STEM Curricula Among Underrepresented Youth
Authors: Konowitz Lily , Lund Terese , Lincoln Brenna , Reed Madeline , Liang Belle , Barnett Mike , Blustein David
Published: October 2022

Despite the desirability of working in science, technology, engineering, and math (STEM), Black and Latinx people are underrepresented in these fields. Sustaining engagement in STEM is central to addressing the representation gap. This qualitative study examined whether and how a STEM-based after-school program (Changemakers) impacted students’ sense of engagement in STEM. Changemakers incorporates the basic tenets of STEM engagement and a purpose curriculum to increase students' sense of engagement. Purpose is an aspiration towards future-oriented goals, active engagement with one’s goals, and intention to contribute to the world. The sample was composed of students, ages 15-17 years old (N=10, 5=M; 5=F), from a public, low-income high school. Findings suggested that three elements helped engage participants with STEM material: challenging and novel curriculum, experiential learning, and supportive relationships. These findings underscore additional STEM programs can enhance their student’s learning and connection to the field by ensuring that their program encapsulates these identified components.
Cocoa Bean Dryer and Cleaner Devise : A Microcontroller Experiment
Authors: Hersyah Mohammad Hafiz , Yolanda Desta , Fatma Nela
Published: October 2022

Cleaning and drying cocoa beans are generally done manually by farmers. The manual cleaning process takes a long time, and the pulp reduction is not optimal. In contrast, drying using sunlight takes a long time when it is done in the rainy season. This causes the cocoa beans to be moldy and have low sale value. In the equipment made by the factory, the two machines are made separately and are hardly affordable by the farmers. Based on these problems, a microcontroller-based cocoa bean dryer (de pulper) was designed with a single container so that both processes could be carried out using just one machine. To elaborate this system, cleaning is carried out on fermented cocoa beans that are pulp shed in a rotating cylinder. In comparison, the drying process is carried out by using a heat source, a soil moisture sensor to detect the moisture content of cocoa beans, a DS18B20 sensor to detect temperatures in the drying container, and a cylindrical container is rotated using an A.C. motor. Based on the experiment results, it takes 10 minutes to clean the cocoa beans from the pulp. The drying process takes 5 hours, 10 minutes, and 5 hours and 40 minutes to dry the cocoa beans to a maximum moisture content of 7%. A rotating drying container can speed up the drying process of cocoa beans compared to drying using sunlight in the rainy season.   The proposed tool in this study can carry out more efficient capacity better than the conventional tool.
Light as a quantum back-action nullifying meter
Authors: Davuluri Sankar , Li Yong
Published: October 2022

We propose a new, to the best of our knowledge, method to overcome quantum back-action in a measurement process using oscillators. An optical oscillator is used as a meter to measure the parameters of another open oscillator. The optical oscillator is synthesized such that the optical restoring force counters any perturbations induced by the quantum back-action phenomena. As a result, it is shown that the quantum back-action in continuous measurement is suppressed in the low frequency regime, i.e., for frequencies much smaller than the resonance frequency of the open oscillator. As the meter plays the role of measuring parameters as well as suppressing the quantum back-action, we call it a quantum back-action nullifying meter. As an application of this method, synthesis of the quantum back-action nullifying optical oscillator for suppressing radiation pressure force noise in linear and non-linear optomechanics is described.
Rapid multiplex ultrafast nonlinear microscopy for material characterization
Authors: Purz Torben L. , Hipsley Blake T. , Martin Eric W. , Ulbricht Ronald , Cundiff Steven T.
Published: October 2022

We demonstrate rapid imaging based on four-wave mixing (FWM) by assessing the quality of advanced materials through measurement of their nonlinear response, exciton dephasing, and exciton lifetimes. We use a WSe2 monolayer grown by chemical vapor deposition as a canonical example to demonstrate these capabilities. By comparison, we show that extracting material parameters such as FWM intensity, dephasing times, excited state lifetimes, and distribution of dark/localized states allows for a more accurate assessment of the quality of a sample than current prevalent techniques, including white light microscopy and linear micro-reflectance spectroscopy. We further discuss future improvements of the ultrafast FWM techniques by modeling the robustness of exponential decay fits to different spacing of the sampling points. Employing ultrafast nonlinear imaging in real-time at room temperature bears the potential for rapid in-situ sample characterization of advanced materials and beyond.
Mixed finite element numerical mode matching method for designing infrared broadband polarization-independent metamaterial absorbers
Authors: Tong Chifeng , Liu Jie , Liu Qing Huo
Published: October 2022

Conventional numerical methods have found widespread applications in the design of metamaterial structures, but their computational costs can be high due to complex three-dimensional discretization needed for large complex problems. In this work, we apply a recently developed numerical mode matching (NMM) method to design a black phosphorus (BP) absorber. NMM transforms a complex three-dimensional (3D) problem into 2D numerical eigenvalue problems plus a 1-D analytical propagation solution, thus it can save a lot of computational costs. BP is treated as a 2D surface and represented by the anisotropic surface conductance. With a realistic simulation study, we show that our method is more accurate and efficient than the standard finite element method (FEM). Our designed absorber can achieve an average absorption of 97.4% in the wavelength range of 15 to 23 μm under normal incidence. Then, we investigate the physical mechanism of the absorber, tuning the geometric parameters and electron doping to optimize the performance. In addition, the absorption spectra under oblique incidence and arbitrary polarization are studied. The results confirm that our absorber is polarization-independent and has high absorption at large incident angles. Our work validates the superiority of NMM and provides a new simulation platform for emerging metamaterial device design.
Multi-signal feature fusion method with an attention mechanism for the Φ-OTDR event recognition system
Authors: Shi Yi , Chen Jiewei , Dai Shangwei , Liu Xinyu , Wei Chuliang
Published: October 2022

Different signal representations show different unique features for classification. In this paper, a feature fusion method with attention mechanism based on multiple signal representations is proposed for Φ-OTDR event classification with buried optical fiber. Each signal representation is fused after feature extraction to get richer and better features. With the help of a layer pruning method based on attention mechanism, the network size can be kept and avoid computation increase. Experiment results show that this method with 3 signal representations can improve the recognition accuracy to 97.93%, with 3.52% improvement compared to single representation approach. It also shows higher recognition accuracy than the tradition multiple signal representations fusion methods at the input stage. Furthermore, when it is used to fuse four representations, the recognition accuracy can be further improved to 99.11%.
Optomechanically induced transparency and directional amplification in a non-Hermitian optomechanical lattice
Authors: Wen Pengyu , Wang Min , Long Gui-Lu
Published: October 2022

In this paper, we propose a 1-dimensional optomechanical lattice which possesses non-Hermitian property due to its nonreciprocal couplings. We calculated the energy spectrum under periodical boundary condition and open boundary condition, respectively. To investigate the transmission property of the system, we calculate the Green function of the system using non-Bloch band theory. By analyzing the Green function and the periodical boundary condition results, we studied the directional amplification of the system and found the frequency that supports the amplification. By adding probe laser on one site and detect the output of the same site, we found that optomechanically induced transparency (OMIT) can be achieved in our system. Different from the traditional OMIT spectrum, quantum interference due to a large number of modes can be observed in our system. When varying the nonreciprocal and other parameters of the system, the OMIT peak can be effectively modulated or even turned into optomechanically induced amplification. Our system is very promising to act as a one-way signal filter. Our model can also be extended to other non-Hermitian optical systems which may possess topological features and bipolar non-Hermitian skin effect.
Field-resolved THz-pump laser-probe measurements with CEP-unstable THz light sources
Authors: Ilyakov I. , Ponomaryov A. , Klopf J. M. , Pashkin A. , Deinert J.-C. , de Oliveira T. V. A. G. , Evtushenko P. , Helm M. , Winnerl S. , Kovalev S.
Published: October 2022

Radiation sources with a stable carrier-envelope phase (CEP) are highly demanded tools for field-resolved studies of light-matter interaction, providing access both to the amplitude and phase information of dynamical processes. At the same time, many coherent light sources, including those with outstanding power and spectral characteristics lack CEP stability, and so far could not be used for this type of research. In this work, we present a method enabling linear and non-linear phase-resolved terahertz (THz) -pump laser-probe experiments with CEP-unstable THz sources. THz CEP information for each pulse is extracted using a specially designed electro-optical detection scheme. The method correlates the extracted CEP value for each pulse with the THz-induced response in the parallel pump-probe experiment to obtain an absolute phase-resolved response after proper sorting and averaging. As a proof-of-concept, we demonstrate experimentally field-resolved THz time-domain spectroscopy with sub-cycle temporal resolution using the pulsed radiation of a CEP-unstable infrared free-electron laser (IR-FEL) operating at 13 MHz repetition rate. In spite of the long history of IR-FELs and their unique operational characteristics, no successful realization of CEP-stable operation has been demonstrated yet. Being CEP-unstable, IR-FEL radiation has so far only been used in non-coherent measurements without phase resolution. The technique demonstrated here is robust, operates easily at high-repetition rates and for short THz pulses, and enables common sequential field-resolved time-domain experiments. The implementation of such a technique at IR-FEL user end-stations will facilitate a new class of linear and non-linear experiments for studying coherent light-driven phenomena with increased signal-to-noise ratio.
Zeeman optical pumping of 87Rb atoms in a hollow-core photonic crystal fiber
Authors: Krehlik Tomasz , Stabrawa Artur , Gartman Rafał , Kaczmarek Krzysztof T. , Löw Robert , Wojciechowski Adam
Published: October 2022

Preparation of an atomic ensemble in a particular Zeeman state is a critical step of many protocols for implementing quantum sensors and quantum memories. These devices can also benefit from optical fiber integration. In this work we describe experimental results supported by a theoretical model of single-beam optical pumping of 87Rb atoms within a hollow-core photonic crystal fiber. The observed 50% population increase in the pumped F = 2, mF = 2 Zeeman substate along with the depopulation of remaining Zeeman substates enabled us to achieve a threefold improvement in the relative population of the mF = 2 substate within the F = 2 manifold, with 60% of the F = 2 population residing in the mF = 2 dark sublevel. Based on theoretical model, we propose methods to further improve the pumping efficiency in alkali-filled hollow-core fibers.
3.1 W mid-infrared fiber laser at 4.16 µm based on HBr-filled hollow-core silica fibers
Authors: Zhou Zhiyue , Huang Wei , Cui Yulong , Li Hao , Pei Wenxi , Li Xuanxi , Li Ziyan , Wang Meng , Wang Zefeng
Published: October 2022

We present the characteristics of a continuous-wave (CW) mid-infrared fiber laser source based on HBr-filled hollow-core fibers (HCFs) made of silica. The laser source delivers a maximum output power of 3.1 W at 4.16 µm, showing a record value for any reported fiber laser beyond 4 µm. Both ends of the HCF are supported and sealed by especially designed gas cells with water cooling and inclined optical windows, withstanding higher pump power accompanied by accumulated heat. The mid-infrared laser exhibits a near-diffraction-limited beam quality with a measured M2 of 1.16. This work paves the way for powerful mid-infrared fiber lasers beyond 4 µm.
Bounded rational decision-making models suggest capacity-limited concurrent motor planning in human posterior parietal and frontal cortex
Authors: Schach Sonja , Lindner Axel , Braun Daniel Alexander
Published: October 2022

While traditional theories of sensorimotor processing have often assumed a serial decision-making pipeline, more recent approaches have suggested that multiple actions may be planned concurrently and vie for execution. Evidence for the latter almost exclusively stems from electrophysiological studies in posterior parietal and premotor cortex of monkeys. Here we study concurrent prospective motor planning in humans by recording functional magnetic resonance imaging (fMRI) during a delayed response task engaging movement sequences towards multiple potential targets. We find that also in human posterior parietal and premotor cortex delay activity modulates both with sequence complexity and the number of potential targets. We tested the hypothesis that this modulation is best explained by concurrent prospective planning as opposed to the mere maintenance of potential targets in memory. We devise a bounded rationality model with information constraints that optimally assigns information resources for planning and memory for this task and determine predicted information profiles according to the two hypotheses. When regressing delay activity on these model predictions, we find that the concurrent prospective planning strategy provides a significantly better explanation of the fMRI-signal modulations. Moreover, we find that concurrent prospective planning is more costly and thus limited for most subjects, as expressed by the best fitting information capacities. We conclude that bounded rational decision-making models allow relating both behavior and neural representations to utilitarian task descriptions based on bounded optimal information-processing assumptions.
CNAViz: An interactive webtool for user-guided segmentation of tumor DNA sequencing data
Authors: Lalani Zubair , Chu Gillian , Hsu Silas , Kagawa Shaw , Xiang Michael , Zaccaria Simone , El-Kebir Mohammed
Published: October 2022

Copy-number aberrations (CNAs) are genetic alterations that amplify or delete the number of copies of large genomic segments. Although they are ubiquitous in cancer and, thus, a critical area of current cancer research, CNA identification from DNA sequencing data is challenging because it requires partitioning of the genome into complex segments with the same copy-number states that may not be contiguous. Existing segmentation algorithms address these challenges either by leveraging the local information among neighboring genomic regions, or by globally grouping genomic regions that are affected by similar CNAs across the entire genome. However, both approaches have limitations: overclustering in the case of local segmentation, or the omission of clusters corresponding to focal CNAs in the case of global segmentation. Importantly, inaccurate segmentation will lead to inaccurate identification of CNAs. For this reason, most pan-cancer research studies rely on manual procedures of quality control and anomaly correction. To improve copy-number segmentation, we introduce CNAViz, a web-based tool that enables the user to simultaneously perform local and global segmentation, thus overcoming the limitations of each approach. Using simulated data, we demonstrate that by several metrics, CNAViz allows the user to obtain more accurate segmentation relative to existing local and global segmentation methods. Moreover, we analyze six bulk DNA sequencing samples from three breast cancer patients. By validating with parallel single-cell DNA sequencing data from the same samples, we show that by using CNAViz, our user was able to obtain more accurate segmentation and improved accuracy in downstream copy-number calling.
Mapping regional cooperation of state actors for health research systems in Africa: A social network analysis
Authors: Hedquist Aaron , Jones Catherine M. , Mijumbi Rhona M. , Sobngwi-Tambekou Joëlle , Parkhurst Justin , Wenham Clare
Published: October 2022

Regional bodies can potentially play an important role in improving health research in Africa. This study analyses the network of African state-based regional organisations for health research and assesses their potential relationship with national health research performance metrics. After cataloguing organisations and their membership, we conducted a social network analysis to determine key network attributes of national governments’ connections via regional organisations supporting functions of health research systems. This data was used to test the hypothesis that state actors with more connections to other actors via regional organisations would have higher levels of health research performance across indicators. With 21 unique regional organisations, the African continent is densely networked around health research systems issues. In general, the regional network for health research is inclusive. No single actor serves as a nexus. However, when statistics are grouped by African Union regions, influential poles emerge, with the most predominate spheres of influence in Eastern and Western Africa. Further, when connectivity data was analysed against national health research performance, there were no statistically significant relationships between increased connectivity and higher performance of key health research metrics. The inclusive and dense network dynamics of African regional organisations for health research strengthening present key opportunities for knowledge diffusion and cooperation to improve research capacity on the continent. Further reflection is needed on appropriate and meaningful ways to assess the role of regionalism and evaluate the influence of regional organisations in strengthening health research systems in Africa.
Community-based wound management in a rural setting of Côte d’Ivoire
Authors: Toppino Simone , Koffi Didier Yao , Kone Bognan Valentin , N’Krumah Raymond T. A. S. , Coulibaly Ismaël Dognimin , Tobian Frank , Pluschke Gerd , Stojkovic Marija , Bonfoh Bassirou , Junghanss Thomas
Published: October 2022

Background

Wounds are a neglected health problem in rural communities of low-income countries, mostly caused by trauma and ulcerative skin diseases including Neglected Tropical Diseases (NTDs) and associated with systemic complications and disability. Rural communities have limited access to high quality health services-based wound care.

Methods

We conducted a prospective observational study on wound management at three levels–community (C), health centre (HC), district hospital (DH)—in a rural community of Côte d’Ivoire. Patients with skin wounds actively identified in a house-to-house survey and passively in the health services in a defined area of the Taabo Health and Demographic Surveillance System were asked to participate and followed-up longitudinally. Endpoints were proportion of wounds closed, time to wound closure, wound size over time, frequency of secondary bacterial infection, need for recapturing after follow-up interruption, and duration of treatment stratified by health service level and wound aetiology.

Results

We enrolled 561 patients with 923 wounds between May 2019 and March 2020. The observation period ended in March 2021. Median age was 10 years (IQR 7–15), 63.0% of patients were male. Almost all (99.5%, 870/874) wounds closed within the observation period, 5.3% (49/923) were lost to follow-up. Wounds primarily treated in C, HC and DH closed within a median time of 10, 16 and 170 days, respectively. Median time to acute wound and chronic wound closure was 13 and 72 days, respectively. Wounds treated in C, HC and DH presented with secondary bacterial infections in 10.3% (36/350), 31.0% (133/429) and 100% (5/5) of cases, respectively. Recapturing was required in 68.3% (630/923) of wounds with participants reporting wound closure as the main reason for not attending follow-up.

Conclusions

We describe a wound management model based on national and WHO recommendations focusing on early identification and treatment in the community with potential for broad implementation in low-income countries.

Trial registration

Registration at ClinicalTrials.gov (NCT03957447).
Wolbachia wAlbB inhibit dengue and Zika infection in the mosquito Aedes aegypti with an Australian background
Authors: Hugo Leon E. , Rašić Gordana , Maynard Andrew J. , Ambrose Luke , Liddington Catherine , Thomas Callum J. E. , Nath Nisa Suraj , Graham Melissa , Winterford Clay , Wimalasiri-Yapa B. M. C. Randika , Xi Zhiyong , Beebe Nigel W. , Devine Gregor J.
Published: October 2022

Biological control of mosquito vectors using the endosymbiotic bacteria Wolbachia is an emerging strategy for the management of human arboviral diseases. We recently described the development of a strain of Aedes aegypti infected with the Wolbachia strain wAlbB (referred to as the wAlbB2-F4 strain) through simple backcrossing of wild type Australian mosquitoes with a wAlbB infected Ae. aegypti strain from the USA. Field releases of male wAlbB2-F4 mosquitoes resulted in the successful suppression of wild populations of mosquitoes in the trial sites by exploiting the strain’s Wolbachia-induced cytoplasmic incompatibility. We now demonstrate that the strain is resistant to infection by dengue and Zika viruses and is genetically similar to endemic Queensland populations. There was a fourfold reduction in the proportion of wAlbB2-F4 mosquitoes that became infected following a blood meal containing dengue 2 virus (16.7%) compared to wild type mosquitoes (69.2%) and a 6–7 fold reduction in the proportion of wAlbB2-F4 mosquitoes producing virus in saliva following a blood meal containing an epidemic strain of Zika virus (8.7% in comparison to 58.3% in wild type mosquitoes). Restriction-site Associated DNA (RAD) sequencing revealed that wAlbB2-F4 mosquitoes have > 98% Australian ancestry, confirming the successful introduction of the wAlbB2 infection into the Australian genomic background through backcrossing. Genotypic and phenotypic analyses showed the wAlbB2-F4 strain retains the insecticide susceptible phenotype and genotype of native Australian mosquitoes. We demonstrate that the Wolbachia wAlbB2-F4, in addition to being suitable for population suppression programs, can also be effective in population replacement programs given its inhibition of virus infection in mosquitoes. The ease at which a target mosquito population can be transfected with wAlbB2, while retaining the genotypes and phenotypes of the target population, shows the utility of this strain for controlling the Ae. aegypti mosquitoes and the pathogens they transmit.
The novel visual cycle inhibitor (±)-RPE65-61 protects retinal photoreceptors from light-induced degeneration
Authors: Wang Yuhong , Ma Xiang , Muthuraman Parthasarathy , Raja Arun , Jayaraman Aravindan , Petrukhin Konstantin , Cioffi Christopher L. , Ma Jian-Xing , Moiseyev Gennadiy
Published: October 2022

The visual cycle refers to a series of biochemical reactions of retinoids in ocular tissues and supports the vision in vertebrates. The visual cycle regenerates visual pigments chromophore, 11-cis-retinal, and eliminates its toxic byproducts from the retina, supporting visual function and retinal neuron survival. Unfortunately, during the visual cycle, when 11-cis-retinal is being regenerated in the retina, toxic byproducts, such as all-trans-retinal and bis-retinoid is N-retinylidene-N-retinylethanolamine (A2E), are produced, which are proposed to contribute to the pathogenesis of the dry form of age-related macular degeneration (AMD). The primary biochemical defect in Stargardt disease (STGD1) is the accelerated synthesis of cytotoxic lipofuscin bisretinoids, such as A2E, in the retinal pigment epithelium (RPE) due to mutations in the ABCA4 gene. To prevent all-trans-retinal—and bisretinoid-mediated retinal degeneration, slowing down the retinoid flow by modulating the visual cycle with a small molecule has been proposed as a therapeutic strategy. The present study describes RPE65-61, a novel, non-retinoid compound, as an inhibitor of RPE65 (a key enzyme in the visual cycle), intended to modulate the excessive activity of the visual cycle to protect the retina from harm degenerative diseases. Our data demonstrated that (±)-RPE65-61 selectively inhibited retinoid isomerase activity of RPE65, with an IC50 of 80 nM. Furthermore, (±)-RPE65-61 inhibited RPE65 via an uncompetitive mechanism. Systemic administration of (±)-RPE65-61 in mice resulted in slower chromophore regeneration after light bleach, confirming in vivo target engagement and visual cycle modulation. Concomitant protection of the mouse retina from high-intensity light damage was also observed. Furthermore, RPE65-61 down-regulated the cyclic GMP-AMP synthase stimulator of interferon genes (cGAS-STING) pathway, decreased the inflammatory factor, and attenuated retinal apoptosis caused by light-induced retinal damage (LIRD), which led to the preservation of the retinal function. Taken together, (±)-RPE65-61 is a potent visual cycle modulator that may provide a neuroprotective therapeutic benefit for patients with STGD and AMD.
Propensity score analysis comparing survival between definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma
Authors: Chang Yi-Lin , Cheng Ya-Fu , Chen Hui-Shan , Wu Siao-Chi , Hung Wei-Heng , Chen Heng-Chung , Huang Chang-Lun , Cheng Ching-Yuan , Wang Bing-Yen
Published: October 2022

Introduction

The purpose of the current study is to compare definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy in patients with cT1-3/N0-3 esophageal squamous cell carcinoma in survival.

Methods

Records from 2008 to 2014 of 4931 patients with clinical T1-3/N0-3 esophageal squamous cell carcinoma receiving definitive chemoradiotherapy or esophagectomy with adjuvant chemoradiotherapy were obtained from the Taiwan Cancer Registry. Univariable and multivariable analyses were performed and propensity score matching was used to minimize the bias. Overall survival was compared between definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy, and also in the three different clinical stages.

Results

Definitive chemoradiotherapy was performed on 4381 patients, and 550 patients received esophagectomy adjuvant chemoradiotherapy. Each group produced 456 patients for comparison after propensity score matching. The 1-year, 2-year, and 3-year overall survival rates for matched patients in with definitive chemoradiotherapy group were 57.18%, 31.92%, and 23.8%. The 1-year, 2-year, and 3-year overall survival rates for matched patients treated in the esophagectomy with adjuvant chemoradiotherapy group were 72.35%, 45.74%, and 34.04%(p<0.0001). In multivariable analysis, treatment modality was an independent prognostic factor. Esophagectomy with adjuvant chemoradiotherapy provided better survival outcome than definitive chemoradiotherapy for patients with clinical stage II/III disease. As for patients with clinical stage I disease, there was no significant survival difference between definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy.

Conclusions

Esophagectomy with adjuvant chemoradiotherapy provided better survival than definitive chemoradiotherapy in clinical II/III esophageal squamous cell carcinoma. However, more data are needed to conduct a convincing conclusion in clinical stage I patients.
Using colony size to measure fitness in Saccharomyces cerevisiae
Authors: Miller James H. , Fasanello Vincent J. , Liu Ping , Longan Emery R. , Botero Carlos A. , Fay Justin C.
Published: October 2022

Competitive fitness assays in liquid culture have been a mainstay for characterizing experimental evolution of microbial populations. Growth of microbial strains has also been extensively characterized by colony size and could serve as a useful alternative if translated to per generation measurements of relative fitness. To examine fitness based on colony size, we established a relationship between cell number and colony size for strains of Saccharomyces cerevisiae robotically pinned onto solid agar plates in a high-density format. This was used to measure growth rates and estimate relative fitness differences between evolved strains and their ancestors. After controlling for edge effects through both normalization and agar-trimming, we found that colony size is a sensitive measure of fitness, capable of detecting 1% differences. While fitnesses determined from liquid and solid mediums were not equivalent, our results demonstrate that colony size provides a sensitive means of measuring fitness that is particularly well suited to measurements across many environments.
Physical exercise during neoadjuvant chemotherapy for breast cancer as a mean to increase pathological complete response rates: Trial protocol of the randomized Neo-ACT trial
Authors: de Boniface Jana , Altena Renske , Haddad Ringborg Cecilia , Bolam Kate A. , Wengström Yvonne
Published: October 2022

Introduction

In early breast cancer, neoadjuvant chemotherapy (NACT) is increasingly used. The proof of efficacy is pathologically complete response (pCR), i.e. the absence of invasive tumour in breast and lymph nodes at surgery. Today, pCR is a common endpoint in pharmaceutical trials since it is significantly associated with survival especially in triple-negative and HER2-positive subtypes. Apart from the mitigation of treatment-related toxicity and symptoms, physical exercise mediates anti-tumoral systemic effects associated with tumour regression in preclinical and clinical models. The aim of Neo-ACT is to test the hypothesis that physical exercise can improve pCR rates in breast cancer patients receiving NACT.

Method

The Neo-ACT trial is a prospective clinical trial, randomising T1-3N0-2 breast cancer patients planned for NACT to either a home-based physical exercise intervention supported by a mobile application or routine care. The primary endpoint is pCR; secondary endpoints are patient-reported quality of life, toxicity-related outcomes, and oncological outcomes such as Residual Cancer Burden, objective radiological tumour response, as well as overall, breast cancer-specific and disease-free survival at 2, 5 and 10 years. The intervention consists of a combination of high-intensity interval and resistance training of progressing intensity, and includes at least 150 min of moderate to vigorous physical activity per week, inclusive of two weekly 60-min exercise sessions. In order to show an improvement in pCR of 10%, a total of 712 participants need to be included in the analysis. The Neo-ACT has been registered at clinicaltrials.gov on January 11, 2022 (NCT05184582).

Expected results

If Neo-ACT can prove the oncological efficacy of physical exercise, implementation of training programmes into NACT schedules will be pursued. The use of a digitally led exercise intervention aims to test the potential of such a strategy for use in rural areas and areas of limited resources.
Facebook as a source of access to medicines
Authors: Zaprutko Tomasz , Kopciuch Dorota , Paczkowska Anna , Sprawka Józefina , Cynar Julia , Pogodzińska Monika , Niewczas Katarzyna , Stolecka Aleksandra , Sygit Maria , Michalak Michał , Ratajczak Piotr , Kus Krzysztof
Published: October 2022

Over the last decade, we’ve observed an enormous social media development, which have recently become commercial services. Hence, we aimed to verify if Facebook might be considered as a source of access to medicines. We also intended to identify prescription (Rx) and over the counter (OTC) medicines if available on that platform. The study was conducted from January 2019 to July 2020. We investigated offers of pharmaceuticals posted on Facebook (individual posts and communities) between 2016 and 2019. Medicines were divided into Rx and OTC brands and in accordance with their possible therapeutic use. We verified whether the medicines were for sale, to exchange, or available for free. Posts and groups were investigated for example, by entering the phrase “for free,” followed by a city in Poland. Out of 409 offers, 380 (92.91%) concerned Rx brands and 29 (7.09%) OTC brands. 315 (77.02%) medications were available “for free”. In 47 (11.49%) cases, an “exchange” was expected, and 47 (11.49%) announcements were marked as “for sale”. Cardiovascular medicines (n = 125; 30.56%) were the most popular. There were also antidiabetics (n = 38; 9.29%) and antipsychotics (n = 28; 6.84%). We also found clear candidates for misuse. These were opioids (n = 7; 1.71%), benzodiazepines (n = 2; 0.48%), clomifene (n = 1; 0.24%), and letrozole (n = 1; 0.24%). Facebook provides the possibility of uncontrolled access to medicines. The majority of offers concerned Rx brands, including opioids and benzodiazepines. Medicines offered on Facebook were mainly accessible for free. The scope and the number of medications offered on Facebook should make this issue a hazardous phenomenon.
Measuring job satisfaction of midwives: A scoping review
Authors: Wangler Sonja , Streffing Joana , Simon Anke , Meyer Gabriele , Ayerle Gertrud M.
Published: October 2022

Background

Given the global shortage of midwives, it is of utmost interest to improve midwives’ job satisfaction and working environments. Precise measurement tools are needed to identify both predictors of job satisfaction and intervention strategies which could increase it. The aim of this study is to collate, describe and analyse instruments used in research to assess the job satisfaction of midwives working in hospitals, to identify valid and reliable tools and to make recommendations for the further development of specific instruments for midwifery practice and future midwifery research.

Methods

We conducted systematic literature searches of the following databases: CINAHL, MEDLINE, PsycINFO, Web of Science Core Collection, Cochrane Database. Studies which assessed the job satisfaction of midwives working in a hospital setting were eligible for inclusion.

Findings

Out of 637 records 36 empirical research articles were analysed, 27 of them cross-sectional studies. The studies had been conducted in 23 different countries, with sample sizes ranging between nine and 5.446 participants. Over 30 different instruments were used to measure midwives’ job satisfaction, with considerable differences in terms of domains evaluated and number of items. Twelve domains relevant for job satisfaction of midwives working in hospitals were identified from the empirical studies. Four instruments met the defined reliability and validity criteria.

Conclusion

Autonomy, the significance of the job, the challenges of balancing work and private life, and the high emotional and physical demands of midwifery are job characteristics which are underrepresented in instruments measuring job satisfaction. The influence of the physical working environment has also not yet been researched. There is a need to develop or adapt instruments to the working environment of midwives.
Insight into the regulatory networks underlying the high lipid perennial ryegrass growth under different irradiances
Authors: Winichayakul Somrutai , Macknight Richard , Le Lievre Liam , Beechey-Gradwell Zac , Lee Robyn , Cooney Luke , Xue Hong , Crowther Tracey , Anderson Philip , Richardson Kim , Zou Xiuying , Maher Dorothy , Bryan Gregory , Roberts Nick
Published: October 2022

Under favourable conditions, perennial ryegrass (Lolium perenne) engineered to accumulated high lipid (HL) carbon sink in their leaves was previously shown to also enhance photosynthesis and growth. The greater aboveground biomass was found to be diminished in a dense canopy compared to spaced pots. Besides, the underlying genetic regulatory network linking between leaf lipid sinks and these physiological changes remains unknown. In this study, we demonstrated that the growth advantage was not displayed in HL Lolium grown in spaced pots under low lights. Under standard lights, analysis of differentiating transcripts in HL Lolium reveals that the plants had elevated transcripts involved in lipid metabolism, light capturing, photosynthesis, and sugar signalling while reduced expression of genes participating in sugar biosynthesis and transportation. The plants also had altered several transcripts involved in mitochondrial oxidative respiration and redox potential. Many of the above upregulated or downregulated transcript levels were found to be complemented by growing the plants under low light. Overall, this study emphasizes the importance of carbon and energy homeostatic regulatory mechanisms to overall productivity of the HL Lolium through photosynthesis, most of which are significantly impacted by low irradiances.
Promoting engagement with quality communication in social media
Authors: Cinelli Matteo , Peruzzi Antonio , Schmidt Ana Lucía , Villa Roberta , Costa Enrico , Quattrociocchi Walter , Zollo Fabiana
Published: October 2022

The COVID-19 pandemic made explicit the issues of communicating science in an information ecosystem dominated by social media platforms. One of the fundamental communication challenges of our time is to provide the public with reliable content and contrast misinformation. This paper investigates how social media can become an effective channel to promote engagement and (re)build trust. To measure the social response to quality communication, we conducted an experimental study to test a set of science communication recommendations on Facebook and Twitter. The experiment involved communication practitioners and social media managers from select countries in Europe, applying and testing such recommendations for five months. Here we analyse their feedback in terms of adoption and show that some differences emerge across platforms, topics, and recommendation categories. To evaluate these recommendations’ effect on users, we measure their response to quality content, finding that the median engagement is generally higher, especially on Twitter. The results indicate that quality communication strategies may elicit positive feedback on social media. A data-driven and co-designed approach in developing counter-strategies is thus promising in tackling misinformation.
Chimeric inheritance and crown-group acquisitions of carbon fixation genes within Chlorobiales: Origins of autotrophy in Chlorobiales and implication for geological biomarkers
Authors: Paoletti Madeline M. , Fournier Gregory P.
Published: October 2022

The geological record of microbial metabolisms and ecologies primarily consists of stable isotope fractionations and the diagenetic products of biogenic lipids. Carotenoid lipid biomarkers are particularly useful proxies for reconstructing this record, providing information on microbial phototroph primary productivity, redox couples, and oxygenation. The biomarkers okenane, chlorobactane, and isorenieratene are generally considered to be evidence of anoxygenic phototrophs, and provide a record that extends to 1.64 Ga. The utility of the carotenoid biomarker record may be enhanced by examining the carbon isotopic ratios in these products, which are diagnostic for specific pathways of biological carbon fixation found today within different microbial groups. However, this joint inference assumes that microbes have conserved these pathways across the duration of the preserved biomarker record. Testing this hypothesis, we performed phylogenetic analyses of the enzymes constituting the reductive tricarboxylic acid (rTCA) cycle in Chlorobiales, the group of anoxygenic phototrophic bacteria usually implicated in the deposition of chlorobactane and isorenieretane. We find phylogenetically incongruent patterns of inheritance across all enzymes, indicative of horizontal gene transfers to both stem and crown Chlorobiales from multiple potential donor lineages. This indicates that a complete rTCA cycle was independently acquired at least twice within Chlorobiales and was not present in the last common ancestor. When combined with recent molecular clock analyses, these results predict that the Mesoproterzoic lipid biomarker record diagnostic for Chlorobiales should not preserve isotopic fractionations indicative of a full rTCA cycle. Furthermore, we conclude that coupling isotopic and biomarker records is insufficient for reliably reconstructing microbial paleoecologies in the absence of a complementary and consistent phylogenomic narrative.