bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of esketamine and treatment expectation in acute major depressive disorder (Expect): study protocol for a pharmacological fMRI study using a balanced placebo design
Authors: Falkenberg Irina , Bitsch Florian , Liu Wei , Matsingos Alexandros , Noor Laila , Vogelbacher Christoph , Yildiz Cüneyt , Kircher Tilo
Published: August 2023

Background

Major depressive disorder (MDD) is a highly prevalent (8–15%), severely disabling disorder and is associated with enormous socioeconomic impact. Antidepressant medication for the treatment of MDD has proven effective in RCTs; however, placebo response is also substantial. Given the potential benefits of modulating the placebo response in patient care and pharmacological research, understanding the mechanisms underlying placebo response is of high clinical relevance. The placebo response is mediated by treatment expectation, i.e. an individual’s belief about whether and how much they will improve as a consequence of their treatment. The mechanisms and moderators of treatment expectation effects in MDD are poorly understood. Initial brain imaging studies on placebo responses in MDD point towards the relevance of the lateral prefrontal cortex and the rostral anterior cingulate cortex (rACC). In this project, we will investigate the neural mechanisms underlying the antidepressant effects of treatment expectation associated with the fast-acting antidepressant esketamine in patients with MDD. Esketamine is an NMDA receptor antagonist inducing antidepressant effects within hours.

Methods

We will employ a fully balanced placebo design with the factors “treatment” (i.v. esketamine / placebo) and verbally induced “expectation” (high / low) combined with fMRI (resting state, emotion and reward processing paradigms) to investigate the psychological and neural mechanisms underlying the antidepressant effects of expectation, and how these interact with the pharmacological effects of esketamine.

Discussion

The insights gained by this project promise fundamental implications for clinical treatment and future drug trials. Unraveling the mechanisms underlying expectation effects on antidepressant treatment may inform (1) strategies to modulate these effects and thus improve assay sensitivity in RCTs and (2) novel treatment regiments aiming to maximize the synergistic effects of expectation and pharmacological treatment in the clinical care of patients with MDD.

Trial registration

This trial has been prospectively registered with the EU Clinical Trials Register: EudraCT-No.: 2020–000784-23 (November 17, 2020).
Rapid assessment of 3-dimensional intra-tumor heterogeneity through cycling temperature capillary electrophoresis
Authors: Połeć Anna , Ekstrøm Per Olaf , Fougner Christian , Sørlie Therese , Norum Jens Henrik
Published: August 2023

Objective

Tumors are heterogeneous three-dimensional masses populated by numerous cell types, including distinct sub-clones of cancerous cells. Various sub-clones within the same tumor mass may respond differently to cancer treatment, and intra-tumor heterogeneity contributes to acquired therapeutic resistance. Thus, one tissue biopsy will in most cases not be representative of the entire genetic landscape of a tumor mass. In this study, we aimed to establish an easily accessible, low cost method to address intra-tumor heterogeneity in three dimensions, for a limited number of DNA alterations.

Results

This study includes analyses of the three-dimensional (3D) distribution of DNA mutations in human colon cancer and mouse mammary gland tumor tissue samples. We used laser capture microdissection for the unbiased collection of tissue in several XY-planes throughout the tumor masses. Cycling temperature capillary electrophoresis was used to determine mutant allele frequency. High-resolution distribution maps of KRAS and Trp53 mutations were generated for each XY-plane in human and mouse tumor samples, respectively. To provide a holistic interpretation of the mutation distribution, we generated interactive 3D heatmaps giving an easily interpretable understanding of the spatial distribution of the analyzed mutations. The method described herein provides an accessible way of describing intra-tumor heterogeneity for a limited number of mutations.
Comparison of four DNA extraction methods for 16s rRNA microbiota profiling of human faecal samples
Authors: Sinclair James , West Nicholas P , Cox Amanda J
Published: August 2023

Objective

Growth in large population-based studies assessing contributions of the gut microbiota to health and disease requires high-throughput sample processing and analysis methods. This study assessed the impact that modifications to a commercially available magnetic bead based, semi-automated DNA extraction kit had on determination of microbial composition, relative to an established in-house method involving a combination of mechanical and chemical lysis. DNA was extracted from faecal samples from healthy adults (n = 12; 34–69 years), microbial composition was determined by V3-V4 16s rRNA sequencing and compared between extraction methods.

Results

Diversity metrics did not differ between extraction methods. Differences in the relative abundance of key phyla, including a significantly lower abundance of the Firmicutes (p = 0.004) and higher relative abundance of the Bacteroidetes (p = 0.005) and Proteobacteria (p = 0.008) phyla were noted where the DNA extraction did not include additional chemical and mechanical lysis. Principal coordinate analysis of family and genera level data also suggested a potential for sample pre-processing to impact microbial composition. Observations of the potential for skewed microbial composition profiles from samples prepared using a semi-automated DNA extraction kit without additional sample pre-processing highlights a need for consideration of standardisation of methodological approaches to increase the comparability of microbial compositional data.
Clinical impact and misdiagnosis of functional ophthalmological symptoms: a case report
Authors: Pozuelo Moyano Beatriz , Duquenne Catherine , Favrat Bernard , Francois-Xavier Borruat , Kokkinakis Ioannis , Tzartzas Konstantinos
Published: August 2023

Background

There is a high prevalence of somatoform disorders and medically unexplained symptoms. When it comes to deciding whether a patient is able to work, it is essential to differentiate a somatoform disorder from a factitious disorder. The case presented demonstrates the impact on disability benefits and the subsequent psychosocial repercussions of misdiagnosing between a factitious disorder and a somatoform disorder.

Case presentation

A 42-year-old Caucasian woman worked as a 100% fiduciary accountant until the age of 32 when she was placed on medical leave due to persistent trigeminal neuralgia. Afterward, she developed total blindness, not explained by a physiological process, accompanied by distress in a crucial emotional context. We evaluated the patient for a revision of a disability income after a diagnosis of factitious disorder with severe consequences such as disability income suspension and family conflict. Our psychiatric examination concluded the diagnoses of pain disorders related to psychological factors and a dissociative neurological symptom disorder with visual disturbance.

Conclusions

Blindness not explained by a physiological process may accompany trauma and psychological distress. Differentiating this pathology from factitious disorder or simulation is essential from an insurance medicine point of view, but also for its treatment.
Metachronous ureteral metastasis of a gastric adenocarcinoma: a case report and review of literature
Authors: Alla Meriem Ait , Chekrine Tarik , Bouchbika Zineb , Benchakroun Nadia , Jouhadi Hassan , Tawfiq Nezha , Chaouki Houda , Marnissi Farida , Karkouri Mehdi , Sahraoui Souha
Published: August 2023

Background

Ureteral metastasis from gastric cancers are rare and can be a cause of ureteral obstruction. There have been few published case reports in the literature. In this paper, we report an additional case and a review of the literature of all the previous reported cases.

Case presentation

A 67 years old North African women who was treated four years before for a gastric adenocarcinoma, presented with abdominal pain. Imaging and endoscopy showed a mural stenosis of the left ureter, without any other abnormality. Histopathology confirmed the gastric origin of the metastasis. A palliative chemotherapy was foreseen, but due to the deterioration of the general condition of the patient, she received palliative care. We have also reviewed the literature and reported the previously published cases of ureteral metastasis from gastric cancer.

Conclusions

It is worth recalling that in a context of neoplasia and with the presence of signs of ureteral obstruction, it is important to keep in mind the possibility of a ureteral metastasis.
Production of omega-5 gliadin monoclonal antibodies for allergenic evaluation of WDEIA-causing wheat varieties
Authors: Sim Jae-Ryeong , Lee Jong-Yeol , Kim Sewon
Published: August 2023

In allergic individuals, ingestion of wheat can lead to wheat-dependent exercise-induced anaphylaxis (WDEIA). Many studies have been conducted to find WDEIA allergen–deficient wheat, including by generating omega-5 gliadin antibodies. However, the reported antibodies have not been specific enough to detect omega-5 gliadins encoded on the 1B chromosome. In this study, we generated monoclonal antibodies against the major allergens causing WDEIA, omega-5 gliadins. Using these antibodies (mono-O5B-1C10), we assessed accumulation of omega-5 gliadins in wild-type and nullisomic-tetrasomic (NT) lines of the wheat (Triticum aestivum) varieties Chinese Spring (CS) by one- and two-dimensional gel electrophoresis, followed by Coomassie blue staining or immunoblotting with mono-O5B-1C10. We also tested mono-O5B-1C10 for major omega-5 gliadins in various wheat germplasms. Our results thus demonstrate the specificity of mono-O5B-1C10 for major omega-5 gliadins and potentially useful for identifying of omega-5 gliadin–deficient wheat varieties that should not cause WDEIA.
First record of rainbow shrimp, exotic species Mierspenaeopsis sculptilis (Heller, 1862), in the Brazilian coastal amazon, validated by DNA barcode
Authors: Ferreira Charles Samuel Moraes , de Mesquita David Carvalho , de Freitas Lutz Ítalo Antônio , Veneza Ivana Barbosa , Martins Thaís Sousa , Santana Paula da Conceição Praxedes , Miranda Josy Alessandra Barreto , de Sousa Jefferson Miranda , Matos Suane Cristina do Nascimento , Holanda Francisco Carlos Alberto Fonteles , da Cunha Sampaio Maria Iracilda , Evangelista-Gomes Grazielle Fernanda
Published: August 2023

Background

This is the first record of the alien shrimp Mierspenaeopsis sculptilis in Brazil. The invasion was detected within Marine Extractive Reserves based on eight specimens accidentally caught by local fishermen using trawlnets focused on fisheries of native species. These specimens were transported to the Laboratory of Applied Genetics and morphologically identified as Mierspenaeopsis sculptilis (rainbow shrimp). The taxonomic status of analyzed samples was confirmed by DNA barcoding using a 627-bp fragment of the Cytochrome C Oxidase Subunit I (COI) gene.

Results

A single haplotype was recovered from the eight specimens, being identical to a haplotype reported in India, where this species naturally occurs, and in Mozambique, where the rainbow shrimp is considered an invasive species. The present analyses indicated a putative invasive route (i.e., India-Mozambique-Brazil) mediated by shipping trade.

Conclusions

This study presents the first record of Mierspenaeopsis sculptilis in Brazil, in areas of extractive reserves on the Amazon coast. Notably exotic species can cause imbalance in the ecosystem, harming native species. In view of this, the registration of new invasions is essential as they contribute to the implementation of control plans.
Validation of the media fill method for Cytokine-Induced killer cells manufacturing process
Authors: Ferrero Ivana , Castiglia Sara , Adamini Aloe , Mandese Alessandra , Sismondi Francesca , Rustichelli Deborah , Leone Marco , Pinnetta Giuseppe , Giordanengo Lucia , Mareschi Katia , Fagioli Franca
Published: August 2023

Background

Media fills are used to demonstrate the adequacy of the aseptic conditions of a pharmaceutical production process, according to good manufacturing practice (GMP), using a growth medium in place of the product solution. For advanced therapy medicinal product (ATMP), where the final product consists of viable cells, the media fill is still a challenge, but represents the starting point for process validation.

Methods

The aim of this paper is to describe the media fill test procedure in the context of ATMP manufacturing, in particular of Cytokine-Induced Killer (CIK) cell expansion process under GMP conditions, including quality control tests and environmental monitoring. The media fill test has been designed to cover all the critical steps of the process, including worst cases and deviations.

Results

From July 2019 to August 2022, we performed 16 media fill tests. During these years, the media fill protocol has been gradually improved and the worst cases were designed to be closer to reality and occurring cases. Although some deviations occurred, all the media fills performed were compliant.

Conclusions

A good media fill design combined with a robust environmental monitoring program provides a high degree of assurance of the microbial safety of ATMPs.
Suzuki–Miyaura cross-couplings for alkyl boron reagent: recent developments—a review
Authors: Ahmed Adnan , Mushtaq Irfan , Chinnam Sampath
Published: August 2023

In the history of catalysis and organic synthesis, boric chemistry has been developed into one of the most varied and practical disciplines. Several useful Suzuki–Miyaura cross-coupling (SMC) reactions as well as hydroborylation reactions are regarded the essential tools inside the chemical synthesis toolkit accompanied by researchers of the industry or the academia. Novel synthesis of the less electrically and sterically ongoing carbon–boron synthetic reagents is carried out to ensure a unique coupling reaction utilizing metals along with these reagents which draws considerable interest in accelerating the discovery of creative uses for otherwise difficult organic adducts in many disciplines. This article details the noteworthy advancements in the use of traditional metal-catalyzed carbon–carbon coupling processes with cutting-edge coupling partners such as carbon–boron reagents often the beta-alkyl Suzuki–Miyaura coupling since 2001. The current review covers alkylboranes, organotrifluoroborates, 9-BBN, alkylboronic acids and boronic esters as useful reagents in SMCs that will help synthetic chemists in developing new compounds.

Graphical Abstract
“The Agriculture Ministry of the Whole World”
Authors: Williams Elizabeth R.
Published: August 2023

In 1905 the establishment of the International Institute of Agriculture (IIA), the forerunner to the Food and Agriculture Organization (FAO) of the United Nations, created a forum for bureaucrats and technocrats from around the globe to exchange information about the latest developments in agricultural practice and administration. Representatives from the Ottoman Empire were active participants in the institute's early activities. This article traces their contributions to the institute's formative debates that aimed to set international standards as well as the imperial-level projects that resulted from their participation. It argues that the institute, in addition to representing a space in which Ottoman officials could assert their expertise and perform their capacity to be a part of global standard-setting processes, provided an impetus for collating and comparing statistics from across the empire. The projects undertaken drew from existing provincial statistics-gathering institutions and served to reveal differences across provinces in a step toward greater empire-wide legibility. Focusing on the empire's Eastern Mediterranean provinces, the article demonstrates how these statistics' public circulation not only enabled Ottoman officials to identify regions they considered ripe for further agricultural development, but also supported French officials' justifications for imposing colonial rule post–World War I.
Introduction
Authors: Abusharaf Rogaia , Chandra Uday , Promodh Irene
Published: August 2023

This special section draws on the dynamic new field of Indian Ocean studies to rethink key concepts such as space and circulation (Jeremy Prestholdt), gender and kinship (Mahmood Kooria), and popular media and infrastructure (Bindu Menon Mannil). Through fresh interdisciplinary insights from the contributors' archives and fieldwork, the articles critically interrogate these concepts from a distinctive intellectual vantage point. Historians and anthropologists based in different parts of the globe come together in this special section to “think with the Indian Ocean.” The authors take a concept that is in wide currency in the humanities and social sciences and then reimagine it creatively in the contexts that they study. In doing so, they decenter familiar ways of seeing and knowing, offering a new decolonial lens to make sense of the circularities and connections that constitute our world.
Ethical issues of involving people with intellectual disabilities in genomic research: a scoping review protocol
Authors: Chepkirui Dorothy , Kipkemoi Patricia , Bitta Mary , Harris Eli , Musesengwa Rosemary , Kamuya Dorcas
Published: August 2023

Background: Psychiatric genomic research is a growing field of research in Africa that is looking at epigenetics of psychiatric disorders; within which a specific focus is neurodevelopmental disorders including intellectual disability (ID). Conducting this type of research is  important to identify etiologies and possible interventions or areas for further research. However, genomic research generally, and psychiatric genomic research, faces many social, ethical, cultural, and legal issues; research involving people with ID is particularly challenging. All research stakeholders - researchers, research review bodies, regulators, patient groups - generally agree that involving people with ID require several considerations, including extra protection. It is also recognized that not involving people with ID in research that is relevant to them means that opportunities to learn on specific issues including lived experiences are missed. In this scoping review, we aim to describe the range of ethical and social-cultural issues concerning involvement of people with intellectual disability in genomic research from existing literature.

Methods: This scoping review will be conducted based on the Joanna Briggs Institute guidance for scoping review and reported using the PRISMA-ScR guidelines. Iterative review stages will include systematic search of six databases (Embase, Ovid Global Health, PubMed, Scopus, PsycInfo and Web of Science core collection), screening, charting and synthesis of the data. Forward and backward citation screening will also be done for the articles included in the final review. We will include peer reviewed journal articles, guidance documents and reports. Screening and selection of studies based on the eligibility criteria will be done independently by three reviewers; conflicts will be resolved through discussion with a third reviewer and other experts.

Results: The results will be included in the scoping review publication.

Conclusions: This scoping review will identify key areas of ethical tensions and possible solutions and inform opportunities for empirical ethics studies.
Iterative Backpropagation Method for Efficient Gradient Estimation in Bilevel Network Equilibrium Optimization Problems
Authors: Patwary A.U.Z , Wang Shuling , Lo Hong K.
Published: August 2023

Network optimization or network design with an embedded traffic assignment (TA) to model user equilibrium principle, sometimes expressed as bilevel problems or mathematical programs with equilibrium constraints (MPEC), is at the heart of transportation planning and operations. For applications to large-scale multimodal networks with high dimensional decision variables, the problem is nontrivial, to say the least. General-purpose algorithms and problem-specific bilevel formulations have been proposed in the past to solve small problems for demonstration purposes. Research gap, however, exists in developing efficient solution methods for large-scale problems in both static and dynamic contexts. This paper proposes an efficient gradient estimation method called Iterative Backpropagation (IB) for network optimization problems with an embedded static TA model. IB exploits the iterative structure of the TA solution procedure and simultaneously calculates the gradients while the TA process converges. IB does not require any additional function evaluation and consequently scales very well with higher dimensions. We apply the proposed approach to origin-destination (OD) estimation, an MPEC problem, of the Hong Kong multimodal network with 49,806 decision variables, 8,797 nodes, 18,207 links, 2,684 transit routes, and 165,509 OD pairs. The calibrated model performs well in matching the link counts. Specifically, the IB-gradient based optimization technique reduces the link volume squared error by 98%, mean absolute percentage error (MAPE) from 95.29% to 21.23%, and the average GEH statistics from 24.18 to 6.09 compared with the noncalibrated case. The framework, even though applied to OD estimation in this paper, is applicable to a wide variety of optimization problems with an embedded TA model, opening up an efficient way to solve large-scale MPEC or bilevel problems.

Funding: The study is supported by IVADO Postdoctoral Fellowship scheme 2021, HSBC 150th Anniversary Charity Programme HKBF17RG01, National Science Foundation of China (71890970, 71890974), General Research Fund (16212819, 16207920) of the HKSAR Government, and the Hong Kong PhD Fellowship.
Metacognition in early years?
Authors: Hubball Amanda
Published: August 2023

Amanda Hubball, deputy head at Alfreton Nursery School, discusses the importance of including metacognition in early years education and strategies for how settings can incorporate it.
Reading: Shifting the focus from phonics to foundations
Authors: Kay Maria
Published: August 2023

Maria Kay, schools advisor and founder of Sounds and Symbols, discusses the importance of giving children wide exposure to literacy experiences before starting phonics teaching, in order to create strong literacy foundations which phonics can build on to successfully teach children to read.
Using technology to support SEND in early years
Authors: Lings Tim
Published: August 2023

Digital technology can be a great learning tool for children with SEND in an Early Years Foundation Stage setting, as well as an invaluable resource for adults who are supporting these children. Tim Lings, director of Digital Learning at Heronsgate Primary School, shares his tips.
Developing key language skills through music and movement
Authors: Newman Sue
Published: August 2023

Sue Newman, director of operations at Boogie Mites, discusses the importance of harnessing the power of music to build strong foundations for children’s language development in early years, ahead of International Literacy Day in September.
Supporting children’s learning with curriculum development
Authors: Swailes Ruth
Published: August 2023

Ruth Swailes, school improvement and early years advisor, discusses her experiences designing the International Early Years curriculum for Oxford University Press, and shares her tips and insights to help practitioners develop their own curriculum.
Researching the impact of Montessori education in low-income areas of England
Authors: Archer Nathan
Published: August 2023

Director of the International Montessori Institute, Dr Nathan Archer, discusses the findings of his research into the work of Montessori nurseries in socio-economically disadvantaged areas of England amid the current economic climate, and the challenges nurseries and families face following the pandemic.
What if Ofsted gets it wrong? Unpicking the aftermath in practice, reality and the future
Authors: Meecha David
Published: August 2023

David Meechan, senior lecturer at the University of Northampton, shares his experiences supporting a private setting that challenged their ‘Inadequate’ rating from an inspection in November 2022. After the complaint, the setting was reinspected in April 2023 and received a ‘Good’ rating across the board.
Weaning: Research into mothers’ experiences of the first four weeks
Authors: Hewison Ruth
Published: August 2023

The second article in this series by Ruth Hewison, Early Childhood Studies graduate, explores and analyses the data from her undergraduate research project into mothers’ experiences of the first four weeks of weaning. She focuses on the first two key themes identified from the research, starting weaning and baby-led and spoon-fed weaning methods.
Professional Book Reviews
Authors: Roberts Elly
Published: August 2023

Elly Roberts, editor of Early Years Educator, reviews a book which discusses the current realities and future priorities for the early years sector. The picture books help reinforce language acquisition, help children to understand their emotions and introduce readers to an important chapter in our history.
Having fun with learning
Authors: Roberts Elly
Published: August 2023

Carole Blackwood, Nursery practitioner at Oakwell Children’s Nursery in Scotland, discusses the importance of creating a fun environment to enable children to learn.
Squaring the Circles: a Genealogy of Principia ’s Dot Notation
Authors: Elkind Landon D. C.
Published: August 2023

Abstract: Russell derived many of his logical symbols from the pioneering notation of Giuseppe Peano. Principia Mathematica (1910–13) made these “Peanese” symbols (and others) famous. Here I focus on one of the more peculiar notational derivatives from Peano, namely, Principia ’s dual use of a squared dot or dots for both conjunction and scope. As Dirk Schlimm has noted, Peano always had circular dots and only used them to symbolize scope distinctions. In contrast, Principia has squared dots and conventions such that some dots mark scope distinctions while others symbolize conjunction. How did this come to pass? In this paper I trace a genealogy of Principia ’s square dots back to Russell’s appropriation of Peano’s use of circular dots. Russell never explicitly justifies appropriating Peano’s notations to symbolize two distinct notions, but below I explain why Russell deployed Peano’s dot notations in this manner. Further, I argue that it was Cambridge University Press who squared the circular dots.
Jean Nicod: Familial Background and Pacifist Commitment
Authors: Gandon Sébastien
Published: August 2023

Abstract: This article has two purposes: first, to describe some archival discoveries about Nicod’s family background, academic development and political life; and second, to publish and comment on a newly discovered article by Nicod about Russell. This article acclaims not only Russell’s achievements in logic and philosophy—as one might expect from such a devoted protégé as Nicod—but also (albeit only in glimpses permitted by France’s wartime censorship) his anti-war politics and writings. As the reader will realize, the two objectives are connected: what the archives reveal and what the article illustrates is a hitherto underappreciated level of political awareness and pacifist commitment in Nicod.
Receptive field sizes and neuronal encoding bandwidth are constrained by axonal conduction delays
Authors: Hladnik Tim C. , Grewe Jan
Published: August 2023

Studies on population coding implicitly assume that spikes from the presynaptic cells arrive simultaneously at the integrating neuron. In natural neuronal populations, this is usually not the case—neuronal signaling takes time and populations cover a certain space. The spread of spike arrival times depends on population size, cell density and axonal conduction velocity. Here we analyze the consequences of population size and axonal conduction delays on the stimulus encoding performance in the electrosensory system of the electric fishApteronotus leptorhynchus. We experimentally locate p-type electroreceptor afferents along the rostro-caudal body axis and relate locations to neurophysiological response properties. In an information-theoretical approach we analyze the coding performance in homogeneous and heterogeneous populations. As expected, the amount of information increases with population size and, on average, heterogeneous populations encode better than the average same-size homogeneous population, if conduction delays are compensated for. The spread of neuronal conduction delays within a receptive field strongly degrades encoding of high-frequency stimulus components. Receptive field sizes typically found in the electrosensory lateral line lobe ofA. leptorhynchusappear to be a good compromise between the spread of conduction delays and encoding performance. The limitations imposed by finite axonal conduction velocity are relevant for any converging network as is shown by model populations of LIF neurons. The bandwidth of natural stimuli and the maximum meaningful population sizes are constrained by conduction delays and may thus impact the optimal design of nervous systems.
Enhancement of capsular hypermucoviscosity in Klebsiella pneumoniae by Acanthamoeba
Authors: Huang Jian-Ming , Sung Ko-Chiang , Lin Wei-Chen , Lai Hong-Yue , Wang Yu-Jen
Published: August 2023

Background

Acanthamoeba and Klebsiella pneumoniae are both environmental commensals. Recently, clinical harm caused by hypermucoviscous K. pneumoniae has been observed. However, the interaction between these microbes and the origin of hypermucoviscous K. pneumoniae have not been reported

Methodology/Principal findings

Here, we report that the bacterial capsule is enlarged when co-cultured with Acanthamoeba using India ink staining, and this effect depends on the number of parasites present. This interaction results in an enhancement of capsular polysaccharide production in the subsequent generations of K. pneumoniae, even without co-culturing with Acanthamoeba. The hypermucoviscosity of the capsule was examined using the sedimentation assay and string test. We also screened other K. pneumoniae serotypes, including K1, K2, K5, and K20, for interaction with Acanthamoeba using India ink staining, and found the same interaction effect

Conclusions/Significance

These findings suggest that the interaction between Acanthamoeba and K. pneumoniae could lead to harmful consequences in public health and nosocomial disease control, particularly hypermucoviscous K. pneumoniae infections.
Service reliability evaluation of highway tunnel based on digital image processing
Authors: Dai Chunquan , Zhou Zhaochen , Zhang Huidi , Jiang Kun , Li Haisheng , Yu Haiyang
Published: August 2023

China is gradually transitioning from the "tunnel construction exploration era" to the "tunnel high-quality construction and operation era", and the maintenance demand of highway tunnels has increased sharply. Therefore, there is an urgent need for an evaluation method to evaluate the service reliability of highway tunnels, so as to provide reference for tunnel maintenance personnel to carry out maintenance work. Taking highway tunnels as the research object, this paper extracts three parameters, including length, maximum width and fractal dimension, from the binary image of highway tunnel lining cracks. The standard for dividing the length of the highway tunnel section is 500m as the tunnel section, and a section disease sample space including multiple highway tunnels is constructed. The EM clustering algorithm was used to determine the number of graded grades of disease, and the relative Euclidean distance was used as the evaluation index to divide the safety grade of the tunnel into five grades: normal, degraded, inferior, deteriorated and hazardous. The partial least squares method is used to establish the lining service reliability evaluation formula and verify the residual of each sample point in the sample space. The smaller the average value of the residual, the better fitting effect of the established evaluation formula. The service reliability evaluation method proposed in this paper is applied to engineering practice and compared with the expert scoring method and the national standard method, which proves that the evaluation method in this paper has the advantages of strong visibility, simple evaluation method, and is conducive to engineering practice.
Evaluation the validity and reliability of the perceived medical school stress scale in Turkish medical students
Authors: Çınar Tanrıverdi Esra , Yılmaz Sinan , Çayır Yasemin
Published: August 2023

Medical education can be a challenging and stressful process. Additional stressors can make the medical education process even more complex and impair a student’s attention and concentration. To the authors’ knowledge, there is no valid and reliable scale to measure medical school stress in Turkish medical students. Therefore, this study aimed to determine the validity and reliability of the Perceived Medical School Stress (PMSS) Scale in Turkish medical students. The Perceived Medical School Stress Scale is a self-assessment tool developed to measure medical school-induced stress in medical students. It consists of 13 items divided into two subdimensions. Scale items are answered using a four-point (0–4) Likert system The total score that can be obtained from the PMSS ranges from 0 to 52, with higher scores indicating higher levels of perceived stress. First, the scale was applied as a pilot to 52 students by performing the scale’s back-and-forth translation into Turkish. Then, the scale was applied to 612 volunteer medical students to ensure validity. Convergent validity and confirmatory factor analysis are used to assess the construct validity of a scale. Test-retest, item correlations, and Cronbach’s alpha coefficients are used to evaluate the reliability of a scale. As a result of confirmatory factor analysis, the two-factor structure of the original scale was confirmed. The fit indices of the model obtained showed excellent fit. The Generalized Anxiety Disorder-7 (GAD-7) Scale was used for convergent validity. The GAD-7 is a self-assessment tool that measures the level of generalized anxiety. It is answered with a four-point Likert scale for the last two weeks. The score that can be obtained from the scale is between 0–21. A score of ten or more indicates possible anxiety disorder. The students’ mean perceived medical school stress score was 39.80±8.09, and their GAD-7 score was 11.0±5.5. A significant positive relationship was found between the total scores of the scales (r = .48, P < .001). The Cronbach’s alpha value of the scale was .81, and test-retest reliability was significant for all scale items (P < .001 for all). No item was deleted according to Cronbach’s alpha values and item-total correlations. There was no significant relationship between Turkish version of the PMSS and GAD-7 scores and age, sex, income status, tobacco use, or exercise (P>.05). The Turkish version of the Perceived Medical School Stress Scale is a valid and reliable scale that can be used to investigate the medical school-specific stress of students.
Regadenoson for the treatment of COVID-19: A five case clinical series and mouse studies
Authors: Rabin Joseph , Zhao Yunge , Mostafa Ezzat , Al-Suqi Manal , Fleischmann Emily , Conaway Mark R. , Mann Barbara J. , Chhabra Preeti , Brayman Kenneth L. , Krupnick Alexander , Linden Joel , Lau Christine L.
Published: August 2023

Background

Adenosine inhibits the activation of most immune cells and platelets. Selective adenosine A2A receptor (A2AR) agonists such as regadenoson (RA) reduce inflammation in most tissues, including lungs injured by hypoxia, ischemia, transplantation, or sickle cell anemia, principally by suppressing the activation of invariant natural killer T (iNKT) cells. The anti-inflammatory effects of RA are magnified in injured tissues due to induction in immune cells of A2ARs and ecto-enzymes CD39 and CD73 that convert ATP to adenosine in the extracellular space. Here we describe the results of a five patient study designed to evaluate RA safety and to seek evidence of reduced cytokine storm in hospitalized COVID-19 patients.

Methods and findings

Five COVID-19 patients requiring supplemental oxygen but not intubation (WHO stages 4–5) were infused IV with a loading RA dose of 5 μg/kg/h for 0.5 h followed by a maintenance dose of 1.44 μg/kg/h for 6 hours, Vital signs and arterial oxygen saturation were recorded, and blood samples were collected before, during and after RA infusion for analysis of CRP, D-dimer, circulating iNKT cell activation state and plasma levels of 13 proinflammatory cytokines. RA was devoid of serious side effects, and within 24 hours from the start of infusion was associated with increased oxygen saturation (93.8 ± 0.58 vs 96.6 ± 1.08%, P<0.05), decreased D-dimer (754 ± 17 vs 518 ± 98 ng/ml, P<0.05), and a trend toward decreased CRP (3.80 ± 1.40 vs 1.98 ± 0.74 mg/dL, P = 0.075). Circulating iNKT cells, but not conventional T cells, were highly activated in COVID-19 patients (65% vs 5% CD69+). RA infusion for 30 minutes reduced iNKT cell activation by 50% (P<0.01). RA infusion for 30 minutes did not influence plasma cytokines, but infusion for 4.5 or 24 hours reduced levels of 11 of 13 proinflammatory cytokines. In separate mouse studies, subcutaneous RA infusion from Alzet minipumps at 1.44 μg/kg/h increased 10-day survival of SARS-CoV-2-infected K18-hACE2 mice from 10 to 40% (P<0.001).

Conclusions

Infused RA is safe and produces rapid anti-inflammatory effects mediated by A2A adenosine receptors on iNKT cells and possibly in part by A2ARs on other immune cells and platelets. We speculate that iNKT cells are activated by release of injury-induced glycolipid antigens and/or alarmins such as IL-33 derived from virally infected type II epithelial cells which in turn activate iNKT cells and secondarily other immune cells. Adenosine released from hypoxic tissues, or RA infused as an anti-inflammatory agent decrease proinflammatory cytokines and may be useful for treating cytokine storm in patients with Covid-19 or other inflammatory lung diseases or trauma.
Robust visual detection of brake-lights in front for commercialized dashboard camera
Authors: Moon Jiyong , Park Seongsik
Published: August 2023

The collision avoidance system (CAS) is an essential system for safe driving that alerts the driver or automatically applies the brakes in an expected situation of a vehicle collision. To realize this, an autonomous system that can quickly and precisely detect brake-lights of preceding vehicle is essential and this should works well in various environments for safety reason. Our proposed vision algorithm solves these objectives focusing on simple color features rather than a learning algorithm with a high computational cost, since our target system is a real-time embedded device, i.e., forward-facing dashboard camera. However, the existing feature-based algorithms are vulnerable to the ambient noise (noise problem), and cannot be flexibly applied to various environments (applicability problem). Therefore, our method is divided into two stages:rear-lights region detectionusing gamma correction for noise problem, andbrake-lights detectionusing HSV color space for applicability problem, respectively. (i)Rear-lights region detection: we confirm the presence of the vehicle in front and derive the rear-lights region, and used non-linear mapping of gamma correction to make the detected region robust to noise. (ii)Brake-lights detection: from the detected rear-lights region, we extract color features using the HSV color range so that we can classify brake on and off in various conditions. Experimental results show that our algorithm overcomes the noise problem and applicability problem in various environments.
A novel CNN gap layer for growth prediction of palm tree plantlings
Authors: Kumar T. Ananth , Rajmohan R. , Adeola Ajagbe Sunday , Gaber Tarek , Zeng Xiao-Jun , Masmoudi Fatma
Published: August 2023

Monitoring palm tree seedlings and plantlings presents a formidable challenge because of the microscopic size of these organisms and the absence of distinguishing morphological characteristics. There is a demand for technical approaches that can provide restoration specialists with palm tree seedling monitoring systems that are high-resolution, quick, and environmentally friendly. It is possible that counting plantlings and identifying them down to the genus level will be an extremely time-consuming and challenging task. It has been demonstrated that convolutional neural networks, or CNNs, are effective in many aspects of image recognition; however, the performance of CNNs differs depending on the application. The performance of the existing CNN-based models for monitoring and predicting plantlings growth could be further improved. To achieve this, a novel Gap Layer modified CNN architecture (GL-CNN) has been proposed with an IoT effective monitoring system and UAV technology. The UAV is employed for capturing plantlings images and the IoT model is utilized for obtaining the ground truth information of the plantlings health. The proposed model is trained to predict the successful and poor seedling growth for a given set of palm tree plantling images. The proposed GL-CNN architecture is novel in terms of defined convolution layers and the gap layer designed for output classification. There are two 64×3 conv layers, two 128×3 conv layers, two 256×3 conv layers and one 512×3 conv layer for processing of input image. The output obtained from the gap layer is modulated using the ReLU classifier for determining the seedling classification. To evaluate the proposed system, a new dataset of palm tree plantlings was collected in real time using UAV technology. This dataset consists of images of palm tree plantlings. The evaluation results showed that the proposed GL-CNN model performed better than the existing CNN architectures with an average accuracy of 95.96%.
Mesenchymal stem cell-neural progenitors are enriched in cell signaling molecules implicated in their therapeutic effect in multiple sclerosis
Authors: Harris Violaine K. , Wollowitz Jaina , Greenwald Jacelyn , Carlson Alyssa L. , Sadiq Saud A.
Published: August 2023

Mesenchymal stem cell-neural progenitors (MSC-NP) are a neural derivative of MSCs that are being investigated in clinical trials as an autologous intrathecal cell therapy to treat patients with secondary progressive (SP) or primary progressive (PP) multiple sclerosis (MS). MSC-NPs promote tissue repair through paracrine mechanisms, however which secreted factors mediate the therapeutic potential of MSC-NPs and how this cell population differs from MSCs remain poorly understood. The objective of this study was to define the transcriptional profile of MSCs and MSC-NPs from MS and non-MS donors to better characterize each cell population. MSCs derived from SPMS, PPMS, or non-MS bone marrow donors demonstrated minimal differential gene expression, despite differences in disease status. MSC-NPs from both MS and non-MS-donors exhibited significant differential gene expression compared to MSCs, with 2,156 and 1,467 genes upregulated and downregulated, respectively. Gene ontology analysis demonstrated pronounced downregulation of cell cycle genes in MSC-NPs compared to MSC consistent with reduced proliferation of MSC-NPs in vitro. In addition, MSC-NPs demonstrated significant enrichment of genes involved in cell signaling, cell communication, neuronal differentiation, chemotaxis, migration, and complement activation. These findings suggest that increased cell signaling and chemotactic capability of MSC-NPs may support their therapeutic potential in MS.
Study on the China’s real interest rate after including housing price factor into CPI
Authors: Ding Shiting , Pan Qintian , Zhang Yanming , Zhang Jingru , Yang Qiong , Luan Jingdong
Published: August 2023

The Chinese economy has undergone a long-term transition reform, but there is still a planned economy characteristic in the financial sector, which is financial repression. Due to the existence of financial repression, China’s actual interest rate level should be lower than the Consumer Price Index (CPI). However, based on official China’s interest rates and CPI, over half of the years China’s actual interest rate remained higher than CPI by our calculation from 1999 to 2022. This is inconsistent with the financial repression that exists in China, and the main reason is the calculation methods of China’s CPI. China’s CPI measurement system originated from the planned economy era, which did not fully consider the rise in housing purchase prices, so the current CPI measurement system can be more realistically presented by taking the rise in housing prices into consider. The core idea of this study is to mining relevant official statistical data and calculate the proportion of Chinese residents’ expenditure on purchasing houses to their total expenditure. By taking the proportion of house purchases as the weight of house price factor, and taking the proportion of other consumption as the weight of official CPI, the Generalized CPI (GCPI) is formulated. The GCPI is then compared with market interest rates to determine the actual interest rate situation in China over the past 20 years. This study has found that if GCPI is used as a measure, China’s real interest rates have been negative for most years since 1999. Chinese residents have suffered the negative effects of financial repression over the past 20 years, and their property income cannot keep up with the actual losses caused by inflation. Therefore, it is believed that China’s CPI calculation method should be adjusted to take into account the rise in housing prices, so China’s actual inflation level could be more accurately reflected. In view of the above, deepening interest rate marketization reform and expand channels for financial investment are the future development goals of China’s financial system.
Effects of non-pharmacological interventions on patients with sarcopenic obesity: A meta-analysis
Authors: Xu Jiajia , Hu Qingqing , Li Jiaying , Zhou Yixi , Chu Ting
Published: August 2023

Objective

Systematic evaluation of the improvement effect of non-pharmacological intervention on patients with sarcopenic obesity.

Methods

Wanfang, VIP, China National Knowledge Infrastructure (CNKI), SinoMed, Web of Science, Cochrane Library, PubMed, and Embase databases were searched systematically for randomized controlled trials (RCTS) and experimental studies of non-pharmacological interventions on patients with sarcopenic obesity. The retrieval period was from the establishment of the databases to October 31, 2022. Meta-analysis was conducted using RevMan 5.4.

Results

A total of 18 studies involving 1,109 patients were included. Meta-analysis results showed that non-pharmacological interventions improved patients’ body weight [mean difference, MD = −2.74, 95% CI (−4.79, −0.70), P = 0.009], body fat percentage [MD = −0.67, 95% CI (−0.96, −0.38), P<0.00001], grip strength [MD = 1.29, 95% CI (0.81, 1.77), P<0.00001], gait speed [MD = 0.05, 95% CI (0.03, 0.07), P<0.00001], and knee extension strength [MD = 2.56, 95% CI (1.30, 3.82), P<0.0001].

Conclusions

Non-pharmacological interventions can effectively improve the clinical symptoms and signs of patients with sarcopenic obesity. Dissemination of this information will be therapeutically useful.

Trial registration

Registration. The PROSPERO No. is CRD42023403341.