bluuebunny/crossref_metadata_2025 huggingface dataset:
Royle, Modern Britain - A Social History, 1750-1985. Lloyd, Empire to Welfare State - English History, 1906-1985
Authors: Ellefson C. Ashley
Published: February 2024

Both of these books illustrate the failure of a society to solve the problems that have plagued it ever since the industrial revolution. England has never, except for the few years after World War II, possessed the will even seriously to try to confront those problems. Inequality and misery have not been the result simply of temporary malfunctions of English capitalism but rather have been necessary and inevitable features of it.
Edward Royle's Modern Britain: A Social History, 1750-1985, should give pause to those enthusiasts for economic change who believe that displaced workers can easily be absorbed into new industries. The wealthiest classes have always "benefited disproportionately" from economic change. They have always moved into the suburbs and left an inner city of "deteriorating housing ... and a rash of cheap, speculative . . . building." The cities have provided "scenes of human degradation" above which hang "palls of smoke and industrial fumes" and "the inescapable stench of animal and human excrement."
Socially Responsible Leadership and Job Engagement in University Context: Mediation of Psychological Safety
Authors: Kyambade Mahadih , Namatovu Afulah , Mugambwa Joshua , Namuddu Regis , Namubiru Bridget
Published: February 2024

Purpose - This study looks into the connection between job engagement (JE) and socially responsible leadership (SRL) in public universities in Uganda.Methodology - The study is quantitative in nature and consisted of personnel working at Uganda's public universities supplied data. The information was gathered using a five-point Likert scale in an organized questionnaire. Expert judgment and content validity were used to assess the validity of the instrument. Warp PLS and smart PLS-SEM analysis was run on 214 legitimate responses among 250 public university staff. Findings - The findings demonstrated a positive correlation between JE and SRL. PS and SRL were found to be positively correlated. Furthermore, the results showed a positive correlation between PS and JE. Additionally, the findings demonstrated that PS acts as mediation in the relationship between SRL and JE. Originality – The study contributes to the understanding of the approaches related to improving employee job engagement in the education sector. The study adds to the body of knowledge concerning the association between job engagement and psychological safety a crucial aspect of socially responsible leadership by examining data from developing countries in addition to other countries which had previously been ignored. Practical implications - This study contributes to the corpus of research on SRL and PS, especially in the context of universities, in terms of JE. Additionally, it provides advice on how to use PS and SRL to enhance university workplace conditions such as JE. By emphasizing the crucial roles that a psychologically safe environment and leadership style that is socially responsible play in promoting positive social interactions at work, our article advances the understanding of social exchange theory.
Death on the Roads: Motoring with Agatha Christie
Authors: Plain Gill
Published: February 2024

Over the course of her autobiography, Agatha Christie makes some fascinating observations about cars, and what their growing ubiquity meant to a young woman transitioning from Victorian girlhood to interwar modernity. In her interwar novels, meanwhile, the car functions variously as a marker of status, an index of character and a symbol of female agency. However, this initially optimistic embrace of motoring modernity began to change in the second half of Christie's career, with the result that the car would come to signify not just a changing relationship between gender and mobility, but also a transition in detective methodology. Exploring novels from the interwar, war and postwar periods – including Why Didn’t They Ask Evans? (1934), The Hollow (1946) and By the Pricking of My Thumbs (1968) – this article follows the car to map transitions in how, why, and what Christie detects.
The Bulletin, ‘Londonisation’ and Scottish Politics in the 1940s and 1950s
Authors: Cameron Ewen A.
Published: February 2024

This article seeks to examine Scottish politics in the decade or so following the Second World War. The objective is to uncover the texture of Scottish politics in a period that has been characterised rather simplistically. Much of the evidence for the paper is drawn from the Scottish popular press, most notably newspapers such as the Bulletin, which was a Glasgow publication with a unionist outlook, motivated by a concern to keep Scottish issues to the fore and to resist centralisation. The article will examine the way in which interpretations of this period in Scottish politics, as being one dominated by a unionism that was common to the main parties, serve to flatten what was an interesting and contested landscape. There is a considerable literature on this period in British historiography that engages in a debate about the value of the idea of ‘consensus’ in British politics. The apparent consensus over the Union hid a range of important debates about the way in which the Union ought to operate that were of such an extent as to bring the idea of a unionist consensus into question. Given that the Scottish National Party was such a marginal force in Scottish politics in this period, it seems more sensible to focus on the debates about the meaning of the Union rather than to adopt an existential focus that was simply not present in day-to-day political debate in the decade following the Second World War.
Postprocedural delirium following mechanical thrombectomy for acute ischemic stroke: a retrospective study
Authors: Sachdev Alisha , Torrez Daniel , Sun Sarah , Michapoulos George , Rigler Nicholas C. , Feldner Alexandra L. , Hong Young Soo , McCarthy Robert J.
Published: February 2024

Introduction

National representative estimates on in-hospital delirium after acute ischemic stroke are not well established and there is limited data on the impact of delirium on clinical outcomes following mechanical thrombectomy. We evaluated risk factors for delirium and the impact on outcomes following mechanical thrombectomy for acute ischemic stroke.

Methods

This is a retrospective study of patients who underwent mechanical thrombectomy for acute ischemic stroke at a single tertiary comprehensive stroke center between April 2011 and December 2019. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit. Patient characteristics, comorbidities, laboratory data, elapsed times, tissue plasminogen activator use, duration of the procedure, type of anesthesia, National Institute of Health stroke scores (NIHSS), sedation scores, reperfusion grades, complications, length of hospital stay, discharge disposition, and 90-day mortality were evaluated.

Results

Five hundred and two patients were evaluated, and post-procedural delirium was identified in 24/467 (5.1%) patients. Thirty-five patients could not be assessed for delirium due to excessive sedation. The incidence of delirium in white vs. non-white patients <65 years was 5/137 (3.6%) compared to 0/91 (0%), and 7/176 (4.0%) compared to 12/63 (19%) in patients ≥65 years, P = 0.006. Bias reduction multi-variable analysis identified low postprocedural hemoglobin level odds ratio of 0.76 (95% CI 0.61–0.92, P = 0.006), greater age (odds ratio 1.04, 95% CI 1.01–1.009, P = 0.024), and non-white race odds ratio of 2.52 (95% CI 1.06–6.38, P = 0.030) as factors associated with delirium [Brier score = 0.045, C-index = 0.800, and Akaike Information Criterion (AIC) = 174]. General anesthesia was not associated with an increased delirium risk. NIHSS at 24 and 48 h and discharge, length of stay, and 90-day mortality were not different between delirium and no-delirium groups. Delirium patients had a reduced odds ratio of 0.13 (05% CI 0.01–1.00, P = 0.02) for home discharge.

Discussion

Delirium following mechanical thrombectomy for acute ischemic stroke primarily affected older patients and was associated with reduced odds of home discharge following hospitalization. Changes in NIHSS during hospitalization and 90-day mortality were not adversely affected by the presence of delirium. General anesthesia was not associated with an increased delirium risk following mechanical thrombectomy.
Bibliometric analysis of antimalarial drug resistance
Authors: Zhang Jialu , Shahbaz Muhammad , Ijaz Muhammad , Zhang Huimin
Published: February 2024

Background

Malaria has always been a serious infectious disease prevalent in the world. Antimalarial drugs such as chloroquine and artemisinin have been the main compounds used to treat malaria. However, the massive use of this type of drugs accelerates the evolution and spread of malaria parasites, leading to the development of resistance. A large number of related data have been published by researchers in recent years. CiteSpace software has gained popularity among us researchers in recent years, because of its ability to help us obtain the core information we want in a mass of articles. In order to analyze the hotspots and develop trends in this field through visual analysis, this study used CiteSpace software to summarize the available data in the literature to provide insights.

Method

Relevant literature was collected from the Web of Science Core Collection (WOSCC) from 1 January 2015 to 29 March 2023. CiteSpace software and Microsoft Excel were used to analyze and present the data, respectively.

Results

A total of 2,561 literatures were retrieved and 2,559 literatures were included in the analysis after the removal of duplicates. An irrefutable witness of the ever-growing interest in the topic of antimalarial drug resistance could be expressed by the exponentially increased number of publications and related citations from 2015 to 2022, and its sustained growth trend by 2023. During the past 7 years, USA, Oxford University, and David A Fidock are the country, institution, and author with the most publications in this field of research, respectively. We focused on the references and keywords from literature and found that the research and development of new drugs is the newest hotspot in this field. A growing number of scientists are devoted to finding new antimalarial drugs.

Conclusion

This study is the first visual metrological analysis of antimalarial drug resistance, using bibliometric methods. As a baseline information, it is important to analyze research output published globally on antimalarial drug resistance. In order to better understand the current research situation and future research plan agenda, such baseline data are needed accordingly.
Are there literature reviews about gamification to foster Inclusive Teaching? A scoping review of gamification literature reviews
Authors: Ruiz-Navas Santiago , Ackaradejraungsri Pajaree , Dijk Sandra
Published: February 2024

Introduction

Gamification can support the practical application of Inclusive Teaching. However, gamification literature reviews to implement Inclusive Teaching are scarce or not existent. Therefore, we conducted a scoping review of gamification literature reviews to identify what themes are covered and specifically if Inclusive Teaching has been explored.

Method

The scoping literature review comprises network and content analyses of gamification literature reviews retrieved from the Web of Science. We analyzed a multimode network of papers and keywords and used their eigenvector centrality to identify themes. The content analysis comprised of a human and automatic tagging process to identify each paper’s discipline/context.

Results

We mapped the themes explored in 125 gamification literature reviews to answer our first research question, what are the areas of knowledge covered by gamification literature reviews? The central topic is gamification and education to increase motivation, followed by gamification itself and understanding the implementation of gamification in various contexts. We identified 12 contexts and the top five frequent were Education, Business, Gamification, and Political Science. From the year-by-year analysis, we separated the themes into four periods: beginning (2014–2015), understanding (2016–2017), focus 2018 and focus and emergence (2019–2022). Regarding our second research question, how is the topic of Inclusive Teaching explored in gamification literature reviews? We did not find literature reviews about gamification to support Inclusive Teaching in the existing dataset.

Discussion

We report on the benefits of organizing central keywords by quartiles and using multimode networks to support scoping reviews; and disadvantages and advantages of using literature reviews as data sources for scoping reviews. We invite researchers to create more gamification literature reviews, to investigate gamification ethics in the light of recent technological developments such as generative models, and to reconnect gamification to the game design elements part of its definition, which goes beyond game elements.
A nomogram based on clinicopathological and ultrasound characteristics to predict central neck lymph node metastases in papillary thyroid cancer
Authors: Chen Fei , Jiang Shuiping , Yao Fan , Huang Yixi , Cai Jiaxi , Wei Jia , Li Chengxu , Wu Yanxuan , Yi Xiaolin , Zhang Zhen
Published: February 2024

Purpose

Papillary thyroid cancer (PTC) has grown rapidly in prevalence over the past few decades, and central neck lymph node metastasis (CNLNM) is associated with poor prognoses. However, whether to carry out preventive central neck lymph node dissection (CNLND) is still controversial. We aimed to construct a prediction model of CNLNM to facilitate making clinical surgical regimens.

Methods

A total of 691 patients with PTC between November 2018 and December 2021 were included in our study. Univariate and multivariate analyses were performed on basic information and clinicopathological characteristics, as well as ultrasound characteristics (American College of Radiology (ACR) scores). The prediction model was constructed and performed using a nomogram, and then discriminability, calibrations, and clinical applicability were evaluated.

Results

Five variables, namely, male, age >55 years, clinical lymph node positivity, tumor size ≥1 cm, and ACR scores ≥6, were independent predictors of CNLNM in the multivariate analysis, which were eventually included to construct a nomogram model. The area under the curve (AUC) of the model was 0.717, demonstrating great discriminability. A calibration curve was developed to validate the calibration of the present model by bootstrap resampling, which indicated that the predicted and actual values were in good agreement and had no differentiation from the ideal model. The decision curve analysis (DCA) indicated that the prediction model has good clinical applicability.

Conclusions

Our non-invasive prediction model combines ACR scores with clinicopathological features presented through nomogram and has shown good performance and application prospects for the prediction of CNLNM in PTCs.
Nomogram model based on preoperative clinical characteristics of unilateral papillary thyroid carcinoma to predict contralateral medium-volume central lymph node metastasis
Authors: Wu Fan , Huang Kaiyuan , Huang Xuanwei , Pan Ting , Li Yuanhui , Shi Jingjing , Ding Jinwang , Pan Gang , Peng You , Teng Yueping , Zhou Li , Luo Dingcun , Zhang Yu
Published: February 2024

Objectives

To explore the preoperative high-risk clinical factors for contralateral medium-volume central lymph node metastasis (conMVCLNM) in unilateral papillary thyroid carcinoma (uPTC) and the indications for dissection of contralateral central lymph nodes (conCLN).

Methods

Clinical and pathological data of 204 uPTC patients who underwent thyroid surgery at the Hangzhou First People’s Hospital from September 2010 to October 2022 were collected. Univariate and multivariate logistic regression analyses were conducted to determine the independent risk factors for contralateral central lymph node metastasis (conCLNM) and conMVCLNM in uPTC patients based on the preoperative clinical data. Predictive models for conCLNM and conMVCLNM were constructed using logistic regression analyses and validated using receiver operating characteristic (ROC) curves, concordance index (C-index), calibration curves, and decision curve analysis (DCA).

Results

Univariate and multivariate logistic regression analyses showed that gender (P < 0.001), age (P < 0.001), tumor diameter (P < 0.001), and multifocality (P = 0.008) were independent risk factors for conCLNM in uPTC patients. Gender(P= 0.026), age (P = 0.010), platelet-to-lymphocyte ratio (PLR) (P =0.003), and tumor diameter (P = 0.036) were independent risk factors for conMVCLNM in uPTC patients. A predictive model was established to assess the risk of conCLNM and conMVCLNM, with ROC curve areas of 0.836 and 0.845, respectively. The C-index, the calibration curve, and DCA demonstrated that the model had good diagnostic value.

Conclusion

Gender, age, tumor diameter, and multifocality are high-risk factors for conCLNM in uPTC patients. Gender, age, tumor diameter, and PLR are high-risk factors for conMVCLNM in uPTC patients, and preventive conCLN dissection should be performed.
Spectrum of genetic variants in bilateral sensorineural hearing loss
Authors: Ali Amanat , Tabouni Mohammed , Kizhakkedath Praseetha , Baydoun Ibrahim , Allam Mushal , John Anne , Busafared Faiza , Alnuaimi Ayesha , Al-Jasmi Fatma , Alblooshi Hiba
Published: February 2024

Background: Hearing loss (HL) is an impairment of auditory function with identified genetic forms that can be syndromic (30%) or non-syndromic (70%). HL is genetically heterogeneous, with more than 1,000 variants across 150 causative genes identified to date. The genetic diagnostic rate varies significantly depending on the population being tested. Countries with a considerably high rate of consanguinity provide a unique resource for studying rare forms of recessive HL. In this study, we identified genetic variants associated with bilateral sensorineural HL (SNHL) using whole-exome sequencing (WES) in 11 families residing in the United Arab Emirates (UAE).

Results: We established the molecular diagnosis in six probands, with six different pathogenic or likely pathogenic variants in the genes MYO15A, SLC26A4, and GJB2. One novel nonsense variant, MYO15A:p.Tyr1962Ter*, was identified in a homozygous state in one family, which has not been reported in any public database. SLC26A4 and GJB2 were found to be the most frequently associated genes in this study. In addition, six variants of uncertain significance (VUS) were detected in five probands in the genes CDH23, COL11A1, ADGRV1, NLRP3, and GDF6. In total, 12 variants were observed in eight genes. Among these variants, eight missense variants (66.7%), three nonsense variants (25.0%), and one frameshift (8.3%) were identified. The overall diagnostic rate of this study was 54.5%. Approximately 45.5% of the patients in this study came from consanguineous families.

Conclusion: Understanding the genetic basis of HL provides insight for the clinical diagnosis of hearing impairment cases through the utilization of next-generation sequencing (NGS). Our findings contribute to the knowledge of the heterogeneous genetic profile of HL, especially in a population with a high rate of consanguineous marriage in the Arab population.
From digital voices to vaccine choices: increasing female vaccine acceptance in Sudan through social listening
Authors: Ahmed Islam , Ali Hiba , Ali Sehrish , Van Woerden Simon , Hanna-Amodio Antonio , Chen Katie , Onitolo Elizabeth , Gillespie Amaya
Published: February 2024

The early COVID-19 vaccine rollout in Sudan experienced a gender disparity in vaccine uptake, with women accounting for less than 40% of vaccinations after four months of vaccine access. Initial analysis revealed that demand generation approaches were not sufficiently tailored to address the challenges and concerns of women. Using real-time social media monitoring, also known as social listening, to understand this inequity, we used an analytical tool called “Talkwalker” to track public sentiment and engagement regarding vaccination on social media platforms. The data captured subsequently informed a gender-responsive messaging campaign on social media that directly addressed specific concerns of Sudanese women. Within one week of the campaign's onset in September 2021, we observed a 144% increase in women's COVID-19 related social media engagement. Subsequent campaigns further enhanced women's engagement from 31% to between 35%–47%. Two subsequent campaigns in January and February/March 2022 were complemented with in-person activities, such as group meetings with community members and home visits by health promoters. Women's vaccination rates increased by 9% while the first two campaigns were live. System constraints hindered data linkages for the third campaign. These findings demonstrate the value of integrating real-time feedback with large-scale social media campaigns and the potential of linking online and offline strategies to further refine interventions, particularly in a conflict-prone and low-income country context. Our experience reinforces the notion that “one size does not fit all” when it comes to health-related communication. Responses should be tailored, contextualized, and person-centered, particularly in addressing concerns unique to women.
Homeodomain-only protein suppresses proliferation and contributes to differentiation- and age-related reduced CD8+ T cell expansion
Authors: Yang Qian , Patrick Michael , Lu Jian , Chen Joseph , Zhang Yongqing , Hemani Humza , Lehrmann Elin , De Supriyo , Weng Nan-ping
Published: February 2024

T cell activation is a tightly controlled process involving both positive and negative regulators. The precise mechanisms governing the negative regulators in T cell proliferation remain incompletely understood. Here, we report that homeodomain-only protein (HOPX), a homeodomain-containing protein, and its most abundant isoform HOPXb, negatively regulate activation-induced proliferation of human T cells. We found that HOPX expression progressively increased from naïve (TN) to central memory (TCM) to effector memory (TEM) cells, with a notable upregulation following in vitro stimulation. Overexpression of HOPXb leads to a reduction in TN cell proliferation while HOPX knockdown promotes proliferation of TN and TEM cells. Furthermore, we demonstrated that HOPX binds to promoters and exerts repressive effects on the expression of MYC and NR4A1, two positive regulators known to promote T cell proliferation. Importantly, our findings suggest aging is associated with increased HOPX expression, and that knockdown of HOPX enhances the proliferation of CD8+ T cells in older adults. Our findings provide compelling evidence that HOPX serves as a negative regulator of T cell activation and plays a pivotal role in T cell differentiation and in age-related-reduction in T cell proliferation.
Hosts and impacts of elongate hemlock scale (Hemiptera: Diaspididae): A critical review
Authors: Venette Robert C. , Ambourn Angie , Aukema Brian H. , Jetton Robert M. , Petrice Toby R.
Published: February 2024

Fiorinia externa Ferris, elongate hemlock scale, was inadvertently introduced to North America from Japan. This insect is particularly problematic on hemlock, Tsuga spp., though it has been reported in association with several other conifers. The evidence that other conifers might be hosts, capable of supporting growing populations of the insect, has not been previously reviewed. Our review confirms that F. externa is an oligophagous pest of members of Pinaceae. Although species of Cupressaceae and Taxaceae have been reported as hosts of F. externa, they seem unable to support population growth of this pest. Evidence of the tree-killing potential of the insect, even on suitable hosts, is remarkably scant. The degree of pest risk posed by F. externa with respect to tree mortality in areas beyond the geographic range of hemlock seems modest, but uncertain.
Roles and mechanisms of biomechanical-biochemical coupling in pelvic organ prolapse
Authors: Wu Huaye , Zhang Ling , He Li , Lin Wenyi , Yu Bo , Yu Xia , Lin Yonghong
Published: February 2024

Pelvic organ prolapse (POP) is a significant contributor to hysterectomy among middle-aged and elderly women. However, there are challenges in terms of dedicated pharmaceutical solutions and targeted interventions for POP. The primary characteristics of POP include compromised mechanical properties of uterine ligaments and dysfunction within the vaginal support structure, often resulting from delivery-related injuries. Fibroblasts secrete extracellular matrix, which, along with the cytoskeleton, forms the structural foundation that ensures proper biomechanical function of the fascial system. This system is crucial for maintaining the anatomical position of each pelvic floor organ. By systematically exploring the roles and mechanisms of biomechanical-biochemical transformations in POP, we can understand the impact of forces on the injury and repair of these organs. A comprehensive analysis of the literature revealed that the extracellular matrix produced by fibroblasts, as well as their cytoskeleton, undergoes alterations in patient tissues and cellular models of POP. Additionally, various signaling pathways, including TGF-β1/Smad, Gpx1, PI3K/AKT, p38/MAPK, and Nr4a1, are implicated in the biomechanical-biochemical interplay of fibroblasts. This systematic review of the biomechanical-biochemical interplay in fibroblasts in POP not only enhances our understanding of its underlying causes but also establishes a theoretical foundation for future clinical interventions.
Temporal trend of anisometropia incidence in Chinese school-aged children before and during the COVID-19 pandemic
Authors: Huang Yin , Qiu Kunliang , Li Yuancun , Wang Hongxi , Zhang Mingzhi
Published: February 2024

Objective

To analyze and compare the temporal trends in the incidence of anisometropia among Chinese school-aged children both before and during the COVID-19 pandemic, and to investigate the impact of the pandemic on the incidence of anisometropia.

Methods

We conducted a retrospective study comprising six distinct and independent longitudinal cohorts, each including children aged 6 to 13 years who visited the Joint Shantou International Eye Center between January 2010 and December 2021. Children were grouped into cohorts based on the year of their first eye clinic visit: 2010, 2012, 2014, 2016, 2018, or 2020. Only children without anisometropia at initial visits, followed for 18 ± 6 months, were included. The cumulative incidence and risk factors of anisometropia were analyzed using Kaplan–Meier estimation and Cox proportional hazards regression models. Subgroup analyses were performed based on sex, age groups, initial refractive error status, and initial interocular SE difference. Anisometropic children were further categorized into myopic and non-myopic, with subsequent subgroup analyses conducted.

Results

Of 11,235 children were recruited from six cohorts (2010: n = 1,366; 2012: n = 1,708; 2014: n = 1,896; 2016: n = 2,354; 2018: n = 2,514; 2020: n = 1,397), 869 children developed anisometropia during a mean follow-up of 17.5 ± 3.7 months. After adjustment of confounding factors, we found that the risk of anisometropia remained relatively stable before 2020 but significantly increased in the 2020 cohort (adjusted HR 2.93, 95% CI 2.23 to 3.86; p < 0.001). This trend persisted in studies of spherical anisometropia (adjusted HR 2.52, 95% CI 1.60 to 3.97; p < 0.001) and cylindrical anisometropia (adjusted HR 2.91, 95% CI 1.69 to 3.62; p < 0.001). Older age and a greater initial difference in SE between the two eyes were also significantly associated with a higher risk of developing anisometropia (p < 0.001). Subgroup analyses consistently showed increased risk in the 2020 cohort.

Conclusion

This study reveals a concerning rise in anisometropia incidence among Chinese school-aged children during the period of the COVID-19 pandemic. These findings highlight the worrisome rise in anisometropia risk during the COVID-19 pandemic and emphasize the importance of early detection and management to safeguard children’s visual health.
Dermatological ultrasound in assessing skin aging
Authors: Pequeno Ana Luiza Viana , Bagatin Ediléia
Published: February 2024

Ultrasonography (US) has emerged as a pivotal tool in Dermatology since its inaugural use in 1979. Its evolution encompasses technological advancements, higher frequencies, and diverse applications in clinical, surgical, and research aspects. The discussion centers on its crucial role in assessing skin aging through various parameters such as skin thickness, subepidermal low echogenicity band (SLEB) characterization, and echogenicity assessment. This analysis can help guide interventions in a more personalized manner for each patient and assess the effectiveness of cosmetics and procedures. Despite its widespread utility, challenges persist, including discrepancies in research outcomes, operator dependence, inability to detect minute lesions, and measurement variations throughout the day. Combining US with complementary methodologies is advocated for a better understanding of skin aging in vivo. The cost-effectiveness and non-invasiveness of the US emphasize its promising future in dermatology, but ongoing research remains imperative to enhance its accuracy and expand its applications.
Identification of genes associated with persistence in Mycobacterium smegmatis
Authors: Joshi Hemant , Kandari Divya , Maitra Subhrangsu Sundar , Bhatnagar Rakesh , Banerjee Nirupama
Published: February 2024

The prevalence of bacterial persisters is related to their phenotypic diversity and is responsible for the relapse of chronic infections. Tolerance to antibiotic therapy is the hallmark of bacterial persistence. In this study, we have screened a transposon library of Mycobacterium smegmatis mc2155 strain using antibiotic tolerance, survival in mouse macrophages, and biofilm-forming ability of the mutants. Out of 10 thousand clones screened, we selected ten mutants defective in all the three phenotypes. Six mutants showed significantly lower persister abundance under different stress conditions. Insertions in three genes belonging to the pathways of oxidative phosphorylation msmeg_3233 (cydA), biotin metabolism msmeg_3194 (bioB), and oxidative metabolism msmeg_0719, a flavoprotein monooxygenase, significantly reduced the number of live cells, suggesting their role in pathways promoting long-term survival. Another group that displayed a moderate reduction in CFU included a glycosyltransferase, msmeg_0392, a hydrogenase subunit, msmeg_2263 (hybC), and a DNA binding protein, msmeg_2211. The study has revealed potential candidates likely to facilitate the long-term survival of M. smegmatis. The findings offer new targets to develop antibiotics against persisters. Further, investigating the corresponding genes in M. tuberculosis may provide valuable leads in improving the treatment of chronic and persistent tuberculosis infections.
Unraveling the microbiome-metabolome nexus: a comprehensive study protocol for personalized management of Behçet’s disease using explainable artificial intelligence
Authors: Tangaro Sabina , Lopalco Giuseppe , Sabella Daniele , Venerito Vincenzo , Novielli Pierfrancesco , Romano Donato , Di Gilio Alessia , Palmisani Jolanda , de Gennaro Gianluigi , Filannino Pasquale , Latronico Rosanna , Bellotti Roberto , De Angelis Maria , Iannone Florenzo
Published: February 2024

The presented study protocol outlines a comprehensive investigation into the interplay among the human microbiota, volatilome, and disease biomarkers, with a specific focus on Behçet’s disease (BD) using methods based on explainable artificial intelligence. The protocol is structured in three phases. During the initial three-month clinical study, participants will be divided into control and experimental groups. The experimental groups will receive a soluble fiber-based dietary supplement alongside standard therapy. Data collection will encompass oral and fecal microbiota, breath samples, clinical characteristics, laboratory parameters, and dietary habits. The subsequent biological data analysis will involve gas chromatography, mass spectrometry, and metagenetic analysis to examine the volatilome and microbiota composition of salivary and fecal samples. Additionally, chemical characterization of breath samples will be performed. The third phase introduces Explainable Artificial Intelligence (XAI) for the analysis of the collected data. This novel approach aims to evaluate eubiosis and dysbiosis conditions, identify markers associated with BD, dietary habits, and the supplement. Primary objectives include establishing correlations between microbiota, volatilome, phenotypic BD characteristics, and identifying patient groups with shared features. The study aims to identify taxonomic units and metabolic markers predicting clinical outcomes, assess the supplement’s impact, and investigate the relationship between dietary habits and patient outcomes. This protocol contributes to understanding the microbiome’s role in health and disease and pioneers an XAI-driven approach for personalized BD management. With 70 recruited BD patients, XAI algorithms will analyze multi-modal clinical data, potentially revolutionizing BD management and paving the way for improved patient outcomes.
Trans-kingdom fungal pathogens infecting both plants and humans, and the problem of azole fungicide resistance
Authors: Pintye Alexandra , Bacsó Renáta , Kovács Gábor M.
Published: February 2024

Azole antifungals are abundantly used in the environment and play an important role in managing fungal diseases in clinics. Due to the widespread use, azole resistance is an emerging global problem for all applications in several fungal species, including trans-kingdom pathogens, capable of infecting plants and humans. Azoles used in agriculture and clinics share the mode of action and facilitating cross-resistance development. The extensive use of azoles in the environment, e.g., for plant protection and wood preservation, contributes to the spread of resistant populations and challenges using these antifungals in medical treatments. The target of azoles is the cytochrome p450 lanosterol 14-α demethylase encoded by the CYP51 (called also as ERG11 in the case of yeasts) gene. Resistance mechanisms involve mainly the mutations in the coding region in the CYP51 gene, resulting in the inadequate binding of azoles to the encoded Cyp51 protein, or mutations in the promoter region causing overexpression of the protein. The World Health Organization (WHO) has issued the first fungal priority pathogens list (FPPL) to raise awareness of the risk of fungal infections and the increasingly rapid spread of antifungal resistance. Here, we review the main issues about the azole antifungal resistance of trans-kingdom pathogenic fungi with the ability to cause serious human infections and included in the WHO FPPL. Methods for the identification of these species and detection of resistance are summarized, highlighting the importance of these issues to apply the proper treatment.
Behavioral and neurophysiological effects of buspirone in healthy and depression-like state juvenile salmon
Authors: Shapouri Sheyda , Sharifi Aziz , Folkedal Ole , Fraser Thomas W. K. , Vindas Marco A.
Published: February 2024

A proportion of farmed salmon in seawater show a behaviorally inhibited, growth stunted profile known as a depression-like state (DLS). These DLS fish are characterized by chronically elevated serotonergic signaling and blood plasma cortisol levels and the inability to react further to acute stress, which is suggestive of chronic stress. In this study, we characterize the neuroendocrine profile of growth stunted freshwater parr and confirm that they show a DLS-like neuroendocrine profile with a blunted cortisol response and no serotonergic increase in response to acute stress. Furthermore, we attempted to reverse this DLS-like profile through pharmacological manipulation of the serotonin (5-HT) system with buspirone, an anxiolytic medication that acts as a serotonin receptor agonist (i.e., decreases serotonergic signaling). We found that while buspirone decreases anxiolytic-type behavior in healthy fish, no quantifiable behavioral change was found in DLS-like fish. However, there was a physiological effect of diminished basal serotonergic signaling. This suggests that at the physiological level, buspirone appears to reverse the neuroendocrine DLS profile. With a deeper understanding of what causes DLS profiles and growth stunting in juvenile fish, steps can be taken in terms of husbandry to prevent repeated stressors and the formation of the DLS profile, potentially reducing losses in aquaculture due to chronic stress.
Dynamic event-based optical identification and communication
Authors: von Arnim Axel , Lecomte Jules , Borras Naima Elosegui , Woźniak Stanisław , Pantazi Angeliki
Published: February 2024

Optical identification is often done with spatial or temporal visual pattern recognition and localization. Temporal pattern recognition, depending on the technology, involves a trade-off between communication frequency, range, and accurate tracking. We propose a solution with light-emitting beacons that improves this trade-off by exploiting fast event-based cameras and, for tracking, sparse neuromorphic optical flow computed with spiking neurons. The system is embedded in a simulated drone and evaluated in an asset monitoring use case. It is robust to relative movements and enables simultaneous communication with, and tracking of, multiple moving beacons. Finally, in a hardware lab prototype, we demonstrate for the first time beacon tracking performed simultaneously with state-of-the-art frequency communication in the kHz range.
Preferential transduction of parvalbumin-expressing cortical neurons by AAV-mDLX5/6 vectors
Authors: Yazdan-Shahmorad Padideh , Gibson Shane , Lee Joanne C. , Horwitz Gregory D.
Published: February 2024

A major goal of modern neuroscience is to understand the functions of the varied neuronal types that comprise the mammalian brain. Toward this end, some types of neurons can be targeted and manipulated with enhancer-bearing AAV vectors. These vectors hold great promise to advance basic and translational neuroscience, but to realize this potential, their selectivity must be characterized. In this study, we investigated the selectivity of AAV vectors carrying an enhancer of the murine Dlx5 and Dlx6 genes. Vectors were injected into the visual cortex of two macaque monkeys, the frontal cortex of two others, and the somatosensory/motor cortex of three rats. Post-mortem immunostaining revealed that parvalbumin-expressing neurons were transduced efficiently in all cases but calretinin-expressing neurons were not. We speculate that this specificity is a consequence of differential activity of this DLX5/6 enhancer in adult neurons of different developmental lineages.
Tyro3 promotes the maturation of glutamatergic synapses
Authors: Miao Sheng , Fourgeaud Lawrence , Burrola Patrick G. , Stern Shani , Zhang Yuhan , Happonen Kaisa E. , Novak Sammy Weiser , Gage Fred H. , Lemke Greg
Published: February 2024

The receptor tyrosine kinase Tyro3 is abundantly expressed in neurons of the neocortex, hippocampus, and striatum, but its role in these cells is unknown. We found that neuronal expression of this receptor was markedly up-regulated in the postnatal mouse neocortex immediately prior to the final development of glutamatergic synapses. In the absence of Tyro3, cortical and hippocampal synapses never completed end-stage differentiation and remained electrophysiologically and ultrastructurally immature. Tyro3−/− cortical neurons also exhibited diminished plasma membrane expression of the GluA2 subunits of AMPA-type glutamate receptors, which are essential to mature synaptic function. Correspondingly, GluA2 membrane insertion in wild-type neurons was stimulated by Gas6, a Tyro3 ligand widely expressed in the postnatal brain. Behaviorally, Tyro3−/− mice displayed learning enhancements in spatial recognition and fear-conditioning assays. Together, these results demonstrate that Tyro3 promotes the functional maturation of glutamatergic synapses by driving plasma membrane translocation of GluA2 AMPA receptor subunits.
Motor imagery in autism: a systematic review
Authors: Gowen Emma , Edmonds Eve , Poliakoff Ellen
Published: February 2024

Introduction

Motor Imagery (MI) is when an individual imagines performing an action without physically executing that action and is thought to involve similar neural processes used for execution of physical movement. As motor coordination difficulties are common in autistic individuals it is possible that these may affect MI ability. The aim of this systematic review was to assess the current knowledge around MI ability in autistic individuals.

Methods

A systematic search was conducted for articles published before September 2023, following PRISMA guidance. Search engines were PsycINFO, PubMed, Web of Science, Scopus, Wiley Online Library and PsyArXiv. Inclusion criteria included: (a) Original peer-reviewed and pre-print publications; (b) Autistic and a non-autistic group (c) Implicit or explicit imagery tasks (d) Behavioral, neurophysiological or self-rating measures, (e) Written in the English language. Exclusion criteria were (a) Articles only about MI or autism (b) Articles where the autism data is not presented separately (c) Articles on action observation, recognition or imitation only (d) Review articles. A narrative synthesis of the evidence was conducted.

Results

Sixteen studies across fourteen articles were included. Tasks were divided into implicit (unconscious) or explicit (conscious) MI. The implicit tasks used either hand (6) or body (4) rotation tasks. Explicit tasks consisted of perspective taking tasks (3), a questionnaire (1) and explicit instructions to imagine performing a movement (2). A MI strategy was apparent for the hand rotation task in autistic children, although may have been more challenging. Evidence was mixed and inconclusive for the remaining task types due to the varied range of different tasks and, measures conducted and design limitations. Further limitations included a sex bias toward males and the hand rotation task only being conducted in children.

Discussion

There is currently an incomplete understanding of MI ability in autistic individuals. The field would benefit from a battery of fully described implicit and explicit MI tasks, conducted across the same groups of autistic children and adults. Improved knowledge around MI in autistic individuals is important for understanding whether MI techniques may benefit motor coordination in some autistic people.
Carboplatin, paclitaxel, and pembrolizumab followed by pembrolizumab maintenance for primary treatment of incompletely resected epithelial ovarian cancer
Authors: Uyar Denise , Michener Chad M. , Bishop Erin , Hopp Elizabeth , Simpson Pippa , Zhang Liyun , Rader Janet S. , Rose Peter G. , Mahdi Haider S. , Debernardo Robert , Christian Qiana , Bradley William
Published: February 2024

Objective

Incompletely resected epithelial ovarian cancer represents a poor prognostic subset of patients. Novel treatment strategies are needed to improve outcomes for this population. We evaluated a treatment strategy combining platinum-based chemotherapy with pembrolizumab followed by pembrolizumab maintenance therapy in the first-line treatment after incomplete resection of epithelial ovarian cancer patients.

Methods

This was a single-arm, non-randomized pilot study of carboplatin, taxane, and immune checkpoint inhibitor, pembrolizumab, followed by 12 months of maintenance pembrolizumab in patients with incompletely resected epithelial ovarian cancer (EOC).

Results

A total of 29 patients were enrolled and evaluated for efficacy and safety. The best response to therapy was complete response in 16 (55%) patients, partial response in 9 (31%) patients, and 3 (10%) patients with progression of disease. The median progression-free survival (PFS) was 13.2 months. Grade 3 and 4 toxicities occurred in 20% of patients. In all, 7 patients discontinued therapy due to adverse events. Quality-of-life scores remained high during therapy. Response to therapy did not correlate with PD-L1 tumor expression.

Conclusions

Combination platinum–taxane therapy with pembrolizumab did not increase median progression-free survival in this cohort of patients.

Key message

EOC is an immunogenic disease, but immune checkpoint inhibitor therapy has yet to impact outcomes. The current study utilized pembrolizumab in combination with standard chemotherapy followed by a maintenance treatment strategy in incompletely resected EOC. Progression-free survival was not extended in this poor prognostic group with combined chemotherapy and immunotherapy.

Clinical trial registration

https://clinicaltrials.gov/, identifier NCT 027766582.
The absolute number of small and diminutive adenomas with high-grade dysplasia is substantially higher compared with large adenomas: a retrospective pooled study
Authors: Zhang Jiancheng , Sun Huajun , Xiong Fei , Lei Shan , Zhou Guanyu , Xiao Xun , Liu Lin , Wang Pu
Published: February 2024

Introduction

The risk that a large polyp (≥10 mm) evolves into high-grade dysplasia (HGD) is relatively high compared with that of a small/diminutive polyp (<10 mm). Recently, the detection of small and diminutive polyps has been substantially improved with the advancement of endoscopy. However, further research is needed on the role of the incidence of HGD caused by the co-occurrence of small and diminutive polyps in the progression of HGD. In this study, we aim to investigate whether and how the small and diminutive polyps correlate with the incidence of HGD in the population.

Methods

The pooled data were deeply analyzed from four published randomized controlled trials (RCTs) regarding colon polyp detection. All polyps detected were examined and confirmed by pathologists. The primary outcome was the composition ratio of the HGD polyps in each polyp size category.

Results

Among a total of 3,179 patients with 2,730 polyps identified, there were 83 HGD polyps confirmed, and 68 patients had at least one polyp with HGD. The risk of development of HGD was lower for a single small and diminutive polyp than for one large polyp (2.18% vs. 22.22%, P < 0.0001). On the contrary, the composition ratio for HGD from small and diminutive polyps was significantly higher than that from the large ones (68.67% vs. 31.33%, P < 0.0001). The combined number of HGD presented a trend negatively correlated to size.

Conclusions

Our data demonstrated that the absolute number of HGD significantly derives more from small and diminutive polyps than from the large ones, and the collective number of small and diminutive polyps per patient is indicative of his/her HGD exposure. These findings positively provide novel perspectives on the management of polyps and may further optimize the prevention of colorectal cancer.

Systematic Review Registration

http://www.chictr.org.cn, identifier ChiCTR1900025235, ChiCTR1800017675, ChiCTR1800018058, and ChiCTR1900023086.