bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetes and cardiovascular disease
Authors:   , Helmink Margaretha Adriana Geerte
Published: April 2024

Cardiovascular disease (CVD) and diabetes, both type 1 and type 2, are closely related. Due to an aging population and lifestyle changes, the prevalence of CVD and type 2 diabetes (T2D) is increasing. Pharmacological treatments aimed at reducing the risk of these conditions are associated with costs and risks of side effects. Moreover, an increase in prescribed medications may result in decreased adherence among patients. It is therefore important to identify patients at increased risk and those who would benefit most from treatment.

Part 1 of this thesis focuses on the risk of CVD and the factors influencing this risk in individuals with type 1 diabetes (T1D). The aim is to tailor cardiovascular risk management to the individual patient with T1D by evaluating heterogeneity and cardiovascular risk within this patient group. Factors like age, cholesterol levels, and blood pressure are known to increase the risk of CVD in individuals with T1D. A less well-known risk factor is insulin resistance. This condition, often linked with T2D, is increasingly seen in T1D patients, primarily due to rising obesity levels. We showed that a higher level of insulin resistance is related to an increased risk of CVD in individuals with T1D. Identifying individuals with T1D who are more insulin-resistant is important, as these individuals often require more insulin. We also describe the development and validation of the LIFE-T1D model, designed to predict an individual’s lifetime risk of CVD. This model, based on data from over 43,000 individuals across Sweden, Denmark, and the UK, helps clinicians estimate the benefits of specific treatments for individual patients, thus enabling more efficient medication use and promoting shared decision-making.

Part 2 focuses on the long-term complications arising from adipose tissue dysfunction in those at increased risk of CVD. The CVD2DM model was introduced, which predicts the 10-year and lifetime risk of T2D in individuals with a history of CVD. This model could motivate patients towards healthier lifestyles and assist in the early detection of T2D among those previously affected by CVD. Additionally, we investigated the relationship between adipose tissue dysfunction and the risk of cancer, finding that in individuals without T2D, both increased adipose tissue and its dysfunction are linked to a higher cancer risk. The findings of this study underline the importance of obesity prevention.

In conclusion, CVD and diabetes are closely related and constitute a significant global health problem. Estimating the risk of these conditions, for instance using the models described in this thesis, ensures that patients are better informed. Additionally, it enables us to tailor treatments more closely to individual patients, promoting shared decision-making. With the availability of larger datasets following patients over longer periods, combined with advancements in methodological approaches, the accuracy and clinical applicability of such models are expected to improve further in the future.
British Quota Production and Film Costs in the Early 1930s
Authors: Chapman James
Published: April 2024

This article explores the economic contexts of British film production in the early 1930s through an analysis of the cost data provided in a ledger compiled by the Board of Trade documenting the statutory costs of all British ‘long’ films registered for renters’ quota during the quota year 1 April 1932 to 31 March 1933. This is the most comprehensive source for British film costs in the early 1930s. The evidence provided by the ledger suggests a more nuanced overall picture of the costs of British film-making than the standard narrative of ‘quality or quota’ would allow. It highlights the different production strategies of British and American distributors and sheds new light on the costs of ‘quota quickies’ and their place in the British film industry in the 1930s.
Doc Martin and Comedy, with an Hegelian Twist
Authors: Bacaller Sarah
Published: April 2024

Buffalo Pictures’ long-running television series Doc Martin (ITV, 2004–22) has recently concluded, eighteen years since production began. Filmed every second year – excepting COVID interruption – in idyllic Cornwall, the show begins with exceptional but irascible London vascular surgeon, Martin Ellingham (Martin Clunes), moving into the fictional fishing village of Portwenn as local GP. This show, with its 79 episodes, weaves together situation comedy, medical mystery, drama and idiosyncratic romance. In this article I want to explore layers of comedy in this long-running ‘dramedy’ by heuristically deploying the comedy theory taught by Hegel in his Lectures on Aesthetics. By reference to the ‘three forms of comic action’ found in Hegel’s lectures – the comedies of ‘coincidence’, ‘reduction’ and ‘negation’, to adopt Mark Roche’s terminology – I aim to show how this television serial uses humour to raise questions about what is existentially meaningful within human experience; test the usefulness of Hegel’s ideas on comedy for analysis of contemporary forms of media such as television and film; and contribute to literature on the nature of comedy in television serials, particularly those that utilise situation comedy.
Churchgoing in Glasgow, 1836–2016: The Statistical Record
Authors: Field Clive
Published: April 2024

Historiographical debate about religious change and secularisation in Scotland often fails to take a sufficiently long-term perspective and to subject the sources used to critical scrutiny. In this article, one possible metric of secularisation (churchgoing rates) is investigated for Scotland’s largest city (Glasgow), by a statistical examination of fourteen church censuses between 1836 and 2016. Emphasis is placed on the varying methodologies of the censuses and the limitations to their comparability. Churchgoing in the city has declined, relative to population, since the later nineteenth century, initially among Protestants. The net scale of decrease was mitigated after the Second World War by the Catholic majority in the pews, but even Catholic attendance has shrunk absolutely in recent decades.
Financing Church Extension: The Case of the Edinburgh Savings Bank and St John's Parish Church, Edinburgh
Authors: Sawkins John W.
Published: April 2024

This paper describes the way in which St John's parish church, Edinburgh, was financed; highlighting the part played by the Directors of the Edinburgh Savings Bank. It further analyses the impact of the Disruption on the church's seat rent income; the primary means by which residual debt liquidation was to be accomplished. As a case study, it offers a revealing sidelight on the financial consequences of the Disruption at the congregational level.
Alive Poets Society
Authors: Sundqvist Selma , Håkansson Alma , Jansson Alva , Blomberg Cajsa
Published: April 2024

Vi är fyra studenter som läser språk, litteratur och medier vid Linköpings universitet. Under våren är vårt mål att driva denna blogg för att uppmärksamma personer om det nya fenomenet TikTok-poesi. Vi vill lyfta fram en positiv sida av TikTok-poesin för att visa att poesi inte behöver vara krånglig, dammig eller svårförstådd.
Plant protection consequences in Hungary of the withdrawal of systemic active substances from sugar beet seed treatment
Authors: Jócsák Ildikó , Csima Ferenc , Pál-Fám Ferenc , Somfalvi-Tóth Katalin , Keszthelyi Sándor
Published: April 2024

After decades of development, neonicotinoids were widely used in Hungarian sugar beet production and seeds included thiamethoxam treatment by 2019 increasing protection against early spring pests. In Hungary, neonicotides’ influence on bee health led to their removal of emergency authorization. In the absence of thiamethoxam in 2020, experience showed that multiple treatments were needed to protect beet from pests early spring pests. Repeated applications of mostly pyrethroids have proved suitable; however, in sugar beet, this has resulted in a multiple increase in environmental stress and honey bee mortality, as well as increased input values. The aim of this work is to explore the current state of production and collect new alternative options for applying effectively in Hungarian sugar beet production technology, against early spring pests.
Blood-based biological ageing and red cell distribution width are associated with prevalent Parkinson’s disease: findings from a large Italian population cohort
Authors: Gialluisi Alessandro , Tirozzi Alfonsina , Costanzo Simona , De Bartolo Maria Ilenia , Belvisi Daniele , Magnacca Sara , De Curtis Amalia , Falciglia Stefania , Ricci Moreno , Cerletti Chiara , Donati Maria Benedetta , Berardelli Alfredo , de Gaetano Giovanni , Iacoviello Licia
Published: April 2024

Background

Aging clocks tag the actual underlying age of an organism and its discrepancy with chronological age and have been reported to predict incident disease risk in the general population. However, the relationship with neurodegenerative risk and in particular with Parkinson’s Disease (PD) remains unclear, with few discordant findings reporting associations with both incident and prevalent PD risk.

Objective

To clarify this relationship, we computed a common aging clock based on blood markers and tested the resulting discrepancy with chronological age (ΔPhenoAge) for association with both incident and prevalent PD risk.

Methods

In a large Italian population cohort - the Moli-sani study (N=23,437; age ≥ 35 years; 52% women) - we carried out both Cox Proportional Hazards regressions modelling ΔPhenoAge as exposure and incident PD as outcome, and linear models testing prevalent PD as exposure and ΔPhenoAge as outcome. All models were incrementally adjusted for age, sex, education level completed and other risk/protective factors previously associated with PD risk in the same cohort (prevalent dysthyroidism, hypertension, diabetes, use of oral contraceptives, exposure to paints, daily coffee intake and cigarette smoking).

Results

No significant association between incident PD risk (209 cases, median (IQR) follow-up time 11.19 (2.03) years) and PhenoAging was observed (Hazard Ratio [95% Confidence Interval] = 0.98 [0.71; 1.37]). However, a small but significant increase of ΔPhenoAge was observed in prevalent PD cases vs healthy subjects (β (Standard Error) = 1.39 (0.70)). An analysis of each component biomarker of PhenoAge revealed a significant positive association of prevalent PD status with red cell distribution width (RDW; β (SE) = 0.46 (0.18)). All the remaining markers did not show any significant evidence of association.

Conclusion

The reported evidence highlights systemic effects of prevalent PD status on biological aging and red cell distribution width. Further cohort and functional studies may help shedding a light on the related pathways altered at the organism level in prevalent PD, like red cells variability, inflammatory and oxidative stress mechanisms.
A new method for predicting the oil displacement volume by waterflood huff-puff of the fractured-cavity type carbonate oil reservoirs
Authors: Peng Cao , Peng Wang , Zhiliang Liu , Jiajun Chen , Guohui Li , Yifan Du
Published: April 2024

Introduction: More than two billion tons of oil reserves have been discovered in the fractured-cavity type carbonate reservoirs in Tarim Basin, which is a key field for increasing reserves and production in the future. This type of oil reservoirs is characterized by extremely high heterogeneity, and waterflood huff-puff oil displacement is generally used for secondary development of the oil reservoirs. The conventional methods are dominated by qualitative evaluation, which are insufficient to predict the oil production increase by waterflood huff-puff in various karst zones.

Methods: The new method developed in this study involves four aspects, i.e., establishing a standard well database, optimally selecting the key development indicators, equivalent classification of reservoir space type, and optimally selecting the classification and evaluation methods for oil production increase by waterflood huff-puff. From the perspective of reservoir space type, the result of waterflood huff-puff oil displacement of multi-cave type reservoir (large scale) is better than that of relatively isolated cave type reservoir, followed by the fractured-vuggy type reservoir.

Results and discussion: The new method shows advantages in the following aspects: 1) The differences in reservoir geological genesis and spatial structure characteristics in various karst zones are involved; 2) The difference in internal filling features of the same type of reservoir is integrally determined based on the changes in production performance; 3) The actual development characteristics of waterflood huff-puff oil displacement wells in various karst zones are systematically analyzed, and the criteria for selecting standard wells is formulated; 4) The violin plot is introduced as the main study tool for predicting and discriminating oil production increase by waterflood huff-puff displacement. Therefore, the new method is more capable of predicting the oil production increase by waterflood huff-puff in various karst zones.
A nuclear power plant digital twin for developing robot navigation and interaction
Authors: Vairagade Himanshu , Kim Sungmin , Son Hoojon , Zhang Fan
Published: April 2024

As robot technologies are rapidly improving, an increasing number of new ideas on utilizing robots for automated operation and maintenance tasks in nuclear power plants (NPPs) are being studied. However, due to safety concerns, researchers hardly found opportunities to test their new robot solutions on physical NPPs. In that sense, an efficient and realistic simulation environment plays a vital role in the development of automation systems for an NPP. In this paper, we propose the design of a 3D digital twin system capable of simulating NPP in real-time. This system obtains the data from a full-scope NPP simulator to reproduce the operating conditions of the plant. In addition, a scenario of a team of robots performing inspection tasks like temperature and pressure measurements will highlight its usability. This system enables development of intelligent robot swarms to deploy for inspection and maintenance purposes. It will positively impact autonomous control and operations for many types of reactors by reducing uncertainty in autonomous control and providing the tools necessary for remote intervention.
Sustainable development and the degree of implementation of European Union environmental directives
Authors: Bąk Iwona , Wawrzyniak Katarzyna , Sulikowski Piotr
Published: April 2024

EU Member States must implement environmental policy in accordance with the specified rules, including standards supporting the implementation of the adopted EU policies. The standards (target values) for the levels of environmental indicators are included in EU directives. Compliance with EU environmental standards is already bringing many benefits, but there is still much to be done. The aim of our study is to assess the current levels of environmental indicators in EU countries, since prompt achievement of their target values is a prerequisite for sustainable development in this area. A classical correspondence analysis was used to evaluate the degree of differentiation of the levels of indicators in the EU countries based on the data presented in a binary matrix of indicators. As a result, countries have been identified in which indicators monitoring the state of environmental protection have achieved a level in line with the target values indicated in EU directives, and those in which this level has not been achieved. The research procedure used in the article is universal in the sense that it can be used to assess the situation of the objects under study (countries, regions) regardless of the specifics of the phenomenon under study, provided that comparable data are available.
Comparison of the effectiveness four years after Homo/Hetero prime-boost with 10 μg HP and 20 μg CHO recombinant hepatitis B vaccine at 1 and 6 months in maternal HBsAg-negative children
Authors: Yin Zhiying , Wen Tingcui , Fu Canya , Li Junji , Fang Quanjun , Gong Xiaoying , You Jialing , Wang Shuangqing , Zheng Canjie
Published: April 2024

Introduction

Limited data were available on the effectivenessfour years after Homo or Hetero prime-boost with 10 μg Hansenulapolymorpha recombinant hepatitis B vaccine (HepB-HP) and 20 μgChinese hamster ovary cell HepB (HepB-CHO).

Methods

A crosssectional study was performed in maternalhepatitis B surface antigen (HBsAg)-negative children whoreceived one dose of 10 μg HepB-HP at birth, Homo or Heteroprime-boost with 10 μg HepB-HP and 20 μg HepB-CHO at 1 and 6months. HBsAg and hepatitis B surface antibody (anti-HBs) fouryears after immunization were quantitatively detected by achemiluminescent microparticle immunoassay (CMIA).

Results

A total of 359 children were included; 119 childrenreceived two doses of 10 μg HepB-HP and 120 children receivedtwo doses of 20 μg HepB-CHO, called Homo prime-boost; 120children received Hetero prime-boost with 10 μg HepB-HP and 20μg HepB-CHO. All children were HBsAg negative. The geometricmean concentration (GMC) and overall seropositivity rate (SPR) ofanti-HBs were 59.47 (95%CI: 49.00 – 72.16) mIU/ml and 85.51%(307/359). Nearly 15% of the study subjects had an anti-HBsconcentration < 10 mIU/ml and 5.01% had an anti-HBsconcentration ≤ 2.5 mIU/ml. The GMC of the 20 μg CHO Homoprime-boost group [76.05 (95%CI: 54.97 – 105.19) mIU/ml] washigher than that of the 10 μg HP Homo group [45.86 (95%CI:31.94 – 65.84) mIU/ml] (p = 0.035). The GMCs of the Heteroprime-boost groups (10 μg HP-20 μg CHO and 20 μg CHO-10 μgHP) were 75.86 (95% CI: 48.98 – 107.15) mIU/ml and 43.65(95%CI: 27.54 – 69.18) mIU/ml, respectively (p = 0.041). Aftercontrolling for sex influence, the SPR of the 20 μg CHO Homoprime-boost group was 2.087 times than that of the 10 μg HPHomo group.

Discussion

The HepB booster was not necessary in the generalchildren, Homo/Hetero prime-boost with 20 μg HepB-CHO wouldincrease the anti-HBs concentration four years after immunization,timely testing and improved knowledge about the self-pay vaccinewould be good for controlling hepatitis B.
The interplay between autophagy and cGAS-STING signaling and its implications for cancer
Authors: Schmid Maximilian , Fischer Patrick , Engl Magdalena , Widder Joachim , Kerschbaum-Gruber Sylvia , Slade Dea
Published: April 2024

Autophagy is an intracellular process that targets various cargos for degradation, including members of the cGAS-STING signaling cascade. cGAS-STING senses cytosolic double-stranded DNA and triggers an innate immune response through type I interferons. Emerging evidence suggests that autophagy plays a crucial role in regulating and fine-tuning cGAS-STING signaling. Reciprocally, cGAS-STING pathway members can actively induce canonical as well as various non-canonical forms of autophagy, establishing a regulatory network of feedback mechanisms that alter both the cGAS-STING and the autophagic pathway. The crosstalk between autophagy and the cGAS-STING pathway impacts a wide variety of cellular processes such as protection against pathogenic infections as well as signaling in neurodegenerative disease, autoinflammatory disease and cancer. Here we provide a comprehensive overview of the mechanisms involved in autophagy and cGAS-STING signaling, with a specific focus on the interactions between the two pathways and their importance for cancer.
Bioethical knowledge in students and health professionals: a systematic review
Authors: González-Blázquez Francisco Javier , Ruiz-Hontangas Antonio , López-Mora Clara
Published: April 2024

Introduction

Bioethics training is essential for healthcare professionals as it enables them to address ethical dilemmas in their clinical practice. However, there is still a lack of rigorous teaching programs, and assessing bioethical knowledge poses challenges.

Methodology:

Systematic review using the PRISMA method.

Results

Analysis of 27 studies reveals a lack of ethical knowledge and skills among healthcare professionals and students. Specific training in bioethics is effective in developing bioethical competencies. Different approaches have been employed, including integrated training in academic curricula and intensive or ongoing programs. The results demonstrate improvements in knowledge, attitudes, and ethical values, although regularly updating these courses is recommended.

Conclusion

Specific training, institutional support, and considering regional and disciplinary differences are necessary to enhance ethics in the practice of healthcare professionals.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023437146, identifier CRD42023437146
Knowledge, attitude, and practice of psoriasis patients toward their diseases: a web-based, cross-sectional study
Authors: Tian Jun , Zhang Lei , Zhao Xiangrong , Yang Li
Published: April 2024

Objective

To investigate the knowledge, attitude, and practice (KAP) of psoriasis patients toward the disease.

Methods

A web-based cross-sectional study was conducted among psoriasis patients who were diagnosed at the outpatient of Shaanxi Provincial People’s Hospital in March 2023. A self-designed questionnaire was administered for data collection and KAP assessment.

Results

A total of 526 valid questionnaires were included, including 257 males (48.86%) psoriasis patients. Their mean KAP scores were 8.09 ± 3.60 (possible range: 0–12), 31.94 ± 4.61 (possible range: 10–50), and 51.92 ± 8.83 (possible range: 15–75), respectively. Pearson’s correlation analysis showed a positive correlation between knowledge and attitude (r = 0.186, p < 0.001), a positive correlation between knowledge and practice (r = 0.313, p < 0.001), and a negative correlation between attitude and practice (r = −0.181, p < 0.001). Moreover, structural equation model showed that medication (β = 2.74, 95% CI: 2.17, 3.32, p < 0.001) has significantly positive effect on knowledge. Education (β = 0.56, 95% CI: 0.31, 0.81, p < 0.001) and duration of psoriasis (β = 1.01, 95% CI: 0.54, 1.49, p < 0.001) have significantly positive effect on attitude. Knowledge (β = 1.03, 95% CI: 0.80, 1.26, p < 0.001) and medication (β = 4.59, 95% CI: 2.78, 6.40, p < 0.001) has significantly positive effect on practice, while attitude (β = −0.41, 95% CI: −0.57, −0.26, p < 0.001) and duration of psoriasis (β = −2.53, 95% CI: −3.49, −1.57, p < 0.001) exhibit significantly negative effect on practice.

Conclusion

Psoriasis patients have good knowledge, positive attitude, and proactive practice toward the disease. Education, medication, duration of psoriasis might have effect on their KAP.
The palliative care needs and experiences of patients with advanced Parkinson’s disease: a qualitative scoping review
Authors: Lou Yan , Li Yiting , Chen Yiping
Published: April 2024

Aim

To determine the experiences and needs of palliative care in patients with advanced Parkinson’s disease (PD).

Methods

A scoping literature review methodology, as described by the Joanna Briggs Institute, was employed to search for relevant literature. An electronic search of studies published in English was conducted across five databases from inception to 10 September 2023.

Results

The search yielded a total of 1,205 articles, with 20 meeting the inclusion criteria. The findings were organized into four themes: (1) unmet emotional and informational needs; (2) needs for effective coordination of care; (3) planning for the future; and (4) symptom management. This scoping review highlights the intricate nature of palliative care for patients with PD and sheds light on issues within current palliative care healthcare systems. The findings emphasize the necessity for individualized interventions and services to address the diverse unmet palliative care needs of people with PD.

Conclusion

The study reveals the complex landscape of palliative care for individuals with advanced PD, emphasizing the inadequacies within existing healthcare systems. The identified themes underscore the importance of tailored interventions to address the varied unmet palliative care needs of this population.
Metabolite profiling and bioactivity guided fractionation of Lactobacillaceae and rice bran postbiotics for antimicrobial-resistant Salmonella Typhimurium growth suppression
Authors: Nealon Nora Jean , Worcester Colette R. , Boyer Shea M. , Haberecht Hannah B. , Ryan Elizabeth P.
Published: April 2024

Probiotic-fermented supplements (postbiotics) are becoming increasingly explored for their activity against antibiotic-resistant enteropathogens. Prebiotics are often incorporated into postbiotics to enhance their efficacy, but due to strain differences in probiotic activity, postbiotic antimicrobial effects are poorly understood. To improve postbiotic antimicrobial efficacy, we investigated and compared metabolite profiles of postbiotics prepared with three lactic acid bacteria strains (L. fermentum, L. paracasei, and L. rhamnosus) cultured with and without rice bran, a globally abundant, rich source of prebiotics. At their minimum inhibitory dose, L. fermentum and L. paracasei postbiotics + rice bran suppressed S. Typhimurium growth 42–55% more versus their respective probiotic-alone postbiotics. The global, non-targeted metabolome of these postbiotics identified 109 metabolites increased in L. fermentum and L. paracasei rice bran postbiotics, including 49 amino acids, 20 lipids, and 12 phytochemicals metabolites. To identify key metabolite contributors to postbiotic antimicrobial activity, bioactivity-guided fractionation was applied to L. fermentum and L. paracasei rice bran-fermented postbiotics. Fractionation resulted in four L. fermentum and seven L. paracasei fractions capable of suppressing S. Typhimurium growth more effectively versus the negative control. These fractions were enriched in 15 metabolites that were significantly increased in the global metabolome of postbiotics prepared with rice bran versus postbiotic alone. These metabolites included imidazole propionate (enriched in L. fermentum + rice bran, 1.61-fold increase; L. paracasei + rice bran 1.28-fold increase), dihydroferulate (L. fermentum + rice bran, 5.18-fold increase), and linoleate (L. fermentum + rice bran, 1.82-fold increase; L. paracasei + rice bran, 3.19-fold increase), suggesting that they may be key metabolite drivers of S. Typhimurium growth suppression. Here, we show distinct mechanisms by which postbiotics prepared with lactic acid bacteria and rice bran produce metabolites with antimicrobial activity capable of suppressing S. Typhimurium growth. Probiotic strain differences contributing to postbiotic antimicrobial activity attract attention as adjunctive treatments against pathogens.
Impact of suppression of the SOS response on protein expression in clinical isolates of Escherichia coli under antimicrobial pressure of ciprofloxacin
Authors: Recacha Esther , Kuropka Benno , Díaz-Díaz Sara , García-Montaner Andrea , González-Tortuero Enrique , Docobo-Pérez Fernando , Rodríguez-Rojas Alexandro , Rodríguez-Martínez Jose Manuel
Published: April 2024

Introduction/objective

Suppression of the SOS response in combination with drugs damaging DNA has been proposed as a potential target to tackle antimicrobial resistance. The SOS response is the pathway used to repair bacterial DNA damage induced by antimicrobials such as quinolones. The extent of lexA-regulated protein expression and other associated systems under pressure of agents that damage bacterial DNA in clinical isolates remains unclear. The aim of this study was to assess the impact of this strategy consisting on suppression of the SOS response in combination with quinolones on the proteome profile of Escherichia coli clinical strains.

Materials and methods

Five clinical isolates of E. coli carrying different chromosomally- and/or plasmid-mediated quinolone resistance mechanisms with different phenotypes were selected, with E. coli ATCC 25922 as control strain. In addition, from each clinical isolate and control, a second strain was created, in which the SOS response was suppressed by deletion of the recA gene. Bacterial inocula from all 12 strains were then exposed to 1xMIC ciprofloxacin treatment (relative to the wild-type phenotype for each isogenic pair) for 1 h. Cell pellets were collected, and proteins were digested into peptides using trypsin. Protein identification and label-free quantification were done by liquid chromatography-mass spectrometry (LC–MS) in order to identify proteins that were differentially expressed upon deletion of recA in each strain. Data analysis and statistical analysis were performed using the MaxQuant and Perseus software.

Results

The proteins with the lowest expression levels were: RecA (as control), AphA, CysP, DinG, DinI, GarL, PriS, PsuG, PsuK, RpsQ, UgpB and YebG; those with the highest expression levels were: Hpf, IbpB, TufB and RpmH. Most of these expression alterations were strain-dependent and involved DNA repair processes and nucleotide, protein and carbohydrate metabolism, and transport. In isolates with suppressed SOS response, the number of underexpressed proteins was higher than overexpressed proteins.

Conclusion

High genomic and proteomic variability was observed among clinical isolates and was not associated with a specific resistant phenotype. This study provides an interesting approach to identify new potential targets to combat antimicrobial resistance.
Convergent genetic adaptation of Escherichia coli in minimal media leads to pleiotropic divergence
Authors: Venkataraman Pavithra , Nagendra Prachitha , Ahlawat Neetika , Brajesh Raman G. , Saini Supreet
Published: April 2024

Adaptation in an environment can either be beneficial, neutral or disadvantageous in another. To test the genetic basis of pleiotropic behaviour, we evolved six lines of E. coli independently in environments where glucose and galactose were the sole carbon sources, for 300 generations. All six lines in each environment exhibit convergent adaptation in the environment in which they were evolved. However, pleiotropic behaviour was observed in several environmental contexts, including other carbon environments. Genome sequencing reveals that mutations in global regulators rpoB and rpoC cause this pleiotropy. We report three new alleles of the rpoB gene, and one new allele of the rpoC gene. The novel rpoB alleles confer resistance to Rifampicin, and alter motility. Our results show how single nucleotide changes in the process of adaptation in minimal media can lead to wide-scale pleiotropy, resulting in changes in traits that are not under direct selection.
Safety and feasibility of optimized transcranial direct current stimulation in patients with mild cognitive impairment due to Alzheimer’s disease: a multicenter study protocol for a randomized controlled trial
Authors: Kim TaeYeong , Kang Dong Woo , Salazar Fajardo Jhosedyn Carolaym , Jang Hanna , Um Yoo Hyun , Kim Sunghwan , Wang Sheng-Min , Kim Donghyeon , Lim Hyun Kook
Published: April 2024

Introduction

Transcranial direct current stimulation (tDCS) may effectively preserve and improve cognitive function in patients with mild cognitive impairment (MCI). Research has shown that Individual brain characteristics can influence the effects of tDCS. Computer three-dimensional brain modeling based on magnetic resonance imaging (MRI) has been suggested as an alternative for determining the most accurate tDCS electrode position based on the patients’ individual brain characteristics to enhance tDCS effects. Therefore, this study aims to determine the feasibility and safety of applying tDCS treatment using optimized and personalized tDCS electrode positions in patients with Alzheimer’s disease (AD)-induced MCI using computer modeling and compare the results with those of a sham group to improve cognitive function.

Method

A prospective active-sham group feasibility study was set to recruit 40 participants, who will be randomized into Optimized-tDCS and Sham-tDCS groups. The parameters for tDCS will be 2 mA (disk electrodes R = 1.5 cm) for 30 min during two sets of 15 sessions (2 weeks of resting period in between), using two electrodes in pairs. Using computer modeling, the tDCS electrode positions of each participant will be personalized. Outcome measurements are going to be obtained at three points: baseline, first post-test, and second post-test. The AD assessment scale-cognitive subscale (ADAS-Cog) and the Korean version of Mini-Mental State Examination (K-MMSE), together with other secondary outcomes and safety tests will be used.

Discussion

For the present study, we hypothesize that compared to a sham group, the optimized personalized tDCS application would be effective in improving the cognitive function of patients with AD-induced MCI and the participants would tolerate the tDCS intervention without any significant adverse effects.

Clinical trial registration: https://cris.nih.go.kr, identifier [KCT0008918].
Prognostic significance vestibular examination results in patients with vestibular migraine
Authors: Goto Fumiyuki , Wasano Koichiro , Kaneda Shoji , Okami Kenji
Published: April 2024

Introduction

Vestibular migraine (VM) is a newly defined clinical condition. Several vestibular abnormalities have been reported in patients with VM. However, to date, no specific vestibular examinations are used to define VM. Therefore, the utility of vestibular examinations is limited. Currently, the role of vestibular examination has not been clearly defined. We speculated that the results of vestibular examinations could predict the prognosis of VM. We investigated the relationship between the vestibular examination results and clinical outcomes in patients with VM.

Methods

This study included 25 patients with VM. Vestibular examinations, including the video head impulse test (V-HIT), cervical and ocular vestibular evoked myogenic potential (c-VEMP and o-VEMP), posturography, and several questionnaires, including the Dizziness Handicap Inventory (DHI), were conducted at the initial evaluation. Lifestyle modifications for VM and conventional pharmacological prophylactic treatments, including lomerizine, amitriptyline, and valproic acid, were performed. After 4 weeks of treatment, clinical improvements were evaluated using the Clinical Global Improvement Scale (CGI-s). The relationships among the CGI-S score, several clinical variables, and the results of several vestibular examinations were evaluated. Each patient was further classified into two subgroups according to treatment outcomes concerning vertigo and headache: CGI-S score from 0 to 2 (good response [GR]) and CGI-S score > 3 (poor response [PR]).

Results

Overall, after treatment, most of the patients had improved dizziness and headache, and the CGI-s was 2.7 ± 1.3. There were 12 GRs, and 13 had PRs. Thus, neither V-HIT nor posturography predicted the prognosis. For c-VEMP, patients with GRs had significantly small AR concerning PR (19.2 ± 12.8 and 62.5 ± 42.5, respectively, [p < 0.01]). There were five normal, six unilateral, and 14 bilateral no response in 500hz o-VEMP. CGI-s of normal, unilateral, and bilateral no response was 1.4 ± 0.5, 2.8 ± 1.3, and 3.1 ± 1.2, respectively. There was a statistically significant difference between the normal and bilateral non-response o-VEMP groups (p < 0.05).

Conclusion

Patients with VM had improvements in both headache and vertigo through a combination of lifestyle changes and prophylactic medications. Vestibular examinations, especially o- or c-VEMP, are beneficial for predicting the treatment outcomes of VM. The pathophysiology of VM is closely related to vestibular abnormalities, particularly the otolith-related pathways.
Sex and age effects on gray matter volume trajectories in young children with prenatal alcohol exposure
Authors: Long Madison , Kar Preeti , Forkert Nils D. , Landman Bennett A. , Gibbard W. Ben , Tortorelli Christina , McMorris Carly A. , Huo Yuankai , Lebel Catherine A.
Published: April 2024

Prenatal alcohol exposure (PAE) occurs in ~11% of North American pregnancies and is the most common known cause of neurodevelopmental disabilities such as fetal alcohol spectrum disorder (FASD; ~2–5% prevalence). PAE has been consistently associated with smaller gray matter volumes in children, adolescents, and adults. A small number of longitudinal studies show altered gray matter development trajectories in late childhood/early adolescence, but patterns in early childhood and potential sex differences have not been characterized in young children. Using longitudinal T1-weighted MRI, the present study characterized gray matter volume development in young children with PAE (N = 42, 84 scans, ages 3–8 years) compared to unexposed children (N = 127, 450 scans, ages 2–8.5 years). Overall, we observed altered global and regional gray matter development trajectories in the PAE group, wherein they had attenuated age-related increases and more volume decreases relative to unexposed children. Moreover, we found more pronounced sex differences in children with PAE; females with PAE having the smallest gray matter volumes and the least age-related changes of all groups. This pattern of altered development may indicate reduced brain plasticity and/or accelerated maturation and may underlie the cognitive/behavioral difficulties often experienced by children with PAE. In conjunction with previous research on older children, adolescents, and adults with PAE, our results suggest that gray matter volume differences associated with PAE vary by age and may become more apparent in older children.
Brain functional connectivity correlates of anomalous interaction between sensorily isolated monozygotic twins
Authors: Silberstein Richard B. , Bigelow Felicity J.
Published: April 2024

This study examined brain functional connectivity (FC) changes associated with possible anomalous interactions between sensorily isolated monozygotic (MZ) twins. Brain FC was estimated using the Steady State Visual Evoked Potential-Event Related Partial Coherence (SSVEP-ERPC) methodology. Five twin pairs served twice as participants, with an average interval between sessions of 67 days. In each recording session, one twin, the Sender, viewed a randomized set of 50 general images and 50 personally relevant images, while the other twin, the Receiver, viewed a static personally relevant image for the entire duration of the session. Images appeared on the Sender screen for 1.0 s, with the interval between successive images varied randomly between 4.0 and 8.0 s. Receiver FC changes were calculated based on the appearance times of the images as viewed by the Sender. It was hypothesized that anomalous interactions would be indicated by statistically significant Receiver FC changes when those changes are determined using the Sender image appearance times. For each twin serving as Receiver, FC components were separately analyzed for the 50 general and the 50 personal images, yielding 38 observations (19 twin pairs by 2 conditions). The hypothesis was confirmed in that 11 of the 38 observations yielded statistically significant Receiver FC increases or decreases at the p < 0.01 level only when trials were synchronized to the Sender image appearance times. Overall, this effect was significant at the p = 4 × 10−8 Df = 175. To the best of our knowledge, this is the first study reporting statistically significant FC changes indicative of anomalous interactions between two sensorily isolated individuals.
Coordination among frequent genetic variants imparts substance use susceptibility and pathogenesis
Authors: Veerappa Avinash , Guda Chittibabu
Published: April 2024

Determining the key genetic variants is a crucial step to comprehensively understand substance use disorders (SUDs). In this study, utilizing whole exome sequences of five multi-generational pedigrees with SUDs, we used an integrative omics-based approach to uncover candidate genetic variants that impart susceptibility to SUDs and influence addition traits. We identified several SNPs and rare, protein-function altering variants in genes, GRIA3, NCOR1, and SHANK1; compound heterozygous variants in LNPEP, LRP1, and TBX2, that play a significant role in the neurotransmitter-neuropeptide axis, specifically in the dopaminergic circuits. We also noted a greater frequency of heterozygous and recessive variants in genes involved in the structural and functional integrity of synapse receptors, CHRNA4, CNR2, GABBR1, DRD4, NPAS4, ADH1B, ADH1C, OPRM1, and GABBR2. Variant analysis in upstream promoter regions revealed regulatory variants in NEK9, PRRX1, PRPF4B, CELA2A, RABGEF1, and CRBN, crucial for dopamine regulation. Using family-and pedigree-based data, we identified heterozygous recessive alleles in LNPEP, LRP1 (4 frameshift deletions), and TBX2 (2 frameshift deletions) linked to SUDs. GWAS overlap identified several SNPs associated with SUD susceptibility, including rs324420 and rs1229984. Furthermore, miRNA variant analysis revealed notable variants in mir-548 U and mir-532. Pathway studies identified the presence of extensive coordination among these genetic variants to impart substance use susceptibility and pathogenesis. This study identified variants that were found to be overrepresented among genes of dopaminergic circuits participating in the neurotransmitter-neuropeptide axis, suggesting pleiotropic influences in the development and sustenance of chronic substance use. The presence of a diverse set of haploinsufficient variants in varying frequencies demonstrates the existence of extraordinary coordination among them in attributing risk and modulating severity to SUDs.
Current understanding of the molecular mechanisms of chemotherapy-induced peripheral neuropathy
Authors: Chen Xinyu , Gan Yumeng , Au Ngan Pan Bennett , Ma Chi Him Eddie
Published: April 2024

Chemotherapy-induced peripheral neuropathy (CIPN) is the most common off-target adverse effects caused by various chemotherapeutic agents, such as cisplatin, oxaliplatin, paclitaxel, vincristine and bortezomib. CIPN is characterized by a substantial loss of primary afferent sensory axonal fibers leading to sensory disturbances in patients. An estimated of 19–85% of patients developed CIPN during the course of chemotherapy. The lack of preventive measures and limited treatment options often require a dose reduction or even early termination of life-saving chemotherapy, impacting treatment efficacy and patient survival. In this Review, we summarized the current understanding on the pathogenesis of CIPN. One prominent change induced by chemotherapeutic agents involves the disruption of neuronal cytoskeletal architecture and axonal transport dynamics largely influenced by the interference of microtubule stability in peripheral neurons. Due to an ineffective blood-nerve barrier in our peripheral nervous system, exposure to some chemotherapeutic agents causes mitochondrial swelling in peripheral nerves, which lead to the opening of mitochondrial permeability transition pore and cytochrome c release resulting in degeneration of primary afferent sensory fibers. The exacerbated nociceptive signaling and pain transmission in CIPN patients is often linked the increased neuronal excitability largely due to the elevated expression of various ion channels in the dorsal root ganglion neurons. Another important contributing factor of CIPN is the neuroinflammation caused by an increased infiltration of immune cells and production of inflammatory cytokines. In the central nervous system, chemotherapeutic agents also induce neuronal hyperexcitability in the spinal dorsal horn and anterior cingulate cortex leading to the development of central sensitization that causes CIPN. Emerging evidence suggests that the change in the composition and diversity of gut microbiota (dysbiosis) could have direct impact on the development and progression of CIPN. Collectively, all these aspects contribute to the pathogenesis of CIPN. Recent advances in RNA-sequencing offer solid platform for in silico drug screening which enable the identification of novel therapeutic agents or repurpose existing drugs to alleviate CIPN, holding immense promises for enhancing the quality of life for cancer patients who undergo chemotherapy and improve their overall treatment outcomes.
A pilot randomized controlled trial of transcranial direct current stimulation adjunct to moderate-intensity aerobic exercise in hypertensive individuals
Authors: Silva-Filho Edson , Bikson Marom , Gebodh Nigel , Khadka Niranjan , da Cruz Santos Amilton , Pegado Rodrigo , do Socorro Brasileiro-Santos Maria
Published: April 2024

Background

Hypertension is a global issue that is projected to worsen with increasingly obese populations. The central nervous system including the parts of the cortex plays a key role in hemodynamic stability and homeostatic control of blood pressure (BP), making them critical components in understanding and investigating the neural control of BP. This study investigated the effects of anodal transcranial direct current stimulation (tDCS) associated with aerobic physical exercise on BP and heart rate variability in hypertensive patients.

Methods

Twenty hypertensive patients were randomized into two groups: active tDCS associated with aerobic exercise or sham tDCS associated with aerobic exercise. BP and heart rate variability were analyzed before (baseline) and after twelve non-consecutive sessions. After each tDCS session (2 mA for 20 min), moderate-intensity aerobic exercise was carried out on a treadmill for 40 min.

Results

A total of 20 patients were enrolled (53.9 ± 10.6 years, 30.1 ± 3.7 Kg/m2). There were no significant interactions between time and groups on diastolic BP during wake, sleep, over 24 and 3 h after the last intervention. Heart rate variability variables showed no significant difference for time, groups and interaction analysis, except for HF (ms2) between groups (p < 0.05).

Conclusion

Anodal tDCS over the temporal cortex associated with aerobic exercise did not induce improvements in BP and heart rate variability.

Clinical trial registration

https://ensaiosclinicos.gov.br/rg/RBR-56jg3n/1, identifier: RBR-56jg3n.
Reproducible machine learning research in mental workload classification using EEG
Authors: Demirezen Güliz , Taşkaya Temizel Tuğba , Brouwer Anne-Marie
Published: April 2024

This study addresses concerns about reproducibility in scientific research, focusing on the use of electroencephalography (EEG) and machine learning to estimate mental workload. We established guidelines for reproducible machine learning research using EEG and used these to assess the current state of reproducibility in mental workload modeling. We first started by summarizing the current state of reproducibility efforts in machine learning and in EEG. Next, we performed a systematic literature review on Scopus, Web of Science, ACM Digital Library, and Pubmed databases to find studies about reproducibility in mental workload prediction using EEG. All of this previous work was used to formulate guidelines, which we structured along the widely recognized Cross-Industry Standard Process for Data Mining (CRISP-DM) framework. By using these guidelines, researchers can ensure transparency and comprehensiveness of their methodologies, therewith enhancing collaboration and knowledge-sharing within the scientific community, and enhancing the reliability, usability and significance of EEG and machine learning techniques in general. A second systematic literature review extracted machine learning studies that used EEG to estimate mental workload. We evaluated the reproducibility status of these studies using our guidelines. We highlight areas studied and overlooked and identify current challenges for reproducibility. Our main findings include limitations on reporting performance on unseen test data, open sharing of data and code, and reporting of resources essential for training and inference processes.