bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association between Fibromyalgia, Hypermobility and Neurodivergence Extends To Families: Brief Report
Authors: Kelly Clive
Published: July 2023

Objectives: Fibromyalgia is associated with symptomatic hypermobility. People with these conditions have a higher prevalence of neurodivergent conditions. Many fibromyalgia patients with hypermobility also report similar symptoms within their family. This study explores the presence of diagnosed disorders among close relatives of patients presenting with fibromyalgia and hypermobility. Methods: All patients presenting with both fibromyalgia and hypermobility to the rheumatology clinic were invited to participate. Each of these participants reported all confirmed diagnoses of any of neurodivergence, fibromyalgia or hypermobility among their first- and second-degree relatives. Participants were invited to prepare a family tree detailing these diagnoses. We calculated the incidence of each of neurodivergence, fibromyalgia and hypermobility within these relatives and compared them to the incidence derived from families of case-control patients with osteoarthritis. Results: Among 13 index patients (all female, median age 38 years), 9 had a diagnosed neurodivergent condition (69%). Among their 163 relatives, 68 (42%) had a diagnosed neurodivergent condition, compared to 4.7% among case-control relatives (p>0.00001). The incidence of diagnosed hypermobility and fibromyalgia in relatives of index cases was 36% and 22%, compared to 8% and 4% in case-control relatives (p=0.00001, p=0.00012). Conclusion: This self-reported small case-control study confirms the association of fibromyalgia, hypermobility and neurodivergence, and suggests that close relatives also exhibit this association. Females are disproportionately overrepresented within pain populations, in contrast to neurodivergence in other settings where males predominate, perhaps due to underdiagnosis in females. Gene clustering may contribute to these associations, which extend into the community.
Pattern of Substance Use among Patients Attending De-Addiction Unit in a Nigerian Tertiary Hospital
Authors: Ehigiator Adayonfo , Kehinde Oderinde , Mary Ehimigbai , Enobakhare Uwadiae , Andrew Obi
Published: July 2023

Substance use is a growing public health problem and the consequences of substance use disorder are costly to the community. The absence of data on the pattern of substance-use among drug using patients attending the University of Benin Teaching Hospital (UBTH) and other hospitals in south-south Nigeria and the negative consequences of substance use justified the study. Thus, the objectives of the study were to investigate the pattern of substance use, the socio-demographic characteristics and clinical indices associated with drug use among the patients attending the De-Addiction Unit in UBTH. It was a cross-sectional study that obtained data from casefiles of 48 patients. Cannabis was the most frequently used substance (52.1%), followed by alcohol (18.8%), tobacco (16.7%), tramadol (14.6%) and pentazocine (12.5%). Majority of the respondents were males 38 (79.2%), age group 18 to 27 years (75%), singles 38 (79.2%), multiple substance users 34 (70.8%), reported peer pressure influence 35 (72.9%) and reported ‘smoking’ as route of substance use 32 (66.7%). It was observed that prevalence of use of drugs among females was rising. The commonest psychiatric co-morbidity among them was depression 19 (39.6%), followed by bipolar affective disorder 10 (20.8%) and schizophrenia 7 (14.6%). Substance use prevention, treatment and control measures need to pay attention to males and female users, since the prevalence of substance use among female is rising. Such programs must bear in mind the adolescent and young adult age groups and measures to mitigate the use of common substances such as alcohol and cannabis must continue to enjoy priority. During screening/assessment for substance use, a high index of suspicion for comorbidities especially depression is important. Peer group influence and curiosity, which are identified reasons for initiating substance use, may be checked by targeted health education.
Neuropsychoanalytic Prerequisite for Diagnosis of Psychiatric Unbalance
Authors: Cai Zi-Jian
Published: July 2023

It was recently added by Cai to neuropsychoanalysis the ascending noradrenergic (NA), serotonergic (5-HT) and acetylcholinergic (ACh) systems, differentiating the emotions/memories/conscious balance in waking and sleep for depression, as well as the ascending dopaminergic (DA) and ACh systems to motivation/selfishness/knowledge balance for schizophrenia. For psychiatric diagnosis, it is just delineated the psychological unbalance resulting from the detected pathologies by neuropsychoanalytic interactions and conflicts as indispensable prerequisite.
The role of Halkevi libraries in the early Turkish Republic
Authors: Lacey Eve
Published: July 2023

The tenure of the Halkevleri (‘People's Houses’, 1932–51) spanned most of the single-party period of the early Turkish Republic (1923–46), and their work took place during a widespread public education campaign that focused on literacy, healthcare, and the construction of a national identity. In the aftermath of an alphabet reform and in the midst of a major language reform, Halkevleri libraries were tasked with helping a largely illiterate population to read and write. Their journals, bibliographies, and library instruction manuals reveal the policies (circulation, collection development, public education, and the twinned operations of publishing and archiving) that prepared these institutions to develop a readership for government propaganda. These strategies were employed to stretch literacy as far as possible throughout the halk (people), enabling community libraries to create and conserve a culture that could absorb their readers in a shared project of nation-building.
‘A reading people’: mapping the personal libraries of prominent British Methodists
Authors: Field Clive D.
Published: July 2023

Reading is acknowledged to have been a key means of transmission and reinforcement of the Methodist message in Britain, yet the role played by libraries in the history of the movement has been comparatively neglected, certainly in the aggregate. This article offers a preliminary collective overview of non-institutional private libraries and collections of Wesleyana formed by individual British Methodists, from the eighteenth century to the twenty-first, and seeks to ascertain what became of them over subsequent years. Information is assembled about ninety-five collectors, a combination of ministers and laity, who mostly achieved some prominence in British Methodism. Although the need for further research into the topic is recognised, it has already been possible to detect several trends, not least the historically relatively weak appetite of what is now the Methodist Church of Great Britain for the acquisition and preservation of its library and documentary heritage, a reticence which has contributed to the loss of a significant portion of it overseas.
ANALISIS OPPORTUNITY COST BIOKONVERSI SAMPAH ORGANIK MENGGUNAKAN MAGGOT BSF (BLACK SOLDIER FLY)
Authors: Ambarwati Lilik , Yulianto Prafidhya Dwi
Published: July 2023

This study aims to determine the opportunity cost of processing waste using BSF maggot compared to the monthly waste costs incurred by residents, as well as evaluating residents' decisions in choosing the current waste processing costs. Descriptive analysis is used in this study, intended to provide a clear description and description of opportunity cost analysis in waste management decision making. The Sorosutan Village of Yogyakarta became the object of research, with the result that waste management using BSF maggot saved costs of Rp. 3,331,000 for 108 residents, compared to when residents used cart services with a monthly fee of Rp. 30,000 per head of family. So that the selection of waste management methods carried out by residents is currently not appropriate.
A machine learning framework for neighbor generation in metaheuristic search
Authors: Liu Defeng , Perreault Vincent , Hertz Alain , Lodi Andrea
Published: July 2023

This paper presents a methodology for integrating machine learning techniques into metaheuristics for solving combinatorial optimization problems. Namely, we propose a general machine learning framework for neighbor generation in metaheuristic search. We first define an efficient neighborhood structure constructed by applying a transformation to a selected subset of variables from the current solution. Then, the key of the proposed methodology is to generate promising neighbors by selecting a proper subset of variables that contains a descent of the objective in the solution space. To learn a good variable selection strategy, we formulate the problem as a classification task that exploits structural information from the characteristics of the problem and from high-quality solutions. We validate our methodology on two metaheuristic applications: a Tabu Search scheme for solving a Wireless Network Optimization problem and a Large Neighborhood Search heuristic for solving Mixed-Integer Programs. The experimental results show that our approach is able to achieve a satisfactory trade-offs between the exploration of a larger solution space and the exploitation of high-quality solution regions on both applications.
Comparison of machine learning approaches for near-fall-detection with motion sensors
Authors: Hellmers Sandra , Krey Elias , Gashi Arber , Koschate Jessica , Schmidt Laura , Stuckenschneider Tim , Hein Andreas , Zieschang Tania
Published: July 2023

Introduction

Falls are one of the most common causes of emergency hospital visits in older people. Early recognition of an increased fall risk, which can be indicated by the occurrence of near-falls, is important to initiate interventions.

Methods

In a study with 87 subjects we simulated near-fall events on a perturbation treadmill and recorded them with inertial measurement units (IMU) at seven different positions. We investigated different machine learning models for the near-fall detection including support vector machines, AdaBoost, convolutional neural networks, and bidirectional long short-term memory networks. Additionally, we analyzed the influence of the sensor position on the classification results.

Results

The best results showed a DeepConvLSTM with an F1 score of 0.954 (precision 0.969, recall 0.942) at the sensor position “left wrist.”

Discussion

Since these results were obtained in the laboratory, the next step is to evaluate the suitability of the classifiers in the field.
Students’ systems thinking while modeling a dynamic ecological system
Authors: Lankers Annika , Timm Justin , Schmiemann Philipp
Published: July 2023

The world is facing global ecological changes, making it essential to prepare the future generation with the necessary understanding to effectively navigate and address complex tasks. Previous research has shown that both systems thinking and scientific modeling are particularly relevant in investigating the comprehensive understanding of such complex phenomena. However, there has been little research on the interrelation between systems thinking and scientific modeling. To address this research gap, we conducted a thinking-aloud study with nine high school students by confronting them with a simulation of a dynamic ecological system. Our qualitative content analysis of the students’ statements indicates an interrelation between systems thinking and scientific modeling. The students infrequently show systems thinking during the exploration, whereas when developing a graphical model, the students are involved in identifying the system organization and analyzing the system behavior. When predicting future system states, students engage in modeling the system evolution. Furthermore, during verbalizing analogies and experiences, students refer to the system organization and behavior, whereas in mental modeling, students additionally model the system evolution. These results illustrate a central difference between the two perspectives. Thus, scientific modeling focuses on students’ activities during their understanding process, while systems thinking addresses students’ analysis of systems and their properties. While the phenomenon exploration may not require systems thinking, pattern recognition and model development are frequently associated with identifying the system organization and analyzing the system behavior. Systems thinking must also be applied when deriving possible future system states by modeling the system evolution, an activity that is closely related to the prediction phase of scientific modeling. Interestingly, in our study, the students also demonstrated the modeling of system evolution in their mental modeling. In conclusion, a complementary consideration of systems thinking and scientific modeling affords a deeper understanding of students’ cognitive processes in dealing with complex phenomena.
Effectiveness of universal school-based social-emotional learning programs in promoting social-emotional skills, attitudes towards self and others, positive social behaviors, and improving emotional and conduct problems among Japanese children: a meta-analytic review
Authors: Takizawa Yu , Bambling Matthew , Matsumoto Yuki , Ishimoto Yuma , Edirippulige Sisira
Published: July 2023

The implementation of universal school based Social–Emotional Learning (SEL) programs is increasing in Japanese schools with the aim of enhancing children’s social–emotional skills and reducing mental health problems. However, there is a lack of meta-analyses evaluating the effectiveness of these programs in Japan that specifically include studies with control groups and examine program moderators. Conducting such a meta-analysis would be valuable for improving future implementations of SEL programs in Japan. The present meta-analysis analyzed 85 intervention studies with control groups to examine the effectiveness and moderators of universal school based SEL programs for Japanese children aged 5–18 years. The analysis indicates that these programs have a small overall effect (ES = 0.26), as well as small effects in improving social–emotional skills (ES = 0.24), attitude toward the self and others (ES = 0.30), positive social behavior (ES = 0.31), conduct problem (ES = 0.20), and emotional problem (ES = 0.22) at post-intervention among Japanese children. The analysis further revealed that publication type, number of participants, and school level of children moderated the overall effects of universal school based SEL programs, suggesting potential biases in effect sizes reported in peer-reviewed journals published by scientific societies, lower effectiveness for older children, and decreased effectiveness when programs are delivered to larger numbers of children. Future research should explore more effective delivery methods for SEL programs, particularly for older children and larger groups, such as integrating community components and information and communication technology into the programs.
Pockets of promise: exploring innovation and complexity of remote ECEC service delivery in Australia
Authors: Adamson Elizabeth , Skattebol Jennifer
Published: July 2023

Introduction

The existing funding architectures for early childhood education and care (ECEC) services in Australia are incompatible with the needs of remote and First Nations communities. The Australian system relies on a market-based model for ECEC – characterized by demand-led funding mechanisms where funding flows to users to choose what service to use. This model is not viable or sustainable in remote and First Nations communities. In this paper, we ask what we can learn from alternative models of ECEC that serve remote, largely Indigenous communities.

Methods

This research is based on interviews with 10 key stakeholders. Potential participants were identified using three selection criteria which established their expertise in relation to: advocacy and experience in delivering ECEC services in remote locations (evident in relevant parliamentary reviews and inquiries), in-depth knowledge about First Nations perspectives about ECEC models, and broader understandings of the ECEC system in Australia. Three themes were explored in the interviews: (1) funding context (including impact of recent changes to Budget Based Funding, and role of philanthropy in the ECEC sector); (2) Quality and regulatory context (including workforce challenges and cultural considerations); and (3) Future research (including research gaps, opportunities, and considerations). The study design and analysis of data was guided by policy studies frameworks that advocate for collaboration and coordination among researchers and stakeholders in order to address complex problems.

Results

Analysis of the interviews illuminated the complex structural and cultural elements shaping the design of, and access to, ECEC in remote communities. Stakeholders argued that the ECEC system should be universal in that it delivers services that meet the needs of young children and their families. This requires the development of a definition of ‘universality’ that enables communities to define their own ECEC needs and the types of services best suited to meet those needs. Stakeholders’ views about the importance of community-led design and delivery highlighted the need to align structural and cultural aspects of quality standards and workforce needs, and also to strengthen consultation with First Nations organisations to better understand community-specific solutions.

Discussion

The paper outlines the complexities and nuances of ECEC service delivery in remote communities. The findings are intended to foster discussion about current initiatives, challenges, and futures possibilities for ECEC in remote communities in Australia. These findings concur with other research that argues for community led service delivery and for stronger equity-based partnerships between First Nations and non-First Nations researchers and organizations.
Relationship between serum uric acid and estimated glomerular filtration rate in adolescents aged 12-19 years with different body mass indices: a cross-sectional study
Authors: Tian Qiuwei , He Caixia , Wang Zisai , Hun Marady , Fu Yi-Cheng , Zhao Mingyi , He Qingnan
Published: July 2023

Background

Globally, chronic kidney disease (CKD) is a growing public health concern. Serum uric acid (SUA) is an easily detectable and readily available biochemical indicator that has long been recognized as an independent risk factor for CKD. In addition, studies have indicated a potential relationship between SUA and body mass index (BMI). However, studies on the effect of SUA levels on the estimated glomerular filtration rate (eGFR) in adolescents with different BMIs are very rare.

Methods

Weighted multiple regression analysis was used to estimate the independent relationship between SUA and log-transformed eGFR. Additionally, we used a weighted generalized additive model and smooth curve fitting to describe the nonlinear relationships in the subgroup analysis.

Results

First, SUA was negatively associated with log-transformed eGFR even after adjusting for all covariates (β=-0.0177, 95% CI: -0.0203-0.0151, P<0.0001). Second, the results of the stratified analysis found that after adjusting for all covariates, the decrease in log-transformed eGFR due to changes in per SUA levels (Per 1, mg/dL increase) was elevated in female adolescents (β=-0.0177, 95% CI: -0.0216, -0.0138, P<0.0001), adolescents aged 12-15 years (β=-0.0163, 95% CI: -0.0200, -0.0125, P<0.0001) and black (β=-0.0199, 95% CI: -0.0251, -0.0148, P<0.0001) adolescents. Furthermore, we found that adolescents with a higher BMI had higher SUA levels, and the effect of SUA on eGFR was significantly higher in underweight adolescents (β=-0.0386, 95% CI: (-0.0550, -0.0223), P<0.0001).

Conclusion

SUA was negatively associated with the eGFR in adolescents aged 12-19 years. Furthermore, we found for the first time that SUA affects the eGFR differently in adolescents with different BMIs. This effect was particularly significant in underweight adolescents.
Prospects for deploying microbes against tree-killing beetles (Coleoptera) in Anthropocene
Authors: Gupta Sumanti , Chakraborty Amrita , Roy Amit
Published: July 2023

Forests form rich biodiversity hubs that act as large reservoirs of natural carbon. The spatial and temporal heterogeneity of these complex habitats of forest floors provides ecological services of immense socio-economic importance. However, these socio-economic ecological hotspots are incessantly exposed to multifarious abiotic, biotic, and anthropogenic disturbances, amongst which unpredictable forest pest (i.e., bark beetle) outbreak account for the loss of vegetation and microbiome of measurable quantum. The importance of the microbiome in forming an inseparable functional unit of every host and shaping its interaction with other partners has been well realized. Interestingly, forest pests, including bark beetles, are also reported to rely on their endosymbiotic microbial partners to manipulate tree defense machinery. In contrast, the microbiome forming the holobiont of trees also regulates the overall function and fitness of the host and significantly contributes to tackling these challenging situations. Nevertheless, how the holobiont of trees directly or indirectly influence beetle holobiont is still an enigma. The present review shall elaborate on the role of microbial tools in enhancing tree performance and fitness, which helps counter beetle damage. Besides, it shall also emphasize exploiting the role of microorganisms in acting as biocontrol agents in shielding the trees against beetle destruction. The application of endosymbiont-mediated RNA interference (RNAi) in working with two-tier specificity for controlling beetle devastations shall be discussed as new-age technological advances. All explanations are expected to put forth the potential of the microbial toolbox in offering better and more sustainable beetle management strategies in the future.
NR4A1 as a potential therapeutic target in colon adenocarcinoma: a computational analysis of immune infiltration and drug response
Authors: Li Mei , Zhang Zhongyi , Li Mingzhou , Chen Zhe , Tang Weizhu , Cheng Xiang
Published: July 2023

Background: Colon adenocarcinoma (COAD) is a common malignancy with high morbidity and mortality rates. The immune system plays a crucial role in CRC development and progression, making it a potential therapeutic target. In this study, we analyzed transcriptomic data from CRC patients to investigate immune infiltration and identify potential therapeutic targets.

Method and results: we used CIBERSORT to analyze the immune infiltration in COAD samples and found that the high infiltration of M2 macrophages and neutrophils was associated with poor prognosis. Next, we identified NR4A1 as a potential therapeutic target based on its protective effect in two predict models. Using cancer therapeutics response analysis, we found that high expression levels of NR4A1 were sensitive to OSI-930, a tyrosine kinase inhibitor with anti-tumor effects.

Conclusion: Our findings suggest that targeting NR4A1 with OSI-930 may be a promising therapeutic strategy for COAD patients with high levels of immune infiltration. However, further studies are needed to investigate the clinical efficacy of this approach.
A retrospective review of α-gal syndrome complicating the management of suspected pancreatic exocrine insufficiency in one gastroenterology clinic in central Virginia
Authors: Richards Nathan E. , Wilson Jeffrey M. , Platts-Mills Thomas A. E. , Richards Robert D.
Published: July 2023

The galactose-α-1,3-galactose (α-gal) mammalian meat allergy, α-gal syndrome, often includes diarrhea, abdominal pain, and other gastrointestinal (GI) symptoms. Pancreatic exocrine insufficiency causes similar symptoms. The pancreatic replacement enzymes, referred to here as pancreatic enzymes, used to treat pancreatic insufficiency are porcine products and contain α-gal. Patients with pancreatic insufficiency who also have α-gal syndrome may be intolerant of mammalian products in their diet and of α-gal in pancreatic enzymes. In this article, we describe 40 patients from one GI clinic in central Virginia with suspected pancreatic insufficiency and increased α-gal immunoglobulin E (IgE) levels. Over 50% of these patients had some clinical improvement when mammalian products were removed from the diet. Most patients could tolerate pancreatic enzymes; 10% could not tolerate them due to suspected allergy symptoms, but none developed anaphylaxis. Understanding that α-gal syndrome can be superimposed on pancreatic exocrine insufficiency and exacerbate symptoms, and that treatment with pancreatic enzymes may increase GI and/or allergy symptoms in this group, will lead to improved medical management of this complex patient population.
Salvianolic acid B ameliorates neuroinflammation and neuronal injury via blocking NLRP3 inflammasome and promoting SIRT1 in experimental subarachnoid hemorrhage
Authors: Xia Dayong , Yuan Jinlong , Wu Degang , Dai Haibin , Zhuang Zong
Published: July 2023

The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated immuno-inflammatory response plays a critical role in exacerbating early brain injury (EBI) after subarachnoid hemorrhage (SAH). Salvianolic acid B (SalB) has previously been shown to suppress neuroinflammatory responses in many disorders. Meanwhile, a previous study has demonstrated that SalB mitigated oxidative damage and neuronal degeneration in a prechiasmatic injection model of SAH. However, the therapeutic potential of SalB on immuno-inflammatory responses after SAH remains unclear. In the present study, we explored the therapeutic effects of SalB on neuroinflammatory responses in an endovascular perforation SAH model. We observed that SalB ameliorated SAH-induced functional deficits. Additionally, SalB significantly mitigated microglial activation, pro-inflammatory cytokines release, and neuronal injury. Mechanistically, SalB inhibited NLRP3 inflammasome activation and increased sirtuin 1 (SIRT1) expression after SAH. Administration of EX527, an inhibitor of SIRT1, abrogated the anti-inflammatory effects of SalB against SAH and further induced NLRP3 inflammasome activation. In contrast, MCC950, a potent and selective NLRP3 inflammasome inhibitor, reversed the detrimental effects of SIRT1 inhibition by EX527 on EBI. These results indicated that SalB effectively repressed neuroinflammatory responses and neuronal damage after SAH. The action of SalB appeared to be mediated by blocking NLRP3 inflammasome and promoting SIRT1 signaling.
RSV replication modifies the XBP1s binding complex on the IRF1 upstream enhancer to potentiate the mucosal anti-viral response
Authors: Qiao Dianhua , Xu Xiaofang , Zhang Yueqing , Yang Jun , Brasier Allan R.
Published: July 2023

Introduction

The unfolded protein response (UPR) has emerged as an important signaling pathway mediating anti-viral defenses to Respiratory Syncytial Virus (RSV) infection. Earlier we found that RSV replication predominantly activates the evolutionarily conserved Inositol Requiring Enzyme 1α (IRE1α)-X-Box Binding Protein 1 spliced (XBP1s) arm of the Unfolded Protein Response (UPR) producing inflammation, metabolic adaptation and cellular plasticity, yet the mechanisms how the UPR potentiates inflammation are not well understood.

Methods

To understand this process better, we examined the genomic response integrating RNA-seq and Cleavage Under Targets and Release Using Nuclease (CUT&RUN) analyses. These data were integrated with an RNA-seq analysis conducted on RSV-infected small airway cells ± an IRE1α RNAse inhibitor.

Results

We identified RSV induced expression changes in ~3.2K genes; of these, 279 required IRE1α and were enriched in IL-10/cytokine signaling pathways. From this data set, we identify those genes directly under XBP1s control by CUT&RUN. Although XBP1s binds to ~4.2 K high-confidence genomic binding sites, surprisingly only a small subset of IL10/cytokine signaling genes are directly bound. We further apply CUT&RUN to find that RSV infection enhances XBP1s loading on 786 genomic sites enriched in AP1/Fra-1, RELA and SP1 binding sites. These control a subset of cytokine regulatory factor genes including IFN response factor 1 (IRF1), CSF2, NFKB1A and DUSP10. Focusing on the downstream role of IRF1, selective knockdown (KD) and overexpression experiments demonstrate IRF1 induction controls type I and -III interferon (IFN) and IFN-stimulated gene (ISG) expression, demonstrating that ISG are indirectly regulated by XBP1 through IRF1 transactivation. Examining the mechanism of IRF1 activation, we observe that XBP1s directly binds a 5’ enhancer sequence whose XBP1s loading is increased by RSV. The functional requirement for the enhancer is demonstrated by targeting a dCas9-KRAB silencer, reducing IRF1 activation. Chromatin immunoprecipitation shows that XBP1 is required, but not sufficient, for RSV-induced recruitment of activated phospho-Ser2 Pol II to the enhancer.

Discussion

We conclude that XBP1s is a direct activator of a core subset of IFN and cytokine regulatory genes in response to RSV. Of these IRF1 is upstream of the type III IFN and ISG response. We find that RSV modulates the XBP1s binding complex on the IRF1 5’ enhancer whose activation is required for IRF1 expression. These findings provide novel insight into how the IRE1α-XBP1s pathway potentiates airway mucosal anti-viral responses.
Multi-scale grading utilization based on the characteristics of recycled concrete aggregates: a review
Authors: Feng Qi , Liu Binqing , Zhang Yangpeng , Zhang Chen , Wang Dan
Published: July 2023

The physical and mechanical properties of recycled aggregates (RA) among different particle sizes are compared. Results demonstrate that adhesive mortar content is a significant factor in determining the properties of recycled aggregate concrete (RAC). The adhesive mortar content on the surface of recycled aggregates is critical in selecting the most efficient strengthening treatment, and effects of the strengthening treatment on properties of RA with different particle sizes was reported. The utilization of RA was suggested to classify into fine powder aggregate, fine aggregate, coarse aggregate based on the particle size, i.e., the multi-scale grading utilization. The most suitable strengthening treatment was reviewed for RA with various particle size to improve the it’s utilization efficiency.
The development, validation, and in vivo testing of a high-precision bronchial epithelial lining fluid sampling device
Authors: Gupta Akash , Burgess Janette K. , Slebos Dirk-Jan , Pouwels Simon D.
Published: July 2023

Introduction

Analysis of respiratory biomarkers or pharmaceutical drug concentrations in bronchial epithelial lining fluid (bELF) using a high-precision sampling method is crucial for effective clinical respiratory diagnostics and research. Here, we utilized a cellulose matrix as an absorptive probe for bELF sampling, subsequently testing the design of a device and sampling technique in vivo.

Methods

The absorptive matrix [Whatman® qualitative filter paper (Grade CF-12)] was first tested through tissue-contact experiments on porcine airway tissue. The absorption and elution capacity of the matrix, as well as the laboratory processing and analysis method, was validated with a range of Interleukin-8 (CXCL8) and C-Reactive protein (CRP) stock solutions. Subsequently, the device’s design was optimized for universal in-house production and both, safe and efficient sampling. The airway sampling method was then tested in a group of 10 patients with Chronic Obstructive Pulmonary Disease (COPD). For each patient, a bELF sample was obtained using the newly developed bELF probe, as well as a reference 20 mL saline bronchial wash sample. Supernatants were assessed, using an immunoassay, for levels of the pro-inflammatory markers CXCL8, Myeloperoxidase (MPO), and CRP. The bELF samples were compared to bronchial wash.

Results

The Whatman® qualitative filter paper (Grade CF-12) bELF probes adhered to porcine airway tissue, softening slightly upon wetting. The material maintained architectural integrity following the removal of the probes, leaving no residual fibers on the porcine airway mucosa. The bELF probe design was optimized for bronchoscopic delivery and in-house production. On average, a fully saturated bELF probe carried 32 μL of protein-rich fluid. The mean return of CXCL8 and CRP from samples collected from a serial dilution series (1, 5, 10, 20 ng/mL) was 69% (range 48%–87%). The bELF probe detected, on average, 7 (MPO), 14 (CRP), and 59 (CXCL8) times higher equivalent inflammatory protein concentrations in the collected bELF probe samples compared to the bronchial wash.

Conclusion

The bELF probe is an effective absorptive technology for high-precision bELF sampling without dilution. With a simple in-house production procedure and bronchoscopic sampling technique, this method can be introduced in any bronchoscopic center for a consistent sampling of bELF.
Walking the talk in digital transformation of regulatory review
Authors: Khalil Ramy , Macdonald Judith C. , Gustafson Andrew , Aljuburi Lina , Bisordi Fabio , Beakes-Read Ginny
Published: July 2023

Cloud-based regulatory platforms have the potential to substantially transform how regulatory submissions are developed, transmitted, and reviewed across the full life cycle of drug development. The benefits of cloud-based submission and review include accelerating critical therapies to patients in need globally and efficiency gains for both drug developers and regulators. The key challenge is turning the theoretical promise of cloud-based regulatory platforms into reality to further the application of technology in the regulatory processes. In this publication we outline regulatory policy journeys needed to effect the changes in the external environment that would allow for use of a cloud-based technology, discuss the prerequisites to successfully navigate the policy journeys, and elaborate on future possibilities when adoption of cloud-based regulatory technologies is achieved.
Polyphasic characterization of a novel hot-spring cyanobacterium Thermocoleostomius sinensis gen et sp. nov. and genomic insights into its carbon concentration mechanism
Authors: Jiang Ying , Tang Jie , Liu Xiangjian , Daroch Maurycy
Published: July 2023

Thermophilic cyanobacteria play a crucial role as primary producers in hot spring ecosystems, yet their microbiological, taxonomic, and ecological characteristics are not extensively studied. This study aimed to characterize a novel strain of thermophilic cyanobacteria, PKUAC-SCTA174 (A174), using a combination of traditional polyphasic methods and modern genomic-based approaches. The study included 16S rRNA-based phylogeny, ITS secondary structure prediction, morphological and habitat analyses, as well as high-quality genome sequencing with corresponding phylogenomic analyses. The results of the 16S rRNA, 16S-23S ITS secondary structure, morphology, and habitat analyses supported the classification of the strain as a member of a novel genus within the family Oculatellaceae, closely related to Albertania and Trichotorquatus. Genomic analysis revealed the presence of a sophisticated carbon-concentrating mechanism (CCM) in the strain, involving two CO2 uptake systems NDH-I3, and NDH-I4, three types of bicarbonate transporters (BCT1, bicA, sbtA,) and two distinct putative carboxysomal carbonic anhydrases (ccaA1 and ccaA2). The expression of CCM genes was investigated with a CO2 shift experiment, indicating varying transcript abundance among different carbon uptake systems. Based on the comprehensive characterization, the strain was delineated as Thermocoleostomius sinensis, based on the botanical code. The study of the complete genome of strain A174 contributes valuable insights into the genetic characteristics of the genus Thermocoleostomius and related organisms and provides a systematic understanding of thermophilic cyanobacteria. The findings presented here offer valuable data that can be utilized for future research in taxogenomics, ecogenomics, and geogenomics.
ESKAPEE pathogens newly released from biofilm residence by a targeted monoclonal are sensitized to killing by traditional antibiotics
Authors: Kurbatfinski Nikola , Kramer Cameron N. , Goodman Steven D. , Bakaletz Lauren O.
Published: July 2023

Introduction

The “silent” antimicrobial resistance (AMR) pandemic is responsible for nearly five million deaths annually, with a group of seven biofilm-forming pathogens, known as the ESKAPEE pathogens, responsible for 70% of these fatalities. Biofilm-resident bacteria, as they exist within the disease site, are canonically highly resistant to antibiotics. One strategy to counter AMR and improve disease resolution involves developing methods to disrupt biofilms. These methods aim to release bacteria from the protective biofilm matrix to facilitate their killing by antibiotics or immune effectors. Several laboratories working on such strategies have demonstrated that bacteria newly released from a biofilm display a transient phenotype of significantly increased susceptibility to antibiotics. Similarly, we developed an antibody-based approach for biofilm disruption directed against the two-membered DNABII family of bacterial DNA-binding proteins, which serve as linchpins to stabilize the biofilm matrix. The incubation of biofilms with α-DNABII antibodies rapidly collapses them to induce a population of newly released bacteria (NRel).

Methods

In this study, we used a humanized monoclonal antibody (HuTipMab) directed against protective epitopes of a DNABII protein to determine if we could disrupt biofilms formed by the high-priority ESKAPEE pathogens as visualized by confocal laser scanning microscopy (CLSM) and COMSTAT2 analysis. Then, we demonstrated the potentiated killing of the induced NRel by seven diverse classes of traditional antibiotics by comparative plate count.

Results

To this end, ESKAPEE biofilms were disrupted by 50%−79% using a single tested dose and treatment period with HuTipMab. The NRel of each biofilm were significantly more sensitive to killing than their planktonically grown counterparts (heretofore, considered to be the most sensitive to antibiotic-mediated killing), even when tested at a fraction of the MIC (1/250–1/2 MIC). Moreover, the bacteria that remained within the biofilms of two representative ESKAPEE pathogens after HuTipMab disruption were also significantly more susceptible to killing by antibiotics.

Discussion

New data presented in this study support our continued development of a combinatorial therapy wherein HuTipMab is delivered to a patient with recalcitrant disease due to an ESKAPEE pathogen to disrupt a pathogenic biofilm, along with a co-delivered dose of an antibiotic whose ability to rapidly kill the induced NRel has been demonstrated. This novel regimen could provide a more successful clinical outcome to those with chronic, recurrent, or recalcitrant diseases, while limiting further contribution to AMR.
The halophilic bacteria Gracilibacillus dipsosauri GDHT17 alleviates salt stress on perennial ryegrass seedlings
Authors: Li Xiangying , Zheng Jinyuan , Wei Wei , Gong Zifan , Liu Zhenyu
Published: July 2023

Introduction

Adverse abiotic environmental conditions including excess salt in the soil, constantly challenge plants and disrupt the function of plants, even inflict damage on plants. Salt stress is one of the major limiting factors for agricultural productivity and severe restrictions on plant growth. One of the critical ways to improve plant salt tolerance is halotolerant bacteria application. However, few such halotolerant bacteria were known and should be explored furtherly.

Methods

Halophilic bacterium strain was isolated from saline soil with serial dilution and identified with classical bacteriological tests and 16S rRNA analysis. Perennial ryegrass (Lolium perenne L) was used in this study to evaluate the potential effect of the bacteria.

Results and discussion

A halophilic bacterium strain GDHT17, was isolated from saline soil, which grows in the salinities media with 1.0%, 5.0%, and 10.0% (w/v) NaCl, and identified as Gracilibacillus dipsosauri. Inoculating GDHT17 can significantly promote ryegrass’s seedling height and stem diameter and increase the root length, diameter, and surface area at different salt concentrations, indicating the significant salt stress alleviating effect of GDHT17 on the growth of ryegrass. The alleviating effect on roots growth showed more effective, especially on the root length, which increased significantly by 26.39%, 42.59%, and 98.73% at salt stress of 100 mM, 200 mM, and 300 mM NaCl when the seedlings were inoculated with GDHT17. Inoculating GDHT17 also increases perennial ryegrass biomass, water content, chlorophyll and carotenoid content under salt stress. The contents of proline and malonaldehyde in the seedlings inoculated with GDHT17 increased by 83.50% and 6.87%, when treated with 300 mM NaCl; however, the contents of MDA and Pro did not show an apparent effect under salt stress of 100 mM or 200 mM NaCl. GDHT17-inoculating maintained the Na+/K+ ratio in the salt-stressed ryegrass. The Na+/K+ ratio decreased by 26.52%, 6.89%, and 29.92% in the GDHT17-inoculated seedling roots treated with 100 mM, 200 mM, and 300 mM NaCl, respectively. The GDHT17-inoculating increased the POD and SOD activity of ryegrass seedlings by 25.83% and 250.79%, respectively, at a salt stress of 300 mM NaCl, indicating the properties of GDHT17, improving the activity of antioxidant enzymes of ryegrass at the salt-stress condition. Our results suggest that G. dipsosauri GDHT17 may alleviate salt stress on ryegrass in multiple ways; hence it can be processed into microbial inoculants to increase salt tolerance of ryegrass, as well as other plants in saline soil.
Aerosolization inhalation of non-typeable Haemophilus influenzae outer membrane vesicles contributing to neutrophilic asthma
Authors: Zhang Ying , Wang Hongbo , Zhang Yanqiu , Zhao Peiliang , Li Yanan
Published: July 2023

Background

Neutrophilic asthma is poorly responsive to corticosteroids, and the mechanism underlying its pathogenesis remains unclear. Non-typeable Haemophilus influenzae (NTHi) is the most common bacterium found in induced sputum from patients with neutrophilic asthma. NTHi can release outer membrane vesicles (OMVs), which transfer biomolecules to host cells and the external environment. However, the role and mechanisms of NTHi OMVs in the pathogenesis of neutrophilic asthma remain unclear.

Methods

We conducted assays to investigate whether NTHi OMVs can induce neutrophilic asthma when inhaled. We isolated and purified NTHi OMVs and administered them via a nebulizer to ovalbumin (OVA)-sensitized mice. We collected and sequenced serum, blood, bronchoalveolar lavage fluid, and lung tissue from each group and gathered lung function data.

Results

Inhaled NTHi OMVs-induced neutrophilic asthma in OVA-sensitized mice. High-throughput sequencing revealed that NTHi OMV inhalation in OVA-sensitized mice significantly enriched inflammatory and immune-related signaling pathways. We found increased transcription and secretion of interleukin (IL)-1β and IL-17, which may contribute to neutrophilic asthma. Furthermore, we discovered that airway epithelium is the first receptor cell of NTHi OMVs and releases IL-1β. These findings suggest that NTHi OMVs could be a potential target for neutrophilic asthma therapy.
Effects of grazing prohibition on nirK- and nirS-type denitrifier communities in salt marshes
Authors: Li Niu , Li Jingrou , Nie Ming , Wu Ming , Wu Jihua
Published: July 2023

Introduction

Grazing prohibition is an effective management practice to restore salt marsh functioning. However, the effects of grazing exclusion on denitrifying microbial communities and their controlling factors in salt marshes remain unclear.

Methods

In this study, we surveyed soil physicochemical properties and above- and below-ground biomass and using quantitative polymerase chain reaction and Illumina MiSeq high-throughput sequencing technology to determine the relative abundance, composition, and diversity of nitrite reductase nirS- and nirK-type denitrifying bacterial communities associated with grazing prohibition treatments and elevations.

Results

The abundance of nirS-type denitrifiers increased with grazing prohibition time, whereas the abundance of nirK-type denitrifiers remained unaltered. Moreover, nirS-type denitrifiers were more abundant and diverse than nirK-type denitrifiers in all treatments. Grazing prohibition significantly altered the operational taxonomic unit richness, abundance-based coverage estimator, and Chao1 indices of the nirS-type denitrifying bacterial communities, whereas it only minimally affected the structure of the nirK-type denitrifying bacterial community.

Discussion

The results imply that the nirS community, rather than nirK, should be the first candidate for use as an indicator in the process of salt marsh restoration after grazing prohibition. Substances of concern, total nitrogen, and salinity were the key environmental factors affecting the abundance and community composition of nirS and nirK denitrifiers. The findings of this study provide novel insights into the influence of the length of grazing prohibition and elevation on nirS- and nirK-type denitrifying bacterial community composition in salt marshes.
Cognitive training based on functional near-infrared spectroscopy neurofeedback for the elderly with mild cognitive impairment: a preliminary study
Authors: Lee Ilju , Kim Dohyun , Kim Sehwan , Kim Hee Jung , Chung Un Sun , Lee Jung Jae
Published: July 2023

Introduction

Mild cognitive impairment (MCI) is often described as an intermediate stage of the normal cognitive decline associated with aging and dementia. There is a growing interest in various non-pharmacological interventions for MCI to delay the onset and inhibit the progressive deterioration of daily life functions. Previous studies suggest that cognitive training (CT) contributes to the restoration of working memory and that the brain-computer-interface technique can be applied to elicit a more effective treatment response. However, these techniques have certain limitations. Thus, in this preliminary study, we applied the neurofeedback paradigm during CT to increase the working memory function of patients with MCI.

Methods

Near-infrared spectroscopy (NIRS) was used to provide neurofeedback by measuring the changes in oxygenated hemoglobin in the prefrontal cortex. Thirteen elderly MCI patients who received CT-neurofeedback sessions four times on the left dorsolateral prefrontal cortex (dlPFC) once a week were recruited as participants.

Results

Compared with pre-intervention, the activity of the targeted brain region increased when the participants first engaged in the training; after 4 weeks of training, oxygen saturation was significantly decreased in the left dlPFC. The participants demonstrated significantly improved working memory compared with pre-intervention and decreased activity significantly correlated with improved cognitive performance.

Conclusion

Our results suggest that the applications for evaluating brain-computer interfaces can aid in elucidation of the subjective mental workload that may create additional or decreased task workloads due to CT.