bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscle-driven forward dynamic active hybrid model of the lumbosacral spine: combined FEM and multibody simulation
Authors: Remus Robin , Selkmann Sascha , Lipphaus Andreas , Neumann Marc , Bender Beate
Published: September 2023

Most spine models belong to either the musculoskeletal multibody (MB) or finite element (FE) method. Recently, coupling of MB and FE models has increasingly been used to combine advantages of both methods. Active hybrid FE-MB models, still rarely used in spine research, avoid the interface and convergence problems associated with model coupling. They provide the inherent ability to account for the full interplay of passive and active mechanisms for spinal stability. In this paper, we developed and validated a novel muscle-driven forward dynamic active hybrid FE-MB model of the lumbosacral spine (LSS) in ArtiSynth to simultaneously calculate muscle activation patterns, vertebral movements, and internal mechanical loads. The model consisted of the rigid vertebrae L1-S1 interconnected with hyperelastic fiber-reinforced FE intervertebral discs, ligaments, facet joints, and force actuators representing the muscles. Morphological muscle data were implemented via a semi-automated registration procedure. Four auxiliary bodies were utilized to describe non-linear muscle paths by wrapping and attaching the anterior abdominal muscles. This included an abdominal plate whose kinematics was optimized using motion capture data from upper body movements. Intra-abdominal pressure was calculated from the forces of the abdominal muscles compressing the abdominal cavity. For the muscle-driven approach, forward dynamics assisted data tracking was used to predict muscle activation patterns that generate spinal postures and balance the spine without prescribing accurate spinal kinematics. During calibration, the maximum specific muscle tension and spinal rhythms resulting from the model dynamics were evaluated. To validate the model, load cases were simulated from −10° extension to +30° flexion with weights up to 20 kg in both hands. The biomechanical model responses were compared with in vivo literature data of intradiscal pressures, intra-abdominal pressures, and muscle activities. The results demonstrated high agreement with this data and highlight the advantages of active hybrid modeling for the LSS. Overall, this new self-contained tool provides a robust and efficient estimation of LSS biomechanical responses under in vivo similar loads, for example, to improve pain treatment by spinal stabilization therapies.
Overview of strategies to improve the antibacterial property of dental implants
Authors: Zhai Shaobo , Tian Ye , Shi Xiaolu , Liu Yang , You Jiaqian , Yang Zheng , Wu Yuchuan , Chu Shunli
Published: September 2023

The increasing number of peri-implant diseases and the unsatisfactory results of conventional treatment are causing great concern to patients and medical staff. The effective removal of plaque which is one of the key causes of peri-implant disease from the surface of implants has become one of the main problems to be solved urgently in the field of peri-implant disease prevention and treatment. In recent years, with the advancement of materials science and pharmacology, a lot of research has been conducted to enhance the implant antimicrobial properties, including the addition of antimicrobial coatings on the implant surface, the adjustment of implant surface topography, and the development of new implant materials, and significant progress has been made in various aspects. Antimicrobial materials have shown promising applications in the prevention of peri-implant diseases, but meanwhile, there are some shortcomings, which leads to the lack of clinical widespread use of antimicrobial materials. This paper summarizes the research on antimicrobial materials applied to implants in recent years and presents an outlook on the future development.
Pseudo-nullclines enable the analysis and prediction of signaling model dynamics
Authors: Marrone Juan Ignacio , Sepulchre Jacques-Alexandre , Ventura Alejandra C.
Published: September 2023

A powerful method to qualitatively analyze a 2D system is the use of nullclines, curves which separate regions of the plane where the sign of the time derivatives is constant, with their intersections corresponding to steady states. As a quick way to sketch the phase portrait of the system, they can be sufficient to understand the qualitative dynamics at play without integrating the differential equations. While it cannot be extended straightforwardly for dimensions higher than 2, sometimes the phase portrait can still be projected onto a 2-dimensional subspace, with some curves becoming pseudo-nullclines. In this work, we study cell signaling models of dimension higher than 2 with behaviors such as oscillations and bistability. Pseudo-nullclines are defined and used to qualitatively analyze the dynamics involved. Our method applies when a system can be decomposed into 2 modules, mutually coupled through 2 scalar variables. At the same time, it helps track bifurcations in a quick and efficient manner, key for understanding the different behaviors. Our results are both consistent with the expected dynamics, and also lead to new responses like excitability. Further work could test the method for other regions of parameter space and determine how to extend it to three-module systems.
Cervical aortic arch in the pediatric population: a meta-analysis of individual patient's data
Authors: Baudo Massimo , Varrica Alessandro , Reali Matteo , Saracino Antonio , Carminati Mario , Frigiola Alessandro , Giamberti Alessandro , Lo Rito Mauro
Published: September 2023

Background

This is the first meta-analysis to analyze all reports of published pediatric cases of cervical aortic arch (CAA) by highlighting the clinical characteristics and treatment outcomes using the reported individual data of the patients. The aim of the study is to investigate the clinical features and surgical outcomes of such a rare disease in the pediatric population.

Methods

A comprehensive search was conducted in various academic databases, including PubMed, ScienceDirect, SciELO, DOAJ, and Cochrane Library, until June 2022 for case reports describing the presence of cervical aortic arch in the pediatric age. Case reports and series were included if the following criteria were met: (1) description of the cervical aortic arch; (2) patient of pediatric age; and (3) published in the English language. All other types of publications that lacked patient-specific information were excluded from the analysis. This systematic review was conducted in accordance with the PRISMA guidelines. The primary outcome measure of the analysis was early and late mortality.

Results

The literature search identified 2,272 potentially eligible articles, 72 of which met our inclusion criteria with 96 patients including the author's institutional case. At a median of 365 (90–730) days, the overall cohort registered a 7.3% (7/96) mortality rate. In the subset of patients who underwent surgery, the mortality rate was also 7.3% (4/55), and the mortality rate following surgery to treat only CAA was 2.4% (1/42). Dyspnea was identified as an independent determinant of mortality by employing the univariable Firth bias-reduced logistic regression method.

Conclusion

Cervical aortic arch is a rare congenital heart disease that poses treatment challenges due to the high anatomical variability, diverse clinical presentations, and the presence of other concomitant diseases. The surgical treatment appears to be a safe and effective approach for resolving the symptoms, although it needs to be tailored individually for each patient.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=346826, Identifier: CRD42022346826.
Female youth and mental health service providers' perspectives on the JoyPop™ app: a qualitative study
Authors: Malik Ishaq , Perez Arnaldo , Toombs Elaine , Schmidt Fred , Olthuis Janine V. , Charlton Jaidyn , Grassia Elizabeth , Squier Crystal , Stasiuk Kristine , Bobinski Tina , Mushquash Aislin R.
Published: September 2023

Introduction

Mobile health (mHealth) apps are a promising adjunct to traditional mental health services, especially in underserviced areas. Developed to foster resilience in youth, the JoyPop™ app has a growing evidence base showing improvement in emotion regulation and mental health symptoms among youth. However, whether this novel technology will be accepted among those using or providing mental health services remains unknown. This study aimed to evaluate the JoyPop™ app's acceptance among (a) a clinical sample of youth and (b) mental health service providers.

Method

A qualitative descriptive approach involving one-on-one semi-structured interviews was conducted. Interviews were guided by the Technology Acceptance Model and were analyzed using a deductive-inductive content analysis approach.

Results

All youth (n = 6 females;Mage = 14.60, range 12–17) found the app easy to learn and use and expressed positive feelings towards using the app. Youth found the app useful because it facilitated accessibility to helpful coping skills (e.g., journaling to express their emotions; breathing exercises to increase calmness) and positive mental health outcomes (e.g., increased relaxation and reduced stress). All service providers (n = 7 females;Mage = 43.75, range 32–60) perceived the app to be useful and easy to use by youth within their services and expressed positive feelings about integrating the app into usual care. Service providers also highlighted various organizational factors affecting the app's acceptance. Youth and service providers raised some concerns about apps in general and provided recommendations to improve the JoyPop™ app.

Discussion

Results support youth and service providers' acceptance of the JoyPop™ app and lend support for it as an adjunctive resource to traditional mental health services for youth with emotion regulation difficulties.
Developing machine learning systems worthy of trust for infection science: a requirement for future implementation into clinical practice
Authors: McFadden Benjamin R. , Reynolds Mark , Inglis Timothy J. J.
Published: September 2023

Infection science is a discipline of healthcare which includes clinical microbiology, public health microbiology, mechanisms of microbial disease, and antimicrobial countermeasures. The importance of infection science has become more apparent in recent years during the SARS-CoV-2 (COVID-19) pandemic and subsequent highlighting of critical operational domains within infection science including the hospital, clinical laboratory, and public health environments to prevent, manage, and treat infectious diseases. However, as the global community transitions beyond the pandemic, the importance of infection science remains, with emerging infectious diseases, bloodstream infections, sepsis, and antimicrobial resistance becoming increasingly significant contributions to the burden of global disease. Machine learning (ML) is frequently applied in healthcare and medical domains, with growing interest in the application of ML techniques to problems in infection science. This has the potential to address several key aspects including improving patient outcomes, optimising workflows in the clinical laboratory, and supporting the management of public health. However, despite promising results, the implementation of ML into clinical practice and workflows is limited. Enabling the migration of ML models from the research to real world environment requires the development of trustworthy ML systems that support the requirements of users, stakeholders, and regulatory agencies. This paper will provide readers with a brief introduction to infection science, outline the principles of trustworthy ML systems, provide examples of the application of these principles in infection science, and propose future directions for moving towards the development of trustworthy ML systems in infection science.
Trajectories of academic performance over time: differences by social determinants of health and the COVID-19 pandemic
Authors: Gresham Bria , Corcoran Frederique , Karatekin Canan
Published: September 2023

Introduction

We examined (1) differences in academic performance by structural and intermediary determinants of health, (2) associations between duration of college enrollment during the first year of the Coronavirus disease 2019 (COVID-19) pandemic, and (3) their two-way interactions on academic performance using data from two cohorts of freshmen undergraduate students.

Methods

Participants reported their demographic information, and their structural and intermediary determinants. The university reported academic performance at each semester. Mixed effects models tested repeated measures outcomes (i.e., grade point average (GPA) and courses where the grade received was D, F, Not passing, or Withdrawn (DFNW courses) and generalized linear models tested likelihood of graduation.

Results

More unfavorable structural and intermediary determinants were associated with an increased likelihood of receiving a DFNW grade (b = 0.33 and b = 0.40, p’s < 0.05, respectively). Greater unfavorable intermediary determinants were associated with a lower GPA (b = –0.07, p = 0.159). There were significant interactions between intermediary determinants of health and enrollment duration during COVID-19 for the likelihood of DFNW grades (b = –0.89, p = 0.008) and graduation (b = 1.31, p = 0.025), such that Cohort 1 fared worse than Cohort 2.

Discussion

The findings indicate that for those with more unfavorable intermediary determinants, there may have been an initial “shock” of the pandemic that stabilized over time.
Beyond the usual suspects: using cross-sectoral partnerships to target and engage new citizen scientists
Authors: Iwanycki Ahlstrand Natalie , Tøttrup Anders P.
Published: September 2023

Citizen science offers enormous benefits to enhance public knowledge and understanding of science. Several opportunities to engage and share information with citizens are possible in citizen science projects. Recent evidence demonstrates however that individuals who participate in citizen science projects are demographically speaking not very diverse. For citizen science projects to successfully achieve their full potential in increasing public awareness and understanding of science, a wider social demographic needs to be engaged. We present a nationwide approach developed to achieve just that with respect to targeting and engaging residents in Denmark that did not previously have a prior connection to or interest in nature. Under the auspices of a campaign entitled Our Nature, our approach included the formation of a new, cross-sectoral partnership, and co-creating and implementing of a wide array of communication tactics and nature-based activities, including the development of a new citizen science project. Our cross-sectoral partnership allowed us to broaden the sectors of society that could be reached and develop cross-disciplinary activities to achieve goals for broad engagement. Extensive third-party evaluation revealed that 70% of the Danes interviewed across the country heard about Our Nature, and 70% of these gained more knowledge about Danish nature through the campaign. In addition to presenting our co-created projects and activities by working cross-sectorally and interdisciplinarily, we discuss the successes, challenges and limitations related to reaching our goal, based on evaluation results and our own experiences in citizen science and science communication. The citizen science project Denmark Explores that emerged from this campaign is used as a case study to demonstrate how our approach facilitated the broad engagement of citizens across the country––beyond the usual nature enthusiasts.
Evaluation and driving factors of ecological integrity in the Alxa League from 1990 to 2020
Authors: Sun Haoyu , Cao Weijia , Liu Huan , Zhang Xuefeng , Wang Lixin , Wen Lu
Published: September 2023

Ecological integrity can satisfactorily reflect the comprehensive quality of ecosystems and has become a useful tool for evaluating the ecological environment. Ecological integrity evaluation has been widely applied in various ecosystems. Conducted in the Alxa League, the study established an ecological integrity index based on ecosystem structure, function and resilience and evaluated the ecological integrity of the study area in 1990, 2000, 2010 and 2020. Using hotspots spatial analyses, we analyzed the temporal and spatial variation of ecological integrity index during the study period. The main contributing factors affecting ecological integrity were identified with the help of the geographical detector model. Our results showed that: (1) Ecosystem structure, function and resilience in the Alxa League had obvious spatial heterogeneity and barely changed from 1990 to 2020. (2) Half of the area had a poor ecological integrity index, and the decrease in ecological integrity mainly occurred in the Alxa Left Banner. (3) Among the factors affecting the ecological integrity index, land use intensity was the major driving factor, and desertification was a key reason leading to the decrease. Ecological integrity evaluation can increase public awareness of desert conditions and guide policy makers to make reasonable and sustainable policies or strategies to protect and restore desert ecosystems.
Random amplified microsatellites (RAMS) analysis ascertains genetic variation of Alternaria alternata causing black spot disease on Carya illinoinensis in South Africa
Authors: Achilonu Conrad Chibunna , Gryzenhout Marieka , Marais Gert Johannes , Madisha M. Thabang , Ghosh Soumya
Published: September 2023

Limited information regarding the occurrence of black spot disease of pecan (Carya illinoinensis), caused by A. alternata, in South Africa is known. The pecan industry is growing rapidly, so it is essential to understand the impact of the fungal pathogen to pecan health. In this study, the genetic variation of 364 A. alternata isolates was investigated by two RAMS primers (CCA5 and CGA5). In total, 6,525 alleles were produced, with a minimum of 3,182 alleles on the CGA5 primer and maximum of 3,343 alleles for CCA5 primer. Further analysis of the primers showed relatively low genetic diversity of A. alternata isolate populations, with mean values; (H = 0.12) and Shannon’s information index (I = 0.20). The analysis of molecular variance (AMOVA) revealed significant differences between populations, with 88% of the genetic variation was found within populations (Nm = 3.59, PhiPT = 0.12), and were not significantly different (p > 0.001). While 12% variation was observed among populations (Nm = 2.89, PhiPT = 0.08) and the estimates were statistically significant (p < 0.001). STRUCTURE HARVESTER output showed that K value is K = 8, where ΔK cannot find the true number of populations because of less variation. The dendrogram cluster tree generated by Ward’s analysis unveiled two main distinct clades and 10 sub-clades, revealing similar findings as those of PCoA analysis clusters. Therefore, it was evident that these analyses depicted no distinct relationship between the A. alternata isolates and their geographic locations or the prevalence of distribution among the populations.
Altered plasma metabolites and inflammatory networks in HIV-1 infected patients with different immunological responses after long-term antiretroviral therapy
Authors: Lu Lianfeng , Yang Yang , Yang Zhangong , Wu Yuanni , Liu Xiaosheng , Li Xiaodi , Chen Ling , Han Yang , Song Xiaojing , Kong Ziqing , Cao Wei , Li Taisheng
Published: September 2023

Background

Chronic metabolic changes relevant to human immunodeficiency virus type 1 (HIV-1) infection and in response to antiretroviral therapy (ART) remain undetermined. Moreover, links between metabolic dysfunction caused by HIV and immunological inflammation in long-term treated individuals have been poorly studied.

Methods

Untargeted metabolomics and inflammatory cytokine levels were assessed in 47 HIV-infected individuals including 22 immunological responders (IRs) and 25 non-responders (INRs) before and after ART. The IRs and INRs were matched by age, gender, baseline viral load, and baseline CD4+T cell counts. Another 25 age-matched uninfected healthy individuals were also included as controls.

Results

Among the 770 plasma compounds detected in the current study, significant changes were identified in lipids, nucleotides, and biogenic amino acids between HIV-infected patients and healthy controls. Principal Component Analysis (PCA) and the Random Forest (RF) model suggested that levels of selected metabolites could differentiate HIV-infected patients clearly from healthy controls. However, the metabolite profiles identified in our patients were similar, and only three metabolites, maltotetraose, N, N-dimethyl-5-aminovalerate, and decadienedioic acid (C10:2-DC), were different between IRs and INRs following long-term ART. The pathway enrichment analysis results revealed that disturbances in pyrimidine metabolism, sphingolipid metabolism, and purine metabolism after HIV infection and these changes did not recover to normal levels in healthy controls even with suppressive ART. Correlation analysis of the metabolism-immune network indicated that interleukin (IL)-10, D-dimer, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and TNF-RII were positively correlated with most of the significantly changed lipid and amino acid metabolites but negatively correlated with metabolites in nucleotide metabolism.

Conclusions

Significant changes in many metabolites were observed in HIV-infected individuals before and after ART regardless of their immunological recovery status. The disturbed metabolic profiles of lipids and nucleotides in HIV infection did not recover to normal levels even after long-term ART. These changes are correlated with modified cytokines and biomarkers of chronic non-AIDS events, warranting tryout of interventions other than ART.
Neutrophil extracellular traps and long COVID
Authors: Shafqat Areez , Omer Mohamed H. , Albalkhi Ibrahem , Alabdul Razzak Ghazi , Abdulkader Humzah , Abdul Rab Saleha , Sabbah Belal Nedal , Alkattan Khaled , Yaqinuddin Ahmed
Published: September 2023

Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by a significant number of COVID-19 survivors. The underlying pathophysiology of long COVID has become a topic of intense research discussion. While chronic inflammation in long COVID has received considerable attention, the role of neutrophils, which are the most abundant of all immune cells and primary responders to inflammation, has been unfortunately overlooked, perhaps due to their short lifespan. In this review, we discuss the emerging role of neutrophil extracellular traps (NETs) in the persistent inflammatory response observed in long COVID patients. We present early evidence linking the persistence of NETs to pulmonary fibrosis, cardiovascular abnormalities, and neurological dysfunction in long COVID. Several uncertainties require investigation in future studies. These include the mechanisms by which SARS-CoV-2 brings about sustained neutrophil activation phenotypes after infection resolution; whether the heterogeneity of neutrophils seen in acute SARS-CoV-2 infection persists into the chronic phase; whether the presence of autoantibodies in long COVID can induce NETs and protect them from degradation; whether NETs exert differential, organ-specific effects; specifically which NET components contribute to organ-specific pathologies, such as pulmonary fibrosis; and whether senescent cells can drive NET formation through their pro-inflammatory secretome in long COVID. Answering these questions may pave the way for the development of clinically applicable strategies targeting NETs, providing relief for this emerging health crisis.
Preclinical data do not support the use of amiodarone or dronedarone as antiparasitic drugs for Chagas disease at the approved human dosing regimen
Authors: Francisco Amanda F. , Chen Gong , Wang Wen , Sykes Melissa L. , Escudié Fanny , Scandale Ivan , Olmo Francisco , Shackleford David M. , Zulfiqar Bilal , Kratz Jadel M. , Pham Thao , Saunders Jessica , Hu Meiyu , Avery Vicky M. , Charman Susan A. , Kelly John M. , Chatelain Eric
Published: September 2023

The repurposing of approved drugs is an appealing method to fast-track the development of novel therapies for neglected diseases. Amiodarone and dronedarone, two approved antiarrhythmic agents, have been reported to have potential for the management of Chagas disease patients displaying symptomatic heart pathology. More recently, it has been suggested that both molecules not only have an antiarrhythmic effect, but also have trypanocidal activity against Trypanosoma cruzi, the causative agent of Chagas disease. In this work, we assessed the in vitro activity of these compounds against T. cruzi, the in vivo pharmacokinetics, and pharmacodynamics, to determine the potential for repurposing these drugs as therapies for Chagas disease. Based on these results, we were unable to reproduce the in vitro potencies of amiodarone and dronedarone described in the literature, and both drugs were found to be inactive or cytotoxic against a variety of different mammalian cell lines. The evaluation of in vivo efficacy in a bioluminescent murine model of T. cruzi did not show antiparasitic activity at the highest tolerated dose tested. While the potential of amiodarone and dronedarone as antiarrhythmic agents in Chagas cardiomyopathic patients cannot be completely excluded, a trypanocidal effect in patients treated with these two drugs appears unlikely.
Microplastics ingestion by marine fauna with a particular focus on commercial species: a systematic review
Authors: Marmara Dimitra , Katsanevakis Stelios , Brundo Maria-Violetta , Tiralongo Francesco , Ignoto Sara , Krasakopoulou Evangelia
Published: September 2023

Over the past few decades, the scientific community has extensively investigated microplastics (MPs) and their interactions with marine organisms. MPs ingestion has been one of the most commonly examined topics across marine fauna. In this study, we present a systematic review conducted to gather information on the MPs ingestion by different taxonomic groups, collect MPs abundances and characteristics, and explore the relative literature evolution. Additionally, through meta-analysis, we focused on marine commercial species, aiming to estimate the mean MPs ingestion quantities in Pisces, Mollusca, Crustacea, and Echinodermata. A total of at least 822 marine species were reported to have ingested MPs for the period of 1972–2021. Pisces (class: Teleostei) was the most frequently examined group including 513 species reported to have ingested at least one MP and exhibited the widest range of mean MPs ingestion quantities [0.07–16.33 MPs per individual (MPs/ind) GIT] among the different families. The studies that analyzed soft tissue focused mainly on Gastropoda, Bivalvia, Malacostraca, and Echinodermata (8.85 MPs/ind, 3.64 MPs/ind, and 1.03 MPs/ind, 1.56 MP/g respectively). In total, MPs’ most frequently found characteristics were fibers, measuring less than 1 mm, black in color, and composed of polyethylene. The wide range of MPs descriptions concerning their characteristics and the notable high heterogeneity of the estimated values of MPs ingestion among and within most families highlights the importance of adopting harmonized methodological protocols to more effectively address the MPs issue.
Matrices for radioactive waste immobilization: a review
Authors: Pilania Ritu Kumari , Dube Charu Lata
Published: September 2023

Nuclear energy is considered a clean, reliable, and an inexhaustible energy source for power generation. Nuclear power is harnessed from nuclear fission reactions in a dedicated power plant. The by-products (produced in the nuclear power plant) are radioactive and pose a threat to the environment. The safe disposal of nuclear waste is vital to ensure the sustainable use of the nuclear energy. The immobilization of radioactive waste before final disposal is essential for the interim storage and transportation. This review summarizes the recent work on glass, ceramics, and glass–ceramics matrices to immobilize high-level waste. The synthesis methods, leaching behavior, and radiation resistance of matrices are discussed briefly.
RETRACTED: Application of periodic structural wave impeding block for vibration isolation in foundation
Authors: Ling Yongqiang , Zhu Xiaoli , Song Lei
Published: September 2023

The wave impeding board (WIB) is frequently integrated beneath dynamic machinery, tracks, and subgrades to counteract vibrations emanating from artificial sources. However, conventional WIBs have exhibited a limited isolation frequency band due to their dependence on the soil cut-off frequency of soil. Furthermore, the vibration sources typically encompass intricate frequency components spanning low, medium, and high frequencies. To overcome the technical limitations of WIBs relying on the cut-off frequency of soil, a new periodic structural wave impeding board (PSWIB) is proposed based on the principles of phononic crystals. Theoretical and numerical analyses demonstrate that PSWIB exhibits bandgap characteristics, with the attenuation range achieved by finite periodic structures aligning with the bandgap of an infinite PSWIB. Maximum amplitude reductions of 47 dB and 65 dB are achieved within the vibration attenuation range. Compared to traditional WIB, PSWIB surpasses the constraints imposed by the cut-off frequency of soil and allow for the design of constituent parameters based on the characteristics of the vibration source, enabling effective isolation of the target frequency vibrations.
Validation of the ICEBERG emergency room screening tool for early identification of older patients with geriatric consultation needs
Authors: Bischoff-Ferrari Heike A. , Gagesch Michael , Tsai Dai-Hua , Richter Clara , Lanz Patricia , Sidler Patrick , Can Uenal , Keller Dagmar I. , Minder Markus , von Rickenbach Bettina , Yildirim-Aman Ali , Geiling Katharina , Freystaetter Gregor
Published: September 2023

Background

The growing number of older and oldest-old patients often present in the emergency room (ER) with undiagnosed geriatric syndromes posing them at high risk for complications in acute care.

Objective

To develop and validate an ER screening tool (ICEBERG) to capture 9 geriatric domains of risk in older patients.

Design, setting, and participants

For construct validity we performed a chart-based study in 129 ER patients age 70 years and older admitted to acute geriatric care (pilot 1). For criterion validity we performed a prospective study in 288 ER patients age 70 years and older admitted to acute care (pilot 2).

Exposure

In both validation steps, the exposure was ICEBERG test performance below and above the median score (10, range 0–30).

Outcome measures and analysis

In pilot 1, we compared the exposure with results of nine tests of the Comprehensive Geriatric Assessment (CGA). In pilot 2, we compared the exposure assessed in the ER to following length of hospital stay (LOS), one-on-one nursing care needs, in-hospital mortality, 30-day re-admission rate, and discharge to a nursing home.

Main results

Mean age was 82.9 years (SD 6.7; n = 129) in pilot 1, and 81.5 years (SD 7.0; n = 288) in pilot 2. In pilot 1, scoring ≥10 was associated with significantly worse performance in 8 of 9 of the individual CGA tests. In pilot 2, scoring ≥10 resulted in longer average LOS (median 7 days, IQR 4, 11 vs. 6 days, IQR 3, 8) and higher nursing care needs (median 1,838 min, IQR 901, 4,267 vs. median 1,393 min, IQR 743, 2,390). Scoring ≥10 also increased the odds of one-on-one nursing care 2.9-fold (OR 2.86, 95%CI 1.17–6.98), and the odds of discharge to a nursing home 3.7-fold (OR 3.70, 95%CI 1.74–7.85). Further, scoring ≥10 was associated with higher in-hospital mortality and re-hospitalization rates, however not reaching statistical significance. Average time to complete the ICEBERG tool was 4.3 min (SD 1.3).

Conclusion

Our validation studies support construct validity of the ICEBERG tool with the CGA, and criterion validity with several clinical indicators in acute care.
Regulating the regulatory T cells as cell therapies in autoimmunity and cancer
Authors: Hosseinalizadeh Hamed , Rabiee Fatemeh , Eghbalifard Negar , Rajabi Hamid , Klionsky Daniel J. , Rezaee Aryan
Published: September 2023

Regulatory T cells (Tregs), possess a pivotal function in the maintenance of immune homeostasis. The dysregulated activity of Tregs has been associated with the onset of autoimmune diseases and cancer. Hence, Tregs are promising targets for interventions aimed at steering the immune response toward the desired path, either by augmenting the immune system to eliminate infected and cancerous cells or by dampening it to curtail the damage to self-tissues in autoimmune disorders. The activation of Tregs has been observed to have a potent immunosuppressive effect against T cells that respond to self-antigens, thus safeguarding our body against autoimmunity. Therefore, promoting Treg cell stability presents a promising strategy for preventing or managing chronic inflammation that results from various autoimmune diseases. On the other hand, Tregs have been found to be overactivated in several forms of cancer, and their role as immune response regulators with immunosuppressive properties poses a significant impediment to the successful implementation of cancer immunotherapy. However, the targeting of Tregs in a systemic manner may lead to the onset of severe inflammation and autoimmune toxicity. It is imperative to develop more selective methods for targeting the function of Tregs in tumors. In this review, our objective is to elucidate the function of Tregs in tumors and autoimmunity while also delving into numerous therapeutic strategies for reprogramming their function. Our focus is on reprogramming Tregs in a highly activated phenotype driven by the activation of key surface receptors and metabolic reprogramming. Furthermore, we examine Treg-based therapies in autoimmunity, with a specific emphasis on Chimeric Antigen Receptor (CAR)-Treg therapy and T-cell receptor (TCR)-Treg therapy. Finally, we discuss key challenges and the future steps in reprogramming Tregs that could lead to the development of novel and effective cancer immunotherapies.
Soil nutrient management influences diversity, community association and functional structure of rhizosphere bacteriome under vegetable crop production
Authors: Raimi Adekunle R. , Ezeokoli Obinna T. , Adeleke Rasheed A.
Published: September 2023

Introduction

Rhizosphere bacterial communities play a crucial role in promoting plant and soil ecosystem health and productivity. They also have great potential as key indicators of soil health in agroecosystems. Various environmental factors affect soil parameters, which have been demonstrated to influence soil microbial growth and activities. Thus, this study investigated how rhizosphere bacterial community structure and functions are affected by agronomic practices such as organic and conventional fertiliser application and plant species types.

Methods

Rhizosphere soil of vegetable crops cultivated under organic and conventional fertilisers in different farms was analysed using high-throughput sequencing of the 16S rRNA gene and co-occurrence network pattern among bacterial species. The functional structure was analysed with PICRUSt2 pipeline.

Results

Overall, rhizosphere bacterial communities varied in response to fertiliser type, with soil physicochemical parameters, including NH4, PO4, pH and moisture content largely driving the variations across the farms. Organic farms had a higher diversity richness and more unique amplicon sequence variants than conventional farms. Bacterial community structure in multivariate space was highly differentiated across the farms and between organic and conventional farms. Co-occurrence network patterns showed community segmentation for both farms, with keystone taxa more prevalent in organic than conventional farms.

Discussion

Module hub composition and identity varied, signifying differences in keystone taxa across the farms and positive correlations between changes in microbial composition and ecosystem functions. The organic farms comprised functionally versatile communities characterised by plant growth-promoting keystone genera, such as Agromyces, Bacillus and Nocardioides. The results revealed that organic fertilisers support high functional diversity and stronger interactions within the rhizosphere bacterial community. This study provided useful information about the overall changes in soil microbial dynamics and how the changes influence ecosystem functioning under different soil nutrient management and agronomic practices.
Role of Caveolae family-related proteins in the development of breast cancer
Authors: Han Qinyu , Qiu Shi , Hu Huiwen , Li Wenjing , Li Xiangqi
Published: September 2023

Breast cancer has become the most significant malignant tumor threatening women’s lives. Caveolae are concave pits formed by invagination of the plasma membrane that participate in many biological functions of the cell membrane, such as endocytosis, cell membrane assembly, and signal transduction. In recent years, Caveolae family-related proteins have been found to be closely related to the occurrence and development of breast cancer. The proteins associated with the Caveolae family-related include Caveolin (Cav) and Cavins. The Cav proteins include Cav-1, Cav-2 and Cav-3, among which Cav-1 has attracted the most attention as a tumor suppressor and promoting factor affecting the proliferation, apoptosis, migration, invasion and metastasis of breast cancer cells. Cav-2 also has dual functions of inhibiting and promoting cancer and can be expressed in combination with Cav-1 or play a regulatory role alone. Cav-3 has been less studied in breast cancer, and the loss of its expression can form an antitumor microenvironment. Cavins include Cavin-1, Cavin-2, Cavin-3 and Cavin-4. Cavin-1 inhibits Cav-1-induced cell membrane tubule formation, and its specific role in breast cancer remains controversial. Cavin-2 acts as a breast cancer suppressor, inhibiting breast cancer progression by blocking the transforming growth factor (TGF-β) signaling pathway. Cavin-3 plays an anticancer role in breast cancer, but its specific mechanism of action is still unclear. The relationship between Cavin-4 and breast cancer is unclear. In this paper, the role of Caveolae family-related proteins in the occurrence and development of breast cancer and their related mechanisms are discussed in detail to provide evidence supporting the further study of Caveolae family-related proteins as potential targets for the diagnosis and treatment of breast cancer.
LC-MS/MS assisted biomonitoring of ropivacaine and 3-OH-ropivacaine after plane block anesthesia for cardiac device implantation
Authors: Butiulca Mihaela , Farczadi Lenard , Vari Camil Eugen , Imre Silvia , Pui Mihai , Lazar Alexandra
Published: September 2023

Introduction: Ropivacaine is a popular local anesthetic used for regional anesthesia or for pain management. Although designed as an enantiomerically pure drug, an aspect that reduces the adverse effects, its toxicological effects are still a risk. As such, biomonitoring to assure appropriate dosage and bioavailability are essential to avoid complications during or post-surgery.

Methods: The study focused on developing a sensitive, selective, and accurate liquid chromatography—mass spectrometry (LCMS/MS) method which facilitates the biomonitoring of ropivacaine and its main metabolite in plasma after regional anesthesia using ropivacaine.

Results and Discussion: The method was validated with regards to all relevant parameters, such as sensitivity, selectivity, accuracy, precision, and the effect of sample matrix. The method was successfully used in a pilot study, which included one patient undergoing plane block anesthesia for cardiac device implantation. The results showed the method is appropriate for its intended purpose and could even be used in other, similar applications.
Being friendly: paced mating for the study of physiological, behavioral, and neuroplastic changes induced by sexual behavior in females
Authors: Ventura-Aquino Elisa , Paredes Raúl G.
Published: September 2023

Paced mating in rats is an experimental condition that allows the evaluation of sexual behavior in a way that closely resembles what occurs in seminatural and natural conditions enabling the female to control the rate of the sexual interaction. In conventional non-paced mating tests, females cannot escape from male approaches, which may lead to an unrewarding overstimulation. Paced mating is an alternative laboratory procedure that improves animal welfare and has a higher ethological relevance. The use of this procedure contributed to the identification of physiological and behavioral factors that favor reproduction. Paced mating includes motivational and behavioral components differentiating quantitative and qualitative characteristics that are critical for the induction of the rewarding properties of mating. These positive consequences ensure that the behavior will be repeated, favoring the species’ survival. Sexual reward is an immediate consequence of paced mating, mediated mainly by the endogenous opioid system. Paced mating also induces long-lasting neuroplastic changes, including gene expression, synthesis of proteins, and neurogenesis in sex-relevant brain areas. The interest in paced mating is growing since the complexity of its elements and consequences at different levels in a laboratory setting resembles what occurs in natural conditions. In this review, we analyze the classic studies and recent publications demonstrating the advantages of using paced mating to evaluate different aspects of sexual behavior in females.
Orally administered boldine reduces muscle atrophy and promotes neuromuscular recovery in a rodent model of delayed nerve repair
Authors: Burrell Justin C. , Vu Phuong T. , Alcott Owen J. B. , Toro Carlos A. , Cardozo Christopher , Cullen D. Kacy
Published: September 2023

Peripheral nerve injury often results in poor functional recovery due to a prolonged period of muscle denervation. In particular, absent axonal contact, denervated muscle can undergo irrevocable atrophy and diminished receptiveness for reinnervation over time, ultimately reducing the likelihood for meaningful neuromuscular recovery. While innovative surgical approaches can minimize the harmful effects of denervation by re-routing neighboring—otherwise uninjured—axons, there are no clinically-available approaches to preserve the reinnervation capacity of denervated muscles. Blocking intramuscular connexin hemichannel formation has been reported to improve muscle innervation in vitro and prevent atrophy in vivo. Therefore, the current study investigated the effects of orally administered boldine, a connexin hemichannel inhibitor, on denervated-related muscle changes and nerve regeneration in a rat model of delayed peripheral nerve repair. We found that daily boldine administration significantly enhanced an evoked response in the tibialis anterior muscle at 2 weeks after common peroneal nerve transection, and decreased intramuscular connexin 43 and 45 expression, intraneural Schwann cell expression of connexin 43, and muscle fiber atrophy up to 4 weeks post transection. Additional animals underwent a cross nerve repair procedure (tibial to common peroneal neurorrhaphy) at 4 weeks following the initial transection injury. Here, we found elevated nerve electrophysiological activity and greater muscle fiber maturation at 6 weeks post repair in boldine treated animals. These findings suggest that boldine may be a promising pharmacological approach to minimize the deleterious effects of prolonged denervation and, with further optimization, may improve levels of functional recovery following nerve repair.
Identification of immune-related biomarkers in peripheral blood of schizophrenia using bioinformatic methods and machine learning algorithms
Authors: Zhu Xiaoli , Wang Chuan-lan , Yu Jian-feng , Weng Jianjun , Han Bing , Liu Yanqing , Tang Xiaowei , Pan Bo
Published: September 2023

Schizophrenia is a group of severe neurodevelopmental disorders. Identification of peripheral diagnostic biomarkers is an effective approach to improving diagnosis of schizophrenia. In this study, four datasets of schizophrenia patients’ blood or serum samples were downloaded from the GEO database and merged and de-batched for the analyses of differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WCGNA). The WGCNA analysis showed that the cyan module, among 9 modules, was significantly related to schizophrenia, which subsequently yielded 317 schizophrenia-related key genes by comparing with the DEGs. The enrichment analyses on these key genes indicated a strong correlation with immune-related processes. The CIBERSORT algorithm was adopted to analyze immune cell infiltration, which revealed differences in eosinophils, M0 macrophages, resting mast cells, and gamma delta T cells. Furthermore, by comparing with the immune genes obtained from online databases, 95 immune-related key genes for schizophrenia were screened out. Moreover, machine learning algorithms including Random Forest, LASSO, and SVM-RFE were used to further screen immune-related hub genes of schizophrenia. Finally, CLIC3 was found as an immune-related hub gene of schizophrenia by the three machine learning algorithms. A schizophrenia rat model was established to validate CLIC3 expression and found that CLIC3 levels were reduced in the model rat plasma and brains in a brain-regional dependent manner, but can be reversed by an antipsychotic drug risperidone. In conclusion, using various bioinformatic and biological methods, this study found an immune-related hub gene of schizophrenia – CLIC3 that might be a potential diagnostic biomarker and therapeutic target for schizophrenia.
Exploring the causes of augmentation in restless legs syndrome
Authors: Zeng Pengyu , Wang Tiantian , Zhang Lisan , Guo Fang
Published: September 2023

Long-term drug treatment for Restless Legs Syndrome (RLS) patients can frequently result in augmentation, which is the deterioration of symptoms with an increased drug dose. The cause of augmentation, especially derived from dopamine therapy, remains elusive. Here, we review recent research and clinical progress on the possible mechanism underlying RLS augmentation. Dysfunction of the dopamine system highly possibly plays a role in the development of RLS augmentation, as dopamine agonists improve desensitization of dopamine receptors, disturb receptor interactions within or outside the dopamine receptor family, and interfere with the natural regulation of dopamine synthesis and release in the neural system. Iron deficiency is also indicated to contribute to RLS augmentation, as low iron levels can affect the function of the dopamine system. Furthermore, genetic risk factors, such as variations in the BTBD9 and MEIS1 genes, have been linked to an increased risk of RLS initiation and augmentation. Additionally, circadian rhythm, which controls the sleep–wake cycle, may also contribute to the worsening of RLS symptoms and the development of augmentation. Recently, Vitamin D deficiency has been suggested to be involved in RLS augmentation. Based on these findings, we propose that the progressive reduction of selective receptors, influenced by various pathological factors, reverses the overcompensation of the dopamine intensity promoted by short-term, low-dose dopaminergic therapy in the development of augmentation. More research is needed to uncover a deeper understanding of the mechanisms underlying the RLS symptom and to develop effective RLS augmentation treatments.