bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety of 3-month flushing interval for prevention of occlusion in totally implantable venous access ports: An analysis focused on intraluminal clots
Authors: Yang Woo Jin , Song Myung Gyu , Seo Tae-Seok , Kang Danbee , Park Sung-Joon , Kwak Jung Won
Published: October 2024

Background:

This study aimed to assess the safety and feasibility of a 3-month flushing interval for totally implantable venous access ports (TIVAPs), particularly regarding intraluminal clot formation.

Methods:

Between May 2017 and September 2018, we established a single-center cohort of 151 patients who were referred for TIVAP removal and categorized them into three flushing-interval groups: A (⩽1 month), B (1–2 months), and C (2–3 months). Odds ratios (OR) with 95% confidence intervals (CI) were computed using logistic regression to determine the risk of intraluminal clot occurrence. To compare clot lengths among the groups, we employed linear regression. Restricted cubic splines were used to model the flushing interval as a continuous variable.

Results:

Compared to Group A, Groups B and C had adjusted ORs of 0.82 (0.35–1.92) and 0.78 (0.29–2.11) for intraluminal clot risk. Occlusion was rare (1/151; 0.7%) and successfully treated with mechanical recanalization. Adjusted differences in clot length compared to Group A were 0.01 (−0.85 to 0.87) for Group B and −0.23 (−1.21 to 0.76) for Group C. Spline regression analysis showed no significant association between the flushing interval and clot length ( p for trend = 0.84).

Conclusion:

The incidence and burden of intraluminal clots did not increase significantly within the first 3 months. Occlusion was rare, even in the presence of clots, and was successfully treated. Therefore, a 3-month flushing interval appears to be a safe and practical option, aligning with the common recommendation for surveillance intervals in patients with cancer.
Prolegomena to a genealogy of “society”
Authors: Schmidt Volker H.
Published: October 2024

The article reconstructs the evolution of the semantics of one of the social sciences’ most important concepts, that of society. It follows two main systematizations, those of the societas and the societas civilis, respectively, through a millennia-long history rooted in Graeco-Roman civilization. This history exhibits remarkable continuity across time. Its modern adaptations survive to the present day. But the social sciences appear to know only the latter which, in the form of the nation-state, they adopted as their default model under the intellectual leadership of Parsons. Recent developments in the social world have rendered that model obsolete. This leaves the social sciences in dire straits, as they have failed, with one exception, to develop a persuasive alternative. The exception is Niklas Luhmann's systems theory of world society, a theory barely known outside small niche circles. The article ends on a brief speculative note about what might account for the odd tenacity of a theoretically untenable concept.
Observations from the field: On the body, gender, and Al wehdat camp in Amman, Jordan
Authors: Qudah Nama’a A
Published: October 2024

Coming as a collection of observations from the field, I used this article to reflect on 9 months of fieldwork in Al Wehdat camp in Amman, Jordan. Using feminist research methodologies that make transparent the process of knowledge production, primarily ethnographic field visits and focus group discussions, I relied on the bodies of the camp inhabitants as sites of knowledge to learn more about life in the camp, with all what their embodied knowledge encompasses of ambiguity and the messiness of everyday life, aiming to challenge some of the power structures that otherwise control the process of knowledge production about and in the camp. I also brought myself into the frame of inquiry and used my own body as a tool of investigation, reflecting on my own position as a female researcher that is both an outsider and an insider to the camp context.
Simultaneous Infantile Spasms and Focal Seizures: A Rarely Reported Combined Seizure Phenomenon on Video Electroencephalogram (VEEG)
Authors: Horman Katherine , Bhatia Sonal
Published: October 2024

Focal seizures (FS) have previously been described before or after infantile spasm (IS) clusters, but FS occurring simultaneously with an IS cluster has been rarely reported in the EEG literature. We present three cases where focal seizures (FS) occurred concurrently during an infantile spasm (IS) cluster on VEEG. On VEEG, onset of IS cluster preceded FS in all three patients; however, patient three was diagnosed with FS prior to the onset of IS. FS duration ranged from 10–90 s and was electrographic-only in two out of the three patients. Unfortunately, the first two patients are now deceased, and for patient two no etiology was ever identified. Currently, patient three is free of spasms as well as seizures but has global developmental delay; no definite etiology has been identified for their presentation. Concurrent FS with IS suggests that the seizure types may be generated in different brain areas with one seizure type potentially triggering the other and is generally reflective of multifocal or diffuse cerebral disease with a poor prognosis as was seen in at least two of our patients. Our three cases of IS where FS occurred concurrently contribute to the limited existing data describing this phenomenon on VEEG.
Creatinine and Cystatin C: A Measure of Renal Function in Men With Testosterone-Induced Muscle Hypertrophy
Authors: Ashouri Rani , Lertkitcharoenpon Amica , Maidaa Michael , Brunner Bobby , Velazquez Oscar , Lipshultz Larry , Campbell Kevin
Published: October 2024

Creatinine (Cr) is often used as a standalone gold standard marker of kidney function. Cystatin C (Cys C) is a less physiologically labile marker of renal function, particularly in certain subgroups. Herein, we analyze trends in cystatin C as compared to creatinine in men on testosterone replacement therapy with varying body mass indices and percent body fat (PBF). This retrospective analysis observes 227 men with testosterone-induced muscle hypertrophy who visited a men’s health tertiary care clinic. All participants were characterized as competitive or recreational athletes. In patients with a normal body mass index (BMI), there was no clinically significant correlation between Cr and Cys C. Slight correlation was seen with overweight ( R2 = .27) patients ( p < .0001) and obese ( R2 = .29) patients ( p < .0001). Patients with PBF of 0%–10% ( n = 22) exhibited minimal ( R2 = .23) positive correlation between Cys C and Cr ( p = .03). Positive correlation between Cys C and Cr in patients with PBF of 10%–20% was clinically negligible ( R2 = .17, n = 87), modest ( R2 = .49) in patients with PBF of 20%–30% ( n = 42), and evident ( R2 = 1.00) in patients >30% ( n = 3) ( p < .0001, respectively). Cystatin C measurements display less variance compared with creatinine at differing BMI distinctions. At the upper limit of BMI or PBF in our patient population, cystatin C exhibits minimal to moderate variability compared with creatinine.
Balancing economic efficiency and national security: Industrial policy at the nexus of geopolitics and globalisation
Authors: Gavrilița Natalia
Published: October 2024

This article examines the resurgence of industrial policy in the EU, with a particular focus on its evolving rationale in the context of geopolitical fragmentation and economic security concerns. It explores how recent global events, including the Covid-19 pandemic and Russia’s invasion of Ukraine, have intensified debates about government intervention in the economy and led to a renewed focus on strategic autonomy. The paper analyses the key EU industrial policy initiatives and their implications, particularly in sectors such as energy, defence and critical technologies. Special attention is given to the challenges and opportunities presented by Ukraine’s reconstruction, including potential adaptations to EU state aid rules. The article concludes by proposing principles for effective industrial policy design and implementation, emphasising the importance of maintaining single-market integrity, ensuring transparency and accountability, and balancing interventions with sound macroeconomic policies.
Who owns the wind? Understanding wind energy production through a property chains perspective
Authors: Sonnberger Marco , Pfeiffer Maria , Gross Matthias
Published: October 2024

In this article, we argue that the resourcification of wind is based on a specific entanglement of different property objects - in particular wind, land and wind turbines - and property holders. We depart from an understanding of property as a social phenomenon that is enacted through social practices and thereby becomes relevant within an arrangement of different entities (human, non-human and material) by structuring the relations between these entities. We propose a practice theoretical approach based on Theodore Schatzki's concept of practice-arrangement constellations for understanding how property becomes relevant through socio-material relations which enable the resourcification of wind. Based on this theoretical approach, we show how different entities and practices bring about chains of property objects that enable the transformation of wind into electricity. With our conceptual considerations concerning property chains we hope to deepen the discussion around the significance of property in the resourcification of renewable energy sources.
New developments in the imaging of lung cancer
Authors: T�rnoki �d�m Domonkos , T�rnoki D�vid L�szl� , Dabrowska Marta , Knetki-Wr�blewska Magdalena , Frille Armin , Stubbs Harrison , Blyth Kevin G. , Juul Amanda Dandanell
Published: October 2024

Radiological and nuclear medicine methods play a fundamental role in the diagnosis and staging of patients with lung cancer. Imaging is essential in the detection, characterisation, staging and follow-up of lung cancer. Due to the increasing evidence, low-dose chest computed tomography (CT) screening for the early detection of lung cancer is being introduced to the clinical routine in several countries. Radiomics and radiogenomics are emerging fields reliant on artificial intelligence to improve diagnosis and personalised risk stratification. Ultrasound- and CT-guided interventions are minimally invasive methods for the diagnosis and treatment of pulmonary malignancies. In this review, we put more emphasis on the new developments in the imaging of lung cancer.
Seminal cell-free nucleic acids as possible biomarker in male infertility: a mini-review article
Authors: Javidmehr Davoud , Fesahat Farzaneh , Hassani Fatemeh , Talebi Ali Reza , Shahverdi Abdolhossein
Published: October 2024

Background

Male infertility is a major problem for many couples in the world. Many factors could cause male infertility such as environmental and genetic factors, life style, aging, inflammation, endocrinological etiologies, and antisperm antibodies.

Main body

Circulating cell-free nucleic acids (cfNAs) may play a key role in male infertility. cfNAs are obtained from different body fluids such as blood plasma, cerebrospinal fluid, amniotic fluid, urine, bronchoalveolar lavage fluid, and seminal plasma. The different types of cfNAs present in human semen include cell-free DNAs, cell free RNAs and cell-free mitochondrial DNAs and they are differentially higher than those in other body fluids. Few evidence have been done regarding the direct relationship between cfNAs and male infertility in serum and seminal plasma of infertile men compared to the fertile men.

Conclusions

This document aimed to compile data about the main causes influencing male infertility focusing on seminal cfNA/cfDNA and its possible role as differential biomarker to diagnosis the main source of spermatogenesis abnormalities and male infertility.
Exploring a GIS-based analytic hierarchy process for spatial flood risk assessment in Egypt: a case study of the Damietta branch
Authors: Zhran Mohamed , Ghanem Karim , Tariq Aqil , Alshehri Fahad , Jin Shuanggen , Das Jayanta , Pande Chaitanya Baliram , Pramanik Malay , Hasher Fahdah Falah Ben , Mousa Ashraf
Published: October 2024

Floods are the most common and costly disasters worldwide, while spatial flood risk assessment is still challenging due to fewer observations and method limitations. In this study, the flood risk zonation in the Nile districts of the Damietta branch, Egypt, is delineated and assessed by integrating remote sensing with a geographic information system, and an analytical hierarchy process (AHP). Twelve thematic layers (elevation, slope, normalized difference vegetation index, topographic wetness index, modified normalized difference water index, topographic positioning index, stream power index, modified Fournier index, drainage density, distance to the river, sediment transport index, and lithology) are used for producing flood susceptibility zonation (FSZ) and six parameters (total population, distance to hospital, land use/land cover, population density, road density, and distance to road) are utilized for producing flood vulnerability zonation. Multicollinearity analysis is applied to identify highly correlated independent variables. Sensitivity studies have been used to assess the effectiveness of the AHP model. The results indicate that the high and very high flood risk classes cover 21.40% and 8.26% of the area, respectively. In 14.07%, 27.01%, and 29.26% of the research area, respectively, flood risk zones classified as very low, low, and moderate are found. Finally, FSZ is validated using the receiver operating characteristics curve and area under curve (AUC) analysis. A higher AUC value (0.741) in the validation findings demonstrated the validity of this AHP approach. The results of this study will help planners, hydrologists, and managers of water resources manage areas that are susceptible to flooding and reduce potential harm.
Correlation between the accuracy of the emergency response centre’s urgency assessment and emergency medical services non-conveyance: a retrospective register-based study in Finland
Authors: Salminen Tomi , Kaartinen Kaius , Palonen Mira , Setälä Piritta , Paavilainen Eija , Hoppu Sanna
Published: October 2024

Background

In modern emergency medical services (EMS), ambulances increasingly focus on examining and treating the patient at the scene. This has led to increased levels of non-conveyance. In Finland, for instance, approximately 40% of EMS dispatches end up in non-conveyance. As EMS systems evolve, the proportion of non-conveyance could serve as a cost-effective measure to assess the quality of the dispatch criteria, if a link to the performance of urgency assessment would be established. The purpose of this study was to investigate whether the proportion of non-conveyance is associated with the test performance levels of the urgency assessment. This investigation was done separately within each dispatch category.

Methods

A retrospective evaluation of the data was conducted on all EMS dispatches in the Pirkanmaa Hospital District from 1 August 2021 through 31 August 2021. There were a total of 7,245 EMS dispatches during the study period of which 829 were excluded. This study was conducted by comparing the existing test performance levels (sensitivity, specificity and under- or overestimation) of the emergency response centre’s urgency assessment with the non-conveyance rate (%) of each dispatch category. The relationships between the variables were measured using Spearman’s rank correlation coefficient.

Results

The proportion of over-triage was the only urgency assessment’s test performance variable that had a statistically significant correlation with the proportion of non-conveyance (r = 0.568; p = 0.003). Other test performance variables of the urgency assessment had no or little correlation to the proportion of non-conveyance. Of the 6,416 EMS dispatches in the study period, 42% (2,672) resulted in non-conveyance of the patient. In nine dispatch categories, at least half (51–69%) of the dispatches ended in non-conveyance.

Conclusions

Based on this study, it seems that the percentage of non-conveyance in the dispatch category could be used, with certain limitations, to assess the proportion of over-triage in the dispatch category. The method is particularly applicable in scenarios where the dispatch criteria have undergone modifications and there is a need to monitor the effect of the changes on the level of over-triage.
Barriers and facilitators to providing rehabilitation for long-term care residents with dementia: a qualitative study
Authors: Ibekaku Michael Chigozie , Ripley Sara , Alizadehsaravi Niousha , Affoo Rebecca , Middleton Laura E. , Moody Elaine , Ghanouni Parisa , Weeks Lori E. , McArthur Caitlin
Published: October 2024

Background

Rehabilitation can help long-term care (LTC) residents with dementia maintain their independence. However, many residents do not receive rehabilitation. This study aimed to identify the barriers and facilitators to providing rehabilitation for LTC residents with dementia and propose practical interventions for overcoming them.

Methods

Using a phenomenological research design, we conducted a qualitative study involving 17 privately owned LTC homes in Nova Scotia, Canada. Data were collected through individual interviews and a focus group with residents with dementia (n = 3), family members (n = 4), rehabilitation providers (n = 6), and other staff (n = 3). We analyzed the data using inductive thematic content analysis and mapped the results onto the socioecological framework and the Behaviour Change Wheel (BCW) to classify and analyze barriers and facilitators to rehabilitation. The APEASE criteria (Acceptability, Practicability, Effectiveness, Affordability, Side-effects, and Equity) in the BCW were used to identify feasible interventions and policies linked to the identified barriers and facilitators.

Results

Barriers at the intrapersonal level included communication difficulties, comorbidities, and lack of motivation among residents. Interpersonal factors encompassed the availability of family support and lack of interdisciplinary practice. Policy/environmental factors involved limited resources, complex admission processes, low staff ratios, and restrictive restraint policies. Enhancing communication, reducing the use of restraints, promoting interdisciplinary practice, and increasing accessibility to activity spaces and equipment will improve the provision of rehabilitation for the residents.

Conclusion

Enhancing the capabilities, opportunities, and motivations of all actors in LTC homes can potentially minimize these barriers. Interventions such as staff training on effective communication and dementia care, promoting person-centred and meaningful activities, and improving interdisciplinary collaboration are crucial. Policy measures to improve hospital-to-LTC transitions, increase volunteer involvement, educate families and communities, and recruit more staff are recommended. Addressing these barriers through targeted interventions and policy changes can significantly improve rehabilitation provision for residents with dementia in LTC settings.
Retinol-binding protein type 1 expression predicts poor prognosis in head and neck squamous cell carcinoma
Authors: Fu Ling-ling , Yan Ming , Yu Xin , Shao Min , Gosau Martin , Friedrich Reinhard E. , Vollkommer Tobias , Smeets Ralf , Feng Hong-chao , Xu Liya
Published: October 2024

Background

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy worldwide, with high incidence and poor survival rates. RBP1 is highly expressed in several kinds of cancer and plays a potential prognostic factor. However, the relationship between RBP1 and HNSCC were analyzed based on The Cancer Genome Atlas (TCGA) database.

Materials and methods

RBP1 expression and clinical information were obtained from the Cancer Genome Atlas (TCGA) database. Tumor tissue and adjacent normal tissue of 6 HNSCC patients were collected to analyze the RBP1 mRNA expression level by quantitative PCR. Cox regression analysis was used to evaluate the prognostic values of RBP1 and clinical data in HNSCC. A nomogram was also established to predict the impact of RBP1 on prognosis based on Cox multivariate results. The methylation level of RBP1 in HNSC and its prognosis were analyzed in UALACN and MethSurv. Finally, the potential biological functions of RBP1 were investigated using gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA).

Results

The mRNA expression levels of RBP1 were highly expressed in HNSCC tissue. The Cox analyses demonstrate that highly-expressed RBP1 is an independent prognosis marker(P < 0.05). ROC curve analysis showed that performances of RBP1 (area under the ROC curve: 0.887, sensitivity: 84.1%, specificity: 79.9%). The methylation was increased in HNSCC patients compared with normal subjects(P < 0.05) and was associated with better prognosis at sites cg06208339, cg12298268, cg12497564, cg15288618, cg20532370, cg23448348. Additionally, RBP1 expression is mildly associated with immune cell infiltration and immunological checkpoints.

Conclusion

RBP1 is overexpressed and associated with poor patient prognosis in head and neck squamous cell carcinoma.
Multiple cytokine analysis of aqueous humor in uveitis with or without secondary glaucoma
Authors: Xiao Junyan , Zhao Chan , Cheng Gangwei , Song Hang , Zhang Yang , Zhang Meifen
Published: October 2024

To assess the level of both pro-inflammatory and anti-inflammatory cytokines in the aqueous humor (AH) of patients suffering from uveitis, with or without coexisting glaucoma, and compare them with patients diagnosed with primary open-angle glaucoma (POAG) and those with age-related cataract (ARC). By using Luminex xMAP® multiplex assays analyses, we assessed levels of 11 cytokines and chemokines, and compared them across groups, including uveitis-secondary glaucoma (USG) (n = 16), uveitis without glaucoma (UwoG), (n = 16), POAG (n = 16), and ARC (n = 16) to explore the correlation between these cytokines and the presence of uveitis, as well as intraocular pressure (IOP). Pro-inflammatory factors MCP-1, MIP-1β, IL-6, IL-8, and transforming growth factors TGF-β1 and TGF-β2 were significantly elevated in the AH of USG eyes. In the case of enhanced anti-inflammatory in the perioperative period, the pro-inflammatory factors remained notably elevated in the USG group compared to the UwoG group (P < 0.01). The levels of IL-6, IL-8, and MCP-1 in the AH of the USG group and POAG group had the same trend, which markedly surpassed those of the ARC group (P < 0.01). Significantly increased levels of MCP-1, MIP-1β, IL-6, IL-8, TGF-β1, and TGF-β2 were found in the AH of USG patients, implying a potential role for these mediators in the progression of glaucomatous manifestations within patients with uveitis. Besides the analysis revealed no discernible statistical disparity in cytokine concentrations within the AH of USG eyes whether the preoperative baseline IOP was greater than 30 mmHg or not, indicating that the safety of antiglaucoma surgery in USG patients even with baseline high IOP.
Individualised computerised cognitive training (iCCT) for community-dwelling people with mild cognitive impairment (MCI): results on cognition in the 6-month intervention period of a randomised controlled trial (MCI-CCT study)
Authors: Graessel Elmar , Jank Michael , Scheerbaum Petra , Scheuermann Julia-Sophia , Pendergrass Anna
Published: October 2024

Background

Computerised cognitive training (CCT) can improve the cognitive abilities of people with mild cognitive impairment (MCI), especially when the CCT contains a learning system, which is a type of machine learning (ML) that automatically selects exercises at a difficulty that corresponds to the person’s peak performance and thus enables individualised training.

Methods

We developed one individualised CCT (iCCT) with ML and one basic CCT (bCCT) for an active control group (CG). The study aimed to determine whether iCCT in the intervention group (IG) resulted in significantly greater enhancements in overall cognitive functioning for individuals with MCI (age 60+) compared with bCCT in the CG across a 6-month period. This double-blind randomised controlled study was conducted entirely virtually. The 89 participants were community-dwelling people with a psychometric diagnosis of MCI living in Germany. The iCCT stimulates various cognitive functions, especially working memory, visuo-constructional reasoning, and decision-making. The bCCT includes fewer and simpler tasks. Both CCTs were used at home. At baseline and after 6 months, we assessed cognitive functioning with the Montreal Cognitive Assessment (MoCA). A mixed-model ANCOVA was conducted as the main analysis.

Results

Both CCTs led to significant increases in average global cognition. The estimated marginal means of the MoCA score increased significantly in the CG by an average of 0.9 points (95% CI [0.2, 1.7]) from 22.3 (SE = 0.25) to 23.2 (SE = 0.41) points (p = 0.018); in the IG, the MoCA score increased by an average of 2.2 points (95% CI [1.4, 2.9]) from 21.9 (SE = 0.26) to 24.1 (SE = 0.42) points (p < 0.001). In a confound-adjusted multiple regression model, the interaction between time and group was statistically significant (F = 4.92; p = 0.029). The effect size was small to medium (partial η2 = 0.057). On average, the participants used the CCTs three times per week with an average duration of 34.9 min per application. The iCCT was evaluated as more attractive and more stimulating than the bCCT.

Conclusions

By using a multi-tasking CCT three times a week for 30 min, people with MCI living at home can significantly improve their cognitive abilities within 6 months. The use of ML significantly increases the effectiveness of cognitive training and improves user satisfaction.

Trial registration

ISRCTN14437015; registered February 27, 2020.
Trajectories of triglyceride-glucose index changes and their association with all-cause and cardiovascular mortality: a competing risk analysis
Authors: Lee Jun-Hyuk , Jeon Soyoung , Lee Hye Sun , Lee Ji-Won
Published: October 2024

Background

The association between changes in insulin resistance, reflected by the triglyceride-glucose (TyG) index, and mortality remains unclear. This study investigated whether longitudinal trajectories of TyG index changes are associated with all-cause and cardiovascular disease (CVD) mortality.

Methods

This retrospective cohort study analyzed data from 233,546 adults aged ≥ 19 years from the Korea National Health Insurance Service-National Sample Cohort. Participants were categorized as having increasing, stable, or decreasing TyG index changes during a 4-year exposure period (2009–2014). Mortality outcomes were assessed during an 8.13-year follow-up period (2015–2021). Cox proportional hazards regression and competing risk analysis were used to evaluate all-cause and CVD mortality.

Results

A total of 7918 mortality events, including 651 CVD deaths, were recorded. Compared with the stable group, adjusted hazard ratios for all-cause mortality were 1.09 (95% CI 1.03–1.15) in the increasing group and 1.23 (95% CI 1.01–1.50) for CVD mortality. An increased TyG index was significantly associated with all-cause mortality in individuals aged < 50 years; men; and individuals with obesity, hypertension, diabetes, and/or dyslipidemia. For CVD mortality, significant associations were found in individuals aged 50–69 years, with obesity, with diabetes, or without dyslipidemia.

Conclusion

An increasing TyG index from baseline during follow-up was independently associated with higher risks of all-cause and CVD mortality. Serial monitoring of TyG index changes could enhance risk stratification and inform targeted interventions to reduce insulin resistance, and ultimately lower mortality risk.
Nanoplatelets modified with RVG for targeted delivery of miR-375 and temozolomide to enhance gliomas therapy
Authors: Yang Tingting , Zhang Nan , Liu Yuanyuan , Yang Ruyue , Wei Zhaoyi , Liu Futai , Song Dan , Wang Longwei , Wei Jiangyan , Li Yuanpei , Shen Deliang , Liang Gaofeng
Published: October 2024

Gliomas are one of the most frequent primary brain tumors and pose a serious threat to people’s lives and health. Platelets, a crucial component of blood, have been applied as drug delivery carriers for disease diagnosis and treatment. In this study, we designed engineered nanoplatelets for targeted delivery of therapeutic miR-375 and temozolomide (TMZ, a first-line glioma treatment agent) to enhance glioma therapy. Nanoplatelets were prepared through mild ultrasound, TMZ and miR-375 were co-loaded through ultrasound and electrostatic interactions, respectively, to combine chemotherapy with gene therapy against glioma. To improve the blood brain barrier (BBB) crossing efficiency and glioma targeting ability, the nanoplatelets were modified with central nervous system-specific rabies viral glycoprotein peptide (RVG) through thiol-maleimide click reaction. The RVG modified nanoplatelets co-loaded TMZ and miR-375 (NR/TMZ/miR-375) not only inherited the good stability and remarkable biocompatibility of platelets, but also promoted the cellular uptake and penetration of glioma tissues, and effectively induced cell apoptosis to enhance the therapeutic effect of drugs. In vivo studies showed that NR/TMZ/miR-375 significantly increased the circulation time of TMZ, and exhibited superior combined antitumor effects. In summary, this multifunctional ‘natural’ nanodrug delivery system provides a potent, scalable, and safety approach for platelet-based combined cancer chemotherapy and gene therapy.
Nrf2/Keap1/ARE regulation by plant secondary metabolites: a new horizon in brain tumor management
Authors: Dewanjee Saikat , Bhattacharya Hiranmoy , Bhattacharyya Chiranjib , Chakraborty Pratik , Fleishman Joshua , Alexiou Athanasios , Papadakis Marios , Jha Saurabh Kumar
Published: October 2024

Brain cancer is regarded as one of the most life-threatening forms of cancer worldwide. Oxidative stress acts to derange normal brain homeostasis, thus is involved in carcinogenesis in brain. The Nrf2/Keap1/ARE pathway is an important signaling cascade responsible for the maintenance of redox homeostasis, and regulation of anti-inflammatory and anticancer activities by multiple downstream pathways. Interestingly, Nrf2 plays a somewhat, contradictory role in cancers, including brain cancer. Nrf2 has traditionally been regarded as a tumor suppressor since its cytoprotective functions are considered to be the principle cellular defense mechanism against exogenous and endogenous insults, such as xenobiotics and oxidative stress. However, hyperactivation of the Nrf2 pathway supports the survival of normal as well as malignant cells, protecting them against oxidative stress, and therapeutic agents. Plants possess a pool of secondary metabolites with potential chemotherapeutic/chemopreventive actions. Modulation of Nrf2/ARE and downstream activities in a Keap1-dependant manner, with the aid of plant-derived secondary metabolites exhibits promise in the management of brain tumors. Current article highlights the effects of Nrf2/Keap1/ARE cascade on brain tumors, and the potential role of secondary metabolites regarding the management of the same.
Innovative nebulization delivery of lipid nanoparticle-encapsulated siRNA: a therapeutic advance for Staphylococcus aureus-induced pneumonia
Authors: Meng Meiqi , Li Yue , Wang Jiachao , Han Xiaonan , Wang Xuan , Li Hongru , Xiang Bai , Ma Cuiqing
Published: October 2024

Background

Integrin α5β1 plays a crucial role in the invasion of nonphagocytic cells by Staphylococcus aureus (S. aureus), thereby facilitating infection development. Lipid nanoparticles (LNPs) serve as an effective vehicle for delivering small interfering ribonucleic acids (siRNA) that represent a method to knockdown integrin α5β1 in the lungs through nebulization, thereby potentially mitigating the severity of S. aureus pneumonia. The aim of this study was to harness LNP-mediated targeting to precisely knockdown integrin α5β1, thus effectively addressing S. aureus-induced pneumonia.

Methods

C57 mice (8 week-old females) infected with S. aureus via an intratracheal nebulizing device were utilized for the experiments. The LNPs were synthesized via microfluidic mixing and characterized by their size, polydispersity index, and encapsulation efficiency. Continuous intratracheal nebulization was employed for consistent siRNA administration, with the pulmonary function metrics affirming biosafety. The therapeutic efficacy of LNP-encapsulated siRNAs against pneumonia was assessed through western blotting, bacterial count measurement, quantitative polymerase chain reaction, and histological analyses.

Results

LNPs, which have an onion-like structure, retained integrity post-nebulization, ensuring prolonged siRNA stability and in vivo safety. Intratracheal nebulization delivery markedly alleviated the severity of S. aureus-induced pneumonia, as indicated by reduced bacterial load and bolstered immune response, thereby localizing the infection to the lungs and averting systemic dissemination.

Conclusions

Intratracheal nebulization of LNP-encapsulated siRNAs targeting integrin α5β1 significantly diminished the S. aureus-mediated cellular invasion and disease progression in the lungs, presenting a viable therapeutic approach for respiratory infections.
Very pronounced bowel sparing during radiation therapy for anal carcinoma using a natural spacer (Myoma) – a case report
Authors: Hoeng L. , Exeli A. K. , Krombach G. A. , Schwandner T. , Agolli L. , Habermehl D.
Published: October 2024

Background

Using dose-painted intensity-modulated radiation therapy, specific dose volume constraints or implantation of tissue expanders prior to radiotherapy are validated options for reducing radiation dose on the bowel and therefore minimizing acute gastrointestinal toxicity during chemoradiation for anorectal malignancies. We describe the rare case of a female patient with a locally advanced anal carcinoma where a large myomatous uterus served as a natural spacer to protect the bowel during radiation therapy.

Case presentation

Initially the patient presented with anal pain, proctoscopy followed by an excisional biopsy confirmed the diagnosis of a squamous cell carcinoma of the anus. Imaging examination showed a locally advanced tumor and in addition a large uterus with typical leiomyomas up to 11.5 cm in diameter. The patient underwent chemoradiation; because of the large leiomyomas there was almost no dose burden for the small intestine and therefore practically no gastrointestinal toxicity.

Conclusion

As we know, this report describes the situation that a large myomatous uterus served as a natural spacer during radiation therapy in a way that is unique to date.
Low shear stress protects chondrocytes from IL-1β-induced apoptosis by activating ERK5/KLF4 signaling and negatively regulating miR-143-3p
Authors: Zhao Jun , Xia Yayi
Published: October 2024

Objective

This study investigated the protective effects of low fluid shear stress (FSS ≤ 2 dyn/cm²) against interleukin-1β (IL-1β)-induced chondrocyte apoptosis and explored the underlying molecular mechanisms.

Methods

Chondrocytes were cultured under four conditions: control, IL-1β stimulation, low FSS, and combined low FSS + IL-1β stimulation. Apoptosis was assessed using Hoechst staining and flow cytometry. Western blotting determined the expression of caspase-3 (CASP3), caspase-8 (CASP8), and NF-κB p65. Quantitative real-time PCR measured miR-143-3p expression. The roles of miR-143-3p and the extracellular signal-regulated kinase 5 (ERK5)/Krüppel-like factor 4 (KLF4) signaling pathway were further investigated using miR-143-3p mimics and inhibitors, an ERK5 inhibitor, and a KLF4 overexpression vector.

Results

IL-1β induced significant chondrocyte apoptosis, which was markedly inhibited by low FSS. Mechanistically, low FSS suppressed miR-143-3p expression, thereby enhancing ERK5 signaling. This activated ERK5 subsequently upregulated KLF4 expression, further mitigating IL-1β-induced damage. Importantly, miR-143-3p overexpression under low FSS conditions exacerbated IL-1β-induced apoptosis, while miR-143-3p inhibition attenuated it. Consistent with this, ERK5 inhibition augmented IL-1β-induced apoptosis, whereas KLF4 overexpression suppressed it.

Conclusion

Low FSS protects chondrocytes from IL-1β-induced apoptosis by suppressing miR-143-3p and activating the ERK5/KLF4 signaling pathway. This study reveals a novel mechanism by which mechanical stimulation protects cartilage.
Large-scale annotation of biochemically relevant pockets and tunnels in cognate enzyme–ligand complexes
Authors: Vavra O. , Tyzack J. , Haddadi F. , Stourac J. , Damborsky J. , Mazurenko S. , Thornton J. M. , Bednar D.
Published: October 2024

Tunnels in enzymes with buried active sites are key structural features allowing the entry of substrates and the release of products, thus contributing to the catalytic efficiency. Targeting the bottlenecks of protein tunnels is also a powerful protein engineering strategy. However, the identification of functional tunnels in multiple protein structures is a non-trivial task that can only be addressed computationally. We present a pipeline integrating automated structural analysis with an in-house machine-learning predictor for the annotation of protein pockets, followed by the calculation of the energetics of ligand transport via biochemically relevant tunnels. A thorough validation using eight distinct molecular systems revealed that CaverDock analysis of ligand un/binding is on par with time-consuming molecular dynamics simulations, but much faster. The optimized and validated pipeline was applied to annotate more than 17,000 cognate enzyme–ligand complexes. Analysis of ligand un/binding energetics indicates that the top priority tunnel has the most favourable energies in 75% of cases. Moreover, energy profiles of cognate ligands revealed that a simple geometry analysis can correctly identify tunnel bottlenecks only in 50% of cases. Our study provides essential information for the interpretation of results from tunnel calculation and energy profiling in mechanistic enzymology and protein engineering. We formulated several simple rules allowing identification of biochemically relevant tunnels based on the binding pockets, tunnel geometry, and ligand transport energy profiles.

Scientific contributions

The pipeline introduced in this work allows for the detailed analysis of a large set of protein–ligand complexes, focusing on transport pathways. We are introducing a novel predictor for determining the relevance of binding pockets for tunnel calculation. For the first time in the field, we present a high-throughput energetic analysis of ligand binding and unbinding, showing that approximate methods for these simulations can identify additional mutagenesis hotspots in enzymes compared to purely geometrical methods. The predictor is included in the supplementary material and can also be accessed at https://github.com/Faranehhad/Large-Scale-Pocket-Tunnel-Annotation.git. The tunnel data calculated in this study has been made publicly available as part of the ChannelsDB 2.0 database, accessible at https://channelsdb2.biodata.ceitec.cz/.
Acceptability of “DIDE”, a mobile application designed at facilitating care adherence of patients with substance use disorder
Authors: Stocker Antoine , Navarro Nicolas , Schmitt Laurent , Delagnes Marc , Doualle Aurélie , Mallard Valérie , Entajan Flora , Guivarc’h Karine , Masse Patricia , Chaigneau Lilian , Bonneau Baptiste , Lapeyre-Mestre Maryse , Arbus Christophe , Yrondi Antoine , Salles Juliette
Published: October 2024

Background

Attrition continues to be a major hurdle for addiction treatment. Through the prism of the attachment theory, this phenomenon can be understood as a manifestation of the patient’s insecure attachment style, needing a highly-responsive care delivery. We developed an electronic health mobile application, co-designed with patients, aimed at helping healthcare teams respond to their patients’ needs, and fostering adherence to care. This acceptability study evaluated patients everyday use of the application for eight weeks, assessing their satisfaction with the system, and its integration within professionals’ current practice in our center.

Methods

This single-center, prospective study was conducted between January 2022 and December 2022. 24 adult patients with any type of addiction were included. They were granted access to the application for eight weeks, and were invited to complete the System Usability Scale questionnaire regarding their satisfaction with application’s usability at the end of the study. The application uses active self-reports, which are later discussed with the healthcare team, and foster both the working alliance and the decision-making process.

Results

17 patients out of 24 reached the primary endpoint. On average, over the eight-weeks period, patients logged in the application 38.2 times, and sent 5.9 messages to the healthcare team. Interestingly, 64.3% of the user logins were recorded outside of our center’s working hours (either from 5 p.m. to 9 a.m., or during week-ends and bank holidays), and 70.8% of the patients logged into the application at least one time between 10 p.m. and 8 a.m. 18 patients completed the System Usability Scale questionnaire, which averaged a score of 81.8 out of 100. Healthcare professionals logged in the application’s messaging system 4.5 times a day on average.

Conclusions

This preliminary study shows promising results, as patients engaged well with various components of the application. It was moreover possible for healthcare workers in our center to integrate this tool in their daily activities. More work is needed to better understand the various patients’ needs regarding the application, further strengthen their adherence to the intervention, and understand professionals’ motivations to use the application.

Trial registration

ClinicalTrials.gov, Identifier: NCT04659954. Registered 09 December 2020, https://clinicaltrials.gov/study/NCT04659954.
Services for perinatal patients with opioid use disorder: a comprehensive Baltimore City-wide 2023 assessment
Authors: Ratner Jessica A. , Kirschner Jennifer H. , Spencer Brittney , Terplan Mishka
Published: October 2024

Background

Overdose is a leading cause of maternal mortality; in response, maternal mortality review committees have recommended expanding substance use disorder (SUD) screening, improving collaboration between obstetric and SUD treatment providers, and reducing fragmentation in systems of care. We undertook an analysis of the perinatal SUD treatment landscape in Baltimore, Maryland in order to identify barriers to treatment engagement during pregnancy and the postpartum period and guide system improvement efforts.

Methods

We conducted a survey of seven birthing hospitals, 31 prenatal care practices, and 108 SUD treatment providers in Baltimore from April-June 2023. Organizations were asked to quantify care for perinatal patients with opioid use disorder (OUD) as well as about screening, service availability, referral practices, and support needed to improve care.

Results

61% of the 145 contacted organizations responded. Birthing hospitals reported caring for pregnant persons with OUD with greater frequency than prenatal care practices or SUD treatment programs. Most birthing hospitals and prenatal care practices reported screening for OUD at intake, but the minority reported using validated tools. Service availability varied by type of organization and type of service. In general, prenatal care practices offered the fewest number of SUD-related services. Most SUD treatment programs that offered buprenorphine or methadone to the general population also offered these medications to pregnant patients. Withdrawal management for comorbid alcohol/benzodiazepine use disorders during pregnancy was more limited. The majority of birthing hospitals and prenatal care practices reported offering neither direct naloxone distribution nor prescriptions. Few SUD treatment programs offered tailored services for perinatal patients or for parents of young children, and many programs do not permit children onsite. Respondents reported high levels of interest in education and consultative support on SUD treatment in pregnancy within obstetric settings and on pregnancy-related medical concerns within SUD programs.

Conclusions

This project provides a comprehensive picture of services available for treatment of perinatal OUD in a major US city. Results have served as a guide for ongoing citywide system improvement efforts by our project team and offer a model for other jurisdictions hoping to strengthen services for perinatal OUD and reduce maternal mortality.
A reciprocity-aware, low-rank regularization for multidimensional deconvolution
Authors: Chen Fuqiang , Ravasi Matteo , Keyes David
Published: October 2024

A novel factorization-based, low-rank regularization method is introduced to solve multidimensional deconvolution (MDD) problems in the frequency domain. In this approach, each frequency component of the unknown wavefield is represented as a complex-valued square matrix and approximated as the product of a rectangular matrix and its transpose. The benefit of such a parameterization is twofold. First, each frequency matrix is guaranteed to be symmetric. From a physical standpoint, the recovered wavefield inherently adheres to the principle of reciprocity; in other words, the response to a receiver from a virtual source does not change when the two are swapped. Therefore, we refer to this low-rank parameterization as reciprocity-aware in that it respects the underlying physics of wave propagation associated with the MDD solution. Second, the size of the unknown matrix is greatly reduced compared with that of the original wavefield of interest (and halved compared with the existing factorization-based low-rank approximations). We further show that the associated objective function can be successfully optimized using the accelerated proximal gradient algorithm and present a robust strategy to define the initial guess of the solution. Numerical examples on synthetic and field data demonstrate the effectiveness of our method in compressing the retrieved Green’s function while preserving its accuracy.