bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of risk perception and policy support on the deviation of rural households’ demands and adoption behavior of the forestry socialized service
Authors: Liao Wenmei , Yuan Ruolan , Zhang Xu , Zhang Chang , Li Na
Published: June 2023

This study explores the impact mechanism of risk perception and policy support on the deviation of rural households’ demands and adoption behavior (RHDAB) of the forestry socialized service (FSS). It provides a decision-making basis for promoting the construction of a collective FSS system and realizing the value of ecological products. Survey data from 787 rural households in Zhejiang, Fujian, and Jiangxi provinces were used to quantify the influence of risk perception and policy support on the deviation of RHDAB of the FSS using the Mv-probit model and Poisson model. The results revealed that: 1) there were deviations between RHDAB for different types of FSS, with 57.71% and 66.20% for good seeds and cultivation technology services and product collection and marketing services, respectively. 2) Risk perception accelerated the deviation and degree of deviation between RHDAB of the FSS, particularly the technology risk perception. Meanwhile, policy support was shown to mitigate the effect of risk perception on rural households’ deviation and deviation degree. 3) Business risk perceptions had a more significant impact on the deviation of RHDAB in middle and high-economic development areas compared to technology risk perception and financial risk perceptions in low-economic development areas. Additionally, business risk perception was found to have a significant positive effect on the deviation of small and large operation-scale rural households, while technology risk perception significantly impacted the deviation of small operation-scale rural households. Consequently, this study suggests the need for a sound forestry risk management system to address the variability of the deviation of RHDAB across different regions and operation scales, as well as to improve the service quality of forestry insurance, accelerate the speed and benefit of inclusive rural finance, and cultivate new supply bodies of socialized services, thereby promoting the construction of collective FSS system and realizing the value of ecological products.
A three-step approach for co-locating nature-based solutions within offshore wind farms
Authors: Rendle Emma Jane , Hunt Emily Louise , Bicknell Anthony William James
Published: June 2023

The extent of seabed licensed for offshore renewables is being expanded with the global requirement to reduce carbon emissions. The opportunity for Nature-based Solutions for restoration, conservation, mariculture, infrastructure protection, and carbon sequestration initiatives are being explored internationally. Co-location of marine renewable or structures with conservation initiatives offers the opportunity to support populations of threatened species and contribute to wider ecosystem services and benefits. Building on experience from a North Sea project, we explore the feasibility to co-locate bivalve species at offshore wind farms. We present a three-step approach to identify offshore wind farm sites with the potential to co-locate with compatible species within a marine licensed area, based on environmental and physical conditions and biological tolerances. These steps are, (1) information collection and data synthesis, (2) data analysis through site suitability and species compatibility assessments, and (3) numerical modelling approaches to test the feasibility of pilot studies and scale-up planned operations. This approach supports feasibility assessment by identification of sites where Nature-based Solution project success is more likely or certain, thereby reducing project costs and risk of failure. An example case study is provided using Gunfleet Sands offshore wind farm (southeast England) and the restoration and conservation of the commercially valuable European Flat Oyster (Ostrea edulis).
Downregulation of interleukin 6 signaling might reduce the risk of periodontitis: a drug target Mendelian randomization study
Authors: Nolde Michael , Alayash Zoheir , Reckelkamm Stefan Lars , Kocher Thomas , Ehmke Benjamin , Holtfreter Birte , Baurecht Hansjörg , Georgakis Marios K. , Baumeister Sebastian-Edgar
Published: June 2023

Aim

Interleukin 6 (IL-6) is considered to play a role in the dysbiotic host response in the development of periodontitis. While the inhibition of the IL-6 receptor using monoclonal antibodies is a well-established therapy for some diseases, so far, its potential benefit in patients with periodontitis has not been examined. We tested the association of genetically proxied downregulation of IL-6 signaling with periodontitis to explore whether downregulation of IL-6 signaling could represent a viable treatment target for periodontitis,

Materials and methods

As proxies for IL-6 signaling downregulation, we selected 52 genetic variants in close vicinity of the gene encoding IL-6 receptor that were associated with lower circulating C-reactive protein (CRP) levels in a genome-wide association study (GWAS) of 575 531 participants of European ancestry from the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Associations with periodontitis were tested with inverse-variance weighted Mendelian randomization in a study of 17 353 cases and 28 210 controls of European descent in the Gene-Lifestyle Interactions in Dental Endpoints (GLIDE) consortium. In addition, the effect of CRP reduction independent of the IL-6 pathway was assessed.

Results

Genetically proxied downregulation of IL-6 signaling was associated with lower odds of periodontitis (odds ratio (OR) = 0.81 per 1-unit decrement in log-CRP levels; 95% confidence interval (CI): [0.66;0.99]; P = 0.0497). Genetically proxied reduction of CRP independent of the IL-6 pathway had a similar effect (OR = 0.81; 95% CI: [0.68; 0.98]; P = 0.0296).

Conclusion

In conclusion, genetically proxied downregulation of IL-6 signaling was associated with lower odds of periodontitis and CRP might be a causal target for the effect of IL-6 on the risk of periodontitis.
Case Report: Morbihan disease treated with tofacitinib successfully
Authors: Li Zi-Yun , Chi Chao-Cheng , Cai Sui-Qing
Published: June 2023

Introduction

To date, there is no standard treatment for Morbihan disease. Several studies have reported that Morbihan disease responds well to systemic corticosteroids (prednisone and prednisolone), systemic antibiotics (tetracyclines), antihistamines (ketotifen) and surgical therapy (Lymphaticovenous anastomosis). To our knowledge, Tofacitinib, as a Janus-activated kinase (JAK) inhibitor, plays a vital role in the treatment of inflammatory and autoimmune disorders. Therefore, Tofacitinib may be a promising medical option for patients with Morbihan disease.

Case Presentation

The first case involves a 43-year-old Chinese man who presented a 12-month history of progressive painless swelling of the left upper eyelid. According to the skin biopsy, perivascular dermal edema with dilatation of lymphatic vessels and telangiectasia was observed, accompanied by mixed lymphocyte infiltrate, including histiocytes, plasma cells, and a few eosinophils. The second case involves a Chinese female patient who presented a 2-year history of progressive left-sided facial edema, which was eventually diagnosed as Morbihan disease. The skin biopsy revealed lymphocyte infiltration in the superficial vessels of dermis and some accessories. Based on patients’ clinical presentation, skin biopsy results, and exclusion of differential diagnoses such as systemic lupus erythematosus (SLE), they were diagnosed with Morbihan disease. They were both treated with Tofacitinib (5mg, po twice daily).

Outcomes

Patient 1 underwent a trial of Tofacitinib at a dosage of 5 mg twice daily for one month, with notable improvement. His edema and erythema present on the left face were alleviated. Patient 1 reduced the dosage of Tofacitinib by half (5mg, once daily) and continued using it for 5 months. During the 6-month follow-up, the facial erythema in the patient subsided, and there was a noticeable improvement in the swelling of the left eyelid compared to before. Patient 2, her lesions gradually improved after one-week treatment. She received a one-month treatment of Tofacitinib, and during the subsequent six-month follow-up, there was no evidence of eruption recurrence.

Conclusion

We present the first cases of two patients receiving short-term Tofacitinib as therapy for Morbihan disease and retrieving huge succession. Tofacitinib may be a promising oral alternative for patients with Morbihan disease. However, its safety and efficacy require further assessment through clinical trials.
Understanding recovery of language after stroke: insights from neurovascular MRI studies
Authors: Ivanova Maria V. , Pappas Ioannis
Published: June 2023

Stroke causes a disruption in blood flow to the brain that can lead to profound language impairments. Understanding the mechanisms of language recovery after stroke is crucial for the prognosis and effective rehabilitation of people with aphasia. While the role of injured brain structures and disruptions in functional connectivity have been extensively explored, the relationship between neurovascular measures and language recovery in both early and later stages has not received sufficient attention in the field. Fully functioning healthy brain tissue requires oxygen and nutrients to be delivered promptly via its blood supply. Persistent decreases in blood flow after a stroke to the remaining non-lesioned tissue have been shown to contribute to poor language recovery. The goal of the current paper is to critically examine stroke studies looking at the relationship between different neurovascular measures and language deficits and mechanisms of language recovery via changes in neurovascular metrics. Measures of perfusion or cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) provide complementary approaches to understanding neurovascular mechanisms post stroke by capturing both cerebral metabolic demands and mechanical vascular properties. While CBF measures indicate the amount of blood delivered to a certain region and serve as a proxy for metabolic demands of that area, CVR indices reflect the ability of the vasculature to recruit blood flow in response to a shortage of oxygen, such as when one is holding their breath. Increases in CBF during recovery beyond the site of the lesion have been shown to promote language gains. Similarly, CVR changes, when collateral vessels are recruited to help reorganize the flow of blood in hypoperfused regions, have been related to functional recovery post stroke. In the current review, we highlight the main findings in the literature investigating neurovascular changes in stroke recovery with a particular emphasis on how language abilities can be affected by changes in CBF and CVR. We conclude by summarizing existing methodological challenges and knowledge gaps that need to be addressed in future work in this area, outlining a promising avenue of research.
Demystifying image-based machine learning: a practical guide to automated analysis of field imagery using modern machine learning tools
Authors: Belcher Byron T. , Bower Eliana H. , Burford Benjamin , Celis Maria Rosa , Fahimipour Ashkaan K. , Guevara Isabela L. , Katija Kakani , Khokhar Zulekha , Manjunath Anjana , Nelson Samuel , Olivetti Simone , Orenstein Eric , Saleh Mohamad H. , Vaca Brayan , Valladares Salma , Hein Stella A. , Hein Andrew M.
Published: June 2023

Image-based machine learning methods are becoming among the most widely-used forms of data analysis across science, technology, engineering, and industry. These methods are powerful because they can rapidly and automatically extract rich contextual and spatial information from images, a process that has historically required a large amount of human labor. A wide range of recent scientific applications have demonstrated the potential of these methods to change how researchers study the ocean. However, despite their promise, machine learning tools are still under-exploited in many domains including species and environmental monitoring, biodiversity surveys, fisheries abundance and size estimation, rare event and species detection, the study of animal behavior, and citizen science. Our objective in this article is to provide an approachable, end-to-end guide to help researchers apply image-based machine learning methods effectively to their own research problems. Using a case study, we describe how to prepare data, train and deploy models, and overcome common issues that can cause models to underperform. Importantly, we discuss how to diagnose problems that can cause poor model performance on new imagery to build robust tools that can vastly accelerate data acquisition in the marine realm. Code to perform analyses is provided at https://github.com/heinsense2/AIO_CaseStudy.
A comparison of mesophotic and shallow sponge holobionts resilience to predicted future temperature elevation
Authors: Raijman-Nagar Lilach , Goren Liron , Shefer Sigal , Moskovich Raz , Li Zhiyong , Ilan Micha
Published: June 2023

Climate change is predicted to have detrimental impacts on sessile invertebrates, including sponges. Mesophotic ecosystems have been suggested to play a major role as refugia for coral reef sponge species, however knowledge regarding the ability of mesophotic sponges to cope with thermal stress is scarce. In this study we compared the response of the sponge Diacarnus erythraeanus, a widespread Red Sea sponge, from the shallow and mesophotic reef, to moderate and acute temperature elevation (2°C and 6°C, respectively) for short and long term periods (two and 35 days, respectively) by measuring physiological parameters (respiration, oxygen removal, pumping rates, and photosynthetic efficiency), and the microbiome composition change. The results indicated that mesophotic and shallow populations of D. erythraeanus are highly tolerant to both moderate and acute heat stress, demonstrating a high survival rate (100%) across the experimental treatments, with no visible signs of bleaching or necrosis. Exposure to heat stress resulted in significant alterations in the physiological parameters of sponges, including higher respiration rate and lower photosynthetic efficiency. These alterations were accompanied by correspondingly significant microbial adjustments, thus emphasizing the essential role of the microbiome in the host’s ability to persist when facing essential environmental stress. Moreover, while shallow and mesophotic sponges showed similar physiological tolerance to heat stress, their microbial response differed: while the microbiome diversity of the mesophotic sponges remained stable throughout the experiment, the shallow one significantly changed. This result suggests that their underlying coping mechanisms might differ between mesophotic and shallow populations. Since the associated-microbiome is largely regulated by the sponge-host genetics, difference in microbial adjustments to stress between populations, could indicate genetic variability between hosts. Therefore, while the results of this study support the hypothesis that mesophotic coral reefs could serve as thermal refugia for some sponge species, it raises the question regarding the validity of MCEs as a refuge for shallow populations. Finally, it emphasizes the crucial need to elucidate the underlying mechanisms governing the sponge-microbiome interactions, specifically in the context of the anticipated climate change scenarios.
Polystyrene nanoplastics mediated the toxicity of silver nanoparticles in zebrafish embryos
Authors: Yan Zhenhua , Zhou Yixin , Zhu Peiyuan , Bao Xuhui , Su Pengpeng
Published: June 2023

The widespread distribution of nanoplastics and nanomaterials in aquatic environments is of great concern. Nanoplastics have been found to modulate the toxicity of other environmental pollutants in organisms, while few studies have focused on their influences on nanomaterials. Thus, this study evaluated the influences of polystyrene (PS) nanoplastics on the toxicity of silver nanoparticles (AgNPs) to zebrafish (Danio rerio) embryos, including acute toxicity, oxidative stress, apoptosis, immunotoxicity, and metabolic capability. The results showed that the presence of PS nanoplastics could act as a carrier of the co-existing AgNPs in waters. The release ratio of Ag+ from AgNPs was up to 4.23%. The lethal effects of AgNPs on zebrafish embryos were not significantly changed by the co-added PS nanoplastics. Whereas, the alterations in gene expression related to antioxidant and metabolic capability in zebrafish (sod1, cat, mt2, mtf-1, and cox1) caused by AgNPs were significantly enhanced by the presence of PS nanoplastics, which simultaneously lowered the apoptosis and immunotoxicity (caspase9, nfkβ, cebp, and il-1β) induced by AgNPs. It suggests the presence of PS nanoplastics suppressed the AgNPs-induced genotoxicity in zebrafish. The released Ag+ from AgNPs may be responsible for the toxicity of AgNPs in zebrafish, while the subsequent absorption and agglomeration of AgNPs and the released Ag+ on PS nanoplastics may alleviate the toxicity.
The potential role of the gingival crevicular fluid biomarkers in the prediction of pregnancy complications
Authors: Abouzaid Maryam , Howidi Nourhan , Badran Zahi , Mohammed Ghada , Mousa Noha A.
Published: June 2023

Early and minimally invasive methods are required to predict the risk of multiple adverse pregnancy outcomes. A potential technique with growing interest utilizes the gingival crevicular fluid (GCF), a physiological serum exudate found in the healthy gingival sulcus and in the periodontal pocket in inflammatory conditions. Analysis of biomarkers in the GCF is a minimally invasive method that can be feasible and cost-effective. The potential use of GCF biomarkers along with other clinical indicators in early pregnancy may provide reliable predictors of several adverse pregnancy outcomes, therefore, reducing both maternal and fetal morbidities. Various studies have reported that increased or decreased concentrations of different biomarkers in GCF are associated with a high risk of developing pregnancy complications. In particular, such associations have been commonly demonstrated with gestational diabetes, pre-eclampsia, and pre-term birth. However, limited evidence is available regarding other pregnancy complications such as preterm premature rupture of membranes, recurrent miscarriage, small for gestational age, and hyperemesis gravidarum. In this review, we discuss the reported association between individual GCF biomarkers and common pregnancy complications. Future research is required to provide more solid evidence of the predictive value of those biomarkers in estimating women’s risk for each disorder.
Identification of differentially expressed HERV-K(HML-2) loci in colorectal cancer
Authors: Kang Qian , Guo Xin , Li Tianfu , Yang Caiqin , Han Jingwan , Jia Lei , Liu Yongjian , Wang Xiaolin , Zhang Bohan , Li Jingyun , Wen Hong-Ling , Li Hanping , Li Lin
Published: June 2023

Colorectal cancer is one of the malignant tumors with the highest mortality rate in the world. Survival rates vary significantly among patients at various stages of the disease. A biomarker capable of early diagnosis is required to facilitate the early detection and treatment of colorectal cancer. Human endogenous retroviruses (HERVs) are abnormally expressed in various diseases, including cancer, and have been involved in cancer development. Real-time quantitative PCR was used to detect the transcript levels of HERV-K(HML-2) gag, pol, and env in colorectal cancer to systematically investigate the connection between HERV-K(HML-2) and colorectal cancer. The results showed that HERV-K(HML-2) transcript expression was significantly higher than healthy controls and was consistent at the population and cell levels. We also used next-generation sequencing to identify and characterize HERV-K(HML-2) loci that were differentially expressed between colorectal cancer patients and healthy individuals. The analysis revealed that these loci were concentrated in immune response signaling pathways, implying that HERV-K impacts the tumor-associated immune response. Our results indicated that HERV-K might serve as a screening tumor marker and a target for tumor immunotherapy in colorectal cancer.
Machine learning on large scale perturbation screens for SARS-CoV-2 host factors identifies β-catenin/CBP inhibitor PRI-724 as a potent antiviral
Authors: Kelch Maximilian A. , Vera-Guapi Antonella , Beder Thomas , Oswald Marcus , Hiemisch Alicia , Beil Nina , Wajda Piotr , Ciesek Sandra , Erfle Holger , Toptan Tuna , Koenig Rainer
Published: June 2023

Expanding antiviral treatment options against SARS-CoV-2 remains crucial as the virus evolves under selection pressure which already led to the emergence of several drug resistant strains. Broad spectrum host-directed antivirals (HDA) are promising therapeutic options, however the robust identification of relevant host factors by CRISPR/Cas9 or RNA interference screens remains challenging due to low consistency in the resulting hits. To address this issue, we employed machine learning, based on experimental data from several knockout screens and a drug screen. We trained classifiers using genes essential for virus life cycle obtained from the knockout screens. The machines based their predictions on features describing cellular localization, protein domains, annotated gene sets from Gene Ontology, gene and protein sequences, and experimental data from proteomics, phospho-proteomics, protein interaction and transcriptomic profiles of SARS-CoV-2 infected cells. The models reached a remarkable performance suggesting patterns of intrinsic data consistency. The predicted HDF were enriched in sets of genes particularly encoding development, morphogenesis, and neural processes. Focusing on development and morphogenesis-associated gene sets, we found β-catenin to be central and selected PRI-724, a canonical β-catenin/CBP disruptor, as a potential HDA. PRI-724 limited infection with SARS-CoV-2 variants, SARS-CoV-1, MERS-CoV and IAV in different cell line models. We detected a concentration-dependent reduction in cytopathic effects, viral RNA replication, and infectious virus production in SARS-CoV-2 and SARS-CoV-1-infected cells. Independent of virus infection, PRI-724 treatment caused cell cycle deregulation which substantiates its potential as a broad spectrum antiviral. Our proposed machine learning concept supports focusing and accelerating the discovery of host dependency factors and identification of potential host-directed antivirals.
Fibin regulates cardiomyocyte hypertrophy and causes protein-aggregate-associated cardiomyopathy in vivo
Authors: Petersen Matthias , Schmiedel Nesrin , Dierck Franziska , Hille Susanne , Remes Anca , Senger Frauke , Schmidt Inga , Lüllmann-Rauch Renate , Müller Oliver J. , Frank Derk , Rangrez Ashraf Y. , Frey Norbert , Kuhn Christian
Published: June 2023

Despite the identification of numerous molecular pathways modulating cardiac hypertrophy its pathogenesis is not completely understood. In this study we define an unexpected role for Fibin (“fin bud initiation factor homolog”) in cardiomyocyte hypertrophy. Via gene expression profiling in hypertrophic murine hearts after transverse aortic constriction we found a significant induction of Fibin. Moreover, Fibin was upregulated in another mouse model of cardiac hypertrophy (calcineurin-transgenics) as well as in patients with dilated cardiomyopathy. Immunoflourescence microscopy revealed subcellular localization of Fibin at the sarcomeric z-disc. Overexpression of Fibin in neonatal rat ventricular cardiomyocytes revealed a strong anti-hypertrophic effect through inhibiting both, NFAT- and SRF-dependent signalling. In contrast, transgenic mice with cardiac-restricted overexpression of Fibin developed dilated cardiomyopathy, accompanied by induction of hypertrophy-associated genes. Moreover, Fibin overexpression accelerated the progression to heart failure in the presence of prohypertrophic stimuli such as pressure overload and calcineurin overexpression. Histological and ultrastructural analyses surprisingly showed large protein aggregates containing Fibin. On the molecular level, aggregate formation was accompanied by an induction of the unfolded protein response subsequent UPR-mediated apoptosis and autophagy. Taken together, we identified Fibin as a novel potent negative regulator of cardiomyocyte hypertrophy in vitro. Yet, heart-specific Fibin overexpression in vivo causes development of a protein-aggregate-associated cardiomyopathy. Because of close similarities to myofibrillar myopathies, Fibin represents a candidate gene for cardiomyopathy and Fibin transgenic mice may provide additional mechanistic insight into aggregate formation in these diseases.
Comparison of the effects of remimazolam and dexmedetomidine on early postoperative cognitive function in elderly patients with gastric cancer
Authors: Liao Yong Qing , Min Jia , Wu Zheng Xia , Hu Zhi
Published: June 2023

Purpose

To compare the effects of remimazolam and dexmedetomidine on early postoperative cognitive dysfunction (POCD) in aged gastric cancer patients.

Methods

From June to December 2022, 104 elderly patients (aged 65–80 years) received laparoscopic radical resection of gastric cancer at the First Affiliated Hospital of Nanchang University. Using the random number table approach, the patients were separated into three groups: remimazolam (Group R), dexmedetomidine (Group D), and saline (Group C). The primary outcome was the incidence of POCD, and secondary outcomes included TNF-α and S-100β protein concentrations, hemodynamics, VAS scores, anesthesia recovery indicators, and the occurrence of adverse events within 48 h postoperatively.

Results

At 3 and 7 days after surgery, there were no statistically significant differences in the incidence of POCD, the MMSE and MoCA scores between groups R and D (p > 0.05). However, compared to the saline group, both groups had higher MMSE and MoCA scores and decreased incidences of POCD. These differences were statistically significant (p < 0.05). Between group R and group D, there were no statistically significant changes (p > 0.05) in the levels of TNF-α and S-100β protein at the three time points (at the end of the surgery, 1 day later, and 3 days later). Even though neither group’s concentration of the two factors was as high as that of the saline group, the differences were statistically significant (p < 0.05). At all three time points—following induction (T2), 30 min into the operation (T3), and at the conclusion of the surgery (T4)—the heart rate and blood pressure in group R were greater than those in groups D and C. Statistics showed that the differences were significant (p < 0.05). The incidence of intraoperative hypotension was highest in group D and lowest in group R (p < 0.05). The dose of propofol and remifentanil, group C > group R > group D. Extubation and PACU residence times did not differ statistically significantly (p > 0.05) between the three groups. There was no significant difference in VAS scores between groups R and D after 24 h postoperatively (p > 0.05), although both had lower scores than group C, and the difference was statistically significant (p < 0.05). The VAS scores between the three groups at 72 h (T6) and 7 days (T7) were not statistically significant (p > 0.05). Adverse reactions such as respiratory depression, hypotension, bradycardia, agitation, drowsiness, and nausea and vomiting had the lowest incidence in group R and the highest incidence in group C (p < 0.05).

Conclusion

Remimazolam is similarly beneficial as dexmedetomidine in lowering the incidence of early POCD in aged patients after radical gastric cancer resection, probably due to reduced inflammatory response.
Human-machine interface for two-dimensional steering control with the auricular muscles
Authors: Pinheiro Daniel J. L. L. , Faber Jean , Micera Silvestro , Shokur Solaiman
Published: June 2023

Human-machine interfaces (HMIs) can be used to decode a user's motor intention to control an external device. People that suffer from motor disabilities, such as spinal cord injury, can benefit from the uses of these interfaces. While many solutions can be found in this direction, there is still room for improvement both from a decoding, hardware, and subject-motor learning perspective. Here we show, in a series of experiments with non-disabled participants, a novel decoding and training paradigm allowing naïve participants to use their auricular muscles (AM) to control two degrees of freedom with a virtual cursor. AMs are particularly interesting because they are vestigial muscles and are often preserved after neurological diseases. Our method relies on the use of surface electromyographic records and the use of contraction levels of both AMs to modulate the velocity and direction of a cursor in a two-dimensional paradigm. We used a locking mechanism to fix the current position of each axis separately to enable the user to stop the cursor at a certain location. A five-session training procedure (20–30 min per session) with a 2D center-out task was performed by five volunteers. All participants increased their success rate (Initial: 52.78 ± 5.56%; Final: 72.22 ± 6.67%; median ± median absolute deviation) and their trajectory performances throughout the training. We implemented a dual task with visual distractors to assess the mental challenge of controlling while executing another task; our results suggest that the participants could perform the task in cognitively demanding conditions (success rate of 66.67 ± 5.56%). Finally, using the Nasa Task Load Index questionnaire, we found that participants reported lower mental demand and effort in the last two sessions. To summarize, all subjects could learn to control the movement of a cursor with two degrees of freedom using their AM, with a low impact on the cognitive load. Our study is a first step in developing AM-based decoders for HMIs for people with motor disabilities, such as spinal cord injury.
Increasing reproducibility in preclinical stroke research: the correlation of immunofluorescence intensity measurements and Western blot analyses strongly depends on antibody clonality and tissue pre-treatment in a mouse model of focal cerebral ischemia
Authors: Prehn Anna , Hobusch Constance , Härtig Wolfgang , Michalski Dominik , Krueger Martin , Flachmeyer Bianca
Published: June 2023

In the setting of stroke, ischemia not only impairs neuronal function, but also detrimentally affects the different components of the neurovascular unit, which are shown to be involved in the transition from reversible to long-lasting tissue damage. In this context, the glial proteins myelin basic protein (MBP) and the 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNP) as well as the vasculature-associated basement membrane proteins laminin and collagen IV have been identified as ischemia-sensitive elements. However, available data from immunofluorescence and Western blot analyses are often found to be contradictory, which renders interpretation of the respective data rather difficult. Therefore, the present study investigates the impact of tissue pre-treatment and antibody clonality on immunofluorescence measurements of the mentioned proteins in a highly reproducible model of permanent middle cerebral artery occlusion. Here, immunofluorescence labeling using polyclonal antibodies revealed an increased immunofluorescence intensity of MBP, CNP, laminin and collagen IV in ischemic areas, although Western blot analyses did not reveal increased protein levels. Importantly, contrary to polyclonal antibodies, monoclonal ones did not provide increased fluorescence intensities in ischemic areas. Further, we were able to demonstrate that different ways of tissue pre-treatment including paraformaldehyde fixation and antigen retrieval may not only impact on fluorescence intensity measurements in general, but rather one-sidedly affect either ischemic or unaffected tissue. Therefore, immunofluorescence intensity measurements do not necessarily correlate with the actual protein levels, especially in ischemia-affected tissue and should always be complemented by different techniques to enhance reproducibility and to hopefully overcome the translational roadblock from bench to bedside.
Impact of 1-week preoperative auto-CPAP treatment on postoperative outcomes in patients undergoing heart valve replacement surgery: a prospective randomized controlled trial
Authors: Su Mei , Lin Wei , Xu Qi , Ni Buqing , Zhang Xilong , Zhang Shijiang , Ding Ning
Published: June 2023

Background

Whether preoperative continuous positive airway pressure (CPAP) treatment improves postoperative outcomes in patients undergoing cardiac valve replacement (CVR) remains unknown.

Hypothesis

This study was to evaluate the effects of 1-week perioperative auto-continuous positive airway pressure (CPAP) treatment on postoperative heart and pulmonary outcomes in patients with obstructive sleep apnea (OSA) and valvular heart disease.

Methods

Thirty-two patients with OSA and valvular heart disease were randomly assigned to 1-week CPAP (n = 15) group and non-CPAP treatments (n = 17) group. After the treatment, all patients underwent CVR surgery. The length of ICU and hospital stays, postoperative cardiac and respiratory complications were assessed and compared between the 2 groups.

Results

The results showed there was no significant difference in the baseline characteristics between the CPAP and non-CPAP treatment groups. The length of postoperative ICU and hospital stays, as well as the duration of mechanical ventilation were significantly reduced in the CPAP treatment group compared to the non-CPAP treatment group; however, there were no significant differences in cardiac complications (postoperative arrhythmias, pacemaker use, first dose of dopamine in the ICU, and first dose of dobutamine in the ICU), and respiratory complications (reintubation and pneumonia).

Conclusion

We concluded that in patients underwent CVR, preoperative use of auto-CPAP for OSA significantly decreased the duration of mechanical ventilation, and postoperative stays in the ICU and hospital.

Clinical Trial Registration: https://ClinicalTrials.gov, identifier NCT03398733.
Minimally-invasive bedside catheter haematoma aspiration followed by local thrombolysis in spontaneous supratentorial intracerebral haemorrhage: a retrospective single-center study
Authors: Hieber Maren , Lambeck Johann , Halaby Amjad , Roelz Roland , Demerath Theo , Niesen Wolf-Dirk , Bardutzky Jürgen
Published: June 2023

Background and purpose

The role of surgery in the treatment of intracerebral haemorrhage (ICH) remains controversial. Whereas open surgery has failed to show any clinical benefit, recent studies have suggested that minimal invasive procedures can indeed be beneficial, especially when they are applied at an early time point. This retrospective study therefore evaluated the feasibility of a free-hand bedside catheter technique with subsequent local lysis for early haematoma evacuation in patients with spontaneous supratentorial ICH.

Methods

Patients with spontaneous supratentorial haemorrhage of a volume of >30 mL who were treated with bedside catheter haematoma evacuation were identified from our institutional database. The entry point and evacuation trajectory of the catheter were based on a 3D-reconstructed CT scan. The catheter was inserted bedside into the core of the haematoma, and urokinase (5,000 IE) was administered every 6 h for a maximum of 4 days. Evolution of haematoma volume, perihaemorrhagic edema, midline-shift, adverse events and functional outcome were analyzed.

Results

A total of 110 patients with a median initial haematoma volume of 60.6 mL were analyzed. Haematoma volume decreased to 46.1 mL immediately after catheter placement and initial aspiration (with a median time to treatment of 9 h after ictus), and to 21.0 mL at the end of urokinase treatment. Perihaemorrhagic edema decreased significantly from 45.0 mL to 38.9 mL and midline-shift from 6.0 mm to 2.0 mm. The median NIHSS score improved from 18 on admission to 10 at discharge, and the median mRS at discharge was 4; the latter was even lower in patients who reached a target volume ≤ 15 mL at the end of local lysis. The in-hospital mortality rate was 8.2%, and catheter/local lysis-associated complications occurred in 5.5% of patients.

Conclusion

Bedside catheter aspiration with subsequent urokinase irrigation is a safe and feasible procedure for treating spontaneous supratentorial ICH, and can immediately reduce the mass effects of haemorrhage. Additional controlled studies that assess the long-term outcome and generalizability of our findings are therefore warranted.

Clinical trial registration

[www.drks.de], identifier [DRKS00007908].
Classification of human chronotype based on fMRI network-based statistics
Authors: Mason Sophie L. , Junges Leandro , Woldman Wessel , Facer-Childs Elise R. , Campos Brunno M. de , Bagshaw Andrew P. , Terry John R.
Published: June 2023

Chronotype—the relationship between the internal circadian physiology of an individual and the external 24-h light-dark cycle—is increasingly implicated in mental health and cognition. Individuals presenting with a late chronotype have an increased likelihood of developing depression, and can display reduced cognitive performance during the societal 9–5 day. However, the interplay between physiological rhythms and the brain networks that underpin cognition and mental health is not well-understood. To address this issue, we use rs-fMRI collected from 16 people with an early chronotype and 22 people with a late chronotype over three scanning sessions. We develop a classification framework utilizing the Network Based-Statistic methodology, to understand if differentiable information about chronotype is embedded in functional brain networks and how this changes throughout the day. We find evidence of subnetworks throughout the day that differ between extreme chronotypes such that high accuracy can occur, describe rigorous threshold criteria for achieving 97.3% accuracy in the Evening and investigate how the same conditions hinder accuracy for other scanning sessions. Revealing differences in functional brain networks based on extreme chronotype suggests future avenues of research that may ultimately better characterize the relationship between internal physiology, external perturbations, brain networks, and disease.
Time-related survival prediction in molecular subtypes of breast cancer using time-to-event deep-learning-based models
Authors: Zarean Shahraki Saba , Azizmohammad Looha Mehdi , Mohammadi kazaj Pooya , Aria Mehrad , Akbari Atieh , Emami Hassan , Asadi Farkhondeh , Akbari Mohammad Esmaeil
Published: June 2023

Background

Breast cancer (BC) survival prediction can be a helpful tool for identifying important factors selecting the effective treatment reducing mortality rates. This study aims to predict the time-related survival probability of BC patients in different molecular subtypes over 30 years of follow-up.

Materials and methods

This study retrospectively analyzed 3580 patients diagnosed with invasive breast cancer (BC) from 1991 to 2021 in the Cancer Research Center of Shahid Beheshti University of Medical Science. The dataset contained 18 predictor variables and two dependent variables, which referred to the survival status of patients and the time patients survived from diagnosis. Feature importance was performed using the random forest algorithm to identify significant prognostic factors. Time-to-event deep-learning-based models, including Nnet-survival, DeepHit, DeepSurve, NMLTR and Cox-time, were developed using a grid search approach with all variables initially and then with only the most important variables selected from feature importance. The performance metrics used to determine the best-performing model were C-index and IBS. Additionally, the dataset was clustered based on molecular receptor status (i.e., luminal A, luminal B, HER2-enriched, and triple-negative), and the best-performing prediction model was used to estimate survival probability for each molecular subtype.

Results

The random forest method identified tumor state, age at diagnosis, and lymph node status as the best subset of variables for predicting breast cancer (BC) survival probabilities. All models yielded very close performance, with Nnet-survival (C-index=0.77, IBS=0.13) slightly higher using all 18 variables or the three most important variables. The results showed that the Luminal A had the highest predicted BC survival probabilities, while triple-negative and HER2-enriched had the lowest predicted survival probabilities over time. Additionally, the luminal B subtype followed a similar trend as luminal A for the first five years, after which the predicted survival probability decreased steadily in 10- and 15-year intervals.

Conclusion

This study provides valuable insight into the survival probability of patients based on their molecular receptor status, particularly for HER2-positive patients. This information can be used by healthcare providers to make informed decisions regarding the appropriateness of medical interventions for high-risk patients. Future clinical trials should further explore the response of different molecular subtypes to treatment in order to optimize the efficacy of breast cancer treatments.
Targeting pre-mRNA splicing in cancers: roles, inhibitors, and therapeutic opportunities
Authors: Araki Shinsuke , Ohori Momoko , Yugami Masato
Published: June 2023

Accumulating evidence has indicated that pre-mRNA splicing plays critical roles in a variety of physiological processes, including development of multiple diseases. In particular, alternative splicing is profoundly involved in cancer progression through abnormal expression or mutation of splicing factors. Small-molecule splicing modulators have recently attracted considerable attention as a novel class of cancer therapeutics, and several splicing modulators are currently being developed for the treatment of patients with various cancers and are in the clinical trial stage. Novel molecular mechanisms modulating alternative splicing have proven to be effective for treating cancer cells resistant to conventional anticancer drugs. Furthermore, molecular mechanism-based combination strategies and patient stratification strategies for cancer treatment targeting pre-mRNA splicing must be considered for cancer therapy in the future. This review summarizes recent progress in the relationship between druggable splicing-related molecules and cancer, highlights small-molecule splicing modulators, and discusses future perspectives of splicing modulation for personalized and combination therapies in cancer treatment.
Identification of aberrantly expressed lncRNAs and ceRNA networks in multiple myeloma: a combined high-throughput sequencing and microarray analysis
Authors: Lu Min-Qiu , He Yu-Qin , Wu Yin , Zhou Hui-Xing , Jian Yuan , Gao Wen , Bao Li , Chen Wen-Ming
Published: June 2023

Background

This study aimed to explore the potential effects of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) patients using two detection methods: high-throughput sequencing and microarray.

Methods

In this study, lncRNAs were detected in 20 newly diagnosed MM patients, with 10 patients analyzed by whole transcriptome-specific RNA sequencing and 10 patients analyzed by microarray (Affymetrix Human Clariom D). The expression levels of lncRNAs, microRNAs, and messenger RNAs (mRNAs) were analyzed, and the differentially expressed lncRNAs identified by both methods were selected. The significant differentially expressed lncRNAs were further validated using PCR.

Results

This study established the aberrant expression of certain lncRNAs involved in the occurrence of MM, with AC007278.2 and FAM157C showing the most significant differences. The top 5 common pathways identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were the chemokine signaling pathway, inflammatory mediator regulation, Th17 cell differentiation, apoptosis, and NF-kappa B signaling pathway. Furthermore, three microRNAs (miRNAs) (miR-4772-3p, miR-617, and miR-618) were found to constitute competing endogenous RNA (ceRNA) networks in both sequencing and microarray analyses.

Conclusions

By the combination analysis, our understanding of lncRNAs in MM will be increased significantly. More overlapping differentially expressed lncRNAs were found to predict therapeutic targets precisely.
A multicenter, phase 1, dose escalation clinical trial (G-FORCE-1) of XRT, RRx-001 and temozolomide followed by temozolomide +/- RRx-001 in newly diagnosed glioblastoma
Authors: Fine Howard , Reid Tony , Caroen Scott , Oronsky Bryan , Abrouk Nacer , Butowski Nicholas
Published: June 2023

Introduction

The current standard of care for newly diagnosed glioblastoma (GBM) is maximum surgical resection followed by concurrent treatment with temozolomide (TMZ) and radiotherapy (RT) and then six to twelve cycles of maintenance TMZ. RRx-001, an NLRP3 inhibitor and nitric oxide (NO) donor with chemoradiosensitizing, vascular normalizing and macrophage repolarizing properties, is currently in a Phase III trial for small cell lung cancer (SCLC). The purpose of this non-randomized trial was to establish the safety and look for a signal of clinical activity of RRx-001 as an add-on to RT and TMZ in patients with newly diagnosed glioblastoma.

Methods

In this non-randomized, open-label, two part trial called G-FORCE-1 (NCT02871843), the first four cohorts of adult patients with histologically confirmed high grade gliomas received fractionated radiotherapy (60 Gy in 30 fractions over 6 weeks), daily 75 mg/m2 temozolomide and escalating doses of once weekly RRx-001 from 0.5 mg to 4 mg according to a 3+3 design followed by a 6 week no treatment interval and then standard maintenance TMZ (150 mg/m2 Cycle 1 and 200 mg/m2 in subsequent cycles) until disease progression. The second two cohorts of patients received fractionated radiotherapy (60 Gy in 30 fractions over 6 weeks), daily 75 mg/m2 temozolomide and once weekly RRx-001 4 mg followed by a 6 week no treatment interval and then two different maintenance schedules until disease progression according to the same 3+ 3 design: 1. 0.5 mg RRx-001 once weekly + 100 mg/m2 TMZ 5 days/week for up to 6 cycles of therapy; 2. 4 mg RRx-001 once weekly + 100 mg/m2 TMZ 5 days/week for up to 6 cycles of therapy

The primary endpoint was the recommended dose/maximally tolerated dose of the combination of RRx-001, TMZ and RT. Secondary endpoints were overall survival, progression free survival, objective response rate, duration of response and clinical benefit response.

Results

A total of 16 newly diagnosed glioblastoma patients were enrolled. No dose limiting toxicities were observed and no MTD was reached. The recommended dose is 4 mg. After 24 months of follow up the median OS was 21.9 months (95% CI: 11.7 – NA). PFS median was 8 months (95% CI: 5 – NA). The overall response rate was 18.8% (3 PR out of 16) and the disease control rate was 68.8% (3 PR, 8 SD out of 16).

Conclusions

The addition of RRx-001 to TMZ and RT and to TMZ during maintenance was safe and well-tolerated and deserves further study.