bluuebunny/crossref_metadata_2025 huggingface dataset:
Cold Case of Thrombolysis: Cold Recombinant Tissue Plasminogen Activator Confers Enhanced Neuroprotection in Experimental Stroke
Authors: Huang Yuyou , Gu Shanshan , Han Ziping , Yang Zhenghong , Zhong Liyuan , Li Lingzi , Wang Rongliang , Yan Feng , Luo Yumin , Borlongan Cesario , Lu Jie
Published: September 2023

Background

Thrombolysis and endovascular thrombectomy are the primary treatment for ischemic stroke. However, due to the limited time window and the occurrence of adverse effects, only a small number of patients can genuinely benefit from recanalization. Intraarterial injection of rtPA (recombinant tissue plasminogen activator) based on arterial thrombectomy could improve the prognosis of patients with acute ischemic stroke, but it could not reduce the incidence of recanalization‐related adverse effects. Recently, selective brain hypothermia has been shown to offer neuroprotection against stroke. To enhance the recanalization rate of ischemic stroke and reduce the adverse effects such as tiny thrombosis, brain edema, and hemorrhage, we described for the first time a combined approach of hypothermia and thrombolysis via intraarterial hypothermic rtPA.

Methods and Results

We initially established the optimal regimen of hypothermic rtPA in adult rats subjected to middle cerebral artery occlusion. Subsequently, we explored the mechanism of action mediating hypothermic rtPA by probing reduction of brain tissue temperature, attenuation of blood–brain barrier damage, and sequestration of inflammation coupled with untargeted metabolomics. Hypothermic rtPA improved neurological scores and reduced infarct volume, while limiting hemorrhagic transformation in middle cerebral artery occlusion rats. These therapeutic outcomes of hypothermic rtPA were accompanied by reduced brain temperature, glucose metabolism, and blood–brain barrier damage. A unique metabolomic profile emerged in hypothermic rtPA‐treated middle cerebral artery occlusion rats characterized by downregulated markers for energy metabolism and inflammation.

Conclusions

The innovative use of hypothermic rtPA enhances their combined, as opposed to stand‐alone, neuroprotective effects, while reducing hemorrhagic transformation in ischemic stroke.
Deladenus taedae n. sp. (Nematoda: Neotylenchidae) in Loblolly pine (Pinus taeda) woods from USA intercepted in Ningbo, P.R. China
Authors: Yu Qing , Gu Jianfeng , Ye Weimin
Published: September 2023

Deladenus taedae n. sp. was isolated from loblolly pine wood (Pinus taeda) intercepted in Ningbo, P.R. China, in imports from the USA. This new species is morphologically described and illustrated and characterised molecularly. Both mycetophagous and infective forms were recovered and described. The new species, D. taedae n. sp., resembles some other species of Deladenus in which the excretory pore is situated anterior to the hemizonid. The new species is characterised by the lateral fields with six lines, pointed tail ending and small spermatheca in mycetophagous females and short stylet in infective females. In mycetophagous females, the excretory pore is 74-98 μm from the anterior end and 37-54 μm anterior to the hemizonid. The partial rDNA 18S, complete internal transcribed spacer, 5.8S and partial 28S D2/D3 genes were amplified and sequenced. Phylogenetic analyses of the genes distinguished this new species from all other sequenced Deladenus species.
The Ascetics of Mount Aṭṭhāvaya Become Jain Monks
Authors: Dundas Paul , Bisschop Peter C.
Published: August 2023

This study presents a detailed analysis of the narrative of Goyama and the ascetics of Mount Aṭṭhāvaya in the Āvaśyaka Cūrṇi, including text and translation. By identifying a range of themes, intertexts and allusions in the narrative, a variety of Jain perspectives on the nature of asceticism are uncovered. Topics covered include the Āvaśyaka Cūrṇi as “commentary”, the Āvaśyaka Niryukti background to the Āvaśyaka Cūrṇi narrative, some possible Śaiva allusions in the narrative, the significance of Goyama’s physical appearance, Goyama’s explanation of the canonical story of Puṃḍarīa, and Goyama’s power of bestowing limitless food. In addition to the narrative told in the Āvaśyaka Cūrṇi, its earliest metrical version in the Uttarādhyayana Niryukti is discussed and translated as well.
Effect of Peptide-Lipid Conjugates Loaded PLGA Nanoparticles Against Cancer Cells In-Vitro
Authors: Koyuncu Reyhan , Duruksu Gokhan , Ozcelik Beraat , Mert Serap , Yazir Yusufhan
Published: August 2023

Complexes generated by oleic acid and milk α-lactalbumin, termed BAMLET, attracted attention because of their selective toxicity against a variety of tumors. However, the production efficiency of BAMLET needs to be increased. In this study, α-lactalbumin and
hydrolyzed α-lactalbumin were separately combined with oleic acid to obtain BAMLET and hydrolyzed BAMLET (HBAMLET) respectively. For these complexes, nanoparticles were prepared using double emulsion method and PLGA polymer as carrier. Then the tumoricidal activity and toxicity
of the BAMLET and HBAMLET complexes were analyzed on prostate cancer cells (DU145) and breast cancer cells (MCF7) In-Vitro. The most effective concentration of HBAMLET was found as 6.38 μg/mL, at which the viability of cancer cell lines was reduced to 64.63% (for MCF7) and
47.7% (for DU145). However, BAMLET was found to be less effective, reducing DU145 and MCF7 cell viability by 9.6% and 39.5% of at 2.14 μg/mL and 10 μg/mL, respectively. Unfortunately, BAMLET showed cytotoxicity on fibroblasts at higher concentrations. Encapsulated BAMLET
and HBAMLET showed promising encapsulation efficiency (72.75% and 84.44%, respectively) with a low PDI value (0.098–0.096, respectively). It was concluded that the release of HBAMLET can be controlled and can be used as an active drug agent when it was loaded in PLGA-NPs.
Electrospun Morinda citrifolia Extract-Loaded Wound Dressings Promote Diabetic Wound Healing Through Antiinflammatory and Antioxidative Activities
Authors: Ma Wenhua , Pang Zhongzhuang , Zhao Yonglin
Published: August 2023

In the current study, Morinda citrifolia extract was loaded into gelatin-based electrospun scaffolds to treat diabetic wounds. The produced scaffolds were characterized in vitro using electron microscopy, cell culture studies, antimicrobial assessment, tensile strength
assay, and water uptake capacity measurements. Wound healing function of these dressings was evaluated in a rat model of diabetic wound. Study showed that Morinda citrifolia extract-loaded wound dressings promoted diabetic wound healing by increasing wound size reduction rate and collagen
deposition.
Crucial Biological Roles of Long Noncoding RNA-Mediated Pyroptosis in Urological Tumors
Authors: Xie Jiaogui , Jiang Ying , Wang Yichao , He Dalin
Published: August 2023

Urologic neoplasm is one of the most general neoplasms, including bladder neoplam, prostate neoplasm and renal neoplasm. Researches have shown that tumor formation is a very complicated process, and it is the result of cell proliferation that is seriously out of control. Long noncoding
RNA (lncRNA) and pyroptosis act separately or together on the tumorigenesis, growth and metastasis of urinary tumors, and are related to their treatment and prognosis. In this review, we summarized existing studies and found that lncRNA-mediated pyroptosis can promote or inhibit the development
of urinary tumors. Pyroptosis can be achieved by lncRNA-caspase-gasdermin axis. Abnormal lncRNA expression may cause uncontrolled pyroptosis, thus bringing tumor deterioration and adverse prognosis. Controlling pyroptosis of neoplasm cells by regulating pyroptosis-related lncRNAs may be a
new entry for the treatment of urinary neoplasms.
Cardiomyocyte Exosomal Nanovesicles Mediating p53 to Regulate Autophagy and Protect Myocardial Infarction
Authors: Fan Ming , Xie Fei , Li Jianfeng , Li Junquan , Liang Ting
Published: August 2023

This study explores the protective mechanism of cardiomyocyte exosome nanovesicles on myocardial infarction. Enzyme activity was measured and apoptosis of rat cardiomyocytes was assessed by TdT-mediated dUTP Nick-End Labeling (TUNEL) along with analysis of myocardial function by color
Doppler echocardiogram. In addition, triphenyl tetrazolium chloride (TTC) staining evaluated the myocardial ischemia. BMSCs were co-cultured with primary cardiomyocytes followed by measuring autophagy and exosome morphology of myocardial tissue by transmission electron microscope and protein
expression by Western blot. Exosomes secreted by Bone marrow mesenchymal stem cells (BMSCs) were successfully isolated. LDH, CK, CK-MB activity, cardiomyocyte apoptosis rate, LVESD, LVEDD, LVEDP, myocardial infarction area, cell area occupied by autophagic vesicles and p53 expression in model
group were higher than control group (P <0.05) and they were lower in exosome group than model group. In addition, LVEF, LVFS, and LVSP were lower in model group and higher in exosome group (P <0.05). Model group showed significantly promoted autophagy activation and autophagosome
formation, which were inhibited by cardiomyocyte exosomes. Moreover, exosome-like vesicles were found with a diameter of 60–90 nm. Furthermore, PKH-26 staining showed that cardiomyocytes could uptake exosomes well. Myocardial injury significantly promotes autophagy activation. Moreover,
the apoptosis rate of cardiomyocytes and the area of myocardial ischemia were reduced and the cardiac function of rats with myocardial infarction was improved.
Glucan Coated Iron Oxide Nanoparticles for Regulating Survival, Inflammation and Oxidative Stress in Parkinsons Disease
Authors: Zhu Lichong , Feng Liangshu , Ma Di , Zhao Lingmin , Hao Yulei , Wang Xinyu , Nan Di , Feng Jiachun , Zhang Ying
Published: August 2023

This study assessed the mechanism of Iron Oxide Nanoparticles (IONP) coated with glucan in regulating survival, inflammation and oxidative stress in Parkinson’s disease (PD). IONP coated with glucan (NPs) was established and identified. BV-2 cells were randomly divided into the
following three sets; control set, PD set, and NPs set. Apoptotic activity of nerve cells, expression of TNF-α, IL-6 and IL-1β, and content of reactive oxygen species (ROS) and malondialdehyde (MDA) were was also analyzed. The expression of NF-κB and Inductible
Nitric Oxide Synthase (iNOS) was detected with Western Blot, while content of glialcellline-derivedneurotrophicfactor (GDNF) was analyzed by Proliferation of nerve cells was prompted and apoptosis was restrained in the NPs set. The levels of TNF-α, IL-6 and IL-1β were
reduced while contents of ROS and MDA were reduced. The expression of NF-κB and iNOS were restrained. The levels of inflammatory factors were reduced, while secretion of GDNF was reduced. The survival of nerve cells in the PD was prompted by NPs, while inflammation and oxidative
stress were restrained.
The Efficacy of Nano-Silver Alginate Dressing Combined with Tibial Transverse Transport for Stage III–IV Diabetic Foot Treatment
Authors: Liu Yanqing , Wang Jianguo , Liu Youcai , Wu Meizhen , Wu Yuelong , Zhang Yijun
Published: August 2023

To effectively treat severe diabetic foot (DF) and reduce amputation risk, we explored nano-silver alginate (Ag/Alg) dressings and tibial transverse transport (TTT) to improve circulation and suppress inflammatory responses in lower limbs. First, Ag/Alg dressings were biocompatible
without affecting L-929 cell activity, and they had better hygroscopic properties when compared with conventional dressings. Ag/Alg dressing also markedly inhibited Gram+/Gram− bacterial activity. We also retrospectively analyzed clinical data from DF patients at our hospital and divided
them into control and TTT groups according to treatment modality; the latter group was treated with TTT and Ag/Alg dressings as conventional therapy. We then compared cytokines, inflammatory responses, blood supply to the foot, and ulcer healing characteristics between pre- and post-treatments.
TTT patients displayed significantly higher angiogenesis-related cytokine levels and more effective inflammation control after treatment when compared with patients receiving conventional therapy. Additionally, more significant increases in ankle-brachial index and skin temperature, and a
greater decrease in the visual analog scale were observed in TTT patients. In terms of surface ulcer healing, TTT patients showed better healing, with healing times, amputation rates, and ulcer recurrence rates significantly reduced. Therefore, Ag/Alg dressings combined with TTT showed great
potential for severe DF therapy.
Homeobox D9 Promotes Malignant Progression of Non-Small Cell Lung Cancer Through Negatively Regulating Kallikrein Related Peptidase 9
Authors: Hao Juntao , Shen Zengqiang , Ma Junjun
Published: August 2023

We investigated the association between HOXD9 expression and prognosis in non-small cell lung cancer (NSCLC) and explored its underlying mechanisms in tumor progression. HOXD9 expression was examined in 42 pairs of NSCLC tissue samples using qRT-PCR, and its effects were evaluated in
NSCLC cell lines through lentiviral vector transfection, assessing cell growth and migration using CCK-8 and Transwell assays. Bioinformatics analysis identified KLK9 as a target gene of HOXD9, and their interaction was investigated in vitro and in vivo. HOXD9 mRNA expression
was significantly higher in NSCLC tissues compared to adjacent tissues, positively correlating with metastasis incidence and poor prognosis. HOXD9 knockdown reduced NSCLC cell migration and proliferation, while overexpression had the opposite effect. Luciferase assays confirmed HOXD9′s
binding to KLK9, leading to negative regulation of KLK9 expression. Knockdown of KLK9 reversed the inhibitory effect of HOXD9 on NSCLC cell migration and proliferation, while co-overexpression of KLK9 and HOXD9 had the opposite effect. Our findings demonstrate the close association of high
HOXD9 expression in NSCLC tissues with metastasis incidence and poor prognosis. HOXD9 likely exerts its biological function in NSCLC by negatively regulating KLK9. These results provide valuable insights into the molecular mechanisms driving NSCLC progression, highlighting HOXD9 as a potential
prognostic biomarker and therapeutic target.
The Impact of Frailty on Adjuvant Therapies Not Offered to or Declined by Breast Cancer Surgery Patients
Authors: Solsky Ian , Cairns Ashley , Martin Tamriage , Perko Allison , Friday Sarah , Levine Edward , Howard-McNatt Marissa
Published: September 2023

Introduction

The impact of frailty on adjuvant therapies not offered to or declined by elderly breast cancer surgery patients has been understudied.

Methods

This is a retrospective review of a prospectively managed single-center database including all breast cancer patients >65 years undergoing surgery in 2021. Frailty was determined using an electronic frailty index (eFI) derived from electronic health data. Patients were categorized as Fit (eFI ≤ .10), Pre-frail (.10 < eFI ≤.21), or Frail (eFI > .21). Chart review was performed to collect data on adjuvant therapies not offered or declined. Descriptive statistics and logistic regression were performed.

Results

Of 133 patients, 16.5% were frail, 46.6% were pre-frail, and 36.8% were fit. Demographics were similar among groups except age and comorbidities. Of those with adjuvant therapy indicated (n = 123), 15.4% were not offered at least one indicated therapy. Of those offered therapy, some therapy was declined in 22.7%. Frail patients more often were not offered or declined some therapy (frail: 63.2%, pre-frail 36.2%, fit: 28.2%, P = .03). Frailty was associated with having some therapy not offered or declined on univariate modeling (OR 4.4 95% CI 1.4-13.5, P = .01) but not on multivariate. Being frail was associated with higher odds of readmission at 6 months on multivariate analysis (OR 9.5, 95% CI: 1.7-54.2. P = .01).

Conclusion

Over half of frail patients are not offered or decline some adjuvant therapy. The impact of this requires further study. Given their higher odds of readmission, frail patients require close postoperative monitoring to prevent the interruption of adjuvant therapies.
Knowledge Gaps Regarding Indigenous Health in Occupational Therapy: A National Survey
Authors: Jacek Claire C. , Fritz Kassandra M. , Lizon Monique E. , Packham Tara L.
Published: September 2023

Background. There is a need for the occupational therapy profession to respond to the Truth and Reconciliation Commission of Canada Calls to Action and work towards supporting the health and well-being of Indigenous Peoples. Purpose. (1) To determine the knowledge gaps of occupational therapists about Indigenous health and (2) to create recommendations to address identified gaps and inform responses from the profession. Method. A national needs survey was created and distributed to occupational therapists across Canada to determine the knowledge of occupational therapists about Indigenous health. Survey results were analyzed using thematic analysis and descriptive statistics. Findings. Data collected from 364 survey responses informed six distinct themes representing knowledge gaps of occupational therapists related to Indigenous health as follows: lack of foundational knowledge, power relations, lifelong learner, need for appropriate tools/approaches, respectful collaboration, and environmental influences. Implications. The project offers insight into the role of the occupational therapy profession in the process of reconciliation. Insights are focused on decolonizing occupational therapy practice, building trusting relationships with Indigenous Peoples, and the provision of appropriate training for occupational therapists to engage in culturally safer practices.
Bi-directional passenger flow tracking and statistics analysis in station passageways based on an improved Deep-Sort algorithm
Authors: Wu Jianfan , Xie Zhengyu , Qin Yong , Jia Limin , Guan Ling
Published: September 2023

The normal operation of a integrated hub station is of great significance for the safe operation of the entire city’s transportation network. Accurately monitoring the passenger flow operation status of the station is the fundamental basis for achieving scientific management and control of passenger flow. In response to the urgent need for accurate and real-time detection of passenger flow in station passageways, a Yolov7-based improved Deep-Sort algorithm is proposed to detect and track bi-directional passenger flow in the passageways of integrated hub stations. Based on the Yolov7 detection algorithm, the SimAM attention mechanism was introduced to improve the accuracy of detecting passenger flow in the passageways. On the basis of the Deep-Sort tracking algorithm, the Kalman Filter (KF) method was optimized to make the tracking box of the target more accurate. Meanwhile, the Fast-ReID method was used to improve the long-term tracking of targets, thereby improving the value of IDF1. This algorithm can help to achieve real-time and accurate detection and tracking of bi-directional passenger flow in station passageways. In the event of an abnormal situation, the station staff can react rapidly to improve the station’s operational safety.
Misrepresentation and Sexual Consent: Lessons from the Law of Contract
Authors: Yean Alexander
Published: September 2023

Much has been written in support of the criminalisation of the dishonest inducement of sexual consent, but existing proposals for criminalisation have been subject to numerous powerful criticisms, including the absurdity of criminalising ‘trivial’ deceptions, the undue impingement on the right to privacy, and accusations of excessive moralism. The aim of this article is to propose a new model for the criminalisation of the dishonest inducement of sexual consent based upon the contract law doctrine of misrepresentation – the Misrepresentation Model for Sexual Consent – that addresses, or at least mitigates the force of, some of the most common and potent criticisms levied against the existing proposals for criminalisation. The strengths of the Misrepresentation Model for Sexual Consent will be shown by comparing the Misrepresentation Model for Sexual Consent against Professor Jonathan Herring's much-debated model. Further, in conceptualising and defending the Misrepresentation Model for Sexual Consent, this article will demonstrate that there is much to be gained for the development of criminal law by drawing lessons from private law.
Continuous latent state preintegration for inertial-aided systems
Authors: Le Gentil Cedric , Vidal-Calleja Teresa
Published: September 2023

Traditionally, the pose and velocity prediction of a system at time t2 given inertial measurements from a 6-DoF IMU depends on the knowledge of the system’s state at time t1. It involves a series of integration and double integration that can be computationally expensive if performed regularly, in particular in the context of inertial-aided optimisation-based state estimation. The concept of preintegration consists of creating pseudo-measurements that are independent of the system’s initial conditions (pose and velocity at t1) in order to predict the system’s state at t2. These pseudo-measurements, so-called preintegrated measurements, were originally computed numerically using the integration rectangle rule. This article presents a novel method to perform continuous preintegration using Gaussian processes (GPs) to model the system’s dynamics focusing on high accuracy. It represents the preintegrated measurement’s derivatives in a continuous latent state that is learnt/optimised according to asynchronous IMU gyroscope and accelerometer measurements. The GP models allow for analytical integration and double integration of the latent state to generate accurate preintegrated measurements called unified Gaussian preintegrated measurements (UGPMs). We show through extensive quantitative experiments that the proposed UGPMs outperform the standard preintegration method by an order of magnitude. Additionally, we demonstrate that the UGPMs can be integrated into off-the-shelf multi-modal estimation frameworks with ease based on lidar-inertial, RGBD-inertial, and visual-inertial real-world experiments.
Committed for Social Change: Analysing the Role of Frontline Health Workers During Pandemic in Rural Odisha
Authors: Sahu Skylab , Mehta Pradeep Kumar
Published: September 2023

The frontline health workers take health services directly to communities where access is either absent or often limited. The Aanganwadi workers and Accredited Social Health Activists (ASHA), among the most prominent frontline workers, act as essential to providing health facilities by bringing services to people’s doorsteps. They create awareness, provide nutritional support to children and mothers, promote universal immunisation, provide escort services for Reproductive and Child Health and so on. With the rise of coronavirus disease 2019 (COVID-19), ASHA and Anganwadi Workers (AWWs) have been expected to do supplemented work along with their regular duties. They are engaged in contact tracing, providing food supplements at the doorstep, screening the returning migrant workers, reporting suspected COVID-19 cases, doing door-to-door surveys and ensuring quarantine or isolation. However, they remain the least paid as Corona warriors and are exposed to Corona. The research found that AWWs and ASHAs are denied fundamental dignity and basic rights such as the right to recognition as workers, the right to the minimum salary and basic social security measures, which are the basic entitlement of the frontline workers in the State. The article critically analyses their role and rights during the pandemic.
Problematic parental substance use, childhood family structures and adverse outcomes in young adulthood
Authors: Frederiksen Kirsten Søndergaard , Hesse Morten , Pedersen Mads Uffe
Published: September 2023

Aim: The aim of the present study was to investigate the association between childhood family structures, including the presence or absence of problematic parental substance use (PPSU), and adverse outcomes during adolescence/young adulthood. Methods: The study population included 9,770 young people (aged 15–25 years) from samples drawn for two national surveys in Denmark during 2014–2015. By combining surveys with national register data, five types of childhood family structures were constructed based on whether the child experienced PPSU and/or family separation and the number of years the child lived with a parent with substance use problems. Using binary logistic regression models, the relationships between family structure and adverse outcomes in young adulthood (i.e., hospital admissions, mental disorders and criminality) were investigated. Results: Young people who experienced PPSU and did not live with both parents had higher odds of the different long-term adverse outcomes compared with young people who did not experience PPSU, and similar odds of the outcomes compared to youth who had not experienced PPSU and did not live with both parents. The highest odds of adverse outcomes were found among young people who experienced PPSU and lived with the parent with substance use problems for less than five years. Conclusions: Living with both parents protected against adverse outcomes in young adulthood, and if PPSU was present, the odds of adverse outcomes increased. The hypothesis that there would be a positive association between years living with a parent with substance use problems and adverse outcomes in young adulthood was not supported. Awareness should be raised in health service, educational and legal institutions about the risk for young people from families with PPSU who do not live with both parents.
Sustainable polymers targeted at the surgical and otolaryngological applications: Circularity and future
Authors: Gnatowski Przemysław , Kucińska-Lipka Justyna
Published: September 2023

The ongoing climate changes, high air and noise pollution have significant impact on humans’ health. This influence is especially visible in otolaryngology, which focuses on respiratory and hearing systems disfunctions. However, even though surgeries are done in response to diseases related to climate changes, they also have a negative impact on the environment, mostly connected with the inherence of single-use fossil fuel derived polymers. This leads to a self-perpetuating emission of greenhouse gases, as human beings developed a lot of synthetic materials to combat climate change derived dysfunctions, which itself endangers human health in a chaotic circular chain. Mitigating issues arising from using synthetic plastics would be possible by imparting biodegradable polymers from renewable resources. Nowadays, sustainable polymers are adopted mostly in emerging fields of medicine, such as 3D printing, tissue engineering of drug delivery systems. Sustainable polymers are particularly useful in otolaryngology, e.g., in the form of nasal drug eluting stents or bone substitutions. Nevertheless, some limitations in wider usage of renewable polymers in surgery should also be underlined, mainly related to lack of legislation, clinical considerations, and also inadequate materials’ circularity. Herein we briefly overviewed commonly used polymers in general surgery and otolaryngology, defined the trends in sustainable polymer usage in these fields, and highlighted the limitations in renewable polymers applications together with possible solutions. What this short review emphasizes, is that the significant increase in interest and demand for sustainable solutions will revolutionize the future of clinical treatments, where contribution to climate change and waste management will be centered in decision making protocols.
Treatment consistent with idiopathic multicentric Castleman disease guidelines is associated with improved outcomes
Authors: Pierson Sheila K. , Lim Megan S. , Srkalovic Gordan , Brandstadter Joshua D. , Sarmiento Bustamante Mateo , Shyamsundar Saishravan , Mango Natalie , Lavery Criswell , Austin Bridget , Alapat Daisy , Lechowicz Mary Jo , Bagg Adam , Li Hongzhe , Casper Corey , van Rhee Frits , Fajgenbaum David C.
Published: September 2023

Idiopathic multicentric Castleman disease (iMCD) is a rare hematologic disorder with an unknown etiology. Clinical presentation is heterogeneous, ranging from mild constitutional symptoms with lymphadenopathy to life-threatening multiorgan dysfunction. International, consensus treatment guidelines developed in 2018 relied upon a limited number of clinical trials and small case series; however, to our knowledge, real-world performance of these recommendations has not been subsequently studied. Siltuximab, a monoclonal antibody against interleukin 6 (IL6), is approved for the treatment of iMCD and recommended first-line, and tocilizumab, a monoclonal antibody directed against the IL6 receptor, is recommended when siltuximab is unavailable. Chemotherapy, rituximab, and immunomodulators are recommended as second- and third-line treatments based on limited evidence. Corticosteroid monotherapy is used by clinicians, although not recommended. Here, we draw upon the ACCELERATE Natural History Registry to inventory regimens and evaluate regimen response for 102 expert–confirmed iMCD cases. Siltuximab with/without (w/wo) corticosteroids was associated with a 52% response, whereas corticosteroid monotherapy was associated with a 3% response. Anti-IL6–directed therapy with siltuximab or tocilizumab demonstrated better response and more durability than was observed with rituximab w/wo corticosteroids. Cytotoxic chemotherapy was associated with a 52% response and was predominantly administered in patients characterized by thrombocytopenia, anasarca, fever, renal failure/reticulin fibrosis, and organomegaly. Our results provide evidence in support of current recommendations to administer anti-IL6 as first-line treatment, to administer cytotoxic chemotherapy in patients with severe refractory disease, and to limit corticosteroid monotherapy. Evidence remains limited for effective agents for patients who are refractory to anti-IL6–directed therapy. This trial was registered at www.clinicaltrials.gov as #NCT02817997.
Holistic view of the seascape dynamics and environment impact on macro-scale genetic connectivity of marine plankton populations
Authors: Laso-Jadart Romuald , O’Malley Michael , Sykulski Adam M. , Ambroise Christophe , Madoui Mohammed-Amin
Published: September 2023

Background

Plankton seascape genomics studies have revealed different trends from large-scale weak differentiation to microscale structures. Previous studies have underlined the influence of the environment and seascape on species differentiation and adaptation. However, these studies have generally focused on a few single species, sparse molecular markers, or local scales. Here, we investigated the genomic differentiation of plankton at the macro-scale in a holistic approach using Tara Oceans metagenomic data together with a reference-free computational method.

Results

We reconstructed the FST-based genomic differentiation of 113 marine planktonic taxa occurring in the North and South Atlantic Oceans, Southern Ocean, and Mediterranean Sea. These taxa belong to various taxonomic clades spanning Metazoa, Chromista, Chlorophyta, Bacteria, and viruses. Globally, population genetic connectivity was significantly higher within oceanic basins and lower in bacteria and unicellular eukaryotes than in zooplankton. Using mixed linear models, we tested six abiotic factors influencing connectivity, including Lagrangian travel time, as proxies of oceanic current effects. We found that oceanic currents were the main population genetic connectivity drivers, together with temperature and salinity. Finally, we classified the 113 taxa into parameter-driven groups and showed that plankton taxa belonging to the same taxonomic rank such as phylum, class or order presented genomic differentiation driven by different environmental factors.

Conclusion

Our results validate the isolation-by-current hypothesis for a non-negligible proportion of taxa and highlight the role of other physicochemical parameters in large-scale plankton genetic connectivity. The reference-free approach used in this study offers a new systematic framework to analyse the population genomics of non-model and undocumented marine organisms from a large-scale and holistic point of view.
Intact fibroblast growth factor 23 in heart failure with reduced and mildly reduced ejection fraction
Authors: Vergaro Giuseppe , Del Franco Annamaria , Aimo Alberto , Gentile Francesco , Castiglione Vincenzo , Saponaro Federica , Masotti Silvia , Prontera Concetta , Fusari Niccolò , Emdin Michele , Passino Claudio
Published: September 2023

Background

Fibroblast growth factor-23 (FGF23) has been associated to left ventricular (LV) hypertrophy and heart failure (HF) severity. We aimed to investigate the clinical correlates and prognostic value of intact FGF23 (iFGF23) in HF patients.

Methods

Patients with stable HF and left ventricular ejection fraction (LVEF) < 50% were prospectively enrolled, managed according to current recommendations and followed over time. iFGF23 was measured at baseline with a fully automated immuno-chemiluminescent assay.

Results

We enrolled 150 patients (82% males; median age 65 years). First, second, and third iFGF23 tertiles were < 35.2 pg/mL, 35.2–50.9 pg/mL, and > 50.9 pg/mL. LVEF decreased from the first iFGF23 tertile to the third tertile (p = 0.014). N-terminal pro-B-type natriuretic peptide (NT-proBNP) increased from the first to the third tertile (p = 0.001), while peak oxygen consumption decreased (p < 0.001). Thirty-five patients (23%) experienced the primary endpoint (all-cause death or HF hospitalization at 5 years), and 26 (17%) the secondary endpoint (all-cause death at 5 years). On multivariable analysis, iFGF23 independently predicted the primary endpoint on top of age, gender and LVEF (HR 4.6 [95% CI 2.1–10.3], p < 0.001), age, gender and eGFR (HR 4.1 [95% CI 1.6–10.3], p = 0.003), as well as age, gender and NT-proBNP (HR 3.6 [95% CI 1.6–8.2], p = 0.002). iFGF23 even reclassified patient risk on top of all the 3 models, with NRI values of 0.65 (95% CI 0.30–1.01), 0.55 (95% CI 0.25–0.88), and 0.60 (95% CI 0.24–0.96), respectively (both p < 0.001).

Conclusions

Circulating iFGF23 is associated with disease severity and outcome in HF patients with reduced and mildly reduced ejection fraction.
A protocol-based treatment for ruptured abdominal aortic aneurysm contributed to improving aorta-related mortality: a retrospective cohort study
Authors: Takei Yusuke , Tezuka Masahiro , Saito Shunsuke , Ogasawara Takeshi , Seki Masahiro , Kato Takashi , Kanno Yasuyuki , Hirota Shotaro , Shibasaki Ikuko , Fukuda Hirotsugu
Published: September 2023

Background

Recent guidelines state that improving the survival rate of patients with ruptured abdominal aortic aneurysm (rAAA) requires a protocol or algorithm for the emergency management of these patients. We aimed to investigate whether introducing a protocol treatment for rAAA improves clinical outcomes compared with the pre-protocol strategy.

Methods

At our institution, 92 patients treated for rAAA between June 2008 and August 2022 were retrospectively analyzed. In 2014, the protocol-based treatment was introduced comprising a transfer algorithm to shorten the time to proximal control, use of an endovascular occlusion balloon, strict indications for endovascular aortic aneurysm repair (EVAR) or open surgical repair, and perioperative care, including for abdominal compartment syndrome (ACS). Clinical outcomes were compared between the protocol and pre-protocol group, including operative status, all-cause mortality, and rAAA-related death at 30-day, in-hospital, and 1-year postoperative follow-ups.

Results

Overall, 52 and 40 patients received the protocol-based and pre-protocol treatments, respectively. EVAR was more frequently performed in the protocol group. The rate of achieving time to proximal control was significantly faster, and the transfusion volume was lower in the protocol group. ACS occurred more frequently in the protocol group with a higher EVAR. No difference was found in all-cause mortality between the two groups. The protocol group exhibited fewer rAAA-related deaths than the pre-protocol group during the following time points: 30 days (9.6% vs. 22.5%), during the hospital stay (11.5% vs. 30.0%), and 1 year (14.5% vs. 31.5%).

Conclusions

The protocol-based treatment improved the survival rate of patients with rAAA.
Vector flow mapping analysis of left ventricular vortex performance in type 2 diabetic patients with early chronic kidney disease
Authors: Chen Xiaoxue , Qiu Fang , Wang Wei , Qi Zhengqin , Lyu Damin , Xue Kun , Sun Lijuan , Song Degang
Published: September 2023

Background

Diabetes is the leading cause of chronic kidney disease (CKD) and contributes to an elevated incidence of diastolic dysfunction in the early stages of CKD. Intracardiac vortex is a novel hemodynamic index for perceiving cardiac status. Here, we visualized left ventricular (LV) vortex characteristics using vector flow mapping (VFM) in type 2 diabetic patients with early CKD.

Methods

This cross-sectional study included 67 controls and 89 type 2 diabetic patients with stages 2-3a CKD. All subjects underwent transthoracic echocardiographic examination. LV anterior vortex during early diastole (E-vortex), atrial contraction (A-vortex) and systole (S-vortex) were assessed using VFM in the apical long-axis view. Its relation to glycemia or LV filling echocardiographic parameters were further analyzed using correlation analysis.

Results

Type 2 diabetic patients with early CKD had a small area (439.94 ± 132.37 mm2 vs. 381.66 ± 136.85 mm2, P = 0.008) and weak circulation (0.0226 ± 0.0079 m2/s vs. 0.0195 ± 0.0070 m2/s, P = 0.013) of E-vortex, but a large area (281.52 ± 137.27 mm2 vs. 514.83 ± 160.33 mm2, P ˂ 0.001) and intense circulation (0.0149 ± 0.0069 m2/s vs. 0.0250 ± 0.0067 m2/s, P < 0.001) of A-vortex compared to controls. CKD patients with poorly controlled hyperglycemia had stronger A-vortex (area: 479.06 ± 146.78 mm2 vs. 559.96 ± 159.27 mm2, P = 0.015; circulation: 0.0221 ± 0.0058 m2/s vs. 0.0275 ± 0.0064 m2/s, P < 0.001) and S-vortex (area: 524.21 ± 165.52 mm2 vs. 607.87 ± 185.33 mm2, P = 0.029; circulation: 0.0174 ± 0.0072 m2/s vs. 0.0213 ± 0.0074 m2/s, P = 0.015), and a longer relative duration of S-vortex (0.7436 ± 0.0772 vs. 0.7845 ± 0.0752, P = 0.013) than those who had well-controlled hyperglycemia. Glycemia, and E/A (a LV filling parameter) were respectively found to had close correlation to the features of A-vortex and S-vortex (all P < 0.05).

Conclusions

Abnormal LV vortices were detected in type 2 diabetic patients with early CKD using VFM, especially in those who neglected hyperglycemic control. LV vortex might be a promising parameter to slow or halt the hyperglycemia-induced diastolic dysfunction in early CKD.
A care substitution service in the Netherlands: impact on referral, cost, and patient satisfaction
Authors: Albada Trijntje , Berger Marjolein Y. , Brunninkhuis Wim , van Kalken Daphne , Vermeulen Karin M. , Damstra Robert J. , Holtman Gea A.
Published: September 2023

Background

In care substitution services, medical specialists offer brief consultations to provide general practitioners (GPs) with advice on diagnosis, treatment, or hospital referral. When GPs serve as gatekeepers to secondary care, these regional services could reduce pressures on healthcare systems. The aim is to determine the impact of implementing a care substitution service for dermatology, orthopaedics, and cardiology on the hospital referral rate, health care costs, and patient satisfaction.

Methods

A before-after study was used to evaluate hospital referral rates and health care costs during a follow-up period of 1 year. The study population comprised patients with eligible International Classification of Primary Care codes for referral to the care substitution service (only dermatology, orthopaedic, cardiology indications), as pre-defined by GPs and medical specialists. We compared referral rates before and after implementation by χ2 tests and evaluated patient preference by qualitative analysis.

Results

In total, 4,930 patients were included, 2,408 before and 2,522 after implementation. The care substitution service decreased hospital referrals during the follow-up period from 15 to 11%. The referral rate decreased most for dermatology (from 15 to 9%), resulting in a cost reduction of €10.59 per patient, while the other two specialisms experienced smaller reductions in referral rates. Patients reported being satisfied, mainly because of the null cost, improved organisation, improved care, and positive experience of the consultation.

Conclusions

The care substitution service showed promise for specialisms that require fewer hospital facilities, as exemplified by dermatology.
TRIM69: a marker of metastasis and potential sensitizer to 5-Fluorouracil and PD-1 blockers in colon adenocarcinoma
Authors: Chi Xiao-Jv , Song Yi-Bei , Liu Deng-He , Wei Li-Qiang , Zhao An-Ran , An Xin , Feng Zi-Zhen , Lan Xiao-Hua , Lv Yu-Meng , Li Hong-jun , Lan Dong , He Hui-Min
Published: August 2023

Background

Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD).

Methods

mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients’ clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients.

Results

TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers.

Conclusions

From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.
Elderly and their companion animals, cause for pleasure or for harm, a case report of a non-bite Pasteurella multocida bacteremia in an 85-year-old woman with a fatal outcome
Authors: Ali Evien , Tytgat Niek , Vergote Lieven , Devue Katleen , Nonneman Bart
Published: September 2023

We present a case of an elderly woman suffering from Pasteurella multocida (P. multocida) bacteremia, without obvious bite marks, but owning a pet dog. Although the patient was not immunocompromised, and prompt treatment with intravenous antibiotics was initiated, she developed severe septic shock with multiple organ failure and died. In healthy individuals, an infection caused by these bacteria is easy to treat and often harmless, whereas in elderly serious complications can occur. We believe this report of a fatal outcome of a P. multocida bacteremia in a non-immunocompromised, but elderly patient is important, given the growing cohort of elderly pet-owners seeking medical care. A greater awareness of this zoonosis and its potentially fatal outcome is warranted.
“They said we’re all in it together, but we were kind of separated”: barriers to access, and suggestions for improving access to official information about COVID-19 vaccines for migrants in Australia
Authors: Pourmarzi Davoud , Fitzpatrick Petya , Allen Keeley , Yuen Aidan , Lambert Stephen
Published: September 2023

Background

Vaccination is a cornerstone of public health measures to mitigate the burden of COVID-19 infection. Equitable access to information is necessary to ensure all members of society can make an informed decision about COVID-19 vaccines. We sought to investigate barriers that migrants living in Australia faced in accessing official information about COVID-19 vaccines and identify potential solutions.

Methods

This study used a descriptive qualitative study design. Seventeen adults living in Australia and born in the World Health Organization’s Eastern Mediterranean Region participated in a semi-structured interview conducted via telephone. Participants were recruited using advertising through social media platforms. The interviews were conducted between December 2021 and February 2022. All interviews were audio-recorded and transcribed verbatim. Data were analysed using inductive thematic analysis. In this study official information was defined as information provided by Australian Health system.

Results

Barriers to accessing official information about COVID-19 vaccines were related to unmet language needs, methods of dissemination, and mistrust in official sources of information. To overcome barriers, participants suggested improving the quality and timeliness of language support, using diverse modes of dissemination, working with members of migrant communities, providing opportunities for two-way communication, communicating uncertainty, and building a broader foundation of trust.

Conclusion

Information about COVID-19 vaccines during different stages of the vaccination program should be provided in migrants’ languages at the same time that it is available in English using a variety of methods for dissemination. The acceptability of official information can be improved by communicating uncertainty, acknowledging people’s concerns about the safety and effectiveness of COVID-19 vaccines and providing opportunities for two-way communication. People’s trust in official sources of health information can be improved by working with migrant communities and recognising migrants’ contributions to society. The findings of this study may improve managing the response to COVID-19 and other health emergencies in Australia and in other similar societies.