bluuebunny/crossref_metadata_2025 huggingface dataset:
The potential role of the thymus in immunotherapies for acute myeloid leukemia
Authors: Hino Christopher , Xu Yi , Xiao Jeffrey , Baylink David J. , Reeves Mark E. , Cao Huynh
Published: February 2023

Understanding the factors which shape T-lymphocyte immunity is critical for the development and application of future immunotherapeutic strategies in treating hematological malignancies. The thymus, a specialized central lymphoid organ, plays important roles in generating a diverse T lymphocyte repertoire during the infantile and juvenile stages of humans. However, age-associated thymic involution and diseases or treatment associated injury result in a decline in its continuous role in the maintenance of T cell-mediated anti-tumor/virus immunity. Acute myeloid leukemia (AML) is an aggressive hematologic malignancy that mainly affects older adults, and the disease’s progression is known to consist of an impaired immune surveillance including a reduction in naïve T cell output, a restriction in T cell receptor repertoire, and an increase in frequencies of regulatory T cells. As one of the most successful immunotherapies thus far developed for malignancy, T-cell-based adoptive cell therapies could be essential for the development of a durable effective treatment to eliminate residue leukemic cells (blasts) and prevent AML relapse. Thus, a detailed cellular and molecular landscape of how the adult thymus functions within the context of the AML microenvironment will provide new insights into both the immune-related pathogenesis and the regeneration of a functional immune system against leukemia in AML patients. Herein, we review the available evidence supporting the potential correlation between thymic dysfunction and T-lymphocyte impairment with the ontogeny of AML (II-VI). We then discuss how the thymus could impact current and future therapeutic approaches in AML (VII). Finally, we review various strategies to rejuvenate thymic function to improve the precision and efficacy of cancer immunotherapy (VIII).
Chronic stress boosts systemic inflammation and compromises antiviral innate immunity in Carassius gibel
Authors: Dai Caijiao , Zheng Jianduo , Qi Lin , Deng Ping , Wu Mengke , Li Lijuan , Yuan Junfa
Published: February 2023

It is generally considered that stress causes decreased immune function and render fish vulnerable to infection and diseases. However, the molecular mechanisms between stress responses and susceptibility to infections, especially viral diseases, in fish remain unknown. Understanding and monitoring the biological consequences and mechanisms underlying stress responses in fish may contribute to the improvement of animal welfare and production efficiency. In this study, long-term exposure to a variety of stressors, including chasing, overcrowding, restraint stress, and air exposure mimicking chronic stresses, in aquaculture practices was conducted in Carassius gibel to investigate the consequences of chronic stress on inflammation and antiviral capability. With the continuation of stimulation, experimental fish gradually became insensitive to the stress of net chasing and feeding with the accompaniment of upregulated gene expressed in the HPI axis and elevated levels of stress hormones. As expected, stress-induced hyperglycaemia with a decrease in the insulin signaling pathway and altered gene expression in glycolysis and gluconeogenesis, suggesting the disturbance of glycometabolism. Importantly, a link between intestinal homoeostasis and systemic low-grade inflammation in stressed C. gibel was observed, implying crosstalk among the brain, intestine, and other organs. Furthermore, the compromised antiviral capability with impaired antiviral innate immunity in stressed fish was confirmed by RNA sequencing and infection with Cyprinid herpesvirus 2 (CyHV-2), promoting the understanding of enhanced susceptibility to viral infection in stressed fish.
Inflammation produced by senescent osteocytes mediates age-related bone loss
Authors: Wang Zixuan , Zhang Xiaofei , Cheng Xing , Ren Tianxing , Xu Weihua , Li Jin , Wang Hui , Zhang Jinxiang
Published: February 2023

Purpose

The molecular mechanisms of age-related bone loss are unclear and without valid drugs yet. The aims of this study were to explore the molecular changes that occur in bone tissue during age-related bone loss, to further clarify the changes in function, and to predict potential therapeutic drugs.

Methods

We collected bone tissues from children, middle-aged individuals, and elderly people for protein sequencing and compared the three groups of proteins pairwise, and the differentially expressed proteins (DEPs) in each group were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). K-means cluster analysis was then used to screen out proteins that continuously increased/decreased with age. Canonical signaling pathways that were activated or inhibited in bone tissue along with increasing age were identified by Ingenuity Pathway Analysis (IPA). Prediction of potential drugs was performed using the Connectivity Map (CMap). Finally, DEPs from sequencing were verified by Western blot, and the drug treatment effect was verified by quantitative real-time PCR.

Results

The GO and KEGG analyses show that the DEPs were associated with inflammation and bone formation with aging, and the IPA analysis shows that pathways such as IL-8 signaling and acute-phase response signaling were activated, while glycolysis I and EIF2 signaling were inhibited. A total of nine potential drugs were predicted, with rapamycin ranking the highest. In cellular experiments, rapamycin reduced the senescence phenotype produced by the H2O2-stimulated osteocyte-like cell MLO-Y4.

Conclusion

With age, inflammatory pathways are activated in bone tissue, and signals that promote bone formation are inhibited. This study contributes to the understanding of the molecular changes that occur in bone tissue during age-related bone loss and provides evidence that rapamycin is a drug of potential clinical value for this disease. The therapeutic effects of the drug are to be further studied in animals.
Early stages of development in Mediterranean red coral (Corallium rubrum): The key role of sclerites
Authors: Giordano Bruna , Bramanti Lorenzo , Perrin Jonathan , Kahramanoğulları Ozan , Vielzeuf Daniel
Published: February 2023

Corals are ecosystem engineers whose tree-like structures give three-dimensional complexity to the habitat. Their population dynamics are affected by recruitment and juvenile survival. Therefore, several defense strategies, such as the formation of hard skeletons and/or spicules, have evolved to protect these vulnerable stages. The family Coralliidae, to which “precious corals” belong, represent an exception in the order Scleralcyonacea, as they form hard CaCO3 skeletons and small CaCO3 structures, the sclerites. The skeletogenesis of Corallium species is relatively well documented in adult colonies but remains poorly known in the early stages of the development of new colonies. To shed light on the timing of Corallium rubrum’s early skeleton formation and the role of sclerites, we focused on the first 4-years of life, applying different techniques, from scanning electron microscopy to synchrotron tomography and laser ablation inductively coupled plasma-mass spectrometry. Our results show that: 1) the first visible sclerites in the primary polyp appear at least 12 days after larval settlement, which is associated with a high CaCO3 production rate (4.5 ± 2.3 μg of CaCO3 per day). Furthermore, growth rings are visible in the sclerites, showing that fully matured sclerites grow fast, probably in 3 to 4 days. 2) Sclerites are the only biomineral product in the first year of life of C. rubrum’s colonies. 3) The evidence of a consolidated axial skeleton, intended as the inner part of the skeleton characteristic of the adult red coral (the medullary zone, MZ), is recorded for the first time in 2-year-old colonies. 4) The annular zone (AZ) around the medullary zone starts forming not before four years after settlement. Thus, primary polyp builds a deformable armor made of only sclerites during the first year. This shelter provides mechanical protection from abrasion and predation to early settled colonies. After two years, settlers are firmly and mineralogically attached to the substratum, which makes them less vulnerable to predation than younger recruits that are not anchored by the skeleton.
Bahamian seagrass extent and blue carbon accounting using Earth Observation
Authors: Blume Alina , Pertiwi Avi Putri , Lee Chengfa Benjamin , Traganos Dimosthenis
Published: February 2023

Seagrasses are among the world’s most productive ecosystems due to their vast ‘blue’ carbon sequestration rates and stocks, yet have a largely untapped potential for climate change mitigation and national climate agendas like the Nationally Determined Contributions of the Paris Agreement. To account for the value of seagrasses for these agendas, spatially explicit high-confidence seagrass ecosystem assessments guided by nationally aggregated data are necessary. Modern Earth Observation advances could provide a scalable technological solution to assess the national extent and blue carbon service of seagrass ecosystems. Here, we developed and applied a scalable Earth Observation framework within the Google Earth Engine cloud computing platform to account the national extent, blue carbon stock and sequestration rate of seagrass ecosystems across the shallow waters of The Bahamas—113,037 km2. Our geospatial ecosystem extent accounting was based on big multi-temporal data analytics of over 18,000 10-m Sentinel-2 images acquired between 2017-2021, and deep feature engineering of multi-temporal spectral, color, object-based and textural metrics with Random Forests machine learning classification. The extent accounting was trained and validated using a nationwide reference data synthesis based on human-guided image annotation, recent space-borne benthic habitat maps, and field data collections. Bahamian seagrass carbon stocks and sequestration rates were quantified using region-specific in-situ seagrass blue carbon data. The mapped Bahamian seagrass extent covers an area up to 46,792 km2, translating into a carbon storage of 723 Mg C, and a sequestration rate of 123 Mt CO2 annually. This equals up to 68 times the amount of CO2 emitted by The Bahamas in 2018, potentially rendering the country carbon-neutral. The developed accounts fill a vast mapping blank in the global seagrass map—29% of the global seagrass extent—highlighting the necessity of including their blue carbon fluxes into national climate agendas and showcasing the need for more cost-effective conservation and restoration efforts for their meadows. We envisage that the synergy between our scalable Earth Observation technology and near-future nation-specific in-situ observations can and will support spatially-explicit seagrass and ocean ecosystem accounting, accelerating effective policy-making, blue carbon crediting, and relevant financial investments in and beyond The Bahamas.
Fusion of ocean data from multiple sources using deep learning: Utilizing sea temperature as an example
Authors: Wang Mingqing , Wang Danni , Xiang Yanfei , Liang Yishuang , Xia Ruixue , Yang Jinkun , Xu Fanghua , Huang Xiaomeng
Published: February 2023

For investigating ocean activities and comprehending the role of the oceans in global climate change, it is essential to gather high-quality ocean data. However, existing ocean observation data have deficiencies such as inconsistent spatial and temporal distribution, severe fragmentation, and restricted observation depth layers. Data assimilation is computationally intensive, and other conventional data fusion techniques offer poor fusion precision. This research proposes a novel multi-source ocean data fusion network (ODF-Net) based on deep learning as a solution for these issues. The ODF-Net comprises a number of one-dimensional residual blocks that can rapidly fuse conventional observations, satellite observations, and three-dimensional model output and reanalysis data. The model utilizes vertical ocean profile data as target constraints, integrating physics-based prior knowledge to improve the precision of the fusion. The network structure contains channel and spatial attention mechanisms that guide the network model’s attention to the most crucial features, hence enhancing model performance and interpretability. Comparing multiple global sea temperature datasets reveals that the ODF-Net achieves the highest accuracy and correlation with observations. To evaluate the feasibility of the proposed method, a global monthly three-dimensional sea temperature dataset with a spatial resolution of 0.25°×0.25° is produced by fusing ocean data from multiple sources from 1994 to 2017. The rationality tests on the fusion dataset show that ODF-Net is reliable for integrating ocean data from various sources.
Updated severity and prognosis score of pulmonary alveolar proteinosis: A multi-center cohort study in China
Authors: Bai Jiu-Wu , Huang Jian-nan , Shi Shen-yun , Ge Ai , Lu Hai-wen , Sun Xiao-li , Gu Shu-yi , Liang Shuo , Cheng Ke-bin , Tian Xin-lun , Xiao Yong-long , Xu Kai-feng , Xu Jin-Fu
Published: February 2023

Background

The high-resolution computed tomography (HRCT) score is an important component of the severity and prognosis score of pulmonary alveolar proteinosis (SPSP). However, the HRCT score in SPSP only considers the extent of opacity, which is insufficient.

Methods

We retrospectively evaluated HRCT scores for 231 patients with autoimmune pulmonary alveolar proteinosis (APAP) from three centers of the China Alliance for Rare Diseases. The SPSPII was created based on the overall density and extent, incorporating the SPSP. The severity of APAP patients was assessed using disease severity scores (DSS), SPSP, and SPSPII to determine the strengths and weaknesses of the different assessment methods. We then prospectively applied the SPSPII to patients before treatment, and the curative effect was assessed after 3 months.

Results

The HRCT overall density and extent scores in our retrospective analysis were higher than the extent scores in all patients and every original extent score severity group, as well as higher related to arterial partial oxygen pressure (PaO2) than extent scores. The mild patients accounted for 61.9% based on DSS 1–2, 20.3% based on SPSP 1–3, and 20.8% based on SPSPII 1–3. Based on SPSP or SPSPII, the number of severe patients deteriorating was higher in the mild and moderate groups. When applied prospectively, arterial PaO2 differed between any two SPSPII severity groups. The alveolar-arterial gradient in PaO2 (P[A-a]O2), % predicted carbon monoxide diffusing capacity of the lung (DLCO), and HRCT score were higher in the severe group than in the mild and moderate groups. After diagnosis, mild patients received symptomatic treatment, moderate patients received pure whole lung lavage (WLL) or granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy, and severe patients received WLL and GM-CSF therapy. Importantly, the SPSPII in mild and severe groups were lower than baseline after 3 months.

Conclusion

The HRCT density and extent scores of patients with APAP were better than the extent score. The SPSPII score system based on smoking status, symptoms, PaO2, predicted DLCO, and overall HRCT score was better than DSS and SPSP for assessing the severity and efficacy and predicting the prognosis.

Trial registration

ClinicalTrial.gov, identifier: NCT04516577.
Relationship between gut microbiota and Chinook salmon (Oncorhynchus tshawytscha) health and growth performance in freshwater recirculating aquaculture systems
Authors: Zhao Ruixiang , Symonds Jane E. , Walker Seumas P. , Steiner Konstanze , Carter Chris G. , Bowman John P. , Nowak Barbara F.
Published: February 2023

Gut microbiota play important roles in fish health and growth performance and the microbiome in fish has been shown to be a biomarker for stress. In this study, we surveyed the change of Chinook salmon (Oncorhynchus tshawytscha) gut and water microbiota in freshwater recirculating aquaculture systems (RAS) for 7 months and evaluated how gut microbial communities were influenced by fish health and growth performance. The gut microbial diversity significantly increased in parallel with the growth of the fish. The dominant gut microbiota shifted from a predominance of Firmicutes to Proteobacteria, while Proteobacteria constantly dominated the water microbiota. Photobacterium sp. was persistently the major gut microbial community member during the whole experiment and was identified as the core gut microbiota for freshwater farmed Chinook salmon. No significant variation in gut microbial diversity and composition was observed among fish with different growth performance. At the end of the trial, 36 out of 78 fish had fluid in their swim bladders. These fish had gut microbiomes containing elevated proportions of Enterococcus, Stenotrophomonas, Aeromonas, and Raoultella. Our study supports the growing body of knowledge about the beneficial microbiota associated with modern salmon aquaculture systems and provides additional information on possible links between dysbiosis and gut microbiota for Chinook salmon.
Targeting of client proteins to the VCP/p97/Cdc48 unfolding machine
Authors: Meyer Hemmo , van den Boom Johannes
Published: February 2023

The AAA+ ATPase p97 (also called VCP or Cdc48) is a major protein unfolding machine with hundreds of clients in diverse cellular pathways that are critical for cell homeostasis, proliferation and signaling. In this review, we summarize recent advances in understanding how diverse client proteins are targeted to the p97 machine to facilitate client degradation or to strip clients from binding partners for regulation. We describe an elaborate system that is governed by at least two types of alternative adapters. The Ufd1-Npl4 adapter along with accessory adapters targets ubiquitylated clients in the majority of pathways and uses ubiquitin as a universal unfolding tag. In contrast, the family of SEP-domain adapters such as p37 can target clients directly to p97 in a ubiquitin-independent manner. Despite the different targeting strategies, both pathways converge by inserting the client into the p97 pore to initiate a peptide threading mechanism through the central channel of p97 that drives client protein unfolding, protein extraction from membranes and protein complex disassembly processes.
Potential environmental impacts of a plastic waste export ban in Germany
Authors: Strobel Ronja , Hagedorn Tabea , Lopes Alice do Carmo Precci
Published: February 2023

Up to 800,000 t/a of plastic waste generated in Germany is exported, of which more than a quarter is packaging. However, a sustainable waste management system aims at treating waste under consideration of environmental benefits generation and the reduction of negative environmental impacts. Thus, this brief research deals with the question to what extent negative environmental impacts could be avoided by an export ban. Further, this brief research serves as a preliminary basis for further discussions and studies in the field of the plastic export ban. Two scenarios were developed based on expert interviews to estimate alternative management for the otherwise exported plastic waste generated in Germany. A consequential life cycle assessment (LCA) was carried out to look into the possible Global Warming Potential changes of such scenarios compared to the current situation scenario. The LCA showed that an export ban in Germany offers the possibility of avoiding up to 80 CO2-equivalent per ton of exported packaging plastic. However, this would be only possible if most of the plastic packaging that is no longer exported is recycled and not burned for energy production in the case of Germany.
Study of gray matter atrophy pattern with subcortical ischemic vascular disease-vascular cognitive impairment no dementia based on structural magnetic resonance imaging
Authors: Tan Lin , Xing Jian , Wang Zhenqi , Du Xiao , Luo Ruidi , Wang Jianhang , Zhao Jinyi , Zhao Weina , Yin Changhao
Published: February 2023

Objective

This study explored the structural imaging changes in patients with subcortical ischemic vascular disease (SIVD)-vascular cognitive impairment no dementia (VCIND) and the correlation between the changes in gray matter volume and the field of cognitive impairment to provide new targets for early diagnosis and treatment.

Methods

Our study included 15 patients with SIVD-normal cognitive impairment (SIVD-NCI), 63 with SIVD-VCIND, 26 with SIVD-vascular dementia (SIVD-VD), and 14 normal controls (NC). T1-weighted images of all participants were collected, and DPABI and SPM12 software were used to process the gray matter of the four groups based on voxels. Fisher’s exact test, one-way ANOVA and Kruskal-Wallis H test were used to evaluate all clinical and demographic data and compare the characteristics of diencephalic gray matter atrophy in each group. Finally, the region of interest (ROI) of the SIVD-VCIND was extracted, and Pearson correlation analysis was performed between the ROI and the results of the neuropsychological scale.

Results

Compared to the NC, changes in gray matter atrophy were observed in the bilateral orbitofrontal gyrus, right middle temporal gyrus, superior temporal gyrus, and precuneus in the SIVD-VCIND. Gray matter atrophy was observed in the left cerebellar region 6, cerebellar crural region 1, bilateral thalamus, right precuneus, and calcarine in the SIVD-VD. Compared with the SIVD-VCIND, gray matter atrophy changes were observed in the bilateral thalamus in the SIVD-VD (p < 0.05, family-wise error corrected). In the SIVD-VCIND, the total gray matter volume, bilateral medial orbital superior frontal gyrus, right superior temporal gyrus, middle temporal gyrus, and precuneus were positively correlated with Boston Naming Test score, whereas the total gray matter volume, right superior temporal gyrus, and middle temporal gyrus were positively correlated with overall cognition.

Conclusion

Structural magnetic resonance imaging can detect extensive and subtle structural changes in the gray matter of patients with SIVD-VCIND and SIVD-VD, providing valuable evidences to explain the pathogenesis of subcortical vascular cognitive impairment and contributing to the early diagnosis of SIVD-VCIND and early warning of SIVD-VD.
A Network approach to find poor orthostatic tolerance by simple tilt maneuvers
Authors: Karemaker John M.
Published: February 2023

The approach introduced by Network Physiology intends to find and quantify connectedness between close- and far related aspects of a person’s Physiome. In this study I applied a Network-inspired analysis to a set of measurement data that had been assembled to detect prospective orthostatic intolerant subjects among people who were destined to go into Space for a two weeks mission. The advantage of this approach being that it is essentially model-free: no complex physiological model is required to interpret the data. This type of analysis is essentially applicable to many datasets where individuals must be found that “stand out from the crowd”. The dataset consists of physiological variables measured in 22 participants (4f/18 m; 12 prospective astronauts/cosmonauts, 10 healthy controls), in supine, + 30° and + 70° upright tilted positions. Steady state values of finger blood pressure and derived thereof: mean arterial pressure, heart rate, stroke volume, cardiac output, systemic vascular resistance; middle cerebral artery blood flow velocity and end-tidal pCO2 in tilted position were (%)-normalized for each participant to the supine position. This yielded averaged responses for each variable, with statistical spread. All variables i.e., the “average person’s response” and a set of %-values defining each participant are presented as radar plots to make each ensemble transparent. Multivariate analysis for all values resulted in obvious dependencies and some unexpected ones. Most interesting is how individual participants maintained their blood pressure and brain blood flow. In fact, 13/22 participants had all normalized Δ-values (i.e., the deviation from the group average, normalized for the standard deviation), both for +30° and +70°, within the 95% range. The remaining group demonstrated miscellaneous response patterns, with one or more larger Δ-values, however of no consequence for orthostasis. The values from one prospective cosmonaut stood out as suspect. However, early morning standing blood pressure within 12 h after return to Earth (without volume repletion) demonstrated no syncope. This study demonstrates an integrative way to model-free assess a large dataset, applying multivariate analysis and common sense derived from textbook physiology.
Physical inactivity before stroke is associated with dependency in basic activities of daily living 3 months after stroke
Authors: Susts Jevgenijs , Reinholdsson Malin , Sunnerhagen Katharina Stibrant , Abzhandadze Tamar
Published: February 2023

Background

Physical inactivity is a leading risk factor for non-communicable diseases, including stroke. Moreover, physical inactivity before stroke is associated with stroke severity, which, in turn, can cause disability. However, it remains unclear whether physical inactivity before stroke is associated with dependency in basic activities of daily living (ADL).

Aim

The aim of this study was to evaluate whether physical inactivity before stroke influences ADL dependency 3 months after stroke.

Methods

This longitudinal study was based on data from three Swedish registries. Patients with acute stroke who were admitted to the Sahlgrenska University Hospital between 9 November 2014 and 30 June 2019 were included in the study. Baseline data were collected from the three stroke units, and self-reported questionnaires were used to collect 3-month follow-up data. Physical inactivity before stroke was the primary independent variable that was self-reported using the Saltin–Grimby physical activity level scale. ADL dependency was a composite measure of three tasks: mobility, dressing, and toilet use. A binary logistic regression analysis was used to explain the association between physical inactivity before stroke and basic ADL 3 months after stroke.

Results

In total, 3,472 patients were included in the study. The median age was 75 years, 49% of the patients were physically inactive before stroke, and 75% had a mild stroke. ADL dependency at follow-up was reported to be 32%. Physically inactive patients, compared with physically active patients, had 2.35 times higher odds for ADL dependency 3 months after stroke (odds ratio 2.30 [95% CI 1.89 – 2.80]). The model correctly classified 84% of the patients (the area under the receiver operating characteristic curve was 0.84 [95% CI, 0.83 – 0.86]).

Conclusion

The findings of this study suggest that physical inactivity before stroke is associated with dependency in basic ADL 3 months after stroke. In addition, older age, female sex, pre-stroke living conditions, need for help, previous stroke, and admission stroke severity are significant contributors to dependency.
Prognostic value of inflammation biomarkers for 30-day mortality in critically ill patients with stroke
Authors: Zhao Jun , Feng Jinli , Ma Qian , Li Chunlin , Qiu Feng
Published: February 2023

Objective

To explore the values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), neutrophil to albumin ratio (NAR), prognostic nutritional index (PNI), systemic immune inflammatory index (SII) and red cell distribution width to albumin ratio (RA) for evaluating the risk of 30-day mortality of ischemic stroke or hemorrhagic stroke patients.

Methods

In this cohort study, the data of 1,601 patients diagnosed with stroke were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Among them, 908 were hemorrhagic stroke patients and 693 were ischemic stroke patients. Demographic and clinical variables of patients were collected. Univariate and multivariable Cox regression were performed to evaluate the predictive values of NLR, PLR, SII, NAR, RA, and PNI for 30-day mortality in hemorrhagic stroke or ischemic stroke patients. The receiver operator characteristic (ROC) curves were plotted to assess the predictive values of NLR, NAR, and RA for 30-day mortality of hemorrhagic stroke patients.

Results

At the end of follow-up, 226 hemorrhagic stroke patients and 216 ischemic stroke patients died. The elevated NLR level was associated with increased risk of 30-day mortality in hemorrhagic stroke [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.06–1.29]. The increased NAR level was associated with elevated risk of 30-day mortality in hemorrhagic stroke (HR = 1.16, 95% CI: 1.02–1.30). The high RA level was linked with increased risk of 30-day mortality (HR = 1.44, 95% CI: 1.23–1.69). No significant correlation was observed in these inflammation biomarkers with the risk of 30-day mortality in ischemic stroke patients. The area under the curves (AUCs) of NLR, RA, and NAR for evaluating the risk of 30-day mortality of hemorrhagic stroke patients were 0.552 (95% CI: 0.503–0.601), 0.644 (95% CI: 0.590–0.699) and 0.541 (95% CI: 0.490–0.592).

Conclusion

NLR, NAR, and RA were potential prognostic biomarkers for predicting 30-day mortality of hemorrhagic stroke patients, which might provide clinicians an easy and cheap way to quickly identify patients with high risk of mortality.
A wearable device for at-home obstructive sleep apnea assessment: State-of-the-art and research challenges
Authors: Tran Ngoc Thai , Tran Huu Nam , Mai Anh Tuan
Published: February 2023

In the last 3 years, almost all medical resources have been reserved for the screening and treatment of patients with coronavirus disease (COVID-19). Due to a shortage of medical staff and equipment, diagnosing sleep disorders, such as obstructive sleep apnea (OSA), has become more difficult than ever. In addition to being diagnosed using polysomnography at a hospital, people seem to pay more attention to alternative at-home OSA detection solutions. This study aims to review state-of-the-art assessment techniques for out-of-center detection of the main characteristics of OSA, such as sleep, cardiovascular function, oxygen balance and consumption, sleep position, breathing effort, respiratory function, and audio, as well as recent progress in the implementation of data acquisition and processing and machine learning techniques that support early detection of severe OSA levels.
Computational assessment of the impact of Cu(II) and Al(III) on β-amyloid42 fibrils: Binding sites, structural stability, and possible physiological implications
Authors: Roldán-Martín Lorena , Sodupe Mariona , Maréchal Jean-Didier
Published: February 2023

One of Alzheimer’s disease major hallmarks is the aggregation of β-amyloid peptide, a process in which metal ions play an important role. In the present work, an integrative computational study has been performed to identify the metal-binding regions and determine the conformational impact of Cu(II) and Al(III) ion binding to the β-amyloid (Aβ42) fibrillary structure. Through classical and Gaussian accelerated molecular dynamics, it has been observed that the metal-free fiber shows a hinge fan-like motion of the S-shaped structure, maintaining the general conformation. Upon metal coordination, distinctive patterns are observed depending on the metal. Cu(II) binds to the flexible N-terminal region and induces structural changes that could ultimately disrupt the fibrillary structure. In contrast, Al(III) binding takes place with the residues Glu22 and Asp23, and its binding reinforces the core stability of the system. These results give clues on the molecular impact of the interaction of metal ions with the aggregates and sustain their non-innocent roles in the evolution of the illness.
Effect of the one-day fasting on cortisol and DHEA daily rhythm regarding sex, chronotype, and age among obese adults
Authors: Marciniak Martyna , Sato Maki , Rutkowski Rafał , Zawada Agnieszka , Juchacz Aldona , Mahadea Dagmara , Grzymisławski Marian , Dobrowolska Agnieszka , Kawka Edyta , Korybalska Katarzyna , Bręborowicz Andrzej , Witowski Janusz , Kanikowska Dominika
Published: February 2023

Introduction

Physiological and biochemical processes in the human body occur in a specific order and show rhythmic variability. Time dependence characterizes the secretion of cortisol and dehydroepiandrosterone (DHEA). One-day fasting implies alternating fasting days and eating days. The study aimed to determine how 24-h fasting affects the daily rhythm of cortisol and DHEA levels in obese people while taking into account gender and chronotype.

Methods

Forty-nine obese patients (BMI 32.2–67.1 kg/m2; 25 women and 24 men) underwent a 3-week hospital-controlled calorie restriction diet to reduce body weight. During hospitalization, patients fasted for 1 day, during which only water could be consumed. Samples of whole mixed unstimulated saliva were collected at 2–3-h intervals over a 64-h period and analyzed for cortisol and DHEA by immunoassays. The individual chronotypes were assessed by the morning and evening questionnaire, according to Horne and Östberg. Three components of daily rhythm were evaluated: amplitude, acrophase, and the so-called MESOR.

Results

Cortisol rhythm showed differences in amplitude (p = 0.0127) and acrophase (p = 0.0005). The amplitude on the fasting day was 11% higher (p = 0.224) than the day after. The acrophase advanced on the day of fasting, 48 min earlier than the day before (p = 0.0064), and by 39 min to the day after fasting (p = 0.0005). In the rhythm of DHEA, differences were found in the MESOR (p = 0.0381). The MESOR on the fasting day increased.

Discussion

Our results obtained during 64 consecutive hours of saliva sampling suggest that one-day fasting may affect three components of cortisol and DHEA daily rhythm. Additionally, no differences were found in the daily rhythm between the morning and evening chronotypes and between females and males. Although aging did not influence daily cortisol rhythm, DHEA amplitude, MESOR, and acrophase changed with age. To the best of our knowledge, this is the first presentation of changes in DHEA rhythm during one-day fasting.
Effect of total glycosides of Cistanche deserticola on the energy metabolism of human HepG2 cells
Authors: Feng Duo , Zhou Shi-qi , Zhou Ya-xi , Jiang Yong-jun , Sun Qiao-di , Song Wei , Cui Qian-qian , Yan Wen-jie , Wang Jing
Published: February 2023

To study the anti-tumor effect of Cistanche deserticola Y. Ma, HepG2 cells were treated with 0, 3.5, 10.5, 21, 31.5, and 42 μg/ml of total glycosides (TG) from Cistanche deserticola. The HepG2 cell survival rate and 50% inhibition concentration (IC50) were detected using the CCK-8 method, and the level of reactive oxygen species (ROS) was detected by using a DCFH-DA fluorescence probe. Finally, a Seahorse XFe24 energy analyzer (Agilent, United States) was used to detect cell mitochondrial pressure and glycolytic pressure. The results showed that TG could reduce the survival rate of HepG2 cells and that the IC50 level was 35.28 μg/ml. With increasing TG concentration, the level of ROS showed a concentration-dependent upward trend. Energy metabolism showed that each dose group of TG could significantly decline the mitochondrial respiratory and glycolytic functions of HepG2 cells. In conclusion, TG could significantly inhibit the mitochondrial respiration and glycolysis functions of HepG2 cells, increase the level of ROS, and inhibit cell proliferation. Thus, this experiment pointed out that Cistanche deserticola can be used as a source of anti-cancer foods or drugs in the future. However, further studies on its mechanisms and clinical applications are needed.
A new intronic quantitative PCR method led to the discovery of transformation from human ascites to murine malignancy in a mouse model
Authors: Jin Jiankang , Huo Longfei , Fan Yibo , Wang Ruiping , Scott Ailing W. , Pizzi Melissa Pool , Yao Xiaodan , Shao Shan , Ma Lang , Da Silva Matheus S. , Yamashita Kohei , Yoshimura Katsuhiro , Zhang Boyu , Wu Jingjing , Wang Linghua , Song Shumei , Ajani Jaffer A.
Published: February 2023

Purpose

To establish a fast and accurate detection method for interspecies contaminations in the patient-derived xenograft (PDX) models and cell lines, and to elucidate possible mechanisms if interspecies oncogenic transformation is detected.

Methods

A fast and highly sensitive intronic qPCR method detecting Gapdh intronic genomic copies was developed to quantify if cells were human or murine or a mixture. By this method, we documented that murine stromal cells were abundant in the PDXs; we also authenticated our cell lines to be human or murine.

Results

In one mouse model, GA0825-PDX transformed murine stromal cells into a malignant tumorigenic murine P0825 cell line. We traced the timeline of this transformation and discovered three subpopulations descended from the same GA0825-PDX model: epithelium-like human H0825, fibroblast-like murine M0825, and main passaged murine P0825 displayed differences in tumorigenic capability in vivo. P0825 was the most aggressive and H0825 was weakly tumorigenic. Immunofluorescence (IF) staining revealed that P0825 cells highly expressed several oncogenic and cancer stem cell markers. Whole exosome sequencing (WES) analysis revealed that TP53 mutation in the human ascites IP116-generated GA0825-PDX may have played a role in the human-to-murine oncogenic transformation.

Conclusion

This intronic qPCR is able to quantify human/mouse genomic copies with high sensitivity and within a time frame of a few hours. We are the first to use intronic genomic qPCR for authentication and quantification of biosamples. Human ascites transformed murine stroma into malignancy in a PDX model.
Global scientific trends on matrix metalloproteinase and osteosarcoma: A bibliometric and visualized analysis
Authors: Wu Xin , Ma Shiwei , Wu Zhongguang , Zhao Qiangqiang
Published: February 2023

Objective

This study aimed to identify author, country, institutional, and journal collaborations and their impacts, assess the knowledge base, identify existing trends, and uncover emerging topics related to the role of Metalloproteinase in osteosarcoma.

Methods

945 Articles and reviews associated with the role of Metalloproteinase in osteosarcoma were obtained from the WoSCC and analyzed by Citespace and Vosviewer.

Results

The main aspects of research on the role of MMP in OS are invasion and metastasis. The latest hotspots were found to be the mechanism of MMP promoting invasion and metastasis, lung metastasis, and antitumor activity. Notably, invasion, metastasis, and antitumor activity were potentially turning points in the MMP-OS field. In the future, the primary research hotspot in the field of MMP-OS may be to study the mechanism, explore their role in the OS lung metastasis, and determine their role in the cancer therapy process.

Conclusion

This study thus offers a comprehensive overview of the MMP-OS-related field using bibliometrics and visual methods, which will provide a valuable reference for researchers interested in the field of MMP-OS.
Medical emergencies in pediatric blood & marrow transplant and cellular therapies
Authors: Agarwal Nikki , Rotz Seth , Hanna Rabi
Published: February 2023

Hematopoietic stem cell transplant (HCT) is used for many pediatric malignant and non-malignant diseases. However, these patients are at a high risk for emergencies post-transplant, related to prior comorbidities and treatments for the underlying disease, high dose chemotherapy regimen related toxicities, prolonged myelosuppression, and opportunistic infections due to their immunocompromised state. Emergencies can be during preparative regimen and hematopoietic progenitor cell (HPC) infusion, acute post-transplant (pre-engraftment) and late during post engraftment. Infectious complications are the most common cause of morbidity and mortality in the peri-transplant period. Sinusoidal obstructive syndrome is another life-threatening emergency seen in children undergoing HCT, especially in infants. Timely recognition and administration of defibrotide with/without steroids is key to the management of this complication. Another complication seen is transplant associated thrombotic microangiopathy. It can cause multiorgan failure if left untreated and demands urgent identification and management with complement blockade agents such as eculizumab. Cytokine release syndrome and cytokine storm is an important life-threatening complication seen after cellular therapy, and needs emergent intervention with ICU supportive care and tocilizumab. Other complications in acute period include but are not limited to: seizures from busulfan or other chemotherapy agents, PRES (posterior reversible encephalopathy syndrome), diffuse alveolar hemorrhage, idiopathic pulmonary syndrome and allergic reaction to infusion of stem cells. Acute graft versus host disease (GvHD) is a major toxicity of allogeneic HCT, especially with reduced intensity conditioning, that can affect the skin, liver, upper and lower gastrointestinal tract. There has been major development in new biomarkers for early identification and grading of GvHD, which enables application of treatment modalities such as post-transplant cyclophosphamide and JAK/STAT inhibitors to prevent and treat GvHD. Myelosuppression secondary to the chemotherapy increases risk for engraftment syndrome as well as coagulopathies, thus increasing the risk for clotting and bleeding in the pediatric population. The purpose of this article is to review recent literature in these complications seen with pediatric hematopoietic cell transplant (HCT) and cellular therapies and provide a comprehensive summary of the major emergencies seen with HCT
Postpyloric nutrition to prevent emergencies – a step away from repeat inpatient care in children with methylmalonic acidaemia and propionic acidaemia – a case report of four cases
Authors: Schumann Stefan , Rommel Frank Risto , Cantez Serdar , Alexanidou Evdokia , Kamrath Clemens , de Laffolie Jan
Published: February 2023

Methylmalonic acidaemia (MMA) and propionic acidaemia (PA) are very rare autosomal recessive inherited metabolic diseases from the group of organoacidopathies. Katabolism due to minor infections can lead to metabolic decompensation including hyperammonemia and ketoacidosis, especially in small children. We present data from a small cohort to clarify whether placement of a percutaneous endoscopic gastrostomy with jejunal tube (J-PEG) reduce metabolic imbalances and hospital stays. The aim is to prevent emergencies from occurring by preventing metabolic derailments at an early stage. 4 patients with MMA (N = 3) or PA (N = 1) were included. Data were collected at every investigation, in particular pH value, pCO2, bicarbonate, base excess, ammonia and lactate. Due to repeated metabolic derailments, a percutaneous endoscopic gastrostomy was placed for postpyloric nutrition. In conclusion, placement of a percutaneous endoscopic gastrostomy with postpyloric tube appears to reduce the rate of metabolic decompensations. In addition, hospital stays and especially the number of treatment days can be reduced. This method, especially the placement of a postpyloric tube could enable parents to prevent catabolism when vomiting begins by continuously feeding through the jejunal part, as a step to prevent a metabolic emergency from occurring.
Effect of optimal antenatal care on maternal and perinatal health in Ethiopia
Authors: Tesfay Neamin , Hailu Girmay , Woldeyohannes Fitsum
Published: February 2023

Introduction

Receiving at least four antenatal care (ANC) visits have paramount importance on the health of mothers and perinates. In Ethiopia, several studies were conducted on ANC service utilization; however, limited studies quantified the effect of care on maternal and perinate health. In response to this gap, this study is conducted to quantify the effect of optimal ANC care (≥4 visits) on maternal and perinatal health among women who received optimal care in comparison to women who did not receive optimal care.

Methods

The study utilized the Ethiopian perinatal death surveillance and response (PDSR) system dataset. A total of 3,814 reviewed perinatal deaths were included in the study. Considering the nature of the data, preferential within propensity score matching (PWPSM) was performed to determine the effect of optimal ANC care on maternal and perinatal health. The effect of optimal care was reported using average treatment effects of the treated [ATT].

Result

The result revealed that optimal ANC care had a positive effect on reducing perinatal death, due to respiratory and cardiovascular disorders, [ATT = −0.015, 95%CI (−0.029 to −0.001)] and extending intrauterine life by one week [ATT = 1.277, 95%CI: (0.563–1.991)]. While it's effect on maternal health includes, avoiding the risk of having uterine rupture [ATT = −0.012, 95%CI: (−0.018 to −0.005)], improving the utilization of operative vaginal delivery (OVD) [ATT = 0.032, 95%CI: (0.001–0.062)] and avoiding delay to decide to seek care [ATT = −0.187, 95%CI: (−0.354 to −0.021)].

Conclusion

Obtaining optimal ANC care has a positive effect on both maternal and perinatal health. Therefore, policies and interventions geared towards improving the coverage and quality of ANC services should be the top priority to maximize the benefit of the care.
Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies
Authors: Xiao Chunying , Liu Sheng , Ge Ge , Jiang Hao , Wang Liezhi , Chen Qi , Jin Chong , Mo Jinggang , Li Jin , Wang Kunpeng , Zhang Qianqian , Zhou Jianyu
Published: February 2023

Hepatocellular carcinoma (HCC) is one of the most common digestive malignancies. HCC It ranges as the fifth most common cause of cancer mortality worldwide. While The prognosis of metastatic or advanced HCC is still quite poor. Recently, locoregional treatment, especially local ablation therapies, plays an important role in the treatment of HCC. Radiofrequency ablation (RFA) and high-intensity focused ultrasound (HIFU) ablation are the most common-used methods effective and feasible for treating HCC. However, the molecular mechanisms underlying the actions of ablation in the treatments for HCC and the HCC recurrence after ablation still are poorly understood. Hypoxia-inducible factor (HIF), the key gene switch for adaptive responses to hypoxia, has been found to play an essential role in the rapid aggressive recurrence of HCC after ablation treatment. In this review, we summarized the current evidence of the roles of HIF in the treatment of HCC with ablation. Fifteen relevant studies were included and further analyzed. Among them, three clinical studies suggested that HIF-1α might serve as a crucial role in the RAF treatment of HCC or the local recurrence of HCC after RFA. The remainder included experimental studies demonstrated that HIF-1, 2α might target the different molecules (e.g., BNIP3, CA-IX, and arginase-1) and signaling cascades (e.g., VEGFA/EphA2 pathway), constituting a complex network that promoted HCC invasion and metastasis after ablation. Currently, the inhibitors of HIF have been developed, providing important proof of targeting HIF for the prevention of HCC recurrence after IRFA and HIFU ablation. Further confirmation by prospective clinical and in-depth experimental studies is still warranted to illustrate the effects of HIF in HCC recurrence followed ablation treatment in the future.