bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing the paradigm in health and care services: modern value chains using open innovation for the creation of new digital health solutions
Authors: Carrilho Joana , Videira Diogo , Campos Cláudia , Midão Luis , Costa Elísio
Published: June 2023

Digital Health is a subject of extensive discourse when considering its current and future significance. This significance arises from a convergence of various factors, including the escalating capabilities and cost-effectiveness of computing and communication technology, coupled with the mounting demands and challenges faced by healthcare systems. The integration of health and technology, when studied collectively with the purpose of addressing tangible real-world issues, holds the potential to generate substantial outcomes that greatly influence the provision of clinical and social care, thereby enhancing the overall well-being of both individuals and populations. In this sense, in this paper we propose a collaborative approach, using Open Innovation, where the most relevant stakeholders—health and care professionals, citizens and companies—work together to develop and validate innovative digital solutions for health and care. We have called this approach of value co-creation theCollaborative Ecosystem, and we focus specifically on the potential development of the Regional Ecosystem for Collaborative Innovation in Digital Health and Care, and the envisioned implications of its implementation in economic and social dimensions.
Economic web-building behavior and behavioral investment trade-offs in a cobweb spider
Authors: Zhang Haixin , Wen Lelei , Li Zichang , Li Changchun
Published: June 2023

Web-building spiders that build detritus-based bell-shaped cobwebs are model organisms for studies on behavioral plasticity because their web architecture components are easily quantified and behavioral investments are clearly separated. We investigated the web architectures and behavioral investments of the cobwebs built by Campanicola campanulata under different weight (heavy, medium, and light) detritus to research its cobweb architecture variation and analyzed the investment trade-off between foraging and defense. The results showed that spiders could actively choose lighter detritus to build retreats to reduce material and energy cost. There was a clear trade-off between defense and foraging investment of spiders choosing different weight detritus for their webs. The total length of gumfooted lines (foraging investment) was longer for the spiders that chose lighter detritus, but the energy expenditure during web-building (defense investment) was higher for the spiders that chose heavier detritus.
Plasticity plays a dominant role in regulating the phenological variations of sugar maple populations in Canada
Authors: Guo Xiali , Buttò Valentina , Mohytych Vasyl , Klisz Marcin , Surget-Groba Yann , Huang Jianguo , Delagrange Sylvain , Rossi Sergio
Published: June 2023

Global changes affect the growing conditions of terrestrial ecosystems, causing a mismatch between plant phenology and local climates in Northern regions. Due to their long lifespan and irregular regeneration periods, trees cannot respond quickly enough to climate variability through long-term genetic adaptation. In this study, we explored the phenological plasticity and genetic variation among populations of bud burst in sugar maple (Acer saccharum Marsh.) seedlings from 30 Canadian provenances with contrasting climates planted in two common gardens near and at the northern limit of the species’ range. We tested the hypothesis that phenotypic plasticity and genetic variation among populations affect bud phenology. We expect that phenotypic plasticity is more important in regulating bud phenology due to the high variability in short-term weather events characterizing this part of North America. Bud development and leafing occurred in April–May, with complete bud burst lasting between 21 and 29  days. On average, bud swelling differed by 12  days between common gardens. Both factors site (common gardens) and provenance significantly affected bud burst, demonstrating phenological plasticity and genetic variation of sugar maple, respectively. A significant interaction between site and provenance was also found. Overall, the site (11.8–90.3%) contributed more than provenance (0–3.1%) to the variance in timings of bud burst, indicating a dominant role of plasticity in regulating spring phenology. Our study demonstrated the concurring effects of genetic variation and phenological plasticity of sugar maple and revealed the dominant role of the latter factor. The high plasticity observed in sugar maple has a crucial role in the phenological adaptation of maple and the survival of its local populations in a context of changing climate.
Case report: Chorea and cognitive decline in a young woman: instrumental and genetic assessment of a case originally diagnosed as multiple sclerosis
Authors: Dato Clemente , Micaglio Emanuele , Moresco Giada , Rondinone Ornella , Vitali Paolo , Pappone Carlo , Fontana Laura , Miozzo Monica , Bet Luciano
Published: June 2023

We describe the case of a young woman affected by debilitating chorea and rapidly progressive cognitive decline. While her original diagnosis was multiple sclerosis, we performed a full instrumental and genetic assessement, though which we identified multiple genetic variants, including a novel variant of the APP gene. We propose some possible mechanisms by which such variants may contribute to neuroinflammation and ultimately lead to this devastating clinical course.
Australian parental perceptions of genomic newborn screening for non-communicable diseases
Authors: Casauria Sarah , Lewis Sharon , Lynch Fiona , Saffery Richard
Published: June 2023

Background: Newborn bloodspot screening (NBS) programs have improved neonatal healthcare since the 1960s. Genomic sequencing now offers potential to generate polygenic risk score (PRS) that could be incorporated into NBS programs, shifting the focus from treatment to prevention of future noncommunicable disease (NCD). However, Australian parents’ knowledge and attitudes regarding PRS for NBS is currently unknown.

Methods: Parents with at least one Australian-born child under 18 years were invited via social media platforms to complete an online questionnaire aimed at examining parents’ knowledge of NCDs, PRS, and precision medicine, their opinions on receiving PRS for their child, and considerations of early-intervention strategies to prevent the onset of disease.

Results: Of 126 participants, 90.5% had heard the term “non-communicable disease or chronic condition,” but only 31.8% and 34.4% were aware of the terms “polygenic risk score” and “precision medicine” respectively. A large proportion of participants said they would consider screening their newborn to receive a PRS for allergies (77.9%), asthma (81.0%), cancer (64.8%), cardiovascular disease (65.7%), mental illness (56.7%), obesity (49.5%), and type 2 diabetes (66.7%). Additionally, participants would primarily consider diet and exercise as interventions for specific NCDs.

Discussion: The results from this study will inform future policy for genomic NBS, including expected rate of uptake and interventions that parents would consider employing to prevent the onset of disease.
Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging
Authors: Jin Yunjie , Gao Peng , Liang Lifei , Wang Yuhang , Li Jiawei , Wang Jiyan , Hou Jiangang , Yang Cheng , Wang Xiaolin
Published: June 2023

Objective

Endomyocardial biopsy is the gold standard method for the diagnosis of cardiac allograft rejection. However, it causes damage to the heart. In this study, we developed a noninvasive method for quantification of granzyme B (GzB) in vivo by targeted ultrasound imaging, which detects and provides quantitative information for specific molecules, for acute rejection assessment in a murine cardiac transplantation model.

Methods

Microbubbles bearing anti-GzB antibodies (MBGzb) or isotype antibodies (MBcon) were prepared. Hearts were transplanted from C57BL/6J (allogeneic) or C3H (syngeneic) donors to C3H recipients. Target ultrasound imaging was performed on Days 2 and 5 post-transplantations. A pathologic assessment was performed. The expression of granzyme B and IL-6 in the heart was detected by Western blotting.

Results

After MB injection, we observed and collected data at 3 and 6 min before and after the flash pulse. Quantitative analysis revealed that the reduction in peak intensity was significantly higher in the allogeneic MBGzb group than in the allogeneic MBcon group and the isogeneic MBcon group at PODs 2 and 5. In the allogeneic groups, granzyme B and IL-6 expression levels were higher than those in the isogeneic group. In addition, more CD8 T cells and neutrophils were observed in the allogeneic groups.

Conclusion

Ultrasound molecular imaging of granzyme B can be used as a noninvasive method for acute rejection detection after cardiac transplantation.
Particulate matter 10 exposure affects intestinal functionality in both inflamed 2D intestinal epithelial cell and 3D intestinal organoid models
Authors: Son Ye Seul , Son Naeun , Yu Won Dong , Baek Aruem , Park Young-Jun , Lee Moo-Seung , Lee Seon-Jin , Kim Dae-Soo , Son Mi-Young
Published: June 2023

Background

A growing body of evidence suggests that particulate matter (PM10) enters the gastrointestinal (GI) tract directly, causing the GI epithelial cells to function less efficiently, leading to inflammation and an imbalance in the gut microbiome. PM10 may, however, act as an exacerbation factor in patients with inflamed intestinal epithelium, which is associated with inflammatory bowel disease.

Objective

The purpose of this study was to dissect the pathology mechanism of PM10 exposure in inflamed intestines.

Methods

In this study, we established chronically inflamed intestinal epithelium models utilizing two-dimensional (2D) human intestinal epithelial cells (hIECs) and 3D human intestinal organoids (hIOs), which mimic in vivo cellular diversity and function, in order to examine the deleterious effects of PM10 in human intestine-like in vitro models.

Results

Inflamed 2D hIECs and 3D hIOs exhibited pathological features, such as inflammation, decreased intestinal markers, and defective epithelial barrier function. In addition, we found that PM10 exposure induced a more severe disturbance of peptide uptake in inflamed 2D hIECs and 3D hIOs than in control cells. This was due to the fact that it interferes with calcium signaling, protein digestion, and absorption pathways. The findings demonstrate that PM10-induced epithelial alterations contribute to the exacerbation of inflammatory disorders caused by the intestine.

Conclusions

According to our findings, 2D hIEC and 3D hIO models could be powerful in vitro platforms for the evaluation of the causal relationship between PM exposure and abnormal human intestinal functions.
Loss of the mammalian G-protein coupled receptor, G2A, modulates severity of invasive pulmonary aspergillosis
Authors: Steffan Breanne N. , Calise Dante , Park Sung Chul , Niu Mengyao , Yang Jun , Hammock Bruce D. , Jones MaryJane , Steele Chad , Keller Nancy P.
Published: June 2023

Background

Aspergillus fumigatus is a well-known opportunistic pathogen that causes a range of diseases including the often-fatal disease, invasive pulmonary aspergillosis (IPA), in immunocompromised populations. The severity of IPA is dependent on both host- and pathogen-derived signaling molecules that mediate host immunity and fungal growth. Oxylipins are bioactive oxygenated fatty acids known to influence host immune response and Aspergillus developmental programs. Aspergillus synthesizes 8-HODE and 5,8-diHODE that have structural similarities to 9-HODE and 13-HODE, which are known ligands of the host G-protein-coupled receptor G2A (GPR132).

Materials and methods

Oxylipins were extracted from infected lung tissue to assess fungal oxylipin production and the Pathhunter β-arrestin assay was used to assess agonist and antagonist activity by fungal oxylipins on G2A. An immunocompetent model of A. fumigatus infection was used to assess changes in survival and immune responses for G2A-/- mice.

Results

Here we report that Aspergillus oxylipins are produced in lung tissue of infected mice and in vitro ligand assays suggest 8-HODE is a G2A agonist and 5,8-diHODE is a partial antagonist. To address the hypothesis that G2A could be involved in the progression of IPA, we assessed the response of G2A-/- mice to A. fumigatus infection. G2A-/- mice showed a survival advantage over wild-type mice; this was accompanied by increased recruitment of G2A-/- neutrophils and increased levels of inflammatory markers in A. fumigatus-infected lungs.

Conclusions

We conclude that G2A suppresses host inflammatory responses to Aspergillus fumigatus although it remains unclear if fungal oxylipins are involved in G2A activities.
Hemophagocytic inflammatory syndrome in ADA-SCID: report of two cases and literature review
Authors: Fratini Elena Sophia , Migliavacca Maddalena , Barzaghi Federica , Fossati Claudia , Giannelli Stefania , Monti Ilaria , Casiraghi Miriam , Ferrua Francesca , Recupero Salvatore , Consiglieri Giulia , Calbi Valeria , Tucci Francesca , Gallo Vera , Bernardo Maria Ester , Cenciarelli Sabina , Palmoni Monica , Moni Margherita , Galimberti Luca , Duse Marzia , Leonardi Lucia , Sieni Elena , Soncini Elena , Porta Fulvio , Notarangelo Lucia Dora , De Santis Raffaella , Ladogana Saverio , Aiuti Alessandro , Cicalese Maria Pia
Published: June 2023

Hemophagocytic inflammatory syndrome (HIS) is a rare form of secondary hemophagocytic lymphohistiocytosis caused by an impaired equilibrium between natural killer and cytotoxic T-cell activity, evolving in hypercytokinemia and multiorgan failure. In the context of inborn errors of immunity, HIS occurrence has been reported in severe combined immunodeficiency (SCID) patients, including two cases of adenosine deaminase deficient-SCID (ADA-SCID). Here we describe two additional pediatric cases of ADA-SCID patients who developed HIS. In the first case, HIS was triggered by infectious complications while the patient was on enzyme replacement therapy; the patient was treated with high-dose corticosteroids and intravenous immunoglobulins with HIS remission. However, the patient required HLA-identical sibling donor hematopoietic stem cell transplantation (HSCT) for a definitive cure of ADA-SCID, without HIS relapse up to 13 years after HSCT. The second patient presented HIS 2 years after hematopoietic stem cell gene therapy (GT), secondarily to Varicella-Zoster vaccination and despite CD4+ and CD8+ lymphocytes’ reconstitution in line with other ADA SCID patients treated with GT. The child responded to trilinear immunosuppressive therapy (corticosteroids, Cyclosporine A, Anakinra). We observed the persistence of gene-corrected cells up to 5 years post-GT, without HIS relapse. These new cases of children with HIS, together with those reported in the literature, support the hypothesis that a major dysregulation in the immune system can occur in ADA-SCID patients. Our cases show that early identification of the disease is imperative and that a variable degree of immunosuppression could be an effective treatment while allogeneic HSCT is required only in cases of refractoriness. A deeper knowledge of immunologic patterns contributing to HIS pathogenesis in ADA-SCID patients is desirable, to identify new targeted treatments and ensure patients’ long-term recovery.
Immune responses in healthy adults elicited by a bivalent norovirus vaccine candidate composed of GI.4 and GII.4 VLPs without adjuvant
Authors: Waerlop Gwenn , Janssens Yorick , Jacobs Bart , Jarczowski Franziska , Diessner André , Leroux-Roels Geert , Klimyuk Victor , Leroux-Roels Isabel , Thieme Frank
Published: June 2023

The development of an efficacious vaccine against norovirus is of paramount importance given its potential to reduce the global burden of norovirus-associated morbidity and mortality. Here, we report a detailed immunological analysis of a phase I, double-blind, placebo-controlled clinical trial performed on 60 healthy adults, ages 18 to 40. Total serum immunoglobulin and serum IgA against vaccine strains and cross-reactive serum IgG against non-vaccine strains were measured by enzyme immunoassays, whereas cell-mediated immune responses were quantified using intracellular cytokine staining by flow cytometry. A significant increase in humoral and cellular responses, e.g., IgA and CD4+ polypositive T cells, was triggered by the GI.4 Chiba 407 (1987) and GII.4 Aomori 2 (2006) VLP-based norovirus vaccine candidate rNV-2v, which is formulated without adjuvant. No booster effect was observed after the second administration in the pre-exposed adult study population. Furthermore, a cross-reactive immune response was elicited, as shown by IgG titers against GI.3 (2002), GII.2 OC08154 (2008), GII.4 (1999), GII.4 Sydney (2012), GII.4 Washington (2018), GII.6 Maryland (2018), and GII.17 Kawasaki 308 (2015). Due to viral infection via mucosal gut tissue and the high variety of potentially relevant norovirus strains, a focus should be on IgA and cross-protective humoral and cell-mediated responses in the development of a broadly protective, multi-valent norovirus vaccine.

Clinical trial registration

https://clinicaltrials.gov, identifier NCT05508178. EudraCT number: 2019-003226-25.
Inhibitors of the CD73-adenosinergic checkpoint as promising combinatory agents for conventional and advanced cancer immunotherapy
Authors: Kurago Zoya , Guo Gang , Shi Huidong , Bollag Roni J. , Groves Michael W. , Byrd J. Kenneth , Cui Yan
Published: June 2023

The cell surface enzyme CD73 is increasingly appreciated as a pivotal non-redundant immune checkpoint (IC) in addition to PD-1/PD-L1 and CTLA-4. CD73 produces extracellular adenosine (eADO), which not only inhibits antitumor T cell activity via the adenosine receptor (AR) A2AR, but also enhances the immune inhibitory function of cancer-associated fibroblasts and myeloid cells via A2BR. Preclinical studies show that inhibition of the CD73-adenosinergic pathway in experimental models of many solid tumors either as a monotherapy or, more effectively, in combination with PD-1/PD-L1 or CTLA-4 IC blockades, improves antitumor immunity and tumor control. Consequently, approximately 50 ongoing phase I/II clinical trials targeting the CD73-adenosinergic IC are currently listed on https://clinicaltrials.gov. Most of the listed trials employ CD73 inhibitors or anti-CD73 antibodies alone, in combination with A2AR antagonists, and/or with PD-1/PD-L1 blockade. Recent evidence suggests that the distribution of CD73, A2AR and A2BR in tumor microenvironments (TME) is heterogeneous, and this distribution affects CD73-adenosinergic IC function. The new insights have implications for the optimally effective, carefully tailored approaches to therapeutic targeting of this essential IC. In the mini-review, we briefly discuss the cellular and molecular mechanisms of CD73/eADO-mediated immunosuppression during tumor progression and therapy in the spatial context of the TME. We include preclinical data regarding therapeutic CD73-eADO blockade in tumor models as well as available clinical data from completed trials that targeted CD73-adenosinergic IC with or without PD-1/PD-L1 inhibitors and discuss factors that are potentially important for optimal therapeutic outcomes in cancer patients.
Zoop to poop: assessment of microparticle loads in gray whale zooplankton prey and fecal matter reveal high daily consumption rates
Authors: Torres Leigh G. , Brander Susanne M. , Parker Julia I. , Bloom Elissa M. , Norman Robyn , Van Brocklin Jennifer E. , Lasdin Katherine S. , Hildebrand Lisa
Published: June 2023

The ocean continues to be a sink for microparticle (MP) pollution, which includes microplastics and other anthropogenic debris. While documentation of MP in marine systems is now common, we lack information on rates of MP ingestion by baleen whales and their prey. We collected and assessed MP loads in zooplankton prey and fecal samples of gray whales (Eschrichtius robustus) feeding in coastal Oregon, USA and produced the first estimates of baleen whale MP consumption rates from empirical data of zooplankton MP loads (i.e., not modeled). All zooplankton species examined were documented gray whale prey items (Atylus tridens, Holmesimysis sculpta, Neomysis rayii) and contained an average of 4 MP per gram of tissue, mostly of the microfiber morphotype. We extrapolated MP loads in zooplankton prey to estimate the daily MP consumption rates of pregnant and lactating gray whales, which ranged between 6.5 and 21 million MP/day. However, these estimates do not account for MP ingested from ambient water or benthic sediments, which may be high for gray whales given their benthic foraging strategy. We also assessed MP loads in fecal samples from gray whales feeding in the same spatio-temporal area and detected MP in all samples examined, which included microfibers and significantly larger morphotypes than in the zooplankton. We theorize that gray whales ingest MP via both indirect trophic transfer from their zooplankton prey and directly through indiscriminate consumption of ambient MPs when foraging benthically where they consume larger MP morphotypes that have sunk and accumulated on the seafloor. Hence, our estimated daily MP consumption rates for gray whales are likely conservative because they are only based on indirect MP ingestion via prey. Our results improve the understanding of MP loads in marine ecosystems and highlight the need to assess the health impacts of MP consumption on zooplankton and baleen whales, particularly due to the predominance of microfibers in samples, which may be more toxic and difficult to excrete than other MP types. Furthermore, the high estimated rates of MP consumption by gray whales highlights the need to assess health consequences to individuals and subsequent scaled-up effects on population vital rates.
Wind work on oceanic mesoscale eddies in the Northeast Tropical Pacific Ocean
Authors: Teng Fangyuan , Dong Changming , Lim Kam Sian Kenny Thiam Choy , Ji Jinlin , Zhu Weijun
Published: June 2023

The transfer of atmospheric kinetic energy to the ocean is one of the major concerns in climate research. According to previous studies, the work of wind stress on oceanic mesoscale eddy is negative in most oceans, referred to as “eddy killing”. However, another recent work, finds that the wind work on an eddy varies with interaction time. To better understand the wind work on eddies, the present study uses satellite remote sensing wind stress data and eddy data from 2000 to 2021 to investigate the effects of wind stress on eddies in the northeast tropical Pacific (NETP). The study demonstrates that the work done by the wind stress on eddies in this region varies seasonally and that there is a strong spatiotemporal link between the work done and the wind stress curl. The work of wind stress with positive (negative) curl on the entire area of a cyclonic eddy is positive (negative), and vice versa on an anticyclonic eddy. These results indicate that wind energy input is sensitive to wind stress curl, and eddies do not always hinder wind energy input in this area.
BONCAT-FACS-Seq reveals the active fraction of a biocrust community undergoing a wet-up event
Authors: Trexler Ryan V. , Van Goethem Marc W. , Goudeau Danielle , Nath Nandita , Malmstrom Rex R. , Northen Trent R. , Couradeau Estelle
Published: June 2023

Determining which microorganisms are active within soil communities remains a major technical endeavor in microbial ecology research. One promising method to accomplish this is coupling bioorthogonal non-canonical amino acid tagging (BONCAT) with fluorescence activated cell sorting (FACS) which sorts cells based on whether or not they are producing new proteins. Combined with shotgun metagenomic sequencing (Seq), we apply this method to profile the diversity and potential functional capabilities of both active and inactive microorganisms in a biocrust community after being resuscitated by a simulated rain event. We find that BONCAT-FACS-Seq is capable of discerning the pools of active and inactive microorganisms, especially within hours of applying the BONCAT probe. The active and inactive components of the biocrust community differed in species richness and composition at both 4 and 21 h after the wetting event. The active fraction of the biocrust community is marked by taxa commonly observed in other biocrust communities, many of which play important roles in species interactions and nutrient transformations. Among these, 11 families within the Firmicutes are enriched in the active fraction, supporting previous reports indicating that the Firmicutes are key early responders to biocrust wetting. We highlight the apparent inactivity of many Actinobacteria and Proteobacteria through 21 h after wetting, and note that members of the Chitinophagaceae, enriched in the active fraction, may play important ecological roles following wetting. Based on the enrichment of COGs in the active fraction, predation by phage and other bacterial members, as well as scavenging and recycling of labile nutrients, appear to be important ecological processes soon after wetting. To our knowledge, this is the first time BONCAT-FACS-Seq has been applied to biocrust samples, and therefore we discuss the potential advantages and shortcomings of coupling metagenomics to BONCAT to intact soil communities such as biocrust. In all, by pairing BONCAT-FACS and metagenomics, we are capable of highlighting the taxa and potential functions that typifies the microbes actively responding to a rain event.
Unleashing the potential of dance: a neuroplasticity-based approach bridging from older adults to Parkinson’s disease patients
Authors: Meulenberg Cécil J. W. , Rehfeld Kathrin , Jovanović Saša , Marusic Uros
Published: June 2023

Parkinson’s disease (PD) is a neurodegenerative disorder that affects >1% of individuals worldwide and is manifested by motor symptoms such as tremor, rigidity, and bradykinesia, as well as non-motor symptoms such as cognitive impairment and depression. Non-pharmacological interventions such as dance therapy are becoming increasingly popular as complementary therapies for PD, in addition to pharmacological treatments that are currently widely available. Dance as a sensorimotor activity stimulates multiple layers of the neural system, including those involved in motor planning and execution, sensory integration, and cognitive processing. Dance interventions in healthy older people have been associated with increased activation of the prefrontal cortex, as well as enhanced functional connectivity between the basal ganglia, cerebellum, and prefrontal cortex. Overall, the evidence suggests that dance interventions can induce neuroplastic changes in healthy older participants, leading to improvements in both motor and cognitive functions. Dance interventions involving patients with PD show better quality of life and improved mobility, whereas the literature on dance-induced neuroplasticity in PD is sparse. Nevertheless, this review argues that similar neuroplastic mechanisms may be at work in patients with PD, provides insight into the potential mechanisms underlying dance efficacy, and highlights the potential of dance therapy as a non-pharmacological intervention in PD. Further research is warranted to determine the optimal dance style, intensity, and duration for maximum therapeutic benefit and to determine the long-term effects of dance intervention on PD progression.
Clinical characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease according to their epitopes
Authors: Seok Jin Myoung , Jeon Mi Young , Chung Yeon Hak , Ju Hyunjin , Lee Hye Lim , Kwon Soonwook , Min Ju-Hong , Kang Eun-Suk , Kim Byoung Joon
Published: June 2023

Background

The detection of myelin oligodendrocyte glycoprotein autoantibodies (MOG-Ab) is essential for the diagnosis of MOG-Ab-associated disease (MOGAD). The clinical implications of different epitopes recognized by MOG-Ab are largely unknown. In this study, we established an in-house cell-based immunoassay for detecting MOG-Ab epitopes and examined the clinical characteristics of patients with MOG-Ab according to their epitopes.

Methods

We conducted a retrospective review of patients with MOG-Ab-associated disease (MOGAD) in our single center registry, and collected serum samples from enrolled patients. Human MOG variants were generated to detect epitopes recognized by MOG-Ab. The differences in clinical characteristics according to the presence of reactivity to MOG Proline42 (P42) were evaluated.

Results

Fifty five patients with MOGAD were enrolled. Optic neuritis was the most common presenting syndrome. The P42 position of MOG was a major epitope of MOG-Ab. The patients with a monophasic clinical course and childhood-onset patients were only observed in the group that showed reactivity to the P42 epitope.

Conclusion

We developed an in-house cell-based immunoassay to analyze the epitopes of MOG-Ab. The P42 position of MOG is the primary target of MOG-Ab in Korean patients with MOGAD. Further studies are needed to determine the predictive value of MOG-Ab and its epitopes.
Fluorescence microscopy-based sensitive method to quantify dopaminergic neurodegeneration in a Drosophila model of Parkinson’s disease
Authors: Ayajuddin Mohamad , Chaurasia Rahul , Das Abhik , Modi Priyanka , Phom Limamanen , Koza Zevelou , Yenisetti Sarat Chandra
Published: June 2023

Death of dopaminergic (DAergic) neurons in the substantia nigra pars compacta of the human brain is the characteristic pathological feature of Parkinson’s disease (PD). On exposure to neurotoxicants, Drosophila too exhibits mobility defects and diminished levels of brain dopamine. In the fly model of sporadic PD, our laboratory has demonstrated that there is no loss of DAergic neuronal number, however, a significant reduction in fluorescence intensity (FI) of secondary antibodies that target the primary antibody-anti-tyrosine hydroxylase (TH). Here, we present a sensitive, economical, and repeatable assay to characterize neurodegeneration based on the quantification of FI of the secondary antibody. As the intensity of fluorescence correlates with the amount of TH synthesis, its reduction under PD conditions denotes the depletion in the TH synthesis, suggesting DAergic neuronal dysfunction. Reduction in TH protein synthesis is further confirmed through Bio-Rad Stain-Free Western Blotting. Quantification of brain DA and its metabolites (DOPAC and HVA) using HPLC-ECD further demonstrated the depleted DA level and altered DA metabolism as evident from enhanced DA turnover rate. Together all these PD marker studies suggest that FI quantification is a refined and sensitive method to understand the early stages of DAergic neurodegeneration. FI quantification is performed using ZEN 2012 SP2, a licensed software from Carl Zeiss, Germany. This method will be of good use to biologists, as it with few modifications, can also be implemented to characterize the extent of degeneration of different cell types. Unlike the expensive and cumbersome confocal microscopy, the present method using fluorescence microscopy will be a feasible option for fund-constrained neurobiology laboratories in developing countries.
Micronutrient intake inadequacies in different types of milk consumers in Indonesian children 1–5 years: dietary modeling with young child milk improved nutrient intakes
Authors: Sunardi Diana , Wibowo Yulianti , Mak Tsz Ning , Wang Dantong
Published: June 2023

Background

Indonesian children under-five have a high prevalence of micronutrient deficiencies. Improving young child feeding practices may be the solution. Increasing the consumption of appropriate milk products could help to reduce nutrient inadequacy.

Methods

The objective of this study was to assess nutrient inadequacy in Indonesian children to evaluate the potential improvement using dietary modeling analysis. Data from children aged 1–5 years from the Indonesian Individual Dietary Consumption Survey in 2014 were used in this analysis (n = 11,020). Diet modeling was conducted in two scenarios, substitution volume to volume and calories to calories.

Results

The proportion of children consuming young child milk (YCM) was the highest compared to other milk types across all age groups, followed by condensed milk and cow’s milk. YCM, also called “Growing-Up Milk” (GUM), are marketed as a product specifically formulated for the nutritional needs of young children. YCM consumers had lower prevalence of inadequate intakes in iron, zinc, vitamins A, C and D across age groups when compared to condensed milk consumers. The prevalence of inadequate intakes of nutrients in condensed milk consumers was Vitamin A (67, 64%), folate (92, 91%), Vitamin D (87, 84%), iron (84, 76%), and zinc (76, 76%) in 1–2y and 3–4y, respectively. The substitution of condensed milk with a YCM reduced the prevalence of inadequate intakes of micronutrients, such as Vitamin A, vitamin D, folate, iron and zinc, which are important for immune function. YCM reduced the prevalence of inadequate intakes of micronutrients by 20–40% (Vit A and folate) and 40–50% (Vit D and zinc). The reduction of prevalence of inadequate iron intake was 31% in 1–2y and 63% in 3–4y.

Conclusion

The prevalence of inadequate micronutrient intakes was high among children aged 1–5 years old in Indonesia. YCM consumers had better nutrient intake. The substitution of condensed milk with a YCM reduced the prevalence of inadequate of micronutrient intake. Thus, nutrient intakes could be improved by YCM consumption in 1–5 years old children in Indonesia, along with nutrition education on feeding practices.
Case report: A rare case of synchronous mucinous neoplasms of the renal pelvis and the appendix
Authors: Zou Yuhua , Xie Xiaojuan , Wang Qinlin , Zhong Cunzhi , Liu Quanliang
Published: June 2023

Background

Mucinous neoplasms are tumors arising in the epithelial tissue, characterized by excessive mucin secretion. They mainly emerge in the digestive system and rarely in the urinary system. They also seldom develop in the renal pelvis and the appendix asynchronously or simultaneously. The concurrence of this disease in these two regions has not yet been reported. In this case report, we discuss the diagnosis and treatment of synchronous mucinous neoplasms of the right renal pelvis and the appendix. The mucinous neoplasm of the renal pelvis was preoperatively misdiagnosed as pyonephrosis caused by renal stones, and the patient underwent laparoscopic nephrectomy. Herein, we summarize our experience with this rare case in combination with related literature.

Case presentation

In this case, A 64‐year‐old female was admitted to our hospital with persistent pain in the right lower back for over a year. Computer tomography urography (CTU) showed that the patient was confirmed as right kidney stone with large hydronephrosis or pyonephrosis, and appendiceal mucinous neoplasm (AMN). Subsequently, the patient was transferred to the gastrointestinal surgery department. Simultaneously, electronic colonoscopy with biopsy suggested AMN. Open appendectomy plus abdominal exploration was performed after obtaining informed consent. Postoperative pathology indicated low-grade AMN (LAMN) and the incisal margin of the appendix was negative. The patient was re‐admitted to the urology department, and underwent laparoscopic right nephrectomy because she was misdiagnosed with calculi and pyonephrosis of the right kidney according to the indistinctive clinical symptoms, standard examination of the gelatinous material, and imaging findings. Postoperative pathology suggested a high‐grade mucinous neoplasm of the renal pelvis and mucin residing partly in the interstitium of the cyst walls. Good follow-up results were obtained for 14 months.

Conclusion

Synchronous mucinous neoplasms of the renal pelvis and the appendix are indeed uncommon and have not yet been reported. Primary renal mucinous adenocarcinoma is very rare, metastasis from other organs should be first considered, especially in patients with long-term chronic inflammation, hydronephrosis, pyonephrosis, and renal stones, otherwise, misdiagnosis and treatment delay may occur. Hence, for patients with rare diseases, strict adherence to treatment principles and close follow‐up are necessary to achieve favorable outcomes.
Metagenomic next-generation sequencing in a diagnosis of Pneumocystis pneumonia in an X-linked immunodeficient child: a case report
Authors: Qing Lu , Zhao Yufei , Zhang Ye , Guan Yuanlin , Lu Guoyan
Published: June 2023

Background

The diagnosis ofPneumocystispneumonia (PCP) remains challenging in certain specific clinical situations. Metagenomic next-generation sequencing (mNGS), as a novel diagnostic method, may help in the diagnosis of PCP.

Case presentation

A 6-month-old male child developed acute pneumonia and sepsis. This child had previously suffered fromEscherichia colisepticemia and was cured. However, the fever and dyspnea relapsed. Blood tests revealed a low lymphocyte count (0.69 × 109/L) and acute inflammatory markers such as high-level procalcitonin (8.0 ng/ml) and C-reactive protein (19 mg/dl). Chest imaging showed inflammation and decreased translucency in both lungs but no thymus shadow. Various serology tests, the 1,3-beta-D-glucan test, culture, as well as sputum smear failed to detect any pathogens. mNGS with blood helped identify 133 specific nucleic acid sequences ofPneumocystis jirovecii, suggesting an infection with this pathogen. After treatment with trimethoprim-sulfamethoxazole for 5 days, the patient's condition improved, but the child still needed ventilator support. Unfortunately, the child died soon after because of respiratory failure after his parents decided to abandon treatment. The family declined an autopsy on the child, and therefore, an anatomical diagnosis could not be obtained. Whole-exome sequencing suggested X-linked immunodeficiency. A hemizygous mutation of c.865c > t (p.r289*) was detected in theIL2RGgene, which was inherited from the mother (heterozygous state).

Conclusion

This case report highlights the value of mNGS in diagnosing PCP when conventional diagnostic methods fail to identify the agent. Early onset of recurrent infectious diseases may indicate the presence of an immunodeficiency disease, for which timely genetic analysis and diagnosis are crucial.
Comparison of clinical characteristics and healthcare resource use of pediatric chronic and non-chronic critically ill patients in intensive care units: a retrospective national registry study
Authors: Grandjean Chantal , Perez Marie-Hélène , Ramelet Anne-Sylvie ,   The OCToPuS Consortium
Published: June 2023

Introduction

Chronic critically ill patients (CCI) in pediatric intensive care unit (PICU) are at risk of negative health outcomes, and account for a considerable amount of ICU resources. This study aimed to (a) describe the prevalence of CCI children, (b) compare their clinical characteristics and ICU resources use with non-CCI children, and (c) identify associated risk factors of CCI.

Methods

A retrospective national registry study including 2015–2017 data from the eight Swiss PICUs of five tertiary and three regional hospitals, admitting a broad case-mix of medical and surgical patients, including pre- and full-term infants. CCI patients were identified using an adapted definition: PICU length of stay (LOS) ≥8 days and dependence on ≥1 PICU technology.

Results

Out of the 12,375 PICU admissions, 982 (8%) were CCI children and compared to non-CCI children, they were younger (2.8 vs. 6.7 months), had more cardiac conditions (24% vs. 12%), and higher mortality rate (7% vs. 2%) (p < 0.001). Nursing workload was higher in the CCI compared to the non-CCI group (22 [17–27]; 21 [16–26] respectively p < 0.001). Factors associated with CCI were cardiac (aOR = 2.241) and neurological diagnosis (aOR = 2.062), surgery (aORs between 1.662 and 2.391), ventilation support (aOR = 2.278), high mortality risk (aOR = 1.074) and agitation (aOR = 1.867).

Conclusion

the results confirm the clinical vulnerability and the complexity of care of CCI children as they were defined in our study. Early identification and adequate staffing is required to provide appropriate and good quality care.
Cuproptosis-related genes signature and validation of differential expression and the potential targeting drugs in temporal lobe epilepsy
Authors: Yang Xiaolin , Zhang Xiaoqing , Shen Kaifeng , Wang Zhongke , Liu Guolong , Huang Kaixuan , He Zeng , Li Yang , Hou Zhi , Lv Shengqing , Zhang Chunqing , Yang Hui , Liu Shiyong , Ke Yanyan
Published: June 2023

Introduction: Temporal lobe epilepsy (TLE) is the most common subtype of epilepsy in adults and is characterized by neuronal loss, gliosis, and sprouting mossy fibers in the hippocampus. But the mechanism underlying neuronal loss has not been fully elucidated. A new programmed cell death, cuproptosis, has recently been discovered; however, its role in TLE is not clear.

Methods: We first investigated the copper ion concentration in the hippocampus tissue. Then, using the Sample dataset and E-MTAB-3123 dataset, we analyzed the features of 12 cuproptosis-related genes in TLEs and controls using the bioinformatics tools. Then, the expression of the key cuproptosis genes were confirmed using real-time PCR and immunohistochemical staining (IHC). Finally, the Enrichr database was used to screen the small molecules and drugs targeting key cuproptosis genes in TLE.

Results: The Sample dataset displayed four differentially expressed cuproptosis-related genes (DECRGs; LIPT1, GLS, PDHA1, and CDKN2A) while the E-MTAB-3123 dataset revealed seven DECRGs (LIPT1, DLD, FDX1, GLS, PDHB, PDHA1, and DLAT). Remarkably, only LIPT1 was uniformly upregulated in both datasets. Additionally, these DECRGs are implicated in the TCA cycle and pyruvate metabolism—both crucial for cell cuproptosis—as well as various immune cell infiltrations, especially macrophages and T cells, in the TLE hippocampus. Interestingly, DECRGs were linked to most infiltrating immune cells during TLE’s acute phase, but this association considerably weakened in the latent phase. In the chronic phase, DECRGs were connected with several T-cell subclasses. Moreover, LIPT1, FDX1, DLD, and PDHB were related to TLE identification. PCR and IHC further confirmed LIPT1 and FDX1’s upregulation in TLE compared to controls. Finally, using the Enrichr database, we found that chlorzoxazone and piperlongumine inhibited cell cuproptosis by targeting LIPT1, FDX1, DLD, and PDHB.

Conclusion: Our findings suggest that cuproptosis is directly related to TLE. The signature of cuproptosis-related genes presents new clues for exploring the roles of neuronal death in TLE. Furthermore, LIPT1 and FDX1 appear as potential targets of neuronal cuproptosis for controlling TLE’s seizures and progression.
Identification of signaling pathways modifying human dopaminergic neuron development using a pluripotent stem cell-based high-throughput screening automated system: purinergic pathways as a proof-of-principle
Authors: Boissart Claire , Lasbareilles Marie , Tournois Johana , Chatrousse Laure , Poullion Thifaine , Benchoua Alexandra
Published: June 2023

Introduction: Alteration in the development, maturation, and projection of dopaminergic neurons has been proposed to be associated with several neurological and psychiatric disorders. Therefore, understanding the signals modulating the genesis of human dopaminergic neurons is crucial to elucidate disease etiology and develop effective countermeasures.

Methods: In this study, we developed a screening model using human pluripotent stem cells to identify the modulators of dopaminergic neuron genesis. We set up a differentiation protocol to obtained floorplate midbrain progenitors competent to produce dopaminergic neurons and seeded them in a 384-well screening plate in a fully automated manner.

Results and Discussion: These progenitors were treated with a collection of small molecules to identify the compounds increasing dopaminergic neuron production. As a proof-of-principle, we screened a library of compounds targeting purine- and adenosine-dependent pathways and identified an adenosine receptor 3 agonist as a candidate molecule to increase dopaminergic neuron production under physiological conditions and in cells invalidated for the HPRT1 gene. This screening model can provide important insights into the etiology of various diseases affecting the dopaminergic circuit development and plasticity and be used to identify therapeutic molecules for these diseases.
An anatomically detailed arterial-venous network model. Cerebral and coronary circulation
Authors: Müller Lucas O. , Watanabe Sansuke M. , Toro Eleuterio F. , Feijóo Raúl A. , Blanco Pablo J.
Published: June 2023

In recent years, several works have addressed the problem of modeling blood flow phenomena in veins, as a response to increasing interest in modeling pathological conditions occurring in the venous network and their connection with the rest of the circulatory system. In this context, one-dimensional models have proven to be extremely efficient in delivering predictions in agreement with in-vivo observations. Pursuing the increase of anatomical accuracy and its connection to physiological principles in haemodynamics simulations, the main aim of this work is to describe a novel closed-loop Anatomically-Detailed Arterial-Venous Network (ADAVN) model. An extremely refined description of the arterial network consisting of 2,185 arterial vessels is coupled to a novel venous network featuring high level of anatomical detail in cerebral and coronary vascular territories. The entire venous network comprises 189 venous vessels, 79 of which drain the brain and 14 are coronary veins. Fundamental physiological mechanisms accounting for the interaction of brain blood flow with the cerebro-spinal fluid and of the coronary circulation with the cardiac mechanics are considered. Several issues related to the coupling of arterial and venous vessels at the microcirculation level are discussed in detail. Numerical simulations are compared to patient records published in the literature to show the descriptive capabilities of the model. Furthermore, a local sensitivity analysis is performed, evidencing the high impact of the venous circulation on main cardiovascular variables.