bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma markers of COVID-19 severity: a pilot study
Authors: Beimdiek Julia , Janciauskiene Sabina , Wrenger Sabine , Volland Sonja , Rozy Adriana , Fuge Jan , Olejnicka Beata , Pink Isabell , Illig Thomas , Popov Alexander , Chorostowska Joanna , Buettner Falk F. R. , Welte Tobias
Published: December 2022

Background

SARS-CoV-2 infected patients show heterogeneous clinical presentations ranging from mild symptoms to severe respiratory failure and death. Consequently, various markers reflect this wide spectrum of disease presentations.

Methods

Our pilot cohort included moderate (n = 10) and severe (n = 10) COVID-19 patients, and 10 healthy controls. We determined plasma levels of nine acute phase proteins (APPs) by nephelometry, and full-length (M65), caspase-cleaved (M30) cytokeratin 18, and ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type-1 motif 13) by ELISA. In addition, we examined whole plasma N-glycosylation by capillary gel electrophoresis coupled to laser-induced fluorescence detection (CGE-LIF).

Results

When compared to controls, COVID-19 patients had significantly lower concentrations of ADAMTS13 and albumin (ALB) but higher M30, M65, α1-acid glycoprotein (AGP), α1-antitrypsin (AAT), ceruloplasmin (CP), haptoglobin (HP), and high-sensitivity C-reactive protein (hs-CRP). The concentrations of α1-antichymotrypsin (ACT), α2-macroglobulin (A2MG) and serum amyloid A (SAA) proteins did not differ. We found significantly higher levels of AAT and M65 but lower ALB in severe compared to moderate COVID-19 patients. N-glycan analysis of the serum proteome revealed increased levels of oligomannose- and sialylated di-antennary glycans and decreased non-sialylated di-antennary glycan A2G2 in COVID-19 patients compared to controls.

Conclusions

COVID-19-associated changes in levels and N-glycosylation of specific plasma proteins highlight complexity of inflammatory process and grant further investigations.
Oleic acid from cancer-associated fibroblast promotes cancer cell stemness by stearoyl-CoA desaturase under glucose-deficient condition
Authors: Hwang Sung-Hyun , Yang Yeseul , Jung Jae-Ha , Kim Yongbaek
Published: December 2022

Background

Cancer-associated fibroblasts (CAFs) coordinate the malignancy of cancer cells via secretory materials. Reprogrammed lipid metabolism and signaling play critical roles in cancer biology. Oleic acid (OA) serves as a source of energy under glucose-deficient conditions, but its function in cancer progression remains unclear. The present study investigated that CAFs in xenografted tumors had higher amounts of fatty acids, particularly OA, compared to normal fibroblasts, and promoted the cancer cell stemness in lung adenocarcinoma cells under glucose-deficient condition.

Methods

Xenografts were established in immunodeficient mice by injection of NCI-H460 (H460) cells. Lipids and fatty acids were evaluated using the BODIPY staining and fatty-acid methyl esters analysis. The expression levels of markers for lipid metabolism and cancer stemness were determined by western blot, flow cytometry, and real-time PCR. Cancer cell subclones against stearoyl-CoA desaturase (SCD) were produced by lentiviral vector and CRISPR/cas9 systems. The expression of SCD was examined immunochemically in human adenocarcinoma tissues, and its clinical relevance to survival rate in lung adenocarcinoma patients was assessed by Kaplan–Meier analysis.

Results

Transferred CAF-derived OA through lipid transporter upregulated SCD in cancer cells under glucose-deficient conditions, resulting in enhanced lipid metabolism and autophagosome maturation. By OA treatment under glucose deficient condition, cancer cell stemness was significantly enhanced through sequential activation of SCD, F-actin polymerization and nuclear translocation of yes-associated protein. These findings were confirmed by experiments using chemical inhibitors, SCD-overexpressing cells and SCD-knockout (KO) cells. When xenografted, SCD-overexpressing cells produced larger tumors compared with parental cells, while SCD-KO cells generated much smaller tumors. Analysis of tumor tissue microarray from lung adenocarcinoma patients revealed that SCD expression was the marker for poor prognosis involving tumor grade, clinical stage and survival rate.

Conclusion

Our data indicate that CAFs-derived OA activated lipid metabolism in lung adenocarcinoma cells under glucose-deficient conditions, subsequently enhancing stemness and progression toward malignancy.
Antenna-enhanced mid-infrared detection of extracellular vesicles derived from human cancer cell cultures
Authors: Temperini Maria Eleonora , Di Giacinto Flavio , Romanò Sabrina , Di Santo Riccardo , Augello Alberto , Polito Raffaella , Baldassarre Leonetta , Giliberti Valeria , Papi Massimiliano , Basile Umberto , Niccolini Benedetta , Krasnowska Ewa K. , Serafino Annalucia , De Spirito Marco , Di Gaspare Alessandra , Ortolani Michele , Ciasca Gabriele
Published: December 2022

Background

Extracellular Vesicles (EVs) are sub-micrometer lipid-bound particles released by most cell types. They are considered a promising source of cancer biomarkers for liquid biopsy and personalized medicine due to their specific molecular cargo, which provides biochemical information on the state of parent cells. Despite this potential, EVs translation process in the diagnostic practice is still at its birth, and the development of novel medical devices for their detection and characterization is highly required.

Results

In this study, we demonstrate mid-infrared plasmonic nanoantenna arrays designed to detect, in the liquid and dry phase, the specific vibrational absorption signal of EVs simultaneously with the unspecific refractive index sensing signal. For this purpose, EVs are immobilized on the gold nanoantenna surface by immunocapture, allowing us to select specific EV sub-populations and get rid of contaminants. A wet sample-handling technique relying on hydrophobicity contrast enables effortless reflectance measurements with a Fourier-transform infrared (FTIR) spectro-microscope in the wavelength range between 10 and 3 µm. In a proof-of-principle experiment carried out on EVs released from human colorectal adenocarcinoma (CRC) cells, the protein absorption bands (amide-I and amide-II between 5.9 and 6.4 µm) increase sharply within minutes when the EV solution is introduced in the fluidic chamber, indicating sensitivity to the EV proteins. A refractive index sensing curve is simultaneously provided by our sensor in the form of the redshift of a sharp spectral edge at wavelengths around 5 µm, where no vibrational absorption of organic molecules takes place: this permits to extract of the dynamics of EV capture by antibodies from the overall molecular layer deposition dynamics, which is typically measured by commercial surface plasmon resonance sensors. Additionally, the described metasurface is exploited to compare the spectral response of EVs derived from cancer cells with increasing invasiveness and metastatic potential, suggesting that the average secondary structure content in EVs can be correlated with cell malignancy.

Conclusions

Thanks to the high protein sensitivity and the possibility to work with small sample volumes—two key features for ultrasensitive detection of extracellular vesicles- our lab-on-chip can positively impact the development of novel laboratory medicine methods for the molecular characterization of EVs.

Graphical Abstract
Treg cell-derived exosomes miR-709 attenuates microglia pyroptosis and promotes motor function recovery after spinal cord injury
Authors: Xiong Wu , Li Cong , Kong Guang , Zeng Qiang , Wang Siming , Yin Guoyong , Gu Jun , Fan Jin
Published: December 2022

Neuroinflammation is an important cause of poor prognosis in patients with spinal cord injury. pyroptosis is a new type of inflammatory cell death. Treg cells has been shown to play an anti-inflammatory role in a variety of inflammatory diseases, including inflammatory bowel disease, amyotrophic lateral sclerosis, and arthritis. However, little is known about Treg cells' potential role in pyroptosis following spinal cord injury. The aim of this research was to look into the effect of Treg cells to motor function recovery, pyroptosis and the mechanism behind it after SCI. Here, we found that pyroptosis mainly occurred in microglia on the seventh day after spinal cord injury. Konckout Treg cells resulted in widely pyroptosis and poor motor recovery after SCI. In conversely, over-infiltration of Treg cell in mice by tail vein injection had beneficial effects following SCI.Treg cell-derived exosomes promote functional recovery by inhibiting microglia pyroptosis in vivo. Bioinformatic analysis revealed that miRNA-709 was significantly enriched in Treg cells and Treg cell-secreted exosomes. NKAP has been identified as a miRNA-709 target gene. Moreover, experiments confirmed that Treg cells targeted the NKAP via exosomal miR-709 to reduce microglia pyroptosis and promote motor function recovery after SCI. More importantly, The miR-709 overexpressed exosomes we constructed significantly reduced the inflammatory response and improved motor recovery after spinal cord injury. In brief, our findings indicate a possible mechanism for communication between Treg cells and microglia, which opens up a new perspective for alleviating neuroinflammation after SCI.
Haemostasis patterns in patients with acute-on-chronic liver failure and acute decompensation of cirrhosis including thromboelastometric tests with and without the addition of Protac: a pilot study
Authors: Calvo Andrea , Torrente Miguel Angel , Görlinger Klaus , Fernandez Javier , Reverter Enric , Vidal Julia , Tassies Dolors , Colmenero Jordi , Blasi Annabel , Reverter Juan Carlos
Published: December 2022

Background

Thromboelastometry is considered the best method to assesses hemostasis in liver disease. Diagnostic performance could be improved by adding protein C activators such as thrombomodulin or Protac®.

We assessed changes in ROTEM parameters after the addition of Protac® in patients with acute-on-chronic liver failure (ACLF), acute decompensation (AD), and healthy individuals (HI) to define different hemostasis patterns, considering standard and velocity ROTEM parameters, and assess whether Protac® can improve the definition of the pattern.

Methods

Pre-test, we investigated whether diluted EXTEM reagent improved the effect of Protac® on the clotting time (CT)-ratio with and without Protac®. Ten ACLF and 20 AD patients and 21 HI were included in the main study.

Results

Standard EXTEM was used in the main study. INTEM CFT, INTEM A5 (inverse), and INTEM TPI (inverse) were the parameters that best differentiated liver disease from HI (ROC AUC, 0.921, 0.906, and 0.928, respectively; all P-values < 0.001). Combining INTEM CFT with EXTEM LI60-ratio only slightly improved the diagnostic performance (ROC AUC, 0.948; P < 0.001). EXTEM LI60 and INTEM maxV-t were the parameters that best differentiated between ACLF and AD patients (ROC AUC, 0.743, P = 0.033; and 0.723, P = 0.050; respectively). Combining EXTEM LI60 + INTEM maxV-t moderately improved the diagnostic performance (ROC AUC, 0.81, P < 0.001).

Conclusions

ROTEM velocity, fibrinolysis parameters and the indices calculated improve the diagnosis in combination with standard parameters (e.g., CFT and A5). Ratios calculated with and without Protac® (e.g., EXTEM LI60-ratio) only slightly increased the diagnostic performance in discriminating hemostasis patterns.
An extensive bioinformatics study on the role of mitochondrial solute carrier family 25 in PC and its mechanism behind affecting immune infiltration and tumor energy metabolism
Authors: Zhang Qiang , Tang Yubao , Sun Shuai , Xie Qiuyi , Yao Jie , Wang Xiaodong , Qian Jianjun , Li Zhennan
Published: December 2022

Background

Several metabolic disorders and malignancies are directly related to abnormal mitochondrial solute carrier family 25 (SLC25A) members activity. However, its biological role in pancreatic cancer (PC) is not entirely understood.

Methods

The lasso method was used to create a novel prognostic risk model for PC based on SLC25A members, and its roles in tumor immunology and energy metabolism were explored. Furthermore, co-expression networks were constructed for SLC25A11, SLC25A29, and SLC25A44. Single-cell RNA sequencing (ScRNA-seq) revealed the distribution of gene expression in PC. Tumor immune infiltration was examined with the TIMER database. Lastly, drug sensitivity was investigated, and co-transcriptional factors were predicted.

Results

In the present study, a novel prognostic risk model was established and validated for PC based on SLC25A members. The high-risk group had a lower activation of oxidative phosphorylation and a more abundant immune infiltration phenotype than the low-risk group. According to co-expression network studies, SLC25A11, SLC25A29, and SLC25A44 were involved in the energy metabolism of PC and prevented tumor growth, invasion, and metastasis. ScRNA-seq research also pointed to their contribution to the tumor microenvironment. Moreover, the recruitment of numerous immune cells was positively correlated with SLC25A11 and SLC25A44 but negatively correlated with SLC25A29. Additionally, the sensitivity to 20 Food and Drug Administration-approved antineoplastic medicines was strongly linked to the aforementioned genes, where cisplatin sensitivity increased with the up-regulation of SLC25A29. Finally, the Scleraxis BHLH Transcription Factor (SCX) and other proteins were hypothesized to co-regulate the mRNA transcription of the genes.

Conclusion

SLC25A members are crucial for tumor immune and energy metabolism in PC, and SLC25A11, SLC25A29, and SLC25A44 can be used as favorable prognostic markers. The use of these markers will provide new directions to unravel their action mechanisms in PC.
Phenotypic and functional alterations of monocyte subsets with aging
Authors: Cao Yu , Fan Yang , Li Fangyuan , Hao Yu , Kong Yaxian , Chen Chen , Hao Xing , Han Dannuo , Li Guoli , Wang Zengtao , Song Chuan , Han Junyan , Zeng Hui
Published: December 2022

Background

It has been widely accepted that monocytes are one of the central mediators contributing to inflammaging. However, it remains unclear whether aged monocytes, similar to aged T cells, have characteristics of hyperactivation and increased expression of co-inhibitory molecules.

Methods

Peripheral blood mononuclear cells (PBMCs) were isolated from young (21–40 years old), middle-aged (41–60 years old), and older human subjects (> 60 years old). Flow cytometry was used to monitor changes in the expression of surface molecules of monocyte subsets and cytokine-producing capacity.

Results

We observed increased tumor necrosis factor-α: TNF-α and decreased interleukin-6 (IL-6) production in monocytes from older adults compared with young and middle-aged adults. Older adults had a greater percentage of intermediate and non-classical monocyte subsets, along with increased levels of the immune activation markers human leukocyte antigen-DR (HLA-DR), and adhesion molecules cluster of differentiation molecule 11b (CD11b) and L-selectin (CD62L). Furthermore, we observed increased C–C motif chemokine receptor 2 (CCR2) expression on classical monocytes and decreased C-X3-C motif chemokine receptor 1 (CX3CR1) expression on non-classical monocytes in older adult subjects. The expression of co-inhibitory receptors was reduced on monocyte subsets in older adults.

Conclusions

Circulating monocytes in older adults exhibit increased expression of activation, adhesion, and migration markers, but decreased expression of co-inhibitory molecules.
Evaluation of measures of sustainability and sustainability determinants for use in community, public health, and clinical settings: a systematic review
Authors: Hall Alix , Shoesmith Adam , Doherty Emma , McEvoy Brydie , Mettert Kayne , Lewis Cara C. , Wolfenden Luke , Yoong Serene , Kingsland Melanie , Shelton Rachel C. , Wiltsey Stirman Shannon , Imad Noor , Sutherland Rachel , Nathan Nicole
Published: December 2022

Background

Sustainability is concerned with the long-term delivery and subsequent benefits of evidence-based interventions. To further this field, we require a strong understanding and thus measurement of sustainability and what impacts sustainability (i.e., sustainability determinants). This systematic review aimed to evaluate the quality and empirical application of measures of sustainability and sustainability determinants for use in clinical, public health, and community settings.

Methods

Seven electronic databases, reference lists of relevant reviews, online repositories of implementation measures, and the grey literature were searched. Publications were included if they reported on the development, psychometric evaluation, or empirical use of a multi-item, quantitative measure of sustainability, or sustainability determinants. Eligibility was not restricted by language or date. Eligibility screening and data extraction were conducted independently by two members of the research team. Content coverage of each measure was assessed by mapping measure items to relevant constructs of sustainability and sustainability determinants. The pragmatic and psychometric properties of included measures was assessed using the Psychometric and Pragmatic Evidence Rating Scale (PAPERS). The empirical use of each measure was descriptively analyzed.

Results

A total of 32,782 articles were screened from the database search, of which 37 were eligible. An additional 186 publications were identified from the grey literature search. The 223 included articles represented 28 individual measures, of which two assessed sustainability as an outcome, 25 covered sustainability determinants and one explicitly assessed both. The psychometric and pragmatic quality was variable, with PAPERS scores ranging from 14 to 35, out of a possible 56 points. The Provider Report of Sustainment Scale had the highest PAPERS score and measured sustainability as an outcome. The School-wide Universal Behaviour Sustainability Index-School Teams had the highest PAPERS score (score=29) of the measure of sustainability determinants.

Conclusions

This review can be used to guide selection of the most psychometrically robust, pragmatic, and relevant measure of sustainability and sustainability determinants. It also highlights that future research is needed to improve the psychometric and pragmatic quality of current measures in this field.

Trial registration

This review was prospectively registered with Research Registry (reviewregistry1097), March 2021.
Favourable outcome of acute hepatitis E infection in patients with ANCA-associated vasculitis
Authors: Zeisbrich Markus , Wendel Sarah , Finzel Stephanie , Voll Reinhard E. , Venhoff Nils
Published: December 2022

Background

Hepatitis E virus (HEV) infection is a frequent cause of acute viral hepatitis. Immunocompromised patients are at increased risk for viral infection and chronic courses of hepatitis. Whether patients with autoimmune diseases are at risk of developing clinically relevant hepatitis or even chronic liver disease after HEV infection is discussed controversially. ANCA-associated vasculitis is a rare autoimmune disease with potentially life-threatening organ involvement, thus requiring intensive immunosuppression with glucocorticoids, cyclophosphamide, or rituximab. As there are no reports available on the infection with HEV in patients with ANCA-associated vasculitis, clinical decision making in such cases is based on experiences from other disease entities. Therefore, in this study we analyzed the course of liver disease and the therapeutic management of autoimmune vasculitis in a retrospective cohort of five patients with ANCA-associated vasculitis and acute hepatitis E.

Results

Four patients were on immunosuppressive maintenance therapy and one patient was on remission induction therapy with cyclophosphamide and high dose glucocorticoids. All patients had at least one potentially hepatotoxic co-medication at the time of hepatitis. Hepatitis-associated clinical symptoms were recorded in four of five patients. The course of hepatitis was characterized by strongly elevated transaminases, a temporary liver failure was observed in one case. The management of hepatitis E included cessation of the immunosuppressants in all patients, whereas oral glucocorticoids were not discontinued. Under this regime, all patients cleared the virus without additional anti-viral treatment. Liver enzymes normalized one month after they peaked. In the follow-up period of at least 1.5 years (range 1.5–12 years), no chronic liver disease was observed, although one patient died of cholangiocarcinoma with liver metastases some years after HEV infection. Vasculitis was not active in our patient cohort at the time of HEV infection. However, inflammatory flares occured in three of five patients after discontinuation of the immunosuppressive therapy. Immunosuppressants were paused for a median time of 4 weeks and after their resumption vasculitic disease activity was controlled in all patients.

Conclusions

Acute HEV infection in patients with ANCA-associated vasculitis shows a favorable outcome of liver disease but bears the risk of inflammatory flares due to cessation of immunosuppression.
Single-cell microglial transcriptomics during demyelination defines a microglial state required for lytic carcass clearance
Authors: Zia Sameera , Hammond Brady P. , Zirngibl Martin , Sizov Anastasia , Baaklini Charbel S. , Panda Sharmistha P. , Ho Madelene F. S. , Lee Kelly V. , Mainali Apurba , Burr Mena K. , Williams Sioned , Caprariello Andrew V. , Power Christopher , Simmen Thomas , Kerr Bradley J. , Plemel Jason R.
Published: December 2022

Background

Microglia regulate the response to injury and disease in the brain and spinal cord. In white matter diseases microglia may cause demyelination. However, how microglia respond and regulate demyelination is not fully understood.

Methods

To understand how microglia respond during demyelination, we fed mice cuprizone—a potent demyelinating agent—and assessed the dynamics of genetically fate-mapped microglia. We then used single-cell RNA sequencing to identify and track the microglial subpopulations that arise during demyelination. To understand how microglia contribute to the clearance of dead oligodendrocytes, we ablated microglia starting at the peak of cuprizone-induced cell death and used the viability dye acridine orange to monitor apoptotic and lytic cell morphologies after microglial ablation. Lastly, we treated serum-free primary microglial cultures to model distinct aspects of cuprizone-induced demyelination and assessed the response.

Results

The cuprizone diet generated a robust microglial response by week 4 of the diet. Single-cell RNA sequencing at this time point revealed the presence of several cuprizone-associated microglia (CAM) clusters. These clusters expressed a transcriptomic signature indicative of cytokine regulation and reactive oxygen species production with altered lysosomal and metabolic changes consistent with ongoing phagocytosis. Using acridine orange to monitor apoptotic and lytic cell death after microglial ablation, we found that microglia preferentially phagocytose lytic carcasses. In culture, microglia exposed to lytic carcasses partially recapitulated the CAM state, suggesting that phagocytosis contributes to this distinct microglial state during cuprizone demyelination.

Conclusions

Microglia serve multiple roles during demyelination, yet their transcriptomic state resembles other neurodegenerative conditions. The phagocytosis of cellular debris is likely a universal cause for a common neurodegenerative microglial state.
Buprenorphine in rats: potent analgesic or trigger for fatal side effects?
Authors: Reifenrath Janin , Heider Miriam , Kempfert Merle , Harting Heidi , Weidemann Friederike , Strauss Sarah , Angrisani Nina
Published: December 2022

With ongoing animal welfare efforts, multimodal analgesia is often recommended to implement in study protocols. Buprenorphine with very potent analgesic effect is a standard opioid for the use in this context in rats. In this study, two rat strains (LEW/NHanZtm, n = 6 and Crl:CD(SD), n = 8) underwent orthopaedic surgery and received carprofen, buprenorphine and a local anaesthetic in a multimodal setup. Crl:CD(SD) rats showed severe side effects in the first 24 h after anaesthesia, predominantly manifesting in pica-behaviour and reaching humane endpoints in two of eight animals, while LEW/NHanZtm rats showed only slight depression in the first postoperative days. In the context of improving animal welfare in experimental studies, buprenorphine is highly recommended not to be used in male Crl:CD(SD) rats and should generally be used very carefully and only if required.
Spatial omics technologies at multimodal and single cell/subcellular level
Authors: Park Jiwoon , Kim Junbum , Lewy Tyler , Rice Charles M. , Elemento Olivier , Rendeiro André F. , Mason Christopher E.
Published: December 2022

Spatial omics technologies enable a deeper understanding of cellular organizations and interactions within a tissue of interest. These assays can identify specific compartments or regions in a tissue with differential transcript or protein abundance, delineate their interactions, and complement other methods in defining cellular phenotypes. A variety of spatial methodologies are being developed and commercialized; however, these techniques differ in spatial resolution, multiplexing capability, scale/throughput, and coverage. Here, we review the current and prospective landscape of single cell to subcellular resolution spatial omics technologies and analysis tools to provide a comprehensive picture for both research and clinical applications.
BORN study: a multicenter randomized trial investigating cord blood red blood cell transfusions to reduce the severity of retinopathy of prematurity in extremely low gestational age neonates
Authors: Teofili Luciana , Papacci Patrizia , Orlando Nicoletta , Bianchi Maria , Pasciuto Tina , Mozzetta Iolanda , Palluzzi Fernando , Giacò Luciano , Giannantonio Carmen , Remaschi Giulia , Santosuosso Michela , Beccastrini Enrico , Fabbri Marco , Valentini Caterina Giovanna , Bonfini Tiziana , Cloclite Eleonora , Accorsi Patrizia , Dragonetti Antonella , Cresi Francesco , Ansaldi Giulia , Raffaeli Genny , Villa Stefania , Pucci Giulia , Mondello Isabella , Santodirocco Michele , Ghirardello Stefano , Vento Giovanni
Published: December 2022

Background

Extremely low gestational age neonates (ELGANs, i.e., neonates born before 28 weeks of gestation) are at high risk of developing retinopathy of prematurity (ROP), with potential long-life visual impairment. Due to concomitant anemia, ELGANs need repeated red blood cell (RBC) transfusions. These produce a progressive replacement of fetal hemoglobin (HbF) by adult hemoglobin (HbA). Furthermore, a close association exists between low levels of HbF and severe ROP, suggesting that a perturbation of the HbF-mediated oxygen release may derange retinal angiogenesis and promote ROP.

Methods/design

BORN (umBilical blOod to tRansfuse preterm Neonates) is a multicenter double-blinded randomized controlled trial in ELGANs, to assess the effect of allogeneic cord blood RBC transfusions (CB-RBCs) on severe ROP development. Recruitment, consent, and randomization take place at 10 neonatology intensive care units (NICUs) of 8 Italian tertiary hospitals. ELGANs with gestational age at birth comprised between 24+0 and 27+6 weeks are randomly allocated into two groups: (1) standard RBC transfusions (adult-RBCs) (control arm) and (2) CB-RBCs (intervention arm). In case of transfusion need, enrolled patients receive transfusions according to the allocation arm, unless an ABO/RhD CB-RBC is unavailable. Nine Italian public CB banks cooperate to make available a suitable amount of CB-RBC units for all participating NICUs. The primary outcome is the incidence of severe ROP (stage 3 or higher) at discharge or 40 weeks of postmenstrual age, which occurs first.

Discussion

BORN is a groundbreaking trial, pioneering a new transfusion approach dedicated to ELGANs at high risk for severe ROP. In previous non-randomized trials, this transfusion approach was proven feasible and able to prevent the HbF decrease in patients requiring multiple transfusions. Should the BORN trial confirm the efficacy of CB-RBCs in reducing ROP severity, this transfusion strategy would become the preferential blood product to be used in severely preterm neonates.

Trial registration

ClinicalTrials.gov NCT05100212. Registered on October 29, 2021
Morphological and molecular characterization of the parasite Dipylidium caninum infecting an infant in Colombia: a case report
Authors: Benitez-Bolivar Paula , Rondón Silvia , Ortiz Mario , Díaz-Díaz Juana , León Cielo , Riveros Juan , Molina Helverth , González Camila
Published: December 2022

Background

Dipylidium caninum is the causal agent of dipylidiasis affecting mainly cats and dogs worldwide. Human cases of dipylidiasis are rare, and the diagnosis is prevalently based on morphological features of the parasite. Here we report the diagnosis of dipylidiasis through morphological and molecular characterization of D. caninum infecting an 11-month-old boy in Cajicá, Colombia.

Methods

Fresh faecal samples were obtained from the infant, and morphological identification of the parasite was performed through faecal smears. DNA was extracted from proglottids and used in PCR analyses for amplification of a 653-bp fragment of the nuclear ribosomal RNA (rRNA) encoding the 28S rRNA gene. A phylogeny study to better characterize the obtained DNA sequence was inferred using the maximum likelihood method and the Tamura-Nei model.

Results

After morphological and molecular analyses, D. caninum was identified as the etiological agent causing the infection in the infant. Results of phylogenetical analyses showed that the obtained sequence clusters within the feline genotype clade. After the diagnosis of the parasite, effective treatment with praziquantel was administered to the infant.

Conclusions

This is the third human case of dipylidiasis reported in Colombia, and the first study in South America to provide a molecular identification of D. caninum.

Graphical abstract
Reperfusion injury on computed tomography following endovascular revascularization of acute mesenteric ischemia: prevalence, risk factors, and patient outcome
Authors: Garzelli Lorenzo , Nuzzo Alexandre , Hamon Annick , Ben Abdallah Iannis , Gregory Jules , Raynaud Lucas , Paulatto Luisa , Dioguardi Burgio Marco , Castier Yves , Panis Yves , Vilgrain Valérie , Corcos Olivier , Ronot Maxime
Published: December 2022

Background

Data about reperfusion injury (RI) following acute arterial mesenteric ischemia (AAMI) in humans are scarce. We aimed to assess the prevalence and risk factors of RI following endovascular revascularization of AMI and evaluate its impact on patient outcomes.

Methods

Patients with AAMI who underwent endovascular revascularization (2016–2021) were included in this retrospective cohort. CT performed < 7 days after treatment was reviewed to identify features of RI (bowel wall hypoattenuation, mucosal hyperenhancement). Clinical, laboratory, imaging, and treatments were compared between RI and non-RI patients to identify factors associated with RI. Resection rate and survival were also compared.

Results

Fifty patients (23 men, median 72-yrs [IQR 60–77]) were included, and 22 were diagnosed with RI (44%) after a median 28 h (22–48). Bowel wall hypoattenuation and mucosal hyperenhancement were found in 95% and 91% of patients with post-interventional RI, respectively. Patients with RI had a greater increase of CRP levels after endovascular treatment (p = 0.01). On multivariate analysis, a decreased bowel wall enhancement on baseline CT (HR = 8.2), an embolic cause (HR = 7.4), complete SMA occlusion (HR = 7.0), and higher serum lactate levels (HR = 1.4) were associated with RI. The three-month survival rate was 78%, with no difference between subgroups (p = 0.99). However, the resection rate was higher in patients with RI (32% versus 7%; p = 0.03).

Conclusion

RI is frequent after endovascular revascularization of AAMI, especially in patients who present with decreased bowel wall enhancement on pre-treatment CT, an embolic cause, and a complete occlusion of the SMA. However, its occurrence does not seem to negatively impact short-term survival.
Multiple receptor conversions during the course of metastatic breast cancer therapy: a case report and review of the literature
Authors: Chamorro Yolcar , Sandoval-Leon Ana C. , Vogel Charles L. , Nguyen Michaela T. , Wang Grace
Published: December 2022

Background

Adjuvant systemic therapy decreases recurrence and death from breast cancer, but late relapse still occurs. Therapeutic decisions are based heavily on receptor tissue characterization. Even though the vast majority of metastatic sites do not have receptor conversions, they can occur at the time of metastasis and/or during the course of treatment. However, multiple receptor conversions are uncommon.

Case presentation

We present an unusual case of a Caucasian patient originally diagnosed with an estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor receptor 2-negative primary breast cancer who had a recurrence after 15 years of therapy. Her metastatic tumor had a different receptor status than the original tumor. During the course of therapy, at the time of progression, a new biopsy showed that her tumor had changed once more.

Conclusion/Discussion

Tracking receptor conversions is important in metastatic breast cancer treatment. Single receptor conversions have been documented to occur, but not much is known of multiple receptor conversions. This case sheds light on the possibility of patients having multiple receptor conversions and the importance of performing multiple biopsies during the course of metastatic treatment.
Association of sepsis-induced cardiomyopathy and mortality: a systematic review and meta-analysis
Authors: Lin Yu-Min , Lee Mei-Chuan , Toh Han Siong , Chang Wei-Ting , Chen Sih-Yao , Kuo Fang-Hsiu , Tang Hsin-Ju , Hua Yi-Ming , Wei Dongmei , Melgarejo Jesus , Zhang Zhen-Yu , Liao Chia-Te
Published: December 2022

Background

The implication of sepsis-induced cardiomyopathy (SIC) to prognosis is controversial, and its association with mortality at different stages remains unclear. We conducted a systematic review and meta-analysis to understand the association between SIC and mortality in septic patients.

Methods

We searched and appraised observational studies regarding the mortality related to SIC among septic patients in PubMed and Embase from inception until 8 July 2021. Outcomes comprised in-hospital and 1-month mortality. We adopted the random-effects model to examine the mortality risk ratio in patients with and without SIC. Meta-regression, subgroup, and sensitivity analyses were applied to examine the outcome’s heterogeneity.

Results

Our results, including 20 studies and 4,410 septic patients, demonstrated that SIC was non-statistically associated with increased in-hospital mortality, compared to non-SIC (RR 1.28, [0.96–1.71]; p = 0.09), but the association was statistically significant in patients with the hospital stay lengths longer than 10 days (RR 1.40, [1.02–1.93]; p = 0.04). Besides, SIC was significantly associated with a higher risk of 1-month mortality (RR 1.47, [1.17–1.86]; p < 0.01). Among SIC patients, right ventricular dysfunction was significantly associated with increased 1-month mortality (RR 1.72, [1.27–2.34]; p < 0.01), while left ventricular dysfunction was not (RR 1.33, [0.87–2.02]; p = 0.18).

Conclusions

With higher in-hospital mortality in those hospitalized longer than 10 days and 1-month mortality, our findings imply that SIC might continue influencing the host’s system even after recovery from cardiomyopathy. Besides, right ventricular dysfunction might play a crucial role in SIC-related mortality, and timely biventricular assessment is vital in managing septic patients.
MetaMGC: a music generation framework for concerts in metaverse
Authors: Jin Cong , Wu Fengjuan , Wang Jing , Liu Yang , Guan Zixuan , Han Zhe
Published: December 2022

In recent years, there has been a national craze for metaverse concerts. However, existing meta-universe concert efforts often focus on immersive visual experiences and lack consideration of the musical and aural experience. But for concerts, it is the beautiful music and the immersive listening experience that deserve the most attention. Therefore, enhancing intelligent and immersive musical experiences is essential for the further development of the metaverse. With this in mind, we propose a metaverse concert generation framework — from intelligent music generation to stereo conversion and sound field design for virtual concert stages. First, combining the ideas of reinforcement learning and value functions, the Transformer-XL music generation network is improved and used in training all the music in the POP909 dataset. Experiments show that both improved algorithms have advantages over the original method in terms of objective evaluation and subjective evaluation metrics. In addition, this paper validates a neural rendering method that can be used to generate spatial audio based on a binaural-integrated neural network with a fully convolutional technique. And the purely data-driven end-to-end model performs to be more reliable compared with traditional spatial audio generation methods such as HRTF. Finally, we propose a metadata-based audio rendering algorithm to simulate real-world acoustic environments.
Prevalence of pediatric acute-onset neuropsychiatric syndrome (PANS) in children and adolescents with eating disorders
Authors: Aman Marya , Coelho Jennifer S. , Lin Boyee , Lu Cynthia , Westwell-Roper Clara , Best John R. , Stewart S. Evelyn
Published: December 2022

Background

Pediatric obsessive–compulsive disorder (OCD) and eating disorder symptoms frequently overlap, clouding diagnostic certainty and hypothesized etiologic factors. Pediatric acute-onset neuropsychiatric syndrome (PANS) is defined by abrupt emergence of core obsessive–compulsive behaviours and/or food restriction with concurrent, ancillary cognitive and behavioral symptoms. Inflammatory and immune processes have putative roles in both PANS and a related described condition with cardinal obsessive–compulsive or tic symptoms, known as pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). While prevalence of PANS and PANDAS has been examined in tic, movement disorder and OCD populations, this has not yet been systematically examined in a pediatric eating disorder sample.

Objectives

To identify the lifetime prevalence of those meeting PANS and/or PANDAS criteria within a pediatric eating disorder cohort.

Methods

Convenience sampling method was utilized to select consecutive youth (ages 8–18-years) presenting to an interdisciplinary pediatric eating disorder subspecialty program with a confirmed eating disorder and completed parent-report PANS/PANDAS questionnaire (n = 100). A parent-reported measure was used to establish lifetime prevalence rates for PANS and PANDAS. Descriptive and exploratory comparative analyses were conducted between PANS and non-PANS groups. Continuous measures were analyzed using two-tailed independent sample t-tests and categorical measures were analyzed using two-tailed Fisher’s exact tests.

Results

Among participants, 52% (n = 52) met PANS criteria and 0% (n = 0) met PANDAS diagnostic criteria. Core, abrupt-onset PANS symptoms included both food restriction and obsessive–compulsive symptoms in 63.5% (n = 33), food restriction only in 25% (n = 13), and obsessive–compulsive symptoms only in 11.5% (n = 6) of participants. In comparison to those who did not meet PANS criteria, those in the PANS subgroup were less likely to be male and more commonly prescribed a selective serotonin reuptake inhibitor medication. Significant group differences did not emerge for onset age, body mass index, eating disorder type or comorbid psychiatric/medical/autoimmune illness.

Conclusion

Lifetime prevalence of symptoms in keeping with PANS diagnostic criteria within a pediatric eating disorder cohort was notably higher than that previously reported in OCD or tic disorder cohorts. The overlap between starvation effects and ancillary PANS symptoms may challenge the practical utility of this putative syndrome within the eating disorder population.
The impact of breast cancer on social cognition in female Colombian patients
Authors: Palacio Nicole , Romero Daniela Nicole , Bernal Andrés Mateo , González-Rodríguez Daniela , Solarte-Bothe Daniel , del Pilar García María , Murillo Raúl , Santamaría-García Hernando , Báez Sandra
Published: December 2022

Background

The high prevalence of female breast cancer is a global health concern. Breast cancer and its treatments have been associated with impairments in general cognition, as well as structural and functional brain changes. Considering the social challenges that some of these patients face, it is important to understand the socio-emotional effects of breast cancer as well. Nevertheless, the impact of breast cancer on social cognition has remained underexplored. The objective of this study was to assess social cognition domains and other relevant cognitive and emotional variables (executive functions, anxiety, or depression) in females with breast cancer.

Methods

The participants were 29 female patients diagnosed with breast cancer and 29 female healthy controls. We assessed emotion recognition, theory of mind, empathy, and moral emotions. We also included measures of general cognitive functioning, quality of life, anxiety, and depression. Linear multiple regressions were performed to assess whether the group (patients or controls), GAD-7 scores, emotional and social subscales of EORTC QLQ-C30, and IFS scores predicted the social cognition variables (EET, RMET, MSAT).

Results

Patients with breast cancer showed impairments in emotion recognition and in affective theory of mind. In addition, patients had lower scores in some executive functions. Only theory of mind between group differences remained significant after Bonferroni correction. Emotion recognition was associated with executive functioning, but anxiety levels were not a significant predictor of the changes in social cognition.

Conclusions

Social cognition impairments, especially in theory of mind, may be present in breast cancer, which can be relevant to understanding the social challenges that these patients encounter. This could indicate the need for therapeutic interventions to preserve social cognition skills in patients with breast cancer.
Washover deposits related to tsunami and storm surge along the north coast of the Shimokita Peninsula in northern Japan
Authors: Ishimura Daisuke , Ishizawa Takashi , Yamada Masaki , Aoki Kaori , Sato Kai
Published: December 2022

A decade after the 2011 Tohoku-oki earthquake (Mw 9.0), geological surveys were conducted at multiple sites along the Pacific Coast of the tsunami-inundated Tohoku region in Japan, providing thousands of years of tsunami history. However, the challenges of correlation between historical records and geological tsunami deposits and identifying sources of historical and paleotsunamis have newly surfaced. Particularly the simultaneity and source of the 1611 Keicho tsunami in the Tohoku region and the seventeenth-century tsunami in the Hokkaido region are problematic. To solve such major issues, we conducted a tsunami-deposit survey at Sekinehama on the north coast of Shimokita Peninsula, near the junction of the Japan and Kuril trenches. We performed nondestructive analyses (X-ray computed tomography and micro-X-ray-fluorescence core scanning), grain-size analysis, tephra analysis, and radiocarbon dating of sediments from two coastal outcrops and inland drill cores. We identified five tsunami deposits (TD1–TD5) during the last 6 kyr and correlated them at a 200–400 m distance from the coast. They also correlate with previously identified tsunami deposits around the Shimokita Peninsula. From our study on tsunami deposits, we found other washover deposits in the coastal outcrops that are not represented in the inland cores. These indicate minor washover events related to small tsunamis and infrequent storm surges. The modeled age of the latest tsunami deposit is 500–300 cal yr BP (1450–1650 cal CE). This either correlates with two known tsunamis (the 1611 Keicho tsunami and another seventeenth-century tsunami) or is a previously unknown tsunami that occurred in the fifteenth–seventeenth centuries. If the latest tsunami deposit is to be accurately correlated with tsunami deposits previously identified within a 50-km distance from the study site, we need to consider an unknown fifteenth-century tsunami. Our investigation yields insights regarding the tsunami source in the vicinity of the junction of the Japan and Kuril trenches.
Quantification and dosimetry of small volumes including associated uncertainty estimation
Authors: Carnegie-Peake Lily , Taprogge Jan , Murray Iain , Flux Glenn D. , Gear Jonathan
Published: December 2022

Background

Accurate quantification of radioactivity in a source of interest relies on accurate registration between SPECT and anatomical images, and appropriate correction of partial volume effects (PVEs). For small volumes, exact registration between the two imaging modalities and recovery factors used to correct for PVE are unreliable. There is currently no guidance relating to quantification or the associated uncertainty estimation for small volumes.

Material and methods

A method for quantification of small sources of interest is proposed, which uses multiple oversized volumes of interest. The method was applied to three Na[131I]I activity distributions where a Na[131I]I capsule was situated within a cylindrical phantom containing either zero background, uniform background or non-uniform background and to a scenario with small lesions placed in an anthropomorphic phantom. The Na[131I]I capsule and lesions were quantified using the proposed method and compared with measurements made using two alternative quantification methods. The proposed method was also applied to assess the absorbed dose delivered to a bone metastasis following [131I]mIBG therapy for neuroblastoma including the associated uncertainty estimation.

Results

The method is accurate across a range of activities and in varied radioactivity distributions. Median percentage errors using the proposed method in no background, uniform backgrounds and non-uniform backgrounds were − 0.4%, − 0.3% and 1.7% with median associated uncertainties of 1.4%, 1.4% and 1.6%, respectively. The technique is more accurate and robust when compared to currently available alternative methods.

Conclusions

The proposed method provides a reliable and accurate method for quantification of sources of interest, which are less than three times the spatial resolution of the imaging system. The method may be of use in absorbed dose calculation in cases of bone metastasis, lung metastasis or thyroid remnants.