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Article ; Online: Exploiting pancreatic cancer metabolism: challenges and opportunities.

De Santis, Maria Chiara / Bockorny, B / Hirsch, E / Cappello, P / Martini, M

2024

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive form of pancreatic cancer, known for its challenging diagnosis and limited treatment options. The focus on metabolic reprogramming as a key factor in tumor initiation, progression, and ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive form of pancreatic cancer, known for its challenging diagnosis and limited treatment options. The focus on metabolic reprogramming as a key factor in tumor initiation, progression, and therapy resistance has gained prominence. In this review we focus on the impact of metabolic changes on the interplay among stromal, immune, and tumor cells, as glutamine and branched-chain amino acids (BCAAs) emerge as pivotal players in modulating immune cell functions and tumor growth. We also discuss ongoing clinical trials that explore metabolic modulation for PDAC, targeting mitochondrial metabolism, asparagine and glutamine addiction, and autophagy inhibition. Overcoming challenges in understanding nutrient effects on immune-stromal-tumor interactions holds promise for innovative therapeutic strategies.
Language	English
Publishing date	2024-04-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2036490-8
ISSN	1471-499X ; 1471-4914
ISSN (online)	1471-499X
ISSN	1471-4914
DOI	10.1016/j.molmed.2024.03.008
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Zs.A 4345: Show issues

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Article ; Online: Quantitative ultrasonographic examination of cerebral white matter by pixel brightness intensity as marker of middle-term neurodevelopment: a prospective observational study.

Laccetta, Gianluigi / Di Chiara, Maria / De Nardo, Maria Chiara / Tagliabracci, Monica / Travaglia, Elisa / De Santis, Benedetta / Spiriti, Caterina / Dito, Lucia / Regoli, Daniela / Caravale, Barbara / Cellitti, Raffaella / Parisi, Pasquale / Terrin, Gianluca

Scientific reports

2023 Volume 13, Issue 1, Page(s) 16816

Abstract: Non-cystic white matter (WM) injury has become prevalent among preterm newborns and is associated with long-term neurodevelopmental impairment. Magnetic resonance is the gold-standard for diagnosis; however, cranial ultrasound (CUS) is more easily ... ...

Abstract	Non-cystic white matter (WM) injury has become prevalent among preterm newborns and is associated with long-term neurodevelopmental impairment. Magnetic resonance is the gold-standard for diagnosis; however, cranial ultrasound (CUS) is more easily available but limited by subjective interpretation of images. To overcome this problem, we enrolled in a prospective observational study, patients with gestational age at birth < 32 weeks with normal CUS scans or grade 1 WM injury. Patients underwent CUS examinations at 0-7 days of life (T
MeSH term(s)	Infant, Newborn ; Humans ; Infant ; Infant, Premature ; White Matter/diagnostic imaging ; Ultrasonography ; Gestational Age ; Magnetic Resonance Imaging/methods ; Brain Injuries/pathology ; Brain/diagnostic imaging ; Brain/pathology
Language	English
Publishing date	2023-10-05
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-44083-w
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Article ; Online: 3D ultrasound evaluation of fetal ears in prenatal syndrome diagnosis - a comparative study.

Roosen, Antonia Maria / Oelmeier, Kathrin / Möllers, Mareike / Willy, Daniela / Sondern, Kathleen Marie / Köster, Helen Ann / De Santis, Chiara / Eveslage, Maria / Schmitz, Ralf

Ultraschall in der Medizin (Stuttgart, Germany : 1980)

2024

Abstract: Purpose: The aim of the study was to assess fetal ears on prenatal 3D ultrasound and compare ear surface patterns and measurements between fetuses with syndromes and healthy fetuses.: Materials and methods: Our study is based on 3D ultrasound images ... ...

Title translation	3D-Ultraschall-Beurteilung fetaler Ohren in der pränatalen Syndromdiagnostik – eine Vergleichsstudie.
Abstract	Purpose: The aim of the study was to assess fetal ears on prenatal 3D ultrasound and compare ear surface patterns and measurements between fetuses with syndromes and healthy fetuses. Materials and methods: Our study is based on 3D ultrasound images of 100 fetuses between the 20th and 37th week of gestation. We compared 50 ears of fetuses with syndromes (syndrome group) to 50 gestational age-matched ears of healthy fetuses (control group). The syndrome group consisted of fetuses with Trisomy 21 (n=13), Trisomy 18 (n=9) and other syndromes (n=28). The evaluation was based on measuring the ear length and width as well as developing categories to describe and compare different ear surface anomalies. Results: Ears of fetuses with Trisomy 18 were on average 0.423 cm smaller in length (P<0.001) and 0.123 cm smaller in width (P=0.031) and grew on average 0.046 cm less in length per week of gestation (P=0.027) than those of healthy fetuses. Ears of fetuses with Trisomy 21 differed from healthy fetuses regarding the form of the helix (P=0.013) and the ratio of the concha to the auricle (P=0.037). Fetuses with syndromes demonstrated less ear surface details than their controls (syndrome group: P=0.018, P=0.005; other syndromes subgroup: P=0.020). We saw an increased richness of ear surface details at a later gestational age both in the fetuses with syndromes and the healthy fetuses. Conclusion: Ears of fetuses with Trisomy 18 were smaller than their matched controls. Fetuses with syndromes varied in the evaluation of their ear surface from those of healthy fetuses. The ear surface can be analyzed with 3D ultrasound and might be useful as a screening parameter in syndrome diagnosis in the future.
Language	English
Publishing date	2024-03-04
Publishing country	Germany
Document type	Journal Article
ZDB-ID	801064-x
ISSN	1438-8782 ; 1439-0914 ; 1431-4894 ; 0172-4614
ISSN (online)	1438-8782
ISSN	1439-0914 ; 1431-4894 ; 0172-4614
DOI	10.1055/a-2253-9588
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Zs.A 1572: Show issues

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Article ; Online: The first mitotic division: a perilous bridge connecting the zygote and the early embryo.

Coticchio, Giovanni / Cimadomo, Danilo / Cermisoni, Greta Chiara / Rienzi, Laura / Papaleo, Enrico / Ubaldi, Filippo Maria / Borini, Andrea / De Santis, Lucia

Human reproduction (Oxford, England)

2023 Volume 38, Issue 6, Page(s) 1019–1027

Abstract: Human embryos are very frequently affected by maternally inherited aneuploidies, which in the vast majority of cases determine developmental failure at pre- or post-implantation stages. However, recent evidence, generated by the alliance between diverse ... ...

Abstract	Human embryos are very frequently affected by maternally inherited aneuploidies, which in the vast majority of cases determine developmental failure at pre- or post-implantation stages. However, recent evidence, generated by the alliance between diverse technologies now routinely employed in the IVF laboratory, has revealed a broader, more complex scenario. Aberrant patterns occurring at the cellular or molecular level can impact at multiple stages of the trajectory of development to blastocyst. In this context, fertilization is an extremely delicate phase, as it marks the transition between gametic and embryonic life. Centrosomes, essential for mitosis, are assembled ex novo from components of both parents. Very large and initially distant nuclei (the pronuclei) are brought together and positioned centrally. The overall cell arrangement is converted from being asymmetric to symmetric. The maternal and paternal chromosome sets, initially separate and scattered within their respective pronuclei, become clustered where the pronuclei juxtapose, to facilitate their assembly in the mitotic spindle. The meiotic spindle is replaced by a segregation machinery that may form as a transient or persistent dual mitotic spindle. Maternal proteins assist the decay of maternal mRNAs to allow the translation of newly synthesized zygotic transcripts. The diversity and complexity of these events, regulated in a precise temporal order and occurring in narrow time windows, make fertilization a highly error-prone process. As a consequence, at the first mitotic division, cellular or genomic integrity may be lost, with fatal consequences for embryonic development.
MeSH term(s)	Pregnancy ; Female ; Humans ; Zygote ; Cell Nucleus/metabolism ; Embryonic Development/genetics ; Chromosomes ; Mitosis ; Spindle Apparatus
Language	English
Publishing date	2023-03-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632776-x
ISSN	1460-2350 ; 0268-1161 ; 1477-741X
ISSN (online)	1460-2350
ISSN	0268-1161 ; 1477-741X
DOI	10.1093/humrep/dead067
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Zs.B 2892: Show issues

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Article ; Online: Are they functional hypogonadal men? Testosterone serum levels unravel male idiopathic infertility subgroups.

Spaggiari, Giorgia / Costantino, Francesco / Dalla Valentina, Leonardo / Romeo, Marilina / Furini, Chiara / Roli, Laura / De Santis, Maria Cristina / Canu, Giulia / Trenti, Tommaso / Granata, Antonio R M / Simoni, Manuela / Santi, Daniele

Endocrine

2024

Abstract: Purpose: To evaluate total testosterone distribution in male idiopathic infertility.: Methods: A retrospective, real-world case-control clinical study was conducted. Cases consisted of men evaluated for couple infertility, specifically those with ... ...

Abstract	Purpose: To evaluate total testosterone distribution in male idiopathic infertility. Methods: A retrospective, real-world case-control clinical study was conducted. Cases consisted of men evaluated for couple infertility, specifically those with alterations in semen parameters and normal gonadotropin levels, and after excluding all known causes of male infertility. Controls were male subjects who underwent semen analysis for screening purposes, without any abnormality detected. The total testosterone distribution was evaluated in cases and controls. Further analyses were performed subgrouping cases according to total testosterone reference threshold suggested by scientific societies (i.e., 3.5 ng/mL). Results: Cases included 214 idiopathic infertile men (mean age 38.2 ± 6.2 years) and controls 224 subjects with normozoospermia (mean age 33.7 ± 7.5 years). Total testosterone was not-normally distributed in both cases and controls, with positive asymmetric distribution slightly shifted on the left in cases. The rate of subjects with testosterone lower than 3.5 ng/mL was higher in cases (23.8%) than controls (4.5%) (p < 0.001). In cases with testosterone lower than 3.5 ng/mL, a significant direct correlation between testosterone and the percentage of normal morphology sperms was highlighted, also applying multivariate stepwise linear regression analysis (R = 0.430, standard error = 0.3, p = 0.020). Conclusion: Although idiopathic infertile men show by definition altered semen analysis and gonadotropins within reference ranges, testosterone serum levels are widely variable in this population. Approximately a quarter of these patients present some sort of functional hypogonadism. Our data support the need to better classify idiopathic male infertility and total testosterone serum levels could be a supportive parameter in tracing the patient's therapeutic profile.
Language	English
Publishing date	2024-02-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1194484-5
ISSN	1559-0100 ; 1355-008X ; 0969-711X
ISSN (online)	1559-0100
ISSN	1355-008X ; 0969-711X
DOI	10.1007/s12020-024-03717-3
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Zs.A 3884: Show issues

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Article: Immunotherapy and Pancreatic Cancer: A Lost Challenge?

Laface, Carmelo / Memeo, Riccardo / Maselli, Felicia Maria / Santoro, Anna Natalizia / Iaia, Maria Laura / Ambrogio, Francesca / Laterza, Marigia / Cazzato, Gerardo / Guarini, Chiara / De Santis, Pierluigi / Perrone, Martina / Fedele, Palma

Life (Basel, Switzerland)

2023 Volume 13, Issue 7

Abstract: Although immunotherapy has proved to be a very efficient therapeutic strategy for many types of tumors, the results for pancreatic cancer (PC) have been very poor. Indeed, chemotherapy remains the standard treatment for this tumor in the advanced stage. ... ...

Abstract	Although immunotherapy has proved to be a very efficient therapeutic strategy for many types of tumors, the results for pancreatic cancer (PC) have been very poor. Indeed, chemotherapy remains the standard treatment for this tumor in the advanced stage. Clinical data showed that only a small portion of PC patients with high microsatellite instability/mismatch repair deficiency benefit from immunotherapy. However, the low prevalence of these alterations was not sufficient to lead to a practice change in the treatment strategy of this tumor. The main reasons for the poor efficacy of immunotherapy probably lie in the peculiar features of the pancreatic tumor microenvironment in comparison with other malignancies. In addition, the biomarkers usually evaluated to define immunotherapy efficacy in other cancers appear to be useless in PC. This review aims to describe the main features of the pancreatic tumor microenvironment from an immunological point of view and to summarize the current data on immunotherapy efficacy and immune biomarkers in PC.
Language	English
Publishing date	2023-06-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life13071482
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Article ; Online: Molecular changes underlying decay of sensory responses and enhanced seizure propensity in peritumoral neurons.

Tantillo, Elena / Scalera, Marta / De Santis, Elisa / Meneghetti, Nicolò / Cerri, Chiara / Menicagli, Michele / Mazzoni, Alberto / Costa, Mario / Mazzanti, Chiara Maria / Vannini, Eleonora / Caleo, Matteo

Neuro-oncology

2023 Volume 25, Issue 8, Page(s) 1463–1473

Abstract: Background: Glioblastoma growth impacts on the structure and physiology of peritumoral neuronal networks, altering the activity of pyramidal neurons which drives further tumor progression. It is therefore of paramount importance to identify glioma- ... ...

Abstract	Background: Glioblastoma growth impacts on the structure and physiology of peritumoral neuronal networks, altering the activity of pyramidal neurons which drives further tumor progression. It is therefore of paramount importance to identify glioma-induced changes in pyramidal neurons, since they represent a key therapeutic target. Methods: We longitudinal monitored visual evoked potentials after the orthotopic implant of murine glioma cells into the mouse occipital cortex. With laser microdissection, we analyzed layer II-III pyramidal neurons molecular profile and with local field potentials recordings we evaluated the propensity to seizures in glioma-bearing animals with respect to control mice. Results: We determine the time course of neuronal dysfunction of glioma-bearing mice and we identify a symptomatic stage, based on the decay of visual response. At that time point, we microdissect layer II-III pyramidal neurons and evaluate the expression of a panel of genes involved in synaptic transmission and neuronal excitability. Compared to the control group, peritumoral neurons show a decrease in the expression of the SNARE complex gene SNAP25 and the alpha1 subunit of the GABA-A receptor. No significant changes are detected in glutamatergic (ie, AMPA or NMDA receptor subunit) markers. Further reduction of GABA-A signaling by delivery of a benzodiazepine inverse agonist, DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) precipitates seizures in 2 mouse models of tumor-bearing mice. Conclusions: These studies reveal novel molecular changes that occur in the principal cells of the tumor-adjacent zone. These modifications may be therapeutically targeted to ameliorate patients' quality of life.
MeSH term(s)	Mice ; Animals ; Evoked Potentials, Visual ; Drug Inverse Agonism ; Quality of Life ; Seizures ; Neurons ; Glioma/metabolism
Language	English
Publishing date	2023-02-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2028601-6
ISSN	1523-5866 ; 1522-8517
ISSN (online)	1523-5866
ISSN	1522-8517
DOI	10.1093/neuonc/noad035
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Zs.A 5307: Show issues

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Article ; Online: Determinants of sexual function in men living with HIV younger than 50 years old: Focus on organic, relational, and psychological issues.

De Vincentis, Sara / Decaroli, Maria Chiara / Milic, Jovana / Fanelli, Flaminia / Tartaro, Giulia / Diazzi, Chiara / Mezzullo, Marco / De Santis, Maria Cristina / Roli, Laura / Trenti, Tommaso / Santi, Daniele / Pagotto, Uberto / Guaraldi, Giovanni / Rochira, Vincenzo

Andrology

2023 Volume 11, Issue 6, Page(s) 954–969

Abstract: Background: Sexual dysfunctions, particularly erectile dysfunction, are common in men living with HIV, whose organic and psychological components remain to be clarified. The aim of the study is to investigate the impact of risk factors of sexual ... ...

Abstract	Background: Sexual dysfunctions, particularly erectile dysfunction, are common in men living with HIV, whose organic and psychological components remain to be clarified. The aim of the study is to investigate the impact of risk factors of sexual dysfunctions, including organic, relational, and psychological determinants of erectile function, in men living with HIV younger than 50 years old. Methods: A cross-sectional, observational study was conducted in men living with HIV < 50 years. The questionnaire International Index of Erectile Function-15 was used to assess the prevalence and degree of erectile dysfunction. The structured interview of erectile dysfunction was used to explore the organic (Scale 1), relational (Scale 2), and psychological (Scale 3) components of erectile dysfunction. Total testosterone, estradiol, and dihydrotestosterone were measured by liquid chromatography-tandem-mass spectrometry; free testosterone was calculated by the Vermeulen equation. Results: A total of 313 consecutive men living with HIV were prospectively enrolled (median age 47.0 years; median HIV-infection duration 16.2 years). 187 patients (59.7%) had erectile dysfunction, with a higher prevalence of non-heterosexual (138 out of 187, 73.8%) than heterosexual patients (p = 0.003). Patients with erectile dysfunction showed a worse score of structured interview of erectile dysfunction scale 3 compared to patients without erectile dysfunction (p = 0.025); the International Index of Erectile Function-15 was inversely related to structured interview of erectile dysfunction scale 3 (p = 0.042). No difference was found for sex steroids (total testosterone, estradiol, free testosterone, and dihydrotestosterone) between men living with HIV with and without erectile dysfunction. In the multivariate analysis sexual orientation, and lack of stable relationships were major determinants for erectile dysfunction. Only 35 of 187 patients with erectile dysfunction (18.7%) reported the use of erectile dysfunction medications. Conclusions: Within the multidimensional network of erectile dysfunction in men living with HIV, the psychological component is predominant, highlighting the contribution of peculiar factors related to HIV distress (e.g., fear of virus transmission, stigma) rather than gonadal status and other classical risk factors. In contrast to the high prevalence, only a few patients reported the use of erectile dysfunction medications suggesting a general under-management of such issues.
MeSH term(s)	Humans ; Male ; Female ; Middle Aged ; Erectile Dysfunction/etiology ; Dihydrotestosterone ; Cross-Sectional Studies ; Testosterone/therapeutic use ; Sexual Dysfunction, Physiological/epidemiology ; Sexual Dysfunction, Physiological/drug therapy ; Estradiol ; HIV Infections/complications ; HIV Infections/epidemiology
Chemical Substances	Dihydrotestosterone (08J2K08A3Y) ; Testosterone (3XMK78S47O) ; Estradiol (4TI98Z838E)
Language	English
Publishing date	2023-01-12
Publishing country	England
Document type	Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2696108-8
ISSN	2047-2927 ; 2047-2919
ISSN (online)	2047-2927
ISSN	2047-2919
DOI	10.1111/andr.13372
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Zs.A 6983: Show issues

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Article ; Online: Delayed Macronutrients' Target Achievement in Parenteral Nutrition Reduces the Risk of Hyperglycemia in Preterm Newborn: A Randomized Controlled Trial.

Di Chiara, Maria / Laccetta, Gianluigi / Regoli, Daniela / Dito, Lucia / Spiriti, Caterina / De Santis, Benedetta / Travaglia, Elisa / Prota, Rita / Parisi, Pasquale / Brunelli, Roberto / Boscarino, Giovanni / Terrin, Gianluca

Nutrients

2023 Volume 15, Issue 5

Abstract: Hyperglycemia (HG) is an independent risk factor of mortality and morbidity in very low birth weight newborns (VLBW). Achievement of high nutritional intakes in the first days of life (DoL) by parenteral nutrition (PN) increases the risk of HG. We aim to ...

Abstract	Hyperglycemia (HG) is an independent risk factor of mortality and morbidity in very low birth weight newborns (VLBW). Achievement of high nutritional intakes in the first days of life (DoL) by parenteral nutrition (PN) increases the risk of HG. We aim to assess if a delayed achievement of the PN macronutrient target dose could reduce the occurrence of HG in VLBW. We enrolled 353 VLBW neonates in a randomized controlled clinical trial comparing two PN protocols that differed in the timing of energy and amino acid target dose achievement: (1) early target dose achievement (energy within 4-5 DoL; amino acids within 3-4 DoL) vs. (2) late target dose achievement (energy within 10-12 DoL; amino acids within 5-7 DoL). The primary outcome was the occurrence of HG during the first week of life. An additional endpoint was long-term body growth. We observed a significant difference in the rate of HG between the two groups (30.7% vs. 12.2%,
MeSH term(s)	Infant, Newborn ; Humans ; Parenteral Nutrition/methods ; Infant, Very Low Birth Weight ; Hyperglycemia ; Amino Acids ; Nutrients
Chemical Substances	Amino Acids
Language	English
Publishing date	2023-03-04
Publishing country	Switzerland
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15051279
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Article ; Online: Hepatic and pulmonary involvement in a patient with PR3-ANCA vasculitis following SARS-CoV-2 vaccination: A case report.

Tonutti, Antonio / Simonetta, Edoardo / Stainer, Anna / Suigo, Giulia / De Santis, Maria / Selmi, Carlo / Masetti, Chiara / Lleo, Ana / Terracciano, Luigi Maria / Aliberti, Stefano / Amati, Francesco

Modern rheumatology case reports

2023 Volume 7, Issue 2, Page(s) 440–443

Abstract: We here report the first case of anti-proteinase 3-positive anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis following the severe acute respiratory syndrome coronavirus 2 Pfizer-BioNTech vaccine presenting with prominent liver ... ...

Abstract	We here report the first case of anti-proteinase 3-positive anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis following the severe acute respiratory syndrome coronavirus 2 Pfizer-BioNTech vaccine presenting with prominent liver involvement and alveolar haemorrhage. Two weeks after vaccination, a 49-year-old man developed inflammatory arthralgias and hypertransaminasaemia. Two months later, fever and haemoptysis appeared; the patient tested positive for anti-proteinase 3 autoantibodies. High-dose steroids and rituximab were started, and complete remission was achieved. Systemic autoimmune diseases, including ANCA-associated vasculitis, should always be considered in the differential diagnosis of hypertransaminasaemia, especially when the clinical context is suspicious.
MeSH term(s)	Male ; Humans ; Middle Aged ; Antibodies, Antineutrophil Cytoplasmic ; COVID-19 Vaccines/adverse effects ; SARS-CoV-2 ; COVID-19/diagnosis ; COVID-19/prevention & control ; Myeloblastin ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/etiology ; Vaccination ; Liver
Chemical Substances	Antibodies, Antineutrophil Cytoplasmic ; COVID-19 Vaccines ; Myeloblastin (EC 3.4.21.76)
Language	English
Publishing date	2023-01-24
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	2472-5625
ISSN (online)	2472-5625
DOI	10.1093/mrcr/rxad005
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