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Article ; Online: Spontaneous Extradural Hematoma in a Sickle Cell Anemia Patient with Hyperinflammation and Thrombotic Microangiopathy successfully treated with Eculizumab: A case report and review of the literature.

Ita, Michael Itak / Olesen, Pia / Rosing, Maria / Mørk, Morten / Einarsson, Halldór Bjarki / Riis, Jens Jakob

Journal of neurological surgery. Part A, Central European neurosurgery

2024

Abstract: Background The event of extradural hematoma in the absence of head trauma is a rare central nervous system complication of sickle cell disease. We report here a case of spontaneous extradural hematoma in a patient being treated for sickle cell vaso- ... ...

Abstract	Background The event of extradural hematoma in the absence of head trauma is a rare central nervous system complication of sickle cell disease. We report here a case of spontaneous extradural hematoma in a patient being treated for sickle cell vaso-occlusive crisis complicated by hyperinflammation and thrombotic microangiopathy. The significance of inflammation as an integral component of the pathomechanism of vaso-occlusive crisis in patients with sickle cell disease and the role of heme in activating the complement system's alternative pathway are highlighted in this case report. Case Presentation A teenage patient with sickle cell disease developed a spontaneous right parietal extradural hematoma while receiving treatment for sickle cell vaso-occlusive crisis. The concurrent events of hyperinflammation, disseminated intravascular coagulation, hyperhemolysis syndrome, thrombotic microangiopathy and refractory post-operative bleeding complicated this patient's clinical course after surgical evacuation of extradural hematoma. This patient was subsequently treated with eculizumab and improved in the days following. Conclusion Treatment with the anti-C5 monoclonal antibody eculizumab which targets and inhibits terminal complement system activation reversed the deleterious cascade of events in this patient with sickle cell disease.
Language	English
Publishing date	2024-02-20
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2651663-9
ISSN	2193-6323 ; 2193-6315
ISSN (online)	2193-6323
ISSN	2193-6315
DOI	10.1055/a-2271-8772
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Article: Spontaneous Extradural Hematoma in a Sickle Cell Anemia Patient with Hyperinflammation and Thrombotic Microangiopathy successfully treated with Eculizumab: A case report and review of the literature

Ita, Michael Itak / Olesen, Pia / Rosing, Maria / Mørk, Morten / Einarsson, Halldór Bjarki / Riis, Jens Jakob

Journal of Neurological Surgery Part A: Central European Neurosurgery

2024

Abstract	Background The event of extradural hematoma in the absence of head trauma is a rare central nervous system complication of sickle cell disease. We report here a case of spontaneous extradural hematoma in a patient being treated for sickle cell vaso-occlusive crisis complicated by hyperinflammation and thrombotic microangiopathy. The significance of inflammation as an integral component of the pathomechanism of vaso-occlusive crisis in patients with sickle cell disease and the role of heme in activating the complement system's alternative pathway are highlighted in this case report. Case Presentation A teenage patient with sickle cell disease developed a spontaneous right parietal extradural hematoma while receiving treatment for sickle cell vaso-occlusive crisis. The concurrent events of hyperinflammation, disseminated intravascular coagulation, hyperhemolysis syndrome, thrombotic microangiopathy and refractory post-operative bleeding complicated this patient’s clinical course after surgical evacuation of extradural hematoma. This patient was subsequently treated with eculizumab and improved in the days following. Conclusion Treatment with the anti-C5 monoclonal antibody eculizumab which targets and inhibits terminal complement system activation reversed the deleterious cascade of events in this patient with sickle cell disease.
Language	English
Publishing date	2024-02-20
Publisher	Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	2651663-9
ISSN	2193-6323 ; 2193-6315
ISSN (online)	2193-6323
ISSN	2193-6315
DOI	10.1055/a-2271-8772
Database	Thieme publisher's database

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Article ; Online: Do obstetrics trainees working hours affect caesarean section rates in normal risk women?

Kane, Daniel / Shanahan, Ita / Geary, Michael / Malone, Fergal D / Kent, Etaoin / Burke, Naomi

European journal of obstetrics, gynecology, and reproductive biology

2021 Volume 258, Page(s) 358–361

Abstract: Objectives: The rate of caesarean section (CS) is increasing globally. The nulliparous, term, singleton, vertex presentation, spontaneously labouring woman (Robson Group 1/RG1) is considered low risk for CS. It has been hypothesized that more CS occur ... ...

Abstract	Objectives: The rate of caesarean section (CS) is increasing globally. The nulliparous, term, singleton, vertex presentation, spontaneously labouring woman (Robson Group 1/RG1) is considered low risk for CS. It has been hypothesized that more CS occur at nighttime or at weekends due to doctor fatigue. The European Working Time Directive (EWTD) was implemented in our institution in 2013 to limit doctor working hours, which aimed at reducing fatigue but arguably fractures continuity of care. This study aimed to determine the effect of nocturnal hours and weekend on-call as well as the implementation of EWTD on our RG1 CS rates. Study design: This was a population-based study in a tertiary referral centre from 2008-2017. The inclusion criteria for our study were limited to RG1. Data were analysed from an established clinical database, including mode and time of delivery. Descriptive statistics are presented as number and percent for categorical variables. Relative frequencies were tested using chi-squared test. All statistical analyses were performed using SPSS Version 26. Statistical significance was defined as p < .05. Results: There were 86,473 deliveries over the 10-year study period. There were 18,761 women in RG1. Overall the RG1 CS rate was 12.9 % (n = 2415). Rates of CS in the RG1 were not statistically different between those delivering on weekdays (12.9 %, n = 1726/13,430) and weekends (12.9 %, n = 689/5,331, OR 0.99, 95 % CI = 0.90-1.09, p = .89). During daytime hours the CS rate was 12.1 % (n = 777/6411) and at nighttime was 13.3 % (n = 1638/12,350, OR 1.10, 95 % CI = 1.01-1.21, p = .03). Comparing the time periods pre and post EWTD implementation, there was a significant increase in CS rates (12.1 % n = 1319/10,873 V 13.9 % n = 1096/7,888, OR 1.17, 95 % CI = 1.07-1.27 p < .001). With respect to other modes of delivery in RG1 pre and post EWTD, there was a statistically significant decrease in operative vaginal delivery (OVD) rates (40.1%, n=4,360 V 37.7%, n=2,973, OR 0.90, 95% CI = 0.85-0.95, p = .001) CONCLUSION: This study shows an association between obstetric trainee working practices, RG1 CS and OVD rates; this is most pronounced at night and after the introduction of the EWTD. It is unlikely that obstetric trainee working practices are the only factor related to the increasing CS rate and reduced OVD rate. Consideration should be giving to addressing the needs of obstetric trainees in relation to achieving their competencies with now reduced labour ward exposure. Further study is required to see if alternate arrangements in relation to simulation training could increase the OVD rate and reduce the CS rate.
MeSH term(s)	Cesarean Section ; Delivery, Obstetric ; Female ; Humans ; Labor, Obstetric ; Obstetrics ; Pregnancy ; Risk
Language	English
Publishing date	2021-01-23
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	190605-7
ISSN	1872-7654 ; 0301-2115 ; 0028-2243
ISSN (online)	1872-7654
ISSN	0301-2115 ; 0028-2243
DOI	10.1016/j.ejogrb.2021.01.036
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Zs.A 837: Show issues

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Article ; Online: Therapeutic Response Evaluation in Advanced Melanoma Patients Incorporating Plasma cfDNA, LDH, VEGF, PD-L1, and IFN-γ Measurements.

Ita, Michael I / Wang, Jiang H / Heffron, Cynthia C / Power, Derek G / Nolan, Yvonne / Toulouse, André / Lim, Chris C H / Fanning, Noel / Redmond, Henry P

Anticancer research

2022 Volume 42, Issue 2, Page(s) 801–810

Abstract: Background/aim: Current treatment strategies for advanced melanoma require serial assessment of disease status in affected patients. In this study, we sought to examine the relationship between radiographic tumour burden and blood borne biomarkers ... ...

Abstract	Background/aim: Current treatment strategies for advanced melanoma require serial assessment of disease status in affected patients. In this study, we sought to examine the relationship between radiographic tumour burden and blood borne biomarkers including plasma cfDNA, serum LDH, plasma VEGF, PD-L1 and IFN-γ in advanced melanoma patients receiving immunotherapy. We hypothesized that a combination of these explanatory variables in a suitable regression analysis model may predict changes in tumour burden during patient treatment. Materials and methods: We extracted and quantified circulating cfDNA, LDH, VEGF, PD-L1, and IFN-γ from thirty patients with stage IV melanoma at baseline and at six months. All participating patients were evaluated with paired blood sample collection and CT scan assessments during treatment. Results: Changes in radiographic tumour burden correlated with changes in levels of cfDNA (p≤0.001), LDH (p≤0.001), VEGF (p≤0.001), and PD-L1 (p<0.05) during treatment. Multiple regression analysis consisting of the follow-up to baseline assessment ratios of cfDNA, LDH, VEGF and PD-L1 explained changes in tumour burden (F (4, 23)=32.05, p<0.001); with an R Conclusion: A quantitative measure of cfDNA, LDH, VEGF and PD-L1 may complement current methods of assessing tumour burden in advanced melanoma patients.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen/blood ; Biomarkers, Tumor/blood ; Cell-Free Nucleic Acids/blood ; Female ; Humans ; Immunotherapy ; Interferon-gamma/blood ; L-Lactate Dehydrogenase/blood ; Male ; Melanoma/blood ; Melanoma/pathology ; Melanoma/therapy ; Middle Aged ; Regression Analysis ; Tumor Burden ; Vascular Endothelial Growth Factor A/blood
Chemical Substances	B7-H1 Antigen ; Biomarkers, Tumor ; CD274 protein, human ; Cell-Free Nucleic Acids ; IFNG protein, human ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Interferon-gamma (82115-62-6) ; L-Lactate Dehydrogenase (EC 1.1.1.27)
Language	English
Publishing date	2022-01-29
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.15538
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Zs.A 1642: Show issues

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Article ; Online: Universality in the Classical Limit of Massless Gravitational Scattering.

Bern, Zvi / Ita, Harald / Parra-Martinez, Julio / Ruf, Michael S

Physical review letters

2020 Volume 125, Issue 3, Page(s) 31601

Abstract: We demonstrate the universality of the gravitational classical deflection angle of massless particles through O(G^{3}) by studying the high-energy limit of full two-loop four-graviton scattering amplitudes in pure Einstein gravity as well as N≥4 ... ...

Abstract	We demonstrate the universality of the gravitational classical deflection angle of massless particles through O(G^{3}) by studying the high-energy limit of full two-loop four-graviton scattering amplitudes in pure Einstein gravity as well as N≥4 supergravity. As a by-product, our first-principles calculation provides a direct confirmation of the massless deflection angle in Einstein gravity proposed long ago by Amati, Ciafaloni, and Veneziano, and is inconsistent with a recently proposed alternative.
Language	English
Publishing date	2020-08-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	208853-8
ISSN	1079-7114 ; 0031-9007
ISSN (online)	1079-7114
ISSN	0031-9007
DOI	10.1103/PhysRevLett.125.031601
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Article ; Online: Plasma circulating cell free messenger RNA as a potential biomarker of melanoma.

Ita, Michael Itak / Wang, Jiang Huai / Fanning, Noel / Kaar, George / Lim, Chris / Redmond, Henry Paul

Acta oncologica (Stockholm, Sweden)

2021 Volume 60, Issue 9, Page(s) 1201–1209

Abstract: Background: Blood borne cell free nucleic acids are increasingly emerging as significant non-invasive adjuncts to current methods of disease status evaluation in cancer patients. In this study, we sought to examine whether significant differences exist ... ...

Abstract	Background: Blood borne cell free nucleic acids are increasingly emerging as significant non-invasive adjuncts to current methods of disease status evaluation in cancer patients. In this study, we sought to examine whether significant differences exist in the plasma transcriptomic profile of advanced melanoma patients with a high disease burden compared to patients with a low disease burden or therapeutic response. Methods: Pathway focussed gene expression analysis was performed using cDNA derived from the plasma circulating cell free messenger ribonucleic acid (ccfmRNA) samples of twenty-two patients with advanced melanoma. Patients were assessed with paired blood sample collection and CT scan assessments at baseline and at 3 months follow up. Results: We identified several genes which were significantly over-expressed in patients with a low disease burden or therapeutic response; BCL2L1, CXCL9, IDO1, IL13, MIF, MYD88 and TLR4 ( Conclusion: Significant differences were observed in the plasma transcriptomic profile between the various melanoma patient groups, and we postulate that these differences may be exploited to identify novel therapeutic targets or biomarkers relevant to melanoma.
MeSH term(s)	Biomarkers ; Biomarkers, Tumor/genetics ; Cell-Free Nucleic Acids/genetics ; Humans ; Melanoma/genetics ; Prognosis ; RNA, Messenger/genetics ; Skin Neoplasms
Chemical Substances	Biomarkers ; Biomarkers, Tumor ; Cell-Free Nucleic Acids ; RNA, Messenger
Language	English
Publishing date	2021-06-04
Publishing country	England
Document type	Journal Article
ZDB-ID	896449-x
ISSN	1651-226X ; 0349-652X ; 0284-186X ; 1100-1704
ISSN (online)	1651-226X
ISSN	0349-652X ; 0284-186X ; 1100-1704
DOI	10.1080/0284186X.2021.1928749
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Article ; Online: Assessment of cell-free DNA (cfDNA) concentrations in the perioperative period can predict risk of recurrence in patients with non-metastatic breast cancer.

Hassan, Fara / Wang, Jiang Huai / Cullinane, Carolyn / Ita, Michael / Corrigan, Mark / O'Leary, Donal Peter / Redmond, Henry Paul

Surgical oncology

2022 Volume 42, Page(s) 101753

Abstract: Background: Circulating cell-free DNA (cfDNA) is a potential non-invasive biomarker of disease status in patients with cancer, and provides important diagnostic and prognostic information in breast cancer. The goal of this study was to quantify cfDNA ... ...

Abstract	Background: Circulating cell-free DNA (cfDNA) is a potential non-invasive biomarker of disease status in patients with cancer, and provides important diagnostic and prognostic information in breast cancer. The goal of this study was to quantify cfDNA concentrations during the perioperative period and investigate its potential utility to detect recurrence outcomes in patients with breast cancer. Methods: Sixty-two (n = 62) patients with non-metastatic breast cancer, undergoing curative-intent surgery were screened for inclusion. Blood samples were collected from these patients: pre-operatively (Preop) and post-operatively (PO) at either of the following PO time points; PO week 1-2, PO week 3-4 and PO weeks 5-12 following surgery. cfDNA was extracted and quantified using nanodrop spectrophotometer. Results: In a cohort of 62 patients (age, median (IQR), 51.5(45.0-65.0) years), with a median follow-up of 90 months (interquartile range (IQR),60-120 months), significant association was observed between cfDNA concentrations and risk of recurrence in patients with breast cancer. The group of patients who had disease recurrence during follow-up had significantly higher cfDNA concentrations (cutoff:400 ng/ml) compared to the group of patients who remain disease-free (Preop and PO period: p < 0.0001). The median Recurrence Free Survival (RFS) between the Disease Recurrence (DR) and the Disease Free (DF) groups of patients with breast cancer were 12(20-28.5) months and 72.00 (96-120) months; p < 0.0001). Univariate and multivariate cox regression analysis indicated that postoperative cfDNA concentration (Hazard ratio:5.0, 95% Confidence Interval:1.19-21.28, p = 0.028) was an independent negative prognostic factor for RFS in patients with non-metastatic breast cancer. Conclusion: Our study demonstrated that high postoperative cfDNA is associated with increased risk of future recurrence in patients with non-metastatic breast cancer. Further, prospective studies are warranted to validate its clinical utility in breast cancer.
MeSH term(s)	Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics ; Breast Neoplasms/surgery ; Cell-Free Nucleic Acids ; Female ; Humans ; Perioperative Period ; Prognosis
Chemical Substances	Biomarkers, Tumor ; Cell-Free Nucleic Acids
Language	English
Publishing date	2022-04-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1107810-8
ISSN	1879-3320 ; 0960-7404
ISSN (online)	1879-3320
ISSN	0960-7404
DOI	10.1016/j.suronc.2022.101753
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Zs.A 3409: Show issues

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Article ; Online: Conservative antibiotic treatment for acute uncomplicated appendicitis is feasible.

Steiner, Zvi / Buklan, Genady / Gutermacher, Michael / Litmanovitz, Ita / Landa, Tal / Arnon, Shmuel

Pediatric surgery international

2018 Volume 34, Issue 3, Page(s) 283–288

Abstract: Purpose: Appendectomy versus conservative antibiotic treatment (CAT) for children with acute uncomplicated appendicitis (AUA) remains unresolved, with concerns regarding the practicality of CAT. We analyzed our center's experience with CAT for AUA, ... ...

Abstract	Purpose: Appendectomy versus conservative antibiotic treatment (CAT) for children with acute uncomplicated appendicitis (AUA) remains unresolved, with concerns regarding the practicality of CAT. We analyzed our center's experience with CAT for AUA, using a protocol with strict inclusion, exclusion and treatment criteria. Methods: Non-randomized, prospective cohort study included all children admitted betwee 2014 and 2016, with clinical and laboratory tests suspicious for AUA. Data collected included clinical signs and symptoms; laboratory, ultrasound and pathology results. Follow-up was conducted through clinic visits, telephone conversations and national registry analysis. Results: Included in CAT: 362 children, 19 underwent appendectomy within 1-2 days. Overall, 75 were readmitted for recurrent acute appendicitis during 22 months (6-43) follow-up. Thirty were treated successfully with antibiotics a second time. The remaining 45 had appendectomy. Overall, 86.8% underwent CAT with no surgery. Histology of all recurrent AUA revealed no perforations. Conclusion: We confirm the feasibility of conservative management of AUA in children. A rigorous diagnostic plan with strict inclusion and exclusion criteria will lead to high success rate of CAT with a strong safety profile. CAT does not compete with surgery or render appendectomy unnecessary. It is a safe alternative to surgery in selected cases.
MeSH term(s)	Adolescent ; Anti-Bacterial Agents/therapeutic use ; Appendectomy/statistics & numerical data ; Appendicitis/diagnostic imaging ; Appendicitis/therapy ; Child ; Child, Preschool ; Cohort Studies ; Conservative Treatment ; Feasibility Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Patient Readmission/statistics & numerical data
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2018-03
Publishing country	Germany
Document type	Journal Article
ZDB-ID	632773-4
ISSN	1437-9813 ; 0179-0358
ISSN (online)	1437-9813
ISSN	0179-0358
DOI	10.1007/s00383-018-4226-4
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Article ; Online: Disturbance cues function as a background risk cue but not as an associative learning cue in tadpoles.

Rivera-Hernández, Ita A E / Crane, Adam L / Pollock, Michael S / Ferrari, Maud C O

Animal cognition

2022 Volume 25, Issue 4, Page(s) 881–889

Abstract: Chemical information has an important role in the sensory ecology of aquatic species. For aquatic prey, chemical cues are a vital source of information related to predator avoidance and risk assessment. For instance, alarm cues are released by prey that ... ...

Abstract	Chemical information has an important role in the sensory ecology of aquatic species. For aquatic prey, chemical cues are a vital source of information related to predator avoidance and risk assessment. For instance, alarm cues are released by prey that have been injured by predators. In addition to providing accurate information about current risk, repeated exposure to alarm cues can elicit a fear response to novel stimuli (neophobia) in prey. Another source of chemical information is disturbance cues, released by prey that have been disturbed or harassed (but not injured) by a predator. While disturbance cues have received much less attention than alarm cues, they appear to be useful as an early warning signal of predation risk and have the potential to be used as a priming cue for learning. In this study, we used wood frog (Lithobates sylvaticus) tadpoles to test whether repeated exposure to disturbance cues during the embryonic stage can induce neophobic behaviour. Three weeks following repeated exposure to disturbance cues, tadpoles showed reduced activity when exposed to a novel odour, but they no longer displayed an antipredator response to disturbance cues. In a second experiment, we found that tadpoles failed to learn that a novel odour was dangerous following a pairing with disturbance cues, whereas alarm cues facilitated such learning. Our results add to the growing body of information about disturbance cues and provide evidence of their function as an embryonic risk cue but not as an associative learning cue.
MeSH term(s)	Animals ; Cues ; Larva/physiology ; Learning ; Odorants ; Predatory Behavior
Language	English
Publishing date	2022-01-31
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1466332-6
ISSN	1435-9456 ; 1435-9448
ISSN (online)	1435-9456
ISSN	1435-9448
DOI	10.1007/s10071-022-01599-4
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Article ; Online: Autophagy induced by taurolidine protects against polymicrobial sepsis by promoting both host resistance and disease tolerance.

Huang, Jie / Ita, Michael / Zhou, Huiting / Zhao, He / Hassan, Fara / Bai, Zhenjiang / O'Leary, D Peter / Li, Yiping / Redmond, H Paul / Wang, Jiang Huai / Wang, Jian

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 19, Page(s) e2121244119

Abstract: Sepsis, septic shock, and their sequelae are the leading causes of death in intensive care units, with limited therapeutic options. Disease resistance and tolerance are two evolutionarily conserved yet distinct defense strategies that protect the host ... ...

Abstract	Sepsis, septic shock, and their sequelae are the leading causes of death in intensive care units, with limited therapeutic options. Disease resistance and tolerance are two evolutionarily conserved yet distinct defense strategies that protect the host against microbial infection. Here, we report that taurolidine administered at 6 h before septic challenge led to strong protection against polymicrobial sepsis by promoting both host resistance and disease tolerance characterized by accelerated bacterial clearance, ameliorated organ damage, and diminished vascular and gut permeability. Notably, taurolidine administered at 6 h after septic challenge also rescued mice from sepsis-associated lethality by enhancing disease tolerance to tissue and organ injury. Importantly, this in vivo protection afforded by taurolidine depends on an intact autophagy pathway, as taurolidine protected wild-type mice but was unable to rescue autophagy-deficient mice from microbial sepsis. In vitro, taurolidine induced light chain 3-associated phagocytosis in innate phagocytes and autophagy in vascular endothelium and gut epithelium, resulting in augmented bactericidal activity and enhanced cellular tolerance to endotoxin-induced damage in these cells. These results illustrate that taurolidine-induced autophagy augments both host resistance and disease tolerance to bacterial infection, thereby conferring protection against microbial sepsis.
MeSH term(s)	Animals ; Autophagy ; Mice ; Phagocytosis ; Sepsis/drug therapy ; Sepsis/metabolism ; Taurine/analogs & derivatives ; Thiadiazines/pharmacology
Chemical Substances	Thiadiazines ; Taurine (1EQV5MLY3D) ; taurolidine (8OBZ1M4V3V)
Language	English
Publishing date	2022-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2121244119
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