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Article ; Online: Dataset Growth in Medical Image Analysis Research.

Kiryati, Nahum / Landau, Yuval

2021 Volume 7, Issue 8

Abstract: Medical image analysis research requires medical image datasets. Nevertheless, due to various impediments, researchers have been described as "data starved". We hypothesize that implicit evolving community standards require researchers to use ever- ... ...

Abstract	Medical image analysis research requires medical image datasets. Nevertheless, due to various impediments, researchers have been described as "data starved". We hypothesize that implicit evolving community standards require researchers to use ever-growing datasets. In Phase I of this research, we scanned the MICCAI (Medical Image Computing and Computer-Assisted Intervention) conference proceedings from 2011 to 2018. We identified 907 papers involving human MRI, CT or fMRI datasets and extracted their sizes. The median dataset size had grown by 3-10 times from 2011 to 2018, depending on imaging modality. Statistical analysis revealed exponential growth of the geometric mean dataset size with an annual growth of 21% for MRI, 24% for CT and 31% for fMRI. Thereupon, we had issued a forecast for dataset sizes in MICCAI 2019 well before the conference. In Phase II of this research, we examined the MICCAI 2019 proceedings and analyzed 308 relevant papers. The MICCAI 2019 statistics compare well with the forecast. The revised annual growth rates of the geometric mean dataset size are 27% for MRI, 30% for CT and 32% for fMRI. We predict the respective dataset sizes in the MICCAI 2020 conference (that we have not yet analyzed) and the future MICCAI 2021 conference.
Language	English
Publishing date	2021-08-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2824270-1
ISSN	2313-433X ; 2313-433X
ISSN (online)	2313-433X
ISSN	2313-433X
DOI	10.3390/jimaging7080155
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Article ; Online: Clinical score for early diagnosis and treatment of stroke-like episodes in MELAS syndrome.

Naftali, Jonathan / Mermelstein, Maor / Landau, Yuval E / Barnea, Rani / Shelly, Shahar / Auriel, Eitan / Peretz, Shlomi

Acta neurologica Belgica

2023 Volume 123, Issue 3, Page(s) 1019–1028

Abstract: Background and objectives: Stroke-like episodes (SLEs) in patients with MELAS syndrome are often initially misdiagnosed as acute ischemic stroke (AIS), resulting in treatment delay. We aimed to determine clinical features that may distinguish SLEs from ... ...

Abstract	Background and objectives: Stroke-like episodes (SLEs) in patients with MELAS syndrome are often initially misdiagnosed as acute ischemic stroke (AIS), resulting in treatment delay. We aimed to determine clinical features that may distinguish SLEs from AISs and explore the benefit of early L-arginine treatment on patient outcomes. Methods: We looked retrospectively for MELAS patients admitted between January 2005 and January 2022 and compared them to an AIS cohort with similar lesion topography. MELAS patients who received L-arginine within 40 days of their first SLE were defined as the early treatment group and the remaining as late or no treatment group. Results: Twenty-three SLEs in 10 MELAS patients and 21 AISs were included. SLE patients had significantly different features: they were younger, more commonly reported hearing loss, lower body mass index, had more commonly a combination of headache and/or seizures at presentation, serum lactate was higher, and hemiparesis was less common. An SLE Early Clinical Score (SLEECS) was constructed by designating one point to each above features. SLEECS ≥ 4 had 80% sensitivity and 100% specificity for SLE diagnosis. Compared to late or no treatment, early treatment group patients (n = 5) had less recurrent SLEs (total 2 vs. 11), less seizures (14% vs. 25%, p = 0.048), lower degree of disability at first and last follow-up (modified ranking scale, mRS 2 ± 0.7 vs. 4.2 ± 1, p = 0.005; 2 ± 0.7 vs. 5.8 ± 0.5, p < 0.001, respectively), and a lower mortality (0% vs. 80% p = 0.048). Conclusions: The SLEECS model may aid in the early diagnosis and treatment of SLEs and lead to improved clinical outcomes.
MeSH term(s)	Humans ; Arginine ; Early Diagnosis ; Ischemic Stroke/drug therapy ; MELAS Syndrome/complications ; MELAS Syndrome/diagnosis ; Retrospective Studies ; Seizures/drug therapy ; Stroke/diagnosis ; Stroke/etiology ; Stroke/drug therapy
Chemical Substances	Arginine (94ZLA3W45F)
Language	English
Publishing date	2023-02-15
Publishing country	Italy
Document type	Journal Article
ZDB-ID	127315-2
ISSN	2240-2993 ; 0300-9009
ISSN (online)	2240-2993
ISSN	0300-9009
DOI	10.1007/s13760-023-02196-z
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Article ; Online: A novel SLC25A13 gene splice site variant causes Citrin deficiency in an infant.

Sachs, Nimrod / Wechsberg, Oded / Landau, Yuval E / Krause, Irit / Elgali, Ifat Israel / Darawshe, Malak / Shomron, Noam / Lidzbarsky, Gabriel / Orenstein, Naama

Gene

2023 Volume 874, Page(s) 147483

Abstract: Citrin deficiency is an autosomal recessive disorder associated with SLC25A13 gene pathogenic variants, with more than a hundred known at present. It manifests in neonates as failure to thrive and acute liver insufficiency. We herein describe a case of a ...

Abstract	Citrin deficiency is an autosomal recessive disorder associated with SLC25A13 gene pathogenic variants, with more than a hundred known at present. It manifests in neonates as failure to thrive and acute liver insufficiency. We herein describe a case of a 4-week-old infant who presented with insufficient weight gain and liver failure accompanied by hyperammonemia. She was diagnosed with Citrin deficiency after a thorough biochemical and molecular analysis including amino acid profile, DNA sequencing of genes of interest and RNA splice site evaluation, to reveal a yet unknown damaging variant of the SLC25A13 gene.
MeSH term(s)	Infant, Newborn ; Female ; Humans ; Infant ; Citrullinemia/genetics ; Mutation ; Mitochondrial Membrane Transport Proteins/genetics ; Base Sequence ; Calcium-Binding Proteins/genetics ; Organic Anion Transporters/genetics
Chemical Substances	Mitochondrial Membrane Transport Proteins ; Calcium-Binding Proteins ; Organic Anion Transporters ; SLC25A13 protein, human
Language	English
Publishing date	2023-05-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2023.147483
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Article: Clinicoradiologic Criteria for the Diagnosis of Stroke-like Episodes in MELAS.

Khasminsky, Vadim / Auriel, Eitan / Luckman, Judith / Eliahou, Ruth / Inbar, Edna / Pardo, Keshet / Landau, Yuval / Barnea, Rani / Mermelstein, Maor / Shelly, Shahar / Naftali, Jonathan / Peretz, Shlomi

Neurology. Genetics

2023 Volume 9, Issue 4, Page(s) e200082

Abstract: Background and objectives: Stroke-like episodes (SLEs) in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome are often misdiagnosed as acute ischemic stroke (AIS). We aimed to determine unique ... ...

Abstract	Background and objectives: Stroke-like episodes (SLEs) in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome are often misdiagnosed as acute ischemic stroke (AIS). We aimed to determine unique clinical and neuroimaging features for SLEs and formulate diagnostic criteria. Methods: We retrospectively identified patients with MELAS admitted for SLEs between January 2012 and December 2021. Clinical features and imaging findings were compared with a cohort of patients who presented with AIS and similar lesion topography. A set of criteria was formulated and then tested by a blinded rater to evaluate diagnostic performance. Results: Eleven MELAS patients with 17 SLE and 21 AISs were included. Patients with SLEs were younger (median 45 [37-60] vs 77 [68-82] years, Discussion: Clinicoradiologic criteria based on simple anamnesis and a CT scan at presentation can accurately diagnose SLE and lead to early administration of appropriate therapy. Classification of evidence: This study provides Class III evidence that an algorithm using clinical and imaging features can differentiate stroke-like episodes due to MELAS from acute ischemic strokes.
Language	English
Publishing date	2023-07-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2818607-2
ISSN	2376-7839
ISSN	2376-7839
DOI	10.1212/NXG.0000000000200082
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Article ; Online: Impact of citrulline substitution on clinical outcome after liver transplantation in carbamoyl phosphate synthetase 1 and ornithine transcarbamylase deficiency.

Journal of inherited metabolic disease

2024 Volume 47, Issue 2, Page(s) 220–229

Abstract: Carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) deficiencies are rare urea cycle disorders, which can lead to life-threatening hyperammonemia. Liver transplantation (LT) provides a cure and offers an alternative to medical ... ...

Abstract	Carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) deficiencies are rare urea cycle disorders, which can lead to life-threatening hyperammonemia. Liver transplantation (LT) provides a cure and offers an alternative to medical treatment and life-long dietary restrictions with permanent impending risk of hyperammonemia. Nevertheless, in most patients, metabolic aberrations persist after LT, especially low plasma citrulline levels, with questionable clinical impact. So far, little is known about these alterations and there is no consensus, whether l-citrulline substitution after LT improves patients' symptoms and outcomes. In this multicentre, retrospective, observational study of 24 patients who underwent LT for CPS1 (n = 11) or OTC (n = 13) deficiency, 25% did not receive l-citrulline or arginine substitution. Correlation analysis revealed no correlation between substitution dosage and citrulline levels (CPS1, p = 0.8 and OTC, p = 1). Arginine levels after liver transplantation were normal after LT independent of citrulline substitution. Native liver survival had no impact on mental impairment (p = 0.67). Regression analysis showed no correlation between l-citrulline substitution and failure to thrive (p = 0.611) or neurological outcome (p = 0.701). Peak ammonia had a significant effect on mental impairment (p = 0.017). Peak plasma ammonia levels correlate with mental impairment after LT in CPS1 and OTC deficiency. Growth and intellectual impairment after LT are not significantly associated with l-citrulline substitution.
MeSH term(s)	Humans ; Ornithine Carbamoyltransferase Deficiency Disease/surgery ; Hyperammonemia/drug therapy ; Liver Transplantation ; Citrulline ; Carbamyl Phosphate/metabolism ; Carbamyl Phosphate/therapeutic use ; Ammonia/metabolism ; Retrospective Studies ; Carbamoyl-Phosphate Synthase (Ammonia)/metabolism ; Arginine/therapeutic use ; Ornithine Carbamoyltransferase
Chemical Substances	Citrulline (29VT07BGDA) ; Carbamyl Phosphate (590-55-6) ; Ammonia (7664-41-7) ; Carbamoyl-Phosphate Synthase (Ammonia) (EC 6.3.4.16) ; Arginine (94ZLA3W45F) ; Ornithine Carbamoyltransferase (EC 2.1.3.3)
Language	English
Publishing date	2024-02-20
Publishing country	United States
Document type	Observational Study ; Multicenter Study ; Journal Article
ZDB-ID	438341-2
ISSN	1573-2665 ; 0141-8955
ISSN (online)	1573-2665
ISSN	0141-8955
DOI	10.1002/jimd.12717
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Article ; Online: Biallelic hypomorphic variants in CAD cause uridine-responsive macrocytic anaemia with elevated haemoglobin-A2.

Steinberg-Shemer, Orna / Yacobovich, Joanne / Noy-Lotan, Sharon / Dgany, Orly / Krasnov, Tanya / Barg, Assaf / Landau, Yuval E / Kneller, Katya / Somech, Raz / Gilad, Oded / Brik Simon, Dafna / Orenstein, Naama / Izraeli, Shai / Del Caño-Ochoa, Francisco / Tamary, Hannah / Ramón-Maiques, Santiago

British journal of haematology

2023 Volume 204, Issue 3, Page(s) 1067–1071

Abstract: Biallelic pathogenic variants in CAD, that encode the multienzymatic protein required for de-novo pyrimidine biosynthesis, cause early infantile epileptic encephalopathy-50. This rare disease, characterized by developmental delay, intractable seizures ... ...

Abstract	Biallelic pathogenic variants in CAD, that encode the multienzymatic protein required for de-novo pyrimidine biosynthesis, cause early infantile epileptic encephalopathy-50. This rare disease, characterized by developmental delay, intractable seizures and anaemia, is amenable to treatment with uridine. We present a patient with macrocytic anaemia, elevated haemoglobin-A2 levels, anisocytosis, poikilocytosis and target cells in the blood smear, and mild developmental delay. A next-generation sequencing panel revealed biallelic variants in CAD. Functional studies did not support complete abrogation of protein function; however, the patient responded to uridine supplement. We conclude that biallelic hypomorphic CAD variants may cause a primarily haematological phenotype.
MeSH term(s)	Humans ; Spasms, Infantile/genetics ; Uridine ; Anemia ; Anemia, Macrocytic ; Hemoglobins
Chemical Substances	Uridine (WHI7HQ7H85) ; Hemoglobins
Language	English
Publishing date	2023-11-20
Publishing country	England
Document type	Journal Article
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.19215
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Article ; Online: Long COVID-19 Liver Manifestation in Children.

Cooper, Shiri / Tobar, Ana / Konen, Osnat / Orenstein, Naama / Kropach Gilad, Nesia / Landau, Yuval E / Mozer-Glassberg, Yael / Bar-Lev, Michal Rozenfeld / Shaoul, Ron / Shamir, Raanan / Waisbourd-Zinman, Orith

Journal of pediatric gastroenterology and nutrition

2022 Volume 75, Issue 3, Page(s) 244–251

Abstract: Objectives: Severe acute respiratory syndrome coronavirus 2, the novel coronavirus responsible for coronavirus disease (COVID-19), has been a major cause of morbidity and mortality worldwide. Gastrointestinal and hepatic manifestations during acute ... ...

Abstract	Objectives: Severe acute respiratory syndrome coronavirus 2, the novel coronavirus responsible for coronavirus disease (COVID-19), has been a major cause of morbidity and mortality worldwide. Gastrointestinal and hepatic manifestations during acute disease have been reported extensively in the literature. Post-COVID-19 cholangiopathy has been increasingly reported in adults. In children, data are sparse. Our aim was to describe pediatric patients who recovered from COVID-19 and later presented with liver injury. Methods: This is a retrospective case series study of pediatric patients with post-COVID-19 liver manifestations. We collected data on demographics, medical history, clinical presentation, laboratory results, imaging, histology, treatment, and outcome. Results: We report 5 pediatric patients who recovered from COVID-19 and later presented with liver injury. Two types of clinical presentation were distinguishable. Two infants aged 3 and 5 months, previously healthy, presented with acute liver failure that rapidly progressed to liver transplantation. Their liver explant showed massive necrosis with cholangiolar proliferation and lymphocytic infiltrate. Three children, 2 aged 8 years and 1 aged 13 years, presented with hepatitis with cholestasis. Two children had a liver biopsy significant for lymphocytic portal and parenchyma inflammation, along with bile duct proliferations. All 3 were started on steroid treatment; liver enzymes improved, and they were weaned successfully from treatment. For all 5 patients, extensive etiology workup for infectious and metabolic etiologies was negative. Conclusions: We report 2 distinct patterns of potentially long COVID-19 liver manifestations in children with common clinical, radiological, and histopathological characteristics after a thorough workup excluded other known etiologies.
MeSH term(s)	Adolescent ; COVID-19/complications ; Child ; Humans ; Infant ; Liver/pathology ; Liver Failure, Acute/pathology ; Retrospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome
Language	English
Publishing date	2022-08-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	603201-1
ISSN	1536-4801 ; 0277-2116
ISSN (online)	1536-4801
ISSN	0277-2116
DOI	10.1097/MPG.0000000000003521
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Article ; Online: Genomics in newborn screening.

Landau, Yuval E / Lichter-Konecki, Uta / Levy, Harvey L

The Journal of pediatrics

2014 Volume 164, Issue 1, Page(s) 14–19

MeSH term(s)	Brain Diseases, Metabolic, Inborn/diagnosis ; Brain Diseases, Metabolic, Inborn/epidemiology ; Brain Diseases, Metabolic, Inborn/genetics ; Genetic Techniques ; Genomics/methods ; Global Health ; Humans ; Incidence ; Infant, Newborn ; Neonatal Screening/methods
Language	English
Publishing date	2014-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1016/j.jpeds.2013.07.028
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Article: Hereditary orotic aciduria identified by newborn screening.

Staretz-Chacham, Orna / Damseh, Nadirah S / Daas, Suha / Abu Salah, Nasser / Anikster, Yair / Barel, Ortal / Dumin, Elena / Fattal-Valevski, Aviva / Falik-Zaccai, Tzipora C / Hershkovitz, Eli / Josefsberg, Sagi / Landau, Yuval / Lerman-Sagie, Tally / Mandel, Hanna / Rock, Rachel / Rostami, Nira / Saraf-Levy, Talya / Shaul Lotan, Nava / Spiegel, Ronen /

Tal, Galit / Ulanovsky, Igor / Wilnai, Yael / Korman, Stanley H / Almashanu, Shlomo

Frontiers in genetics

2023 Volume 14, Page(s) 1135267

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-03-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2023.1135267
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Article ; Online: Long-term outcome of expanded newborn screening at Boston children's hospital: benefits and challenges in defining true disease.

Landau, Yuval E / Waisbren, Susan E / Chan, Lawrence M A / Levy, Harvey L

Journal of inherited metabolic disease

2017 Volume 40, Issue 2, Page(s) 209–218

Abstract: Introduction: There is no universal consensus of the disorders included in newborn screening programs. Few studies so far, mostly short-term, have compared the outcome of disorders detected by expanded newborn screening (ENBS) to the outcome of the same ...

Abstract	Introduction: There is no universal consensus of the disorders included in newborn screening programs. Few studies so far, mostly short-term, have compared the outcome of disorders detected by expanded newborn screening (ENBS) to the outcome of the same disorders detected clinically. Methods: We compared the clinical and neurodevelopmental outcomes in patients with metabolic disorders detected by ENBS, including biotinidase testing, with those detected clinically and followed at the Metabolism Clinic at Boston Children's Hospital. Results: One hundred eighty-nine patients came to attention from ENBS and 142 were clinically diagnosed. 3-methylcrotonyl-CoA carboxylase, biotinidase, and carnitine deficiencies were exclusively identified by ENBS and medium chain acyl-CoA dehydrogenase (MCADD) and very long chain acyl-CoA dehydrogenase deficiencies (VLCADD) were predominantly identified by ENBS whereas the organic acid disorders more often came to attention clinically. Only 2% of the ENBS-detected cases had clinically severe outcomes compared to 42% of those clinically detected. The mean IQ score was 103 + 17 for the ENBS-detected cases and 77 + 24 for those clinically detected. Those newly included disorders that seem to derive the greatest benefit from ENBS include the fatty acid oxidation disorders, profound biotinidase deficiency, tyrosinemia type 1, and perhaps carnitine deficiency. Conclusion: Although the NBS-identified and clinically-identified cohorts were not completely comparable, this long-term study shows likely substantial improvement overall in the outcome of these metabolic disorders in the NBS infants. Infants with mild disorders and benign variants may represent a significant number of infants identified by ENBS. The future challenge will be to unequivocally differentiate the disorders most benefitting from ENBS and adjust programs accordingly.
MeSH term(s)	Acyl-CoA Dehydrogenase/metabolism ; Acyl-CoA Dehydrogenase, Long-Chain/deficiency ; Acyl-CoA Dehydrogenase, Long-Chain/metabolism ; Adolescent ; Adult ; Boston ; Cardiomyopathies/diagnosis ; Cardiomyopathies/metabolism ; Carnitine/deficiency ; Carnitine/metabolism ; Child ; Child, Preschool ; Female ; Humans ; Hyperammonemia/diagnosis ; Hyperammonemia/metabolism ; Infant ; Infant, Newborn ; Lipid Metabolism, Inborn Errors/diagnosis ; Lipid Metabolism, Inborn Errors/metabolism ; Male ; Metabolic Diseases/diagnosis ; Metabolic Diseases/metabolism ; Middle Aged ; Mitochondrial Diseases/diagnosis ; Mitochondrial Diseases/metabolism ; Muscular Diseases/diagnosis ; Muscular Diseases/metabolism ; Neonatal Screening/methods ; Young Adult
Chemical Substances	Acyl-CoA Dehydrogenase (EC 1.3.8.7) ; Acyl-CoA Dehydrogenase, Long-Chain (EC 1.3.8.8) ; Carnitine (S7UI8SM58A)
Language	English
Publishing date	2017-01-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	438341-2
ISSN	1573-2665 ; 0141-8955
ISSN (online)	1573-2665
ISSN	0141-8955
DOI	10.1007/s10545-016-0004-4
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