ВАЛИДАЦИЯ ДИАГНОСТИЧЕСКОЙ ТОЧНОСТИ АЛГОРИТМА «ИСКУССТВЕННОГО ИНТЕЛЛЕКТА» ДЛЯ ВЫЯВЛЕНИЯ РАССЕЯННОГО СКЛЕРОЗА В УСЛОВИЯХ ГОРОДСКОЙ ПОЛИКЛИНИКИ

The objective of the study is to evaluate the diagnostic accuracy of an original artificial intelligence (AI) algorithm for detecting MS in the radiology department of primary (outpatient) hospital.Materials and methods. Depersonalized results of brain magnetic resonance imaging (MRI) studies performed in the period from August 22, 2019 to September 26, 2019 in 93 patients (42 men (mean age 47,5±15,9 years) and 51 women (mean age 52,3±16,8 years)) were analyzed. All patients signed a voluntary informed consent form. Brain MRIwere carried out on the VANTAGE Atlas 1,5T MRI scanner (Toshiba, Japan) under a standard protocol.Results. All MRI studies were analyzed by AI-algorithm (index-test). It decisions were compared with a  reference test (groundtruth). The sensitivity of the index-test is 100%, specificity — 75,3%, accuracy —  76,3%, negative predictive value — 100%, area under ROC-curve — 0,861. The algorithm reliably sorts out the studies without signs of MS. The algorithmshows sufficient quality and excellent reproducibility of the results on independent data.Conclusion. The developed AI algorithm ensures effective triage of MRI studies in primary care settings, maintaining an optimal index of suspicion in MS.Цель: оценить диагностическую точность оригинального алгоритма выявления РС в условиях отделения лучевой диагностики медицинской организации, оказывающей первичную (амбулаторно-поликлиническую) медицинскую помощь.Материалы и методы. Проведен анализ деперсонализированных результатов МР-исследований головного мозга, выполненных 93 пациентам в период с 22.08.2019 г. по 26.09.2019 г., из которых 42 мужчины (средний возраст 47,5±15,9 лет) и 51 женщина (средний возраст 52,3±16,8 лет); лица европеоидной расы, жители г. Москвы. Все  пациенты подписали добровольное информированное согласие. Исследования  проводились на томографе VANTAGE Atlas (Toshiba, Япония) с индукцией магнитного поля 1,5 Тл по стандартному протоколу.Результаты. Все МР-исследования проанализированы с применением оригинального  алгоритма «искусственного интеллекта» (ИИ). Решения алгоритма (индекс-теста)  сопоставлены с референс-тестом, значения которого приняты за истинный статус  обследуемых лиц. Чувствительность индекс-теста — 100%, специфичность — 75,3%,  точность — 76,3%, прогностическая ценность отрицательного результата — 100%, площадь под характеристической кривой — 0,861. Результаты свидетельствуют о надежном «отсеивании» алгоритмом результатов исследований без признаков РС.  Показано достаточное качество и отличная воспроизводимость результатов работы  алгоритма на независимых данных.Заключение. Разработанный алгоритм ИИ обеспечивает эффективную сортировку МР-исследований в условиях первичного звена здравоохранения с поддержанием оптимального уровня настороженности относительно РС

Repercussion of megakaryocyte-specific Gata1 Loss on megakaryopoiesis and the hematopoietic precursor compartment

During hematopoiesis, transcriptional programs are essential for the commitment and differentiation of progenitors into the different blood lineages. GATA1 is a transcription factor expressed in several hematopoietic lineages and essential for proper erythropoiesis and megakaryopoiesis. Megakaryocyte-specific genes, such as GP1BA, are known to be directly regulated by GATA1. Mutations in GATA1 can lead to dyserythropoietic anemia and pseudo gray-platelet syndrome. Selective loss of Gata1 expression in adult mice results in macrothrombocytopenia with platelet dysfunction, characterized by an excess of immature megakaryocytes. To specifically analyze the impact of Gata1 loss in mature committed megakaryocytes, we generated Gata1-Lox|Pf4-Cre mice (Gata1cKOMK). Consistent with previous findings, Gata1cKOMK mice are macrothrombocytopenic with platelet dysfunction. Supporting this notion we demonstrate that Gata1 regulates directly the transcription of Syk, a tyrosine kinase that functions downstream of Clec2 and GPVI receptors in megakaryocytes and platelets. Furthermore, we show that Gata1cKOMK mice display an additional aberrant megakaryocyte differentiation stage. Interestingly, these mice present a misbalance of the multipotent progenitor compartment and the erythroid lineage, which translates into compensatory stress erythropoiesis and splenomegaly. Despite the severe thrombocytopenia, Gata1cKOMK mice display a mild reduction of TPO plasma levels, and Gata1cK-OMK megakaryocytes show a mild increase in Pf4 mRNA levels; such a misbalance might be behind the general hematopoietic defects observed, affecting locally normal TPO and Pf4 levels at hematopoietic stem cell niches. © 2016 Meinders et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Multiple Outbreaks of Nosocomial Salmonellosis in Russia and Belarus Caused by a Single Clone of Salmonella enterica Serovar Typhimurium Producing an Extended-Spectrum β-Lactamase

Thirty-four cefotaxime-resistant Salmonella enterica serovar Typhimurium isolates representative of the isolates that caused outbreaks of gastroenteritis in 10 hospitals in seven regions of Russia and Belarus from 1994 to 2003 were analyzed. All isolates produced the CTX-M-5-like extended-spectrum β-lactamase, which confers high-level resistance to cefotaxime and ceftriaxone and decreased susceptibility to ceftazidime. The bla(CTX-M) genes were located on small (7.4- to 12-kb) non-self-transferable plasmids approximately 20 bp downstream of the ISEcp1 insertion sequences. Some isolates carried additional conjugative plasmids mediating resistance to penicillin-inhibitor combinations and various non-β-lactam agents, including tetracycline, chloramphenicol, gentamicin, tobramycin, and co-trimoxazole. Despite the minor differences in susceptibility patterns, all isolates were considered clonally related on the basis of arbitrarily primed PCR and pulsed-field gel electrophoresis analysis. The similarities of the restriction profiles of the CTX-M-coding plasmids further supported the clonal origin of these isolates

Convergent In Vivo and In Vitro Selection of Ceftazidime Resistance Mutations at Position 167 of CTX-M-3 β-Lactamase in Hypermutable Escherichia coli Strains▿

We report on a novel CTX-M extended-spectrum β-lactamase (ESBL), designated CTX-M-42, with enhanced activity toward ceftazidime. CTX-M-42 was identified in a hypermutable Escherichia coli nosocomial isolate (isolate Irk2320) and is a Pro167Thr amino acid substitution variant of CTX-M-3. By molecular typing of ESBL-producing E. coli strains previously isolated in the same hospital ward, we were able to identify a putative progenitor (strain Irk1224) of Irk2320, which had a mutator phenotype and harbored the CTX-M-3 β-lactamase. To reproduce the natural evolution of CTX-M-3, we selected for ceftazidime resistance mutations in blaCTX-M-3 gene in vitro both in clinical isolate Irk1224 and in laboratory-derived hypermutable (mutD5) strain GM2995. These experiments yielded CTX-M-3Pro167Ser and CTX-M-3Asn136Lys mutants which conferred higher levels of resistance to ceftazidime than to cefotaxime. CTX-M-3Asn136Lys had a level of low activity toward ampicillin, which may explain its absence from clinical isolates. We conclude that the selection of CTX-M-42 could have occurred in vivo following treatment with ceftazidime and was likely facilitated by the hypermutable background