Hematologic cancer diagnosis and classification using machine and deep learning: State-of-the-art techniques and emerging research directives.

Hematology is the study of diagnosis and treatment options for blood diseases, including cancer. Cancer is considered one of the deadliest diseases across all age categories. Diagnosing such a deadly disease at the initial stage is essential to cure the disease. Hematologists and pathologists rely on microscopic evaluation of blood or bone marrow smear images to diagnose blood-related ailments. The abundance of overlapping cells, cells of varying densities among platelets, non-illumination levels, and the amount of red and white blood cells make it more difficult to diagnose illness using blood cell images. Pathologists are required to put more effort into the traditional, time-consuming system. Nowadays, it becomes possible with machine learning and deep learning techniques, to automate the diagnostic processes, categorize microscopic blood cells, and improve the accuracy of the procedure and its speed as the models developed using these methods may guide an assisting tool. In this article, we have acquired, analyzed, scrutinized, and finally selected around 57 research papers from various machine learning and deep learning methodologies that have been employed in the diagnosis of leukemia and its classification over the past 20 years, which have been published between the years 2003 and 2023 by PubMed, IEEE, Science Direct, Google Scholar and other pertinent sources. Our primary emphasis is on evaluating the advantages and limitations of analogous research endeavors to provide a concise and valuable research directive that can be of significant utility to fellow researchers in the field.

L'utilisation sécuritaire des médicaments chez les enfants ayant des problèmes médicaux complexes.

Grâce aux progrès de la médecine et aux innovations en technologies de la santé, de nombreux enfants atteints d'affections au pronostic réservé vivent désormais plus longtemps. Ces enfants sont souvent qualifiés d'« enfants ayant des problèmes médicaux complexes ¼, parce qu'ils ont des affections chroniques, utilisent davantage les soins de santé et sont dépendants de la technologie. La complexité de leurs soins et leur fragilité intrinsèque entraînent des risques plus élevés d'erreurs de médication, autant dans un contexte ambulatoire qu'hospitalier. Le taux élevé de fragmentation des soins, de mauvaise communication et de polypharmacie chez les enfants ayant des problèmes médicaux complexes accroissent les possibilités d'erreurs, particulièrement au moment de changer de milieu de soins et de praticiens. Il n'existe pas de données sur les facteurs qui contribuent à un risque plus élevé d'erreurs de médication dans cette population et sur les meilleures mesures pour les éviter. Le présent point de pratique fournit des directives cliniques aux professionnels de la santé afin de s'assurer d'une utilisation sécuritaire des médicaments auprès des enfants ayant des problèmes médicaux complexes et s'attarde sur des stratégies pratiques applicables à la fois en soins ambulatoires et hospitaliers.

Medication safety for children with medical complexity.

Due to advances in medical care and innovations in health technology, many children with life-limiting conditions are now living longer. These children are often referred to as 'children with medical complexity (CMC)', and they are characterized by chronic conditions, increased health care utilization, and technology dependence. Their complexity of care and inherent fragility lead to higher risk for medication errors, both in-community and in-hospital. High rates of care fragmentation, miscommunication, and polypharmacy in CMC increase opportunities for error, particularly as children transition between health care settings and practitioners. Data on the factors contributing to higher risk of medication errors in this population and how they can be effectively addressed are lacking. This practice point provides clinical guidance for health care professionals to ensure medication safety when caring for CMC, with focus on practical strategies for outpatient and inpatient care.

The Healthy Heart-Mind Trial: Randomized Controlled Trial of Melatonin for Prevention of Delirium.

OBJECTIVES: Delirium is a serious medical condition with increased incidence in at-risk surgical populations. We sought to determine if melatonin use reduces the incidence of delirium in individuals undergoing major cardiac surgery. DESIGN: Randomized double-blind placebo-controlled clinical trial (two arms, 1:1 allocation, parallel design). SETTING: The trial took place in two metropolitan hospitals (public tertiary and private) in Perth, Western Australia. PARTICIPANTS: We recruited 210 adults aged 50 years or older who were due to undergo coronary artery bypass grafting or valve replacement surgery. INTERVENTION: Participants were randomly assigned (1:1) to 7 days of treatment with melatonin 3 mg at night or matching placebo, starting 2 days before the surgery. MEASUREMENTS: The primary outcome of interest was incident delirium within 7 days of surgery as assessed via daily clinical assessment that included the Confusion Assessment Method. Secondary outcomes of interest included duration and severity of delirium, length of hospital stay, cognitive function, and mood and anxiety symptoms at discharge and 3 months after the surgery. RESULTS: The groups were well balanced for demographic and clinical parameters. Forty-two participants developed delirium, but it was evenly distributed between the groups (melatonin 21/98, 21.4%; placebo 21/104, 20.2%; adjusted odds ratio [OR] = .78; 95% confidence interval [CI] = .35-1.75). The median duration of delirium was 3 (interquartile range [IQR] = 2-4) and 2 (IQR = 1-3) days for people treated with melatonin and placebo, respectively (z = -1.03; P = .304). A similar proportion of participants experienced severe episodes of delirium in each group (melatonin 9/21, 42.9% vs placebo 6/21, 28.6%; χ2 = .93; P = .334; adjusted OR = 1.98; 95% CI = .40-9.78). The groups did not differ in terms of length of stay, mood, anxiety, and cognitive performance. CONCLUSION: The findings of this randomized double-blind placebo-controlled trial do not support the prophylactic use of melatonin to prevent delirium after major cardiac surgery. J Am Geriatr Soc 68:112-119, 2019.

Use of a molecular decoy to segregate transport from antigenicity in the FrpB iron transporter from Neisseria meningitidis.

FrpB is an outer membrane transporter from Neisseria meningitidis, the causative agent of meningococcal meningitis. It is a member of the TonB-dependent transporter (TBDT) family and is responsible for iron uptake into the periplasm. FrpB is subject to a high degree of antigenic variation, principally through a region of hypervariable sequence exposed at the cell surface. From the crystal structures of two FrpB antigenic variants, we identify a bound ferric ion within the structure which induces structural changes on binding which are consistent with it being the transported substrate. Binding experiments, followed by elemental analysis, verified that FrpB binds Fe(3+) with high affinity. EPR spectra of the bound Fe(3+) ion confirmed that its chemical environment was consistent with that observed in the crystal structure. Fe(3+) binding was reduced or abolished on mutation of the Fe(3+)-chelating residues. FrpB orthologs were identified in other Gram-negative bacteria which showed absolute conservation of the coordinating residues, suggesting the existence of a specific TBDT sub-family dedicated to the transport of Fe(3+). The region of antigenic hypervariability lies in a separate, external sub-domain, whose structure is conserved in both the F3-3 and F5-1 variants, despite their sequence divergence. We conclude that the antigenic sub-domain has arisen separately as a result of immune selection pressure to distract the immune response from the primary transport function. This would enable FrpB to function as a transporter independently of antibody binding, by using the antigenic sub-domain as a 'molecular decoy' to distract immune surveillance.

Refolding, purification and crystallization of the FrpB outer membrane iron transporter from Neisseria meningitidis.

FrpB is an integral outer membrane protein from the human pathogen Neisseria meningitidis. It is a member of the TonB-dependent transporter family and promotes the uptake of iron across the outer membrane. There is also evidence that FrpB is an antigen and hence a potential component of a vaccine against meningococcal meningitis. FrpB incorporating a polyhistidine tag was overexpressed in Escherichia coli into inclusion bodies. The protein was then solubilized in urea, refolded and purified to homogeneity. Two separate antigenic variants of FrpB were crystallized by sitting-drop vapour diffusion. Crystals of the F5-1 variant diffracted to 2.4 Å resolution and belonged to space group C2, with unit-cell parameters a = 176.5, b = 79.4, c = 75.9 Å, ß = 98.3°. Crystal-packing calculations suggested the presence of a monomer in the asymmetric unit. Crystals of the F3-3 variant also diffracted to 2.4 Å resolution and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 85.3, b = 104.6, c = 269.1 Å. Preliminary analysis suggested the presence of an FrpB trimer in the asymmetric unit.

Management of febrile neutropenia in pediatric oncology patients: a Canadian survey.

BACKGROUND: Traditionally, febrile neutropenia in pediatric oncology patients has been managed aggressively with hospital admission and intravenous antibiotics. Recent studies suggest that less intensive interventions are effective for selected children. Study of Canadian practice patterns may help better understand the current context of care for these patients. PROCEDURE: We carried out a cross-sectional mailed survey of the 17 tertiary pediatric centers in Canada. A 36-item questionnaire gathered information on oncology department characteristics, the existence of protocols for management of febrile neutropenia, use of outpatient therapy or early discharge, criteria used to identify patients at low risk, and opinions of oncologists. RESULTS: A total of 16 (94%) completed questionnaires were returned, reflecting a treatment population of approximately 2,100 children with febrile neutropenia/year. Three out of seventeen centers carry out exclusively traditional management. The remaining 14 offer modified treatment for low risk children. The majority (n = 10) carry out an early discharge approach. Two thirds of the episodes of febrile neutropenia are treated this way with good results. The rest (n = 4) implement complete outpatient management. Approximately 120 patients benefit from this annually, with a reportedly high success rate. Most specialists agreed on the benefits of decreased hospitalization for children with cancer. However, about half considered the level of evidence is not sufficient to fully implement complete outpatient management. CONCLUSIONS: Variations in the treatment of pediatric febrile neutropenia have been extensively implemented across Canada. However more evidence, ideally in the form of multicenter clinical trials, appears to be needed to further safely modify practice.

Focal cerebral pathology presenting as tonic seizures.

We report a case of a 14-year-old boy with a dysembryoplastic neuroepithelial tumor and mental retardation with intractable seizures, which were demonstrated to be predominantly tonic seizures by video-electroencephalography (EEG). He did not have any electrographic evidence of Lennox-Gastaut syndrome. Head magnetic resonance imaging (MRI) revealed a right parietal dysembryoplastic neuroepithelial tumor. He has been seizure free since surgical removal of the tumor. Clinicians need to be aware that tonic seizures can be associated with an underlying focal pathology that might be treatable.

Mannitol is required for stress tolerance in Aspergillus niger conidiospores.

D-Mannitol is the predominant carbon compound in conidiospores of the filamentous fungus Aspergillus niger and makes up 10 to 15% of the dry weight. A number of physiological functions have been ascribed to mannitol, including serving as a reserve carbon source, as an antioxidant, and to store reducing power. In this study, we cloned and characterized the A. niger mpdA gene, which encodes mannitol 1-phosphate dehydrogenase (MPD), the first enzyme in the mannitol biosynthesis pathway. The mpdA promoter contains putative binding sites for the development-specific transcription factors BRLA and ABAA. Furthermore, increased expression of mpdA in sporulating mycelium suggests that mannitol biosynthesis is, to a certain extent, developmentally regulated in A. niger. Inactivation of mpdA abolished mannitol biosynthesis in growing mycelium and reduced the mannitol level in conidiospores to 30% that in the wild type, indicating that MPD and mannitol 1-phosphate phosphatase form the major metabolic pathway for mannitol biosynthesis in A. niger. The viability of spores after prolonged storage and germination kinetics were normal in an mpdA null mutant, indicating that mannitol does not play an essential role as a reserve carbon source in A. niger conidia. However, conidiospores of a DeltampdA strain were extremely sensitive to a variety of stress conditions, including high temperature, oxidative stress and, to a lesser extent, freezing and lyophilization. Since mannitol supplied in the medium during sporulation repaired this deficiency, mannitol appears to be essential for the protection of A. niger spores against cell damage under these stress conditions.

Activation of peroxisome proliferator-activated receptors in human airway smooth muscle cells has a superior anti-inflammatory profile to corticosteroids: relevance for chronic obstructive pulmonary disease therapy.

Airway smooth muscle is actively involved in the inflammatory process in diseases such as chronic obstructive pulmonary disease and asthma by 1) contributing to airway narrowing through hyperplasia and hypertrophy and 2) the release of GM-CSF and G-CSF, which promotes the survival and activation of infiltrating leukocytes. Thus, the identification of novel anti-inflammatory pathways in airway smooth muscle will have important implications for the treatment of inflammatory airway disease. This study identifies such a pathway in the activation of peroxisome proliferator-activated receptors (PPARs). PPAR ligands are known therapeutic agents in the treatment of diabetes; however, their role in human airway disease is unknown. We demonstrate, for the first time, that human airway smooth muscle cells express PPAR alpha and -gamma subtypes. Activation of PPAR gamma by natural and synthetic ligands inhibits serum-induced cell growth more effectively than does the steroid dexamethasone, and induces apoptosis. Moreover, PPAR gamma activation, like dexamethasone, inhibits the release of GM-CSF. However, PPAR gamma ligands, but not dexamethasone, similarly inhibits G-CSF release. These results reveal a novel anti-inflammatory pathway in human airway smooth muscle, where PPAR gamma activation has additional anti-inflammatory effects to those of steroids. Hence, PPAR ligands might act as potential treatments in human respiratory diseases.