Assessment of selection pressure exerted on genes from complete pangenomes helps to improve the accuracy in the prediction of new genes.

Bacterial genomes are massively sequenced, and they provide valuable data to better know the complete set of genes of a species. The analysis of thousands of bacterial strains can identify both shared genes and those appearing only in the pathogenic ones. Current computational gene finders facilitate this task but often miss some existing genes. However, the present availability of different genomes from the same species is useful to estimate the selective pressure applied on genes of complete pangenomes. It may assist in evaluating gene predictions either by checking the certainty of a new gene or annotating it as a gene under positive selection. Here, we estimated the selective pressure of 19 271 genes that are part of the pangenome of the human opportunistic pathogen Acinetobacter baumannii and found that most genes in this bacterium are subject to negative selection. However, 23% of them showed values compatible with positive selection. These latter were mainly uncharacterized proteins or genes required to evade the host defence system including genes related to resistance and virulence whose changes may be favoured to acquire new functions. Finally, we evaluated the utility of measuring selection pressure in the detection of sequencing errors and the validation of gene prediction.

Lipid turnover through lipophagy in the newly identified extremophilic green microalga Chlamydomonas urium.

Autophagy is a central degradative pathway highly conserved among eukaryotes, including microalgae, which remains unexplored in extremophilic organisms. In this study, we described and characterized autophagy in the newly identified extremophilic green microalga Chlamydomonas urium, which was isolated from an acidic environment. The nuclear genome of C. urium was sequenced, assembled and annotated in order to identify autophagy-related genes. Transmission electron microscopy, immunoblotting, metabolomic and photosynthetic analyses were performed to investigate autophagy in this extremophilic microalga. The analysis of the C. urium genome revealed the conservation of core autophagy-related genes. We investigated the role of autophagy in C. urium by blocking autophagic flux with the vacuolar ATPase inhibitor concanamycin A. Our results indicated that inhibition of autophagic flux in this microalga resulted in a pronounced accumulation of triacylglycerols and lipid droplets (LDs). Metabolomic and photosynthetic analyses indicated that C. urium cells with impaired vacuolar function maintained an active metabolism. Such effects were not observed in the neutrophilic microalga Chlamydomonas reinhardtii. Inhibition of autophagic flux in C. urium uncovered an active recycling of LDs through lipophagy, a selective autophagy pathway for lipid turnover. This study provided the metabolic basis by which extremophilic algae are able to catabolize lipids in the vacuole.

Paraclinoid aneurysms clipping through an extradural sphenoid ridge keyhole approach.

BACKGROUND: Paraclinoid aneurysms represent a challenge for neurosurgeons due to the anatomical complexity of this region. Then, innovative techniques such as the extradural sphenoid ridge approach are suitable for a safe microsurgical clipping. METHOD: A description of the surgical technique was made by the senior author, a vascular neurosurgeon experienced with the use of this approach in the management of paraclinoid aneurysms exemplified through a clinical case. CONCLUSION: Microsurgical clipping through an extradural sphenoid ridge keyhole approach for small and midsize paraclinoid aneurysms is an excellent treatment modality with good clinical and surgical results.

Effects in air-exposed corn silage of medium chain fatty acids on select spoilage microbes, zoonotic pathogens, and in vitro rumen fermentation.

Medium chain fatty acid (MCFA) treatment (0.75% C6, hexanoic; C8, octanoic; C10, decanoic; or equal proportion mixtures of C6:C8:C10:C12 or C8:C10/g; C12 = dodecanoic acid) of aerobically-exposed corn silage on spoilage and pathogenic microbes and rumen fermentation were evaluated in vitro. After 24 h aerobic incubation (37 °C), microbial enumeration revealed 3 log10 colony-forming units (CFU)/g fewer (P = 0.03) wild-type yeast and molds in C8:C10-treated silage than controls. Compared with controls, wild-type enterococci decreased (P < 0.01) in all treatments except the C6:C8:C10:C12 mixture; lactic acid bacteria were decreased (P < 0.01) in all treatments except C6 and the C6:C8:C10:C12 mixture. Total aerobes and inoculated Staphylococcus aureus or Listeria monocytogenes were unaffected by treatment (P > 0.05). Anaerobic incubation (24 h at 39 °C) of ruminal fluid (10 mL) with 0.02 g overnight air-exposed MCFA-treated corn silage revealed higher hydrogen accumulations (P = 0.03) with the C8:C10 mixture than controls. Methane, acetate, propionate, butyrate, or estimates of fermented hexose were unaffected. Acetate:propionate ratios were higher (P < 0.01) and fermentation efficiencies were marginally lower (P < 0.01) with C8- or C8:C10-treated silage than controls. Further research is warranted to optimize treatments to target unwanted microbes without adversely affecting beneficial microbes.

Operative considerations and surgical treatment of sylvian fissure arteriovenous malformations: a 20-year experience.

OBJECTIVE: Sylvian fissure (SF) arteriovenous malformations (AVMs) are among the most challenging vascular lesions amenable to neurosurgical treatment and account for 10% of all locations. As radiosurgery and endovascular techniques are increasingly involved in multimodal management protocols, the role of microsurgery needs to be reassessed as a stand-alone technique. The aim of this study was to show that total excision can be achieved with reasonable levels of morbidity and mortality in a real-world setting from a specialized high-volume center. METHODS: Forty-three patients with SF AVMs were identified from a series of 577 AVM patients treated microsurgically over a 22-year period. The mean patient age was 33.07 years (range 15-60 years), and there were 22 male and 21 female patients. The mode of presentation was headache in 51.2%, hemorrhage in 34.9%, seizures in 30.2%, and steal phenomenon in 9.3%. The authors analyzed the anatomical basis and angiographic characteristics of such lesions. RESULTS: In the preoperative period, 83.7% of the patients had a modified Rankin Scale (mRS) score of 0-2, and 16.3% had an mRS score of 3-5. After a 12-month follow-up, 95.3% of patients had an mRS score of 0-2, and 4.7% had a score of 3-6. The difference between pre- and postoperative scores was not statistically significant. SF AVMs have several particular features: 1) They produce angiographic steal of the anterior cerebral artery. 2) The nidus is fed by only one of the main trunks of the middle cerebral artery (MCA). 3) Participation of deep perforators is uncommon. 4) They have two or more early draining veins showing their fistulous nature. 5) Preoperative embolization and radiosurgery have a low rate of permanent cure. CONCLUSIONS: These AVMs represent a surgical challenge due to their proximity to critical structures such as the MCA, insula, internal capsule, and speech and memory functions in the dominant hemisphere. Essential key points are the wide opening of the SF and proper differentiation between feeders and normal vessels. Although this location can seem daunting, SF AVMs carry no additional surgical risk if adequately managed.

Ancient evolutionary signals of protein-coding sequences allow the discovery of new genes in the Drosophila melanogaster genome.

BACKGROUND: The current growth in DNA sequencing techniques makes of genome annotation a crucial task in the genomic era. Traditional gene finders focus on protein-coding sequences, but they are far from being exhaustive. The number of this kind of genes continuously increases due to new experimental data and development of improved bioinformatics algorithms. RESULTS: In this context, AnABlast represents a novel in silico strategy, based on the accumulation of short evolutionary signals identified by protein sequence alignments of low score. This strategy potentially highlights protein-coding regions in genomic sequences regardless of traditional homology or translation signatures. Here, we analyze the evolutionary information that the accumulation of these short signals encloses. Using the Drosophila melanogaster genome, we stablish optimal parameters for the accurate gene prediction with AnABlast and show that this new strategy significantly contributes to add genes, exons and pseudogenes regions, yet to be discovered in both already annotated and new genomes. CONCLUSIONS: AnABlast can be freely used to analyze genomic regions of whole genomes where it contributes to complete the previous annotation.

Engineered LINE-1 retrotransposition in nondividing human neurons.

Half the human genome is made of transposable elements (TEs), whose ongoing activity continues to impact our genome. LINE-1 (or L1) is an autonomous non-LTR retrotransposon in the human genome, comprising 17% of its genomic mass and containing an average of 80-100 active L1s per average genome that provide a source of inter-individual variation. New LINE-1 insertions are thought to accumulate mostly during human embryogenesis. Surprisingly, the activity of L1s can further impact the somatic human brain genome. However, it is currently unknown whether L1 can retrotranspose in other somatic healthy tissues or if L1 mobilization is restricted to neuronal precursor cells (NPCs) in the human brain. Here, we took advantage of an engineered L1 retrotransposition assay to analyze L1 mobilization rates in human mesenchymal (MSCs) and hematopoietic (HSCs) somatic stem cells. Notably, we have observed that L1 expression and engineered retrotransposition is much lower in both MSCs and HSCs when compared to NPCs. Remarkably, we have further demonstrated for the first time that engineered L1s can retrotranspose efficiently in mature nondividing neuronal cells. Thus, these findings suggest that the degree of somatic mosaicism and the impact of L1 retrotransposition in the human brain is likely much higher than previously thought.

Pseudomyxoma-type Invasion in Gastrointestinal Adenocarcinomas of Endometrium and Cervix: A Report of 2 Cases.

This paper presents a clinicopathologic and immunohistochemical report of 2 gastrointestinal-type tumors, one in the endometrium and the other in the cervix. Both showed extensive invasion into the pelvic structures with acellular mucin, identical to pseudomyxoma but in the absence of appendiceal or ovarian tumors. Case 1 was an 81-yr-old female with a Stage III endometrial gastrointestinal-type adenocarcinoma who had had an endometrial polyp with intestinal metaplasia 4 years previously. Case 2 was a 68-yr-old female with Stage IIIB endocervical gastrointestinal-type adenocarcinoma. Both were associated with a pseudomyxoma type of invasion, which in the endometrial case was transmural through the myometrium, and in the cervical case involved parametria, pelvic floor, and lymph nodes. Immunohistochemically, both tumors had a gastrointestinal phenotype coexpressing cytokeratins 7 and 20, CDX2, villin, MUC2, MUC5AC, and MUC6 and were negative for human papillomavirus, analyzed by real-time polymerase chain reaction. The first case exemplifies intestinal endometrial metaplasia as a precursor lesion of the rare gastrointestinal type of adenocarcinoma and also proves its progression into carcinoma. The second case exemplifies the highly aggressive nature of cervical invasion forming mucin lakes. Extensive pseudomyxoma in the uterus and cervix was associated with high clinical stages with marked lymphovascular invasion and lymph node metastases.

A randomised controlled trial of an automated oxygen delivery algorithm for preterm neonates receiving supplemental oxygen without mechanical ventilation.

AIM: Providing consistent levels of oxygen saturation (SpO2 ) for infants in neonatal intensive care units is not easy. This study explored how effectively the Auto-Mixer(®) algorithm automatically adjusted fraction of inspired oxygen (FiO2 ) levels to maintain SpO2 within an intended range in extremely low birth weight infants receiving supplemental oxygen without mechanical ventilation. METHODS: Twenty extremely low birth weight infants were randomly assigned to the Auto-Mixer(®) group or the manual intervention group and studied for 12 h. The SpO2 target was 85-93%, and the outcomes were the percentage of time SpO2 was within target, SpO2 variability, SpO2 >95%, oxygen received and manual interventions. RESULTS: The percentage of time within intended SpO2 was 58 ± 4% in the Auto-Mixer(®) group and 33.7 ± 4.7% in the manual group, SpO2 >95% was 26.5% vs 54.8%, average SpO2 and FiO2 were 89.8% vs 92.2% and 37% vs 44.1%, and manual interventions were 0 vs 80 (p < 0.05). Brief periods of SpO2  < 85% occurred more frequently in the Auto-Mixer(®) group. CONCLUSION: The Auto-Mixer(®) effectively increased the percentage of time that SpO2 was within the intended target range and decreased the time with high SpO2 in spontaneously breathing extremely low birth weight infants receiving supplemental oxygen.

The most exposed regions of SARS-CoV-2 structural proteins are subject to strong positive selection and gene overlap may locally modify this behavior.

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic that emerged in 2019 has been an unprecedented event in international science, as it has been possible to sequence millions of genomes, tracking their evolution very closely. This has enabled various types of secondary analyses of these genomes, including the measurement of their sequence selection pressure. In this work, we have been able to measure the selective pressure of all the described SARS-CoV-2 genes, even analyzed by sequence regions, and we show how this type of analysis allows us to separate the genes between those subject to positive selection (usually those that code for surface proteins or those exposed to the host immune system) and those subject to negative selection because they require greater conservation of their structure and function. We have also seen that when another gene with an overlapping reading frame appears within a gene sequence, the overlapping sequence between the two genes evolves under a stronger purifying selection than the average of the non-overlapping regions of the main gene. We propose this type of analysis as a useful tool for locating and analyzing all the genes of a viral genome when an adequate number of sequences are available.IMPORTANCEWe have analyzed the selection pressure of all severe acute respiratory syndrome coronavirus 2 genes by means of the nonsynonymous (Ka) to synonymous (Ks) substitution rate. We found that protein-coding genes are exposed to strong positive selection, especially in the regions of interaction with other molecules (host receptor and genome of the virus itself). However, overlapping coding regions are more protected and show negative selection. This suggests that this measure could be used to study viral gene function as well as overlapping genes.

Prototype of Low-Cost Microvascular Clips for Laboratory Use.

BACKGROUND: Vascular neurosurgical procedures require temporary or permanent surgical clips to treat cerebral aneurysms, arteriovenous malformations, or bypass surgery. In this scenario, surgical clips should have specific characteristics such as high-quality material, proper design, closing force, and biocompatibility. Due to these characteristics, the price of these clips does not allow their availability at the experimental surgery laboratory worldwide. METHODS: We describe here the technique for manufacturing handcrafted clips of low cost, using dental stainless steel or titanium wire of 0.18 mm, 0.20 mm, or 0.22 mm in diameter. We must complete six steps to obtain the clip using our hands and small electrician needle nose pliers for wire molding. RESULTS: These clips have a closing force of 30-60 gr/cm2 (depending on the wire diameter). They can be used in the experimental surgery laboratory to clip arteries or veins during vascular microsurgery procedures. Also, they can be used as temporary clips with confidence in low-flow bypass (v.gr. superficial temporal artery to middle cerebral artery or occipital artery to posterior inferior cerebellar artery anastomoses). CONCLUSIONS: Making practical low-cost clips for use in laboratory procedures or during low-flow anastomosis as temporary clips is possible. The main advantages are the low cost and the worldwide availability of the basic materials. The main disadvantage is the learning curve to get the ability to master the manufacturing of these clips.

Impact of excitation pulse width on the upconversion luminescence lifetime of NaYF4:Yb3+,Er3+ nanoparticles.

The upconversion luminescence (UCL) lifetime has a wide range of applications, serving as a critical parameter for optimizing the performance of upconversion nanoparticles (UCNPs) in various fields. It is crucial to understand that this lifetime does not directly correlate with the decay time of the emission level; rather, it represents a compilation of all the physical phenomena taking place in the upconversion process. To delve deeper into this, we analyzed the dependence of the UCL lifetime on the excitation pulse width for ß-NaYF4:Yb3+,Er3+ nanoparticles. The results revealed a significant increase in the UCL lifetime with both the excitation pulse width and the excitation intensity. The laser fluence was identified as the parameter governing the UCL decay dynamics. We showcased the universality of the pulse-width-dependent UCL lifetime phenomenon by employing UCNPs of various sizes, surface coatings, host matrices, Yb3+ and Er3+ ratios, and dispersing UCNPs in different solvents. Theoretical explanations for the experimental findings were derived through a rate equation analysis. Finally, we discussed the implications of these results in UCNP-FRET (Förster resonance energy transfer)-based applications.

Fluorescein videoangiography (FL-VAG) as a predictor of cerebral bypass patency.

Background: The fluorescein videoangiography (FL-VAG) has become a valuable adjunct tool in vascular neurosurgery. This work describes using the FL-VAG during bypass surgery and proposes a classification method for evaluating surgical results. Methods: We analyzed 26 patients with 50 cerebral bypasses from September 2018 to September 2022. We used a three grades classification method based on the pass of intravenous fluorescein through the anastomosis. Grade 1 represents the synchronous and total filling of the "T" shape ("green T″) formed by the donor and recipient vessel, Grade 2, the asynchronous filling of the anastomosis (incomplete/asynchronous "green T″), and Grade 3, a non-patent anastomosis (absence of "green T″). Results: Of the 26 patients, 8 underwent one bypass, 14 underwent double bypass, 2 underwent three bypasses, and 2 underwent four bypasses in two different interventions. The type of bypass was end-to-side anastomosis in 47 (94%) cases, internal maxillary artery to middle cerebral artery bypass with a radial artery graft (IMax-MCA anastomosis) in 2 (4%), and PICA-VA transposition in one (2%). We made 24 (48%) bypasses on the right side and 26 (52%) on the left side. After the initial surgery, thirty-nine (78%) bypasses were considered as Grade 1, 5 (10%) as Grade 2, and 6 (12%) as Grade 3. After intraoperative bypass patency assessment (IBPA), 45 (90%) of the bypasses were considered Grade 1 and remained patent on CTA. Conclusions: Using FL-VAG and a three-tier classification method is a reliable tool to predict bypass patency. It is safe, low-risk, and available worldwide.

ASACO: Automatic and Serial Analysis of CO-expression to discover gene modifiers with potential use in drug repurposing.

Massive gene expression analyses are widely used to find differentially expressed genes under specific conditions. The results of these experiments are often available in public databases that are undergoing a growth similar to that of molecular sequence databases in the past. This now allows novel secondary computational tools to emerge that use such information to gain new knowledge. If several genes have a similar expression profile across heterogeneous transcriptomics experiments, they could be functionally related. These associations are usually useful for the annotation of uncharacterized genes. In addition, the search for genes with opposite expression profiles is useful for finding negative regulators and proposing inhibitory compounds in drug repurposing projects. Here we present a new web application, Automatic and Serial Analysis of CO-expression (ASACO), which has the potential to discover positive and negative correlator genes to a given query gene, based on thousands of public transcriptomics experiments. In addition, examples of use are presented, comparing with previous contrasted knowledge. The results obtained propose ASACO as a useful tool to improve knowledge about genes associated with human diseases and noncoding genes. ASACO is available at http://www.bioinfocabd.upo.es/asaco/.

Bone anatomic variations of the parasellar region and its technical implications in para clinoid and posterior communicating segment aneurysms microsurgical clipping - Technical note.

Background: Microsurgical treatment of paraclinoid aneurysms is a complex task that generally requires anterior clinoid process (ACP) removal to obtain adequate surgical exposure. This procedure poses a considerable technical difficulty due to the association of the ACP to critical neurovascular structures. Furthermore, anatomical variations in the parasellar region, such as the caroticoclinoid foramen (CCF) or an interclinoid bridge (ICB), may impose additional challenges and increase surgical complications. The present study aims to briefly review some anatomic variations in the parasellar region and describe a step-by-step surgical technique for a hybrid anterior clinoidectomy based on the senior author's experience. Methods: We present two cases with bone variations on the parasellar region in patients with a paraclinoid aneurysm and another with a posterior communicating segment aneurysm treated by microsurgical clipping at our hospital. Results: We focused on safely dealing with these variations during surgery, without further complications, and with good postoperative results. Patients were discharged with no significant deficit. Postoperative control, computed tomography angiography showed complete exclusion of aneurysms. Conclusion: Although anatomical variations in the parasellar region can complicate surgical clipping of these aneurysms, it is essential to ensure the best possible surgical outcome to conduct thorough preoperative and radiological evaluations.

Trajectories of Cancer Care in Latin America: A Scope Review: Trayectorias de atención al cáncer en América Latina. Una revisión de alcance.

OBJECTIVES: In recent decades there has been a development of research on cancer care trajectories in Latin America; however, the diversity of theoretical-methodological uses of this approach can be confusing and difficult for the academic and professional community to use. To analyze studies that have been carried out in Latin America on cancer care trajectories to propose a typology of the approaches developed and synthesize key findings. METHODS: A scope review of studies published in journals indexed in PubMed, LILACS, and SciELO databases in the period 2006-2021 was conducted. RESULTS: 22 articles were analyzed. A typology of descriptive, evaluative, and interpretative approaches was proposed. From the key findings, the following were identified: the importance of pleasure and the feeling of power in the development of risky practices; the role of popular explanatory models for the identification of abnormality and the search for attention; the interaction of various personal, interpersonal, organizational, and structural barriers that limited timely diagnosis and continuity of treatment; the sequential or parallel use of different forms of care, public and private; and the importance of social support networks. CONCLUSIONS: The proposed typology clarifies the different uses of the approach. The informative synthesis evidences problematic knots regarding multiple barriers to access and allows us to propose as priorities in future research the study of types of cancer, stages, and populations that have been scarcely addressed, as well as the diversification of methodological approaches.

Analysis of bacterial pangenomes reduces CRISPR dark matter and reveals strong association between membranome and CRISPR-Cas systems.

CRISPR-Cas systems are prokaryotic acquired immunity mechanisms, which are found in 40% of bacterial genomes. They prevent viral infections through small DNA fragments called spacers. However, the vast majority of these spacers have not yet been associated with the virus they recognize, and it has been named CRISPR dark matter. By analyzing the spacers of tens of thousands of genomes from six bacterial species, we have been able to reduce the CRISPR dark matter from 80% to as low as 15% in some of the species. In addition, we have observed that, when a genome presents CRISPR-Cas systems, this is accompanied by particular sets of membrane proteins. Our results suggest that when bacteria present membrane proteins that make it compete better in its environment and these proteins are, in turn, receptors for specific phages, they would be forced to acquire CRISPR-Cas.

Microvascular decompression for hemifacial spasm: Complications after 292 procedures without neurophysiological monitoring.

Background: Hemifacial spasm (HFS) is characterized by involuntary, progressive, and intermittent spasms in the upper and lower facial muscles. Due to the high success rate, microvascular decompression (MVD) is the treatment of choice, and intraoperative neuromonitoring (INM) is considered useful for achieving safe surgery. Still, most centers do not have this technology. Methods: We analyzed 294 patients with HFS treated with MVD without INM. We only included patients with a neurovascular etiology while excluding other causes, such as tumors. As part of the postoperative evaluation, we assessed preoperative magnetic resonance imaging and pure-tone audiometry. Results: The main complication was peripheral facial paralysis in 50 patients, followed by hypoacusis in 22 patients and deafness in 17 patients, associated with a failed surgical outcome (P = 0.0002). The anterior inferior cerebellar artery (AICA) was an offending vessel, and the involvement of more than one vessel was significantly associated with the development of facial nerve palsy (P = 0.01). AICA was also associated with hearing impairment (P = 0.04). Over 90% of immediate complications improve in the follow-up (6 months), and one patient did not show a cure for initial HFS. Conclusion: MVD is the method with the highest long-term cure rates for treating HFS; however, we must inquire into the multiple factors of the patient and the surgeon to predict surgical outcomes. INM is not a must during MVD for HFS. We recommend its use depending on the availability and mainly on the surgeon's skills, for surgeons.

Limitation of fenestrated clips during clipping of middle cerebral artery aneurysm: Technical note.

Background: The middle cerebral artery (MCA) is a common site of cerebral aneurysms and 82.6% occur at the bifurcation. When surgery is selected as a therapeutic option, it intends to clip the neck completely because if some remnant occurs, there exists the possibility of regrowth and bleeding in the short- or long-term. Methods: We analyzed one drawback of the fenestrated clips of Yasargil and Sugita types to occlude the neck totally at a specific point formed by the union of the fenestra with the blades, creating a triangular space where the aneurysm can protrude, giving place to a remnant that can lead to a future recurrence and rebleeding. We show two cases of ruptured MCA aneurysms in which a cross-clipping technique occluded a broad base and dysmorphic aneurysm using straight fenestrated clips. Results: In both cases (one using a Yasargil clip and the other with a Sugita clip), a small remnant was visualized when fluorescein videoangiography (FL-VAG) was used. In both cases, the small remnant was clipped with a 3 mm straight miniclip. Conclusion: We should be aware of this drawback when clipping aneurysms using fenestrated clips to ensure a complete obliteration of the aneurysm's neck.

Classification of Alzheimer's disease stages from magnetic resonance images using deep learning.

Alzheimer's disease (AD) is a progressive type of dementia characterized by loss of memory and other cognitive abilities, including speech. Since AD is a progressive disease, detection in the early stages is essential for the appropriate care of the patient throughout its development, going from asymptomatic to a stage known as mild cognitive impairment (MCI), and then progressing to dementia and severe dementia; is worth mentioning that everyone suffers from cognitive impairment to some degree as we age, but the relevant task here is to identify which people are most likely to develop AD. Along with cognitive tests, evaluation of the brain morphology is the primary tool for AD diagnosis, where atrophy and loss of volume of the frontotemporal lobe are common features in patients who suffer from the disease. Regarding medical imaging techniques, magnetic resonance imaging (MRI) scans are one of the methods used by specialists to assess brain morphology. Recently, with the rise of deep learning (DL) and its successful implementation in medical imaging applications, it is of growing interest in the research community to develop computer-aided diagnosis systems that can help physicians to detect this disease, especially in the early stages where macroscopic changes are not so easily identified. This article presents a DL-based approach to classifying MRI scans in the different stages of AD, using a curated set of images from Alzheimer's Disease Neuroimaging Initiative and Open Access Series of Imaging Studies databases. Our methodology involves image pre-processing using FreeSurfer, spatial data-augmentation operations, such as rotation, flip, and random zoom during training, and state-of-the-art 3D convolutional neural networks such as EfficientNet, DenseNet, and a custom siamese network, as well as the relatively new approach of vision transformer architecture. With this approach, the best detection percentage among all four architectures was around 89% for AD vs. Control, 80% for Late MCI vs. Control, 66% for MCI vs. Control, and 67% for Early MCI vs. Control.