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International Journal of Molecular... Mar 2021Alzheimer's disease (AD) is a complex and severe neurodegenerative disease that still lacks effective methods of diagnosis. The current diagnostic methods of AD rely on...
BACKGROUND
Alzheimer's disease (AD) is a complex and severe neurodegenerative disease that still lacks effective methods of diagnosis. The current diagnostic methods of AD rely on cognitive tests, imaging techniques and cerebrospinal fluid (CSF) levels of amyloid-β1-42 (Aβ42), total tau protein and hyperphosphorylated tau (p-tau). However, the available methods are expensive and relatively invasive. Artificial intelligence techniques like machine learning tools have being increasingly used in precision diagnosis.
METHODS
We conducted a meta-analysis to investigate the machine learning and novel biomarkers for the diagnosis of AD.
METHODS
We searched PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews for reviews and trials that investigated the machine learning and novel biomarkers in diagnosis of AD.
RESULTS
In additional to Aβ and tau-related biomarkers, biomarkers according to other mechanisms of AD pathology have been investigated. Neuronal injury biomarker includes neurofiliament light (NFL). Biomarkers about synaptic dysfunction and/or loss includes neurogranin, BACE1, synaptotagmin, SNAP-25, GAP-43, synaptophysin. Biomarkers about neuroinflammation includes sTREM2, and YKL-40. Besides, d-glutamate is one of coagonists at the NMDARs. Several machine learning algorithms including support vector machine, logistic regression, random forest, and naïve Bayes) to build an optimal predictive model to distinguish patients with AD from healthy controls.
CONCLUSIONS
Our results revealed machine learning with novel biomarkers and multiple variables may increase the sensitivity and specificity in diagnosis of AD. Rapid and cost-effective HPLC for biomarkers and machine learning algorithms may assist physicians in diagnosing AD in outpatient clinics.
Topics: Aged; Alzheimer Disease; Biomarkers; Chromatography, High Pressure Liquid; Diagnosis, Computer-Assisted; Female; Humans; Machine Learning; Middle Aged
PubMed: 33803217
DOI: 10.3390/ijms22052761 -
BMC Cancer May 2018Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer. The prognosis of women with NECC is poor and there is no standardized therapy for...
BACKGROUND
Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer. The prognosis of women with NECC is poor and there is no standardized therapy for this type of malignancy based on controlled trials.
METHODS
We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials describing the management and outcome of women with NECC.
RESULTS
Three thousand five hundred thirty-eight cases of NECC in 112 studies were identified. The pooled proportion of NECC among women with cervical cancer was 2303/163470 (1.41%). Small cell NECC, large cell NECC, and other histological subtypes were identified in 80.4, 12.0, and 7.6% of cases, respectively. Early and late stage disease presentation were evenly distributed with 1463 (50.6%) and 1428 (49.4%) cases, respectively. Tumors expressed synaptophysin (424/538 cases; 79%), neuron-specific enolase (196/285 cases; 69%), chromogranin (323/486 cases; 66%), and CD56 (162/267; 61%). The most common primary treatment was radical surgery combined with chemotherapy either as neoadjuvant or adjuvant chemotherapy, described in 42/48 studies. Radiotherapy-based primary treatment schemes in the form of radiotherapy, radiochemotherapy, or radiotherapy with concomitant or followed by chemotherapy were also commonly used (15/48 studies). There is no standard chemotherapy regimen for NECC, but cisplatin/carboplatin and etoposide (EP) was the most commonly used treatment scheme (24/40 studies). Overall, the prognosis of women with NECC was poor with a mean recurrence-free survival of 16 months and a mean overall survival of 40 months. Immune checkpoint inhibitors and targeted agents were reported as being active in three case reports.
CONCLUSION
NECC is a rare variant of cervical cancer with a poor prognosis. Multimodality treatment with radical surgery and neoadjuvant/adjuvant chemotherapy with cisplatin and etoposide with or without radiotherapy is the mainstay of treatment for early stage disease while chemotherapy with cisplatin and etoposide or topotecan, paclitaxel, and bevacizumab is appropriate for women with locally advanced or recurrent NECC. Immune checkpoint inhibitors may be beneficial, but controlled evidence for their efficacy is lacking.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Neuroendocrine; Cervix Uteri; Chemoradiotherapy, Adjuvant; Clinical Trials as Topic; Female; Humans; Hysterectomy; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Survival Rate; Treatment Outcome; Uterine Cervical Neoplasms
PubMed: 29728073
DOI: 10.1186/s12885-018-4447-x -
Current Urology Apr 2017The purpose of this study is to study the main epidemiological, clinical, para clinical, pathological, therapeutic, and evolutionary features of patients with testicular... (Review)
Review
PURPOSE
The purpose of this study is to study the main epidemiological, clinical, para clinical, pathological, therapeutic, and evolutionary features of patients with testicular neuroendocrine tumors (TNET).
MATERIALS AND METHODS
Nine case series and sixteen case reports were identified by searching PubMed database and qualified for inclusion in this study. We added the data of one case treated in the department of urology in Habib Bourguiba Hospital in Sfax, to the published cases.
RESULTS
A total of 132 cases were collected. Median age at diagnosis was 39 years old (range 10- 83 years). The most common presenting symptom was either a testicular mass or a swelling in 38.46% of cases. Carcinoid syndrome was documented in 10.60% of patients. The clinical examination revealed a palpable mass in 44.70% of patients. This mass was painless and firm in most cases. Serum tumor markers (β-gonadotrophine chorionique humaine, α-feto protein, and lactate dehydrogenase) were within normal limits in all patients except in one case. Most testicular neuroendocrine tumors (76.52%) were primary and pure. The tumors were positive for chromogranin (100%), synaptophysin (100%) and cytokeratin (93.10%). Metastases were detected at time of diagnosis in eight cases (6.06%). The main treatment was radical orchiectomy performed in 127 patients (96.21%). The 5-year overall survival rate was 78.70% and the 5-year specific survival rate was 84.30%.
CONCLUSION
The diagnosis of testicular carcinoids is based on the immunohistochemistry study. The treatment of choice for these tumors is radical orchiectomy. Somatostatin analogues were reported to be effective in patients with carcinoid syndrome.
PubMed: 28559773
DOI: 10.1159/000447146 -
Molecular Psychiatry Mar 2022The pathophysiological mechanisms underlying bipolar (BD) and major depressive disorders (MDD) are multifactorial but likely involve synaptic dysfunction and... (Meta-Analysis)
Meta-Analysis
The pathophysiological mechanisms underlying bipolar (BD) and major depressive disorders (MDD) are multifactorial but likely involve synaptic dysfunction and dysregulation. There are multiple synaptic proteins but three synaptic proteins, namely SNAP-25, PSD-95, and synaptophysin, have been widely studied for their role in synaptic function in human brain postmortem studies in BD and MDD. These studies have yielded contradictory results, possibly due to the small sample size and sourcing material from different cortical regions of the brain. We performed a systematic review and meta-analysis to understand the role of these three synaptic proteins and other synaptic proteins, messenger RNA (mRNA) and their regional localizations in BD and MDD. A systematic literature search was conducted and the review is reported in accordance with the MOOSE Guidelines. Meta-analysis was performed to compare synaptic marker levels between BD/MDD groups and controls separately. 1811 papers were identified in the literature search and screened against the preset inclusion and exclusion criteria. A total of 72 studies were screened in the full text, of which 47 were identified as eligible to be included in the systematic review. 24 of these 47 papers were included in the meta-analysis. The meta-analysis indicated that SNAP-25 protein levels were significantly lower in BD. On average, PSD-95 mRNA levels were lower in BD, and protein levels of SNAP-25, PSD-95, and syntaxin were lower in MDD. Localization analysis showed decreased levels of PSD-95 protein in the frontal cortex. We found specific alterations in synaptic proteins and RNAs in both BD and MDD. The review was prospectively registered online in PROSPERO international prospective register of systematic reviews, registration no. CRD42020196932.
Topics: Bipolar Disorder; Brain; Depressive Disorder, Major; Disks Large Homolog 4 Protein; Humans; Mood Disorders; RNA, Messenger
PubMed: 35022529
DOI: 10.1038/s41380-021-01410-9 -
BJU International Oct 2022To perform a systematic review and meta-analysis of the literature to understand the variation in the reporting of neuroendocrine staining and determine the influence of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To perform a systematic review and meta-analysis of the literature to understand the variation in the reporting of neuroendocrine staining and determine the influence of reporting neuroendocrine staining at diagnosis on patient outcomes.
METHODS
Medical databases were searched to identify studies in which adenocarcinoma specimens were stained with any of the following four neuroendocrine markers: chromogranin A (CgA), neuron-specific enolase (NSE), synaptophysin and CD56. The prevalence of neuroendocrine staining and correlation of the prevalence of neuroendocrine staining to patient outcomes were analysed using a random-effects model. All statistical tests were two-sided.
RESULTS
Sixty-two studies spanning 7616 patients were analysed. The pooled prevalence for the most common marker, CgA (41%), was similar to that of NSE (39%) and higher than that of synaptophysin (31%). The prevalence of CgA staining was significantly influenced by reporting criteria, where objective thresholds reduced the variation in prevalence to 26%. No correlation was found between CgA prevalence and tumour grade. Patients positive for CgA staining using objective criteria had more rapid biochemical progression (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.49 to 2.65) and poorer prostate cancer-specific survival (HR 7.03, 95% CI 2.55 to 19.39) compared to negative patients, even among those with low-risk cancers.
CONCLUSION
Discrepancies in the reported prevalence of neuroendocrine cells in adenocarcinoma are driven by the inconsistent scoring criteria. This study unequivocally demonstrates that when neuroendocrine cell staining is assessed with objective criteria it identifies patients with poor clinical outcomes. Future studies are needed to determine the exact quantifiable thresholds for use in reporting neuroendocrine cell staining to identify patients at higher risk of progression.
Topics: Adenocarcinoma; Biomarkers, Tumor; Chromogranin A; Humans; Male; Neuroendocrine Cells; Phosphopyruvate Hydratase; Prostatic Neoplasms; Synaptophysin
PubMed: 34784097
DOI: 10.1111/bju.15647 -
Folia Medica Cracoviensia Apr 2023Carcinoma of unknown primary (CUP) is a heterogeneous group of oncological diseases in which it is impossible to determine the primary tumor. The incidence is 3-5% of...
Carcinoma of unknown primary (CUP) is a heterogeneous group of oncological diseases in which it is impossible to determine the primary tumor. The incidence is 3-5% of oncologic patients, but the survival time varies from 6 weeks to 5 months. The diagnostics should begin with a clinical evaluation and basic laboratory tests. For CUP placed in head and neck the positron emission tomography - computed tomography is recommended; pancreatic or lung neoplasms are diagnosed with the computed tomography as well. Recently, the magnetic resonance, especially whole-body diffusion-weighted imaging has been introduced to the imaging panel. The lesion obtained during surgically removed metastases or biopsy material should be histopathological and molecularly examined to define the type of tumor. The basic immunoexpression panel should include cytokeratin-5/6, -7 and -20, EMA, synaptophysin, chromogranin, vimentin and GATA3 and molecular expression of ERBB2, PIK3CA, NF1, NF2, BRAF, IDH1, PTEN, FGFR2, EGFR, MET and CDK6. During the accurate diagnostics enable to classify malignancy of undefined primary origin as provisional CUP or finally confirmed CUP in which the primary place of tumor remains undetectable. The detailed diagnostics should be performed in highly specified centers to establish an accurate diagnosis and to initiate personalized treatment. Majority of patients are diagnosed with adenocarcinoma (70%), undifferentiated carcinoma (20%), squamous cell or transitional cell/uroepithelial carcinoma (5-10%), neuroendocrine tumor (5%) and with minor incidence other histological types, including melanoma.
Topics: Humans; Neoplasms, Unknown Primary; Carcinoma; Adenocarcinoma; Tomography, X-Ray Computed; Magnetic Resonance Imaging; Head and Neck Neoplasms
PubMed: 37406274
DOI: 10.24425/fmc.2023.145427 -
Molecular Psychiatry Apr 2019Although synaptic loss is thought to be core to the pathophysiology of schizophrenia, the nature, consistency and magnitude of synaptic protein and mRNA changes has not... (Meta-Analysis)
Meta-Analysis
Although synaptic loss is thought to be core to the pathophysiology of schizophrenia, the nature, consistency and magnitude of synaptic protein and mRNA changes has not been systematically appraised. Our objective was thus to systematically review and meta-analyse findings. The entire PubMed database was searched for studies from inception date to the 1st of July 2017. We selected case-control postmortem studies in schizophrenia quantifying synaptic protein or mRNA levels in brain tissue. The difference in protein and mRNA levels between cases and controls was extracted and meta-analysis conducted. Among the results, we found a significant reduction in synaptophysin in schizophrenia in the hippocampus (effect size: -0.65, p < 0.01), frontal (effect size: -0.36, p = 0.04), and cingulate cortices (effect size: -0.54, p = 0.02), but no significant changes for synaptophysin in occipital and temporal cortices, and no changes for SNAP-25, PSD-95, VAMP, and syntaxin in frontal cortex. There were insufficient studies for meta-analysis of complexins, synapsins, rab3A and synaptotagmin and mRNA measures. Findings are summarised for these, which generally show reductions in SNAP-25, PSD-95, synapsin and rab3A protein levels in the hippocampus but inconsistency in other regions. Our findings of moderate-large reductions in synaptophysin in hippocampus and frontal cortical regions, and a tendency for reductions in other pre- and postsynaptic proteins in the hippocampus are consistent with models that implicate synaptic loss in schizophrenia. However, they also identify potential differences between regions and proteins, suggesting synaptic loss is not uniform in nature or extent.
Topics: Adult; Brain; Case-Control Studies; Disks Large Homolog 4 Protein; Female; Gyrus Cinguli; Hippocampus; Humans; Male; Middle Aged; RNA, Messenger; Schizophrenia; Synapses; Synapsins; Synaptic Vesicles; Synaptophysin; Synaptosomal-Associated Protein 25; Temporal Lobe; rab3A GTP-Binding Protein
PubMed: 29511299
DOI: 10.1038/s41380-018-0041-5 -
Frontiers in Psychiatry 2023Ketamine and psychedelics have abuse liability. They can also induce "transformative experiences" where individuals experience enhanced states of awareness. This... (Review)
Review
BACKGROUND
Ketamine and psychedelics have abuse liability. They can also induce "transformative experiences" where individuals experience enhanced states of awareness. This enhanced awareness can lead to changes in preexisting behavioral patterns which could be beneficial in the treatment of substance use disorders (SUDs). Preclinical and clinical studies suggest that ketamine and psychedelics may alter markers associated with synaptic density, and that these changes may underlie effects such as sensitization, conditioned place preference, drug self-administration, and verbal memory performance. In this scoping review, we examined studies that measured synaptic markers in animals and humans after exposure to ketamine and/or psychedelics.
METHODS
A systematic search was conducted following PRISMA guidelines, through PubMed, EBSCO, Scopus, and Web of Science, based on a published protocol (Open Science Framework, DOI: 10.17605/OSF.IO/43FQ9). Both and studies were included. Studies on the following synaptic markers were included: dendritic structural changes, PSD-95, synapsin-1, synaptophysin-1, synaptotagmin-1, and SV2A.
RESULTS
Eighty-four studies were included in the final analyses. Seventy-one studies examined synaptic markers following ketamine treatment, nine examined psychedelics, and four examined both. Psychedelics included psilocybin/psilocin, lysergic acid diethylamide, N,N-dimethyltryptamine, 2,5-dimethoxy-4-iodoamphetamine, and ibogaine/noribogaine. Mixed findings regarding synaptic changes in the hippocampus and prefrontal cortex (PFC) have been reported when ketamine was administered in a single dose under basal conditions. Similar mixed findings were seen under basal conditions in studies that used repeated administration of ketamine. However, studies that examined animals during stressful conditions found that a single dose of ketamine counteracted stress-related reductions in synaptic markers in the hippocampus and PFC. Repeated administration of ketamine also counteracted stress effects in the hippocampus. Psychedelics generally increased synaptic markers, but results were more consistently positive for certain agents.
CONCLUSION
Ketamine and psychedelics can increase synaptic markers under certain conditions. Heterogeneous findings may relate to methodological differences, agents administered (or different formulations of the same agent), sex, and type of markers. Future studies could address seemingly mixed results by using meta-analytical approaches or study designs that more fully consider individual differences.
PubMed: 37435405
DOI: 10.3389/fpsyt.2023.1197890 -
Gynecologic Oncology Mar 2017Neuroendocrine tumors (NETs) are aggressive diseases developing from neuroendocrine cells that most frequently involve the gastro-entero-pancreatic tract and the lung,... (Review)
Review
Neuroendocrine tumors (NETs) are aggressive diseases developing from neuroendocrine cells that most frequently involve the gastro-entero-pancreatic tract and the lung, but more rarely are found in almost all body tissues. Limited biological and clinical data are currently available for NETs in uncommon sites, such as female genital tract. NETs represent 0.9% to 1.5% of the tumors of the uterine cervix. They are more likely to have lymph-vascular space invasion and lymph node involvement, and to develop local and distant relapses when compared with the mostly common cervical squamous cell carcinomas or adenocarcinomas. Positive immunostaining for synaptophysin, chromogranin, CD56, and neuron-specific enolase is often detected in cervical NETs . The most recent editions of the World Health Organization Classification of Gynecologic Tract tumors grouped cervical carcinoid tumor and atypical carcinoid tumor into low-grade NETs and cervical small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma into high-grade NETs. High-risk HPV DNA is detected in almost all cervical high-grade NETs. No treatment guidelines, based on prospective, well-designed clinical trials, are currently available due to the rarity of these tumors. Many authors have reported different multimodality approaches, mainly derived from NETs of the lung. These usually consist in radical hysterectomy followed by adjuvant chemotherapy or concurrent chemoradiation for early stage disease, definitive concurrent chemoradiation sometimes preceded by neoadjuvant chemotherapy and followed by adjuvant chemotherapy for locally advanced disease, and palliative chemotherapy for metastatic disease. In this systematic review, we address the histologic classification of cervical NETs, analyze their pathogenesis and overall prognosis, and evaluate the different treatment modalities described in the literature, in order to offer a possible algorithm that may help the clinicians in diagnosing and treating patients with these uncommon and aggressive malignancies.
Topics: Female; Humans; Neuroendocrine Tumors; Uterine Cervical Neoplasms
PubMed: 28057354
DOI: 10.1016/j.ygyno.2016.12.003 -
Journal of Geriatric Psychiatry and... Jul 2023Accurately diagnosing neurodegenerative dementia is often challenging due to overlapping clinical features. Disease specific biomarkers could enhance diagnostic... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Accurately diagnosing neurodegenerative dementia is often challenging due to overlapping clinical features. Disease specific biomarkers could enhance diagnostic accuracy. However, CSF analysis procedures and advanced imaging modalities are either invasive or high-priced, and routinely unavailable. Easily accessible disease biomarkers would be of utmost value for accurate differential diagnosis of dementia subtypes.
OBJECTIVE
To assess the diagnostic accuracy of blood-based biomarkers for the differential diagnosis of AD from Frontotemporal Lobar Degeneration (FTLD), or AD from Dementia with Lewy Bodies (DLB).
METHODS
Systematic review. Three databases (PubMed, Scopus, and Web of Science) were searched. Studies assessing blood-based biomarkers levels in AD versus FTLD, or AD versus DLB, and its diagnostic accuracy, were selected. When the same biomarker was assessed in three or more studies, a meta-analysis was performed. QUADAS-2 criteria were used for quality assessment.
RESULTS
Twenty studies were included in this analysis. Collectively, 905 AD patients were compared to 1262 FTLD patients, and 209 AD patients were compared to 246 DLB patients. Regarding biomarkers for AD versus FTLD, excellent discriminative accuracy (AUC >0.9) was found for p-tau181, p-tau217, synaptophysin, synaptopodin, GAP43 and calmodulin. Other biomarkers also demonstrated good accuracy (AUC = 0.8-0.9). For AD versus DLB distinction, only miR-21-5p and miR-451a achieved excellent accuracy (AUC >0.9).
CONCLUSION
Encouraging results were found for several biomarkers, alone or in combination. Prospective longitudinal designs and consensual protocols, comprising larger cohorts and homogeneous testing modalities across centres, are essential to validate the clinical value of blood biomarkers for the precise etiological diagnosis of dementia.
Topics: Humans; Alzheimer Disease; tau Proteins; Amyloid beta-Peptides; Prospective Studies; Frontotemporal Lobar Degeneration; Frontotemporal Dementia; Diagnosis, Differential; Biomarkers; MicroRNAs; Lewy Body Disease
PubMed: 36423207
DOI: 10.1177/08919887221141651