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Article ; Online: Computational Modeling of Extrasynaptic NMDA Receptors: Insights into Dendritic Signal Amplification Mechanisms.

Makarov, Mark / Papa, Michele / Korkotian, Eduard

International journal of molecular sciences

2024 Volume 25, Issue 8

Abstract: Dendritic structures play a pivotal role in the computational processes occurring within neurons. Signal propagation along dendrites relies on both passive conduction and active processes related to voltage-dependent ion channels. Among these channels, ... ...

Abstract	Dendritic structures play a pivotal role in the computational processes occurring within neurons. Signal propagation along dendrites relies on both passive conduction and active processes related to voltage-dependent ion channels. Among these channels, extrasynaptic N-methyl-D-aspartate channels (exNMDA) emerge as a significant contributor. Prior studies have mainly concentrated on interactions between synapses and nearby exNMDA (100 nm-10 µm from synapse), activated by presynaptic membrane glutamate. This study concentrates on the correlation between synaptic inputs and distal exNMDA (>100 µm), organized in clusters that function as signal amplifiers. Employing a computational model of a dendrite, we elucidate the mechanism underlying signal amplification in exNMDA clusters. Our findings underscore the pivotal role of the optimal spatial positioning of the NMDA cluster in determining signal amplification efficiency. Additionally, we demonstrate that exNMDA subunits characterized by a large conduction decay constant. Specifically, NR2B subunits exhibit enhanced effectiveness in signal amplification compared to subunits with steeper conduction decay. This investigation extends our understanding of dendritic computational processes by emphasizing the significance of distant exNMDA clusters as potent signal amplifiers. The implications of our computational model shed light on the spatial considerations and subunit characteristics that govern the efficiency of signal amplification in dendritic structures, offering valuable insights for future studies in neurobiology and computational neuroscience.
MeSH term(s)	Receptors, N-Methyl-D-Aspartate/metabolism ; Dendrites/metabolism ; Synapses/metabolism ; Computer Simulation ; Animals ; Models, Neurological ; Humans ; Signal Transduction
Chemical Substances	Receptors, N-Methyl-D-Aspartate
Language	English
Publishing date	2024-04-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25084235
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Regional Microglial Response in Entorhino-Hippocampal Slice Cultures to Schaffer Collateral Lesion and Metalloproteinases Modulation.

Virtuoso, Assunta / Galanis, Christos / Lenz, Maximilian / Papa, Michele / Vlachos, Andreas

International journal of molecular sciences

2024 Volume 25, Issue 4

Abstract: Microglia and astrocytes are essential in sustaining physiological networks in the central nervous system, with their ability to remodel the extracellular matrix, being pivotal for synapse plasticity. Recent findings have challenged the traditional view ... ...

Abstract	Microglia and astrocytes are essential in sustaining physiological networks in the central nervous system, with their ability to remodel the extracellular matrix, being pivotal for synapse plasticity. Recent findings have challenged the traditional view of homogenous glial populations in the brain, uncovering morphological, functional, and molecular heterogeneity among glial cells. This diversity has significant implications for both physiological and pathological brain states. In the present study, we mechanically induced a Schaffer collateral lesion (SCL) in mouse entorhino-hippocampal slice cultures to investigate glial behavior, i.e., microglia and astrocytes, under metalloproteinases (MMPs) modulation in the lesioned area, CA3, and the denervated region, CA1. We observed distinct response patterns in the microglia and astrocytes 3 days after the lesion. Notably, GFAP-expressing astrocytes showed no immediate changes post-SCL. Microglia responses varied depending on their anatomical location, underscoring the complexity of the hippocampal neuroglial network post-injury. The MMPs inhibitor GM6001 did not affect microglial reactions in CA3, while increasing the number of Iba1-expressing cells in CA1, leading to a withdrawal of their primary branches. These findings highlight the importance of understanding glial regionalization following neural injury and MMPs modulation and pave the way for further research into glia-targeted therapeutic strategies for neurodegenerative disorders.
MeSH term(s)	Mice ; Animals ; Microglia/pathology ; Schaffer Collaterals ; Hippocampus/pathology ; Astrocytes/pathology ; Matrix Metalloproteinases
Chemical Substances	Matrix Metalloproteinases (EC 3.4.24.-)
Language	English
Publishing date	2024-02-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25042346
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Article: Presenilins and mitochondria-an intriguing link: mini-review.

Makarov, Mark / Kushnireva, Liliia / Papa, Michele / Korkotian, Eduard

Frontiers in neuroscience

2023 Volume 17, Page(s) 1249815

Abstract: This review uncovers the intricate relationship between presenilins, calcium, and mitochondria in the context of Alzheimer's disease (AD), with a particular focus on the involvement of presenilin mutations in mitochondrial dysfunction. So far, it is ... ...

Abstract	This review uncovers the intricate relationship between presenilins, calcium, and mitochondria in the context of Alzheimer's disease (AD), with a particular focus on the involvement of presenilin mutations in mitochondrial dysfunction. So far, it is unclear whether the impairment of mitochondrial function arises primarily from damage inflicted by
Language	English
Publishing date	2023-07-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2023.1249815
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Article ; Online: Automated Natural Language Processing-Based Supplier Discovery for Financial Services.

Papa, Mauro / Chatzigiannakis, Ioannis / Anagnostopoulos, Aris

Big data

2023 Volume 12, Issue 1, Page(s) 30–48

Abstract: Public procurement is viewed as a major market force that can be used to promote innovation and drive small and medium-sized enterprises growth. In such cases, procurement system design relies on intermediates that provide vertical linkages between ... ...

Abstract	Public procurement is viewed as a major market force that can be used to promote innovation and drive small and medium-sized enterprises growth. In such cases, procurement system design relies on intermediates that provide vertical linkages between suppliers and providers of innovative services and products. In this work we propose an innovative methodology for decision support in the process of supplier discovery, which precedes the final supplier selection. We focus on data gathered from community-based sources such as Reddit and Wikidata and avoid any use of historical open procurement datasets to identify small and medium sized suppliers of innovative products and services that own very little market shares. We look into a real-world procurement case study from the financial sector focusing on the Financial and Market Data offering and develop an interactive web-based support tool to address certain requirements of the Italian central bank. We demonstrate how a suitable selection of natural language processing models, such as a part-of-speech tagger and a word-embedding model, in combination with a novel named-entity-disambiguation algorithm, can efficiently analyze huge quantity of textual data, increasing the probability of a full coverage of the market.
MeSH term(s)	Natural Language Processing ; Algorithms
Language	English
Publishing date	2023-07-07
Publishing country	United States
Document type	Journal Article
ISSN	2167-647X
ISSN (online)	2167-647X
DOI	10.1089/big.2022.0215
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Article ; Online: Peripheral and central neurobiological effects of botulinum toxin A (BoNT/A) in neuropathic pain: a systematic review.

Moreau, Nathan / Korai, Sohaib Ali / Sepe, Giovanna / Panetsos, Fivos / Papa, Michele / Cirillo, Giovanni

Pain

2024

Abstract: Abstract: Botulinum toxin (BoNT), a presynaptic inhibitor of acetylcholine (Ach) release at the neuromuscular junction (NMJ), is a successful and safe drug for the treatment of several neurological disorders. However, a wide and recent literature review ...

Abstract	Abstract: Botulinum toxin (BoNT), a presynaptic inhibitor of acetylcholine (Ach) release at the neuromuscular junction (NMJ), is a successful and safe drug for the treatment of several neurological disorders. However, a wide and recent literature review has demonstrated that BoNT exerts its effects not only at the "periphery" but also within the central nervous system (CNS). Studies from animal models, in fact, have shown a retrograde transport to the CNS, thus modulating synaptic function. The increasing number of articles reporting efficacy of BoNT on chronic neuropathic pain (CNP), a complex disease of the CNS, demonstrates that the central mechanisms of BoNT are far from being completely elucidated. In this new light, BoNT might interfere with the activity of spinal, brain stem, and cortical circuitry, modulating excitability and the functional organization of CNS in healthy conditions. Botulinum toxins efficacy on CNP is the result of a wide and complex action on many and diverse mechanisms at the basis of the maladaptive plasticity, the core of the pathogenesis of CNP. This systematic review aims to discuss in detail the BoNT's mechanisms and effects on peripheral and central neuroplasticity, at the basis for the clinical efficacy in CNP syndromes.
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	193153-2
ISSN	1872-6623 ; 0304-3959
ISSN (online)	1872-6623
ISSN	0304-3959
DOI	10.1097/j.pain.0000000000003204
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Article ; Online: Use of teplizumab in children and adolescents at risk of type 1 diabetes: perspectives of parents and caregivers from an Italian Pediatric Diabetes Center.

Bombaci, Bruno / Passanisi, Stefano / Pecoraro, Maria / Sorrenti, Lacrima / Papa, Mattia / Salzano, Giuseppina / Lombardo, Fortunato

Acta diabetologica

2024 Volume 61, Issue 5, Page(s) 635–642

Abstract: Aims: In view of the imminent introduction of a novel category of disease-modifying treatments for type 1 diabetes (T1D) in European countries, it becomes imperative to understand the existing awareness and viewpoints of parents and caregivers of ... ...

Abstract	Aims: In view of the imminent introduction of a novel category of disease-modifying treatments for type 1 diabetes (T1D) in European countries, it becomes imperative to understand the existing awareness and viewpoints of parents and caregivers of children and adolescents predisposed to T1D. This study aims to evaluate the perspectives of a cohort of parents and caregivers regarding using teplizumab to delay the onset of T1D in predisposed children and adolescents. Methods: This single-center study used a survey-based approach. Parents or caregivers of children and adolescents with T1D having at least one additional child without T1D answered 15 questions assessing their awareness about teplizumab, their potential willingness to provide consent for its administration in case of eligibility, and their expectations regarding potential outcomes. Results: Approximately half of the participants (52.6%) expressed readiness to consent to teplizumab administration for their child if the prescription criteria were met in the future. Only 6.3% of parents claimed detailed knowledge about this innovative medication. Notably, parents with prior experience of diabetic ketoacidosis (DKA) demonstrated a higher inclination to consent to teplizumab treatment (p = 0.018). Conclusions: Our findings underscore the necessity for comprehensive awareness campaigns spreading the current evidence concerning teplizumab in terms of both effectiveness and possible side effects. Additionally, our study reinforces the pivotal role of DKA prevention in successfully integrating disease-modifying treatments into clinical practice.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 1/drug therapy ; Adolescent ; Child ; Male ; Female ; Parents/psychology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Caregivers/psychology ; Caregivers/statistics & numerical data ; Italy/epidemiology ; Adult ; Surveys and Questionnaires ; Child, Preschool ; Health Knowledge, Attitudes, Practice
Chemical Substances	Antibodies, Monoclonal, Humanized ; teplizumab (S4M959U2IJ)
Language	English
Publishing date	2024-02-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1097676-0
ISSN	1432-5233 ; 0940-5429
ISSN (online)	1432-5233
ISSN	0940-5429
DOI	10.1007/s00592-024-02245-w
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Article: Alzheimer's Disease from the Amyloidogenic Theory to the Puzzling Crossroads between Vascular, Metabolic and Energetic Maladaptive Plasticity.

Cerasuolo, Michele / Papa, Michele / Colangelo, Anna Maria / Rizzo, Maria Rosaria

Biomedicines

2023 Volume 11, Issue 3

Abstract: Alzheimer's disease (AD) is a progressive and degenerative disease producing the most common type of dementia worldwide. The main pathogenetic hypothesis in recent decades has been the well-known amyloidogenic hypothesis based on the involvement of two ... ...

Abstract	Alzheimer's disease (AD) is a progressive and degenerative disease producing the most common type of dementia worldwide. The main pathogenetic hypothesis in recent decades has been the well-known amyloidogenic hypothesis based on the involvement of two proteins in AD pathogenesis: amyloid β (Aβ) and tau. Amyloid deposition reported in all AD patients is nowadays considered an independent risk factor for cognitive decline. Vascular damage and blood-brain barrier (BBB) failure in AD is considered a pivotal mechanism for brain injury, with increased deposition of both immunoglobulins and fibrin. Furthermore, BBB dysfunction could be an early sign of cognitive decline and the early stages of clinical AD. Vascular damage generates hypoperfusion and relative hypoxia in areas with high energy demand. Long-term hypoxia and the accumulation within the brain parenchyma of neurotoxic molecules could be seeds of a self-sustaining pathological progression. Cellular dysfunction comprises all the elements of the neurovascular unit (NVU) and neuronal loss, which could be the result of energy failure and mitochondrial impairment. Brain glucose metabolism is compromised, showing a specific region distribution. This energy deficit worsens throughout aging. Mild cognitive impairment has been reported to be associated with a glucose deficit in the entorhinal cortex and in the parietal lobes. The current aim is to understand the complex interactions between amyloid β (Aβ) and tau and elements of the BBB and NVU in the brain. This new approach aimed at the study of metabolic mechanisms and energy insufficiency due to mitochondrial impairment would allow us to define therapies aimed at predicting and slowing down the progression of AD.
Language	English
Publishing date	2023-03-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11030861
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Article ; Online: Pancreatic fistula: interventional radiological treatment by collection. Jejunal loop internal drainage.

Papa, Maurizio / Tripodi, Vincenzo / P Francioso, Antonio / Bisagni, Pietro

Annali italiani di chirurgia

2023 Volume 94

Abstract: Pancreaticoduodenectomy is a major surgical procedure associated with various and important complications, often difficult to be managed. Pancreatic fistula is due to leakage of pancreatic juice in the abdominal cavity and is the main and most frequent ... ...

Abstract	Pancreaticoduodenectomy is a major surgical procedure associated with various and important complications, often difficult to be managed. Pancreatic fistula is due to leakage of pancreatic juice in the abdominal cavity and is the main and most frequent complication after pancreatic surgery. The treatment of pancreatic fistula may change according to degree. Interventional radiology (IR) can offer powerful minimally invasive alternatives in managing pancreatic fistulas. We report the case of a patient affected by ampullar adenocarcinoma who underwent pancreaticoduodenectomy. Surgery was complicated by high-flow pancreatic fistula treated conservatively with CT guided percutaneous transhepatic drainage. Due to persistent leak of pancreatic fluid the abdominal effusion was drained percutaneously in the jejunal loop by Interventional radiology. KEY WORDS: Pancreatic fistula, Jejunal loop internal drainage, Radiological treatment.
MeSH term(s)	Humans ; Pancreatic Fistula/etiology ; Pancreatic Fistula/surgery ; Radiology, Interventional ; Drainage ; Radiography ; Pancreaticoduodenectomy/adverse effects
Language	English
Publishing date	2023-09-08
Publishing country	Italy
Document type	Case Reports ; Journal Article
ZDB-ID	418927-9
ISSN	2239-253X ; 0003-469X
ISSN (online)	2239-253X
ISSN	0003-469X
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Article: [Clean margins in breast surgery, mission impossible?].

Papa, Moshe

Harefuah

2015 Volume 154, Issue 4, Page(s) 251–3, 279

Abstract: Background: Surgical margin involvement is a major cause for local recurrence of breast cancer. In many cases, surgical margin involvement entails re-operation in order to achieve clean margins. The "MarginProbe" device uses radiowave spectroscopy to ... ...

Abstract	Background: Surgical margin involvement is a major cause for local recurrence of breast cancer. In many cases, surgical margin involvement entails re-operation in order to achieve clean margins. The "MarginProbe" device uses radiowave spectroscopy to identify malignant tissue in excised tumor specimens. The current paper describes our experience with "MarginProbe" to evaluate the margin status during surgery. Methods: MarginProbe was used consecutively to evaluate margin involvement of histology-proven breast cancer patients. The excised tumor specimen was assessed visually as well as by palpation and specimen radiography. Results: Forty-five patients who underwent breast preserving surgery were assessed with "MarginProbe" during surgery. Ten patients (22%) underwent re-excisions during the operation as indicated by the probe, which led to clear margins as the end result of surgery. In 2 patients (4.4%) additional surgery was performed at a later date to clear the margins. No adverse effects were noted due to the use of the probe. Summary and conclusions: Use of the "MarginProbe" during breast preserving surgery helps identify involved margins and assists in reaching clear margins following tumor excision. Probe use was effective for infiltrating as well as in situ cancers. Routine use of the probe may contribute to a decreased re-operation rate for involved margins.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/pathology ; Breast Neoplasms/surgery ; Female ; Humans ; Mastectomy, Segmental/methods ; Middle Aged ; Neoplasm Recurrence, Local/prevention & control ; Radio Waves ; Reoperation/statistics & numerical data ; Spectrum Analysis/methods
Language	Hebrew
Publishing date	2015-04
Publishing country	Israel
Document type	English Abstract ; Journal Article
ZDB-ID	953872-0
ISSN	0017-7768
ISSN	0017-7768
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Article: Ventricular Septal Defect and Right-Sided Infective Endocarditis.

Sforna, Stefano / Padoan, Laura / Del Papa, Marco / Grikstaite, Egle / Sardone, Mariagrazia / Savino, Ketty

Journal of cardiovascular echography

2023 Volume 33, Issue 2, Page(s) 95–97

Abstract: Right-sided infective endocarditis (IE), which represents a small but not negligible percentage of IE cases, can be observed in patients with congenital heart diseases. We discuss the case of a young woman with unrepaired perimembranous ventricular ... ...

Abstract	Right-sided infective endocarditis (IE), which represents a small but not negligible percentage of IE cases, can be observed in patients with congenital heart diseases. We discuss the case of a young woman with unrepaired perimembranous ventricular septal defect and repeated episodes of right ventricle and tricuspid valve IE with septic embolism.
Language	English
Publishing date	2023-08-14
Publishing country	India
Document type	Case Reports
ZDB-ID	2734045-4
ISSN	2347-193X ; 2211-4122
ISSN (online)	2347-193X
ISSN	2211-4122
DOI	10.4103/jcecho.jcecho_25_23
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