Astrocyte Proximity Protects Synapses From Human Amyloid-Beta Induced Degeneration in a Mouse Ex Vivo Model of Early Alzheimer's Disease.
The 4 matches
- [1] § Materials and Methods › Data Analysis › Analysis of Calcium Activity and Event Extraction ↔ Synapse_Event_Detection_Runme.ipynb, lines 69–192 · score 0.92 · constrained_foopsi, optimize_g, s_min, PRE recordings, scored normalised, Event frequency
- [2] § Results › Multicolour Imaging of Synaptic Activity and Astrocyte–Neuron Interactions ↔ Single_event_calculation.ipynb, lines 511–536 · score 0.74 · GCaMP6s, jGCaMP8s, peak amplitude, jGCaMP7b, GECI, variants
- [3] § Materials and Methods › Structural and Calcium Imaging › Comparison of GCaMP Variants ↔ Single_event_calculation.ipynb, lines 511–536 · score 0.65 · GCaMP6s, jGCaMP8s, jGCaMP7b, Variants
- [4] § Materials and Methods › Data Analysis › Comparison of GCaMP Variants ↔ Synapse_Event_Detection_Runme.ipynb, lines 69–192 · score 0.62 · event detection, scored normalised, raw, optimize, OASIS, frame
Paper
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The authors' code
Jupyter notebook · 448 lines · 14 KB · Apache-2.0 · 2 matches
- # %%
- import pandas as pd
- import numpy as np
- import matplotlib.pyplot as plt
- import seaborn as sns
- import os
- import matplotlib as mpl
- import caiman as cm
- from caiman.source_extraction import cnmf
- from caiman.utils.utils import download_demo
- from caiman.utils.visualization import inspect_correlation_pnr
- from caiman.source_extraction.cnmf import params as params
- from caiman.source_extraction.cnmf.deconvolution import constrained_foopsi
- from caiman.source_extraction.cnmf.deconvolution import constrained_oasisAR2
- def Okada_filter(trace):
- """Trace is a list.
- This will apply Okada filter to it as described in Ishikawa et al, STAR Protocols 2020"""
- x=trace.copy()
- M=np.mean(x)
- SD=np.std(x)
- T=len(x)
- for t in range(2, T-1):
- Z=abs(x[t+1]-M)/SD
- if (x[t]-x[t+1])*(x[t]-x[t+1])>0:
- x[t]=(x[t-1]+Z*x[t]+x[t+1])/(2+Z)
- return x
- def subtract_baseline(trace, order):
- x=np.linspace(0,len(trace)*0.05,len(trace))
- p = np.poly1d(np.polyfit(x, trace, int(order)))
- return p
- def dFF(trace):
- """Trace is a list.
- This will calculate deltaF/F0"""
- x=trace.copy()
- M=np.mean(trace)
- T=len(trace)
- for t in range(0, T):
- x[t]=(trace[t]-M)/M
- return x
- def process(trace, polynomial_order=10, Okada_order=4):
- """Trace is a list.
- This will subtract the background with a nth order polynomial and apply Okada filter (m interactions)
- n=polynomial_order (default is 10)
- m=number of consecutive Okada iteraction (default is 4)
- """
- x=trace.tolist().copy()
- baseline=subtract_baseline(x,polynomial_order)
- t = np.linspace(0, len(x)*0.05,len(x))
- x = [a - b for a, b in zip(x, baseline(t))]
- for i in range(Okada_order):
- x=Okada_filter(x)
- return x
- framerate=20 #Hz for interframe time 50ms
- # %%
- #Select PRE ROIs
- folder=r'\\AA06299633\S2410250541\Results' # Input folder
- file="20241210_S2410250541_field01_day1_mScarletxCre_Ch1mScarlet-Ch2GCaMP7b_PRE_Results.csv" #File location of PRE recording
- df=pd.read_csv(os.path.join(folder, file))
- df=df.iloc[:, 1:]
- for column in df.columns:
- if column[:4]!='Mean' :
- df=df.drop(column, axis=1)
- elif column[:4]=='Mean' :
- df=df.rename(columns={column:'ROI'+column[4:]})
- df2=df.copy()
- for column in df2.columns:
- df2[column]=dFF(df2[column]) #calculates Delta F/F
- df2[column]=process(df2[column]) # subtracts background and filters noise
- cells=df.columns
- from matplotlib import gridspec
- from sklearn.preprocessing import normalize
- #plotting params
- mpl.rcParams['axes.facecolor'] = 'white'
- mpl.rcParams['axes.edgecolor'] = 'black'
- mpl.rcParams['axes.linewidth'] = '0.5'
- mpl.rcParams['axes.labelsize'] = '8'
- mpl.rcParams['axes.labelcolor'] = 'black'
- mpl.rcParams['xtick.color'] = 'black'
- mpl.rcParams['xtick.labelsize'] = '4'
- mpl.rcParams['ytick.labelsize'] = '4'
- mpl.rcParams['ytick.color'] = 'black'
- bl=None
- c1=None #initial calcium concentation (value)
- g=None
- sn=10 #noise SD
- p=1
- method_deconvolution='oasis'
- bas_nonneg=True #baseline estimation
- noise_range=[0.25, 0.75] #frquency range to estimate noise
- noise_method='logmexp' #method to estimate noise
- lags=5
- fudge_factor=.99
- verbosity=False
- solvers=None
- optimize_g=5
- s_min=2.5 #if z-scored use s_min=2.5 equivalent to 2.5SD ; elsse use s_min between .1 and .25 (usually .2)
- #--------------------------------------
- trace_dlc = np.array(df2.values.astype(float)).transpose()[:]
- cells_tv = cells[:]
- all_events = []
- all_events_count=[]
- all_events_frequency=[]
- for cell in range(len(trace_dlc)):
- raw_trace = trace_dlc[cell]
- raw_trace = np.array(raw_trace)#/max(np.array(raw_trace)) #If we want traces between 0 and 1 (OPTIONAL)
- raw_trace = (raw_trace - np.mean(raw_trace))/np.std(raw_trace) #z-score normalised
- #OASIS function run through
- events = constrained_foopsi(raw_trace,
- bl=bl,
- c1=c1,
- g=g,
- sn=sn,
- p=p,
- method_deconvolution=method_deconvolution,
- bas_nonneg=bas_nonneg,
- noise_range=noise_range,
- noise_method=noise_method,
- lags=lags,
- fudge_factor=fudge_factor,
- verbosity=verbosity,
- solvers=solvers,
- optimize_g=optimize_g,
- s_min=s_min)
- all_events.append(events[5])
- all_events_frequency.append(np.count_nonzero(events[5])/len(events[5])*framerate)
- all_events_count.append(np.count_nonzero(events[5]))
- #Visualising data
- fig, axs = plt.subplots(3, 1, figsize=(5,1), dpi=400, facecolor='w', edgecolor='k' )
- gs = gridspec.GridSpec(3, 1, height_ratios=[1,1,1], )
- fig.suptitle(cells_tv[cell], fontsize=10)
- for ax in fig.get_axes():
- ax.tick_params(bottom=False, labelbottom=False, left=False, labelleft=False)
- #Raw traces
- axs[0] = plt.subplot(gs[0])
- axs[0] = plt.plot( raw_trace, c='green', linewidth=.5)
- #OASIS noise consideration
- axs[1] = plt.subplot(gs[1])
- axs[1] = plt.plot(events[0], c='b', linewidth=.5)
- #Events plotted on raw trace
- axs[2] = plt.subplot(gs[2])
- axs[2] = plt.plot(raw_trace, c='k', alpha=0.1, linewidth=.5)
- axs[2] = plt.scatter( np.arange(0,len(events[5]),1),events[5], c='r', s=.5)
- fig.text(0.5, -0.1, 'Frame', ha='center', fontsize=5)
- fig.text(0.05, 0.5, u'Δ F/F (z-score)', va='center', rotation='vertical', fontsize=5)
- plt.subplots_adjust(wspace=0, hspace=0)
- plt.show()
- df_events=pd.DataFrame(data={'ROI':cells,'PRE_n':all_events_count,'PRE_Hz':all_events_frequency})
- # %%
- #Select POST ROIs
- file="20241210_S2410250541_field01_day1_mScarletxCre_Ch1mScarlet-Ch2GCaMP7b_POST_Results.csv" #File location of POST recording
- df=pd.read_csv(os.path.join(folder, file))
- df=df.iloc[:, 1:]
- for column in df.columns:
- if column[:4]!='Mean' :
- df=df.drop(column, axis=1)
- elif column[:4]=='Mean' :
- df=df.rename(columns={column:'ROI'+column[4:]})
- df2=df.copy()
- for column in df2.columns:
- df2[column]=dFF(df2[column]) #calculates Delta F/F
- df2[column]=process(df2[column]) # subtracts background and filters noise
- cells=df.columns
- from matplotlib import gridspec
- from sklearn.preprocessing import normalize
- #plotting params
- mpl.rcParams['axes.facecolor'] = 'white'
- mpl.rcParams['axes.edgecolor'] = 'black'
- mpl.rcParams['axes.linewidth'] = '0.5'
- mpl.rcParams['axes.labelsize'] = '8'
- mpl.rcParams['axes.labelcolor'] = 'black'
- mpl.rcParams['xtick.color'] = 'black'
- mpl.rcParams['xtick.labelsize'] = '4'
- mpl.rcParams['ytick.labelsize'] = '4'
- mpl.rcParams['ytick.color'] = 'black'
- bl=None
- c1=None #initial calcium concentation (value)
- g=None
- sn=10 #noise SD
- p=1
- method_deconvolution='oasis'
- bas_nonneg=True #baseline estimation
- noise_range=[0.25, 0.75] #frquency range to estimate noise
- noise_method='logmexp' #method to estimate noise
- lags=5
- fudge_factor=.99
- verbosity=False
- solvers=None
- optimize_g=5
- s_min=2.2 #if z-scored use s_min=2 equivalent to 2SD ; elsse use s_min between .1 and .25 (usually .2)
- #--------------------------------------
- trace_dlc = np.array(df2.values.astype(float)).transpose()[:]
- cells_tv = cells[:]
- all_events = []
- all_events_count=[]
- all_events_frequency=[]
- for cell in range(len(trace_dlc)):
- raw_trace = trace_dlc[cell]
- raw_trace = np.array(raw_trace)#/max(np.array(raw_trace)) #If we want traces between 0 and 1 (OPTIONAL)
- raw_trace = (raw_trace - np.mean(raw_trace))/np.std(raw_trace) #z-score normalised
- #OASIS function run through
- events = constrained_foopsi(raw_trace,
- bl=bl,
- c1=c1,
- g=g,
- sn=sn,
- p=p,
- method_deconvolution=method_deconvolution,
- bas_nonneg=bas_nonneg,
- noise_range=noise_range,
- noise_method=noise_method,
- lags=lags,
- fudge_factor=fudge_factor,
- verbosity=verbosity,
- solvers=solvers,
- optimize_g=optimize_g,
- s_min=s_min)
- all_events.append(events[5])
- all_events_frequency.append(np.count_nonzero(events[5])/len(events[5])*framerate)
- all_events_count.append(np.count_nonzero(events[5]))
- #Viualising data
- fig, axs = plt.subplots(3, 1, figsize=(5,1), dpi=400, facecolor='w', edgecolor='k' )
- gs = gridspec.GridSpec(3, 1, height_ratios=[1,1,1], )
- fig.suptitle(cells_tv[cell], fontsize=10)
- for ax in fig.get_axes():
- ax.tick_params(bottom=False, labelbottom=False, left=False, labelleft=False)
- #Raw traces
- axs[0] = plt.subplot(gs[0])
- axs[0] = plt.plot( raw_trace, c='green', linewidth=.5)
- #OASIS noise consideration
- axs[1] = plt.subplot(gs[1])
- axs[1] = plt.plot(events[0], c='b', linewidth=.5)
- #Events plotted on raw trace
- axs[2] = plt.subplot(gs[2])
- axs[2] = plt.plot(raw_trace, c='k', alpha=0.1, linewidth=.5)
- axs[2] = plt.scatter( np.arange(0,len(events[5]),1),events[5], c='r', s=.5)
- fig.text(0.5, -0.1, 'Frame', ha='center', fontsize=5)
- fig.text(0.05, 0.5, u'Δ F/F (z-score)', va='center', rotation='vertical', fontsize=5)
- plt.subplots_adjust(wspace=0, hspace=0)
- plt.show()
- df_events_post=pd.DataFrame(data={'ROI':cells,'POST_n':all_events_count,'POST_Hz':all_events_frequency})
- df_events=pd.merge(df_events, df_events_post, on='ROI')
- # %%
- #Select POST ROIs
- file="20241210_S2410250541_field01_day1_mScarletxCre_Ch1mScarlet-Ch2GCaMP7b_POST2_Results.csv" #Optional :File location of second POST recording
- df=pd.read_csv(os.path.join(folder, file))
- df=df.iloc[:, 1:]
- for column in df.columns:
- if column[:4]!='Mean' :
- df=df.drop(column, axis=1)
- elif column[:4]=='Mean' :
- df=df.rename(columns={column:'ROI'+column[4:]})
- df2=df.copy()
- for column in df2.columns:
- df2[column]=dFF(df2[column]) #calculates Delta F/F
- df2[column]=process(df2[column]) # subtracts background and filters noise
- cells=df.columns
- from matplotlib import gridspec
- from sklearn.preprocessing import normalize
- #plotting params
- mpl.rcParams['axes.facecolor'] = 'white'
- mpl.rcParams['axes.edgecolor'] = 'black'
- mpl.rcParams['axes.linewidth'] = '0.5'
- mpl.rcParams['axes.labelsize'] = '8'
- mpl.rcParams['axes.labelcolor'] = 'black'
- mpl.rcParams['xtick.color'] = 'black'
- mpl.rcParams['xtick.labelsize'] = '4'
- mpl.rcParams['ytick.labelsize'] = '4'
- mpl.rcParams['ytick.color'] = 'black'
- bl=None
- c1=None #initial calcium concentation (value)
- g=None
- sn=10 #noise SD
- p=1
- method_deconvolution='oasis'
- bas_nonneg=True #baseline estimation
- noise_range=[0.25, 0.75] #frquency range to estimate noise
- noise_method='logmexp' #method to estimate noise
- lags=5
- fudge_factor=.99
- verbosity=False
- solvers=None
- optimize_g=5
- s_min=2.2 #if z-scored use s_min=2 equivalent to 2SD ; elsse use s_min between .1 and .25 (usually .2)
- #--------------------------------------
- trace_dlc = np.array(df2.values.astype(float)).transpose()[:]
- cells_tv = cells[:]
- all_events = []
- all_events_count=[]
- all_events_frequency=[]
- for cell in range(len(trace_dlc)):
- raw_trace = trace_dlc[cell]
- raw_trace = np.array(raw_trace)#/max(np.array(raw_trace)) #If we want traces between 0 and 1 (OPTIONAL)
- raw_trace = (raw_trace - np.mean(raw_trace))/np.std(raw_trace) #z-score normalised
- #OASIS function run through
- events = constrained_foopsi(raw_trace,
- bl=bl,
- c1=c1,
- g=g,
- sn=sn,
- p=p,
- method_deconvolution=method_deconvolution,
- bas_nonneg=bas_nonneg,
- noise_range=noise_range,
- noise_method=noise_method,
- lags=lags,
- fudge_factor=fudge_factor,
- verbosity=verbosity,
- solvers=solvers,
- optimize_g=optimize_g,
- s_min=s_min)
- all_events.append(events[5])
- all_events_frequency.append(np.count_nonzero(events[5])/len(events[5])*framerate)
- all_events_count.append(np.count_nonzero(events[5]))
- #Viualising data
- fig, axs = plt.subplots(3, 1, figsize=(5,1), dpi=400, facecolor='w', edgecolor='k' )
- gs = gridspec.GridSpec(3, 1, height_ratios=[1,1,1], )
- fig.suptitle(cells_tv[cell], fontsize=10)
- for ax in fig.get_axes():
- ax.tick_params(bottom=False, labelbottom=False, left=False, labelleft=False)
- #Raw traces
- axs[0] = plt.subplot(gs[0])
- axs[0] = plt.plot( raw_trace, c='green', linewidth=.5)
- #OASIS noise consideration
- axs[1] = plt.subplot(gs[1])
- axs[1] = plt.plot(events[0], c='b', linewidth=.5)
- #Events plotted on raw trace
- axs[2] = plt.subplot(gs[2])
- axs[2] = plt.plot(raw_trace, c='k', alpha=0.1, linewidth=.5)
- axs[2] = plt.scatter( np.arange(0,len(events[5]),1),events[5], c='r', s=.5)
- fig.text(0.5, -0.1, 'Frame', ha='center', fontsize=5)
- fig.text(0.05, 0.5, u'Δ F/F (z-score)', va='center', rotation='vertical', fontsize=5)
- plt.subplots_adjust(wspace=0, hspace=0)
- plt.show()
- df_events_post=pd.DataFrame(data={'ROI':cells,'POST2_n':all_events_count,'POST2_Hz':all_events_frequency})
- df_events=pd.merge(df_events, df_events_post, on='ROI')
- # %%
- df_events
- # %%
- df_events.to_csv(os.path.join(folder, file[:21]+'EVE.csv'))
- # %%
Synapse_Event_Detection_Runme.ipynb at commit 48fd558, under Apache-2.0 · at the source
Overview
- Institute for Neuroscience and Cardiovascular Research and UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK
- Department of Molecular Physiology, Centre for Integrative Physiology and Molecular Medicine (CIPMM), University of Saarland, Homburg, Germany
- Department of Biological Sciences, Tokyo Metropolitan University, Tokyo, Japan
Abstract
Synapse loss is the strongest pathological correlate of cognitive decline in Alzheimer's disease (ad) and is most pronounced around amyloid plaque pathology in the brain. Although mechanisms remain incompletely understood, hyperactivity downstream of soluble amyloid beta (Aβ) is strongly implicated in synapse degeneration. Engulfment of synapses by reactive astrocytes was observed in end‐stage disease tissue, particularly around plaques. Due to astrocytes' role in synaptic modulation, we hypothesised that astrocytes could modulate synapse degeneration downstream of soluble Aβ earlier in disease pathogenesis. To test this, we challenged organotypic mouse brain slices with human ad brain homogenates containing Aβ. Changes in synaptic activity were detected 2 h after Aβ challenge, and spine loss was seen after 24 h. We observe that Aβ‐containing homogenate induces a significant loss of spines compared with controls. Aβ‐containing homogenate also causes a significant increase in the frequency of synaptic calcium events, particularly in synapses lost at 24 h. Dendritic spines associated with astrocytic processes were significantly more likely to survive at 24 h after Aβ challenge and had reduced levels of externalised phosphatidyl serine despite no effect of astrocyte proximity on synaptic activity. Inhibiting astrocytic glutamate transporters prevented the protective effects of astrocytes on synapses, indicating that astrocytes are protective of synapses at least in part through removing excess glutamate from the synaptic microenvironment. Our findings suggest that an organotypic mouse brain slice model challenged with disease tissue homogenates effectively recapitulates key features of early AD, including synapse loss and hyperexcitability. Moreover, they indicate that astrocytes play a protective role in preserving synapses, particularly during short‐term exposure to low concentrations of toxic Aβ. Future work is needed to elucidate the role of astrocyte‐mediated synapse phagocytosis in response to chronic Aβ exposure.
Reproduced under the paper's license (CC BY), from the paper cited above.
Repository
Its files are read in the Code ↔ Paper reader above, with 4 matches between paragraphs and lines of code.
francesco-gobbo/astrocyte-proximity-protects-synapses-in-ad
48fd5583b2f733ef8b43398879ae458aa4b03ce1, 9 February 2026Availability: 1 check, the latest on 28 September 2026: the link answers
- 28 September 2026: the link answers
6 files
- Bleaching_Analysis.ipynb
, Jupyter, 107 lines - R Analysis/
Gobbo_et_al_Data_Analysi , R, 1,569 liness.Rmd - Single_event_calculation
.ipynb , Jupyter, 554 lines, 2 matches - Synapse_Event_Detection_
Runme.ipynb , Jupyter, 448 lines, 2 matches - LICENSE, License, 201 lines
- README.md, Text, 18 lines
The paper's code and data availability statement is in the Data section.
Tracing map
Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.
What the map holds:
- 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
- 4 scripts, each with its path and the digest of its content;
- 4 matches between paragraphs of the paper and lines of the code (method lexical-v1);
- neither the text of the paper nor the code itself.
Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.
Data
No dataset and no data link were found in the paper.
Data Availability Statement
The code used in the paper is available at https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 2, 28 September 2026
- Publisher: n/a → Wiley
Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 5 keywords, 12 MeSH terms, 5 funders, 85 references.
Cite
This paper
Gobbo, F., King, D., Tulloch, J., Gobbo, D., Bonthron, C., Meftah, S., Stoddart‐Campbelton, C., Tamura, A., Rose, J., Smith, C., Durrant, C., & Spires‐Jones, T. L. (2026). Astrocyte Proximity Protects Synapses From Human Amyloid-Beta Induced Degeneration in a Mouse Ex Vivo Model of Early Alzheimer's Disease. The European journal of neuroscience, 63(7), e70480. https://
BibTeX
@article{gobbo2026astroc
author = {Gobbo, Francesco and King, Declan and Tulloch, Jane and Gobbo, Davide and Bonthron, Calum and Meftah, Soraya and Stoddart‐Campbelton, Caleb and Tamura, Arisa and Rose, Jamie and Smith, Colin and Durrant, Claire and Spires‐Jones, Tara L},
title = {{Astrocyte Proximity Protects Synapses From Human Amyloid-Beta Induced Degeneration in a Mouse Ex Vivo Model of Early Alzheimer's Disease}},
journal = {The European journal of neuroscience},
year = {2026},
month = apr,
volume = {63},
number = {7},
pages = {e70480},
publisher = {Wiley},
issn = {0953-816X},
doi = {10.1111/
url = {https://
pmid = {41902755},
pmcid = {PMC13032744}
}
RIS
TY - JOUR
AU - Gobbo, Francesco
AU - King, Declan
AU - Tulloch, Jane
AU - Gobbo, Davide
AU - Bonthron, Calum
AU - Meftah, Soraya
AU - Stoddart‐Campbelton, Caleb
AU - Tamura, Arisa
AU - Rose, Jamie
AU - Smith, Colin
AU - Durrant, Claire
AU - Spires‐Jones, Tara L
TI - Astrocyte Proximity Protects Synapses From Human Amyloid-Beta Induced Degeneration in a Mouse Ex Vivo Model of Early Alzheimer's Disease
T2 - The European journal of neuroscience
J2 - Eur J Neurosci
PY - 2026
DA - 2026/
VL - 63
IS - 7
SP - e70480
SN - 0953-816X
PB - Wiley
DO - 10.1111/
UR - https://
LA - en
ER -
CSL-JSON
{
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"type": "article-journal",
"title": "Astrocyte Proximity Protects Synapses From Human Amyloid-Beta Induced Degeneration in a Mouse Ex Vivo Model of Early Alzheimer's Disease",
"container-title": "The European journal of neuroscience",
"author": [
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"family": "Gobbo",
"given": "Francesco"
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{
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"given": "Arisa"
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"given": "Claire"
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{
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"given": "Tara L"
}
],
"container-title-short":
"volume": "63",
"issue": "7",
"page": "e70480",
"DOI": "10.1111/
"PMID": "41902755",
"PMCID": "PMC13032744",
"ISSN": "0953-816X",
"publisher": "Wiley",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
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}
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