bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesoporous silica nanoparticles functionalized with folic acid for targeted release Cis-Pt to glioblastoma cells
Authors: Ortiz-Islas Emma , Sosa-Arróniz Anahí , Manríquez-Ramírez Ma Elena , Rodríguez-Pérez C. Ekaterina , Tzompantzi Francisco , Padilla Juan Manuel 
Published: January 2021

Abstract
This work reports the preparation, characterization, and a drug release study of mesoporous silica nanoparticles (MNPSiO2) functionalized with folic acid (FA) and loaded with Cis-Pt as a targeted release system to kill glioblastoma cancer cells. The MNPSiO2 were synthesized by the Stöber method using hexadecyltrimethylammonium bromide as the templating agent, which was finally removed by calcination at 550°C. The folic acid was chemically anchored to the silica nanoparticles surface by a carbodiimide reaction. Several physicochemical techniques were used for the MNPSiO2 characterization, and a triplicate in vitro Cis-Pt release test was carried out. The release Cis-Pt experimental values were fitted to different theoretical models to find the Cis-Pt release mechanism. The cytotoxicity evaluation of the MNPSiO2 was performed using LN 18 cells (human GBM cells). Homogeneous and well-defined nanoparticles with well-distributed and homogeneous porosity were obtained. The spectroscopic results show the proper functionalization of the mesoporous nanoparticles; besides, MNPSiO2 showed high surface area and large pore size. High correlation coefficients were obtained. Though the best fitted was the Korsmeyer-Peppas kinetic model, the Higuchi model adjusted better to the results obtained for our system. The MNPSiO2-FA were highly biocompatible, and they increased the cytotoxic effect of Cis-Pt loaded in them.
Glaubensüberzeugungen von Fachpersonen aus dem Gesundheitswesen – Ein integrativer Review zum internationalen Forschungsstand
Authors: Hefti René , Albisser Judith 
Published: January 2021

Zusammenfassung
Vorliegender integrativer Review gibt einen systematischen Überblick über den internationalen Forschungsstand zum Thema „Health professionals’ beliefs“ unter Einbezug quantitativer und qualitativer Studien. Er untersucht die Glaubensüberzeugungen von Fachpersonen aus dem Gesundheitswesen, ihren Einfluss auf die berufliche Praxis und das Verständnis des Zusammenhanges von Glauben und Gesundheit. Eine systematische Literaturrecherche in den Datenbanken Google Scholar, PubMed und PsycINFO, ergab 32 Studien, die die Einschlusskriterien erfüllten und die spezifischen Fragestellungen aufgriffen. Die Ergebnisse verdeutlichen die Relevanz von Glaubensüberzeugungen bei Gesundheitsfachpersonen und ihren Einfluss auf die berufliche Praxis. Die konkrete Umsetzung im beruflichen Alltag ist aber unterschiedlich ausgeprägt und bedarf eines weiteren Diskurses. Dabei müssen die institutionellen Rahmenbedingungen in den Gesundheitseinrichtungen wie auch geeignete Aus-, Weiter- und Fortbildungsangebote thematisiert werden.
Color Tuning of Face-Selective Neurons in Macaque Inferior Temporal Cortex
Authors: Duyck Marianne , Chang Audrey L. Y. , Gruen Tessa J. , Tello Lawrence Y. , Eastman Serena , Fuller-Deets Joshua , Conway Bevil R. 
Published: January 2021

AbstractWhat role does color play in the neural representation of complex shapes? We approached the question by measuring color responses of face-selective neurons, using fMRI-guided microelectrode recording of the middle and anterior face patches of inferior temporal cortex (IT) in rhesus macaques. Face-selective cells responded weakly to pure color (equiluminant) photographs of faces. But many of the cells nonetheless showed a bias for warm colors when assessed using images that preserved the luminance contrast relationships of the original photographs. This bias was also found for non-face-selective neurons. Fourier analysis uncovered two components: the first harmonic, accounting for most of the tuning, was biased toward reddish colors, corresponding to the L>M pole of the L-M cardinal axis. The second harmonic showed a bias for modulation between blue and yellow colors axis, corresponding to the S-cone axis. To test what role face-selective cells play in behavior, we related the information content of the neural population with the distribution of face colors. The analyses show that face-selective cells are not optimally tuned to discriminate face colors, but are consistent with the idea that face-selective cells contribute selectively to processing the green-red contrast of faces. The research supports the hypothesis that color-specific information related to the discrimination of objects, including faces, is handled by neural circuits that are independent of shape-selective cortex, as captured by the multistage parallel processing framework of IT (Lafer-Sousa and Conway, 2013).
TRPM3 Channels Play Roles in Heat Hypersensitivity and Spontaneous Pain after Nerve Injury
Authors: Su Songxue , Yudin Yevgen , Kim Nawoo , Tao Yuan-Xiang , Rohacs Tibor 
Published: January 2021

Transient receptor potential melastatin 3 (TRPM3) is a heat-activated ion channel in primary sensory neurons of the dorsal root ganglia (DRGs). Pharmacological and genetic studies implicated TRPM3 in various pain modalities, but TRPM3 inhibitors were not validated in TRPM3−/−mice. Here we tested two inhibitors of TRPM3 in male and female wild-type and TRPM3−/−mice in nerve injury-induced neuropathic pain. We found that intraperitoneal injection of either isosakuranetin or primidone reduced heat hypersensitivity induced by chronic constriction injury (CCI) of the sciatic nerve in wild-type, but not in TRPM3−/−mice. Primidone was also effective when injected locally in the hindpaw or intrathecally. Consistently, intrathecal injection of the TRPM3 agonist CIM0216 reduced paw withdrawal latency to radiant heat in wild-type, but not in TRPM3−/−mice. Intraperitoneal injection of 2 mg/kg, but not 0.5 mg/kg isosakuranetin, inhibited cold and mechanical hypersensitivity in CCI, both in wild-type and TRPM3−/−mice, indicating a dose-dependent off-target effect. Primidone had no effect on cold sensitivity, and only a marginal effect on mechanical hypersensitivity. Genetic deletion or inhibitors of TRPM3 reduced the increase in the levels of the early genes c-Fos and pERK in the spinal cord and DRGs in CCI mice, suggesting spontaneous activity of the channel. Intraperitoneal isosakuranetin also inhibited spontaneous pain related behavior in CCI in the conditioned place preference assay, and this effect was eliminated in TRPM3−/−mice. Overall, our data indicate a role of TRPM3 in heat hypersensitivity and in spontaneous pain after nerve injury.SIGNIFICANCE STATEMENTNeuropathic pain is a major unsolved medical problem. The heat-activated TRPM3 ion channel is a potential target for novel pain medications, but the pain modalities in which it plays a role are not clear. Here we used a combination of genetic and pharmacological tools to assess the role of this channel in spontaneous pain, heat, cold, and mechanical hypersensitivity in a nerve injury model of neuropathic pain in mice. Our findings indicate a role for TRPM3 in heat hyperalgesia, and spontaneous pain, but not in cold and mechanical hypersensitivity. We also find that not only TRPM3 located in the peripheral nerve termini, but also TRPM3 in the spinal cord or proximal segments of DRG neurons are important for heat hypersensitivity.
Brief Sensory Deprivation Triggers Cell Type-Specific Structural and Functional Plasticity in Olfactory Bulb Neurons
Authors: Galliano Elisa , Hahn Christiane , Browne Lorcan P. , R. Villamayor Paula , Tufo Candida , Crespo Andres , Grubb Matthew S. 
Published: January 2021

Can alterations in experience trigger different plastic modifications in neuronal structure and function, and if so, how do they integrate at the cellular level? To address this question, we interrogated circuitry in the mouse olfactory bulb responsible for the earliest steps in odor processing. We induced experience-dependent plasticity in mice of either sex by blocking one nostril for one day, a minimally invasive manipulation that leaves the sensory organ undamaged and is akin to the natural transient blockage suffered during common mild rhinal infections. We found that such brief sensory deprivation produced structural and functional plasticity in one highly specialized bulbar cell type: axon-bearing dopaminergic neurons in the glomerular layer. After 24 h naris occlusion, the axon initial segment (AIS) in bulbar dopaminergic neurons became significantly shorter, a structural modification that was also associated with a decrease in intrinsic excitability. These effects were specific to the AIS-positive dopaminergic subpopulation because no experience-dependent alterations in intrinsic excitability were observed in AIS-negative dopaminergic cells. Moreover, 24 h naris occlusion produced no structural changes at the AIS of bulbar excitatory neurons, mitral/tufted and external tufted cells, nor did it alter their intrinsic excitability. By targeting excitability in one specialized dopaminergic subpopulation, experience-dependent plasticity in early olfactory networks might act to fine-tune sensory processing in the face of continually fluctuating inputs.SIGNIFICANCE STATEMENTSensory networks need to be plastic so they can adapt to changes in incoming stimuli. To see how cells in mouse olfactory circuits can change in response to sensory challenges, we blocked a nostril for just one day, a naturally relevant manipulation akin to the deprivation that occurs with a mild cold. We found that this brief deprivation induces forms of axonal and intrinsic functional plasticity in one specific olfactory bulb cell subtype: axon-bearing dopaminergic interneurons. In contrast, intrinsic properties of axon-lacking bulbar dopaminergic neurons and neighboring excitatory neurons remained unchanged. Within the same sensory circuits, specific cell types can therefore make distinct plastic changes in response to an ever-changing external landscape.
α-Synuclein Oligomers Induce Glutamate Release from Astrocytes and Excessive Extrasynaptic NMDAR Activity in Neurons, Thus Contributing to Synapse Loss
Authors: Trudler Dorit , Sanz-Blasco Sara , Eisele Yvonne S. , Ghatak Swagata , Bodhinathan Karthik , Akhtar Mohd Waseem , Lynch William P. , Piña-Crespo Juan C. , Talantova Maria , Kelly Jeffery W. , Lipton Stuart A. 
Published: January 2021

Synaptic and neuronal loss are major neuropathological characteristics of Parkinson's disease. Misfolded protein aggregates in the form of Lewy bodies, comprised mainly of α-synuclein (αSyn), are associated with disease progression, and have also been linked to other neurodegenerative diseases, including Lewy body dementia, Alzheimer's disease, and frontotemporal dementia. However, the effects of αSyn and its mechanism of synaptic damage remain incompletely understood. Here, we show that αSyn oligomers induce Ca2+-dependent release of glutamate from astrocytes obtained from male and female mice, and that mice overexpressing αSyn manifest increased tonic release of glutamatein vivo. In turn, this extracellular glutamate activates glutamate receptors, including extrasynaptic NMDARs (eNMDARs), on neurons both in culture and in hippocampal slices of αSyn-overexpressing mice. Additionally, in patch-clamp recording from outside-out patches, we found that oligomerized αSyn can directly activate eNMDARs. In organotypic slices, oligomeric αSyn induces eNMDAR-mediated synaptic loss, which can be reversed by the drug NitroSynapsin. When we expose human induced pluripotent stem cell-derived cerebrocortical neurons to αSyn, we find similar effects. Importantly, the improved NMDAR antagonist NitroSynapsin, which selectively inhibits extrasynaptic over physiological synaptic NMDAR activity, protects synapses from oligomeric αSyn-induced damage in our model systems, thus meriting further study for its therapeutic potential.SIGNIFICANCE STATEMENTLoss of synaptic function and ensuing neuronal loss are associated with disease progression in Parkinson's disease (PD), Lewy body dementia (LBD), and other neurodegenerative diseases. However, the mechanism of synaptic damage remains incompletely understood. α-Synuclein (αSyn) misfolds in PD/LBD, forming Lewy bodies and contributing to disease pathogenesis. Here, we found that misfolded/oligomeric αSyn releases excessive astrocytic glutamate, in turn activating neuronal extrasynaptic NMDA receptors (eNMDARs), thereby contributing to synaptic damage. Additionally, αSyn oligomers directly activate eNMDARs, further contributing to damage. While the FDA-approved drug memantine has been reported to offer some benefit in PD/LBD (Hershey and Coleman-Jackson, 2019), we find that the improved eNMDAR antagonist NitroSynapsin ameliorates αSyn-induced synaptic spine loss, providing potential disease-modifying intervention in PD/LBD.
The Neurophysiological Representation of Imagined Somatosensory Percepts in Human Cortex
Authors: Bashford Luke , Rosenthal Isabelle , Kellis Spencer , Pejsa Kelsie , Kramer Daniel , Lee Brian , Liu Charles , Andersen Richard A. 
Published: January 2021

Intracortical microstimulation (ICMS) in human primary somatosensory cortex (S1) has been used to successfully evoke naturalistic sensations. However, the neurophysiological mechanisms underlying the evoked sensations remain unknown. To understand how specific stimulation parameters elicit certain sensations we must first understand the representation of those sensations in the brain. In this study we record from intracortical microelectrode arrays implanted in S1, premotor cortex, and posterior parietal cortex of a male human participant performing a somatosensory imagery task. The sensations imagined were those previously elicited by ICMS of S1, in the same array of the same participant. In both spike and local field potential recordings, features of the neural signal can be used to classify different imagined sensations. These features are shown to be stable over time. The sensorimotor cortices only encode the imagined sensation during the imagery task, while posterior parietal cortex encodes the sensations starting with cue presentation. These findings demonstrate that different aspects of the sensory experience can be individually decoded from intracortically recorded human neural signals across the cortical sensory network. Activity underlying these unique sensory representations may inform the stimulation parameters for precisely eliciting specific sensations via ICMS in future work.SIGNIFICANCE STATEMENTElectrical stimulation of human cortex is increasingly more common for providing feedback in neural devices. Understanding the relationship between naturally evoked and artificially evoked neurophysiology for the same sensations will be important in advancing such devices. Here, we investigate the neural activity in human primary somatosensory, premotor, and parietal cortices during somatosensory imagery. The sensations imagined were those previously elicited during intracortical microstimulation (ICMS) of the same somatosensory electrode array. We elucidate the neural features during somatosensory imagery that significantly encode different aspects of individual sensations and demonstrate feature stability over almost a year. The correspondence between neurophysiology elicited with or without stimulation for the same sensations will inform methods to deliver more precise feedback through stimulation in the future.
Phosphodiesterase 4A confers resistance to PGE2‐mediated suppression in CD25+/CD54+ NK cells
Authors: Chen Ziqing , Yang Ying , Neo Shi Y , Shi Hao , Chen Yi , Wagner Arnika K , Larsson Karin , Tong Le , Jakobsson Per‐Johan , Alici Evren , Wu Jing , Cao Yihai , Wang Kai , Liu Lisa L , Mao Yumeng , Sarhan Dhifaf , Lundqvist Andreas 
Published: January 2021

AbstractInadequate persistence of tumor‐infiltrating natural killer (NK) cells is associated with poor prognosis in cancer patients. The solid tumor microenvironment is characterized by the presence of immunosuppressive factors, including prostaglandin E2 (PGE2), that limit NK cell persistence. Here, we investigate if the modulation of the cytokine environment in lung cancer with IL‐2 or IL‐15 renders NK cells resistant to suppression by PGE2. Analyzing Cancer Genome Atlas (TCGA) data, we found that high NK cell gene signatures correlate with significantly improved overall survival in patients with high levels of the prostaglandin E synthase (PTGES). In vitro, IL‐15, in contrast to IL‐2, enriches for CD25+/CD54+ NK cells with superior mTOR activity and increased expression of the cAMP hydrolyzing enzyme phosphodiesterase 4A (PDE4A). Consequently, this distinct population of NK cells maintains their function in the presence of PGE2 and shows an increased ability to infiltrate lung adenocarcinoma tumors in vitro and in vivo. Thus, strategies to enrich CD25+/CD54+ NK cells for adoptive cell therapy should be considered.
Pre-term birth in women exposed to Cushing’s disease: the baby-cush study
Authors: Hochman Clarisse , Cristante Justine , Geslot Aurore , Salenave Sylvie , Sonnet Emmanuel , Briet Claire , Bachelot Anne , Chevalier Nicolas , Gilly Olivier , Brue Thierry , Hadjadj Samy , Kerlan Veronique , Chanson Philippe , Vezzosi Delphine , Chabre Olivier , Drui Delphine , Castinetti Frederic 
Published: January 2021

Design
Hypercortisolism during pregnancy is a risk factor for prematurity. Long-term exposure to hypercortisolism may lead to permanent comorbidities, such as hypertension or diabetes, even after remission. Our aim was to determine whether women with a history of Cushing’s disease (and being eu-, hypo- or hypercortisolic at the time of pregnancy) had the same risks of comorbidities, and especially prematurity, during pregnancy.

Methods
It was a retrospective multicentric study focusing on mothers with a history of Cushing’s disease or diagnosed during pregnancy, followed in French tertiary referral centers. We compared the outcomes of pregnancies depending on the cortisolic status at the time of pregnancy.

Results
A total of 60 patients (78 pregnancies including 21 with hypercortisolism, 32 with hypocortisolism and 25 in eucortisolism in 25) were evaluated. The overall rate of preterm birth was 24.3%, with a peak in women diagnosed during pregnancy (62.5%), a high risk in hypercortisolic (33%) and hypocortisolic (19.3%), and a low risk (8%) in eucortisolic women Gestational diabetes and hypertension were observed in 21% and 10.4% of the whole cohort, with a higher risk in hypercortisolic women. Cesarean delivery was performed in 33.7% of the cohort.

Conclusions
Being non-eucortisolic at the time of pregnancy increases the risk of prematurity and comorbidities compared to the general population. Women with a history of Cushing’s disease should thus be carefully monitored during pregnancy. The high rate of cesarean delivery emphasizes the fact that these pregnancies should always be considered at risk.
TEORÍA SOCIAL COMO «MÚSICA DE PALABRAS». ELEMENTOS DE ANÁLISIS (QUE NO SERÁN BIENVENIDOS) EN TORNO AL MARXISMO EDULCORADO DEL VENDEHÚMOS ACADEMICUS S. ŽIŽEK
Authors: Haba Enrique Pedro 
Published: January 2021

Aquí se someten a escudriñamientos de orden analítico-realista los contenidos del difundido debate Peterson-Žižek, «Felicidad: Capitalismo vs. Marxismo». Queda así en evidencia el simplismo, la gran indeterminación (fórmulas vacías) y en general el escapismo de planteamientos (esencialismo, falacia intelectualista, etc.) como los ofrecidos por Žižek. Fue un pseudo-«debate»: no existe contradicción propiamente dicha, ni aun parcial, entre lo alegado respectivamente por esos académicos en sus exposiciones iniciales («vorbeireden»); y menos que menos la hubo en cuanto a los enfoques de índole esencialmente parateologal hacia los cuales dirigieron su atención principal durante la segunda mitad de ese evento, sobre los que llegaron ambos a concordar hasta de manera expresa. Finalmente se añaden, al margen, unas observaciones sobre ciertas consideraciones de Žižek ulteriores: sus arengas (siempre en clave musica di paroli) de futurología esperanzada en el quehacer del covid-19 —muy bienvenido, pues debe abrir cauce a la definitiva ingeniería social salvífica globalista, gerenciada mediante imperium soberano de la alta burocracia internacional (onu)—.
Manajemen Strategik Customer Relationship Management (CRM) dalam Menjaga Loyalitas Donatur
Authors: Awaliah Dewi , Rahman Arif , Kuswana Dadang 
Published: January 2021

Penelitian ini bertujuan untuk mengetahui manajemen strategik Customer Relationship Management (CRM) dalam menjaga loyalitas donatur di lembaga zakat Sinergi Foundation. Metode yang digunakan dalam penelitian ini ialah metode deskriptif dengan pendekatan kualitatif. Hasil penelitian manajemen strategik Customer Relationship Management (CRM) dalam menjaga loyalitas donatur di Sinergi Foundation dilakukan dengan baik sesuai dengan teori tahapan manajemen strategik yaitu pengamatan atau analisis lingkungan yang terdiri dari kekuatan, kelemahan, peluang dan ancaman dilakukan oleh Sinergi Foundation sebagai bahan untuk perumusan strategi. Perumusan strategi dilakukan dengan membentuk visi misi, implementasi strategi dilakukan dengan memperkuat sisi kelembagaan dan sistem organisasi dengan meningkatkan peran divisi masing-masing, evaluasi dan pengendalian dengan melihat analisa jumlah donatur dari tahun ke tahun serta mengadakan rapat evaluasi bulanan internal. Dengan demikian, ini menunjukan bahwa manajemen strategic Customer Relationship Management (CRM) Sinergi Foundation dalam menjaga loyalitas donaturnya sudah berjalan dengan baik dan mendapatkan hasil yang optimal.
This research aims to determine the strategic management of Customer Relationship Management (CRM) in maintaining the loyalty of donors in the zakat institutions of Sinergi Foundation. The method used in this research is descriptive method with qualitative approach. The result of strategic management of Customer Relationship Management (CRM) in maintaining donor loyalty in Sinergi Foundation is done well in accordance with strategic management stage theory that is observation or environmental analysis consisting of strengths, weaknesses, opportunities and threats done by Sinergi Foundation as material for strategy formulation. Strategy formulation is done by establishing mission vision, strategy implementation is done by strengthening institutional and organizational system by increasing the role of each division, evaluation and controlling by looking at the analysis of the number of donors from year to year and holding monthly internal evaluation meetings. Thus, this shows that the strategic management of Customer Relationship Management (CRM) Sinergi Foundation in maintaining donor loyalty is running well and get optimal results.