bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonplasmacytoid, High IFN-α–Producing, Bone Marrow Dendritic Cells
Authors: O’Keeffe Meredith , Fancke Ben , Suter Mark , Ramm Georg , Clark Joan , Wu Li , Hochrein Hubertus 
Published: March 2012

Abstract
Plasmacytoid dendritic cells (pDC) are the producers of type I IFNs in response to TLR9 ligands. However, we have found that when bone marrow is depleted of pDC, the IFN-α produced in response to TLR9 ligands is not fully removed. We assign the source of this non-pDC IFN-α as a newly described DC type. It displays the high IFN-α producing activity of pDC but to a more limited range of viruses. Unlike pDC, the novel DC display high T cell stimulation capacity. Moreover, unlike mouse pDC, they are matured with GM-CSF and are less prone to apoptosis upon activation stimuli, including viruses. We propose that these DC constitute a novel bone marrow inflammatory DC type, ideally geared to linking innate and adaptive immune responses in bone marrow via their potent IFN-α production and high T cell stimulatory capacity.
The Fusion Protein of IFN-α and Apolipoprotein A-I Crosses the Blood–Brain Barrier by a Saturable Transport Mechanism
Authors: Fioravanti Jessica , Medina-Echeverz José , Ardaiz Nuria , Gomar Celia , Parra-Guillén Zinnia P. , Prieto Jesús , Berraondo Pedro 
Published: March 2012

AbstractIFN-α is widely used for the treatment of chronic viral hepatitis and malignancies. However, systemic IFN-α treatment causes severe neuropsychiatric complications in humans, including depression, anxiety, and cognitive impairments. We have previously reported that the fusion protein formed by IFN-α and apolipoprotein A-I (IA) circulates bound to high-density lipoproteins (HDLs) and exhibits liver targeting, increased half-life, enhanced immunostimulatory activity, and reduced cytotoxicity. As the transport of HDLs across the blood–brain barrier is a highly complex and regulated process, in this study, we examine the effects of IA on the brain. Determination of IFN-α in brain and serum after hydrodynamic administration of different doses of a plasmid encoding IFN-α or IA showed that IA penetrated into the brain by a saturable transport mechanism. Thus, at high serum levels of the transgenes, the induction of IFN-sensitive genes and the number of phospho-STAT1+ cell nuclei in the brain were substantially higher with IFN-α than with IA. This was associated with attenuation of neurodepression in mice given IA, as manifested by shorter immobility time in the tail suspension test. However, when given low doses of rIFN-α or the same antiviral units of HDLs containing IA, the induction of IFN-stimulated genes in the brain was significantly greater with the latter. In conclusion, IA crosses the blood–brain barrier not by diffusion, as is the case of IFN-α, but by a facilitated saturable transport mechanism. Thus, linkage to apolipoprotein A-I may serve to modulate the effects of IFN-α on the CNS.
Complement Component C1q Regulates Macrophage Expression of Mer Tyrosine Kinase To Promote Clearance of Apoptotic Cells
Authors: Galvan Manuel D. , Foreman Deborah B. , Zeng Erliang , Tan John C. , Bohlson Suzanne S. 
Published: March 2012

Abstract
Failure to efficiently clear apoptotic cells is linked to defects in development and the onset of autoimmunity. Complement component C1q is required for efficient engulfment of apoptotic cells in mice and humans; however, the molecular mechanisms leading to C1q-dependent engulfment are not fully understood. In this study, we used primary mouse macrophages to identify and characterize a novel molecular mechanism for macrophage-mediated C1q-dependent engulfment of apoptotic cells. We found that macrophage activation with C1q resulted in cycloheximide-sensitive enhanced engulfment, indicating a requirement for de novo protein synthesis. To investigate the cycloheximide-sensitive pathway, C1q-elicited macrophage transcripts were identified by microarray. C1q triggered the expression of Mer tyrosine kinase (Mer) and the Mer ligand growth arrest-specific 6: a receptor–ligand pair that mediates clearance of apoptotic cells. Full-length native C1q, and not the collagen-like tail or heat-denatured protein, stimulated Mer expression. This novel pathway is specific to C1q because mannose-binding lectin, a related collectin, failed to upregulate Mer expression and function. Soluble Mer-Fc fusion protein inhibited C1q-dependent engulfment of apoptotic cells, indicating a requirement for Mer. Moreover, Mer-deficient macrophages failed to respond to C1q with enhanced engulfment. Our results suggest that C1q elicits a macrophage phenotype specifically tailored for apoptotic cell clearance, and these data are consistent with the established requirement for C1q in prevention of autoimmunity.
Early Induction of CCL7 Downstream of TLR9 Signaling Promotes the Development of Robust Immunity to Cryptococcal Infection
Authors: Qiu Yafeng , Zeltzer Stuart , Zhang Yanmei , Wang Fuyuan , Chen Gwo-Hsiao , Dayrit Jeremy , Murdock Benjamin J. , Bhan Urvashi , Toews Galen B. , Osterholzer John J. , Standiford Theodore J. , Olszewski Michal A. 
Published: March 2012

Abstract
We investigated mechanisms by which TLR9 signaling promoted the development of the protective response to Cryptococcus neoformans in mice with cryptococcal pneumonia. The afferent (week 1) and efferent (week 3) phase immune parameters were analyzed in the infected wild-type (TLR9+/+) and TLR-deficient (TLR9−/−) mice. TLR9 deletion diminished 1) accumulation and activation of CD11b+ dendritic cells (DCs), 2) the induction of IFN-γ and CCR2 chemokines CCL7, CCL12, but not CCL2, at week 1, and 3) pulmonary accumulation and activation of the major effector cells CD4+ and CD8+ T cells, CD11b+ lung DCs, and exudate macrophages at week 3. The significance of CCL7 induction downstream of TLR9 signaling was investigated by determining whether CCL7 reconstitution would improve immunological parameters in C. neoformans-infected TLR9−/− mice. Early reconstitution with CCL7 1) improved accumulation and activation of CD11b+ DCs at week 1, 2) restored early IFN-γ production in the lungs, and 3) restored the accumulation of major effector cell subsets. CCL7 administration abolished the difference in lung fungal burdens between TLR9+/+ and TLR9−/− mice at week 3; however, significant reduction of fungal burdens between PBS- and CCL7-treated mice has not been observed, suggesting that additional mechanism(s) apart from early CCL7 induction contribute to optimal fungal clearance in TLR9+/+ mice. Collectively, we show that TLR9 signaling during the afferent phase contributes to the development of protective immunity by promoting the early induction of CCL7 and IFN-γ and the subsequent early recruitment and activation of DCs and additional effector cells in mice with cryptococcal pneumonia.
CD27 Stimulation Promotes the Frequency of IL-7 Receptor-Expressing Memory Precursors and Prevents IL-12–Mediated Loss of CD8+ T Cell Memory in the Absence of CD4+ T Cell Help
Authors: Dong Han , Franklin Nathan A. , Roberts Drew J. , Yagita Hideo , Glennie Martin J. , Bullock Timothy N. J. 
Published: March 2012

Abstract
Fully functional CD8+ T cell memory is highly dependent upon CD4+ T cell support. CD4+ T cells play a critical role in inducing the expression of CD70, the ligand for CD27, on dendritic cells. In this study, we demonstrate that CD27 stimulation during primary CD8+ T cell responses regulates the ability to mount secondary CD8+ T cell responses. CD27 stimulation during vaccinia and dendritic cell immunization controls the expression of the IL-7R (CD127), which has been shown to be necessary for memory CD8+ T cell survival. Furthermore, CD27 stimulation during primary CD8+ T cell responses to vaccinia virus restrained the late expression on memory precursor cells of cytokine receptors that support terminal differentiation. The formation of CD8+ T cell memory precursors and secondary CD8+ T cell responses was restored in the absence of CD27 costimulation when endogenous IL-12 was not available. Similarly, the lesion in CD8+ T cell memory that occurs in the absence of CD4+ T cells did not occur in mice lacking IL-12. These data indicate that CD4+ T cell help and, by extension, CD27 stimulation support CD8+ T cell memory by modulating the expression of cytokine receptors that influence the differentiation and survival of memory CD8+ T cells.
Cutting Edge: Protein Phosphatase 2A Confers Susceptibility to Autoimmune Disease through an IL-17–Dependent Mechanism
Authors: Crispín José C. , Apostolidis Sokratis A. , Rosetti Florencia , Keszei Marton , Wang Ninghai , Terhorst Cox , Mayadas Tanya N. , Tsokos George C. 
Published: March 2012

Abstract
The contribution of individual molecular aberrations to the pathogenesis of systemic lupus erythematosus (SLE), an autoimmune disease that affects multiple organs, is often difficult to evaluate because of the presence of abundant confounding factors. To assess the effect of increased expression of the phosphatase protein phosphatase 2A (PP2A) in T cells, as recorded in SLE patients, we generated a transgenic mouse that overexpresses the PP2Ac subunit in T cells. The transgenic mouse displays a heightened susceptibility to immune-mediated glomerulonephritis in the absence of other immune defects. CD4+ T cells produce increased amounts of IL-17 while the number of neutrophils in the peripheral blood is increased. IL-17 neutralization abrogated the development of glomerulonephritis. We conclude that increased PP2Ac expression participates in SLE pathogenesis by promoting inflammation through unchecked IL-17 production and facilitating the development of end-organ damage.
Client-Centered Approach to Develop a Seating Clinic Satisfaction Questionnaire: A Qualitative Study
Authors: McComas Joan , Kosseim Mylène , Macintosh Diana 
Published: March 2012

Abstract
Objective. The purpose of this study was to develop a program evaluation tool through a client-centered approach. Client satisfaction questionnaires previously developed for service recipients of a pediatric seating clinic have reflected the professionals’ views on what should be asked.
Method. Seven parents and caregivers of recent service recipients of the seating clinic participated in tape-recorded semistructured interviews. They were asked their views on the seating clinic, how the service could be improved, and the quality of the seat received through the clinic.
Results. Data were coded into nine themes related to the process and the product. Using these themes and the vocabulary used by the participants, we developed a satisfaction questionnaire. The validity of the questionnaire was evaluated by requesting feedback on clarity, content, and design from all participants and from a panel of five health professionals.
Conclusion. A client-centered approach can be used to develop a client satisfaction tool that reflects the needs of the users. Future work will involve testing the tool in the clinical setting.
Migration, Trade and Unemployment
Authors: Heid Benedikt , Larch Mario 
Published: March 2012

Abstract
A source of anxiety of policy makers and the public in general is the detrimental impact of trade and immigration on unemployment. The transitory restrictions for worker migration after the EU enlargements of 2004 and 2007 exemplify the supposed negative effect of immigration on labor markets. This paper aims to identify the effects of immigration alongside trade on unemployment controlling for the high correlation between immigration and goods flows in order to prevent an omitted variable bias. The authors use data from 24 OECD countries over the period from 1997 to 2007 and employ instrumental variables fixed effects and dynamic panel estimators in order to account for unobserved heterogeneity as well as the potential endogeneity of migration flows and the high persistence of unemployment. We find no significant effect of immigration on unemployment on average.
Human Induced Pluripotent Stem Cells: Differentiation into Dopaminergic nNeurons
Authors: Malchenko Sergey , Bonaldo Maria de Fatima , Vanin Elio F. , Galat Vasily , Crispino John , Soares Marcelo B. 
Published: March 2012

AbstractIn vitro neural differentiation of human embryonic stem cells (hESC), or induced pluripotent stem cells (iPSCs) is a powerful system to study early neural development, instrumental for cell replacement therapy and neuropharmacological studies. Here we report the derivation of tyrosine hydroxylase (TH) positive cells from human iPSCs, indicating the differentiation into dopaminergic neurons.
Overdose, Behavioral Health Services, and Medications for Opioid Use Disorder After a Nonfatal Overdose
Authors: Jones Christopher M. , Shoff Carla , Blanco Carlos , Losby Jan L. , Ling Shari M. , Compton Wilson M. 
Published: June 2024

ImportanceRecognizing and providing services to individuals at highest risk for drug overdose are paramount to addressing the drug overdose crisis.ObjectiveTo examine receipt of medications for opioid use disorder (MOUD), naloxone, and behavioral health services in the 12 months after an index nonfatal drug overdose and the association between receipt of these interventions and fatal drug overdose.Design, Setting, and ParticipantsThis cohort study was conducted in the US from January 2020 to December 2021 using claims, demographic, mortality, and other data from the Centers for Medicare &amp;amp; Medicaid Services, the Centers for Disease Control and Prevention, and other sources. The cohort comprised Medicare fee-for-service beneficiaries aged 18 years or older with International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes for a nonfatal drug overdose. Data analysis was performed from February to November 2023.ExposuresDemographic and clinical characteristics, substance use disorder, and psychiatric comorbidities.Main Outcomes and MeasuresReceipt of MOUD, naloxone, and behavioral health services as well as subsequent nonfatal and fatal drug overdoses.ResultsThe cohort consisted of 136 762 Medicare beneficiaries (80 140 females [58.6%]; mean (SD) age of 68.2 [15.0] years) who experienced an index nonfatal drug overdose in 2020. The majority of individuals had Hispanic (5.8%), non-Hispanic Black (10.9%), and non-Hispanic White (78.8%) race and ethnicity and lived in metropolitan areas (78.9%). In the 12 months after their index nonfatal drug overdose, 23 815 beneficiaries (17.4%) experienced at least 1 subsequent nonfatal drug overdose and 1323 (1.0%) died of a fatal drug overdose. Opioids were involved in 72.2% of fatal drug overdoses. Among the cohort, 5556 (4.1%) received any MOUD and 8530 (6.2%) filled a naloxone prescription in the 12 months after the index nonfatal drug overdose. Filling a naloxone prescription (adjusted odds ratio [AOR], 0.70; 95% CI, 0.56-0.89), each percentage of days receiving methadone (AOR, 0.98; 95% CI, 0.98-0.99) or buprenorphine (AOR, 0.99; 95% CI, 0.98-0.99), and receiving behavioral health assessment or crisis services (AOR, 0.25; 95% CI, 0.22-0.28) were all associated with reduced adjusted odds of fatal drug overdose in the 12 months after the index nonfatal drug overdose.Conclusions and RelevanceThis cohort study found that, despite their known association with reduced risk of a fatal drug overdose, only a small percentage of Medicare beneficiaries received MOUD or filled a naloxone prescription in the 12 months after a nonfatal drug overdose. Efforts to improve access to behavioral health services; MOUD; and overdose-prevention strategies, such as prescribing naloxone and linking individuals to community-based health care settings for ongoing care, are needed.
Implantable MicroLED‐Mediated Chemo‐Photodynamic Combination Therapy for Glioma Treatment
Authors: Kim Jeongrae , Lee Hin Kiu , Park Junwon , Jeon Seong Ik , Lee Il Seong , Yun Wan Su , Moon Yujeong , Choi Jiwoong , Shim Man Kyu , Kim Jinseong , Cho Hanhee , Shim Nayeon , Hwang Namcheol , Koirala Gyan Raj , Gwak Minjun , Han Sangheon , Kim Dong‐Hwee , Chang Won Seok , Kim Tae‐il , Kim Kwangmeyung 
Published: June 2024

AbstractPhotodynamic therapy shows promise for glioma treatment with powerful efficacy and low resistance, however, its effectiveness is significantly lowered by inadequate light delivery through the skull. Herein, a needle‐type implantable microLED device and cathepsin B‐responsive prodrug nanoparticles (PNPs) are newly exploited for glioma's chemo‐photodynamic combination therapy. The microLED containing four small LEDs on the tip of its guide needle can be implanted into the center of glioma tissues without large area opening of skull, uniformly irradiating light to deep glioma tissues. PNPs are formulated via self‐assembly of heterobifunctional prodrug composed of doxorubicin, verteporfin, and cathepsin B‐cleavable peptide linker, wherein they stably maintain inactive nanoparticle structures in normal physiological conditions and specifically deliver therapeutic age to cathepsin B‐overexpressed glioma tissues. In vitro cellular assays, PNPs irradiated with showed the synergistic cytotoxicity of DOX and VFP only in cathepsin B‐overexpressed cancer cells rather than normal cells. In tumor‐bearing mice, PNPs showed high tumor accumulation via the nanoparticle‐driven enhanced permeation and retention (EPR) effect and they also exhibited remarkable therapeutic efficacy against glioma under microLED‐mediated light irradiation via chemo‐photodynamic combination therapy. Accordingly, applying microLED with PNPs is an outstanding strategy to defeat glioma with cooperative chemo‐photodynamic effects, minimal invasiveness, and desirable systemic/local safety.
A Triple‐Role Nano‐Therapy by NADH@HMONs‐AAL for Precision Treatment of Cognitive Dysfunction Induced by Neuroinflammation through the Nose‐Brain Pathway
Authors: Du Xiyu , Zhao Gang , Zhou Yushan , Yang Li , Jiang Zhaoshun , Liu Songbin , Zhang Xixue , Lu Min , Lu Han , Gu Weidong 
Published: June 2024

AbstractSepsis‐associated encephalopathy (SAE) occurs in 70% of severely infected patients and the incidence rate of 17.7%. Previous studies have shown that Nicotinamide adenine dinucleotide (NADH) may treat nerve damage, but its inability to directly penetrate cell membranes limits its application. In this study, a nanoparticle (NADH@HMONs‐AAL) with one modification of triple‐role nano‐therapy is creatively prepared to treat SAE, and it is delivered to the brain through intranasal administration. There are three‐fold to introduce aleuria aurantia lectin (AAL) to modify the surface of NADH@HMONs. First, AAL adhered to HMONs as a mesoporous blocker to prevent drug leakage. Then, AAL increases the hydrophilic and hydrophobic properties of the nanoparticles, making NADH@HMONs more easily enter cells. Third, AAL allowed NADH@HMONs to bind to L‐fucose residues expressed on the olfactory epithelium, reducing clearance by cilia and effectively transporting NADH@HMONs‐AAL to the brain. This research indicates that NADH@HMONs‐AAL can directly enter the brain through intranasal administration and rapidly release NADH within cells. It repairs neuronal damage in the hippocampus and improves cognitive dysfunction in SAE‐induced cognitive neuroinflammatory mice. In conclusion, the nanoparticle prepared in this study using precision can alleviate the cognitive dysfunction caused by SAE, and provide a promising delivery route and method for treating neurological diseases.
Bioinspired Wearable Pulse Sensors for Ambulant Cardiovascular Monitoring and Biometric Authentication
Authors: Meng Keyu , Liu Zixiao , Xiao Xiao , Manshaii Farid , Li Pei , Yin Junyi , Wang Haiyan , Mei Haixia , Sun Yubo , He Ximin , Yang Jun , Chen Jun 
Published: June 2024

AbstractThe measurement accuracy of current wearable pulse sensors is grandly challenged by motion artifacts caused by body biomechanical activities. In this study, a honeycomb‐structure‐inspired wearable pulse sensor is reported which not only performs ambulant cardiovascular monitoring but also realizes biometric authentication utilizing the acquired individual pulse wave profiles. The sensor showcases an impressive sensitivity of 46.2 mV Pa−1, a swift response time of 21 ms, and exceptional durability (minimal degradation after 6000 cycles). For practical application in clinical settings, the sensor is able to record pulse signals continuously and accurately from individuals aged between 27 and 57 years, especially including a 29‐year‐old pregnant woman. Leveraging deep learning algorithms, the sensor further utilizes individual pulse wave profiles for biometric authentication, reaching a classification accuracy of up to 99.4%. The honeycomb‐structure‐inspired wearable pulse sensor marks a significant advancement in the field of practical cardiovascular monitoring and biometric authentication.
Marine‐Derived Nanozyme‐Crosslinked Self‐Adaptive Hydrogels for Programmed Regulating the Regeneration Process
Authors: Wang Tianyi , Wen Mengyao , Li Na , Zhang Lianbing , Xue Yumeng , Shang Li 
Published: June 2024

AbstractSelf‐adaptive hydrogels that can specifically respond to pathological cues and match the highly ordered tissue regeneration process are significantly on‐demand for effective wound management. Herein, multifunctional marine‐derived gold clusterzyme (AuNCs)‐based self‐adaptive hydrogels with microenvironment triggered release behavior are elaborately fabricated for on‐demand antioxidant, anti‐inflammatory and immunoregulation. The marine mussel‐derived catechol ligands (L‐3,4‐dihydroxyphenylalanine) endow AuNCs with enhanced superoxide dismutase‐mimic activity due to their high affinity to superoxide anion free radical (O2−•) and unique electron transfer mechanism, leading to 100% inhibition of O2−•. Upon uniformly crosslinking with phenylboronic acid‐modified marine‐derived sodium alginate (PBA‐Sa), the obtained AuNCs@PBA‐Sa hydrogels exhibit outstanding self‐healing property, tunable degradation and good removability. Meanwhile, AuNCs can greatly enhance the mechanical property and confer the hydrogel with favorable tissue adhesion for rapid hemostasis. Furthermore, injectable AuNCs@PBA‐Sa hydrogels can not only adapt their shape to the irregular wound, but also smartly adapt their microstructure to the physiological microenvironment of diabetic wound, leading to the responsive release of AuNCs upon the break of boronate ester bonds. The released gold clusterzymes can actively induce the generation of M2‐macrophage, demonstrating an outstanding anti‐inflammatory and pro‐regeneration effect. Therefore, the present multifunctional clusterzyme‐based self‐adaptive hydrogels hold great potential for remolding the dynamic tissue regeneration microenvironment and smart wound management.