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Safety switch optimization enhances antibody-mediated elimination of CAR T cells. 安全开关优化增强了抗体介导的 CAR T 细胞清除能力。
Journal of clinical case reports Pub Date : 2022-10-11 eCollection Date: 2022-01-01 DOI: 10.3389/fmmed.2022.1026474
Tamer B Shabaneh, Howell F Moffett, Sylvia M Stull, Thomas Derezes, Leah J Tait, Spencer Park, Stan R Riddell, Marc J Lajoie
{"title":"Safety switch optimization enhances antibody-mediated elimination of CAR T cells.","authors":"Tamer B Shabaneh, Howell F Moffett, Sylvia M Stull, Thomas Derezes, Leah J Tait, Spencer Park, Stan R Riddell, Marc J Lajoie","doi":"10.3389/fmmed.2022.1026474","DOIUrl":"10.3389/fmmed.2022.1026474","url":null,"abstract":"<p><p>Activation of a conditional safety switch has the potential to reverse serious toxicities arising from the administration of engineered cellular therapies, including chimeric antigen receptor (CAR) T cells. The functionally inert, non-immunogenic cell surface marker derived from human epidermal growth factor receptor (EGFRt) is a promising safety switch that has been used in multiple clinical constructs and can be targeted by cetuximab, a clinically available monoclonal antibody. However, this approach requires high and persistent cell surface expression of EGFRt to ensure that antibody-mediated depletion of engineered cells is rapid and complete. Here we show that incorporating a short juxtamembrane sequence into the EGFRt polypeptide enhances its expression on the surface of T cells and their susceptibility to antibody-dependent cellular cytotoxicity (ADCC). Incorporating this optimized variant (EGFRopt) into bicistronic and tricistronic CAR designs results in more rapid <i>in vivo</i> elimination of CAR T cells and robust termination of their effector activity compared to EGFRt. These studies establish EGFRopt as a superior safety switch for the development of next-generation cell-based therapeutics.</p>","PeriodicalId":73664,"journal":{"name":"Journal of clinical case reports","volume":"3 1","pages":"1026474"},"PeriodicalIF":0.0,"publicationDate":"2022-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89667794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Keratoacanthomas Induced by Cat Scratches in an Elderly Woman 老年妇女猫抓致角膜棘瘤1例
Journal of clinical case reports Pub Date : 2021-03-06 DOI: 10.26420/AUSTINJCLINCASEREP.2021.1197
Alawami Az, Elberg Jj, Tannous Zs
{"title":"Keratoacanthomas Induced by Cat Scratches in an Elderly Woman","authors":"Alawami Az, Elberg Jj, Tannous Zs","doi":"10.26420/AUSTINJCLINCASEREP.2021.1197","DOIUrl":"https://doi.org/10.26420/AUSTINJCLINCASEREP.2021.1197","url":null,"abstract":"Background: Keratoacanthomas (KAs) are relatively common self-limited squamous proliferations. It is a matter of debate, whether they are a variant of squamous cell carcinoma or benign neoplasms. The exact etiology is uncertain, but is believed to be multifactorial, and is reportedly associated with trauma. This report describes an elderly woman with multiple keratoacanthomas developing at sites scratched by a pet cat. Methods: A case of a 92-year-old woman with Alzheimer’s disease, presented with multiple rapidly growing, bizarre looking lesions on the left leg. The lesions appeared several weeks after being scratched by a cat. Results: Tissue cultures for bacteria, fungi and atypical mycobacteria were negative. Histopathologic examination was consistent with keratoacanthoma. Conclusion: The development of Keratoacanthomas (KAs) have been associated with actinic damage, genetic susceptibility, carcinogens, immunosuppression and viruses. It also seems that keratoacanthoma has predilection for sites with previous trauma. Our case is a further evidence that trauma and keratoacanthoma are closely related.","PeriodicalId":73664,"journal":{"name":"Journal of clinical case reports","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45494639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cardiac Tamponade - A Hypothyroidism Associated Emergency: A Report of 2 Cases 心脏填塞-甲状腺功能减退相关急症2例报告
Journal of clinical case reports Pub Date : 2021-03-01 DOI: 10.26420/AUSTINJCLINCASEREP.2021.1194
S. Tripathi, Sharma Jb, P Vijayvergia, S. Khichar, Garg Mk
{"title":"Cardiac Tamponade - A Hypothyroidism Associated Emergency: A Report of 2 Cases","authors":"S. Tripathi, Sharma Jb, P Vijayvergia, S. Khichar, Garg Mk","doi":"10.26420/AUSTINJCLINCASEREP.2021.1194","DOIUrl":"https://doi.org/10.26420/AUSTINJCLINCASEREP.2021.1194","url":null,"abstract":"Pericardial effusion in commonly seen in-patient with hypothyroidism but effusion large enough to cause cardiac tamponade is not a common presenting feature whereas myxedema coma is a commonly defined medical emergency in-patient with hypothyroidism. We report 2 cases of hypothyroid associated medical emergencies. First case is a young female with history of recurrent pericardial effusion presenting to the emergency department with cardiac tamponade and later on diagnosed as having hypothyroidism. The second patient is a known case of hypothyroidism non-compliant to thyroid supplement and presented with lethargy, fatigue, decreased talking and breathlessness who was later diagnosed as having myxedema coma and impending cardiac tamponade. Both the patient required percutaneous pericardiocentesis and improved with medical management.","PeriodicalId":73664,"journal":{"name":"Journal of clinical case reports","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45208376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Rare Case of Extensive Spondylodiscitis 一例罕见的广泛性脊柱炎
Journal of clinical case reports Pub Date : 2021-02-01 DOI: 10.26420/AUSTINJCLINCASEREP.2021.1192
S. Nicolau, M. Moniz, J. Jardim, M. Grego
{"title":"A Rare Case of Extensive Spondylodiscitis","authors":"S. Nicolau, M. Moniz, J. Jardim, M. Grego","doi":"10.26420/AUSTINJCLINCASEREP.2021.1192","DOIUrl":"https://doi.org/10.26420/AUSTINJCLINCASEREP.2021.1192","url":null,"abstract":"A 71-year-old man with a history of diabetes mellitus was admitted to our hospital with a 2-week history of fever and low back pain. Physical examination showed fever (38.1°C), painful palpation of the lower lumbar vertebrae and right lower limb paresis. Blood examination revealed an increased white blood cell count (16700x109/L) and C- reactive protein (22,39 mg/dL). Magnetic resonance imaging showed extensive spondylodiscitis, with osteomyelitis of the L5, S1 and S2 vertebral bodies, discitis, large epidural empyema, paraspinal and epidural abscesses. Patient was submitted to surgical treatment and was started on empirical antimicrobial therapy. Blood and intraoperative cultures were negative. Brucellosis and tuberculosis testing was negative. A 10- week course of antimicrobial therapy was performed with progressive decline of acute-phase reactants, reduction in pain and improvement of the neurological deficit. At 1-year follow up with light residual lower back pain and no neurological deficit.","PeriodicalId":73664,"journal":{"name":"Journal of clinical case reports","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43881028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anagrelide Treatment and Congestive Heart Failure in the COVID-19 Era: A Case Report 新冠肺炎时代阿那格列特治疗与充血性心力衰竭1例
Journal of clinical case reports Pub Date : 2021-01-01 DOI: 10.37421/2165-7920.2021.11.1444
Corsini Anna, Fiorini Giulia, Zuffa Elisa, Borghi Claudio, Galie’ Nazzareno
{"title":"Anagrelide Treatment and Congestive Heart Failure in the COVID-19 Era: A Case Report","authors":"Corsini Anna, Fiorini Giulia, Zuffa Elisa, Borghi Claudio, Galie’ Nazzareno","doi":"10.37421/2165-7920.2021.11.1444","DOIUrl":"https://doi.org/10.37421/2165-7920.2021.11.1444","url":null,"abstract":"Background: This case report emphasises the importance of differential diagnosis in dilated cardiomyopathy and the frequent misdiagnosis of congestive heart failure in the COVID-19 era. Case presentation: A patient with Polycythaemia Vera (PV) and no history of cardiac disease developed dyspnoea and radiological signs of pulmonary congestion. He was then treated as a suspected COVID-19 patient. However, echocardiogram showed biventricular dysfunction and severely reduced Left Ventricular Ejection Fraction (LVEF) (22%) without regional wall motion abnormalities. We hypothesised drug-related cardiotoxicity. Conclusion: Particular attention should be paid to patient admitted to Emergency Department (ED) with respiratory symptoms and clinical signs of congestion in order to correctly differentiate COVID-19 related respiratory disease from cardiogenic dyspnoea. Cardiotoxicity should always be ruled out in dilated-hypokinetic cardiomyopathy.","PeriodicalId":73664,"journal":{"name":"Journal of clinical case reports","volume":"11 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70049159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
A Rare Case of Infective Endocarditis Complicated with a Cardiac Abscess Causing Heart Block 感染性心内膜炎合并心脓肿致心脏传导阻滞1例
Journal of clinical case reports Pub Date : 2021-01-01 DOI: 10.37421/2165-7920.2021.11.1456
Veshesh Patel, Collin Tacy, B. Ramírez, Alfredo Lindo, M. Suárez
{"title":"A Rare Case of Infective Endocarditis Complicated with a Cardiac Abscess Causing Heart Block","authors":"Veshesh Patel, Collin Tacy, B. Ramírez, Alfredo Lindo, M. Suárez","doi":"10.37421/2165-7920.2021.11.1456","DOIUrl":"https://doi.org/10.37421/2165-7920.2021.11.1456","url":null,"abstract":"Individuals that have undergone cardiac surgery or heart valve replacement are at increased risk for developing Infective Endocarditis (IE). IE has numerous signs and symptoms as well as complications. However, an interesting and unique presentation of IE can be in an individual showing a complete heart block on EKG. A heart block from an IE will typically present with a cardiac abscess on Transesophageal Echocardiogram (TEE) and coronary Computed Tomography Angiography (CTA). This individual, with a past medical history of transcatheter aortic valve replacement in 2011, was found to have Enterococcus faecalis bacteremia and endocarditis. Soon after discovery of the infection, CTA of the coronaries showed a 7.6 × 4.6 × 2.5 cm loculated pericardial collection consistent of a cardiac abscess. Despite the initiation of antibiotic therapy, this gentleman with bacterial endocarditis had an increased risk of immediate mortality, due to the complete heart block and additional complications. High clinical suspicion and early intervention are warranted for cases of infective endocarditis.","PeriodicalId":73664,"journal":{"name":"Journal of clinical case reports","volume":"11 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70049543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Jordanian Girl with Juvenile Granulose Cell Tumor Presented as Precocious Puberty: A Case Report 以性早熟为表现的约旦女孩少年颗粒细胞瘤1例报告
Journal of clinical case reports Pub Date : 2021-01-01 DOI: 10.37421/2165-7920.2021.11.1463
F. F. Ayyash, Abdalrazzaq Ahmmad Alyassen, Samer Sukre Karadsheh, Ibrahim Mohammad Sawalha, Alia MusaAl-Khlaifat, Alaeddin Ali Saleh, Omar Ashokaibi, Mustafa Al-haji
{"title":"Jordanian Girl with Juvenile Granulose Cell Tumor Presented as Precocious Puberty: A Case Report","authors":"F. F. Ayyash, Abdalrazzaq Ahmmad Alyassen, Samer Sukre Karadsheh, Ibrahim Mohammad Sawalha, Alia MusaAl-Khlaifat, Alaeddin Ali Saleh, Omar Ashokaibi, Mustafa Al-haji","doi":"10.37421/2165-7920.2021.11.1463","DOIUrl":"https://doi.org/10.37421/2165-7920.2021.11.1463","url":null,"abstract":"Objective: Our objective is to explain precocious puberty, type, etiology, investigation, how to differentiate between central and peripheral precocious puberty, and focus on one of the rarest causes of precocious puberty. Case report: In our case of precocious puberty, a two-year-old female presented with bilateral breast enlargement, vaginal secretion, pubic hair, and abdominal swelling. An abdominal and pelvic CT shows a very large ovarian mass. Asalpino-oophorectomy was carried out with regression of symptoms and signs and improvement in laboratory exams. The biopsy showed Juvenile Granulosa Cell Tumors (JGCT). Discussion: Due to an increase in the levels of estradiol and no increase in the gonadotropins (LH, FSH), advanced bone age and height age are compatible with the chronic age of 2 years old, so we think about peripheral precocious puberty. Due to abdominal swelling and patient age (small age), we suspect malignancy, so we did a CT scan and sonography of the pelvis. Conclusion: Every patient with signs and symptoms of precocious puberty must do all the investigation that leads to diagnosis, especially when there is a red flag like in our patient (very small age).","PeriodicalId":73664,"journal":{"name":"Journal of clinical case reports","volume":"11 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70049731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effort Rupture of the Oesophagus (Boerhaave's Syndrome) 食道破裂(布尔哈夫综合征)
Journal of clinical case reports Pub Date : 2021-01-01 DOI: 10.37421/2165-7920.2021.11.1470
J. Callaghan
{"title":"Effort Rupture of the Oesophagus (Boerhaave's Syndrome)","authors":"J. Callaghan","doi":"10.37421/2165-7920.2021.11.1470","DOIUrl":"https://doi.org/10.37421/2165-7920.2021.11.1470","url":null,"abstract":"Boerhaave's Syndrome is a rare condition that develops when the distal oesophagus ruptures, resulting in a high risk of morbidity and fatality. Oesophageal perforations are rare, with an incidence of 3.1 per 1,000,000 per year. Patients with a normal underlying oesophagus are more likely to develop Boerhaave's syndrome. A portion of patients with Boerhaave's syndrome, however, have underlying eosinophilic esophagitis, medication-induced esophagitis, Barrett's disease, or infectious ulcers. A longitudinal oesophageal perforation occurs when a sudden increase in intra-oesophageal pressure is paired with negative intrathoracic pressure, as in severe straining or vomiting, and less frequently in childbirth, seizure, continuous coughing or laughing, or weightlifting.","PeriodicalId":73664,"journal":{"name":"Journal of clinical case reports","volume":"11 1","pages":"1-1"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70049556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fat Embolism in Common Carotid Artery after Temporal Lipofilling in Post-Cancer Reconstruction: A Case Report and Review of the Literature 癌后重建颞部充脂后颈总动脉脂肪栓塞一例报告及文献复习
Journal of clinical case reports Pub Date : 2021-01-01 DOI: 10.37421/2165-7920.2021.11.1462
A. Aydin, M. GomesDavid, S. Cortese, F. Marchal, G. Dolivet
{"title":"Fat Embolism in Common Carotid Artery after Temporal Lipofilling in Post-Cancer Reconstruction: A Case Report and Review of the Literature","authors":"A. Aydin, M. GomesDavid, S. Cortese, F. Marchal, G. Dolivet","doi":"10.37421/2165-7920.2021.11.1462","DOIUrl":"https://doi.org/10.37421/2165-7920.2021.11.1462","url":null,"abstract":"Background: Lipofilling is a common aesthetic and reconstructive procedure. Embolism is a possible complication of every filler, which can be lethal. We describe the case of a 56 years old man who had a fat embolism in the common carotid artery with fatal issue. Case presentation: Our patient initially had a left oropharynx cancer, treated by surgery and adjuvant radiotherapy. Many flaps and graft procedure has been tried to treat an ankyloglossia sequelae, and the effective procedure was a forearm free flap. Lipofilling was performed for a temporal defect after a temporal myocutaneous flap. A common carotid embolism was the source of a severe unilateral stroke, leading patient to the death 15 days after initial surgery. Discussion and conclusion: Reverse-flow mechanism explains the artery tropism of fat embolism in the face, contrary to veinous tropism for fat embolism in the body. Pressure of injection, needle (in contrast to blunt end cannula) and large syringe use are the factors of fat embolism in lipofilling procedure. Volume is not a significative factor.","PeriodicalId":73664,"journal":{"name":"Journal of clinical case reports","volume":"11 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70049692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Langerhans Cell Histiocytosis with Multisystem Involvement in a Young Woman: A Case Report and Literature Review 年轻女性朗格汉斯细胞组织细胞增多症伴多系统累及:1例报告及文献复习
Journal of clinical case reports Pub Date : 2021-01-01 DOI: 10.37421/2165-7920.2021.11.1452
Sheniz Yuzeir, Hinko Varbanov, T. Yordanova, I. Micheva
{"title":"Langerhans Cell Histiocytosis with Multisystem Involvement in a Young Woman: A Case Report and Literature Review","authors":"Sheniz Yuzeir, Hinko Varbanov, T. Yordanova, I. Micheva","doi":"10.37421/2165-7920.2021.11.1452","DOIUrl":"https://doi.org/10.37421/2165-7920.2021.11.1452","url":null,"abstract":"Langerhans Cell Histiocytosis (LCH), also known as Histiocytosis X (HX), is a group of hyperplastic cellular diseases of unknown causes. LCH could affect bones, lungs, central nervous system, liver, thymus, skin, and also lymph nodes. The diagnosis of LCH is difficult to enforce and rarely found in adults, with just about 5 cases per million per year. The present study reports the case of a young woman with LCH with multisystem involvement, including that of the bone, orbit, pulmonary system and central nervous system. The patient received chemotherapy for 6 months and exhibited rapid improvement in the involved systems. The last PET/CT showed metabolic activity in the right iliac bone. One year after completion of the therapy, the patient returned to the hospital showing deteriorating health. The clinical case is interesting not only because of the registered clinical, morphological, and imaging data of histiocytosis but also because of the unclear prognostic and diagnostic importance of this phenomenon.","PeriodicalId":73664,"journal":{"name":"Journal of clinical case reports","volume":"11 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70049825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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