bluuebunny/crossref_metadata_2025_split huggingface dataset:
Otolaryngology–Head and Neck Surgery Physician Work Force Issues
Authors: Kim Jin Suk C. , Cooper Richard A. , Kennedy David W. 
Published: February 2012

ObjectiveTo predict future trends in the otolaryngology workforce and propose solutions to correct the identified discrepancies between supply and demand.Study DesignEconomic modeling and analysis.SettingData sets at national medical and economic organizations.Subjects and MethodsBased on current American Academy of Otolaryngology–Head and Neck Surgery, American Medical Association, and National Residency Matching Program data sets, population census data, and historical physician growth demand curves, the future otolaryngology workforce supply and demand were modeled. Adjustments were made for projected increases in mid‐level providers, increased insurance coverage, and the potential effects of lifestyle preferences.ResultsThere are currently approximately 8600 otolaryngologists in the United States. Estimated demand by 2025 is 11,127 based on projected population growth and anticipated increase in insurance coverage. With an average retirement age of 65 years and no increase in PGY‐1 positions for the specialty, the number of otolaryngologists in 2025 will be approximately 2500 short of projected demand. This shortfall will not be adequately compensated by mid‐level providers performing less intensive services and may be increased by lifestyle preferences and changing demographics among medical students and residents. The current geographic maldistribution of otolaryngologists is likely to be exacerbated.ConclusionThe specialty needs to actively plan for the coming otolaryngologist shortage and train mid‐level providers within the specialty. Failure to plan appropriately may result in a reduction in scope of practice of high‐intensity services, which will likely remain a physician prerogative. Given the limited likelihood of a significant increase in residency slots, strong consideration should be given to shortening the base otolaryngology training program length.
Revision of Failed Osteochondral Autologous Transplantation Procedure for Chronic Talus Osteochondral Lesion With Iliac Crest Graft and Autologous Matrix-Induced Chondrogenesis
Authors: Wiewiorski Martin , Miska Matthias , Nicolas Guillaume , Valderrabano Victor 
Published: February 2012

This article describes a novel technique for treatment of recurrent large osteochondral lesions of the talus using autologous matrix-induced chondrogenesis with a collagen I/III matrix. Level of evidence: Therapeutic level IV
Efficacy of repeat myeloablative chemotherapy with autologous stem-cell support in multiple myeloma
Authors: Menzel Helge , Hinmüller Katarzyna , Kolb Hans-Jochem , Schuster Tibor , Hoellein Alexander , Peschel Christian , Dechow Tobias , Keller Ulrich 
Published: February 2012

Objective: Induction high-dose chemotherapy followed by myeloablative melphalan (HD-Mel) treatment and autologous hematopoietic stem-cell support (autoSCT) is a standard treatment for multiple myeloma (MM) either upfront or in relapse after conventional treatment. We performed a retrospective analysis of consecutive patients undergoing a late repeat HD-Mel/autoSCT treatment for MM. Methods: Data from 24 consecutive patients with MM who underwent a myeloablative treatment with HD-Mel late after completion of upfront first high-dose therapy were assessed for toxicity, response, progression-free survival (PFS) and time to next treatment (TTNT). These data were correlated with the results obtained after the initial high dose therapy and autoSCT. Results: A total of 23 patients were treated with novel drugs (lenalidomide, thalidomide, bortezomib) after relapse to initial autoSCT. The median overall survival (OS) of all patients was 90 months. 19 patients (79%) achieved a very good partial remission (VGPR) or complete remission (CR) after initial autoSCT, compared with 42% after late autoSCT. PFS and TTNT were 19 and 24 months after initial compared with 13 and 21 months after late autoSCT. Univariate analysis identified initial response duration and the achievement of a CR/VGPR after the initial transplantation to be associated with prolonged response after repeat autoSCT. Conclusions: Our data indicate that late high-dose treatment followed by autoSCT is safe and effective after upfront intensive treatment, can bridge to allogeneic SCT, and encourage collection of an additional graft.
Identification of TRIB1 R107L gain-of-function mutation in human acute megakaryocytic leukemia
Authors: Yokoyama Takashi , Toki Tsutomu , Aoki Yoshihiro , Kanezaki Rika , Park Myoung-ja , Kanno Yohei , Takahara Tomoko , Yamazaki Yukari , Ito Etsuro , Hayashi Yasuhide , Nakamura Takuro 
Published: February 2012

Abstract
Trib1 has been identified as a myeloid oncogene in a murine leukemia model. Here we identified a TRIB1 somatic mutation in a human case of Down syndrome–related acute megakaryocytic leukemia. The mutation was observed at well-conserved arginine 107 residue in the pseudokinase domain. This R107L mutation remained in leukocytes of the remission stage in which GATA1 mutation disappeared, suggesting the TRIB1 mutation is an earlier genetic event in leukemogenesis. The bone marrow transfer experiment showed that acute myeloid leukemia development was accelerated by transducing murine bone marrow cells with the R107L mutant in which enhancement of ERK phosphorylation and C/EBPα degradation by Trib1 expression was even greater than in those expressing wild-type. These results suggest that TRIB1 may be a novel important oncogene for Down syndrome–related acute megakaryocytic leukemia.
Calcium blockers decrease the bortezomib resistance in mantle cell lymphoma via manipulation of tissue transglutaminase activities
Authors: Jung Hyun Joo , Chen Zheng , Wang Michael , Fayad Luis , Romaguera Jorge , Kwak Larry W. , McCarty Nami 
Published: February 2012

AbstractAlthough bortezomib is clinically approved for the treatment of mantle cell lymphoma (MCL), only limited effects of this treatment have been demonstrated. To improve survival for bortezomib-resistant patients, it is necessary to develop new therapeutic strategies. In the present study, we used biochemical and molecular methodologies to demonstrate that tissue transglutaminase (TG) activates downstream NF-κB signaling pathways. The signaling axis from TG to NF-κB could be a new therapeutic target to overcome bortezomib resistance in MCL. TG2 is a calcium-dependent protein cross-linking enzyme reported to be overexpressed in various cancer cells. We found that MCL cells expressed elevated levels of TG2 and that the modification of TG2 activities altered NF-κB expression and downstream signaling in MCL cells. When TG2 signaling was inhibited by calcium blockers, the combination of a calcium blocker (perillyl alcohol) with bortezomib suppressed NF-κB expression and improved the cytotoxicity of bortezomib in MCL cells. Our study is the first to show the expression of TG2 and the contribution of TG2 to NF-κB signaling in MCL. TG2 inhibition may be used as an alternative target anti-MCL therapy, and calcium blockers may be combined with bortezomib to overcome the bortezomib resistance in MCL.
In vivo effects of eltrombopag on platelet function in immune thrombocytopenia: no evidence of platelet activation
Authors: Psaila Bethan , Bussel James B. , Linden Matthew D. , Babula Bracken , Li Youfu , Barnard Marc R. , Tate Chinara , Mathur Kanika , Frelinger Andrew L. , Michelson Alan D. 
Published: February 2012

AbstractThe effects of eltrombopag, a thrombopoietin-receptor agonist, on platelet function in immune thrombocytopenia (ITP) are not fully characterized. This study used whole blood flow cytometry to examine platelet function in 20 patients receiving eltrombopag treatment at days 0, 7, and 28. Platelet surface expression of activated GPIIb/IIIa, P-selectin, and GPIb was measured with and without low and high adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP) concentrations. Before eltrombopag treatment with no ex vivo agonist, platelet activation was higher in ITP patients than controls. Platelet GPIb and activated GPIIb/IIIa expression without added agonist was unchanged following eltrombopag treatment, whereas a slight increase in P-selectin was observed. Expression of P-selectin and activated GPIIb/IIIa in response to high-dose ADP was lower during eltrombopag treatment than at baseline. Eltrombopag led to a slight increase in platelet reactivity to TRAP only in responders to eltrombopag but not to levels above those in controls; whole blood experiments demonstrated that this increase was probably because of higher platelet counts rather than higher platelet reactivity. In conclusion, although thrombocytopenic ITP patients have higher baseline platelet activation than controls, eltrombopag did not cause platelet activation or hyper-reactivity, irrespective of whether the platelet count increased.
Caspase-9 mediates the apoptotic death of megakaryocytes and platelets, but is dispensable for their generation and function
Authors: White Michael J. , Schoenwaelder Simone M. , Josefsson Emma C. , Jarman Kate E. , Henley Katya J. , James Chloé , Debrincat Marlyse A. , Jackson Shaun P. , Huang David C. S. , Kile Benjamin T. 
Published: February 2012

Abstract
Apoptotic caspases, including caspase-9, are thought to facilitate platelet shedding by megakaryocytes. They are known to be activated during platelet apoptosis, and have also been implicated in platelet hemostatic responses. However, the precise requirement for, and the regulation of, apoptotic caspases have never been defined in either megakaryocytes or platelets. To establish the role of caspases in platelet production and function, we generated mice lacking caspase-9 in their hematopoietic system. We demonstrate that both megakaryocytes and platelets possess a functional apoptotic caspase cascade downstream of Bcl-2 family-mediated mitochondrial damage. Caspase-9 is the initiator caspase, and its loss blocks effector caspase activation. Surprisingly, steady-state thrombopoiesis is unperturbed in the absence of caspase-9, indicating that the apoptotic caspase cascade is not required for platelet production. In platelets, loss of caspase-9 confers resistance to the BH3 mimetic ABT-737, blocking phosphatidylserine (PS) exposure and delaying ABT-737–induced thrombocytopenia in vivo. Despite this, steady-state platelet lifespan is normal. Casp9−/− platelets are fully capable of physiologic hemostatic responses and functional regulation of adhesive integrins in response to agonist. These studies demonstrate that the apoptotic caspase cascade is required for the efficient death of megakaryocytes and platelets, but is dispensable for their generation and function.
Inequalities for convex and s-convex functions on Δ = [a, b] × [c, d]
Authors: Özdemir Muhamet Emin , Kavurmaci Havva , Akdemir Ahmet Ocak , Avci Merve 
Published: February 2012

AbstractIn this article, two new lemmas are proved and inequalities are established for co-ordinated convex functions and co-ordinateds-convex functions.Mathematics Subject Classification (2000): 26D10; 26D15.
From red to white urine: a patient's nightmare with a rather benign outcome
Authors: Knier Benjamin , Büschges-Seraphin Beatrix , Hilgers Karl F , Amann Kerstin U , Uder Michael , Eckardt Kai-Uwe , Jacobi Johannes 
Published: February 2012

Abstract

Background
Chyluria is a medical condition with presence of chyle in the urine. The disease is most prevalent in endemic regions of Africa and the Indian subcontinent where it is mostly caused by parasitic infections, particularly lymphatic filariasis due to wucheria bancrofti. Non-parasitic chyluria, however, is a very rare finding.

Case Presentation
We report the case of a 48 year old woman who developed a lymphorenal fistula with chyluria following ureterrenoscopy with biopsies taken for urological work-up of persistent macrohematuria. Renal biopsy confirmed the diagnosis of benign familial hematuria due to thin basement nephropathy, a condition frequently associated with episodes of macrohematuria.

Conclusions
This case highlights a rare case of non-parasitic chyluria as a complication of urological work-up for macrohematuria of benign nature.
Brain metastases from hepatocellular carcinoma: clinical features and prognostic factors
Authors: Jiang Xiao-Bing , Ke Chao , Zhang Guan-Hua , Zhang Xiang-Heng , Sai Ke , Chen Zhong-Ping , Mou Yong-Gao 
Published: February 2012

Abstract

Background
Brain metastases (BM) from hepatocellular carcinoma (HCC) are extremely rare and are associated with a poor prognosis. The aim of this study was to define clinical outcome and prognostic determinants in patients with BM from HCC.

Methods
Between January 1994 and December 2009, all patients with HCC and BM treated in Sun Yat-sen University Cancer Center were retrospectively reviewed. Univariate and multivariate survival analyses were performed to identify possible prognostic factors.

Results
Forty-one patients were diagnosed with BM from HCC, an incidence of 0.47%. The median age at diagnosis of BM was 48.5 years. Thirty-three patients (80.5%) developed extracranial metastases at diagnosis of BM, and 30 patients (73.2%) had hepatitis B. Intracranial hemorrhage occurred in 19 patients (46.3%). BM were treated primarily either with whole brain radiation therapy (WBRT; 5 patients), stereotactic radiosurgery (SRS; 7 patients), or surgical resection (6 patients). The cause of death was systemic disease in 17 patients and neurological disease in 23. Patients in a high RPA (recursive partitioning analysis) class, treated with conservatively and without lung metastases, tended to die from neurological disease. Median survival after the diagnosis of BM was 3 months (95% confidence interval: 2.2-3.8 months). In multivariate analysis, the presence of extracranial metastases, a low RPA class and aggressive treatment, were positively associated with improved survival.

Conclusions
BM from HCC is rare and associated with an extremely poor prognosis. However, patients with a low RPA class may benefit from aggressive treatment. The clinical implication of extracranial metastases in HCC patients with BM needs further assessment.
Adenovirus-mediated delivery of CALR and MAGE-A3 inhibits invasion and angiogenesis of glioblastoma cell line U87
Authors: Liu Xin-Li , Zhao Dan , Sun Da-Peng , Wang Yang , Li Yan , Qiu Feng-Qi , Ma Ping 
Published: February 2012

Abstract

Background
The management of patients with glioblastoma multiforme is difficult. Poor results have led to a search for novel therapeutic approaches. Gene therapy that could be both anti-invasive and antiangiogenic would be ideal. In this study, we constructed the recombinant adenoviral vector Ad-CALR/MAGE-A3 and evaluated its antitumor effects on glioblastoma in vitro and in vivo.

Methods
In this study, CALR and MAGE-A3 genes were delivered to the glioblastoma cell line U87, using adenovirus (Ad-CALR/MAGE-A3). U87 glioblastoma cells were transfected with Ad-green fluorescent protein to identify the multiplicity of infection. The expressions of CALR and MAGE-A3 were detected by PCR and Western blot. Cell proliferation was measured by MTT assay. Cell apoptosis was assessed by Annexin-V FITC/PI double staining flow cytometry. The invasive potential of U87 cells was determined by Matrigel invasion assay. Tube formation assay was used to detect the effects on angiogenesis of human umbilical vein endothelial cells. Protein expressions of PI3K/AKT, Erk1/2 and MMP-2/-9 in transfected cells were detected by Western blot. In vivo, the effects of Ad-CALR/MAGE-A3 on tumor growth and angiogenesis of U87 glioblastoma xenografts in nude mice were investigated.

Results
The expressions of CALR and MAGE-A3 in U87 cells resulted in the suppression of cell proliferation and invasion properties, and induced cell apoptosis. The Erk MAPK, PI3K/AKT pathways and expressions of MMP-2/-9 were inhibited in Ad-CALR/MAGE-A3-transfected cells. Outcomes of the tube formation assay confirmed the antiangiogenic effect of CALR. Moreover, in the in vivo model of glioblastoma, intratumoral injection of Ad-CALR/MAGE-A3 suppressed tumor growth and angiogenesis.

Conclusion
Although Ad-CALR/MAGE-A3 and Ad-CALR demonstrated antiangiogenic effects on U87 cells, the repression of invasion was significant only in Ad-CALR/MAGE-A3-treated cells. To our knowledge, this is the first description of a role for combined CALR and MAGE-A3 in the anti-invasion and antiangiogenesis of U87.
Antibody-mediated encephalitis: a treatable cause of schizophrenia
Authors: Lennox Belinda R. , Coles Alasdair J. , Vincent Angela 
Published: February 2012

SummaryPsychiatrists need to be vigilant for the newly recognised and treatable disorder of antibody-mediated encephalitis. Psychiatric symptoms are common, and individuals with the disorder often present initially to psychiatric services. We describe the clinical features of the disorder and make recommendations for further investigations.
Putting the efficacy of psychiatric and general medicine medication into perspective: review of meta-analyses
Authors: Leucht Stefan , Hierl Sandra , Kissling Werner , Dold Markus , Davis John M. 
Published: February 2012

BackgroundThe efficacy of psychopharmacological treatments has been called into question. Psychiatrists are unfamiliar with the effectiveness of common medical drugs.AimsTo put the efficacy of psychiatric drugs into the perspective of that of major medical drugs.MethodWe searched Medline and the Cochrane Library for systematic reviews on the efficacy of drugs compared with placebo for common medical and psychiatric disorders, and systematically presented the effect sizes for primary efficacy outcomes.ResultsWe included 94 meta-analyses (48 drugs in 20 medical diseases, 16 drugs in 8 psychiatric disorders). There were some general medical drugs with clearly higher effect sizes than the psychotropic agents, but the psychiatric drugs were not generally less efficacious than other drugs.ConclusionsAny comparison of different outcomes in different diseases can only serve the purpose of a qualitative perspective. The increment of improvement by drug over placebo must be viewed in the context of the disease's seriousness, suffering induced, natural course, duration, outcomes, adverse events and societal values.
Negative childhood experiences and mental health: theoretical, clinical and primary prevention implications
Authors: Read John , Bentall Richard P. 
Published: February 2012

SummaryAfter decades of ignoring or minimising the prevalence and effects of negative events in childhood, researchers have recently established that a broad range of adverse childhood events are significant risk factors for most mental health problems, including psychosis. Researchers are now investigating the biological and psychological mechanisms involved. In addition to the development of a traumagenic neurodevelopmental model for psychosis, the exploration of a range of psychological processes, including attachment and dissociation, is shedding light on the specific aetiologies of discrete phenomena such as hallucinations and delusions. It is argued that the theoretical, clinical and primary prevention implications of our belated focus on childhood are profound.
Use of ECT in patients with an intellectual disability: review
Authors: Collins Jessica , Halder Neel , Chaudhry Nasim 
Published: February 2012

Aims and methodThe literature on the use of electroconvulsive therapy (ECT) in patients with an intellectual disability is scarce, despite a higher prevalence of psychiatric disorders than in the general adult population. We carried out a review of articles published before March 2010. All age ranges, severity of disability and diagnoses were included.ResultsWe found 72 case reports, a retrospective chart review study and other reviews, but no controlled studies. Most patients (79%) showed a positive outcome following ECT. Complications were seen only in 13% and there were no reports of cognitive decline. Many patients relapsed following ECT (32%) and the majority were maintained with medication at follow-up (71%).Clinical implicationsElectroconvulsive therapy is a valuable treatment for this patient group and should be considered earlier as opposed to as a last resort. Obstacles to its use include diagnostic difficulties, ethical and legal issues, a lack of objective measurements and uncertainty about its safety in this population.
Recovery Star: validating user recovery
Authors: Dickens Geoff , Weleminsky Judy , Onifade Yetunde , Sugarman Philip 
Published: February 2012

Aims and methodMental Health Recovery Star is a multifaceted 10-item outcomes measure and key-working tool that has been widely adopted by service providers in the UK. We aimed to explore its factorial validity, internal consistency and responsiveness. Recovery Star readings were conducted twice with 203 working-age adults with moderate to severe mental health problems attending a range of mental health services, and a third time with 113 of these individuals.ResultsMental Health Recovery Star had high internal consistency and appeared to measure an underlying recovery-oriented construct. Results supported a valid two-factor structure which explained 48% of variance in Recovery Star ratings data. Two Recovery Star items (‘relationships’ and ‘addictive behaviour’) did not load onto either factor. There was good statistically significant item responsiveness, and no obvious item redundancy. Data for a small number of variables were not normally distributed and the implications of this are discussed.Clinical implicationsRecovery Star has been received enthusiastically by both mental health service providers and service users. This study provides further evidence for its adoption in recovery-focused mental health services and indicates that items relating to addictive behaviour, responsibilities and work could be further developed in future.
Psychiatric in-patients, violence and the criminal justice system
Authors: Wilson Simon , Murray Kevin , Harris Mike , Brown Michael 
Published: February 2012

SummaryThere is ambivalence about prosecuting psychiatric in-patients for violent offences. This ambivalence is reflected in the Memorandum of Understanding that exists between the Crown Prosecution Service and the NHS Security Management Service. This has led to an unwelcome change in practice when the police ask for information from an individual's consultant psychiatrist, the police requesting information about the individual's cognitive abilities at the time of the alleged offence and using this to make decisions about prosecution. However, there is also guidance on this area from other sources. We describe this and make further suggestions for dealing with these requests.