bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher rate of skin rash in a phase II trial with weekly nanoparticle albumin-bound paclitaxel and cisplatin combination in Chinese breast cancer patients
Authors: Tang Li Chen , Wang Bi Yun , Sun Si , Zhang Jian , Jia Zhen , Lu Yun Hua , Di Geng Hong , Shao Zhi Ming , Hu Xi Chun 
Published: May 2013

Abstracts

Background
The aim of this sub-study is to explore the incidence of skin rash among advanced breast cancer(ABC) patients in a phase II trial treated with weekly nab-paclitaxel and cisplatin combination.

Methods
Nab-paclitaxel(125 mg/m2) was administered on days 1, 8, 15, followed by cisplatin(75 mg/m2) on day 1 every 28 day cycle until disease progression, intolerable toxicities or the maximum of 6 cycles. Patients who received at least one injection of the study drug were included in this analysis of the incidence of skin rash among Chinese patients. Toxicity was graded using the CTCAE4.0 criteria. Statistical analysis was carried out by using SPSS 16.0 (SPSS Inc, Chicago, IL).

Results
Seventy three patients were enrolled and eligible for analysis. A total of 384 cycles were administered at the time of this analysis. Rash was presented in 27 patients (37.0%). The most common sites involved were face (14/27), neck (14/27), limbs (18/27) and frictional parts of the trunk (10/27). Macular and papular rash with pruritus commonly occurred 2 (95% CI: 1–7) days after the first day of chemotherapy. Only one patient developed Grade 3 skin toxicity with generalized erythroderma and disfigurement of the face requiring dose reduction. The rash gradually regressed 2 (95% CI: 1–10) days after antihistamines used, but pigmentation remained in 13/27 cases. The incidence rate of skin rash was significantly higher than what has been described for western patients (approximate 4%, P < 0.0001).

Conclusion
A higher rate of maculo-papular rash occurred in Chinese breast cancer patients treated with weekly nab-paclitaxel compared to western patients. The albumin component of nab-paclitaxel might be the cause of the skin disorder.

Trial registration

NCT01149798
Details acquired from medical history and patients’ experience of empathy – two sides of the same coin
Authors: Ohm Friedemann , Vogel Daniela , Sehner Susanne , Wijnen-Meijer Marjo , Harendza Sigrid 
Published: May 2013

AbstractBackgroundHistory taking and empathetic communication are two important aspects in successful physician-patient interaction. Gathering important information from the patient’s medical history is needed for effective clinical decision making while empathy is relevant for patient satisfaction. We wanted to investigate whether medical students near graduation are able to combine both skills as required in daily medical practice.MethodsThirty near graduates from Hamburg Medical School participated in an assessment for clinical competences including a consultation hour with five standardized patients. Each patient interview was videotaped and standardized patients rated participants with the CARE questionnaire for consultation and relational empathy. All videotaped interviews were rated with a checklist based on the number of important medical aspects for each case. Data were analysed with the linear mixed model to correct for random effects. Regression analysis was performed to look for correlations between the number of questions asked by a participant and their respective empathy rating.ResultsOf the 123 aspects that could have been gathered in total, students only requested 56.4% (95% CI 53.5-59.3). While no difference between male and female participants was found, a significant difference (p < .001) was observed between the two parts of the checklist with 61.1% (95% CI 57.9-64.3) of aspects asked for in part 1 (patient’s symptoms) versus 52.0 (95 47.4-56.7) in part 2 (further history). All female standardized patients combined rated female participants (mean score 14.2, 95% CI 12.3-16.3) to be significantly (p < .01) more empathetic than male participants (mean score 19.2, 95% CI 16.3-22.6). Regression analysis revealed no correlation between the number of medical aspects gathered by a participant and his or her respective empathy score given by the standardized patient in the CARE questionnaire.ConclusionGathering sufficient medical data from a patient’s history and empathetic communication are two completely separate sides of the coin of history taking. While both skills have to be acquired during medical school training with particular focus on their respective learning objectives, medical students need to be provided with additional learning and feedback opportunities where they can be observed exercising both skills combined as required in physicians’ daily practice.
Use of V(D)J recombination excision circles to identify T- and B-cell defects and to monitor the treatment in primary and acquired immunodeficiencies
Authors: Serana Federico , Chiarini Marco , Zanotti Cinzia , Sottini Alessandra , Bertoli Diego , Bosio Andrea , Caimi Luigi , Imberti Luisa 
Published: May 2013

AbstractT-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) are circular DNA segments generated in T and B cells during their maturation in the thymus and bone marrow. These circularized DNA elements persist in the cells, are unable to replicate, and are diluted as a result of cell division, thus are considered markers of new lymphocyte output. The quantification of TRECs and KRECs, which can be reliably performed using singleplex or duplex real-time quantitative PCR, provides novel information in the management of T- and B-cell immunity-related diseases. In primary immunodeficiencies, when combined with flow cytometric analysis of T- and B-cell subpopulations, the measure of TRECs and KRECs has contributed to an improved characterization of the diseases, to the identification of patients’ subgroups, and to the monitoring of stem cell transplantation and enzyme replacement therapy. For the same diseases, the TREC and KREC assays, introduced in the newborn screening program, allow early disease identification and may lead to discovery of new genetic defects. TREC and KREC levels can also been used as a surrogate marker of lymphocyte output in acquired immunodeficiencies. The low number of TRECs, which has in fact been extensively documented in untreated HIV-infected subjects, has been shown to increase following antiretroviral therapy. Differently, KREC number, which is in the normal range in these patients, has been shown to decrease following long-lasting therapy. Whether changes of KREC levels have relevance in the biology and in the clinical aspects of primary and acquired immunodeficiencies remains to be firmly established.
A possible role for CCR5 in the progression of atherosclerosis in HIV-infected patients: a cross-sectional study
Authors: Fernández-Sender Laura , Alonso-Villaverde Carlos , Rull Anna , Rodríguez-Gallego Esther , Riera-Borrull Marta , Hernández-Aguilera Anna , Camps Jordi , Beltrán-Debón Raúl , Aragonès Gerard , Menendez Javier A , Joven Jorge 
Published: May 2013

AbstractBackgroundChemokines can block viral entry by interfering with HIV co-receptors and are recognised mediators of atherosclerosis development. A number of experimental drugs that inhibit HIV entry arrest the development of atherosclerosis in animal models. We hypothesised that the expression of chemokine receptors in circulating leukocytes is associated with the rate of atherosclerosis progression in HIV-infected patients.MethodsThe increase in intima-media thickness during a 2-year follow-up was used to classify HIV-infected patients (n = 178) as progressors (n = 142) or non-progressors (n = 36) with respect to atherosclerosis. Logistic regression was used to assess variables associated with atherosclerosis progression. Mutations in the CCR5Δ32, CCR2 64I, and CX3CR1 (T280M and V249I) co-receptors as well as the levels of CCR5, CXCR4, CX3CR1, and CCR2 mRNA expression in circulating leukocytes were analysed as independent variables.ResultsAmong the baseline variables, only genetic variants explained the dichotomous outcome. The expression of CCR2 and CXCR4 did not discriminate between progressors and non-progressors. Conversely, CCR5 and CX3CR1 expression was higher in not only progressors but also patients with detectable viral load. The logistic regression, however, demonstrated a significant role for CCR5 expression as a predictor of atherosclerosis progression (B = 2.1, OR = 8.1, p = 0.04) and a negligible effect for CXC3R1 and CCR2 expression.ConclusionsAvailable CCR5 antagonists should be investigated for their potential to delay the course of atherosclerosis in HIV-infected patients.
HER2 expression and relevant clinicopathological features in gastric and gastroesophageal junction adenocarcinoma in a Chinese population
Authors: Shan Ling , Ying Jianming , Lu Ning 
Published: May 2013

Abstract

Background
With varied immunohistochemistry scoring criteria and patient cohorts, HER2-positivity rates in gastric cancer (GC) and gastroesophageal junction (GEJ) adenocarcinoma have been reported with a wide range. Recently standardized scoring criteria for GC and GEJ cancer has been established and recommended. In this study, the frequency of HER2 expression and the relationship between HER2 expression and clinicopathological features were examined in a large cohort of Chinese GC and GEJ cancer patients.

Methods
A total of 1463 patients, including 929 primary GCs and 534 primary GEJ adenocarcinomas, was retrospectively analyzed for HER2 overexpression by immunohistochemistry (IHC). Fluorescence in situ hybridization (FISH) analysis was used in 308 GCs and GEJ adenocarcinoma cases to assess HER2 gene amplification.

Results
HER2 overexpression (3+) was detected in 9.8% of carcinomas and more frequently observed in GEJ cancer cases, in the intestinal type, and in the well or moderately differentiated type (P=0.003, 0.000, and 0.000, respectively). HER2 equivocal (2+) was detected in 14.4% of cases. As for the 308 cases analyzed by FISH, 39 (of 40, 97.5%) IHC 3+ cases, 11 (of 38, 28.9%) IHC 2+ cases, and 3 (of 230, 1.3%) IHC 1+/0 cases showed HER2 gene amplification. A high concordance rate (98.5%) between IHC and FISH was demonstrated.

Conclusions
Approximately 10% of Chinese patients with primary GC and GEJ adenocarcinoma were HER2-positive on IHC. HER2 overexpression was associated with GEJ site, intestinal cancer subtype, and well or moderately differentiated carcinomas.

Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1935951199941072.
Clinico- pathological profile of patients with breast diseases
Authors: Aslam Hafiz Muhammad , Saleem Shafaq , Shaikh Hiba Arshad , Shahid Nazish , Mughal Anum , Umah Ribak 
Published: May 2013

AbstractBackgroundTo evaluate the spectrum of breast diseases and their association with presenting complains of patients.MethodologyIt was a cross sectional study conducted from 1stJanuary 2010 – 30thDecember 2012. A total of 254 breast specimens of patients, who were admitted in Civil Hospital Karachi with breast complaints, were included. Specimens were collected either from mastectomy, lumpectomy or needle biopsy from the admitted patients. Informed written consent was taken from all the patients. All patients with primary breast diseases were included. Patients undergoing chemotherapy or with secondary breast disease and slides with insufficient specimen were excluded. All data was entered and analyzed through SPSS 19.ResultThere were 254 breast lesions, histologically diagnosed in 3 year review period. The overall mean age of patients with breast lesion was 25.18, SD ± 11.73 with a wide age range of 12–74 years. Most common cases identified are benign 191(75.3%), followed by inflammatory 30(11.8%) and malignant lesions 30(11.8%). Most patients presenting with the complain of pain have diagnosis of fibroadenoma 24 (63.2%) while patient with complain of lump also have the most common diagnosis of fibroadenoma 147 (72.8%).ConclusionsStudy shows that in Pakistani females, mostly encountered breast lesion was fibroadenoma. Due to lack of awareness breast diseases present lately. Awareness must be created among women to reduce the mortality and morbidity with breast lesions.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1037059088969395.
The wooly mutation (wly) on mouse chromosome 11 is associated with a genetic defect in Fam83g
Authors: Radden Legairre A , Child Kevin M , Adkins Elisabeth B , Spacek Damek V , Feliciano Aaron M , King Thomas R 
Published: May 2013

Abstract

Background
Mice homozygous for the spontaneous wooly mutation (abbreviated wly) are recognized as early as 3–4 weeks of age by the rough or matted appearance of their coats. Previous genetic analysis has placed wly in a 5.9 Mb interval on Chromosome 11 that contains over 200 known genes. Assignment of wly to one of these genes is needed in order to provide probes that would ultimately facilitate a complete molecular analysis of that gene’s role in the normal and disrupted development of the mammalian integument.

Results
Here, a large intraspecific backcross family was used to genetically map wly to a smaller (0.8 Mb) span on mouse Chromosome 11 that includes fewer than 20 genes. DNA sequencing of the coding regions in two of these candidates known to be expressed in skin has revealed a 955 bp, wly-specific deletion. This deletion, which lies within the coordinates of both Slc5a10 [for solute carrier family 5 (sodium/glucose cotransporter), member 10] and Fam83g (for family with sequence similarity 83, member G), alters the splicing of mutant Fam83g transcripts only, and is predicted to result in a severely truncated (probably non-functional) protein product.

Conclusion
We suggest that this mutation in Fam83g is the likely basis of the mouse wooly phenotype.
Chimeric antigen receptor containing ICOS signaling domain mediates specific and efficient antitumor effect of T cells against EGFRvIII expressing glioma
Authors: Shen Chan-Juan , Yang Yu-Xiu , Han Ethan Q , Cao Na , Wang Yun-Fei , Wang Yi , Zhao Ying-Ying , Zhao Li-Ming , Cui Jian , Gupta Puja , Wong Albert J , Han Shuang-Yin 
Published: May 2013

Abstract

Background
Adoptive transfer of chimeric antigen receptor (CAR)-modified T cells appears to be a promising immunotherapeutic strategy. CAR combines the specificity of antibody and cytotoxicity of cytotoxic T lymphocytes, enhancing T cells’ ability to specifically target antigens and to effectively kill cancer cells. Recent efforts have been made to integrate the costimulatory signals in the CAR to improve the antitumor efficacy. Epidermal growth factor receptor variant III (EGFRvIII) is an attractive therapeutic target as it frequently expresses in glioma and many other types of cancers. Our current study aimed to investigate the specific and efficient antitumor effect of T cells modified with CAR containing inducible costimulator (ICOS) signaling domain.

Methods
A second generation of EGFRvIII/CAR was generated and it contained the EGFRvIII single chain variable fragment, ICOS signaling domain and CD3ζ chain. Lentiviral EGFRvIII/CAR was prepared and human CD3+ T cells were infected by lentivirus encoding EGFRvIII/CAR. The expression of EGFRvIII/CAR on CD3+ T cells was confirmed by flow cytometry and Western blot. The functions of EGFRvIII/CAR+ T cells were evaluated using in vitro and in vivo methods including cytotoxicity assay, cytokine release assay and xenograft tumor mouse model.

Results
Chimeric EGFRvIIIscFv-ICOS-CD3ζ (EGFRvIII/CAR) was constructed and lentiviral EGFRvIII/CAR were made to titer of 106 TU/ml. The transduction efficiency of lentiviral EGFRvIII/CAR on T cells reached around 70% and expression of EGFRvIII/CAR protein was verified by immunoblotting as a band of about 57 kDa. Four hour 51Cr release assays demonstrated specific and efficient cytotoxicity of EGFRvIII/CAR+ T cells against EGFRvIII expressing U87 cells. A robust increase in the IFN-γ secretion was detected in the co-culture supernatant of the EGFRvIII/CAR+ T cells and the EGFRvIII expressing U87 cells. Intravenous and intratumor injection of EGFRvIII/CAR+ T cells inhibited the in vivo growth of the EGFRvIII expressing glioma cells.

Conclusions
Our study demonstrates that the EGFRvIII/CAR-modified T cells can destroy glioma cells efficiently in an EGFRvIII specific manner and release IFN-γ in an antigen dependent manner. The specific recognition and effective killing activity of the EGFRvIII-directed T cells with ICOS signaling domain lays a foundation for us to employ such approach in future cancer treatment.
ATP13A2 (PARK9) protein levels are reduced in brain tissue of cases with Lewy bodies
Authors: Murphy Karen E , Cottle Louise , Gysbers Amanda M , Cooper Antony A , Halliday Glenda M 
Published: May 2013

Abstract

Background

ATP13A2 (PARK9) loss of function mutations are a genetic cause of an early-onset form of Parkinson’s disease (PD), with in vitro studies showing that ATP13A2 deficits lead to lysosomal and mitochondrial dysfunction and α-synuclein accumulation, while elevated ATP13A2 expression reduces α-synuclein toxicity. The three human brain tissue studies assessing changes in ATP13A2 expression in PD produced divergent results; mRNA is increased while protein levels were observed to be either increased or decreased. This apparent conflict in protein levels might have arisen from examining Lewy body disease cases with coexisting Alzheimer-type pathologies.
To assess whether ATP13A2 levels in Lewy body disease are modified by Alzheimer-type β-amyloid deposition, we evaluated cases of pure PD and pure dementia with Lewy bodies (DLB) for changes in ATP13A2, α-synuclein and β-amyloid protein levels in cortical regions with and without Lewy bodies.

Results
In all Lewy body disease cases, we identified decreased ATP13A2 protein levels that correlated with increases in both α-synuclein and β-amyloid. Partial colocalization was observed between ATP13A2 and α-synuclein in Lewy bodies, whereas ATP13A2 did not colocalize with pathological β-amyloid deposition.

Conclusions
Our data show that patients with Lewy body diseases have an overall deficit in ATP13A2 protein levels, with the remaining protein being more insoluble and partially redistributing towards Lewy bodies. This supports the concept that increasing ATP13A2 levels may offer potential therapeutic benefits to patients with Lewy body diseases.
Extensive aggregation of α-synuclein and tau in juvenile-onset neuroaxonal dystrophy: an autopsied individual with a novel mutation in the PLA2G6 gene-splicing site
Authors: Riku Yuichi , Ikeuchi Takeshi , Yoshino Hiroyo , Mimuro Maya , Mano Kazuo , Goto Yoji , Hattori Nobutaka , Sobue Gen , Yoshida Mari 
Published: May 2013

Abstract

Background
Infantile neuroaxonal dystrophy (INAD) is a rare autosomal-recessive neurodegenerative disorder. Patients with INAD usually show neurological symptoms with infant onset and die in childhood. Recently, it was reported that mutations in the PLA2G6 gene cause INAD, but neuropathological analysis of genetically confirmed individuals with neuroaxonal dystrophy has been limited.

Results
Here, we report a Japanese individual with neuroaxonal dystrophy associated with compound heterozygous mutations in the PLA2G6 gene. A novel splice-site mutation resulting in skipping and missense mutations (p.R538C) in exon 9 was identified in the patient. This patient initially presented with cerebellar ataxia at the age of 3 years, which was followed by symptoms of mental retardation, extrapyramidal signs, and epileptic seizure. The patient survived until 20 years of age. Neuropathological findings were characterized by numerous axonal spheroids, brain iron deposition, cerebellar neuronal loss, phosphorylated alpha-synuclein-positive Lewy bodies (LBs), and phosphorylated-tau-positive neurofibrillary tangles. In particular, LB pathology exhibited a unique distribution with extremely severe cortical involvement.

Conclusions
Our results support a genetic clinical view that compound heterozygous mutations with potential residual protein function are associated with a relatively mild phenotype. Moreover, the severe LB pathology suggests that dysfunction of the PLA2G6 gene primarily contributes to LB formation.
Filamentous white matter prion protein deposition is a distinctive feature of multiple inherited prion diseases
Authors: Reiniger Lilla , Mirabile Ilaria , Lukic Ana , Wadsworth Jonathan DF , Linehan Jacqueline M , Groves Michael , Lowe Jessica , Druyeh Ronald , Rudge Peter , Collinge John , Mead Simon , Brandner Sebastian 
Published: May 2013

Abstract

Background
Sporadic, inherited and acquired prion diseases show distinct histological patterns of abnormal prion protein (PrP) deposits. Many of the inherited prion diseases show striking histological patterns, which often associate with specific mutations. Most reports have focused on the pattern of PrP deposition in the cortical or cerebellar grey matter.

Results
We observed that the subcortical white matter in inherited prion diseases frequently contained filamentous depositions of abnormal PrP, and we have analysed by immunohistochemistry, immunofluorescence and electron microscopy 35 cases of inherited prion disease seen at the UK National Prion Clinic. We report here that filamentous PrP is abundantly deposited in myelinated fibres in inherited prion diseases, in particular in those with N-terminal mutations.

Conclusions
It is possible that the presence of filamentous PrP is related to the pathogenesis of inherited forms, which is different from those sporadic and acquired forms.
Liver X receptor activation inhibits osteoclastogenesis by suppressing NF-κB activity and c-Fos induction and prevents inflammatory bone loss in mice
Authors: Kim Hyun-Ju , Yoon Kyung-Ae , Yoon Hye-Jin , Hong Jung Min , Lee Min-Jung , Lee In-Kyu , Kim Shin-Yoon 
Published: May 2013

ABSTRACT
LXRs are nuclear receptors that function as important regulators of lipid homeostasis and inflammatory responses. LXR activation has been shown to suppress RANKL-induced osteoclast differentiation, but its underlying mechanisms and its influence on inflammatory bone destruction remain unclear. In this study, we report that the LXR agonists T0901317 and GW3965 inhibit osteoclastogenesis from primary BMMs in a dose-dependent manner. LXR activation suppressed RANKL-induced transcriptional activity of NF-κB without affecting IκBα degradation and the phosphorylation of p38. LXR agonists significantly suppressed RANKL-induced expression of c-Fos and NFATc1, which are crucial transcription factors for osteoclastogenesis. The activation of LXRs also inhibited RANKL-mediated AP-1 transcriptional activity. Furthermore, LXR activation attenuated PPARγ ligand-induced c-Fos expression, and LXR suppressed AP-1 promoter activity by PPARγ. The inhibitory effect of LXR activation on osteoclastogenesis was reversed by overexpression of c-Fos, suggesting that c-Fos is a downstream target of the antiosteoclastogenic action of LXRs. In addition to osteoclast differentiation, LXR activation accelerated apoptosis in mature osteoclasts by the induction of caspase-3 and -9 activity and Bim expression. Consistent with the in vitro effects we observed, the administration of a LXR agonist protected from bone loss induced by LPS in vivo. Together, our data provide evidence that LXRs may have potential as therapeutic targets for bone resorption-associated diseases.