bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-PD1 Following Ipilimumab for Mucosal Melanoma: Durable Tumor Response Associated with Severe Hypothyroidism and Rhabdomyolysis
Authors: Min Le , Hodi F. Stephen 
Published: October 2013

Abstract
Treatment with fully human monoclonal antibodies against programmed death 1 (PD1) receptor has shown great promise for a number of advanced malignancies. Although inflammatory adverse events have been well described with anti-CTL antigen 4 (CTLA4) therapy, experience with the range of adverse effects of anti-PD1 remains comparatively limited. Here, we report on a patient with advanced mucosal melanoma who received four doses of MK-3475, a fully human monoclonal antibody against PD1, and experienced a durable near-complete response but developed severe hypothyroidism, rhabdomyolysis, and acute kidney injury. To our knowledge, this is the first case reported of a patient with advanced mucosal melanoma who responded to anti-PD1 therapy. With the promising antitumor effects of anti-PD1 in a wide array of tumors, we expect an increasing number of patients to be exposed to anti-PD1 therapies. Recognition of infrequent presentations of adverse events such as elevated creatine kinase levels and thyroid disorders in patients who receive anti-PD1 therapy is important. Cancer Immunol Res; 2(1); 15–18. ©2014 AACR.
Effect of Combined Systolic and Diastolic Functional Parameter Assessment for Differentiation of Cardiac Amyloidosis From Other Causes of Concentric Left Ventricular Hypertrophy
Authors: Liu Dan , Hu Kai , Niemann Markus , Herrmann Sebastian , Cikes Maja , Störk Stefan , Gaudron Philipp Daniel , Knop Stefan , Ertl Georg , Bijnens Bart , Weidemann Frank 
Published: October 2013

Background—
Differentiation of cardiac amyloidosis (CA) from other causes of concentric left ventricular hypertrophy remains a clinical challenge, especially in patients with preserved ejection fraction at the early disease stages.

Methods and Results—

Consecutive hypertrophic patients with CA, isolated arterial hypertension, Fabry disease, and Friedreich ataxia (n=25 per group) were investigated; 25 healthy volunteers served as a control group. Standard echocardiography was performed, and segmental longitudinal peak systolic strain (LSsys) in the septum was assessed by 2-dimensional speckle tracking imaging. Indices of left ventricular hypertrophy and ejection fraction were similar among all patient groups. Deceleration time of early filling was significantly lower in patients with CA (147±46 milliseconds) compared with those with isolated arterial hypertension, Fabry disease, or control subjects (all
P
<0.0125). Septal basal LSsys (−6±2%) was significantly lower in patients with CA compared with those with isolated arterial hypertension (−14±6%), Fabry disease (−12±5%), Friedreich ataxia (−16±2%), or control subjects (−17±3%; all
P
<0.001), whereas septal apical LSsys was similar among all patient groups and control subjects (all
P
>0.05). A data-driven cutoff value for the ratio of septal apical to basal LSsys ratio >2.1 differentiated CA from other causes of left ventricular hypertrophy (sensitivity, 88%; specificity, 85%; positive predictive value, 67%; negative predictive value, 96%). The prevalence of septal apical to basal LSsys ratio >2.1 plus deceleration time of early filling <200 milliseconds was 88% in CA but 0% in all other groups.

Conclusions—
A systolic septal longitudinal base-to-apex strain gradient (septal apical to basal LSsys ratio >2.1), combined with a shortened diastolic deceleration time of early filling (deceleration time of early filling <200 milliseconds), aids in differentiating CA from other causes of concentric left ventricular hypertrophy.
Time for a Paradigm Shift With Computerized Adaptive Testing of General Physical Function Outcomes Measurements
Authors: Hung Man , Franklin Jeremy D. , Hon Shirley D. , Cheng Christine , Conrad Jillian , Saltzman Charles L. 
Published: October 2013

Background: Patient-reported outcomes (PRO) are critical to understanding the value of orthopedic treatments. We hypothesized that use of the computerized adaptive testing from a well-characterized physical function item bank would show superiority in assessing all levels of physical function compared to current standard generic physical function outcomes instruments for foot and ankle patients. Methods: In a population of 126 foot and ankle patients we compared the psychometric properties for three PROs: the Physical Function subscale of the Medical Outcomes General Health Survey (SF-36 PF) version 2, the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Computerized Adaptive Test (CAT), and the Lower Extremity (LE) CAT. A Rasch item response theory (IRT) model was applied to assess and compare the fit, dimensionality, reliability, validity, and coverage. Results: The unexplained variance for the PF CAT was 3.9% and the LE CAT was 2.1%, suggesting each instrument explained a single concept. The SF-36 PF had more concerning unexplained variance of 7.6%. We found no floor or ceiling effects for the PF CAT, a minimal floor effect (1.6%) but no ceiling effect for the LE CAT, and an 11.1% floor effect and 9.5% ceiling effect for the SF-36 PF. Conclusion: Foot and ankle clinicians and researchers interested in measuring patient perceived functional outcomes with a generic instrument should consider using either the PF CAT or the LE CAT rather than the SF-36 PF. Further studies comparing these CATs to anatomic specific instruments are needed. Level of Evidence: Level I, diagnostic study.
Group therapy for anxiety in children with autism spectrum disorder
Authors: McConachie Helen , McLaughlin Eleanor , Grahame Victoria , Taylor Helen , Honey Emma , Tavernor Laura , Rodgers Jacqui , Freeston Mark , Hemm Cahley , Steen Nick , Le Couteur Ann 
Published: October 2013

Aim: To investigate the acceptability and feasibility of adapted group therapy for anxiety in children with autism spectrum disorder in a pilot randomised controlled trial. Method: A total of 32 children aged 9–13 years were randomised to immediate or delayed therapy using the ‘Exploring Feelings’ manual (Attwood, 2004). Child and parent groups were run in parallel, for seven weekly sessions, under the supervision of experienced psychologists. The primary blinded outcome measures addressed change in overall functioning and in severity of the primary anxiety diagnosis after 3 months. Results: Children met diagnostic criteria for 1–6 anxiety disorders (median 3). At end point, both parents and children in the immediate therapy group were more likely to report a reduction in anxiety symptoms. Fidelity of delivery of the group therapy was high, and attendance was 91%. Conclusions: This pilot trial established that children and families were willing to be recruited and randomised, the outcome measures were acceptable, the format and content of the groups were feasible within UK child and adolescent mental health services, the intervention was appreciated by families and attrition was very small.
Researching collaborative processes in domestic violence perpetrator programs: Benchmarking for situation improvement
Authors: Diemer Kristin , Humphreys Cathy , Laming Chris , Smith Joanie 
Published: October 2013

Summary This article reports on research undertaken in Victoria, Australia with workers from men’s behavior change programs (perpetrator programs) to explore the extent of the collaborative processes established with police, child protection, and other human service organizations. It poses the question: how do regional collaborative arrangements and the pathways to referral reflect the responsiveness of men’s behavior change programs to domestic violence service integration? It builds on a strand of research highlighting the significance of the wider domestic violence intervention system in holding men who use violence accountable. Findings A research tool was designed around a Practice Matrix to outline different dimensions against which expectations of collaboration could be benchmarked in men’s behavior change programs. It was found that at this early stage within the domestic violence reform process in Victoria that the integration of programs within the wider domestic violence sector was relatively undeveloped. The feedback loops between agencies, which enable reporting on attendance, breaches of intervention orders, changes to the risk assessment, and progress at formal review points were relatively undeveloped. However, the formal engagement within domestic violence regional committees and with police was more developed. Application Social workers, particularly in the vulnerable children’s area provide referrals to men’s behavior change programs. Active involvement in feedback, risk assessment review, monitoring for change support the accountability and collaborative effort required to strengthen the effectiveness of men’s behavior change and enhance the safety of women and their children.
Education and employment training supports for newcomers to Canada’s middle-sized urban/rural regions: Implications for social work practice
Authors: Sethi Bharati 
Published: October 2013

The last decade has witnessed the movement of immigrants from Canada’s largest urban centers—Toronto, Vancouver, and Montreal—to smaller urban-rural communities. Nevertheless, very little scholarship exists on newcomer integration in these communities. Furthermore, social work literature examining the perspective of service providers who work with newcomers is lacking. Grand Erie is a middle-sized urban/rural region in Ontario, Canada that is experiencing increased migration of newcomers. This paper focuses on a part of a larger Community-based participatory research on ‘Newcomer Settlement and Integration in Education, Training, Employment, Health and Social Support’ in Grand Erie and discusses the findings in the education and training domain. Data were gathered from 212 newcomers (men and women) and 237 service providers using survey questionnaires. Findings Most of the newcomers in this study had not taken any education or employment courses post-migration. The qualitative and quantitative responses from participants (newcomers and service providers) highlight a lack of affordable child care and poor transportation infrastructure in this region as significant barriers to newcomers’ ability to take education or employment courses especially in case of visible minority women. Applications The results of the study suggest that there is an opportunity for social workers to build partnerships with community agencies as well as with policy-makers at regional and provincial levels to foster the social, economic, and political integration of new immigrants in the host society.
metaBEETL: high-throughput analysis of heterogeneous microbial populations from shotgun DNA sequences
Authors: Ander Christina , Schulz-Trieglaff Ole B , Stoye Jens , Cox Anthony J 
Published: October 2013

Abstract
Environmental shotgun sequencing (ESS) has potential to give greater insight into microbial communities than targeted sequencing of 16S regions, but requires much higher sequence coverage. The advent of next-generation sequencing has made it feasible for the Human Microbiome Project and other initiatives to generate ESS data on a large scale, but computationally efficient methods for analysing such data sets are needed.
Here we present metaBEETL, a fast taxonomic classifier for environmental shotgun sequences. It uses a Burrows-Wheeler Transform (BWT) index of the sequencing reads and an indexed database of microbial reference sequences. Unlike other BWT-based tools, our method has no upper limit on the number or the total size of the reference sequences in its database. By capturing sequence relationships between strains, our reference index also allows us to classify reads which are not unique to an individual strain but are nevertheless specific to some higher phylogenetic order.
Tested on datasets with known taxonomic composition, metaBEETL gave results that are competitive with existing similarity-based tools: due to normalization steps which other classifiers lack, the taxonomic profile computed by metaBEETL closely matched the true environmental profile. At the same time, its moderate running time and low memory footprint allow metaBEETL to scale well to large data sets.
Code to construct the BWT indexed database and for the taxonomic classification is part of the BEETL library, available as a github repository at git@github.com:BEETL/BEETL.git.
Messenger RNA levels of podocyte-associated proteins in subjects with different degrees of glucose tolerance with or without nephropathy
Authors: do Nascimento Jonathan Fraportti , Canani Luis H , Gerchman Fernando , Rodrigues Patricia G , Joelsons Gabriel , dos Santos Mariane , Pereira Sane , Veronese Francisco V 
Published: October 2013

Abstract

Background
To investigate gene expression of podocyte-specific proteins in urine of diabetes and prediabetes subjects and the association of these proteins with albuminuria.

Methods
Fifteen controls, 19 prediabetes, and 67 diabetes subjects were included. Messenger RNA of nephrin, podocin, podocalyxin, synaptopodin, TRPC6, alpha-actinin-4, and TGF-β1 were measured using RT-PCR. Podocyte marker expression was correlated with albuminuria, glycemic control, and renal function. The diagnostic performance of the genes used to detect increased albuminuria was assessed using ROC curves and Poisson regressions.

Results
Podocyte marker expression was significantly higher in diabetic subjects. Urinary nephrin was correlated with increasing levels of albuminuria; risk of albuminuria increased by 20% for every one-unit increase in the log10 of nephrin mRNA. Nephrinuria was found in 53%, 71%, and 90% of normo-, micro-, and macroalbuminuric diabetes subjects, respectively (p = 0.023). Urinary nephrin, podocalyxin, TRPC6, podocin, and alpha actinin-4 were correlated with glycemic control and albuminuria but not with renal function.

Conclusions
Diabetes subjects had higher urinary mRNA levels of podocyte proteins than nondiabetic subjects, even the normoalbuminuric patients. Nephrinuria was correlated with diabetic nephrophathy stage and predicted pathological albuminuria. Urinary mRNA levels of podocyte markers of prediabetic subjects did not differ from controls.
Metallothionein 1G functions as a tumor suppressor in thyroid cancer through modulating the PI3K/Akt signaling pathway
Authors: Fu Jiao , Lv Hongjun , Guan Haixia , Ma Xiaoying , Ji Meiju , He Nongyue , Shi Bingyin , Hou Peng 
Published: October 2013

Abstract

Background

MT1G inactivation mediated by promoter methylation has been reported in thyroid cancer. However, the role of MT1G in thyroid carcinogenesis remains unclear. The aim of this study is to examine the biological functions and related molecular mechanisms of MT1G in thyroid cancer.

Methods
Methylation-specific PCR (MSP) was performed to analyze promoter methylation of MT1G and its relationship with clinicopathological characteristics of papillary thyroid cancer (PTC) patients. Conventional and real-time quantitative RT-PCR assays were used to evaluate mRNA expression. The functions of ectopic MT1G expression were determined by cell proliferation and colony formation, cell cycle and apoptosis, as well as cell migration and invasion assays.

Results

MT1G expression was frequently silenced or down-regulated in thyroid cancer cell lines, and was also significantly decreased in primary thyroid cancer tissues compared with non-malignant thyroid tissues. Promoter methylation, along with histone modification, contributes to MT1G inactivation in thyroid tumorigenesis. Moreover, our data showed that MT1G hypermethylation was significantly positively associated with lymph node metastasis in PTC patients. Importantly, restoring MT1G expression in thyroid cancer cells dramatically suppressed cell growth and invasiveness, and induced cell cycle arrest and apoptosis through inhibiting phosphorylation of Akt and Rb.

Conclusions
We have for the first time revealed that MT1G appears to be functional tumor suppressor involved in thyroid carcinogenesis mainly through modulating the phosphatidylinositol-3-kinase (PI3K)/Akt pathway and partially through regulating the activity of Rb/E2F pathway in this study.
Antioxidant potential, cytotoxic activity and total phenolic content of Alpinia pahangensis rhizomes
Authors: Phang Chung-Weng , Malek Sri Nurestri Abd , Ibrahim Halijah 
Published: October 2013

Abstract

Background

Alpinia pahangensis, a wild ginger distributed in the lowlands of Pahang, Malaysia, is used by the locals to treat flatulence. In this study, the antioxidant and cytotoxic activities of the crude aqueous methanol and fractionated extracts of Alpinia pahangensis against five different cancer and one normal cell lines were investigated. The total phenolic content of each extract and its fractions were also quantified. This is the first report on the antioxidant and cytotoxic activities of Alpinia pahangensis extract.

Methods
In the current study, the crude methanol and fractionated extract of the rhizomes of Alpinia pahangensis were investigated for their antioxidant activity using four different assays namely, the DPPH scavenging activity, superoxide anion scavenging, β-carotene bleaching and reducing power assays whilst their phenolic contents were measured by the Folin-Ciocalteu’s method.

In vitro neutral red cytotoxicity assay was employed to evaluate the cytotoxic activity against five different cancer cell lines, colon cancer (HCT 116 and HT-29), cervical cancer (Ca Ski), breast cancer (MCF7) and lung cancer (A549) cell lines, and one normal cell line (MRC-5). The extract that showed high cytotoxic activity was further investigated for its chemical constituents by GC-MS (gas chromatography–mass spectrometry) analysis.

Results
The ethyl acetate fraction showed the strongest DPPH radical scavenging (0.35 ± 0.094 mg/ml) and SOD activities (51.77 ± 4.9%) whilst the methanol extract showed the highest reducing power and also the strongest antioxidant activity in the β-carotene bleaching assays in comparison to other fractions. The highest phenolic content was found in the ethyl acetate fraction, followed by the crude methanol extract, hexane and water fractions. The results showed a positive correlation between total phenolic content with DPPH radical scavenging capacities and SOD activities. The hexane fraction showed potent cytotoxic effect against KB, Ca Ski and HCT 116 cell lines with IC50 of 5.8 ± 0.1 and 9.1 ± 2.0 ug/ml, respectively. The major components of hexane fraction analysed by GC-MS analysis were mostly methyl esters.

Conclusions
The current study suggests that the methanol extract and ethyl acetate fraction of A. pahangensis is a potential source of natural antioxidant for protective as well as prevention of life-threatening diseases. The hexane fraction of A. pahangensis may have the potential to be developed into therapeutic option for treating cancer.
Reversal of chemosensitivity and induction of cell malignancy of a non-malignant prostate cancer cell line upon extracellular vesicle exposure
Authors: Panagopoulos Kiriaki , Cross-Knorr Sam , Dillard Christen , Pantazatos Dionysios , Del Tatto Michael , Mills David , Goldstein Lisa , Renzulli Joseph , Quesenberry Peter , Chatterjee Devasis 
Published: October 2013

Abstract

Background
Extracellular vesicle (EV) trafficking is a fundamental cellular process that occurs in cells and is required for different aspects of pathophysiology. EV trafficking leads to changes in cellular function including apoptosis, angiogenesis and proliferation required for increased tumor formation.

Results
We report several phenotypic changes mediated by EVs isolated from non-malignant and malignant prostate cells as well as patient biopsied prostate tumor samples. EVs can reverse the resistance of prostate cancer cells to camptothecin EVs isolated from non-malignant PrECs (Prostate Epithelial Cells) can reverse soft agar colony formation of malignant DU145 cells, with the reciprocal effect observed. Isolation of EVs from 2 Gleason grade 8 prostate cancer patients significantly induced soft agar colony formation of non-malignant PrECs. We have identified proteins via antibody and Mass spectrometry analysis that may be responsible for the phenotypic changes. Mass spectrometry analysis of protein lysates using ProteoIQ revealed protein candidates associated with gene ontology annotations that may be responsible for this phenotypic change. Ingenuity Pathway Analysis was used to identify statistically relevant canonical pathways and functions associated the protein IDs and expression values obtained using ProteoIQ. Western blot analysis confirmed the increase of 14-3-3 zeta, pRKIP and prohibitin protein levels in PrEC cells co-cultured with patient EVs. 14-3-3 proteins were also found as common proteins of 3 other Gleason grade 8 patients.

Conclusion
Our study provides a rational basis to further investigate putative proteins, such as 14-3-3 and prohibitin and genetic factors that may be responsible for phenotypic changes that are associated with prostate cancer progression.
Notch signaling activation contributes to cardioprotection provided by ischemic preconditioning and postconditioning
Authors: Zhou Xue-liang , Wan Li , Xu Qi-rong , Zhao Yong , Liu Ji-chun 
Published: October 2013

Abstract

Background
Notch signaling is known to be activated following myocardial ischemia, but its role in cardioprotection provided by ischemic preconditioning (IPC) and ischemic postconditioning (IPost) remains unclear.

Methods
Lentiviral vectors were constructed to overexpress or knockdown N1ICD in H9c2 cardiomyocyte and rat heart exposed to ischemia reperfusion injury (IRI), IPC or IPost.

Results
Notch1 signaling was activated during myocardial IPC and IPost, and could enhance cell viability and inhibit apoptosis. Furthermore, activated Notch1 signaling stabilized mitochondrial membrane potential and reduced reactive oxygen species induced by IRI. The cardioprotection provided by activated Notch1 signaling resembled that of IPC and IPost, which was related to Stat3 activation and regulation of apoptosis related proteins. Furthermore, in langendorff heart perfusion model, activated Notch1 signaling restored cardiac function, decreased lactate dehydrogenase release and limited infarct size after myocardial ischemia. Conclusions: Notch1 signaling is activated and mediates cardioprotection provided by IPC and Ipost. Notch1 signaling may represent a potential new pharmacologic mimic for cardioprotection of ischemic heart disease.