bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical determinants of bipolar mitotic spindle assembly and stability in fission yeast
Authors: Blackwell Robert , Edelmaier Christopher , Sweezy-Schindler Oliver , Lamson Adam , Gergely Zachary R. , O’Toole Eileen , Crapo Ammon , Hough Loren E. , McIntosh J. Richard , Glaser Matthew A. , Betterton Meredith D.
Published: January 2017

A physical model that exhibits de novo bipolar spindle assembly is used to study the mechanisms of spindle bipolarity.
Dynamic interactions between a membrane binding protein and lipids induce fluctuating diffusivity
Authors: Yamamoto Eiji , Akimoto Takuma , Kalli Antreas C. , Yasuoka Kenji , Sansom Mark S. P.
Published: January 2017

The number of interacting lipids regulates the diffusivity of a peripheral membrane protein bound on a membrane surface.
Complement C5a receptor is the key initiator of neutrophil adhesion igniting immune complex–induced arthritis
Authors: Miyabe Yoshishige , Miyabe Chie , Murooka Thomas T. , Kim Edward Y. , Newton Gail A. , Kim Nancy D. , Haribabu Bodduluri , Luscinskas Francis W. , Mempel Thorsten R. , Luster Andrew D.
Published: January 2017

C5aR directly initiates neutrophil adhesion required for immune complex–induced arthritis.
Decentralising and integrating HIV services in community-based health systems: a qualitative study of perceptions at macro, meso and micro levels of the health system
Authors: Otiso Lilian , McCollum Rosalind , Mireku Maryline , Karuga Robinson , de Koning Korrie , Taegtmeyer Miriam
Published: January 2017

Introduction

HIV services at the community level in Kenya are currently delivered largely through vertical programmes. The funding for these programmes is declining at the same time as the tasks of delivering HIV services are being shifted to the community. While integrating HIV into existing community health services creates a platform for increasing coverage, normalising HIV and making services more sustainable in high-prevalence settings, little is known about the feasibility of moving to a more integrated approach or about how acceptable such a move would be to the affected parties.

Methods

We used qualitative methods to explore perceptions of integrating HIV services in two counties in Kenya, interviewing national and county policymakers, county-level implementers and community-level actors. Data were recorded digitally, translated, transcribed and coded in NVivo10 prior to a framework analysis.

Results

We found that a range of HIV-related roles such as counselling, testing, linkage, adherence support and home-based care were already being performed in the community in an ad hoc manner. However, respondents expressed a desire for a more coordinated approach and for decentralising the integration of HIV services to the community level as parallel programming had resulted in gaps in HIV service and planning. In particular, integrating home-based testing and counselling within government community health structures was considered timely.

Conclusions

Integration can normalise HIV testing in Kenyan communities, integrate lay counsellors into the health system and address community desires for a household-led approach.
Expression of the interleukin-21 and phosphorylated extracellular signal regulated kinase 1/2 in Kimura disease
Authors: Chen Qing-li , Li Chen-xi , Shao Bo , Gong Zhong-cheng , Liu Hui , Ling Bin , Abasi Keremu , Hu Lu-lu , Wang Bing , Yin Xiao-peng
Published: January 2017

Objective

To investigate the expressions of interleukin (IL)-21 and phosphorylated extracellular signal regulated kinase 1/2 (pERK1/2) in Kimura disease (KD) and to correlate the findings with clinical and prognostic variables.

Methods

Immunohistochemical analysis of IL-21 and pERK1/2 was performed in 18 cases of KD and five gender- and age-matched control samples. Clinical data were extracted and patients followed up for a mean period of 32.1 months.

Results

After a mean follow-up period of 32.1 months (range 1–102 months), recurrence was diagnosed as the end point for seven patients—that is, a 44% (7/16) cumulative recurrence rate. In comparison with gender- and age-matched controls, patients showed strong in situ expressions of IL-21 and pERK1/2, respectively (p<0.05). Patients with strong IL-21 staining intensity and overexpression of pERK1/2 had a lower recurrence rate than those with moderate staining intensity (p=0.049, p=0.019, respectively). However, differences were not statistically significant by gender, age, eosinophils, location, multiplicity, laterality, size, duration and primary outbreak. pERK1/2 was the independent prognostic factor (p=0.020), while age, gender, eosinophils, multiplicity, laterality, size, duration, primary outbreak and expression of IL-21 were not.

Conclusions

This study suggests that the IL-21/pERK1/2 pathway is activated in KD, and pERK1/2 might be considered as a potential prognostic indicator in KD.
Ophthalmic artery occlusion after Pipeline Embolization Device placement with reconstitution of flow via an endoleak: a report of two cases
Authors: Adix Michael L , Kaminsky Ian A , Choi In Sup
Published: January 2017

The Pipeline Embolization Device (PED) is a flow diverting stent used in the treatment of a wide variety of intracranial aneurysms. The device differs from traditional stents used in stent-assisted coil embolization in that it has a tighter lattice structure with smaller cell sizes designed specifically to disrupt blood flow into aneurysms rather than only to retain coils within aneurysms. While the PED has been shown to be safe and effective, it has a unique risk profile that includes side branch and perforator vessel occlusion. Side branch occlusion in particular has been noted in several articles to occur at a relatively high rate with coverage of the ophthalmic artery origin by the PED. In this series, we present two cases of ophthalmic artery occlusion after PED placement with reconstitution of flow via an endoleak.
Relay-balloon technique for recanalization of acute symptomatic proximal internal carotid artery occlusion with short balloon-tipped guiding catheter landing zone
Authors: Lee Sang Hun , Lee Dong Geun , Kwon Sun U , Lee Deok Hee
Published: January 2017

Background

Endovascular recanalization of a completely occluded proximal internal carotid artery (ICA) with underlying stenosis may be challenging owing to a possible thrombotic component. This is especially true when the landing zone for a balloon-tipped guiding catheter (BGC) at the bulb portion is insufficient. Sequential application of the balloons of a BGC and an angioplasty catheter may prevent thromboembolism during revascularization. This study analyzed the safety and effectiveness of this relay-balloon technique.

Methods

Ten consecutive patients with acute symptomatic proximal ICA occlusion were treated by the relay-balloon technique. Outcomes analyzed included technical success rate, procedure-related complications, and short-term clinical outcomes.

Results

Successful revascularization was achieved in all 10 patients. One patient experienced a post-procedural infarct extension, but there was no change in National Institutes of Health Stroke Scale (NIHSS) score. Mean NIHSS score decreased from 12.0±5.6 (range 0–18) initially to 6.8±5.4 (range 0–18) at discharge.

Conclusions

The relay-balloon technique is safe and effective in the endovascular revascularization of acute symptomatic proximal ICA occlusions, which are at high risk of distal thromboembolism due to insufficient landing zone for the BGC.
Right heart function during simulated altitude in patients with pulmonary arterial hypertension
Authors: Seccombe Leigh M , Chow Vincent , Zhao Wei , Lau Edmund M T , Rogers Peter G , Ng Austin C C , Veitch Elizabeth M , Peters Matthew J , Kritharides Leonard
Published: January 2017

Objective

Patients with pulmonary arterial hypertension (PAH) are often recommended supplemental oxygen for altitude travel due to the possible deleterious effects of hypoxia on pulmonary haemodynamics and right heart function. This includes commercial aircraft travel; however, the direct effects and potential risks are unknown.

Methods

Doppler echocardiography and gas exchange measures were investigated in group 1 patients with PAH and healthy patients at rest breathing room air and while breathing 15.1% oxygen, at rest for 20 min and during mild exertion.

Results

The 14 patients with PAH studied were clinically stable on PAH-specific therapy, with functional class II (n=11) and III (n=3) symptoms when tested. Measures of right ventricular size and function were significantly different in the PAH group at baseline as compared to 7 healthy patients (p<0.04). There was no evidence of progressive right ventricular deterioration during hypoxia at rest or under exertion. Pulmonary arterial systolic pressure (PASP) increased in both groups during hypoxia (p<0.01). PASP in hypoxia correlated strongly with baseline PASP (p<0.01). Pressure of arterial oxygen correlated with PASP in hypoxia (p<0.03) but not at baseline, with three patients with PAH experiencing significant desaturation. The duration and extent of hypoxia in this study was tolerated well despite a mild increase in symptoms of breathlessness (p<0.01).

Conclusions

Non-invasive measures of right heart function in group 1 patients with PAH on vasodilator treatment demonstrated a predictable rise in PASP during short-term simulated hypoxia that was not associated with a deterioration in right heart function.
SDHDPromoter Mutations Ablate GABP Transcription Factor Binding in Melanoma
Authors: Zhang Tongwu , Xu Mai , Makowski Matthew M. , Lee Christine , Kovacs Michael , Fang Jun , Willems Esther , Trent Jeffrey M. , Hayward Nicholas K. , Vermeulen Michiel , Brown Kevin M.
Published: January 2017

SDHD encodes subunit D of the succinate dehydrogenase complex, an integral membrane protein. Across cancer types, recurrent SDHD promoter mutations were reported to occur exclusively in melanomas, at a frequency of 4% to 5%. These mutations are predicted to disrupt consensus ETS transcription factor–binding sites and are correlated with both reduced SDHD gene expression and poor prognosis. However, the consequence of these mutations on SDHD expression in melanoma is still unclear. Here, we found that expression of SDHD in melanoma correlated with the expression of multiple ETS transcription factors, particularly in SDHD promoter wild-type samples. Consistent with the predicted loss of ETS transcription factor binding, we observed that recurrent hotspot mutations resulted in decreased luciferase activity in reporter assays. Furthermore, we demonstrated specific GABPA and GABPB1 binding to probes containing the wild-type promoter sequences, with binding disrupted by the SDHD hotspot promoter mutations in both quantitative mass spectrometry and band-shift experiments. Finally, using siRNA-mediated knockdown across multiple melanoma cell lines, we determined that loss of GABPA resulted in reduced SDHD expression at both RNA and protein levels. These data are consistent with a key role for GABPA/B1 as the critical ETS transcription factors deregulating SDHD expression in the context of highly recurrent promoter mutations in melanoma and warrant a detailed search for other recurrent promoter mutations that create or disrupt GABPA consensus sequences. Cancer Res; 77(7); 1649–61. ©2017 AACR.
Bone Marrow Adipocytes Facilitate Fatty Acid Oxidation Activating AMPK and a Transcriptional Network Supporting Survival of Acute Monocytic Leukemia Cells
Authors: Tabe Yoko , Yamamoto Shinichi , Saitoh Kaori , Sekihara Kazumasa , Monma Norikazu , Ikeo Kazuho , Mogushi Kaoru , Shikami Masato , Ruvolo Vivian , Ishizawa Jo , Hail Numsen , Kazuno Saiko , Igarashi Mamoru , Matsushita Hiromichi , Yamanaka Yasunari , Arai Hajime , Nagaoka Isao , Miida Takashi , Hayashizaki Yoshihide , Konopleva Marina , Andreeff Michael
Published: January 2017

Leukemia cells in the bone marrow must meet the biochemical demands of increased cell proliferation and also survive by continually adapting to fluctuations in nutrient and oxygen availability. Thus, targeting metabolic abnormalities in leukemia cells located in the bone marrow is a novel therapeutic approach. In this study, we investigated the metabolic role of bone marrow adipocytes in supporting the growth of leukemic blasts. Prevention of nutrient starvation–induced apoptosis of leukemic cells by bone marrow adipocytes, as well as the metabolic and molecular mechanisms involved in this process, was investigated using various analytic techniques. In acute monocytic leukemia (AMoL) cells, the prevention of spontaneous apoptosis by bone marrow adipocytes was associated with an increase in fatty acid β-oxidation (FAO) along with the upregulation of PPARγ, FABP4, CD36, and BCL2 genes. In AMoL cells, bone marrow adipocyte coculture increased adiponectin receptor gene expression and its downstream target stress response kinase AMPK, p38 MAPK with autophagy activation, and upregulated antiapoptotic chaperone HSPs. Inhibition of FAO disrupted metabolic homeostasis, increased reactive oxygen species production, and induced the integrated stress response mediator ATF4 and apoptosis in AMoL cells cocultured with bone marrow adipocytes. Our results suggest that bone marrow adipocytes support AMoL cell survival by regulating their metabolic energy balance and that the disruption of FAO in bone marrow adipocytes may be an alternative, novel therapeutic strategy for AMoL therapy. Cancer Res; 77(6); 1453–64. ©2017 AACR.
Differential PI3Kδ Signaling in CD4+ T-cell Subsets Enables Selective Targeting of T Regulatory Cells to Enhance Cancer Immunotherapy
Authors: Ahmad Shamim , Abu-Eid Rasha , Shrimali Rajeev , Webb Mason , Verma Vivek , Doroodchi Atbin , Berrong Zuzana , Samara Raed , Rodriguez Paulo C. , Mkrtichyan Mikayel , Khleif Samir N.
Published: January 2017

To modulate T-cell function for cancer therapy, one challenge is to selectively attenuate regulatory but not conventional CD4+ T-cell subsets [regulatory T cell (Treg) and conventional T cell (Tconv)]. In this study, we show how a functional dichotomy in Class IA PI3K isoforms in these two subsets of CD4+ T cells can be exploited to target Treg while leaving Tconv intact. Studies employing isoform-specific PI3K inhibitors and a PI3Kδ-deficient mouse strain revealed that PI3Kα and PI3Kβ were functionally redundant with PI3Kδ in Tconv. Conversely, PI3Kδ was functionally critical in Treg, acting there to control T-cell receptor signaling, cell proliferation, and survival. Notably, in a murine model of lung cancer, coadministration of a PI3Kδ-specific inhibitor with a tumor-specific vaccine decreased numbers of suppressive Treg and increased numbers of vaccine-induced CD8 T cells within the tumor microenvironment, eliciting potent antitumor efficacy. Overall, our results offer a mechanistic rationale to employ PI3Kδ inhibitors to selectively target Treg and improve cancer immunotherapy. Cancer Res; 77(8); 1892–904. ©2017 AACR.
Somatic Ephrin Receptor Mutations Are Associated with Metastasis in Primary Colorectal Cancer
Authors: Mathot Lucy , Kundu Snehangshu , Ljungström Viktor , Svedlund Jessica , Moens Lotte , Adlerteg Tom , Falk-Sörqvist Elin , Rendo Verónica , Bellomo Claudia , Mayrhofer Markus , Cortina Carme , Sundström Magnus , Micke Patrick , Botling Johan , Isaksson Anders , Moustakas Aristidis , Batlle Eduard , Birgisson Helgi , Glimelius Bengt , Nilsson Mats , Sjöblom Tobias
Published: January 2017

The contribution of somatic mutations to metastasis of colorectal cancers is currently unknown. To find mutations involved in the colorectal cancer metastatic process, we performed deep mutational analysis of 676 genes in 107 stages II to IV primary colorectal cancer, of which half had metastasized. The mutation prevalence in the ephrin (EPH) family of tyrosine kinase receptors was 10-fold higher in primary tumors of metastatic colorectal than in nonmetastatic cases and preferentially occurred in stage III and IV tumors. Mutational analyses in situ confirmed expression of mutant EPH receptors. To enable functional studies of EPHB1 mutations, we demonstrated that DLD-1 colorectal cancer cells expressing EPHB1 form aggregates upon coculture with ephrin B1 expressing cells. When mutations in the fibronectin type III and kinase domains of EPHB1 were compared with wild-type EPHB1 in DLD-1 colorectal cancer cells, they decreased ephrin B1–induced compartmentalization. These observations provide a mechanistic link between EPHB receptor mutations and metastasis in colorectal cancer. Cancer Res; 77(7); 1730–40. ©2017 AACR.
Prostate Cancer Patients with Late Radiation Toxicity Exhibit Reduced Expression of Genes Involved in DNA Double-Strand Break Repair and Homologous Recombination
Authors: van Oorschot Bregje , Uitterhoeve Lon , Oomen Ilja , ten Cate Rosemarie , Medema Jan Paul , Vrieling Harry , Stalpers Lukas J.A. , Moerland Perry D. , Franken Nicolaas A.P.
Published: January 2017

Severe late damage to normal tissue is a major limitation of cancer radiotherapy in prostate cancer patients. In a recent retrospective study, late radiation toxicity was found to relate to a decreased decay of γ-H2AX foci and reduced induction of DNA double-strand break repair genes. Here, we report evidence of prognostic utility in prostate cancer for γ-H2AX foci decay ratios and gene expression profiles derived from ex vivo–irradiated patient lymphocytes. Patients were followed ≥2 years after radiotherapy. Clinical characteristics were assembled, and toxicity was recorded using the Common Terminology Criteria (CTCAE) v4.0. No clinical factor was correlated with late radiation toxicity. The γ-H2AX foci decay ratio correlated negatively with toxicity grade, with a significant difference between grade ≥3 and grade 0 patients (P = 0.02). A threshold foci decay ratio, determined in our retrospective study, correctly classified 23 of 28 patients with grade ≥3 toxicity (sensitivity 82%) and 9 of 14 patients with grade 0 toxicity (specificity 64%). Induction of homologous recombination (HR) repair genes was reduced with increasing toxicity grade. The difference in fold induction of the HR gene set was most pronounced between grade 0 and grade ≥3 toxicity (P = 0.008). Notably, reduced responsiveness of HR repair genes to irradiation and inefficient double-strand break repair correlated with severe late radiation toxicity. Using a decay ratio classifier, we correctly classified 82% of patients with grade ≥3 toxicity, suggesting a prognostic biomarker for cancer patients with a genetically enhanced risk for late radiation toxicity to normal tissues after radiotherapy. Cancer Res; 77(6); 1485–91. ©2017 AACR.
Biomarker Dynamics in B-cell Lymphoma: A Longitudinal Prospective Study of Plasma Samples Up to 25 Years before Diagnosis
Authors: Späth Florentin , Wibom Carl , Krop Esmeralda J.M. , Johansson Ann-Sofie , Bergdahl Ingvar A. , Vermeulen Roel , Melin Beatrice
Published: January 2017

The B-cell activation markers CXCL13, sCD23, sCD27, and sCD30 are associated with future lymphoma risk. However, a lack of information about the individual dynamics of marker–disease association hampers interpretation. In this study, we identified 170 individuals who had donated two prediagnostic blood samples before B-cell lymphoma diagnosis, along with 170 matched cancer-free controls from the Northern Sweden Health and Disease Study. Lymphoma risk associations were investigated by subtype and marker levels measured at baseline, at the time of the repeated sample, and with the rate of change in the marker level. Notably, we observed strong associations between CXCL13, sCD23, sCD27, and sCD30 and lymphoma risk in blood samples collected 15 to 25 years before diagnosis. B-cell activation marker levels increased among future lymphoma cases over time, while remaining stable among controls. Associations between slope and risk were strongest for indolent lymphoma subtypes. We noted a marked association of sCD23 with chronic lymphocytic leukemia (ORSlope = 28, Ptrend = 7.279 × 10−10). Among aggressive lymphomas, the association between diffuse large B-cell lymphoma risk and slope was restricted to CXCL13. B-cell activation seemed to play a role in B-cell lymphoma development at early stages across different subtypes. Furthermore, B-cell activation presented differential trajectories in future lymphoma patients, mainly driven by indolent subtypes. Our results suggest a utility of these markers in predicting the presence of early occult disease and/or the screening and monitoring of indolent lymphoma in individual patients. Cancer Res; 77(6); 1408–15. ©2017 AACR.
Disease Characteristics and Prognostic Implications of Cell-Surface FLT3 Receptor (CD135) Expression in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group
Authors: Tarlock Katherine , Alonzo Todd A. , Loken Michael R. , Gerbing Robert B. , Ries Rhonda E. , Aplenc Richard , Sung Lillian , Raimondi Susana C. , Hirsch Betsy A. , Kahwash Samir B. , McKenney Amy , Kolb E. Anders , Gamis Alan S. , Meshinchi Soheil
Published: January 2017

Purpose: The FLT3 cell-surface receptor tyrosine kinase (CD135) is expressed in a majority of both acute lymphoid leukemia (ALL) and myeloid leukemia (AML). However, the prognostic significance of CD135 expression in AML remains unclear. We therefore evaluated the association between FLT3 surface expression and disease characteristics and outcomes in pediatric patients with AML.

Experimental Design: We analyzed FLT3 receptor expression on AML blasts by multi-dimensional flow cytometry and its association with disease characteristics, clinical outcomes, and FLT3 transcript level in 367 children with AML treated on the Children's Oncology Group trial AAML0531.

Results: There was high variability in blast CD135 cell-surface expression across specimens. CD135 expression measured by flow cytometry was not correlated with FLT3 transcript expression determined by quantitative RT-PCR. Overall, CD135 expression was not significantly different for patients with FLT3/WT, FLT3/ITD, or FLT3/ALM (P = 0.25). High cell-surface CD135 expression was associated with FAB M5 subtype (P < 0.001), KMT2A rearrangements (P = 0.009), and inversely associated with inv(16)/t(16;16) (P < 0.001). Complete remission rate, overall survival, disease-free survival, and relapse rates were not significantly different between patients with low and high CD135 expression.

Conclusions: FLT3 cell-surface expression did not vary by FLT3 mutational status, but high FLT3 expression was strongly associated with KMT2A rearrangements. Our study found that there was no prognostic significance of FLT3 cell surface expression in pediatric AML. Clin Cancer Res; 23(14); 3649–56. ©2017 AACR.
Bispecific Antibodies and Antibody–Drug Conjugates (ADCs) Bridging HER2 and Prolactin Receptor Improve Efficacy of HER2 ADCs
Authors: Andreev Julian , Thambi Nithya , Perez Bay Andres E. , Delfino Frank , Martin Joel , Kelly Marcus P. , Kirshner Jessica R. , Rafique Ashique , Kunz Arthur , Nittoli Thomas , MacDonald Douglas , Daly Christopher , Olson William , Thurston Gavin
Published: January 2017

The properties of cell surface proteins targeted by antibody–drug conjugates (ADCs) have not been fully exploited; of particular importance are the rate of internalization and the route of intracellular trafficking. In this study, we compared the trafficking of HER2, which is the target of the clinically approved ADC ado-trastuzumab emtansine (T-DM1), with that of prolactin receptor (PRLR), another potential target in breast cancer. In contrast to HER2, we found that PRLR is rapidly and constitutively internalized, and traffics efficiently to lysosomes, where it is degraded. The PRLR cytoplasmic domain is necessary to promote rapid internalization and degradation, and when transferred to HER2, enhances HER2 degradation. In accordance with these findings, low levels of cell surface PRLR (∼30,000 surface receptors per cell) are sufficient to mediate effective killing by PRLR ADC, whereas cell killing by HER2 ADC requires higher levels of cell surface HER2 (∼106 surface receptors per cell). Noncovalently cross-linking HER2 to PRLR at the cell surface, using a bispecific antibody that binds to both receptors, dramatically enhances the degradation of HER2 as well as the cell killing activity of a noncompeting HER2 ADC. Furthermore, in breast cancer cells that coexpress HER2 and PRLR, a HER2xPRLR bispecific ADC kills more effectively than HER2 ADC. These results emphasize that intracellular trafficking of ADC targets is a key property for their activity and, further, that coupling an ADC target to a rapidly internalizing protein may be a useful approach to enhance internalization and cell killing activity of ADCs. Mol Cancer Ther; 16(4); 681–93. ©2017 AACR.
Inflammatory Molecule, PSGL-1, Deficiency Activates Macrophages to Promote Colorectal Cancer Growth through NFκB Signaling
Authors: Li Jiangchao , Zhou Zeqi , Zhang Xiaohan , Zheng Li , He Dan , Ye Yuxiang , Zhang Qian-Qian , Qi Cui-Ling , He Xiao-Dong , Yu Chen , Shao Chun-kui , Qiao Liang , Wang Lijing
Published: January 2017

P-selectin glycoprotein ligand 1 (SELPLG/PSGL-1) is an inflammatory molecule that is functionally related to immune cell differentiation and leukocyte mobilization. However, the role of PSGL-1 in tumor development remains unknown. Therefore, this study investigates the mechanistic role of PSGL-1 in the development of intestinal tumors in colorectal cancer. ApcMin/+ mice are highly susceptible to spontaneous intestinal adenoma formation, and were crossbred with PSGL1-null mice to generate compound transgenic mice with a ApcMin/+;PSGL-1−/− genotype. The incidence and pathologic features of the intestinal tumors were compared between the ApcMin/+ mice and ApcMin/+;PSGL-1−/− mice. Importantly, PSGL-1–deficient mice showed increased susceptibility to develop intestinal tumors and accelerated tumor growth. Mechanistically, increased production of the mouse chemokine ligand 9 (CCL9/MIP-1γ) was found in the PSGL-1–deficient mice, and the macrophages are likely the major source of macrophage inflammatory protein-1 gamma (MIP-1γ). Studies in vitro demonstrated that macrophage-derived MIP-1γ promoted colorectal cancer tumor cell growth through activating NFκB signaling. Conversely, restoration of the PSGL-1 signaling via bone marrow transplantation reduced MIP-1γ production and attenuated the ability of ApcMin/+;PSGL-1−/− mice to generate intestinal tumors. In human colorectal cancer clinical specimens, the presence of PSGL-1–positive cells was associated with a favorable tumor–node–metastasis staging and decreased lymph node metastasis.

Implications: PSGL-1 deficiency and inflammation render intestinal tissue more vulnerable to develop colorectal tumors through a MIP-1γ/NFκB signaling axis. Mol Cancer Res; 15(4); 467–77. ©2017 AACR.
Macropinocytosis of Nab-paclitaxel Drives Macrophage Activation in Pancreatic Cancer
Authors: Cullis Jane , Siolas Despina , Avanzi Antonina , Barui Sugata , Maitra Anirban , Bar-Sagi Dafna
Published: January 2017

Pancreatic cancer is a devastating disease that is largely refractory to currently available treatment strategies. Therapeutic resistance is partially attributed to the dense stromal reaction of pancreatic ductal adenocarcinoma tumors that includes a pervasive infiltration of immunosuppressive (M2) macrophages. Nab-paclitaxel (trade name Abraxane) is a nanoparticle albumin-bound formulation of paclitaxel that, in combination with gemcitabine, is currently the first-line treatment for pancreatic cancer. Here, we show that macrophages internalized nab-paclitaxel via macropinocytosis. The macropinocytic uptake of nab-paclitaxel induced macrophage immunostimulatory (M1) cytokine expression and synergized with IFNγ to promote inducible nitric oxide synthase expression in a TLR4-dependent manner. Nab-paclitaxel was internalized by tumor-associated macrophages in vivo, and therapeutic doses of nab-paclitaxel alone, and in combination with gemcitabine, increased the MHCII+CD80+CD86+ M1 macrophage population. These data revealed an unanticipated role for nab-paclitaxel in macrophage activation and rationalized its potential use to target immune evasion in pancreatic cancer. Cancer Immunol Res; 5(3); 182–90. ©2017 AACR.
Outcomes of Women and Men With Acute Coronary Syndrome Treated With and Without Percutaneous Coronary Revascularization
Authors: Udell Jacob A. , Koh Maria , Qiu Feng , Austin Peter C. , Wijeysundera Harindra C. , Bagai Akshay , Yan Andrew T. , Goodman Shaun G. , Tu Jack V. , Ko Dennis T.
Published: January 2017

Background

Women hospitalized with a non‐
ST
segment elevation acute coronary syndrome (
ACS
) have worse clinical outcomes compared with men. An early invasive strategy with prompt coronary revascularization may mitigate sex differences in outcomes. However, few contemporary studies have evaluated whether clinical outcomes differ between women and men presenting with
ACS
treated with an early invasive strategy.

Methods and Results

A population‐based cohort of hospitalized
ACS
patients who received prompt cardiac catheterization from 2008 to 2011 in Ontario, Canada and followed for up to 2 years was studied. Clinical outcomes were compared between men and women, stratified by the use of coronary revascularization. Inverse probability weighting using the propensity score accounted for measured differences in baseline characteristics between men and women. Among the 23 473
ACS
patients who received cardiac catheterization during an index hospitalization, 66.1% of men and 51.8% of women received coronary revascularization during the same hospitalization. In the propensity‐weighted cohort of patients who received coronary revascularization, the 1‐year rate of death or recurrent
ACS
was 10.6% for men (referent) compared with 13.1% for women (hazard ratio 1.24; 95%
CI
1.16–1.33). In contrast, outcomes for patients who did not receive coronary revascularization did not differ significantly between women and men at 1 year (17.8% versus 16.9%; hazard ratio 1.06; 95%
CI
0.99–1.14) or at longer follow‐up.

Conclusions

An increased risk of adverse clinical outcomes was observed for women with
ACS
undergoing an early invasive strategy and coronary revascularization compared with men.
Timing of Decompressive Hemicraniectomy for Stroke
Authors: Dasenbrock Hormuzdiyar H. , Robertson Faith C. , Vaitkevicius Henrikas , Aziz-Sultan M. Ali , Guttieres Donovan , Dunn Ian F. , Du Rose , Gormley William B.
Published: January 2017

Background and Purpose—

Previous clinical trials were not designed to discern the optimal timing of decompressive craniectomy for stroke, and the ideal surgical timing in patients with space-occupying infarction who do not exhibit deterioration within 48 hours is debated.

Methods—

Patients undergoing decompressive craniectomy for stroke were extracted from the Nationwide Inpatient Sample (2002–2011). Multivariable logistic regression evaluated the association of surgical timing with mortality, discharge to institutional care, and poor outcome (a composite end point including death, tracheostomy and gastrostomy, or discharge to institutional care). Covariates included patient demographics, comorbidities, year of admission, and hospital characteristics. However, standard stroke severity scales and infarct volume were not available.

Results—

Among 1301 admissions, 55.8% (n=726) underwent surgery within 48 hours. Teaching hospital admission was associated with earlier surgery (
P
=0.02). The timing of intervention was not associated with in-hospital mortality. However, when evaluated continuously, later surgery was associated with increased odds of discharge to institutional care (odds ratio, 1.17; 95% confidence interval, 1.05–1.31,
P
=0.005) and of a poor outcome (odds ratio, 1.12; 95% confidence interval, 1.02–1.23;
P
=0.02). When evaluated dichotomously, the odds of discharge to institutional care and of a poor outcome did not differ at 48 hours after hospital admission, but increased when surgery was pursued after 72 hours. Subgroup analyses found no association of surgical timing with outcomes among patients who had not sustained herniation.

Conclusion

s—In this nationwide analysis, early decompressive craniectomy was associated with superior outcomes. However, performing decompression before herniation may be the most important temporal consideration.
Revolt in the Novel: Muḥammad Muṣṭafā Ghandūr’s Thaʾr al-damm (Blood Revenge) and the 1936-1939 Rebellion in Palestine
Authors: Macaluso Pasquale
Published: January 2017

Contrary to the inveterate opinion of most scholars, a Palestinian author actually dealt with political issues before the Nakbah in the novel Thaʾr al-damm (Blood Revenge). Published in Damascus in 1939 by Muḥammad Muṣṭafā Ghandūr from Acre, this work of fiction remained in oblivion for decades because the French Mandate authorities confiscated most of its copies soon after publication. It narrates the story of a young physician who forms an armed band to avenge the rape of his younger sister by British soldiers during the 1936-1939 uprising in Palestine; the woman, disguised as a man, joins the rebels and eventually dies in a fight.

Through the symbolism behind the retaliation for the maiden’s rape, Thaʾr al-damm provides a literary interpretation of the Palestinians’ shift to organized insurgency against the British Mandate in the late 1930s. By pivoting the plot around the tropes of injury and revenge, Ghandūr translated the feelings of humiliation and threat, and the consequent quest for revenge and liberation shared by many Palestinians into a novel. The action of this story takes place in the Palestinian countryside, in a village community portrayed as a spotless model of national solidarity and harmoniously merged with its environment. Ghandūr sketches a protagonist who exemplifies the theme of the political radicalization of modern-educated youth and argues for the leading role that they should assume in the struggle, while the only female character illustrates village women’s actual involvement in the revolt.
Characterization of Developmental Immature Fiber (im) Mutant and Texas Marker-1 (TM-1) Cotton Fibers Using Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy
Authors: Liu Yongliang , Kim Hee-Jin
Published: January 2017

The immature fiber ( im) mutant is one type of cotton fiber mutant with unique characteristics of non-fluffy cotton bolls. Compared to its near-isogenic wild type Texas Marker-1 (TM-1), im fiber has a thin secondary cell wall and is less mature. In this work, we applied the previously proposed principal component analysis (PCA) and simple algorithms to analyze the attenuated total reflection Fourier transform infrared (ATR FT-IR) spectra of developmental im and TM-1 fibers. The results from these approaches could not effectively and consistently indicate the inherent difference between TM-1 and im fibers at the same developmental stage. The difference between TM-1 and corresponding im fibers was detected when comparing the normalized intensity variations of the 730 cm−1 bands. The 730 cm−1 band intensities in developmental im fibers are temporally lower than those in developmental TM-1 fibers although they became similar when the TM-1 and im fibers are fully mature. The observation might imply the likelihood of temporal reduction of amorphous regions in developmental im fibers rather than in developmental TM-1 fibers.
Least Squares Moving-Window Spectral Analysis
Authors: Lee Young Jong
Published: January 2017

Least squares regression is proposed as a moving-windows method for analysis of a series of spectra acquired as a function of external perturbation. The least squares moving-window (LSMW) method can be considered an extended form of the Savitzky–Golay differentiation for nonuniform perturbation spacing. LSMW is characterized in terms of moving-window size, perturbation spacing type, and intensity noise. Simulation results from LSMW are compared with results from other numerical differentiation methods, such as single-interval differentiation, autocorrelation moving-window, and perturbation correlation moving-window methods. It is demonstrated that this simple LSMW method can be useful for quantitative analysis of nonuniformly spaced spectral data with high frequency noise.
Determination of the Zinc Concentration in Human Fingernails Using Laser-Induced Breakdown Spectroscopy
Authors: Riberdy Vlora A. , Frederickson Christopher J. , Rehse Steven J.
Published: January 2017

The absolute concentration of Zn in human fingernail clippings was determined ex vivo using 1064 nm laser-induced breakdown spectroscopy and confirmed by speciated isotope dilution mass spectrometry. A nail testing protocol that sampled across the nail (perpendicular to the direction of growth) was developed and validated by scanning electron microscopy energy-dispersive X-ray spectrometry. Using this protocol, a partial least squares (PLS) regression model predicted the Zn concentration in the fingernails of five people to within an average of 7 ppm. The variation in the Zn concentration with depth into the nail determined by laser-induced breakdown spectroscopy was studied and showed no systematic variation for up to 15 subsequent laser pulses in one location. The effects of nail hydration (dehydrated and over-hydrated) and nail surface roughness were investigated to explain an anomalously large scatter observed in the measurements. This scatter was attributed to the layered nature and fibrous structure of the fingernails, which resulted in non-uniform ablation as determined by scanning electron microscopy. This work demonstrates that a protocol consisting of low pulse energy (<10 mJ) 1064 nm laser pulses incident on human fingernail clippings in an Ar environment can produce quantifiable Zn emission in the laser-induced plasma and that the measured Zn intensity can be used to accurately predict the Zn concentration in human fingernails.
Automated Measurement of Magnesium/Calcium Ratios in Gastropod Shells Using Laser-Induced Breakdown Spectroscopy for Paleoclimatic Applications
Authors: Cobo Adolfo , García-Escárzaga Asier , Gutiérrez-Zugasti Igor , Setién Jesús , González-Morales Manuel R. , López-Higuera José Miguel
Published: January 2017

The chemical composition of mollusk shells offers information about environmental conditions present during the lifespan of the organism. Shells found in geological deposits and in many archeological sites can help to reconstruct past climatic conditions. For example, a correlation has been found between seawater temperature and the amount of some substituent elements (e.g., magnesium, strontium) in the biogenerated calcium carbonate matrix of the shell, although it is very species-specific. Here we propose the use laser-induced breakdown spectroscopy (LIBS) to estimate Mg/Ca ratios in modern specimens of the common limpet Patella vulgata. An automated setup was used to obtain a sequence of Mg/Ca ratios across a sampling path that could be compared with the seawater temperatures recorded during the organism’s lifespan. Results using four shells collected in different months of the year showed a direct relationship between the Mg/Ca ratios and the seawater temperature, although the sequences also revealed small-scale (short-term) variability and an irregular growth rate. Nevertheless, it was possible to infer the season of capture and the minimum and maximum seawater temperatures from the LIBS sequences. This fact, along with the reduction in sampling and measurement time compared with other spectrometric techniques (such as inductively coupled plasma mass spectrometry [ICP-MS]), makes LIBS useful in paleoclimatic studies.
Sleep problems and suicide associated with mood instability in the Adult Psychiatric Morbidity Survey, 2007
Authors: McDonald Keltie C , Saunders Kate EA , Geddes John R
Published: January 2017

Objective:

Mood instability is common in the general population. Mood instability is a precursor to mental illness and associated with a range of negative health outcomes. Sleep disturbance appears to be closely linked with mood instability. This study assesses the association between mood instability and sleep disturbance and the link with suicidal ideation and behaviour in a general population sample in England.

Method:

The Adult Psychiatric Morbidity Survey, 2007 collected detailed information about mental health symptoms and correlates in a representative sample of adult household residents living in England ( n = 7303). Mood instability was assessed using the Structured Clinical Interview for DSM-IV Axis-II. Sleep problems were defined as sleeping more than usual or less than usual during the past month. Other dependent variables included medication use and suicidal ideation and behaviour (response rate 57%). Generalized linear modelling was used to estimate the prevalence of mood instability and sleep problems. Logistic regression was used to estimate odds ratios. All estimates were weighted.

Results:

The prevalence of mood instability was 14.7% (95% confidence interval [13.6%, 15.7%]). Sleep problems occurred in 69.8% (95% confidence interval: [66.6%, 73.1%]) of those with mood instability versus 37.6% (95% confidence interval: [36.2%, 39.1%]) of those without mood instability. The use of sedating and non-sedating medications did not influence the association. Sleep problems were significantly associated with suicidal ideation and behaviour even after adjusting for mood instability.

Conclusion:

Sleep problems are highly prevalent in the general population, particularly among those with mood instability. Sleep problems are strongly associated with suicidal ideation and behaviour. Treatments that target risk and maintenance factors that transcend diagnostic boundaries, such as therapies that target sleep disturbance, may be particularly valuable for preventing and addressing complications related to mood instability such as suicide.
Correlation Tests Detecting Order Restrictions in Binary Response
Authors: Bandyopadhyay Uttam , Chakrabarti Parthasarathi
Published: January 2017

The work is on detection of order restrictions in 2 × k cohort study. The existing tests in the literature are mostly based on subjective choice of column scores. Moreover, when the marginal distributions of the column totals differ, it is observed that the normal approximation to the null distribution (having no difference in the disease risks among the exposure categories) of the relevant test statistic for small samples is violated in most of the cases. As a remedy, utilizing such variation in column distributions, single contrast tests are proposed for this purpose. Performance of the proposed tests are assessed numerically and are compared with that of an existing competitor.
Revisiting Basu's Circus Example: Another Look at the Horvitz-Thompson Estimator
Authors: Ghosh Malay , Haziza David
Published: January 2017

The objective of this article is a critical appraisal of the classical Horvitz-Thompson (HT) estimator used in survey sampling, and examine when and where it is effective. For illustration, we have brought in the hilarious circus example of Basu's [1] where the HT estimator led to a disastrous result. We have pointed out what went wrong with this example and, in the process, have also discussed what one needs for a successful application of the HT estimator. We also provide a model-based interpretation of the HT estimator, and again discuss the success or failure of the HT estimator from a model-based perspective.
One-way ANOVA Model with Underreported Counts
Authors: Sengupta Debjit , Roy Surupa
Published: January 2017

The focus of this article is on testing the equality of treatment means in a one-way analysis of variance setting with count response. The count data is further subject to misclassification, resulting in undercount of the event. Four asymptotically optimal tests are developed after correcting for the underreporting of the count. A simulation study is conducted to compare how these tests compete with each other with respect to level and power. The impact of ignoring undercount on the level of the tests is also investigated through this study. A comparison of these tests with the normal theory-based inference is also done after appropriate transformation of count data to a continuous measurement.
On Optimal Allocation of Experimental Units with Known Covariates into Multiple Treatment Groups
Authors: Hore Samrat , Dewanji Anup , Chatterjee Aditya
Published: January 2017

Finding the optimal design for allocating two or more treatments to a fixed group of experimental units with several known covariates is an important problem in many studies. With the objective of efficient estimation of the treatment effect or the covariate effects or both with regard to the well-known D- and or A- D s- and A s- optimalities, as well as some other robustness criteria, Hore et al. [1] considered this allocation problem in case of two treatments. In the present article, the method has been extended to r(≥2) treatments and the proposed design has been compared with several other allocation rules available in the literature including the most popular one, the randomized allocation rule. It is to be noted that finding the exact optimal allocation design with the above objective is computationally intractable in case of large number of experimental units having information on multiple covariates. By generalizing the algorithm of Hore et al. [1] , a near-optimum allocation design may be obtained with less computational burden. Some simulation studies and real life data analysis have been undertaken to demonstrate the efficacy of the proposed algorithm in comparison with others for the case of multiple treatments.
Forecasting Inflation with Mixed Frequency Data in India
Authors: Maji Bikash , Das Abhiman
Published: January 2017

In the standard approach of building prediction models, macroeconomic data is matched with monthly or quarterly or annual aggregates of financial series, since macroeconomic data are typically available at those frequencies. Such aggregation leads to the loss of useful forward-looking information of financial data. This is so because financial data are usually observed with higher periodicity than monthly data. Recent empirical evidence suggests that a Mixed Data Sampling (MIDAS) regression technique improves the predictive power of the models that incorporates data of different frequencies. In this article, we propose an autoregressive MIDAS model for forecasting monthly inflation in India using daily treasury yield information. Empirical results show that the proposed model has better predicting power over forecasting inflation in India.
Symmetric Beta-Cauchy Distribution and Estimation of Parameters Using Order Statistics
Authors: Thomas P. Yageen , Priya R.S.
Published: January 2017

In this work, we have considered a class of distributions called symmetric beta-Cauchy family of distributions (SBCD), and pointed out instances where SBCD appears as a good model to study the stochastic nature of the variable under investigation. We have derived the Best linear unbiased estimators (BLUE) based on order statistics of the location and scale parameters of SBCD for some given values of the shape parameter. Considering these BLUE's as kernels of degree m(≤ 5), we have further estimated the location and scale parameters of SBCD by U-statistics as seen developed recently by Thomas and Sreekumar for any sample of size n. The exact variances of the U-statistics have been obtained. The efficiency of the obtained estimators relative to some of the standard estimators has been also evaluated. An illustration describing the supremacy of U-statistics estimation method over the classical maximum likelihood method is also given.