bluuebunny/crossref_metadata_2025 huggingface dataset:
Depth profiling and recessional history of the Hamtah and Parang glaciers in Lahaul and Spiti, Himachal Pradesh, Indian Himalaya
Authors: Swain A. K. , Mukhtar M. A. , Majeed Z. , Shukla S. P.
Published: November 2017

The Himalaya are often referred to as the third pole of the Earth because they host the largest areal extent of glaciation outside the polar regions. Estimating the volume of these glaciers is challenging because the ice thickness of most of the glaciers is not accurately known. Depth profiling of the north-facing Hamtah and Parang glaciers was carried out using ground-penetrating radar surveys. The 6 km long Hamtah glacier and the 2.5 km long Parang glacier, with average widths of 350 and 250 m, respectively, are located in different U-shaped valleys. The depth of the ice–bedrock interface varied from 35 to 95 m in the Hamtah glacier and from 40 to 140 m in the Parang glacier. The valley profiles and ground-penetrating radar data were combined to obtain the volumes of the glaciers. The total volumes of ice in the Parang and Hamtah glaciers were estimated to be 0.179 and 0.375 km
3
, respectively. Shape analyses of different parts of these glaciers suggest that mathematical equations can be used to describe their sequential development. The retreat rates of the Parang and Hamtah glaciers were estimated to be 11.04 and 16.10 m a
−1
, respectively.
Forward-Looking Estimates of Interest-Rate Distributions
Authors: Wright Jonathan H.
Published: November 2017

This article reviews methods for extracting both risk-neutral and physical density forecasts for interest rates. It presents some applications, with particular focus on issues pertaining to forward guidance and the zero lower bound. Several important applied questions in macroeconomics and monetary economics can be very directly addressed using the wealth of information in interest-rate derivative securities.
Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction
Authors: Walsted Emil S. , Faisal Azmy , Jolley Caroline J. , Swanton Laura L. , Pavitt Matthew J. , Luo Yuan-Ming , Backer Vibeke , Polkey Michael I. , Hull James H.
Published: November 2017

Exercise-induced laryngeal obstruction (EILO), a phenomenon in which the larynx closes inappropriately during physical activity, is a prevalent cause of exertional dyspnea in young individuals. The physiological ventilatory impact of EILO and its relationship to dyspnea are poorly understood. The objective of this study was to evaluate exercise-related changes in laryngeal aperture on ventilation, pulmonary mechanics, and respiratory neural drive. We prospectively evaluated 12 subjects (6 with EILO and 6 healthy age- and gender-matched controls). Subjects underwent baseline spirometry and a symptom-limited incremental exercise test with simultaneous and synchronized recording of endoscopic video and gastric, esophageal, and transdiaphragmatic pressures, diaphragm electromyography, and respiratory airflow. The EILO and control groups had similar peak work rates and minute ventilation (V̇e) (work rate: 227 ± 35 vs. 237 ± 35 W; V̇e: 103 ± 20 vs. 98 ± 23 l/min; P > 0.05). At submaximal work rates (140–240 W), subjects with EILO demonstrated increased work of breathing ( P < 0.05) and respiratory neural drive ( P < 0.05), developing in close temporal association with onset of endoscopic evidence of laryngeal closure ( P < 0.05). Unexpectedly, a ventilatory increase ( P < 0.05), driven by augmented tidal volume ( P < 0.05), was seen in subjects with EILO before the onset of laryngeal closure; there were however no differences in dyspnea intensity between groups. Using simultaneous measurements of respiratory mechanics and diaphragm electromyography with endoscopic video, we demonstrate, for the first time, increased work of breathing and respiratory neural drive in association with the development of EILO. Future detailed investigations are now needed to understand the role of upper airway closure in causing exertional dyspnea and exercise limitation.

NEW & NOTEWORTHY Exercise-induced laryngeal obstruction is a prevalent cause of exertional dyspnea in young individuals; yet, how laryngeal closure affects breathing is unknown. In this study we synchronized endoscopic video with respiratory physiological measurements, thus providing the first detailed commensurate assessment of respiratory mechanics and neural drive in relation to laryngeal closure. Laryngeal closure was associated with increased work of breathing and respiratory neural drive preceded by an augmented tidal volume and a rise in minute ventilation.
Improvements in force variability and structure from vision- to memory-guided submaximal isometric knee extension in subacute stroke
Authors: Chow John W. , Stokic Dobrivoje S.
Published: November 2017

We examined changes in variability, accuracy, frequency composition, and temporal regularity of force signal from vision-guided to memory-guided force-matching tasks in 17 subacute stroke and 17 age-matched healthy subjects. Subjects performed a unilateral isometric knee extension at 10, 30, and 50% of peak torque [maximum voluntary contraction (MVC)] for 10 s (3 trials each). Visual feedback was removed at the 5-s mark in the first two trials (feedback withdrawal), and 30 s after the second trial the subjects were asked to produce the target force without visual feedback (force recall). The coefficient of variation and constant error were used to quantify force variability and accuracy. Force structure was assessed by the median frequency, relative spectral power in the 0–3-Hz band, and sample entropy of the force signal. At 10% MVC, the force signal in subacute stroke subjects became steadier, more broadband, and temporally more irregular after the withdrawal of visual feedback, with progressively larger error at higher contraction levels. Also, the lack of modulation in the spectral frequency at higher force levels with visual feedback persisted in both the withdrawal and recall conditions. In terms of changes from the visual feedback condition, the feedback withdrawal produced a greater difference between the paretic, nonparetic, and control legs than the force recall. The overall results suggest improvements in force variability and structure from vision- to memory-guided force control in subacute stroke despite decreased accuracy. Different sensory-motor memory retrieval mechanisms seem to be involved in the feedback withdrawal and force recall conditions, which deserves further study.

NEW & NOTEWORTHY We demonstrate that in the subacute phase of stroke, force signals during a low-level isometric knee extension become steadier, more broadband in spectral power, and more complex after removal of visual feedback. Larger force errors are produced when recalling target forces than immediately after withdrawing visual feedback. Although visual feedback offers better accuracy, it worsens force variability and structure in subacute stroke. The feedback withdrawal and force recall conditions seem to involve different memory retrieval mechanisms.
Effects of Treated Cow Dung Addition on the Strength of Carbon-Bearing Iron Ore Pellets
Authors: Meng Qing-min , Li Jia-xin , Chun Tie-jun , He Xiao-feng , Wei Ru-fei , Wang Ping , Long Hong-ming
Published: November 2017

It is of particular interest to use biomass as an alternative source of fuel in direct-reduction ironmaking to ease the current reliance on fossil fuel energy. The influence of cow dung addition on the strength of carbon-bearing iron ore pellets composed of cow dung, iron ore, anthracite, and bentonite was investigated, the quality of green and dry pellet was evaluated based on FTIR analysis, and the mechanism of strength variation of the reduced pellets was investigated by analysing the phase composition and microstructure using XRD and SEM. The results show that cow dung addition decreased the green pellet strength due to expansion of the amorphous region of the cellulose in the cow dung; however, the dry pellet strength increased substantially. In the process of reduction roasting, it was found that cow dung addition can promote aggregation of iron crystals and increase the density of the pellets, resulting in increased strength of the reduction roasted pellets, while excessive cow dung addition resulted in lower strength.
Growth Characteristics ofMethanomassiliicoccus luminyensisand Expression of Methyltransferase Encoding Genes
Authors: Kröninger Lena , Gottschling Jacqueline , Deppenmeier Uwe
Published: November 2017

DNA sequence analysis of the human gut revealed the presence a seventh order of methanogens referred to as Methanomassiliicoccales.Methanomassiliicoccus luminyensisis the only member of this order that grows in pure culture. Here, we show that the organism has a doubling time of 1.8 d with methanol + H2and a growth yield of 2.4 g dry weight/mol CH4.M. luminyensisalso uses methylamines + H2(monomethylamine, dimethylamine, and trimethylamine) with doubling times of 2.1–2.3 d. Similar cell yields were obtained with equimolar concentrations of methanol and methylamines with respect to their methyl group contents. The transcript levels of genes encoding proteins involved in substrate utilization indicated increased amounts of mRNA from themtaBC2gene cluster in methanol-grown cells. When methylamines were used as substrates, mRNA of themtb/mttoperon and of themtmBC1cluster were found in high abundance. The transcript level ofmtaC2was almost identical in methanol- and methylamine-grown cells, indicating that genes for methanol utilization were constitutively expressed in high amounts. The same observation was made with resting cells where methanol always yielded the highest CH4production rate independently from the growth substrate. Hence,M. luminyensisis adapted to habitats that provide methanol + H2as substrates.
Experimental Gait Analysis to Study Stress Distribution of the Human Foot
Authors: Nandikolla Vidya K. , Bochen Robin , Meza Steven , Garcia Allan
Published: November 2017

Researchers and clinicians are increasingly using plantar pressure and force measurement system to evaluate foot functions. This research evaluates the quality and reliability of a Tekscan HR mat to study the plantar pressures and forces acting during walking, running, jumping, and standing of healthy subjects. The following regions of the foot were investigated: heel, mid foot, metatarsophalangeal joint, hallux, and the toes. The arches of both feet of the three healthy subjects in the gait analysis were presented which addresses the balancing issues of the body during locomotion. The results indicated that the peaks at the big toe (79.4 ± 8.5 N/cm2, p = 0.0001) were the maximum compared to forefoot (40.3 ± 3.3 N/cm2, p = 0.001), to midfoot (7.5 ± 1.3 N/cm2, p = 0.001), and to heel (27.8 ± 3.9 N/cm2, p = 0.0002) for jump activity. The running activity demonstrated similar results as jump where the maximum peak pressures were absorbed at the big toe region. The heel region during running (86.3 ± 12.6 N/cm2, p = 0.001) showed three times the pressure peak compared to the jump land (27.8 ± 3.9 N/cm2, p = 0.0002) activity. The measurement system proved to be highly capable of detecting heel strike and toe-off moments.
Hand Rehabilitation Robotics on Poststroke Motor Recovery
Authors: Yue Zan , Zhang Xue , Wang Jing
Published: November 2017

The recovery of hand function is one of the most challenging topics in stroke rehabilitation. Although the robot-assisted therapy has got some good results in the latest decades, the development of hand rehabilitation robotics is left behind. Existing reviews of hand rehabilitation robotics focus either on the mechanical design on designers’ view or on the training paradigms on the clinicians’ view, while these two parts are interconnected and both important for designers and clinicians. In this review, we explore the current literature surrounding hand rehabilitation robots, to help designers make better choices among varied components and thus promoting the application of hand rehabilitation robots. An overview of hand rehabilitation robotics is provided in this paper firstly, to give a general view of the relationship between subjects, rehabilitation theories, hand rehabilitation robots, and its evaluation. Secondly, the state of the art hand rehabilitation robotics is introduced in detail according to the classification of the hardware system and the training paradigm. As a result, the discussion gives available arguments behind the classification and comprehensive overview of hand rehabilitation robotics.
Macular Retinal Vessel Oxygen Saturation Elevation in Chinese Central Serous Chorioretinopathy
Authors: Li Cheng , Feng Xiaoxiao , Wen Xin , Qian Xiaobing , Zheng Qishan , Yuan Yongguang , Fu Yue , Shao Wanwen , Li Yujie , Lin Xiaofeng , Gao Qianying
Published: November 2017

Purpose. To evaluate the retinal vessel oxygen saturation in central serous chorioretinopathy (CSC) cases among the Chinese. Methods. Relative oxygen saturation of retinal blood vessels was measured in 33 Chinese patients with single-eye CSC using the Oxymap T1 retinal oximeter. The contralateral eyes were the control. The mean saturation of the retinal arteriole (AS) and venule (VS), arteriovenous difference (AVS), and arteriole and venule diameters (AD, VD) was analyzed in the optic disc area and macular region. Results. In the optic disc area, the inferotemporal quadrant (TI) AS (93.2 ± 10.2%) and inferonasal quadrant (NI) VS (61.3 ± 7.3%) were higher in the affected eyes than in the contralateral eyes (88.7 ± 7.7% and 56.9 ± 6.5%) and AVS in NI (36.7 ± 10.4%) decreased compared to the contralateral eyes (41.5 ± 11.2%). The VD in TI was expanded (19.9 ± 2.5 pixels versus 18.1 ± 3.4 pixels). Around the macular region, AS was 93.6 ± 7.6%, higher than in the contralateral eyes (89.5 ± 6.3%). No other significant changes were found. Conclusions. AS increased in the TI, and VS decreased in the NI in the eyes with CSC. In addition, AS also increased around the macular region, suggesting that these are contributors to CSC pathophysiology.
Hypoxia Induces Apoptosis through HIF-1α Signaling Pathway in Human Uterosacral Ligaments of Pelvic Organ Prolapse
Authors: Zhao Xinrui , Ma Congcong , Li Rui , Xue Jing , Liu Lidong , Liu Peishu
Published: November 2017

The purpose of this study is to evaluate the expression of hypoxia-inducible factor-1α (HIF-1α) in women uterosacral ligament tissues with pelvic organ prolapse and women with normal uterine support structures and illuminate its relationship with apoptosis. Samples were collected from 38 women with pelvic organ prolapse and 31 age matched controls. The expression levels of HIF-1α and BNIP3 in the uterosacral ligaments were measured using immunohistochemistry, qRT-PCR, and Western blot. To assess apoptosis we performed TUNEL assay and Western blot analyses. Lastly, the short form of the Pelvic Floor Impact Questionnaire-7 (PFIQ-7) was used to evaluate prognosis of surgical patients and twenty patients finished the follow-up. The expressions of HIF-1α and BNIP3 in the uterosacral ligaments were significantly higher in patients with pelvic organ prolapse than in control group. Pearson’s correlation test revealed significant positive correlations between HIF-1α and apoptosis index. Similarly, Western blot analysis showed the expression of proapoptosis proteins (Bax and Bad), Cytochrome-c, cleaved caspase-3, and caspase-9 in patients with pelvic organ prolapse was upregulated. The PFIQ-7 scores were higher in HIF-1α positive group than in the negative group. Hypoxia may contribute to the pathological process of pelvic organ prolapse by increasing apoptosis via activating HIF-1α signaling pathway.
Black Titanium Dioxide Nanomaterials in Photocatalysis
Authors: Yan Xiaodong , Li Yong , Xia Ting
Published: November 2017

Titanium dioxide (TiO2) nanomaterials are widely considered to be state-of-the-art photocatalysts for environmental protection and energy conversion. However, the low photocatalytic efficiency caused by large bandgap and rapid recombination of photo-excited electrons and holes is a challenging issue that needs to be settled for their practical applications. Structure engineering has been demonstrated to be a highly promising approach to engineer the optical and electronic properties of the existing materials or even endow them with unexpected properties. Surface structure engineering has witnessed the breakthrough in increasing the photocatalytic efficiency of TiO2 nanomaterials by creating a defect-rich or amorphous surface layer with black color and extension of optical absorption to the whole visible spectrum, along with markedly enhanced photocatalytic activities. In this review, the recent progress in the development of black TiO2 nanomaterials is reviewed to gain a better understanding of the structure-property relationship with the consideration of preparation methods and to project new insights into the future development of black TiO2 nanomaterials in photocatalytic applications.
Adaptive Evolution of the GDH2 Allosteric Domain Promotes Gliomagenesis by Resolving IDH1R132H-Induced Metabolic Liabilities
Authors: Waitkus Matthew S. , Pirozzi Christopher J. , Moure Casey J. , Diplas Bill H. , Hansen Landon J. , Carpenter Austin B. , Yang Rui , Wang Zhaohui , Ingram Brian O. , Karoly Edward D. , Mohney Robert P. , Spasojevic Ivan , McLendon Roger E. , Friedman Henry S. , He Yiping , Bigner Darell D. , Yan Hai
Published: November 2017

Hotspot mutations in the isocitrate dehydrogenase 1 (IDH1) gene occur in a number of human cancers and confer a neomorphic enzyme activity that catalyzes the conversion of α-ketoglutarate (αKG) to the oncometabolite D-(2)-hydroxyglutarate (D2HG). In malignant gliomas, IDH1R132H expression induces widespread metabolic reprogramming, possibly requiring compensatory mechanisms to sustain the normal biosynthetic requirements of actively proliferating tumor cells. We used genetically engineered mouse models of glioma and quantitative metabolomics to investigate IDH1R132H-dependent metabolic reprogramming and its potential to induce biosynthetic liabilities that can be exploited for glioma therapy. In gliomagenic neural progenitor cells, IDH1R132H expression increased the abundance of dipeptide metabolites, depleted key tricarboxylic acid cycle metabolites, and slowed progression of murine gliomas. Notably, expression of glutamate dehydrogenase GDH2, a hominoid-specific enzyme with relatively restricted expression to the brain, was critically involved in compensating for IDH1R132H-induced metabolic alterations and promoting IDH1R132H glioma growth. Indeed, we found that recently evolved amino acid substitutions in the GDH2 allosteric domain conferred its nonredundant, glioma-promoting properties in the presence of IDH1 mutation. Our results indicate that among the unique roles for GDH2 in the human forebrain is its ability to limit IDH1R132H-mediated metabolic liabilities, thus promoting glioma growth in this context. Results from this study raise the possibility that GDH2-specific inhibition may be a viable therapeutic strategy for gliomas with IDH mutations.

Significance: These findings show that the homonid-specific brain enzyme GDH2 may be essential to mitigate metabolic liabilities created by IDH1 mutations in glioma, with possible implications to leverage its therapeutic management by IDH1 inhibitors. Cancer Res; 78(1); 36–50. ©2017 AACR.
Understanding Mitochondrial Polymorphisms in Cancer
Authors: Bussard Karen M. , Siracusa Linda D.
Published: November 2017

Alterations in mitochondrial DNA (mtDNA) were once thought to be predominantly innocuous to cell growth. Recent evidence suggests that mtDNA undergo naturally occurring alterations, including mutations and polymorphisms, which profoundly affect the cells in which they appear and contribute to a variety of diseases, including cardiovascular disease, diabetes, and cancer. Furthermore, interplay between mtDNA and nuclear DNA has been found in cancer cells, necessitating consideration of these complex interactions for future studies of cancer mutations and polymorphisms. In this issue of Cancer Research, Vivian and colleagues utilize a unique mouse model, called Mitochondrial Nuclear eXchange mice, that contain the nuclear DNA from one inbred mouse strain, and the mtDNA from a different inbred mouse strain to examine the genome-wide nuclear DNA methylation and gene expression patterns of brain tissue. Results demonstrated there were alterations in nuclear DNA expression and DNA methylation driven by mtDNA. These alterations may impact disease pathogenesis. In light of these results, in this review, we highlight alterations in mtDNA, with a specific focus on polymorphisms associated with cancer susceptibility and/or prognosis, mtDNA as cancer biomarkers, and considerations for investigating the role of mtDNA in cancer progression for future studies. Cancer Res; 77(22); 6051–9. ©2017 AACR.
Uncoupling the Oncogenic Engine
Authors: Schambach Axel , Schott Juliane W. , Morgan Michael A.
Published: November 2017

Inhibition of oncogenic signaling and correction of aberrant metabolic processes may be key paradigms to eliminate cancer cells. The high incidence of activating RAS mutations and hyperactivated ERK1/2 signaling observed in many human tumors and the lack of effective targeted therapies to elicit long-term inhibition of the RAS-ERK1/2 signaling pathway add to the importance of discovering novel strategies to treat malignancies characterized by elevated RAS-ERK1/2 signaling. In this review, we describe connections between oncogenic signaling and cancer cell metabolism and how these links may be exploited for novel modern molecular medicine approaches. Cancer Res; 77(22); 6060–4. ©2017 AACR.
RAZOR: A Phase II Open Randomized Trial of Screening Plus Goserelin and Raloxifene Versus Screening Alone in Premenopausal Women at Increased Risk of Breast Cancer
Authors: Howell Anthony , Ashcroft Linda , Fallowfield Lesley , Eccles Diana M. , Eeles Rosalind A. , Ward Ann , Brentnall Adam R. , Dowsett Mitchell , Cuzick Jack M. , Greenhalgh Rosemary , Boggis Caroline , Motion Jamie , Sergeant Jamie C. , Adams Judith , Evans D. Gareth
Published: November 2017

Background: Ovarian suppression in premenopausal women is known to reduce breast cancer risk. This study aimed to assess uptake and compliance with ovarian suppression using the luteinizing hormone releasing hormone (LHRH) analogue, goserelin, with add-back raloxifene, as a potential regimen for breast cancer prevention.

Methods: Women at ≥30% lifetime risk breast cancer were approached and randomized to mammographic screening alone (C-Control) or screening in addition to monthly subcutaneous injections of 3.6 mg goserelin and continuous 60 mg raloxifene daily orally (T-Treated) for 2 years. The primary endpoint was therapy adherence. Secondary endpoints were toxicity/quality of life, change in bone density, and mammographic density.

Results: A total of 75/950 (7.9%) women approached agreed to randomization. In the T-arm, 20 of 38 (52%) of women completed the 2-year period of study compared with the C-arm (27/37, 73.0%). Dropouts were related to toxicity but also the wish to have established risk-reducing procedures and proven chemoprevention. As relatively few women completed the study, data are limited, but those in the T-arm reported significant increases in toxicity and sexual problems, no change in anxiety, and less cancer worry. Lumbar spine bone density declined by 7.0% and visually assessed mammographic density by 4.7% over the 2-year treatment period.

Conclusions: Uptake is somewhat lower than comparable studies with tamoxifen for prevention with higher dropout rates. Raloxifene may preserve bone density, but reduction in mammographic density reversed after treatment was completed.

Impact: This study indicates that breast cancer risk reduction may be possible using LHRH agonists, but reducing toxicity and preventing bone changes would make this a more attractive option. Cancer Epidemiol Biomarkers Prev; 27(1); 58–66. ©2017 AACR.
Diabetes and Overall Survival among Breast Cancer Patients in the U.S. Military Health System
Authors: Shao Stephanie , Gill Abegail A. , Zahm Shelia H. , Jatoi Ismail , Shriver Craig D. , McGlynn Katherine A. , Zhu Kangmin
Published: November 2017

Background: Although research suggests that type II diabetes mellitus (DM-2) is associated with overall and breast cancer–specific decreased survival, most prior studies of breast cancer survival investigated the effect of preexisting DM-2 without assessing the effect of DM-2 diagnosed at or after breast cancer diagnosis. This study examined the relationship between DM-2 diagnosed before and after breast cancer diagnosis and overall survival.

Methods: This study uses linked Department of Defense cancer registry and medical claims data from 9,398 women diagnosed with breast cancer between 1998 and 2007. Cox proportional hazards models were used to assess the association between DM-2 and overall survival.

Results: Our analyses showed that women with DM-2 diagnosed before breast cancer diagnosis tended to have a higher risk of mortality compared with women without diabetes [HR = 1.17; 95% confidence interval (CI), 0.95–1.44] after adjustment for potential confounders. Similarly, patients diagnosed with DM-2 at or after breast cancer diagnosis had increased mortality compared with women without DM-2 (HR = 1.39; 95% CI, 1.16–1.66). The similar tendency was also observed among most subgroups when results were stratified by race, menopausal status, obesity, tumor hormone receptor status, and stage.

Conclusions: Using data from a health system that provides universal health care to its beneficiaries, this study showed an increased risk of death associated with DM-2, regardless of whether it was diagnosed before or at/after breast cancer diagnosis.

Impact: These results suggest the potential effects of factors independent of the timing of DM-2 clinical diagnosis on the association of DM-2 with overall survival. Cancer Epidemiol Biomarkers Prev; 27(1); 50–57. ©2017 AACR.
Trapping Cancers as They Adapt to Survive
Authors: Haq Rizwan
Published: November 2017

Summary: The evolution of cancer cells limits the efficacy of nearly all treatments for patients with solid tumors. Characterizing how cancers adapt to treatment could therefore lead to approaches that overcome resistance to therapy. In this issue of Cancer Discovery, Song and colleagues describe the evolution of melanomas upon exposure to BRAF inhibitors, demonstrating that adaptive changes in the tumor create a vulnerability that can be targeted with immune checkpoint inhibitors. Cancer Discov; 7(11); 1216–7. ©2017 AACR.

See related article by Song et al., p. 1248.
Nonfunctional Redundant Acts Characterize OCD, Even in OCD-Unrelated Tasks: A Demonstration in Questionnaire Completion
Authors: Amitai Maya , Arnon Nitzan , Shaham Noa , Gur Shay , Apter Alan , Weizman Abraham , Hermesh Haggai
Published: November 2017

Background: Ethological methods used to analyze human obsessive-compulsive disorder (OCD) rituals demonstrated excess of unnecessary repetitions as well as irrelevant, idiosyncratic acts (additions) compared to normal activity. A question that still remains is whether these well-known repetitions and additions are manifested in behaviors unrelated to the OCD rituals. Our objectives were to: (1) assess whether OCD-related repetitions and additions as found in previous studies also affect the patients' activity of filling out questionnaires and (2) evaluate the specificity of these behaviors to OCD as opposed to other anxiety disorders and healthy controls. Sampling and Methods: Several standardized disorder-specific self-report questionnaires were used in order to assess the patient's psychopathologies. The style of filling-out these questionnaires by OCD and non-OCD anxiety outpatients and normal controls was analyzed. Four categories were used: omissions, repetitions, corrections, and additions. Results: The OCD group scored significantly higher on the number of additions as compared with both the anxiety group and the nonclinical group, and significantly higher on the number of corrections and repetitions as compared with the nonclinical group. Conclusions: The hallmarks of OCD, repetitions and additions, are manifested not only in the patient's rituals and thoughts, but in apparently “neutral” tasks that do not a priori involve the intrusive thoughts, urges, and images typical of obsessive-compulsive behavior. Additions seem to be more specific to OCD than repetitions. These two executive faults impede routine functionality of OCD patients in tasks related and unrelated to their rituals. Our study delineates simple, observable behavioral characteristics that distinguish between OCD and non-OCD anxiety patients as well as healthy individuals. These symptomatic behaviors may offer a clue to personality traits or deficits in executive functions that possibly play a part in the pathophysiology of OCD. Our results are an additional indication that nonfunctionality in obsessive-compulsive behavior deserves full attention for a better understanding of the psychopathological mechanisms of OCD.
Combination Therapy with Renin-Angiotensin System Blockers and Vitamin D Receptor Activators for Predialysis Patients Is Associated with the Incidence of Cardiovascular Events after Dialysis Initiation: A Multicenter Nonrandomized Prospective Cohort Study
Authors: Inaguma Daijo , Ito Eri , Koide Shigehisa , Takahashi Kazuo , Hayashi Hiroki , Hasegawa Midori , Yuzawa Yukio
Published: November 2017

Background: Several human studies reported that the combined use of renin-angiotensin system blockers (RASBs) and vitamin D receptor activators (VDRAs) resulted in decreased urinary protein excretion. However, it is unknown whether this combination therapy influences the incidence of cardiovascular (CV) events in dialysis patients. Methods: The study was a multicenter nonrandomized prospective cohort analysis including 1,518 patients. Patients were classified into 4 groups based on medications prescribed before dialysis initiation: those who did not receive RASBs or oral VDRAs (N group), those receiving only RASBs, those receiving only VDRAs, and those receiving a combination of RASBs and VDRAs (RD group). CV events after dialysis initiation were compared using the log-rank test. Factors contributing to the incidence of CV events were examined using multivariate Cox proportional hazard regression analysis. Results: Significant differences were observed in the incidence of CV events and all-cause mortality between the 4 groups (p = 0.021 and p = 0.001, respectively). Cox proportional hazard analysis revealed that the incidence of CV events was significantly lower in the RD group than in the N group (hazard ratio [HR] = 0.65, 95% confidence interval [CI]: 0.50-0.86, p = 0.002). Multivariate analysis revealed that the incidence of CV events was significantly lower in the RD group than in the N group (HR = 0.66, 95% CI: 0.47-0.93, p = 0.016). Conclusion: Combination therapy with RASBs and VDRAs in patients before dialysis initiation was associated with a reduction in CV events during maintenance dialysis.
Online Self-Help as an Add-On to Inpatient Psychotherapy: Efficacy of a New Blended Treatment Approach
Authors: Zwerenz Rüdiger , Becker Jan , Knickenberg Rudolf J. , Siepmann Martin , Hagen Karin , Beutel Manfred E.
Published: November 2017

Background: Depression is one of the most frequent and costly mental disorders. While there is increasing evidence for the efficacy of online self-help to improve depression or prevent relapse, there is little evidence in blended care settings, especially combined with inpatient face-to-face psychotherapy. Therefore, we evaluated whether an evidence-based online self-help program improves the efficacy of inpatient psychotherapy. Methods: A total of 229 depressed patients were randomly allocated either to an online self-help program (intervention group [IG]; Deprexis) or an active control group (CG; weekly online information on depression) in addition to inpatient psychodynamic psychotherapy. Both groups had access to their respective experimental intervention for 12 weeks, regardless of inpatient treatment duration. Reduction of depressive symptoms, as measured with the Beck Depression Inventory-II, was the primary outcome at the end of the intervention (T2). Results: Depressive symptoms were statistically significantly lower in the IG compared to the active CG at T2 with a moderate between-group effect size of d = 0.44. The same applied to anxiety (d = 0.33), quality of life (d = 0.34), and self-esteem (d = 0.38) at discharge from inpatient treatment (T1). No statistically significant differences were found regarding dysfunctional attitudes (d = 0.14) and work ability (d = 0.08) at T1. Conclusions: This is the first evidence for blended treatment combining online self-help with inpatient psychotherapy. The study opens new and promising avenues for increasing the efficacy of inpatient psychotherapy. Future studies should determine how integration of online self-help into the therapeutic process can be developed further.
Radiation Retinopathy 47 Years following Brachytherapy for Retinoblastoma
Authors: Bellerive Claudine , Singh Arun D.
Published: November 2017

A 50-year-old female who had undergone enucleation in the left eye and brachytherapy in the right eye for retinoblastoma at the age of 2 years was diagnosed with nonproliferation radiation retinopathy 47 years following the initial treatment. The patient had noticed black spots in her vision (scotomas) that interfered with reading. New onset of microaneurysms and lipid exudation threatening the foveola was noted on examination of the right eye. Initial visual acuity (VA) was 20/25. Optical coherence tomography showed no evidence of macular edema, but parafoveal lipid exudation was present. On fluorescein angiography, no sign of neovascularization or macular ischemia was observed. Direct focal treatment of microaneurysms was performed to prevent progression of the radiation retinopathy and vision loss. At 18 months' follow-up following focal laser, VA remained stable at 20/25 and there was a regression of the retinopathy.
Frequency, Aetiology, and Outcome of Small Cerebellar Infarction
Authors: Calic Zeljka , Cappelen-Smith Cecilia , Cuganesan Ramesh , Anderson Craig S. , Welgampola Miriam , Cordato Dennis J.
Published: November 2017

Background and Purpose: Strokes due to small (<2 cm) cerebellar infarction are under-recognised, and their profile and aetiology have not been well characterised. We aimed to determine the frequency, clinical features, aetiology, and outcome of small as compared to large cerebellar infarction. Methods: This study is a retrospective analysis of clinical and imaging features of a prospectively assessed series of 108 consecutive patients with acute cerebellar infarction admitted to Liverpool Hospital, Sydney, NSW, Australia, during 2011–2015. Results: The mean age of the patients was 67 years, and 33 (31%) had small cerebellar infarction. Compared to large cerebellar infarction, those with small cerebellar infarction had a comparable distribution of vascular risk factors but significantly less nausea and vomiting, gait disturbance, limb ataxia, and dysarthria. The posterior (n = 22, 67%) lobe was most commonly affected, followed by the anterior (n = 9, 27%) and flocculonodular (n = 2) lobes. Dizziness, limb ataxia, and nystagmus were significantly more common in patients with anterior lobe infarction. Vertebrobasilar disease was the presumed aetiology in 40 patients (37%), and was less commonly seen in small as compared to large cerebellar infarction. Cardioembolism affected 37% of the patients, irrespective of the size or topography of the cerebellar infarction, and there was no relation of supratentorial white matter lucencies (WMLs) to the size of cerebellar infarction. At 3 months, 65% of the patients were functionally independent (according to modified Rankin Scale scores of 0–2), and having a poor outcome was significantly related to moderate-to-severe supratentorial WML and large cerebellar infarction. Conclusions: Small cerebellar infarction accounted for one-third of the ischaemic strokes in this location, most often involved the posterior lobe, causing fewer clinical features, and had a better clinical outcome than large cerebellar infarction. Patients with small cerebellar infarction require appropriate vascular management including investigation for a cardioembolic source.
A Rare Case of Intraductal Tubulopapillary Neoplasm of the Pancreas Rupturing and Causing Acute Peritonitis
Authors: Umemura Akira , Ishida Kazuyuki , Nitta Hiroyuki , Takahara Takeshi , Hasegawa Yasushi , Makabe Kenji , Sasaki Akira
Published: November 2017

An intraductal tubulopapillary neoplasm (ITPN) is a very rare pancreatic tumor. Here we report an extremely rare case of an ITPN rupturing and causing acute peritonitis. A 50-year-old woman presented with left flank pain and vomiting. A computed tomography (CT) scan revealed gigantic multilocular cysts in the pancreatic tail and massive fluid collection in the abdominal cavity. The serum, urine, and abdominal fluid amylase levels were highly elevated, so she was conservatively treated with intraperitoneal drainage and antibiotics for a diagnosis of ruptured pancreatic cysts. After this patient recovered, a CT scan revealed a 2-cm low-density mass located in the body of the pancreas. This was diagnosed as a pancreatic ductal adenocarcinoma of the pancreatic body with an intraductal papillary mucinous neoplasm, and a distal pancreatectomy was performed. The tumor was composed of cuboidal high-grade dysplastic cells proliferating in a tubulopapillary growth pattern without mucin production. An immunohistochemical examination revealed that the tumor cells were positive for MUC1 and CK7, but negative for MUC5AC. These features led to the final diagnosis of ITPN. In this case, the solid ITPN growth obstructed the lumen of the main pancreatic duct, and the intraductal pressure of the distal side rose gradually. Then, pancreatic cysts formed and burst into the abdominal cavity when the intraductal pressure was at its maximum. However, an ITPN consists of high-grade atypical cells derived from the pancreatic ductal epithelium in principle, so the rupture may be an independent risk factor for peritonitis carcinomatosa in the future.
Prehospital Computed Tomography Angiography in Acute Stroke Management
Authors: Kettner Michael , Helwig Stefan Alexander , Ragoschke-Schumm Andreas , Schwindling Lenka , Roumia Safwan , Keller Isabel , Martens Daniel , Kulikovski Johann , Manitz Matthias , Lesmeister Martin , Walter Silke , Grunwald Iris Quasar , Schlechtriemen Thomas , Reith Wolfgang , Fassbender Klaus
Published: November 2017

Background: An ambulance equipped with a computed tomography (CT) scanner, a point-of-care laboratory, and telemedicine capabilities (mobile stroke unit [MSU]) has been shown to enable the delivery of thrombolysis to stroke patients directly at the emergency site, thereby significantly decreasing time to treatment. However, work-up in an MSU that includes CT angiography (CTA) may also potentially facilitate triage of patients directly to the appropriate target hospital and specialized treatment, according to their individual vascular pathology. Methods: Our institution manages a program investigating the prehospital management of patients with suspicion of acute stroke. Here, we report a range of scenarios in which prehospital CTA could be relevant in triaging patients to the appropriate target hospital and to the individually required treatment. Results: Prehospital CTA by use of an MSU allowed to detect large vessel occlusion of the middle cerebral artery in one patient with ischemic stroke and occlusion of the basilar artery in another, thereby allowing rational triage to comprehensive stroke centers for immediate intra-arterial treatment. In complementary cases, prehospital imaging not only allowed diagnosis of parenchymal hemorrhage with a spot sign indicating ongoing bleeding in one patient and of subarachnoid hemorrhage in another but also clarified the underlying vascular pathology, which was relevant for subsequent triage decisions. Conclusion: Defining the vascular pathology by CTA directly at the emergency site may be beneficial in triaging patients with various cerebrovascular diseases to the most appropriate target hospital and specialized treatment.
Androgen Triggers the Pro-Migratory CXCL12/CXCR4 Axis in AR-Positive Breast Cancer Cell Lines: Underlying Mechanism and Possible Implications for the Use of Aromatase Inhibitors in Breast Cancer
Authors: Azariadis Kalliopi , Kiagiadaki Fotini , Pelekanou Vasiliki , Bempi Vasiliki , Alexakis Kostas , Kampa Marilena , Tsapis Andreas , Castanas Elias , Notas George
Published: November 2017

Background/Aims: Reports regarding the role of androgen in breast cancer (BC) are conflicting. Some studies suggest that androgen could lead to undesirable responses in the presence of certain BC tumor characteristics. We have shown that androgen induces C-X-C motif chemokine 12 (CXCL12) in BC cell lines. Our aim was to identify the mechanisms regulating the phenotypic effects of androgen-induced CXCL12 on Androgen Receptor (AR) positive BC cell lines. Methods: We analyzed the expression of CXCL12 and its receptors with qPCR and ELISA and the role of Nuclear Receptor Coactivator 1 (NCOA1) in this effect. AR effects on the CXCL12 promoter was studied via Chromatin-immunoprecipitation. We also analyzed publically available data from The Cancer Genome Atlas to verify AR-CXCL12 interactions and to identify the effect or Aromatase Inhibitors (AI) therapy on CXCL12 expression and disease progression in AR positive cases. Results: CXCL12 induction occurs only in AR-positive BC cell lines, possibly via an Androgen Response Element, upstream of the CXCL12 promoter. The steroid receptor co-regulator NCOA1 is critical for this effect. Androgen only induced the motility of p53-mutant BC cells T47D cells via upregulation of CXCR4 expression while they had no effect on wild-type p53 MCF-7 cells. Loss of CXCR4 expression and depletion of CXCL12 abolished the effect of androgen in T47D cells while inhibition of p53 expression in MCF-7 cells made them responsive to androgen and increased their motility in the presence to androgen. Patients with estrogen receptor positive (ER+)/AR+ BC treated with AIs were at increased risk of disease progression compared to ER+/AR+ non-AI treated and ER+/AR- AI treated cases. Conclusion: AIs may lead to unfavorable responses in some ER/AR positive BC cases, especially in patients with AR+, p53 mutant tumors.
Refrigeration-Induced Binding of von Willebrand Factor Facilitates Fast Clearance of Refrigerated Platelets
Authors: Chen Wenchun , Druzak Samuel A. , Wang Yingchun , Josephson Cassandra D. , Hoffmeister Karin M. , Ware Jerry , Li Renhao
Published: November 2017

Objective—

Apheresis platelets for transfusion treatment are currently stored at room temperature because after refrigeration platelets are rapidly cleared on transfusion. In this study, the role of von Willebrand factor (VWF) in the clearance of refrigerated platelets is addressed.

Approach and Results—

Human and murine platelets were refrigerated in gas-permeable bags at 4°C for 24 hours. VWF binding, platelet signaling events, and platelet post-transfusion recovery and survival were measured. After refrigeration, the binding of plasma VWF to platelets was drastically increased, confirming earlier studies. The binding was blocked by peptide OS1 that bound specifically to platelet glycoprotein (GP)Ibα and was absent in VWF
−
/
−
plasma. Although surface expression of GPIbα was reduced after refrigeration, refrigeration-induced VWF binding under physiological shear induced unfolding of the GPIbα mechanosensory domain on the platelet, as evidenced by increased exposure of a linear epitope therein. Refrigeration and shear treatment also induced small elevation of intracellular Ca
2+
, phosphatidylserine exposure, and desialylation of platelets, which were absent in VWF
−/−
platelets or inhibited by OS1, which is a monomeric 11-residue peptide (CTERMALHNLC). Furthermore, refrigerated VWF
−/−
platelets displayed increased post-transfusion recovery and survival than wild-type ones. Similarly, adding OS1 to transgenic murine platelets expressing only human GPIbα during refrigeration improved their post-transfusion recovery and survival.

Conclusions—

Refrigeration-induced binding of VWF to platelets facilitates their rapid clearance by inducing GPIbα-mediated signaling. Our results suggest that inhibition of the VWF–GPIbα interaction may be a potential strategy to enable refrigeration of platelets for transfusion treatment.
Sildenafil Is Associated With Reduced Device Thrombosis and Ischemic Stroke Despite Low-Level Hemolysis on Heart Mate II Support
Authors: Saeed Omar , Rangasamy Sabarivinoth , Selevany Ibrahim , Madan Shivank , Fertel Jeremy , Eisenberg Ruth , Aljoudi Mohammad , Patel Snehal R. , Shin Julia , Sims Daniel B. , Reyes Gil Morayma , Goldstein Daniel J. , Slepian Marvin J. , Billett Henny H. , Jorde Ulrich P.
Published: November 2017

Background:

Persistent low-level hemolysis (LLH) during continuous-flow mechanical circulatory support is associated with subsequent thrombosis. Free hemoglobin from ongoing hemolysis scavenges nitric oxide (NO) to create an NO deficiency which can augment platelet function leading to a prothrombotic state. The phosphodiesterase-5 inhibitor, sildenafil, potentiates NO signaling to inhibit platelet function. Accordingly, we investigated the association of sildenafil administration and thrombotic events in patients with LLH during Heart Mate II support.

Methods and Results:

A single-center review of all patients implanted with a Heart Mate II who survived to discharge (n=144). LLH was defined by a discharge lactate dehydrogenase level of 400 to 700 U/L. Patients were categorized as (1) LLH not on sildenafil, (2) LLH on sildenafil, (3) no LLH not on sildenafil, and (4) no LLH on sildenafil. Age, sex, platelet count, and mean platelet volume were similar between groups. Seventeen patients had either device thrombosis or ischemic stroke. Presence of LLH was associated with a greater risk of thrombosis (adjusted hazard ratio, 15; 95% confidence interval, 4.5–50;
P
<0.001 versus no LLH, not on sildenafil). This risk was reduced in patients with LLH on sildenafil (adjusted hazard ratio, 1.7; 95% confidence interval, 0.2–16.1;
P
=0.61). Device thrombosis and ischemic stroke were associated with an increase in mean platelet volume (9.6±0.5 to 10.9±0.8 fL,
P
<0.001). Patients with LLH not on sildenafil had a greater increase in mean platelet volume in comparison to those with LLH on sildenafil (
P
<0.001).

Conclusions:

Sildenafil is associated with reduced device thrombosis and ischemic stroke during ongoing LLH on Heart Mate II support.