bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring End User Programming Needs in Home Automation
Authors: Brich Julia , Walch Marcel , Rietzler Michael , Weber Michael , Schaub Florian
Published: April 2017

Home automation faces the challenge of providing ubiquitous, unobtrusive services while empowering users with approachable configuration interfaces. These interfaces need to provide sufficient expressiveness to support complex automation, and notations need to be devised that enable less tech-savvy users to express such scenarios. Rule-based and process-oriented paradigms have emerged as opposing ends of the spectrum; however, their underlying concepts have not been studied comparatively. We report on a contextual inquiry study in which we collected qualitative data from 18 participants in 12 households on the current potential and acceptance of home automation, as well as explored the respective benefits and drawbacks of these two notation paradigms for end users. Results show that rule-based notations are sufficient for simple automation tasks but not flexible enough for more complex use cases. The resulting insights can inform the design of interfaces for smart homes to enable usable real-world home automation for end users.
Absence of the NOD2 protein renders epithelia more susceptible to barrier dysfunction due to mitochondrial dysfunction
Authors: Saxena Alpana , Lopes Fernando , Poon Karen K. H. , McKay Derek M.
Published: April 2017

Irregular mitochondria structure and reduced ATP in some patients with IBD suggest that metabolic stress contributes to disease. Loss-of-function mutation in the nucleotide-binding oligomerization domain (NOD)-2 gene is a major susceptibility trait for IBD. Hence, we assessed if loss of NOD2 further impairs the epithelial barrier function instigated by disruption of mitochondrial ATP synthesis via the hydrogen ionophore dinitrophenol (DNP). NOD2 protein (virtually undetectable in epithelia under basal conditions) was increased in T84 (human colon cell line) cells treated with noninvasive Escherichia coli + DNP (16 h). Increased intracellular bacteria in wild-type (WT) and NOD2 knockdown (KD) cells and colonoids from NOD2−/−mice were mediated by reactive oxygen species (ROS) and the MAPK ERK1/2 pathways as determined by cotreatment with the antioxidant mitoTEMPO and the ERK inhibitor U0126: ROS was upstream of ERK1/2 activation. Despite increased E. coli in DNP-treated NOD2 KD compared with WT cells, there were no differences in the internalization of fluorescent inert beads or dead E. coli particles. This suggests that lack of killing in the NOD2 KD cells was responsible for the increased numbers of viable intracellular bacteria; a conclusion supported by evidence of reduced autophagy in NOD2 KD T84 epithelia. Thus, in a two-hit hypothesis, decreased barrier function due to dysfunctional mitochondrial is amplified by lack of NOD2 in transporting enterocytes: subsequently, greater numbers of bacteria entering the mucosa would be a significant inflammatory threat especially since individuals with NOD2 mutations have compromised macrophage and Paneth cell responses to bacteria.

NEW & NOTEWORTHY Increased internalization of bacteria by epithelia with dysfunctional mitochondria (reduced ATP) is potentiated if the cells lack nucleotide-binding oligomerization domain 2 (NOD2), mutations in which are inflammatory bowel disease-susceptibility traits. Uptake of bacteria was dependent on reactive oxygen species and MAP-kinase activity, and the increased viable intracellular bacteria in NOD2−/−cells likely reflect a reduced ability to recognize and kill bacteria. Thus a significant barrier defect occurs with NOD2 deficiency in conjunction with metabolic stress that could contribute to inflammation.
Desmin loss and mitochondrial damage precede left ventricular systolic failure in volume overload heart failure
Authors: Guichard Jason L. , Rogowski Michael , Agnetti Giulio , Fu Lianwu , Powell Pamela , Wei Chih-Chang , Collawn James , Dell’Italia Louis J.
Published: April 2017

Heart failure due to chronic volume overload (VO) in rats and humans is characterized by disorganization of the cardiomyocyte desmin/mitochondrial network. Here, we tested the hypothesis that desmin breakdown is an early and continuous process throughout VO. Male Sprague-Dawley rats had aortocaval fistula (ACF) or sham surgery and were examined 24 h and 4 and 12 wk later. Desmin/mitochondrial ultrastructure was examined by transmission electron microscopy (TEM) and immunohistochemistry (IHC). Protein and kinome analysis were performed in isolated cardiomyocytes, and desmin cleavage was assessed by mass spectrometry in left ventricular (LV) tissue. Echocardiography demonstrated a 40% decrease in the LV mass-to-volume ratio with spherical remodeling at 4 wk with ACF and LV systolic dysfunction at 12 wk. Starting at 24 h and continuing to 4 and 12 wk, with ACF there is TEM evidence of extensive mitochondrial clustering, IHC evidence of disorganization associated with desmin breakdown, and desmin protein cleavage verified by Western blot analysis and mass spectrometry. IHC results revealed that ACF cardiomyocytes at 4 and 12 wk had perinuclear translocation of αB-crystallin from the Z disk with increased α, β-unsaturated aldehyde 4-hydroxynonelal. Use of protein markers with verification by TUNEL staining and kinome analysis revealed an absence of cardiomyocyte apoptosis at 4 and 12 wk of ACF. Significant increases in protein indicators of mitophagy were countered by a sixfold increase in p62/sequestosome-1, which is indicative of an inability to complete autophagy. An early and continuous disruption of the desmin/mitochondrial architecture, accompanied by oxidative stress and inhibition of apoptosis and mitophagy, suggests its causal role in LV dilatation and systolic dysfunction in VO.

NEW & NOTEWORTHY This study provides new evidence of early onset (24 h) and continuous (4−12 wk) desmin misarrangement and disruption of the normal sarcomeric and mitochondrial architecture throughout the progression of volume overload heart failure, suggesting a causal link between desmin cleavage and mitochondrial disorganization and damage.
Cardiac myofibrillar contractile properties during the progression from hypertension to decompensated heart failure
Authors: Hanft Laurin M. , Emter Craig A. , McDonald Kerry S.
Published: April 2017

Heart failure arises, in part, from a constellation of changes in cardiac myocytes including remodeling, energetics, Ca2+ handling, and myofibrillar function. However, little is known about the changes in myofibrillar contractile properties during the progression from hypertension to decompensated heart failure. The aim of the present study was to provide a comprehensive assessment of myofibrillar functional properties from health to heart disease. A rodent model of uncontrolled hypertension was used to test the hypothesis that myocytes in compensated hearts exhibit increased force, higher rates of force development, faster loaded shortening, and greater power output; however, with progression to overt heart failure, we predicted marked depression in these contractile properties. We assessed contractile properties in skinned cardiac myocyte preparations from left ventricles of Wistar-Kyoto control rats and spontaneous hypertensive heart failure (SHHF) rats at ~3, ~12, and >20 mo of age to evaluate the time course of myofilament properties associated with normal aging processes compared with myofilaments from rats with a predisposition to heart failure. In control rats, the myofilament contractile properties were virtually unchanged throughout the aging process. Conversely, in SHHF rats, the rate of force development, loaded shortening velocity, and power all increased at ~12 mo and then significantly fell at the >20-mo time point, which coincided with a decrease in left ventricular fractional shortening. Furthermore, these changes occurred independent of changes in β-myosin heavy chain but were associated with depressed phosphorylation of myofibrillar proteins, and the fall in loaded shortening and peak power output corresponded with the onset of clinical signs of heart failure.

NEW & NOTEWORTHY This novel study systematically examined the power-generating capacity of cardiac myofilaments during the progression from hypertension to heart disease. Previously undiscovered changes in myofibrillar power output were found and were associated with alterations in myofilament proteins, providing potential new targets to exploit for improved ventricular pump function in heart failure.
Diminished responsiveness to dobutamine as an inotrope in mice with cecal ligation and puncture-induced sepsis: attribution to phosphodiesterase 4 upregulation
Authors: Sakai Mari , Suzuki Tokiko , Tomita Kengo , Yamashita Shigeyuki , Palikhe Sailesh , Hattori Kohshi , Yoshimura Naoki , Matsuda Naoyuki , Hattori Yuichi
Published: April 2017

Dobutamine has been used in septic shock for many years as an only inotrope, but its benefit has been questioned. We weighed the effects of dobutamine and milrinone as inotropes in mice with cecal ligation and puncture (CLP)-induced polymicrobial sepsis. CLP-induced septic mice exhibited significant cardiac inflammation, as indicated by greatly increased mRNAs of proinflammatory cytokines and robust infiltration of inflammatory cells in the ventricular myocardium. Elevations of plasma cardiac troponin-I showed cardiac injury in CLP mice. Noninvasive echocardiographic assessment of cardiac function revealed that despite preserved left ventricular function in the presence of fluid replacement, the dobutamine inotropic response was significantly impaired in CLP mice compared with sham-operated controls. By contrast, milrinone exerted inotropic effects in sham-operated and CLP mice in an equally effective manner. Surface expression levels of β1-adrenoceptors and α-subunits of three main G protein families in the myocardium were unaffected by CLP-induced sepsis. Plasma cAMP levels were significantly elevated in both sham-operated and CLP mice in response to milrinone but only in sham-operated controls in response to dobutamine. Of phosphodiesterase (PDE) isoforms, PDE4D, but not PDE3A, both of which are responsible for cardiac cAMP hydrolysis, was significantly upregulated in CLP mouse myocardium. We define a novel mechanism for the impaired responsiveness to dobutamine as an inotrope in sepsis, and understanding the role of PDE4D in modulating cardiac functional responsiveness in sepsis may open the potential of a PDE4D-targeted therapeutic option in septic patients with low cardiac output who have a need for inotropic support.

NEW & NOTEWORTHY Advisability of the usefulness of dobutamine in septic shock management is limited. Here, we reveal that the effect of dobutamine as a positive inotrope is impaired in mice with cecal ligation and puncture-induced sepsis without changes in cardiac β1-adrenoceptor signaling as a result of cAMP breakdown achieved by upregulated phosphodiesterase 4D.
Longitude Position in a Time Zone and Cancer Risk in the United States
Authors: Gu Fangyi , Xu Shangda , Devesa Susan S. , Zhang Fanni , Klerman Elizabeth B. , Graubard Barry I. , Caporaso Neil E.
Published: April 2017

Background: Circadian disruption is a probable human carcinogen. From the eastern to western border of a time zone, social time is equal, whereas solar time is progressively delayed, producing increased discrepancies between individuals' social and biological circadian time. Accordingly, western time zone residents experience greater circadian disruption and may be at an increased risk of cancer.

Methods: We examined associations between the position in a time zone and age-standardized county-level incidence rates for total cancers combined and 23 specific cancers by gender using the data of the Surveillance, Epidemiology, and End Results Program (2000–2012), including four million cancer diagnoses in white residents of 607 counties in 11 U.S. states. Log-linear regression was conducted, adjusting for latitude, poverty, cigarette smoking, and state. Bonferroni-corrected P values were used as the significance criteria.

Results: Risk increased from east to west within a time zone for total and for many specific cancers, including chronic lymphocytic leukemia (both genders) and cancers of the stomach, liver, prostate, and non-Hodgkin lymphoma in men and cancers of the esophagus, colorectum, lung, breast, and corpus uteri in women.

Conclusions: Risk increased from the east to the west in a time zone for total and many specific cancers, in accord with the circadian disruption hypothesis. Replications in analytic epidemiologic studies are warranted.

Impact: Our findings suggest that circadian disruption may not be a rare phenomenon affecting only shift workers, but is widespread in the general population with broader implications for public health than generally appreciated. Cancer Epidemiol Biomarkers Prev; 26(8); 1306–11. ©2017 AACR.
Long-Term Results of Serial Transverse Enteroplasty with Neovalve Creation for Extreme Short Bowel Syndrome: Report of Two Cases
Authors: Botey Mireia , Alastrué Antonio , Haetta Henrik , Fernández-Llamazares Jaume , Clavell Arantxa , Moreno Pau
Published: April 2017

Objective: The aim of this article was to determine whether serial transverse enteroplasty (STEP) and the creation of a new ileocecal valve in extreme short bowel syndrome (SBS) cases (<45 cm) is effective in intestinal adaptation and improvement of nutritional parameters and serum citrulline levels. Patients and Methods: We present 2 cases of SBS treated with STEP. Enterectomy was performed for massive intestinal ischemia secondary to a gastrointestinal stromal tumor in the first case and to catastrophic antiphospholipid syndrome in the second. After enterectomy, the short residual bowel measured 34 cm in the first patient and 45 cm in the second. In both cases STEP, cholecystectomy, and gastrostomy were performed. In the first case a Brooke neovalve was created, and in the other the ileocecal valve was preserved. Results: Both patients could finally be weaned off total parenteral nutrition (TPN) and gastrostomy feeding, maintaining a good nutritional status 1 year after surgery. Conclusions: In extreme SBS, a minimum length of 80–90 cm of functioning small bowel and an intact ileocecal valve are necessary. We plead for the use of STEP with preservation of the ileocecal valve or creation of a neovalve using the Brooke technique in order to achieve the ultimate goal, which is to wean patients off TPN. After a critical review of different surgical techniques, a treatment algorithm is proposed.
Expression and Characterization of Serotype 2 Streptococcus suis Arginine Deiminase
Authors: Maneerat Krissana , Yongkiettrakul Suganya , Jiemsup Surasak , Tongtawe Pongsri , Gottschalk Marcelo , Srimanote Potjanee
Published: April 2017

Background: Arginine deiminase (ArcA) has been speculated to facilitate the intracellular survival of Streptococcus suis under acidic conditions. However, the physical and biological properties and function of SS2-ArcA have not yet been elucidated. Methods: Recombinant SS2-ArcA (rSS2-ArcA) was expressed and purified using Ni-NTA affinity chromatography. Under various pH and temperature conditions, the enzymatic properties of purified rSS2-ArcA and crude native SS2-ArcA were determined. Results: The SS2-arcA-deduced amino acid sequence contained a conserved catalytic triad (Cys399-His273-Glu218). The optimum temperature and pH of 47-kDa rSS2-ArcA and crude native SS2-ArcA were 42°C and pH 7.2. The rSS2-ArcA and crude native SS2-ArcA were stable for 3 h at 4 and 25°C, respectively. The pH stability and dependency tests suggested that rSS2-ArcA and crude native SS2-ArcA were functionally active in acidic conditions. The L-arginine substrate binding affinity (Km) values of rSS2-ArcA (specific activity 16.00 U/mg) and crude native SS2-ArcA (specific activity 0.23 U/mg) were 0.058 and 0.157 mM, respectively. rSS2-ArcA exhibited a weak binding affinity with the common ArcA inhibitors L-canavanine and L-NIO. Furthermore, the partial inactivation of SS2-ArcA significantly impaired the viability and growth of SS2 at pH 4.0, 6.0, and 7.5. Conclusions: This study profoundly demonstrated the involvement of ArcA enzymatic activity in S. suis survival under acidic conditions.
Limbal Stem Cell-Sparing Corneoscleroplasty with Peripheral Intralamellar Tuck: A New Surgical Technique for Keratoglobus
Authors: Jarade Elias , Antonios Rafic , el-Khoury Sylvain
Published: April 2017

Purpose: To describe the technique of limbal stem cell-sparing corneoscleroplasty for the management of advanced keratoglobus. Methods: A patient with bilateral advanced keratoglobus, with best-corrected visual acuity of 20/400 in the right eye and 20/200 in the left eye, underwent limbal stem cell-sparing corneoscleroplasty of the right eye. Initially, a 360-degree limbal incision with 200-μm depth was created, followed by a sublimbal tunnel dissection into the sclera, in order to conserve stem cells. Next, a limbus-to-limbus lamellar keratectomy at 200-μm depth was performed. Meanwhile, a donor corneoscleral button with preserved endothelium of the central 8 mm was fashioned. Prior to suturing the donor corneoscleral graft using a modified suturing technique to cover its scleral component, a full-thickness trephination of 8-mm diameter was completed in the central host cornea. Results: Reepithelialization occurred within the first week. No episodes of rejection, intraocular pressure spikes, or epithelial breakdown were observed postoperatively. At the 6-month follow-up, the patient had 20/70 best-corrected vision and a smooth cornea with regular astigmatism on topography. Conclusion: Limbal stem cell-sparing corneoscleroplasty is a single-step technique for restoring the structural integrity of the cornea in advanced keratoglobus while preserving the host limbal stem cells.
Changes in Cerebral Oxygenation Associated with Intradialytic Blood Transfusion in Patients with Severe Anemia Undergoing Hemodialysis
Authors: Ito Kiyonori , Ookawara Susumu , Ueda Yuichiro , Miyazawa Haruhisa , Kofuji Masaya , Hayasaka Hideyuki , Uchida Takayuki , Yanai Katsunori , Ishii Hiroki , Shindo Mitsutoshi , Kitano Taisuke , Hirai Keiji , Kaku Yoshio , Hoshino Taro , Tabei Kaoru , Morishita Yoshiyuki
Published: April 2017

Background: Hemodialysis (HD) patients frequently suffer from severe anemia caused by various hemorrhagic disorders in addition to renal anemia. Intradialytic blood transfusion is sometimes performed; however, the cerebral oxygenation changes associated with this procedure remain unclear. Methods: Sixteen HD patients with severe anemia who required intradialytic blood transfusion were included (12 men and 4 women; mean age, 64.8 ± 9.8 years). Cerebral regional oxygen saturation (rSO2) was monitored using near-infrared spectroscopy, and cerebral fractional oxygen extraction (FOE) was calculated before and after HD. Twenty-five HD patients with well-maintained hemoglobin (Hb) levels were included as a control group. Results: Cerebral rSO2 values were significantly lower in HD patients with severe anemia than in the control group (42.4 ± 9.9 vs. 52.5 ± 8.5%, p = 0.001). Following intradialytic blood transfusion (385 ± 140 mL of concentrated red blood cells), Hb levels significantly increased (from 7.2 ± 0.9 to 9.1 ± 1.1 g/dL, p < 0.001), and cerebral rSO2 values significantly improved after HD (from 42.4 ± 9.9 to 46.3 ± 9.0%, p < 0.001). Cerebral FOE values before HD in patients with severe anemia were significantly higher than those in the control group (severe anemia, 0.56 ± 0.10; controls, 0.45 ± 0.08; p < 0.001). After HD with intradialytic blood transfusion, these values significantly decreased (0.52 ± 0.09 after HD versus 0.56 ± 0.10 before HD, p = 0.002). Conclusion: HD patients with severe anemia represented cerebral oxygen metabolism deterioration, which could be significantly improved by intradialytic blood transfusion.
Identification of Two Additional Susceptibility Loci for Inflammatory Bowel Disease in a Chinese Populationy
Authors: Lan Xiucai , Lan Xiuhua , Chang Ying , Zhang Xiaomin , Liu Jing , Vikash Vikash , Wang Wei , Huang Meifang , Wang Xiaobing , Zhou Feng , Chen Liping , Zhao Qiu
Published: April 2017

Background/Aims: To investigate the associations between the rs1250569 (zinc finger MIZ-type containing 1, ZMIZ1), rs1042522 (tumour protein p53, TP53), and rs10114470 (tumour necrosis factor-like cytokine 1A, TL1A) polymorphisms and the development of inflammatory bowel disease (IBD) in a Chinese (Han) population. We analysed the expression of genes that predispose patients to Crohn’s disease (CD) and ulcerative colitis (UC). Methods: A total of 381 IBD patients and 517 healthy controls were recruited into our study. Polymorphisms at the three loci were genotyped using polymerase chain reaction-ligation detection reactions (PCR-LDR). Genotype-phenotype correlations were analysed. Blood and gut samples were obtained and analysed using quantitative real-time PCR (qRT-PCR), western blot analysis, and immunohistochemistry to investigate the mRNA and protein levels and in situ expression of genes found to predispose patients to IBD. Furthermore, the expression of susceptible genes was further verified using a mouse dextran sulphate sodium (DSS)-induced acute colitis model. Results: No significant association was detected between rs1250569 and rs1042522 genotypes and CD or UC susceptibility. However, the frequency of allele A of rs1250569 was much higher in CD patients than that in healthy controls (55.03% vs. 48.48%, respectively; p = 0.044). The mutation rates at rs10114470 were dramatically lower at both the genotype and allele level in patients than those in healthy controls (p = 0.002 at both the genotype and allele level). Additionally, increased ZMIZ1 and TL1A levels were detected in intestinal samples obtained from both IBD patients and DSS-treated mice. Conclusion: rs1250569 (ZMIZ1) and rs10114470 (TL1A) are two novel loci that indicate susceptibility to IBD in Han-Chinese patients. Consistent with previous studies, TL1A expression levels were higher in Chinese Han IBD patients and DSS-treated mice. Most importantly, we found that ZMIZ1 expression was markedly higher in both IBD patients and mice with experimentally induced colitis, suggesting that ZMIZ1 plays important roles in the pathogenesis of IBD.
Implications of CHA2DS2-VASc Score in Stroke Patients with Atrial Fibrillation: An Analysis of 938 Korean Patients
Authors: Hwang Jaechun , Chung Jong-Won , Lee Mi Ji , Kim Gyeong-Moon , Chung Chin-Sang , Lee Kwang Ho , Bang Oh Young
Published: April 2017

Background and Aims: The aim of this study was to investigate the stroke mechanisms and associated conditions influencing the decision regarding stroke thromboprophylaxis in patients with atrial fibrillation (AF) plus ischemic stroke, according to the CHA2DS2-VASc score. Methods: We evaluated 938 consecutive patients with a diagnosis of AF plus transient ischemic attack/ischemic stroke. Based on the CHA2DS2-VASc scores, patients were stratified as score 0 or 1 (n = 151), score 2 (n = 146), score 3 (n = 213), score 4 (n = 185), or score ≥5 (n = 243). Results: Patients with a higher CHA2DS2-VASc score were more likely to have noncardioembolic stroke mechanism (p = 0.001). Large-artery atherosclerosis causing stenosis >50% was more frequently observed in the high CHA2DS2-VASc group (p < 0.001). Coronary artery disease and the use of antiplatelet agents were more prevalent in the higher group (p < 0.001). A high CHA2DS2-VASc score was associated with a higher frequency of cerebral microbleeds and a higher Fazekas grade for leukoaraiosis (p < 0.001). The HAS-BLED score was correlated with the CHA2DS2-VASc score (γ = 0.650; p < 0.001). Conclusions: A higher CHA2DS2-VASc score is associated with noncardioembolic mechanisms of stroke and with a higher risk of bleeding. Strategies to treat macro/microangiopathy such as use of statin for plaque stabilization, as well as oral anticoagulants with a lower bleeding risk, are needed in these patients.
Branch Retinal Vein Occlusion, Macular Ischemia, and Intravitreal Anti-VEGF Therapy
Authors: Bertelmann Thomas , Frank Hans Ulrich , Fuchs Hendrik Ansgar , Feltgen Nicolas
Published: April 2017

Purpose: To report a case with ischemic macular edema (ME) due to an acute branch retinal vein occlusion (BRVO) which was treated with repeated intravitreal anti-VEGF injections. Methods: Retrospective case presentation. Results: A 66-year-old female patient was treated with repeated intravitreal anti-VEGF injections due to ischemic ME following an acute BRVO. Over a period of 2.5 years best corrected visual acuity increased from 0.06 to 0.6 (decimal notation) accompanied by a reduction in central retinal thickness from 546 to 292 µm. Overall 17 anti-VEGF injections were administered to treat repeated recurrence of ME. Macular ischemia did not worsen during this profound intravitreal anti-VEGF therapy. Conclusion: Intravitreal anti-VEGF therapy can be a beneficial treatment strategy even in ischemic ME following an acute BRVO.
Giant Orbital Melanoma in a Heroin Abuser
Authors: Furdova Alena , Babal Pavel
Published: April 2017

Purpose: The aim of this report was to report a heroin abuser with nondiagnosed giant uveal melanoma infiltrating the orbit and prolapsing through the face. Methods: We conducted a case report of the patient with giant melanoma. Results: In March 2013, a 39-year-old male with bleeding from the right side of his face was taken to the Emergency Center of the University Hospital Bratislava by ambulance. The heroin abusing, homeless male who had never been treated before reported a 2-year history of a prolapsed, dark colored mass from his eye. Acute computed tomography confirmed a solid mass 20 × 20 cm prolapsing from the orbit. The patient rejected primary care, accepted only 1 transfusion and left the hospital. Two months later, he was admitted to the hospital due to anemia after many collapses. Liver metastasis was present. Surgical palliative therapy was not possible due to his general status. The patient started fractionated external radiotherapy with 8.0 Gy Co60. Histopathological examination of the biopsy specimen showed malignant melanoma of the epitheloid type G2–3. The patient died in December 2013. Conclusion: Extraorbital formation of a melanoma mass may progress to a giant volume, and without treatment, led to metastases in the liver and to death after 9 months in our patient with anemia.
Samuel Thomas Soemmerring (1755-1830): The Naming of Cranial Nerves
Authors: Pearce John M.S.
Published: April 2017

Samuel Thomas Soemmerring was a Prussian polymathic doctor with remarkable achievements in anatomy, draftsmanship and inventions. His naming of 12 pairs of cranial nerves in his graduation thesis is of particular importance. He also gave original descriptions of the macula, sensory pathways and of the substantia nigra. His non-medical contributions were diverse and included criticism of the guillotine, invention of a telegraphic system, and discoveries in palaeontology.
Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa and X/Xa, emicizumab, depends on its ability to bridge the antigens
Authors: Kitazawa Takehisa , Esaki Keiko , Tachibana Tatsuhiko , Ishii Shinya , Soeda Tetsuhiro , Muto Atsushi , Kawabe Yoshiki , Igawa Tomoyuki , Tsunoda Hiroyuki , Nogami Keiji , Shima Midori , Hattori Kunihiro
Published: April 2017

Emicizumab, a humanised bispecific antibody recognising factors (F) IX/IXa and X/Xa, can accelerate FIXa-catalysed FX activation by bridging FIXa and FX in a manner similar to FVIIIa. However, details of the emicizumab–antigen interactions have not been reported so far. In this study, we first showed by surface plasmon resonance analysis that emicizumab bound FIX, FIXa, FX, and FXa with moderate affinities (K D = 1.58, 1.52, 1.85, and 0.978 μM, respectively). We next showed by immunoblotting analysis that emicizumab recognised the antigens’ epidermal growth factor (EGF)-like domains. We then performed K D-based simulation of equilibrium states in plasma for quantitatively predicting the ways that emicizumab would interact with the antigens. The simulation predicted that only a small part of plasma FIX, FX, and emicizumab would form antigen-bridging FIX–emicizumab–FX ternary complex, of which concentration would form a bell-shaped relationship with emicizumab concentration. The bell-shaped concentration dependency was reproduced by plasma thrombin generation assays, suggesting that the plasma concentration of the ternary complex would correlate with emicizumab’s cofactor activity. The simulation also predicted that at 10.0–100 μg/ml of emicizumab–levels shown in a previous study to be clinically effective–the majority of plasma FIX, FX, and emicizumab would exist as monomers. In conclusion, emicizumab binds FIX/FIXa and FX/FXa with micromolar affinities at their EGF-like domains. The K D-based simulation predicted that the antigen-bridging ternary complex formed in circulating plasma would correlate with emicizumab’s cofactor activity, and the majority of FIX and FX would be free and available for other coagulation reactions.

Institution where the work was carried out: Research Division, Chugai Pharmaceutical Co., Ltd.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Relationship Between Lifelong Exercise Volume and Coronary Atherosclerosis in Athletes
Authors: Aengevaeren Vincent L. , Mosterd Arend , Braber Thijs L. , Prakken Niek H.J. , Doevendans Pieter A. , Grobbee Diederick E. , Thompson Paul D. , Eijsvogels Thijs M.H. , Velthuis Birgitta K.
Published: April 2017

Background:

Higher levels of physical activity are associated with a lower risk of cardiovascular events. Nevertheless, there is debate on the dose-response relationship of exercise and cardiovascular disease outcomes and whether high volumes of exercise may accelerate coronary atherosclerosis. We aimed to determine the relationship between lifelong exercise volumes and coronary atherosclerosis.

Methods:

Middle-aged men engaged in competitive or recreational leisure sports underwent a noncontrast and contrast-enhanced computed tomography scan to assess coronary artery calcification (CAC) and plaque characteristics. Participants reported lifelong exercise history patterns. Exercise volumes were multiplied by metabolic equivalent of task (MET) scores to calculate MET-minutes per week. Participants’ activity was categorized as <1000, 1000 to 2000, or >2000 MET-min/wk.

Results:

A total of 284 men (age, 55±7 years) were included. CAC was present in 150 of 284 participants (53%) with a median CAC score of 35.8 (interquartile range, 9.3–145.8). Athletes with a lifelong exercise volume >2000 MET-min/wk (n=75) had a significantly higher CAC score (9.4 [interquartile range, 0–60.9] versus 0 [interquartile range, 0–43.5];
P
=0.02) and prevalence of CAC (68%; adjusted odds ratio [OR
adjusted
]=3.2; 95% confidence interval [CI], 1.6–6.6) and plaque (77%; OR
adjusted
=3.3; 95% CI, 1.6–7.1) compared with <1000 MET-min/wk (n=88; 43% and 56%, respectively). Very vigorous intensity exercise (≥9 MET) was associated with CAC (OR
adjusted
=1.47; 95% CI, 1.14–1.91) and plaque (OR
adjusted
=1.56; 95% CI, 1.17–2.08). Among participants with CAC>0, there was no difference in CAC score (
P
=0.20), area (
P
=0.21), density (
P
=0.25), and regions of interest (
P
=0.20) across exercise volume groups. Among participants with plaque, the most active group (>2000 MET-min/wk) had a lower prevalence of mixed plaques (48% versus 69%; OR
adjusted
=0.35; 95% CI, 0.15–0.85) and more often had only calcified plaques (38% versus 16%; OR
adjusted
=3.57; 95% CI, 1.28–9.97) compared with the least active group (<1000 MET-min/wk).

Conclusions:

Participants in the >2000 MET-min/wk group had a higher prevalence of CAC and atherosclerotic plaques. The most active group, however, had a more benign composition of plaques, with fewer mixed plaques and more often only calcified plaques. These observations may explain the increased longevity typical of endurance athletes despite the presence of more coronary atherosclerotic plaque in the most active participants.
Seven new species of Trichoderma (Hypocreales) in the Harzianum and Strictipile clades
Authors: QIN WEN-TAO , ZHUANG WEN-YING
Published: April 2017

Among 240 specimens of Trichoderma producing sexual states collected in different regions of China, 80 specimens representing 21 species possess green ascospores. Species were identified based on integrated studies of phenotypic features, culture characteristics and molecular analyses of RNA polymerase II subunit b and translation elongation factor 1-α genes. Of these 21 species, seven are recognized here as new: T. angustum, T. crystalligenum, T. globoides, T. perviride, T. purpureum, T. tenue and T. viridulum. Trichoderma angustum and T. crystalligenum belong to the Strictipile clade, and the remaining five species are in the Harzianum clade. Trichoderma angustum inhabits herbaceous stems and possesses trichoderma- to verticillium-like conidiophores. Trichoderma crystalligenum forms brownish yellow pulvinate stromata, pachybasium-like conidiophores, and abundant yellow crystals in culture. Trichoderma globoides and T. perviride share a common ancestor with but are different from T. alni, T. christiani, T. corneum and T. italicum. Trichoderma purpureum is a sister of T. epimyces, and is distinguished by its purplish red stromata. Trichoderma tenue is closely related to T. priciliae and T. rufobrunneum, and is characterized by verticillium-like conidiophores and slender phialides. Trichoderma viridulum is associated with T. cerinum, T. tomentosum and T. ceraceum; it is distinguishable by trichoderma-like rather than pachybasium-like conidiophores. Morphological distinctions between the new species and their allies are discussed. This study updates our knowledge of species diversity of the group.
Caamembeca salicifolia, a new combination for a Brazilian species of Polygalaceae
Authors: PASTORE JOSÉ FLORIANO B.
Published: April 2017

The effort to revise all South American names in Polygala L. has revealed the earliest epithet for the species known as Caamembeca laureola (A.St.-Hil. & Moq.) J.F.B.Pastore to be conspecific with Polygala salicifolia Poir. The name P. salicifolia was erroneously interpreted by De Candolle to belong to the genus Monnina Ruiz & Pav., thus it was transferred as Monnina longifolia DC. Finally, P. salicifolia seems to have been overlooked during the last century. The new combination Caamembeca salicifolia is provided.
Phyllactinia braunii sp. nov. (Erysiphales) on Cordia myxa from Central India
Authors: KUSHWAHA PRAKASH , SINGH RAGHVENDRA , CHAURASIA BALMUKUND , KUMAR SHAMBHU
Published: April 2017

Phyllactinia braunii sp. nov., discovered on living leaves of Cordia myxa (Boraginaceae) in a dry deciduous forest of Central India, is described and illustrated. It is compared with P. thirumalachari and its anamorph-typified synonym Ovulariopsis cordiae, a morphologically similar species known from India and Taiwan on Cordia dichotoma.
Taxonomy and evolutionary diversification of the Central European endemic Spergularia echinosperma (Caryophyllaceae)
Authors: KÚR PAVEL , AMARELL UWE , JAGE HORST , ŠTECH MILAN
Published: April 2017

The patterns of morphological variation and distribution of the rare Central European endemic Spergularia echinosperma were investigated. Morphometric analyses revealed the existence of two distinct morphotypes differing each other mainly in seed color, which is either brown or black. Other differences are in density of the seed surface papillae, height and shape of the papillae, seed width, pedicel/capsule and internode/leaf ratios, and leaf length. A geographic separation of the morphotypes also exists. The black-seeded morphotype occurred nearly exclusively in drained fishponds in the south-western part of the Czech Republic, the brown-seeded morphotype was found in drained fishponds in the eastern part of the Czech Republic and in alluvial pools and river deposits of the Elbe River (Germany). We hypothesize that the black-seeded morphotype may have been indigenous in former natural lakes which were widespread in the SW-Czech Republic and they were frequently transformed into fishponds. The brown-seeded morphotype may have its origin in river alluvia of the Elbe (Germany) and possibly also of other rivers in the Czech Republic. Since the two morphotypes are morphologically and geographically well separated, we propose to describe the brown-seeded morphotype as a new subspecies for science, S. echinosperma subsp. albensis subsp. nov.
A re-investigation of three Frenguelli’s Caloneis taxa (Pinnulariaceae, Bacillariophyta) from Argentina
Authors: SUNESEN INES , TARDIVO KUBIS JONAS A. , SAR EUGENIA A.
Published: April 2017

Caloneis mendosina var. mendosina, Caloneis mendosina var. minor and Caloneis quilinensis from slides of the Frenguelli Collection deposited at the Herbarium of the División Ficología ‘Dr. Sebastián A. Guarrera’ (LPC), were investigated using light microscope (LM). Unmounted material related to these slides was observed using the scanning electron microscope (SEM). Specimens of both varieties of C. mendosina found in the original material show a continuous range of size and stria density, and are ultrastructurally similar; thus the taxa are considered conspecific. Specimens of C. quilinensis found in the original material show more variability than described in the protologue. A continuous range of size, stria density, shape of the frustules and valve outline was observed between C. mendosina and C. quilinensis. Additionally, ultrastructural comparison of both taxa showed numerous features in common including shape of the valve surface, morphology of the valve mantle, shape of the axial area, shape of the fascia, position of the raphe, morphology and orientation of the external central and distal raphe fissures, and size and position of the elliptical apertures of the alveolate striae. The evidence that there is no morphologic and morphometric discontinuity between these Frenguelli taxa and that they come from similar diatomaceous earth deposits, justify considering them conspecific. Based on the principle of priority the correct name of the species is Caloneis mendosina. The description of C. mendosina was emended, a lectotype slide was selected, and a comparison with some allied species was conducted.
Comparison of TRMM-Derived Rainfall Products for General and Extreme Rains over the Maritime Continent
Authors: Sekaranom Andung Bayu , Masunaga Hirohiko
Published: April 2017

Properties of the rain estimation differences between Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR) 2A25, TRMM Microwave Imager (TMI) 2A12, and TRMM Multisatellite Precipitation Analysis (TMPA) 3B42 are investigated with a focus on distinguishing between nonextreme and extreme rains over the Maritime Continent from 1998 to 2014. Statistical analyses of collocated TMI 1B11 85-GHz polarization-corrected brightness temperatures, PR 2A23 storm-top heights, and PR 2A25 vertical rain profiles are conducted to identify possible sources of the differences. The results indicate that a large estimation difference exists between PR and TMI for the general rain rate (extreme and nonextreme events). The PR–TMI rain-rate differences are larger over land and coast than over ocean. When extreme rain is isolated, a higher frequency of occurrence is identified by PR over ocean, followed by TMI and TMPA. Over land, TMI yields higher rain frequencies than PR with an intermediate range of rain rates (between 15 and 25 mm h−1), but it gives way to PR for the highest extremes. The turnover at the highest rain rates arises because the heaviest rain depicted by PR does not necessarily accompany the strongest ice-scattering signals, which TMI relies on for estimating precipitation over land and coast.
The Role of Natural Climate Variability in Recent Tropical Expansion
Authors: Allen Robert J. , Kovilakam Mahesh
Published: April 2017

Observations show the tropical belt has widened over the past few decades, a phenomenon associated with poleward migration of subtropical dry zones and large-scale atmospheric circulation. Coupled climate models also simulate tropical belt widening, but less so than observed. Reasons for this discrepancy, and the mechanisms driving the expansion remain uncertain. Here, the role of unforced, natural climate variability—particularly natural sea surface temperature (SST) variability—in recent tropical widening is shown. Compared to coupled ocean–atmosphere models, atmosphere-only simulations driven by observed SSTs consistently lead to larger rates of tropical widening, especially in the Northern Hemisphere (NH), highlighting the importance of recent SST evolution. Assuming the ensemble mean SSTs from historical simulations accurately represent the externally forced response, the observed SSTs can be decomposed into a forced and an unforced component. Targeted simulations with the Community Atmosphere Model, version 5 (CAM5), show that natural SST variability accounts for nearly all of the widening associated with recent SST evolution. This is consistent with the similarity of the unforced SSTs to the observed SSTs, both of which resemble a cold El Niño–Southern Oscillation/Pacific decadal oscillation (ENSO/PDO)-like SST pattern, which is associated with a wider tropical belt. Moreover, CAM5 coupled simulations with observed central to eastern tropical Pacific SSTs yield more than double the rate of widening compared to analogous simulations without prescribed tropical Pacific SSTs and reproduce the magnitude of tropical widening in atmosphere-only simulations. The results suggest that the bulk of recent tropical widening, particularly in the NH, is due to unforced, natural SST variability, primarily related to recent ENSO/PDO variability.
“I Alone” vs. “Stronger Together”: Contrasting Visions in the 2016 Nomination Acceptance Addresses
Authors: Smith Craig Allen
Published: April 2017

Nomination acceptance addresses perform two major functions: They reconstitute the factions splintered by the primaries into a unified party and they frame the general election campaign as a clash between two narrative visions of America. In 2016, Donald Trump co-opted Republicans into his empire, conflated imagining and remembering to envision an American dystopia caused mainly by Clinton, claimed that he alone could fix things using unspecified mechanisms, and promised to provide an immediate American utopia. Clinton envisioned a cooperative nation with fewer recent successes than problems, explained that only together could we improve our prospects for a better future by working hard to enact unspecified policies, and warned us against making a bad man our potentate. Donald Trump and Hillary Clinton performed the rhetorical functions of consolidating support and framing the campaign but, to date, no rhetor has found a way to reconcile them into a unifying American vision.
Prediction of Lignin Content in Different Parts of Sugarcane Using Near-Infrared Spectroscopy (NIR), Ordered Predictors Selection (OPS), and Partial Least Squares (PLS)
Authors: Assis Camila , Ramos Rachel S. , Silva Lidiane A. , Kist Volmir , Barbosa Márcio H.P. , Teófilo Reinaldo F.
Published: April 2017

The building of multivariate calibration models using near-infrared spectroscopy (NIR) and partial least squares (PLS) to estimate the lignin content in different parts of sugarcane genotypes is presented. Laboratory analyses were performed to determine the lignin content using the Klason method. The independent variables were obtained from different materials: dry bagasse, bagasse-with-juice, leaf, and stalk. The NIR spectra in the range of 10 000–4000 cm−1were obtained directly for each material. The models were built using PLS regression, and different algorithms for variable selection were tested and compared: iPLS, biPLS, genetic algorithm (GA), and the ordered predictors selection method (OPS). The best models were obtained by feature selection with the OPS algorithm. The values of the root mean square error prediction (RMSEP), correlation of prediction ( RP), and ratio of performance to deviation (RPD) were, respectively, for dry bagasse equal to 0.85, 0.97, and 2.87; for bagasse-with-juice equal to 0.65, 0.94, and 2.77; for leaf equal to 0.58, 0.96, and 2.56; for the middle stalk equal to 0.61, 0.95, and 3.24; and for the top stalk equal to 0.58, 0.96, and 2.34. The OPS algorithm selected fewer variables, with greater predictive capacity. All the models are reliable, with high accuracy for predicting lignin in sugarcane, and significantly reduce the time to perform the analysis, the cost and the chemical reagent consumption, thus optimizing the entire process. In general, the future application of these models will have a positive impact on the biofuels industry, where there is a need for rapid decision-making regarding clone production and genetic breeding program.
Colocated Mental Health/Developmental Care
Authors: Levy Sheryl L. , Hill Elena , Mattern Kathryn , McKay Kevin , Sheldrick R. Christopher , Perrin Ellen C.
Published: April 2017

The inadequacy of mental health and developmental services for children is a widely recognized and growing problem. Although a variety of solutions have been proposed, none has been generally successful or feasible. This research describes models of colocation that have evolved in primary care settings in Massachusetts and reports on pediatricians’ and their colocated colleagues’ impressions of their benefits and challenges. Pediatricians in 18 practices that included a colocated mental health/developmental specialist (MH/DS) were identified through a survey administered through the state American Academy of Pediatrics Chapter, and interviewed. Practices varied widely in the professional expertise/training and roles of the MH/DSs, communication among providers, and financial arrangements. The majority of pediatricians and MH/DSs reported being pleased with their colocated arrangements, despite the costs rarely being supported by billing revenues. This study suggests that further development of such systems hold promise to meet the growing need for accessible pediatric mental and developmental health care.
Random Versus Blocked Practice to Enhance Mental Representation in Golf Putting
Authors: Fazeli Davoud , Taheri HamidReza , Saberi Kakhki Alireza
Published: April 2017

The purpose of this study was to investigate changes in mental representation from either random or blocked practice when engaged in golf putting. Thirty participants were randomly assigned to random practice, blocked practice, and no-practice groups. First, we measured novice golfers’ initial mental representation levels and required them to perform 18 putting trials as a pre-test. We then asked random and blocked groups to practice in accordance with their group assignment for six consecutive days (10 blocks each day, 18 trials each). A week after the last practice session, we re-measured all participants’ final mental representation levels and required them to perform 18 putting trials to evaluate learning retention through practice. While those engaged in the random practice method putted more poorly during acquisition (i.e., practice) than those in blocked practice, the random practice group experienced more accurate retention during the final putting trials, and they showed a more structured mental representation than those in blocked practice, one that was more similar to that of skilled golfers. These results support the acquisition of a rich mental representation through random versus blocked practice.
Can Withdrawing Citizenship Be Justified?
Authors: Barry Christian , Ferracioli Luara
Published: April 2017

Denationalisation – withdrawing citizenship from a person – is a practice with a long historic pedigree that continues to affect the lives of many people today. Are there conditions under which denationalisation is morally justified? If so, what are they? And can legal and political norms that authorise states to engage in citizenship withdrawal be justified? This article provides answers to these questions.