bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacologic Inhibitor of DNA-PK, M3814, Potentiates Radiotherapy and Regresses Human Tumors in Mouse Models
Authors: Zenke Frank T. , Zimmermann Astrid , Sirrenberg Christian , Dahmen Heike , Kirkin Vladimir , Pehl Ulrich , Grombacher Thomas , Wilm Claudia , Fuchss Thomas , Amendt Christiane , Vassilev Lyubomir T. , Blaukat Andree
Published: March 2020

Physical and chemical DNA-damaging agents are used widely in the treatment of cancer. Double-strand break (DSB) lesions in DNA are the most deleterious form of damage and, if left unrepaired, can effectively kill cancer cells. DNA-dependent protein kinase (DNA-PK) is a critical component of nonhomologous end joining (NHEJ), one of the two major pathways for DSB repair. Although DNA-PK has been considered an attractive target for cancer therapy, the development of pharmacologic DNA-PK inhibitors for clinical use has been lagging. Here, we report the discovery and characterization of a potent, selective, and orally bioavailable DNA-PK inhibitor, M3814 (peposertib), and provide in vivo proof of principle for DNA-PK inhibition as a novel approach to combination radiotherapy. M3814 potently inhibits DNA-PK catalytic activity and sensitizes multiple cancer cell lines to ionizing radiation (IR) and DSB-inducing agents. Inhibition of DNA-PK autophosphorylation in cancer cells or xenograft tumors led to an increased number of persistent DSBs. Oral administration of M3814 to two xenograft models of human cancer, using a clinically established 6-week fractionated radiation schedule, strongly potentiated the antitumor activity of IR and led to complete tumor regression at nontoxic doses. Our results strongly support DNA-PK inhibition as a novel approach for the combination radiotherapy of cancer. M3814 is currently under investigation in combination with radiotherapy in clinical trials.
Facial Pain: A Comprehensive Review and Proposal for a Pragmatic Diagnostic Approach
Authors: Van Deun Laura , de Witte Muriel , Goessens Thaïs , Halewyck Stijn , Ketelaer Marie-Christine , Matic Milica , Moens Maarten , Vaes Peter , Van Lint Michel , Versijpt Jan
Published: March 2020

Background: Facial pain, alone or combined with other symptoms, is a frequent complaint. Moreover, it is a symptom situated at, more than any other pain condition, a crosspoint where several disciplines meet, for example, dentists; manual therapists; ophthalmologists; psychologists; and ear-nose-throat, pain, and internal medicine physicians besides neurologists and neurosurgeons. Recently, a new version of the most widely used classification system among neurologists for headache and facial pain, the International Classification of Headache Disorders, has been published. Objective: The aims of this study were to provide an overview of the most prevalent etiologies of facial pain and to provide a generic framework for the neurologist on how to manage patients presenting with facial pain. Methods: An overview of the different etiologies of facial pain is provided from the viewpoint of the respective clinical specialties that are confronted with facial pain. Key message: Caregivers should “think outside their own box” and refer to other disciplines when indicated. If not, a correct diagnosis can be delayed and unnecessary treatments might be given. The presented framework is aimed at excluding life- or organ-threatening diseases, providing several clinical clues and indications for technical investigations, and ultimately leading to the correct diagnosis and/or referral to other disciplines.
Childhood Cat Bites Relate to Increased Adulthood Severity of Schizotypy, Psychotic-Like Experiences, and Social Anhedonia in a Transdiagnostic Psychiatric Sample
Authors: Bedwell Jeffrey S. , Spencer Christopher C. , Southwell Amber L.
Published: March 2020

Introduction: Previous research has linked childhood cat scratches and bites to an increased risk for depression, and childhood cat ownership to increased risk of schizophrenia, bipolar disorder, and social anhedonia. Our group previously reported that childhood cat bites, but not ownership, related to increased schizotypy severity in an undergraduate sample. Methods: The current study expands this research by inquiring about cat bites and ownership in a transdiagnostic adult sample (N = 162; 51% female; mean age = 38.15, SD = 10.65), composed of schizophrenia spectrum disorders (n = 30), bipolar disorders (n = 30), unipolar depression (n = 23), and nonpsychiatric participants (n = 79). Participants completed a diagnostic interview, scales of symptom severity, and a cat interaction history interview. Results: Across the entire sample, self-report of cat bites prior to age 13, but not after, related to greater current severity of overall schizotypy, self-reported and clinician-rated psychotic-like symptoms, and social anhedonia, when compared to individuals who reported no lifetime cat bites. Cat bites prior to age 13 did not relate to severity of depression, non-social anhedonia, or clinician-rated negative symptoms. Self-report of residing with a cat prior to age 13, or a first cat bite after age 12, did not relate to any symptom severity measure examined. Conclusions: One theory for these findings is that an unknown infectious agent common in cat saliva interacted with brain development in childhood to increase the likelihood of these symptoms. A novel theory for the infectious agent Pasteurella multocidais discussed. Future research can examine candidate infectious agents to identify potential causal mechanisms for these relationships.
Persistence of Intraluminal Thrombus Makes Saccular Aneurysm More Biologically Active than Fusiform in an Experimental Rat Model
Authors: Etienne Harry , Journé Clément , Rouchaud Aymeric , Senemaud Jean , Louedec Liliane , Pellenc Quentin , Coscas Raphaël , Gouya Laurent , Dupont Sébastien , Michel Jean-Baptiste
Published: March 2020

Introduction: Saccular aneurysms are thought to have a worse prognosis than fusiform aneurysms in humans, due to hemodynamic reasons. However, data comparing hemodynamic and biology in saccular and fusiform aneurysms are lacking. The main objective was to evaluate the impact of aneurysm morphology on intra-luminal thrombus (ILT) formation and activity. Methods: Forty Lewis rats were ran­domly divided into 2 groups of 20: “saccular” (Group A) and “fusiform” (Group B) aneurysms. Decellularized thoracic aortas from guinea pigs were xenografted to create saccular or fusiform aneurysms. Final imaging evaluation of the aneurysms was carried out during the third week, by quantitative Doppler ultrasound and magnetic resonance imaging. Assays of myeloperoxidase (MPO), platelet factor 4 (PF4), advanced oxidation protein products (AOPPs) iron and matrix metallopeptidase-9 (MMP-9) were performed as biological criteria. Results: Quantitatively, saccular aneurysms are characterized by a more thicker ILT, lower inflow velocities and more important relative backflow velocities as compared to fusiform aneurysms. Compared to fusiform, saccular aneurysms released significantly more MPO (p = 0.004), PF4 (p = 0.02), AOPPs (p < 0.002), iron (p < 0.0001) and MMP-9 (p < 0.04). Conclusion: Experimental saccular and fusiform aneurysms show differential specific hemodynamics, which seem to impact the histology and the biology of the ILT in each type of aneurysm.
The Origin of the Idea That Herpes Labialis Is of Prognostic Importance in Bacterial Meningitis
Authors: Koehler Peter J.
Published: March 2020

Objective:The aim of the work was to study the origin of the idea that herpes labialis (HL) in patients with pneumonia and meningitis was believed to be of prognostic importance. Background:HL is caused by a primary infection or reactivation of herpes simplex type I. In the past, it has been related to pneumonia and meningitis; moreover, HL was believed to be of prognostic importance. Methods:A selection of 19th- and 20th-century textbooks and referred articles was consulted. The relation between meningitis and herpes, type of meningitis, and attributed diagnostic and prognostic importance were studied. In addition, the HL-pneumonia association was studied. Results:The Strasbourg physician Charles-Polydore Forget was the first to describe the HL-meningitis association in 1843. Tourdes (1843), Drasche (1859), and Salomon (1864) attributed a favorable prognostic importance to the HL-meningitis relation. In a comprehensive monograph (1866), August Hirsch, although confirming the association, denied the prognostic importance through critical analysis of the data. Few authors attributed a diagnostic importance to the occurrence of HL, suggesting meningococcal meningitis. Conclusions:The HL-meningitis relation, but not the prognostic importance, has been mentioned in most neurological textbooks since then. In contrast to meningitis, in which a prognostic attribution of HL was only a short-lived 19th-century idea, the favorable prognostic importance of HL in pneumonia continued to be described until the 1950s. A possible protective effect of herpesviruses has been found in recent years. One could speculate that the disappearance of the prognostic HL-pneumonia relation could be related to the introduction of antibiotics in the late 1940s.
A Retrospective Analysis of Clinical Trial Accrual of Patients Presented in a Multidisciplinary Tumor Board at a Tertiary Health Care Center and Associated Barriers
Authors: Mobley Erin M. , Swami Umang , Mott Sarah , Ounda Agnes , Milhem Mohammed , Monga Varun
Published: March 2020

Introduction: Cancer clinical trial accruals have been historically low and are affected by several factors. Multidisciplinary Tumor Board Meetings (MTBM) are conducted regularly and immensely help to devise a comprehensive care plan including discussions about clinical trial availability and eligibility. Objectives: To evaluate whether patient discussion at MTBM was associated with a higher consent rate for clinical trials at a single tertiary care center. Methods: Institutional electronic medical records (EMR) and clinical trials management system (OnCore) were queried to identify all new patient visits in oncology clinics, consents to clinical trials, and MTBM notes between January 1, 2011 and December 31, 2015. The association between MTBM discussion and subsequent clinical trial enrollment within 16 weeks of the new patient visit was evaluated using a χ2 test. Results: Between January 1, 2011 and December 31, 2015, 11,794 new patients were seen in oncology clinics, and 2,225 patients (18.9%) were discussed at MTBMs. MTBM discussion conferred a higher rate of subsequent clinical trial consent within 16 weeks following the patient’s first consultation in an oncology clinic: 4.1% for those who were discussed at a MTBM compared to 2.8% for those not discussed (p < 0.01). Conclusions: This study provides evidence that MTBMs may be effective in identifying patients eligible for available clinical trials by reviewing eligibility criteria during MTBM discussions. We recommend discussion of all new patients in MTBM to improve the quality of care provided to those with cancer and enhanced clinical trial accrual.
Identification of a Novel Arginine Vasopressin Receptor 2 Mutation (p.V183M) in a Chinese Family with Nephrogenic Diabetes Insipidus
Authors: Liu Ji-Shi , Huang Hao , Jin Jie-Yuan , Du Ran , Wang Chen-Yu , Fan Liang-Liang
Published: March 2020

Loss of function of arginine vasopressin receptor 2 (AVPR2) may affect the recognition and binding of arginine vasopressin (AVP) which, in turn, may prevent the activation of Gs/adenylate cyclase and reduce the reabsorption of water by renal tubules and combined tubes. Finally, the organism may suffer from nephrogenic diabetes insipidus (NDI), a kind of kidney disorder featured by polyuria and polydipsia, due to a break of water homeostasis. In this study, we enrolled a Chinese family with polyuria and polydipsia. The proband presented abnormal fluid intake and excessive urine output. A water deprivation and AVP stimulation test further indicated that this patient had NDI. By sequencing known causative genes for diabetes insipidus, we identified a novel mutation in AVPR2 (c.547G>A; p.V183M) in the family. This mutation, located in a conserved site of AVPR2 and predicted to be disease-causing by informatics programs, was absent in our 200 controls and other public databases. Our study not only further confirms the clinical diagnosis, but also expands the spectrum of AVPR2 mutations and contributes to genetic diagnosis and counseling of patients with NDI.
Bivalirudin Versus Heparin Monotherapy in Elderly Patients With Myocardial Infarction
Authors: Wester Axel , Attar Rubina , Mohammad Moman A. , Isma Nazim , James Stefan , Omerovic Elmir , Erlinge David , Koul Sasha
Published: March 2020

Background:

Elderly patients with acute myocardial infarction undergoing percutaneous coronary intervention are at increased risk of both ischemic and bleeding complications. The optimal anticoagulation strategy in these patients is uncertain. Therefore, we compared bivalirudin to heparin monotherapy in a contemporary cohort of such patients.

Methods:

A prespecified subgroup analysis of elderly patients with myocardial infarction (≥75 years) from the VALIDATE-SWEDEHEART trial (Bivalirudin Versus Heparin in ST-Segment and Non–ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) was performed. In the trial, patients were randomized to either bivalirudin or heparin monotherapy during percutaneous coronary intervention, with mandatory potent P2Y12 inhibition, routine radial artery access, and only bail-out glycoprotein IIb/IIIa inhibition. Kaplan-Meier event rates were assessed for the primary end point, consisting of a composite of all-cause death, myocardial reinfarction, or major bleeding, within 180 days.

Results:

The elderly (n=1592) had more than twice the risk of all events compared with younger patients (n=4406). Baseline and periprocedural characteristics were equal between bivalirudin (n=799) and heparin (n=793) treated patients ≥75 years. No differences were found in the elderly between bivalirudin and heparin monotherapy regarding the primary end point (180-day all-cause death, myocardial reinfarction, or major bleeding), the individual components of the primary end point, definite stent thrombosis, or stroke.

Conclusions:

In this prespecified subgroup analysis of the VALIDATE-SWEDEHEART trial, elderly patients with myocardial infarction had a highly increased risk of all events. However, no difference in outcomes could be observed with an anticoagulation strategy with either bivalirudin or heparin as monotherapy in this patient group.
CSC Expert Consensus on Principles of Clinical Management of Patients With Severe Emergent Cardiovascular Diseases During the COVID-19 Epidemic
Authors: Han Yaling , Zeng Hesong , Jiang Hong , Yang Yuejin , Yuan Zuyi , Cheng Xiang , Jing Zhicheng , Liu Bin , Chen Jiyan , Nie Shaoping , Zhu Jianhua , Li Fei , Ma Changsheng
Published: March 2020

In response to the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, the Chinese Society of Cardiology (CSC) issued this consensus statement after consulting with 125 medical experts in the fields of cardiovascular disease and infectious disease. The over-arching principles laid out here are the following: 1) Consider the prevention and control of COVID-19 transmission as the highest priority, including self-protection of medical staff; 2) Patient risk assessment of both infection and cardiovascular issues. Where appropriate, preferential use of conservative medical therapeutic approaches to minimize disease spread; 3) At all times, medical practices and interventional procedures should be conducted in accordance with the directives of the infection control department of local hospitals and local health commissions.
Between Apologetics, Emancipation and Imperial Paternalism
Authors: Urbaniak Jakub , Motsisi Mooketsi
Published: March 2020

Scholarship on the abolition of the slave trade and slavery has given little attention to specifically theological factors behind the movement. This article seeks to interrogate three themes that underpinned the activism of the British abolitionists, namely, deliverance/liberty, love of neighbor, and imago Dei. These are examined, first, within their own biblical-theological frame of reference and, second, in relation to other intellectual currents of the era as well as, anachronistically, in the light of some key features of liberation theology. The article considers whether the British abolitionists, whose rhetoric oscillated around apologetics and emancipation and was marked by imperial paternalism, developed a form of proto-liberation theology.
The Relationship between Third-party Countermeasures and the Security Council’s Chapter vii Powers: Enforcing Obligations erga omnes in International Law
Authors: Bills Amanda
Published: March 2020

The article examines the relationship between third-party countermeasures and the Security Council’s powers to adopt measures under Chapter vii of the United Nations Charter in response to breaches of obligations erga omnes. It is shown that the resort to third-party countermeasures is neither precluded nor subject to limitations as a result of the relationship to the Security Council’s Chapter vii powers, even when both types of measures are adopted concurrently. Moreover, the fears that third-party countermeasures would interfere with or undermine the effective application of Security Council measures do not appear to have materialised in practice.
A new species of Asphondylia (Diptera: Cecidomyiidae) causing leaf galls on jujube, Ziziphus jujuba Mill. (Rhamnaceae) in India
Authors: VASANTHAKUMAR DURAIKANNU , PALANISAMY SENTHILKUMAR , PETER VINNY R. , SHARMA RADHESHYAM M.
Published: March 2020

Jujube Ziziphus jujuba Mill. (Rhamnaceae), known as “Ber” in India, is an evergreen thorny shrub with reddish-brown fruits, chiefly found in Southeast Asia (Reza 2014). Up to now three species of gall midges have been associated with jujube: Phyllodiplosis jujubae Grover & Bakshi, and Silvestrina jujubae Chandra in India and Dasineura jujubifolia Jiao & Bu in China (Grover & Bakhshi 1978; Chandra 1988; Jiao et al. 2017). Between 2015 and 2018 during field trips by DV & VRP to Singanallur lake area, Coimbatore, Tamil Nadu, one of us (DV) noticed and collected leaves of Z. jujuba containing small galls on the midrib region of leaves. In the laboratory the leaves were dissected, and causative agent identified as a gall midge. The adults were reared and identified as undescribed species of gall midge, here described and named Asphondylia singanallurensis Vasanthakumar & Sharma. Type specimens were processed and mounted in Canada balsam as per the method in Kolesik et al. (2015). Holotype and paratypes were prepared and deposited in the collection of the Zoological Survey of India, WRC, Pune.
Four new Burmese species of Hemiphyllodactylus Bleeker (Squamata: Gekkonidae) from distantly related parapatric clades from the Shan Plateau and Salween Basin
Authors: GRISMER L. LEE , WOOD PERRY L. JR. , QUAH EVAN S. H. , THURA MYINT KYAW , OAKS JAMIE R. , LIN AUNG
Published: March 2020

An integrative taxonomic analysis based on morphology, color pattern, and the mitochondrial gene ND2 recovered four new species of Hemiphyllodactylus Bleeker that are endemic to the Shan Plateau or Salween Basin in eastern Myanmar. Hemiphyllodactylus ngwelwini sp. nov. from the Shan Plateau is part of the earlier described “eastern Myanmar clade” renamed herein as the north lineage and H. kyaiktiyoensis sp. nov. and H. pinlaungensis sp. nov. of the Shan Plateau and H. zwegabinensis sp. nov. of the Salween Basin compose an entirely new Burmese clade herein referred to as the south lineage. Although the north and south lineages come within 46 km of one another on the Shan Plateau, they are not sister lineages but sequentially separated by two lineages from Yunnan, China and another from northwestern Thailand. Hemiphyllodactylus zwegabinensis sp. nov. is the first species of this genus to be recorded from the Salween Basin and is known only from a wind-blown cloud forest on the top of the insular, karstic mountain Zwegabin in Kayin State. All other Burmese species except for H. typus, are endemic to the various localities throughout the Shan Plateau. These four new species bring the total number of Hemiphyllodactylus in Myanmar to at least 10 which is certainly an extreme underestimate of the diversity of this genus given that we discover new species at every upland locality we survey.
Description of a new diminutive Hyloxalus (Anura: Dendrobatidae: Hyloxalinae) from the Magdalena Valley of Colombia
Authors: ACOSTA-GALVIS ANDRÉS R. , VARGAS-RAMÍREZ MARIO , ANGANOY-CRIOLLO MARVIN , IBARRA OSCAR A. , GONZÁLES SANDRA
Published: March 2020

Using different sources of evidence (i.e., integrative taxonomy), we describe a new species of Hyloxalus, Hyloxalus arliensis sp. nov. The new species occurs in the middle Magdalena River valley on slopes between the Cordillera Central and Cordillera Oriental of the Andes of Colombia. Previously, the new species was referred to as Hyloxalus “Ibagué” but was not formally described. Phylogenetic re-analyses of 2440 base pairs (bp) of mitochondrial DNA (mtDNA), revealed the species to be a sister taxon of H. lehmanni, within a monophyletic clade also comprising H. delatorreae lineage 1, H. pulchellus and H. vertebralis. The adult males of H. arliensis sp. nov. have a pale arm gland, which differentiates it from all other species of the genus, except for H. saltarius. The new species also differs from other species of Hyloxalus by its smaller size, disc on Finger III not expanded, toes unwebbed, dorsolateral stripe absent, oblique lateral stripe present, white spots on ventrolateral flanks in life and cloacal tubercles absent. The advertisement call consists of long trains of a single note repeated at a rate of 89–132 notes/min with a dominant frequency ranging from 4808–6387 Hz. The new species is a tiny frog that inhabits the sheltered areas around streams in sub-Andean forests. Aspects of its natural history are described.
Axiidean ghost shrimps (Decapoda: Axiidae, Callianassidae, Callichiridae, Micheleidae) of the Trindade and Martin Vaz Archipelago, Vitória-Trindade Seamounts Chain and Abrolhos, off southeastern Brazil
Authors: PACHELLE PAULO P.G. , TAVARES MARCOS
Published: March 2020

The Trindade and Martin Vaz (TMV) volcanic archipelago is highly isolated, being located some 1200 km off the Brazilian coast and about 4200 km away from the nearest African coast. The only axiidean known from the archipelago is Coralaxius nodulosus (Meinert, 1877), a species extensively reported in the western Atlantic. From 2012 to 2018, 263 SCUBA diving and intertidal samplings were conducted at TMV and yielded 46 axiidean specimens in three species, one of which is a new species: Corallianassa longiventris (A. Milne-Edwards, 1870), Neocallichirus grandimana (Gibbes, 1850), and Fragillianassa joeli sp. nov., a species closely related to F. fragilis (Biffar, 1970). Hitherto unreported specimens from along the Vitória-Trindade Seamounts Chain (VTSC) and the Abrolhos Bank were also included in this report, namely C. nodulosus and Michelea vandoverae (Gore, 1987). The occurrence of M. vandoverae at the Abrolhos Bank extends its range into the southwestern Atlantic. Coralaxius abelei Kensley & Gore, 1981 is herein considered a junior synonym of Coralaxius nodulosus (Meinert, 1877). Meinertaxius Sakai, 2011, therefore becomes a subjective synonym of Coralaxius Kensley & Gore, 1981. Axiideans from the tropical southern-central Atlantic oceanic islands (Ascension, Fernando de Noronha, Rocas Atoll, Saint Helena, Trindade and Martin Vaz) are listed with their gross distribution in the Atlantic Ocean revealing a strongly depauperate axiidean insular fauna, totaling six species. Except for Axiopsis serratifrons (A. Milne-Edwards, 1873), a pantropical species, the insular southwestern-central Atlantic axiideans are entirely of western Atlantic affinities, with F. joeli sp. nov. being the only endemic so far.
A new species of turtle-headed sea Snake (Emydocephalus: Elapidae) endemic to Western Australia
Authors: NANKIVELL JAMES H. , GOIRAN CLAIRE , HOURSTON MATHEW , SHINE RICHARD , RASMUSSEN ARNE R. , THOMSON VICKI A. , SANDERS KATE L.
Published: March 2020

We describe a new species of turtle-headed sea snake Emydocephalus orarius sp. nov. (Elapidae) from Western Australia’s Coral Coast, Pilbara and Kimberley regions. Phylogenetic analysis of mitochondrial markers places the new species as the sister lineage to the two currently recognised species in Emydocephalus: E. annulatus from the Timor Sea reefs and Coral Sea, and E. ijimae from the Ryukyu Islands. Analysis of nuclear SNP data from the new species and E. annulatus from Australia and New Caledonia provides additional independent evidence of their evolutionary distinctiveness. The new taxon is usually morphologically diagnosable from its congeners using a combination of scalation and colour pattern characters, and appears to reach greater total lengths (>1 m in the new species versus typically ~80 cm in E. annulatus/E. ijimae). The new species is known largely from soft-bottomed trawl grounds, unlike E. annulatus and E.ijimae which usually inhabit coral reefs. The discovery of this new species brings the number of sea snake species endemic to Western Australia to six.
Ghost-moths of Trinidad and Tobago with description of a new genus and a new species (Lepidoptera: Hepialidae)
Authors: MIELKE CARLOS G.C. , GREHAN JOHN R. , COCK MATTHEW J.W.
Published: March 2020

The Hepialidae species of Trinidad and Tobago are documented and two species are recognized. The new and monotypic genus Wallacella, gen. n., (Lepidoptera, Hepialidae) is erected to include Phassus guianensis Schaus of Guyana (Wallacella guianensis, comb. n.). The male holotype and genitalia are also illustrated for the first time. Potential generic affinities with Druceiella (Viette) and Pfitzneriana (Viette) are considered. Gymelloxes juliusboosi sp. n. is described from Trinidad and Tobago and compared to its congeneric species. The sternite VIII and male genitalia are diagnostic for this new species. The male holotype is deposited in the collection of the Natural History Museum, London, UK.
Simultaneously Strengthening and Toughening Poly(lactic acid) by Co-Additions of Poly(ɛ-caprolactone), Tributyl Citrate Plasticizer and Functionalized Multiwall Carbon Nanotube
Authors: Lin Guangyi , Wang Jia , Lv Ningning , Wang Honghao , Wang Hong , Yu Boquan , Liu Shouyi , Liang Dong , Wang Quanjie , Yu Kaiben
Published: March 2020

In order to strengthen and toughen poly(lactic acid) (PLA), poly(ɛ-caprolactone) (PCL), tributyl citrate (TBC) plasticizer and sodium dodecylbenzene sulfonate (SDBS) modified multi-walled carbon nanotubes (s-MWCNTs) were melt compounded with PLA materials for the first time. The
effect of s-MWCNTs on the morphology, as well as mechanical and thermal properties of PLA/PCL blends (containing 8 wt% TBC) was investigated. By co- additions of PCL, TBC, and s-MWCNTs at an optimized composition (containing 10 phr∼PCL, 8 phr∼TBC, 3 phr∼s-MWCNTs (phr∼parts
per hundred)), simultaneously strengthening and toughening of PLA could be achieved, where the tensile strength and elongation at break of the nanocomposites were greatly enhanced by 8% and 147.9%, respectively, as compared to the neat PLA. The toughening mechanism was attributed to the synergistic
effect of the flexibility of PCL and plasticizer effect of TBC, and the strengthen mechanism was attributed to the reinforcing effect of s-MWCNTs. In addition, the s-MWCNTs could be served as a nucleation agent and promote the growth rate of PLA crystallization. Overall, we proposed a simple
and effective method to fabricate high-performance PLA materials with balanced mechanical properties.
Study on Mechanical Model of Balance and Stiffness Characteristics of Fiber Reinforced Bellows Type Rubber Hose
Authors: Hua Gao , Changgeng Shuai , Guomin Xu
Published: March 2020

The mechanical model related to the balance and stiffness characteristics of the bellows type rubber hose under internal pressure was studied. Based on the thin shell theory without considering bending moments and shear force, the equilibrium equation of the bellows type hose was established
to obtain the mechanical equilibrium angle under different mechanical environments. Considering the deformation characteristics of the rope structure and the mechanical equilibrium angle of the hose, the deformation of the bellows type rubber hose was divided into two stages, including winding
angle deflection and tensile deformation of fiber. Then the constitutive model of anisotropic material was introduced, and the physical equation of the bellows type hose was established to obtain the mechanical model of the balance and stiffness characteristics. According to the mechanical
model, the influence of initial fiber winding angle, fiber layer thickness, the radius at the two ends of the hose, the length of hose, the curvature radius and internal pressure of hose on the balance and stiffness characteristics of hose was studied. Eventually, the structure of the hose
was designed based on the mechanical model, to optimize the balance and stiffness characteristics of hose. The balance and stiffness characteristics of the optimized hose were verified by experiments. The theoretical and experimental results indicated that, the mechanical model of the balance
and stiffness characteristics of the hose can be the theoretical basis for the optimization of structural parameters.
Detection of Human Influence on Precipitation Extremes in Asia
Authors: Dong Siyan , Sun Ying , Li Chao
Published: March 2020

This paper examines the possible influence of external forcings on observed changes in precipitation extremes in the mid-to-high latitudes of Asia during 1958–2012 and attempts to identify particular extreme precipitation indices on which there are better chances to detect the influence of external forcings. We compare a recently compiled dataset of observed extreme indices with those from phase 5 of the Coupled Model Intercomparison Project (CMIP5) simulations using an optimal fingerprinting method. We consider six indices that characterize different aspects of extreme precipitation, including annual maximum amount of precipitation falling in 1 day (Rx1day) or 5 days (Rx5day), the total amount of precipitation from the top 5% or top 1% daily amount on wet days, and the fraction of the annual total precipitation from these events. For single-signal analysis, the fingerprints of external forcings including anthropogenic agents are robustly detected in most studied extreme indices over all Asia and for midlatitude Asia but not for high-latitude Asia. For two-signal analysis, anthropogenic influence is detectable in these indices over Asia at 5% or slightly less than 5% significance level, whereas natural influence is not detectable. In high-latitude Asia, anthropogenic influence is detected only in a fractional index, representing a stark contrast to the midlatitude and full Asia results. We find relatively smaller internal variability and thus higher signal-to-noise ratio in the fractional indices when compared with the other ones. Our results point to the need for studying precipitation extreme indices that are less affected by internal variability while still representing the relevant nature of precipitation extremes to improve the possibility of detecting a forced signal if one is present in the data.
Characteristics and mechanical properties of composites based on nitrile butadiene rubber using graphene nanoplatelets
Authors: Vozniakovskii AA , Vozniakovskii AP , Kidalov SV , Otvalko J , Yu Neverovskaia A
Published: March 2020

This paper presents the results of a study of the strength and thermophysical properties of the composite material graphene nanoplatelets (GNP)–nitrile butadiene rubber (NBR) (GNP@NBR). High-quality GNP were massively produced by self-propagating high-temperature synthesis (SHS) method. It was found that the introduction of GNP in concentrations up to 6 wt.% leads to an increase in tensile strength up to 62%, resistance to tearing up to 64% thermal conductivity up to 2. The use of GNP allowed increasing the maximum operating temperature of the NBR to 125℃. Also, GNP@NBR composite showed an exceptional improvement in antifriction properties – it drops more than twice the coefficient of friction on steel under loads to 500 Newtons.
The Financial Identity Scale (FIS): A multinational validation and measurement invariance study among emerging adults
Authors: Sorgente Angela , Vosylis Rimantas , Lanz Margherita , Serido Joyce , Shim Soeyon
Published: March 2020

The transition from financial dependence on one’s parents to financial self-sufficiency is one of the most relevant transitions during emerging adulthood. It is important to have an instrument able to assess emerging adults’ financial capabilities and to detect its change over time. The current article aims to collect international evidence of the Financial Identity Scale (FIS) validity and reliability. Cross-sectional data collected from 2,501 emerging adults aged 18–25 and belonging to three different countries—U.S. ( n = 1,535), Italy ( n = 485), and Lithuania ( n = 481)—were adopted to test score structure validity, generalizability, sensitivity to difference, criterion-related validity, and internal consistency. Instead, four-wave longitudinal data, available for the American sample only ( n = 1,900), were adopted to test FIS structural stability and sensitivity to change. As recommended by the contemporary view of validity, different structural equation models were performed. Findings suggest that FIS scores are valid and reliable. The implications for researchers and practitioners are discussed.
Long-term safety and efficacy of erenumab in patients with chronic migraine: Results from a 52-week, open-label extension study
Authors: Tepper Stewart J , Ashina Messoud , Reuter Uwe , Brandes Jan Lewis , Doležil David , Silberstein Stephen D , Winner Paul , Zhang Feng , Cheng Sunfa , Mikol Daniel D
Published: March 2020

Background

This study reports the long-term safety and efficacy of erenumab in chronic migraine patients.

Methods

This was a 52-week open-label extension study of a 12-week double-blind treatment phase study. During the double-blind treatment phase, patients received placebo or once-monthly erenumab 70 mg or 140 mg. During the open-label treatment phase, the initial monthly dose was erenumab 70 mg. Following protocol amendment, patients continued to receive erenumab 70 mg if they had already completed their Week 28 visit, otherwise, patients switched from 70 mg to 140 mg; if enrolled after the amendment, patients received 140 mg monthly throughout.

Results

In all, 451/609 (74.1%) enrolled patients completed the study. The exposure-adjusted patient incidence rate for any adverse event was 126.3/100 patient-years for the overall erenumab group. Overall, the adverse event profile was similar to that observed in the double-blind treatment phase. Adverse event incidence rates did not increase with long-term erenumab treatment compared with the double-blind treatment phase, and no new serious or treatment-emergent events were seen. Efficacy was sustained throughout the 52 weeks. Clinically significant reductions from double-blind treatment phase baseline (about half) were observed for monthly migraine days and migraine-specific medication days. Achievement of ≥50%, ≥75% and 100% reductions from the double-blind treatment phase baseline in monthly migraine days at Week 52 were reported by 59.0%, 33.2% and 8.9% of patients, respectively, for the combined dose group. A numerically greater benefit was observed with 140 mg compared with 70 mg at Weeks 40 and 52.

Conclusions

Sustained efficacy of long-term erenumab treatment in patients with chronic migraine is demonstrated, with safety results consistent with the known safety profile of erenumab and adverse event rates comparable to placebo adverse event rates in the double-blind treatment phase.

Trial registration:

This study is registered at ClinicalTrials.gov (NCT02174861)
Fabrication and characterization of a novel semi-interpenetrating network hydrogel based on sodium carboxymethyl cellulose and poly(methacrylic acid) for oral insulin delivery
Authors: Li Shunying , Chen Zhiru , Wang Jun , Yan Libiao , Chen Tingting , Zeng Qingbing
Published: March 2020

In this research, pH-sensitive semi-interpenetrating polymer network hydrogels based on sodium carboxymethyl cellulose and poly(methacrylic acid) were synthesized using free radical polymerization and semi-interpenetrating polymer network approach for oral administration of insulin. The chemical structure and thermal stability of the hydrogels were characterized using Fourier transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis measurements. The interior morphology was observed by scanning electron microscopy and the inner structure exhibited a porous honeycomb-like shape. The investigations on the swelling properties of hydrogels revealed their ability to response to pH value change. The in vitro release behavior of insulin was pH dependent and the release of insulin was much lower at pH 1.2 compared to pH 6.8. In vitro cytotoxicity assay indicated that the hydrogels were noncytotoxic to HeLa cells. A sustained reduction in blood glucose level was observed after oral administration of insulin-loaded hydrogel to diabetic rats at 75 IU/kg. These results indicated that the hydrogel would be a promising vehicle for oral insulin delivery systems.
Influence of the temperature- and frequency-dependent dynamic properties of rail pads on the vibration characteristics of rails at low temperature
Authors: Ping Wang , Yinling Dou , Shaohua Wang , Feng Wang , Wei Kai
Published: March 2020

The dynamic properties of railway tracks and rail pads are significant for accurately predicting both the wheel–rail system vibration and rolling noise. The effect that the dynamic properties of rail pads have on the dynamic characteristics of railway tracks at extremely low temperatures was not adequately studied in previous research. In order to better predict the attenuation of the rail vibration, the viscoelastic dynamic properties of rail pads varying nonlinearly with temperature and frequency were first tested, in a wide temperature range (−60 ℃ to 20 ℃), and represented by the fractional derivative Zener model. Then, rail vibration and its attenuation characteristics were investigated by accounting for the frequency-dependent, temperature-dependent and frequency- and temperature-dependent properties, respectively. To be more specific, the frequency and amplitude of the rail first-order bending resonance and pinned–pinned resonance, as well as the rail decay rate were analyzed for the three cases. In conclusion, the study shows that the temperature/frequency-dependent properties of the rail pad have a significant effect on the first-order bending resonance of the rail, but no influence on the pinned–pinned resonance frequency. The rail decay rate indicates a clear increasing trend in the entire frequency domain with the decrease of temperature (especially below about −20 ℃). The frequency dependence mainly affects the vibration and its attenuation characteristics of the rail below about 400 Hz, which should not be ignored in the track dynamics modelling. Therefore, when the analyzed environmental temperature is below −20 ℃, the temperature dependence of rail pads should be considered.
Donor-Specific Regulatory T Cell-Mediated Immune Tolerance in an Intrahepatic Murine Allogeneic Islet Transplantation Model with Short-Term Anti-CD154 mAb Single Treatment
Authors: Lee Seok-Joo , Kim Hyun-Je , Byun Na-ri , Park Chung-Gyu
Published: March 2020

Anti-CD154 blockade-based regimens remain unequaled in prolonging graft survival in various organ transplantation models. Several studies have focused on transplantation tolerance with the anti-CD154 blockade, but none of these studies has investigated the mechanisms associated with its use as the sole treatment in animal models, delaying our understanding of anti-CD154 blockade-mediated immune tolerance. The purpose of this study was to investigate the mechanism underlying the anti-CD154 monoclonal antibody (mAb) blockade in inducing immune tolerance using an intrahepatic murine allogeneic islet transplantation model. Allogeneic BALB/c AnHsd (BALB/c) islets were infused into the liver of diabetic C57BL/6 (B6) mice via the cecal vein. Anti-CD154 mAb (MR1) was administered on −1, 0, 1, 3, 5, and 7 d posttransplantation at 0.5 mg per mouse. We showed that short-term MR1 monotherapy could prolong the allogeneic islet grafts to more than 250 d in the murine intrahepatic islet transplantation model. The second islet grafts transplanted under the kidney capsule of the recipients were protected from rejection. We also found that rejection of same-donor skin grafts transplanted to the tolerant mice was modestly delayed. Using a DEREG mouse model, FoxP3+ regulatory T (Treg) cells were shown to play important roles in transplantation tolerance. In mixed lymphocyte reactions, Treg cells from the tolerant mice showed more potency in suppressing BALB/c splenocyte-stimulated Teff cell proliferation than those from naïve mice. In this study, we demonstrated for the first time that a short-term anti-CD154 mAb single treatment could induce FoxP3+ Treg cell-mediated immune tolerance in the intrahepatic murine allogeneic islet transplantation model.
Impact of congenital heart disease on siblings: A review
Authors: Parker Roses , Houghton Sarah , Bichard Elizabeth , McKeever Stephen
Published: March 2020

Congenital heart disease (CHD) is the most common birth defect. Little is known of the impact of having a sibling with CHD. Available literature documents negative impact of having a sibling with other chronic conditions. This literature review considers empirical evidence investigating the impact of having a sibling with CHD. Twelve databases were searched, and 202 articles retrieved. Eleven articles met the inclusion criteria and were subject to data extraction, quality appraisal, and narrative synthesis. Three themes emerged: changes in normal life, impact on siblings, and factors affecting the extent of impact on siblings. Only one intervention study was identified, 5 of 10 studies were conducted over 20 years ago, and only 4 studies included children as participants. Evidence suggests siblings of children with CHD experience adverse life changes which lead to negative impacts in several domains. Evidence is inconclusive regarding mitigating factors of these impacts. Further research is needed to understand the experiences of being a sibling of a child with CHD.
Leaving lights on – A conscious choice or wasted light? Use of indoor lighting in Swedish homes
Authors: Gerhardsson Kiran M. , Laike Thorbjörn , Johansson Maria
Published: March 2020

Promoting resource- and energy-efficient home lighting through technology and behaviour change requires an understanding of how residents currently use lighting and what they want from it. However, users' needs and desires relating to lighting in homes are poorly understood, as research is still limited. This paper aims to provide a fuller picture of residents' experiences with their home lighting. Interviews about how residents perceive the character of lighting and luminaires and lighting use suggest that home lighting has nine capabilities: to enable vision; to facilitate visual tasks; to display objects; to send a message; to support a particular atmosphere; to shape the architectural space; to offer a visual aesthetic experience; to maintain or change rhythmicity; and to evoke memories. Secondary data confirmed five of them. The identified capabilities relate to behavioural goals, psychological wellbeing and social needs. We conclude that seemingly wasted light in people's homes, i.e. lights left on in unoccupied rooms, can serve a purpose for the residents, such as avoiding visual or aesthetic discomfort, making the home inviting, benefitting people outside and providing safety. Findings have implications for the further development of new lighting technologies and design, energy-saving campaigns targeting residents and for urban outdoor environments.
The interrupted world: Surrealist disruption and altered escapes from reality
Authors: Jones Scott , Cronin James , Piacentini Maria
Published: March 2020

Following Breton’s writings on surreality, we outline how unexpected challenges to consumers’ assumptive worlds have the potential to alter how their escape from reality is experienced. We introduce the concept of ‘surrealist disruption’ to describe ontological discontinuities that disrupt the common-sense frameworks normally used by consumers and that impact upon their ability to suspend their disbeliefs and experience self-loss. To facilitate our theorization, we draw upon interviews with consumers about their changing experiences as viewers of the realist political TV drama House of Cards against a backdrop of disruptive real-world political events. Our analyses reveal that, when faced with a radically altered external environment, escape from reality changes from a restorative, playful experience to an uneasy, earnest one characterized by hysteretic angst, intersubjective sense-making and epistemological community-building. This reconceptualizes escapism as more emotionally multivalenced than previously considered in marketing theory and reveals consumers’ subject position to an aggregative social fabric beyond their control.
WGCNA analysis of the subcutaneous fat transcriptome in a novel tree shrew model
Authors: Han Yuanyuan , Wang Wenguang , Jia Jie , Sun Xiaomei , Kuang Dexuan , Tong Pinfen , Li Na , Lu Caixia , Zhang Huatang , Dai Jiejie
Published: March 2020

Obesity involves genetic and environmental factors. The co-expression gene network in relevant tissues in different obesity groups provides an entrance for profiling and identifying associated pathways and genes. We aim to identify the meaningful co-expressed gene network in mRNA extracted from adipose tissues representing different obesity phenotypes in a new tree shrew model. Furthermore, to find the potential drug target based on analyzing the possible pathways and hub genes responsible for obesity. Ten tree shrews were selected from F1 populations and divided into three groups based on their Lee’s index for mRNA sequencing. We identified clusters of highly correlated genes (modules) in differently expressed genes by weighted gene co-expression network analysis. Three modules were firmly correlated with not less than one obesity phenotype (associations ranging from −0.94 to 0.85, P < 0.01). The genes from the blue module (including 481 genes) are mostly enriched in the ribosome pathway. The genes from the brown module (including 389 genes) are mostly enriched in the lysosome pathway. The genes from the turquoise module (including 1781 genes) are mostly enriched in the ubiquitin-mediated proteolysis pathway. The hub gene in each module was determined, including UBA52 in the blue module, AKT1 in the brown module, and LRRK2 in the turquoise module. After profiling and analyzing the co-expression gene network of obese tree shrew, we identified differently expressed genes and pathways (ribosome, lysosome and ubiquitin-mediated proteolysis pathway) that might be involved in the development of obesity. Further study of the differently expressed genes and pathways might provide new targets for the prevention and therapy of obesity.

Impact statement

We constructed the transcriptomic network in adipose tissue in lean, moderate obesity and severe obesity groups of tree shrew for the first time. Compared to other laboratory animal models, the tree shrew is a prospective laboratory animal that has a closer genetic association with primates than with rodents. It is widely used in biomedical researches. Enrichment analyses revealed several molecular biological processes were involved in the ribosome, lysosome, and ubiquitin-mediated proteolysis process. These results provided insights into new targets for the prevention and therapy of obesity and a novel research model for obesity.