bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffuse large B-cell lymphoma in Southeast Asian cohort: expression patterns of B-cell receptor (BCR) repertoire and its linkage with molecular subtypes and response to R-CHOP therapy
Authors: Masir Noraidah , Akhter Ariz , Roshan Tariq M , Florence Chandramaya Sabrina , Abdul-Rahman Faridah , Tumian Nor Rafeah , Kean-Chang Phang , Elyamany Ghaleb , Shabani-Rad Meer-Taher , Mansoor Adnan
Published: June 2019

Aims

Heightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia.

Methods

79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS).

Results

Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, highBTKexpression exerted poor response to R-CHOP, while OS in ABC-DLBCL with lowBTKexpression was similar to GCB-DLBCL subtype (p=0.004). HighLYNexpression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression ofBTK/LYN(BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, highBTKandLYNexpression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05).

Conclusions

Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.
TNFRSF21 mutations cause high myopia
Authors: Pan Hong , Wu Shijing , Wang Jing , Zhu Tian , Li Tengyan , Wan Bo , Liu Beihong , Luo Yan , Ma Xu , Sui Ruifang , Wang Binbin
Published: June 2019

Background

High myopia (HM) is one of the leading causes of vision impairment worldwide, accompanied by a series of pathological ocular complications. Studies have shown that genetic factors play an important role in the pathogenesis of HM. The aim of our study is to identify a candidate gene for a large family with non-syndromic HM.

Methods

A large Chinese family, including 12 patients with non-syndromic HM, and 220 unrelated patients with HM, were recruited from the Department of Ophthalmology, Peking Union Medical College Hospital. Three affected subjects from the large family were selected to perform whole exome sequencing (WES). Rare heterozygous variants shared by all three subjects were retained and then Sanger sequencing was used to determine whether any of the remaining variants cosegregated with the disease phenotype. Furthermore, all coding regions of the candidate genes were analysed in 220 unrelated patients with HM. Immunofluorescence assay was used to detect the expression of the candidate gene in the eye. Annexin V/PI staining and flow cytometry were applied to detect cell apoptotic changes.

Results

WES identified a novel TNF receptor superfamily member 21 (TNFRSF21) variant, P146A, in a large Chinese family with HM, and another three rare heterozygous variants (P202L, E240* and A440G) in TNFRSF21 were found in 220 unrelated cases with HM. Immunofluorescence assay indicated that it is strongly expressed in the mouse eye. Compared with the wild type, the P146A variant could significantly increase adult retinal pigment epithelial cell line-19 cell apoptotic levels.

Conclusions

Variants in TNFRSF21 cause non-syndromic HM in Chinese population.
Impact of natural menopause on multiple sclerosis: a multicentre study
Authors: Baroncini Damiano , Annovazzi Pietro Osvaldo , De Rossi Nicola , Mallucci Giulia , Torri Clerici Valentina , Tonietti Simone , Mantero Vittorio , Ferrò Maria Teresa , Messina Maria Josè , Barcella Valeria , La Mantia Loredana , Ronzoni Marco , Barrilà Caterina , Clerici Raffaella , Susani Emanuela Laura , Fusco Maria Letizia , Chiveri Luca , Abate Lucia , Ferraro Ottavia , Capra Ruggero , Colombo Elena , Confalonieri Paolo , Zaffaroni Mauro
Published: June 2019

Objective

To study the effect of natural menopause on multiple sclerosis clinical course.

Methods

This was an observational, retrospective, multicentre, cohort study. Menopause onset was defined by the final menstrual period (FMP) beyond which no menses occurred for 12 months. We included multiple sclerosis (MS) patients with FMP occurred after 2005 and a recorded follow-up of at least 2 years pre-FMP and post-FMP. We excluded patients with primary progressive course, iatrogenic menopause and with other confounders that could mask menopause onset. We compared relapse-rate and expanded disability status scale (EDSS) scores pre-FMP and post-FMP, searching for possible interactions with age, disease duration, cigarette smoking and nulliparity status.

Results

148 patients were included (mean observation: 3.5 years pre-FMP and post-FMP). Most patients (92%) received disease-modifying therapies, mainly first-lines. After menopause the annualised relapse rate (ARR) significantly decreased (from 0.21±0.31 to 0.13± 0.24; p=0.005), while disability worsened (increase of mean 0.4 vs 0.2 points after menopause; p<0.001). Older age and long-lasting disease were associated with ARR reduction (p=0.013), but not with disability worsening. Cigarette smokers showed a trend to a higher disability accumulation after menopause (p=0.059).

Conclusion

Natural menopause seems to be a turning point to a more progressive phase of MS. Relapse rate is also reduced after menopause, but this effect could be driven most by ageing and shifting to progressive phase in patients with long-lasting disease. Cigarette smoking could speed up disability progression after menopause.
Is it acceptable to contact an anonymous egg donor to facilitate diagnostic genetic testing for the donor-conceived child?
Authors: Horton Rachel , Bell Benjamin , Fenwick Angela , Lucassen Anneke M
Published: June 2019

We discuss a case where medically optimal investigations of health problems in a donor-conceived child would require their egg donor to participate in genetic testing. We argue that it would be justified to contact the egg donor to ask whether she would consider this, despite her indicating on a historical consent form that she did not wish to take part in future research and that she did not wish to be informed if she was found to be a carrier of a ‘harmful inherited condition’. We suggest that we cannot conjecture what her current answer might be if, by participating in clinical genetic testing, she might help reach a diagnosis for the donor-conceived child. At the point that she made choices regarding future contact, it was not yet evident that the interests of the donor-conceived child might be compromised by her answers, as it was not foreseen that the egg donor’s genome might one day have the potential to enable diagnosis for this child. Fertility consent forms tend to be conceptualised as representing incontrovertible historical boundaries, but we argue that rapid evolution in genomic practice means that consent in such cases is better seen as an ongoing and dynamic process. It cannot be possible to compel the donor to aid in the diagnosis of the donor-conceived child, but she should be given the opportunity to do so.
Home care aides’ experiences of verbal abuse: a survey of characteristics and risk factors
Authors: Karlsson Nicole D , Markkanen Pia K , Kriebel David , Gore Rebecca J , Galligan Catherine J , Sama Susan R , Quinn Margaret M
Published: June 2019

Objective

Violence from care recipients and family members, including both verbal and physical abuse, is a serious occupational hazard for healthcare and social assistance workers. Most workplace violence studies in this sector focus on hospitals and other institutional settings. This study examined verbal abuse in a large home care (HC) aide population and evaluated risk factors.

Methods

We used questionnaire survey data collected as part of a larger mixed methods study of a range of working conditions among HC aides. This paper focuses on survey responses of HC aides (n=954) who reported on verbal abuse from non-family clients and their family members. Risk factors were identified in univariate and multivariable analyses.

Results

Twenty-two per cent (n=206) of aides reported at least one incident of verbal abuse in the 12 months before the survey. Three factors were found to be important in multivariable models: clients with dementia (relative risk (RR) 1.38, 95% CI 1.07 to 1.78), homes with too little space for the aide to work (RR 1.52, 95% CI 1.17 to 1.97) and predictable work hours (RR 0.74, 95% CI 0.58 to 0.94); two additional factors were associated with verbal abuse, although not as strongly: having clients with limited mobility (RR 1.35, 95% CI 0.94 to 1.93) and an unclear plan for care delivery (RR 1.27, 95% CI 0.95 to 1.69). Aides reporting verbal abuse were 11 times as likely to also report physical abuse (RR 11.53; 95% CI 6.84 to 19.45).

Conclusions

Verbal abuse is common among HC aides. These findings suggest specific changes in work organisation and training that may help reduce verbal abuse.
Movements of the wrist and the risk of carpal tunnel syndrome: a nationwide cohort study using objective exposure measurements
Authors: Lund Christina Bach , Mikkelsen Sigurd , Thygesen Lau Caspar , Hansson Gert-Åke , Thomsen Jane Frølund
Published: June 2019

Objectives

We conducted a large cohort study to investigate the association between work-related wrist movements and carpal tunnel syndrome (CTS).

Methods

Electro-goniometric measurements of wrist movements were performed for 30 jobs (eg, office work, child care, laundry work and slaughterhouse work). We measured wrist angular velocity, mean power frequency (MPF) and range of motion (ROM). We established a cohort of Danish citizens born 1940–1979 who held one of these jobs from age 18–80 years, using Danish national registers with annual employment information from 1992 to 2014. We updated the cohort by calendar year with job-specific and sex-specific means of measured exposures. Dates of a first diagnosis or operation because of CTS were retrieved from the Danish National Patient Register. The risk of CTS by quintiles of preceding exposure levels was assessed by adjusted incidence rate ratios (IRRadj) using Poisson regression models.

Results

We found a clear exposure–response association between wrist angular velocity and CTS with an IRRadj of 2.31 (95% CI 2.09 to 2.56) when exposed to the highest level compared with the lowest. MPF also showed an exposure–response pattern, although less clear, with an IRRadj of 1.83 (1.68 to 1.98) for the highest compared with the lowest exposure level. ROM showed no clear pattern. Exposure–response patterns were different for men and women.

Conclusions

High levels of wrist movement were associated with an increased risk of CTS. Preventive strategies should be aimed at jobs with high levels of wrist movements such as cleaning, laundry work and slaughterhouse work.
High willingness to use novel HIV and bacterial sexually transmitted infection partner notification, testing, and treatment strategies among gay and bisexual men
Authors: John Steven A , Starks Tyrel J , Rendina H Jonathon , Parsons Jeffrey T , Grov Christian
Published: June 2019

Objectives

We sought to determine willingness of gay and bisexual men (GBM) to give HIV self-testing (HIVST) kits with patient-delivered partner therapy (PDPT) and engage in geosocial sexual networking (GSN) app-based partner notification.

Methods

A nationwide sample of GBM who self-tested HIV negative (n
=
786) were asked about their willingness to give recent sex partners (main and casual) PDPT with an HIVST kit (PDPT+HIVST) after hypothetical bacterial STI (BSTI) diagnosis. Men were also asked about their willingness to notify sexual partners met on GSN apps using an anonymous app function after BSTI diagnosis. We examined associations of relationship status and condomless anal sex with casual partners, recent BSTI diagnosis and perceived risk of HIV on PDPT+HIVST and anonymous app-based partner notification willingness (dichotomised) using binary logistic regressions, adjusting for age, race/ethnicity, education and US region. From the partner’s perspective after receiving an app-based referral, frequency measures were used to report intentions for obtaining subsequent HIV/BSTI counselling and testing, engaging in HIVST if provided a free voucher, and obtaining BSTI treatment from a pharmacy with prescription voucher.

Results

Most (90.1%) were willing to give PDPT+HIVST to recent sex partners after STI diagnosis, and nearly all (96.4%) were willing to notify sex partners met online using an anonymous function within GSN apps. Regardless of casual partner condomless anal sex engagement, partnered GBM had higher odds of reporting willingness to give PDPT+HIVST compared with single men who recently engaged in condomless anal sex with a casual partner. If anonymously notified via an app, 92.5% reported they would likely obtain counselling and testing, 92.8% would engage in HIVST if provided a free voucher, and 93.4% would obtain treatment from a pharmacy with prescription voucher.

Conclusions

GBM generally found novel partner notification, testing, and treatment strategies acceptable, indicating the need for feasibility and cost-effectiveness evaluations.
Study of superradiance in the Lambert-W potential barrier
Authors: Puente Luis , Cocha Carlos , Rojas Clara
Published: June 2019

We present a new potential barrier that presents the phenomenon of superradiance when the reflection coefficient [Formula: see text] is greater than one. We calculated the transmission and reflection coefficients for three different regions. The results are compared with those obtained for the hyperbolic tangent potential barrier and the step potential barrier. We also present the solution of the Klein–Gordon equation with the Lambert-[Formula: see text] potential barrier in terms of the Heun Confluent functions.
Einstein’s dream
Authors: Hammond Richard T.
Published: June 2019

It is shown the antisymmetric part of the metric tensor is the potential for the torsion field, which arises from intrinsic spin. To maintain gauge invariance, the nonsymmetric part of the metric tensor must be generalized to include the electromagnetic field. This result leads to a link between the cosmological constant and the electromagnetic field.
How low can vacuum energy go when your fields are finite-dimensional?
Authors: Cao ChunJun , Chatwin-Davies Aidan , Singh Ashmeet
Published: June 2019

According to the holographic bound, there is only a finite density of degrees of freedom in space when gravity is taken into account. Conventional quantum field theory does not conform to this bound, since in this framework, infinitely many degrees of freedom may be localized to any given region of space. In this paper, we explore the viewpoint that quantum field theory may emerge from an underlying theory that is locally finite-dimensional, and we construct a locally finite-dimensional version of a Klein–Gordon scalar field using generalized Clifford algebras. Demanding that the finite-dimensional field operators obey a suitable version of the canonical commutation relations makes this construction essentially unique. We then find that enforcing local finite dimensionality in a holographically consistent way leads to a huge suppression of the quantum contribution to vacuum energy, to the point that the theoretical prediction becomes plausibly consistent with observations.
Experimental and Numerical Analyses of R134a Flow Boiling Heat Transfer Characteristics in an Evaporator Tube of Refrigeration System
Authors: Yasser Zahraa Kareem , Hamad Ahmed J.
Published: June 2019

The heat transfer characteristics of R134a flow boiling in a horizontal tube of an evaporator section for a refrigeration system of 310-W capacity are investigated experimentally and numerically. The experimental work was conducted using an evaporator tube test section of inner diameter 5.8[Formula: see text]mm and length 600[Formula: see text]mm. The ranges of investigated experimental data for heat flux, mass flux, saturation temperature and vapor quality were 13.8–36.6[Formula: see text]kW/m2, 52–105[Formula: see text]kg/m2[Formula: see text][Formula: see text][Formula: see text]s, [Formula: see text]–[Formula: see text]C and 0.2–1, respectively. Numerical analysis was based on two-phase flow turbulent model and this model was solved using the Ansys-18 code. The results showed that the effects of heat flux, mass velocity and saturation temperature on local heat transfer coefficient and pressure drop were greater compared to that of the refrigerant vapor quality. The enhancements in local heat transfer coefficient due to the increase in heat flux, mass and saturation temperature were 38%, 57% and 64%, respectively, within the prescribed test conditions. The influence of mass flux variation on pressure drop along the evaporator channel was higher in the range of 27% compared to the heat flux effect. The average deviations between experimental and numerical results of heat transfer coefficient and pressure gradient were 14% and 17%, respectively, while the same between the experimental and predicted results were 16% and 33%, respectively.
Building Sustainable Cities in China: Experience, Challenges, and Prospects
Authors: KANG Wenmei , WANG Mou , LIU Junyan , LV Xianhong , ZHANG Ying , LUO Dongshen , WANG Dawei
Published: June 2019

According to the 2030 Agenda for Sustainable Development, the sustainable development goal 11 is to “make cities and human settlement inclusive, safe, resilient and sustainable”. China has been making great effort in this respect. With the advancement in science and technology, the concepts of green development, environmental friendliness, and fair development are gradually moving from theories to practices, guiding the construction and development of sustainable cities in China. Over the past 40 years of reform and opening up, the overall process of China’s construction of sustainable cities and development can be divided into three stages: the initial practice stage (1986–2000), the stage focusing on transformation (2001–2012), and the stage emphasizing coordinated development and social fairness (2012 to present). During the process, China has proposed and carried out a series of pilot demonstrations of sustainable cities, eco-cities, garden cities, low-carbon cities, livable cities, resilient cities, sanitary cities, sponge cities, and circular economy cities. It has achieved remarkable results with valuable experience; meanwhile, it still faces many challenges considering the current practices. With the integration of planning for the national economy and social development, rural and urban development, land use, and other aspects, as well as the implementation of the 2030 Agenda for Sustainable Development, sustainable urban practices in China will receive more policy support and effective administrative support. As the largest developing country in the world, China’s practice in sustainable urban development undoubtedly has a broad demonstration effect and can contribute to global sustainable development.
Prognostic Factors to Achieve Higher Pregnancy and Live Birth Rate in Intrauterine Insemination Among Subfertile Women
Authors: Tan Shiuan Yee , Lee Yi-Xuan , Chan Cindy , Tzeng Chii-Ruey
Published: June 2019

Background: The purpose of this study was to evaluate the prognostic factors that could affect the clinical pregnancy rate (CPR) and live birth rate (LBR) among subfertile women undergoing intrauterine insemination (IUI).

Methods: A retrospective analysis study of a total of 2186 cycles of IUI among 1784 subfertile women between 2012 and 2017 at the infertility clinic in Taipei Medical University Hospital was conducted. Social demographics, CPR, and LBR were measured. Eleven prognostic factors were analysed with multivariable logistic regression.

Results: Of the 2186 cycles, 569 became pregnant (26.0%), resulting in 454 live births. The LBR per cycle and per patient were 20.8% and 24.6%, respectively. Eight factors were found to significantly predict the obstetric outcome among the women who underwent IUI (p [Formula: see text] 0.05). Age, [Formula: see text] 35.0 years old; serum anti-Müllerian hormone (AMH) level, [Formula: see text] 1.2 ng/mL; delayed sperm insemination, [Formula: see text] 36.0 hour following human chorionic gonadotropin (HCG) injection; serum estradiol level, [Formula: see text] 500 pg/mL; endometrial thickness, [Formula: see text] 7.0 mm on the day of HCG administration; and post-wash total motile sperm count (TMSC), [Formula: see text] 5 million/mL were found to be prognostic factors in determining the CPR and LBR (p [Formula: see text] 0.05). However, duration of subfertility and the presence of urine luteinizing hormone surge during the day of the HCG trigger inversely affected the LBR (p = 0.006 and p = 0.033, respectively) but not the CPR (p [Formula: see text] 0.05). The type of infertility, total antral follicle count, and pre-wash TMSC were not able to predict pregnancy outcome (p [Formula: see text] 0.05).

Conclusions: Six out of 11 factors were identified as strong prognostic factors for successful pregnancies and live births: age, serum AMH and serum estradiol levels, endometrial thickness, post-wash TMSC, and delayed sperm insemination after HCG injection.
Geology, Engineering and Humanities: three sciences behind the Malpasset dam failure (France, 2 December 1959)
Authors: Duffaut P. , Larouzée J.
Published: June 2019

On 2 December 1959, the Malpasset arch dam in SE France suddenly failed, flooding the valley down to the sea, causing huge destruction and more than 400 deaths. Built from 1952 to 1954 for water supply and irrigation, filling of the reservoir was delayed 5 years and the failure occurred following a flash flood of the river the dam was closing. Post-failure studies and expertise during a trial revealed poor field investigations on a micaschist rock foundation crisscrossed by faults, and poor management of construction of the structure. The failure was ascribed to uplift, which moved a rock dihedron defined by a conspicuous fault and a tear along foliation. This paper shows that, in addition to the many traps listed by previous investigations (mostly geological and geotechnical), the human and organizational factors can also shed a new light on this catastrophe. Keeping lessons from Malpasset alive and increasing the knowledge about this case is relevant, as worldwide, after the catastrophe, not only did new regulations on dams appear but also the new fields of geological engineering and rock mechanics were developed. Thus, consciously or not, every geological engineer or rock mechanics specialist is somehow a descendant of this case.
ANP-stimulated Na+ secretion in the collecting duct prevents Na+ retention in the renal adaptation to acid load
Authors: Cheval Lydie , Bakouh Naziha , Walter Christine , Tembely Dignê , Morla Luciana , Escher Geneviève , Vogt Bruno , Crambert Gilles , Planelles Gabrielle , Doucet Alain
Published: June 2019

We have recently reported that type A intercalated cells of the collecting duct secrete Na+ by a mechanism coupling the basolateral type 1 Na+-K+-2Cl− cotransporter with apical type 2 H+-K+-ATPase (HKA2) functioning under its Na+/K+ exchange mode. The first aim of the present study was to evaluate whether this secretory pathway is a target of atrial natriuretic peptide (ANP). Despite hyperaldosteronemia, metabolic acidosis is not associated with Na+ retention. The second aim of the present study was to evaluate whether ANP-induced stimulation of Na+ secretion by type A intercalated cells might account for mineralocorticoid escape during metabolic acidosis. In Xenopus oocytes expressing HKA2, cGMP, the second messenger of ANP, increased the membrane expression, activity, and Na+-transporting rate of HKA2. Feeding mice with a NH4Cl-enriched diet increased urinary excretion of aldosterone and induced a transient Na+ retention that reversed within 3 days. At that time, expression of ANP mRNA in the collecting duct and urinary excretion of cGMP were increased. Reversion of Na+ retention was prevented by treatment with an inhibitor of ANP receptors and was absent in HKA2-null mice. In conclusion, paracrine stimulation of HKA2 by ANP is responsible for the escape of the Na+-retaining effect of aldosterone during metabolic acidosis.
Detection of cellular hypoxia by pimonidazole adduct immunohistochemistry in kidney disease: methodological pitfalls and their solution
Authors: Ow Connie P. C. , Ullah Md Mahbub , Ngo Jennifer P. , Sayakkarage Adheeshee , Evans Roger G.
Published: June 2019

Pimonidazole adduct immunohistochemistry is one of the few available methods for assessing renal tissue hypoxia at the cellular level. It appears to be prone to artifactual false positive staining under some circumstances. Here, we assessed the nature of this false positive staining and, having determined how to avoid it, reexamined the nature of cellular hypoxia in rat models of kidney disease. When a mouse-derived anti-pimonidazole primary antibody was used, two types of staining were observed. First, there was diffuse staining of the cytoplasm of tubular epithelial cells, which was largely absent when the primary antibody was omitted from the incubation protocol or in tissues known not to contain pimonidazole adducts. Second, there was staining of the apical membranes of tubular epithelial cells, debris within the lumen of renal tubules, including tubular casts, and the interstitium; this latter staining was present even when the primary antibody was omitted from the incubation protocol. Such false positive staining was particularly prominent in acutely injured kidneys. It could not be avoided by preincubation of sections with a mouse IgG blocking reagent. Furthermore, preadsorption of the secondary antibody against rat Ig abolished all staining; however, when a rabbit-derived polyclonal anti-pimonidazole primary antibody was used, the false positive staining was largely avoided. Using this method, we confirmed the presence of hypoxia, localized mainly to the tubular epithelium, in the acute phase of severe renal ischemia-reperfusion injury, adenine-induced chronic kidney disease, and polycystic kidney disease. We conclude that this new method provides improved detection of renal cellular hypoxia.
Endovenous Laser Ablation for Treatment of a Partially Thrombosed Proximal Great Saphenous Vein
Authors: Spinedi Luca , Stricker Hans , Staub Daniel , Uthoff Heiko
Published: June 2019

Introduction. Superficial vein thrombosis of the great saphenous vein near to the saphenofemoral junction is generally treated with anticoagulation or surgically. Report. We present the case of a 70-year-old man with varicosities and a partially thrombosed great saphenous vein near to the saphenofemoral junction, treated with endovenous laser ablation of the great saphenous vein. Discussion. The case illustrates an alternative treatment option for superficial vein thrombosis of the great saphenous vein, which permits avoiding a prolonged anticoagulation or surgical procedure.
Early Detection of Microvascular Changes in Patients with Diabetes Mellitus without and with Diabetic Retinopathy: Comparison between Different Swept-Source OCT-A Instruments
Authors: Vujosevic Stela , Toma Caterina , Villani Edoardo , Gatti Valentina , Brambilla Marco , Muraca Andrea , Ponziani Maria Chantal , Aimaretti Gianluca , Nuzzo Alessandro , Nucci Paolo , De Cilla’ Stefano
Published: June 2019

Optical coherence tomography angiography (OCT-A) has recently improved the ability to detect subclinical and early clinically visible microvascular changes occurring in patients with diabetes mellitus (DM). The aim of the present study is to evaluate and compare early quantitative changes of macular perfusion parameters in patients with DM without DR and with mild nonproliferative DR (NPDR) evaluated by two different swept-source (SS) OCT-A instruments using two scan protocols (3×3 mm and 6×6 mm). One hundred eleven subjects/eyes were prospectively evaluated: 18 healthy controls (control group), 73 eyes with DM but no DR (no-DR group), and 20 eyes with mild NPDR (DR group). All quantitative analyses were performed using ImageJ and included vessel and perfusion density, area and circularity index of the FAZ, and vascular complexity parameters. The agreement between methods was assessed according to the method of Bland-Altman. A significant decrease in the majority of the considered parameters was found in the DR group versus the controls with both instruments. The results of Bland-Altman analysis showed the presence of a systemic bias between the two instruments with PLEX Elite providing higher values for the majority of the tested parameters when considering 6×6 mm angiocubes and a less definite difference in 3×3 mm angiocubes. In conclusion, this study documents early microvascular changes occurring in the macular region of patients at initial stages of DR, confirmed with both SS OCT-A instruments. The fact that early microvascular alterations could not be detected with one instrument does not necessarily mean that these alterations are not actually present, but this could be an intrinsic limitation of the device itself. Further, larger longitudinal studies are needed to better understand microvascular damage at very early stages of diabetic retinal disease and to define the strengths and weaknesses of different OCT-A devices.
A Review of Semantic Sensor Technologies in Internet of Things Architectures
Authors: Honti Gergely Marcell , Abonyi Janos
Published: June 2019

Intelligent sensors should be seamlessly, securely, and trustworthy interconnected to enable automated high‐level smart applications. Semantic metadata can provide contextual information to support the accessibility of these features, making it easier for machines and humans to process the sensory data and achieve interoperability. The unique overview of sensor ontologies according to the semantic needs of the layers of IoT solutions can serve a guideline of engineers and researchers interested in the development of intelligent sensor‐based solutions. The explored trends show that ontologies will play an even more essential role in interlinked IoT systems as interoperability and the generation of controlled linkable data sources should be based on semantically enriched sensory data.
Thermogravimetric Analysis and Kinetics of Mixed Combustion of Waste Plastics and Semicoke
Authors: Xing Xiangdong , Wang Sha , Zhang Qiuli
Published: June 2019

The thermogravimetric method was applied to study the combustion characteristics of waste plastics and semicoke mixture at different heating rates with temperature ranging from room temperature to 1173 K. Also, the kinetic parameters of combustion process were also estimated by fitting the experimental data to the calculated data. The results showed that the mixed combustion process of waste plastics and semicoke could be divided into volatile combustion stage and fixed carbon combustion stage. The addition of waste plastics could increase the comprehensive combustion characteristic index (S) and flammability index (C). It showed synergistic effect in the mixed combustion process. When the additive amount of waste plastics was 60%, the S value and C value reached peak point at the heating rate of 20 K/min. The heating rate had a promotion effect on combustion rate. The mixed combustion process of waste plastics and semicoke could be well simulated by the n-order rate model of double parallel reactions. The activation energies E in the first stage of combustion of the mixture were higher than that in the second stage, and the preexponential factor k was opposite. Meanwhile, a marked kinetic compensation effect was presented between the activation energy and the preexponential factor.
Noncoding RNAs Act as Tumor-Derived Molecular Components in Inducing Premetastatic Niche Formation
Authors: Zhang Zhedong , Qiao Jiao , Zhang Dafang , Zhu Weihua , Zhu Jiye , Leng Xisheng , Li Shu
Published: June 2019

Cancer metastasis has been demonstrated as it is the culmination of a cascade of priming steps. Increasing evidence has shown that tumor-derived molecular components (TDMCs) are known as extra cellular vesicle and nonvesicle factors and serve as versatile intercellular communication vehicles which can mediate signaling in the tumor microenvironment while creating the premetastatic niche. Noncoding RNAs (ncRNAs) as one of the TDMCs have been proved in participating in the formation of the premetastatic niche. Understanding the premetastatic niche formation mechanisms through TDMCs, especially ncRNAs may open a new avenue for cancer metastasis therapeutic strategies. In this review, recent findings regarding ncRNAs function were summarized, and then the interaction with the premetastatic niche formation was studied, which highlight the potential of using ncRNAs for cancer diagnosis and therapeutic effect.
Loss of EZH2 Reprograms BCAA Metabolism to Drive Leukemic Transformation
Authors: Gu Zhimin , Liu Yuxuan , Cai Feng , Patrick McKenzie , Zmajkovic Jakub , Cao Hui , Zhang Yuannyu , Tasdogan Alpaslan , Chen Mingyi , Qi Le , Liu Xin , Li Kailong , Lyu Junhua , Dickerson Kathryn E. , Chen Weina , Ni Min , Merritt Matthew E. , Morrison Sean J. , Skoda Radek C. , DeBerardinis Ralph J. , Xu Jian
Published: June 2019

Epigenetic gene regulation and metabolism are highly intertwined, yet little is known about whether altered epigenetics influence cellular metabolism during cancer progression. Here, we show that EZH2 and NRASG12D mutations cooperatively induce progression of myeloproliferative neoplasms to highly penetrant, transplantable, and lethal myeloid leukemias in mice. EZH1, an EZH2 homolog, is indispensable for EZH2-deficient leukemia-initiating cells and constitutes an epigenetic vulnerability. BCAT1, which catalyzes the reversible transamination of branched-chain amino acids (BCAA), is repressed by EZH2 in normal hematopoiesis and aberrantly activated in EZH2-deficient myeloid neoplasms in mice and humans. BCAT1 reactivation cooperates with NRASG12D to sustain intracellular BCAA pools, resulting in enhanced mTOR signaling in EZH2-deficient leukemia cells. Genetic and pharmacologic inhibition of BCAT1 selectively impairs EZH2-deficient leukemia-initiating cells and constitutes a metabolic vulnerability. Hence, epigenetic alterations rewire intracellular metabolism during leukemic transformation, causing epigenetic and metabolic vulnerabilities in cancer-initiating cells.

Significance:

EZH2 inactivation and oncogenic NRAS cooperate to induce leukemic transformation of myeloproliferative neoplasms by activating BCAT1 to enhance BCAA metabolism and mTOR signaling. We uncover a mechanism by which epigenetic alterations rewire metabolism during cancer progression, causing epigenetic and metabolic liabilities in cancer-initiating cells that may be exploited as potential therapeutics.

See related commentary by Li and Melnick, p. 1158.

This article is highlighted in the In This Issue feature, p. 1143
Analysis of Post-Sample Collection EDTA Effects on Mean Platelet Volume Values in Relation to Overweight and Obese Patient Status
Authors: Pinto Renata V.L. , Rodrigues Genilson , Simões Rafael L. , Porto Luís Cristóvão
Published: June 2019

Background: Mean platelet volume (MPV) may be a useful biomarker for platelet activation in obese patients. However, storage duration and use of anticoagulant K3-ethylenediaminetetraacetic acid (EDTA) may interfere with these measurements. Objectives: The aim of this study was to measure the variability of MPV in obese patients following exposure to EDTA. Method: A total of 160 patients were divided into 3 groups according to body mass index (BMI; normal: <25 kg/m2; overweight: 25–30 kg/m2; obese: >30 kg/m2). Blood was collected in sterile tubes containing K3-EDTA. Blood cell counts were obtained using the CELL-DYN Ruby system immediately and 1, 2, and 3 h after collection. Results: MPV was found to be directly proportional to BMI. With the addition of EDTA, MPV was increased in the first hour after collection; MPV then decreased to levels that were lower than initial baseline measurements. Conclusions: K3-EDTA use alters platelet volume. The time from collection to measurement should be standardized to reduce MPV value variance. MPV should be determined within 1 h of collection to avoid anticoagulant use-related interference.
Use of Both Serum Cystatin C and Creatinine as Diagnostic Criteria for Cardiac Surgery-Associated Acute Kidney Injury and Its Correlation with Long-Term Major Adverse Events
Authors: Che Miaolin , Wang Xudong , Xie Bo , Huang Ritai , Liu Shang , Yan Yucheng , Zhu Mingli , Lu Renhua , Qian Jiaqi , Zhang Weiming , Gu Leyi , Mou Shan , Ni Zhaohui , Xue Song
Published: June 2019

Background/Aims: Cardiac surgery-associated acute kidney injury (CSA-AKI) was traditionally defined as an increase in serum creatinine (sCr) after cardiac surgery. Recently, serum cystatin C (sCyC) has been proposed to be a better biomarker in the prediction of AKI. The clinical utility and performance of combining sCyC and sCr in patients with AKI, particularly for the prediction of long-term outcomes, remain unknown. Methods: We measured sCyC together with sCr in 628 patients undergoing cardiac surgery. sCyC and sCr were assessed at baseline and 24 and 48 h after surgery. CSA-AKI determined by sCr (CSA-AKIsCr) was defined as an sCr increase greater than 0.3 mg/dL or 50% from baseline. Major adverse events (MAEs; including death of any cause and dialysis) at 3 years were assessed. Results: CSA-AKIsCr developed in 178 patients (28.3%). Three-year follow-up was available for 621 patients; MAEs occurred in 42 patients (6.8%). An increase in sCyC concentration ≥30% within 48 h after surgery was detected in 228 patients (36.3%). This was the best sCyC cutoff for CSA-AKIsCr detection (negative predictive value = 88.8%, positive predictive value = 58.3%). To evaluate the use of both sCyC and sCr as CSA-AKI diagnostic criteria, we stratified patients into 3 groups: non-CSA-AKI, CSA-AKI detected by a single marker, and CSA-AKI detected by both markers. By multivariable logistic regression analysis, the independent predictors of MAEs at 3 years were group 2 (non-CSA-AKI group as the reference, CSA-AKI detected by a single marker: odds ratio [OR] = 3.48, 95% confidence interval [CI]: 1.27–9.58, p = 0.016), group 3 (CSA-AKI detected by both markers: OR = 5.12, 95% CI: 2.01–13.09; p = 0.001), and baseline glomerular filtration rate (OR = 2.24; 95% CI: 1.27–3.95; p = 0.005). Conclusion: Combining sCyC and sCr to diagnose CSA-AKI would be beneficial for risk stratification and prognosis in patients after cardiac surgery.
Immunocytochemical Evidence for Electrical Synapses in the Dorsal Descending and Dorsal Anterior Octaval Nuclei in the Goldfish, Carassius auratus
Authors: McCormick Catherine A.
Published: June 2019

The dorsal portion of the descending octaval nucleus (dDO), the main first-order auditory nucleus in jawed fish, includes four lateral and three medial neuronal populations that project to the auditory midbrain. One medial population and one lateral population contain neurons that receive a remarkably large axon terminal from the utricular branch of the octaval nerve. Immunocytochemistry for connexin 35 (Cx35) was used to determine whether this connection includes electrical synapses. Although Cx35 was not localized to these large contacts, it was observed in the three other lateral dDO populations. Another first-order nucleus, the dorsal portion of the anterior octaval nucleus (dAO), primitively projects to the auditory midbrain in jawed fishes and contains neurons positive for Cx35. Utricular branch terminals were coincident with some Cx35 puncta in dDO and dAO. The results are discussed in light of what is known about the occurrence of electrical synapses in first-order auditory and vestibular nuclei in fish and tetrapods.
Beraprost Upregulates KV Channel Expression and Function via EP4 Receptor in Pulmonary Artery Smooth Muscle Cells Obtained from Rats with Hypoxia-Induced Pulmonary Hypertension
Authors: Tian Hua , Fan Fenling , Geng Jie , Deng Jizhao , Tian Hongyan
Published: June 2019

The reduced expression and function of voltage-dependent potassium (KV) channels have been involved in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH), leading to pulmonary vasoconstriction and vascular remodeling, while the upregulation of KV channels is of therapeutic significance for pulmonary hypertension. Beraprost sodium (BPS) has been shown to be effective in patients with pulmonary hypertension. However, the effect of BPS on O2-sensitive KV channels in pulmonary artery smooth muscle cells (PASMCs) remains unclear. In the present study, the effect of BPS on rats with HPH was observed, and the influence of BPS on the expression and function of O2-sensitive KV channels in PASMCs was investigated. The results revealed that BPS reduced mean pulmonary artery pressure, suppressed right ventricular hypertrophy, and attenuated the remodeling of pulmonary arteries in rats exposed to discontinuous hypoxia for 4 weeks (8 h/day). This was accompanied with the significantly upregulated expression of KV channel α-subunits (KV1.2, KV1.5 and KV2.1) and O2-sensitive voltage-gated K+ (KV) channel current (IK(V)) in small pulmonary arteries in HPH model rats, as well as in hypoxia-induced PASMCs. Furthermore, in vitrostudies have revealed that the upregulation of BPS on O2-sensitive KV channels was significantly inhibited after treatment with prostaglandin E2 receptor subtype EP4 antagonist GW627368X. Taken together, these results suggest that BPS attenuates the development of HPH through the upregulation of O2-sensitive KV channels, which was probably via the EP4 receptor-related pathway.
Brain Volume-Related Polymorphisms of the Glycogen Synthase Kinase-3β Gene and Their Effect on Antidepressant Treatment in Major Depressive Disorder
Authors: Sunada Naotaka , Takekita Yoshiteru , Nonen Shinpei , Wakeno Masataka , Koshikawa Yosuke , Ogata Haruhiko , Kinoshita Toshihiko , Kato Masaki
Published: June 2019

Background: Glycogen synthase kinase-3β (GSK-3β) polymorphisms are known to influence hippocampal brain tissue volume in individuals with major depressive disorder (MDD). However, the effects of the GSK-3β gene single nucleotide polymorphisms (SNPs) in those receiving antidepressant therapy are unknown. Objectives: In the present study, we examined the relationship between brain volume-related SNPs of the GSK-3β gene and antidepressant treatment effects in patients with MDD. Methods: Paroxetine, fluvoxamine, or milnacipran was administered to 143 Japanese patients with MDD. Two SNPs of the GSK-3β gene (rs6438552 and rs12630592) that influence brain volume in the hippocampus were genotyped. For the primary outcome, the relationship between genetic variations in the SNPs and the percent change in the Hamilton Rating Scale for Depression (HAM-D) score at week 6 was examined. In addition, rs334558, which has been reported repeatedly, was also genotyped. Results: There was a significant correlation between the two SNPs and the percent change in the HAM-D scores at week 6 (rs6438552 A/A vs. A/G + G/G: p = 0.016; rs12630592 G/G vs. G/T + T/T: p = 0.016). There was high linkage disequilibrium between the rs6438552 and rs12630592 SNPs. The correlation between high therapeutic response over time and the two SNPs were also confirmed (rs6438552 A/A vs. others: p = 0.031; rs12630592 G/G vs. others: p = 0.031). Conclusions: Our results suggest that two GSK-3β variants that influence brain volume were associated with changes in the HAM-D scores at week 6 in patients with MDD.
Short-Term Prediction of Adverse Outcomes Using the sFlt-1 (Soluble fms-Like Tyrosine Kinase 1)/PlGF (Placental Growth Factor) Ratio in Asian Women With Suspected Preeclampsia
Authors: Bian Xuming , Biswas Arijit , Huang Xianghuang , Lee Kyoung Jin , Li Thomas Kwok-To , Masuyama Hisashi , Ohkuchi Akihide , Park Joong Shin , Saito Shigeru , Tan Kok Hian , Yamamoto Tatsuo , Dietl Angela , Grill Sonja , Verhagen-Kamerbeek Wilma D.J. , Shim Jae-Yoon , Hund Martin
Published: June 2019

Current diagnostic criteria have limited clinical value for prediction of preeclampsia and fetal adverse outcomes. The prediction of short-term outcome in pregnant women with suspected preeclampsia study in Asia (PROGNOSIS Asia) was a prospective, multicenter study designed to investigate the value of the sFlt-1 (soluble fms-like tyrosine kinase 1)/PlGF (placental growth factor) ratio for predicting adverse outcomes in pregnant Asian women with suspected preeclampsia. Seven hundred sixty-four pregnant women at gestational week 20+0 days (18+0 days in Japan) to 36+6 days were enrolled at 25 sites in Asia. The primary objectives were to demonstrate the value of the sFlt-1/PlGF ratio for ruling out preeclampsia within 1 week and ruling in preeclampsia within 4 weeks. The value of the ratio for predicting fetal adverse outcomes was also assessed. Seven hundred patients were evaluable for primary end point analysis. The prevalence of preeclampsia was 14.4%. An sFlt-1/PlGF ratio of ≤38 had a negative predictive value of 98.6% (95% CI, 97.2%–99.4%) for ruling out preeclampsia within 1 week, with 76.5% sensitivity and 82.1% specificity. The positive predictive value of a ratio of >38 for ruling in preeclampsia within 4 weeks was 30.3% (95% CI, 23.0%–38.5%), with 62.0% sensitivity and 83.9% specificity. An sFlt-1/PlGF ratio of ≤38 had a negative predictive value of 98.9% (95% CI, 97.6%–99.6%) for ruling out fetal adverse outcomes within 1 week and a ratio of >38 had a positive predictive value of 53.5% (95% CI, 45.0%–61.8%) for ruling in fetal adverse outcomes within 4 weeks. The sFlt-1/PlGF ratio cutoff of 38 demonstrated clinical value for the short-term prediction of preeclampsia in Asian women with suspected preeclampsia, potentially helping to prevent unnecessary hospitalization and intervention.
A Palaeographic and Codicological (Re)assessment of the Opisthograph 4Q433a/4Q255
Authors: Aksu Ayhan
Published: June 2019

A consideration of both the palaeographic and material features of a scroll provides scholars the opportunity to investigate the scribal culture in which a particular manuscript emerged. This article examines the papyrus opisthograph from Qumran containing 4QpapHodayot-like Text B, 4Q433a, and 4QpapSerekh ha-Yaḥada, 4Q255, on either side. There has been scholarly disagreement about this opisthograph with regard to a number of questions: (1) which of the two compositions was inscribed on the recto, (2) how the two compositions should be dated, and (3) which of the two texts was written first. This article looks at both compositions by means of palaeography and codicology. From this combined approach I deduce that 4Q433a was written first, on the recto of this papyrus manuscript. 4Q255 was added later, on the verso. Both compositions can be dated to the early first century BCE. This reconstruction makes it plausible that 4Q255 was a personal copy.