bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex crater fields formed by steam-driven eruptions: Lake Okaro, New Zealand
Authors: Montanaro Cristian , Cronin Shane , Scheu Bettina , Kennedy Ben , Scott Bradley
Published: January 2020

Steam-driven eruptions are caused by explosive vaporization of water within the pores and cracks of a host rock, mainly within geothermal or volcanic terrains. Ground or surface water can be heated and pressurized rapidly from below (phreatic explosions), or already hot and pressurized fluids in hydrothermal systems may decompress when host rocks or seals fail (hydrothermal eruptions). Deposit characteristics and crater morphology can be used in combination with knowledge of host-rock lithology to reconstruct the locus, dynamics, and possible triggers of these events. We investigated a complex field of >30 craters formed over three separate episodes of steam-driven eruptions at Lake Okaro within the Taupo volcanic zone, New Zealand. Fresh unaltered rock excavated from initially >70 m depths in the base of phase I breccia deposits showed that eruptions were deep, “bottom-up” explosions formed in the absence of a preexisting hydrothermal system. These phreatic explosions were likely triggered by sudden rise of magmatic fluids/gas to heat groundwater within an ignimbrite 70 m below the surface. Excavation of a linear set of craters and associated fracture development, along with continued heat input, caused posteruptive establishment of a large hydrothermal system within shallow, weakly compacted, and unconsolidated deposits, including the phase I breccia. After enough time for extensive hydrothermal alteration, erosion, and external sediment influx into the area, phase II occurred, possibly triggered by an earthquake or hydrological disruption to a geothermal system. Phase II produced a second network of craters into weakly compacted, altered, and pumice-rich tuff, as well as within deposits from phase I. Phase II breccias display vertical variation in lithology that reflects top-down excavation from shallow levels (10–20 m) to >70 m. After another hiatus, lake levels rose. Phase III hydrothermal explosions were later triggered by a sudden lake-level drop, excavating into deposits from previous eruptions. This case shows that once a hydrothermal system is established, repeated highly hazardous hydrothermal eruptions may follow that are as large as initial phreatic events.
Hyperkinetic reaction to dihydrocodeine
Authors: van Oppen James David , Patel Neeta , Tarique Aamir
Published: January 2020

A young man was using dihydrocodeine analgesia for ear pain having had suppurative otitis media. He attended the emergency department with restlessness and twitching movements in his arms and legs. He had fever with otherwise normal vital signs. He had no signs of cerebellar pathology. Investigations were normal. The working diagnosis was of hyperkinetic reaction to dihydrocodeine. Symptoms resolved within 48 hours of withdrawing the drug. Serotonin toxicity is a rare side effect of dihydrocodeine. There is a theoretical basis for increased side effects when taken with cannabidiol-based substances.
Habitual physical activity, renal function and chronic kidney disease: a cohort study of nearly 200 000 adults
Authors: Guo Cui , Tam Tony , Bo Yacong , Chang Ly-yun , Lao Xiang Qian , Thomas G Neil
Published: January 2020

Background

There is limited information on the association between habitual physical activity (PA) and renal function.

Objective

To report the longitudinal association between self-reported habitual PA and measures of renal function in a large cohort in Taiwan.

Methods

A total of 199 421 participants (aged ≥20 years) were selected from a Taiwan cohort between 1996 and 2014. All participants underwent at least two standardised medical examinations between 1996 and 2014. Self-administrated questionnaires were used to collect information on habitual PA. We used a generalised linear mixed model to investigate the associations between habitual PA and yearly change in estimated glomerular filtration rate (eGFR). The Cox proportional hazard regression model was used to investigate the associations between habitual PA and incident chronic kidney disease (CKD).

Results

Participants had a median follow-up duration of 4.2 years (0.2–18.9). The yearly mean (±SD) decrease in eGFR in participants with baseline very low-PA, low-PA, moderate-PA and high-PA was 0.46±1.01, 0.36±0.97, 0.30±0.94 and 0.27±0.91 mL/min/1.73 m
2
, respectively. Relative to the participants with very low-PA, the coefficients of yearly eGFR change were −43.93 (95% CI −79.18 to −8.68), 35.20 (95% CI −2.56 to 72.96) and 53.56 (95% CI 10.42 to 96.70) µL
/
min/1.73 m
2
, respectively, for the participants with low-PA, moderate-PA and high-PA, after controlling for a wide range of covariates. Relative to the very low-PA participants, those who had low-PA, moderate-PA and high-habitual PA had HRs of 0.93 (95% CI 0.88 to 0.98), 0.94 (95% CI 0.89 to 0.99) and 0.91 (95% CI 0.85 to 0.96) to develop CKD, respectively, after controlling for the covariates.

Conclusions

A higher level of habitual PA is associated with a smaller decrease in the level of eGFR and a lower risk of developing CKD.
Multiplex immunohistochemistry/immunofluorescence (mIHC/IF) for PD-L1 testing in triple-negative breast cancer: a translational assay compared with conventional IHC
Authors: Yeong Joe , Tan Tira , Chow Zi Long , Cheng Qing , Lee Bernett , Seet Amanda , Lim Johnathan Xiande , Lim Jeffrey Chun Tatt , Ong Clara Chong Hui , Thike Aye Aye , Saraf Sahil , Tan Benjamin, Yong Cheng , Poh Yong Cheng , Yee Sidney , Liu Jin , Lim Elaine , Iqbal Jabed , Dent Rebecca , Tan Puay Hoon
Published: January 2020

Background

Programmed death-ligand 1 (PD-L1) monoclonal antibody therapy has recently gained approval for treating metastatic triple-negative breast cancer (TNBC) -, in particular in the PD-L1+patient subgroup of the recent IMpassion130 trial. The SP142 PD-L1 antibody clone was used as a predictive assay in this trial, but this clone was found to be an outlier in previous harmonisation studies in lung cancer.

Aims

To address the comparability of PD-L1 clones in TNBC, we evaluated the concordance between conventional immunohistochemistry (IHC) and multiplex immunohistochemistry/immunofluorescence (mIHC/IF) that allowed simultaneous quantification of three different PD-L1 antibodies (22C3, SP142 and SP263).

Methods

Our cohort comprised 25 TNBC cases, 12 non-small-cell lung carcinomas and 8 other cancers. EpCAM labelling was used to distinguish tumour cells from immune cells.

Results

Moderate-to-strong correlations in PD-L1 positivity were found between results obtained through mIHC/IF and IHC. Individual concordance rates in the study ranged from 67% to 100%, with Spearman’s rank correlation coefficient values up to 0.88.

Conclusions

mIHC/IF represents a promising tool in the era of cancer immunotherapy, as it can simultaneously detect and quantify PD-L1 labelling with multiple antibody clones, and allow accurate evaluation of tumour and immune cells. Clinicians and pathologists require this information to predict patient response to anti-PD-1/PD-L1 therapy. The adoption of this assay may represent a significant advance in the management of therapeutically challenging cancers. Further analysis and assay harmonisation are essential for translation to a routine diagnostic setting.
Procalcitonin Predicts the Severity of Cystic Fibrosis Pulmonary Exacerbations and Readmissions in Adult Patients: A Prospective Cohort Study
Authors: Bailey Kristina L , Murphy Peter J , Lineberry Olena K , Haack Matthew R , Dickinson John D , Kalil Andre C
Published: January 2020

Patients with cystic fibrosis (CF) experience multiple pulmonary exacerbations throughout their lifetime, resulting in repeated antibiotic exposure and hospital admissions. Reliable diagnostic markers to guide antibiotic treatment in patients with CF, however, are lacking. Given that the CF airway is characterized by persistent and frequent bacterial infection, our goal was to determine if procalcitonin (PCT) could be used as a severity and prognostic marker of CF exacerbation. We enrolled 40 participants at the time of diagnosis of CF pulmonary exacerbation. Inclusion criteria: age ≥19 years with exacerbation requiring antibiotics as determined by the treating physician. Exclusion criteria: antibiotics initiated more than 48 hours prior to enrollment, and pregnancy. Blood samples were collected on enrollment day and after 7-10 days of treatment. Of the 40 patients enrolled, 23 (57.5%) had detectable levels of PCT (≥0.05 ng/mL). PCT levels were significantly associated with pulmonary exacerbation scores (p=0.01) and per cent decrease in forced expiratory volume in 1 second (FEV1) (p=0.01) compared with the best in the last 12 months. Those who had worsening PCT during treatment had less improvement in FEV1 (p=0.001) and were more likely to be readmitted to the hospital sooner (p<0.0001). Likewise, those who had a detectable PCT at the time of admission were more likely to be readmitted sooner (p=0.03). PCT elevation during antibiotic treatment is associated with less improvement in FEV1 and earlier readmission. A detectable PCT level occurs only in more severe CF exacerbations. Multicenter trials are needed to confirm whether PCT may play a role in the clinical care of patients with CF.
2 A rare cause of stroke in young: moyamoya disease
Authors: Ali Asem , Abbas Munzar , Saeed Umer
Published: January 2020

Background and aims

Moyamoya disease is a rare chronic progressive cerebrovascular disease characterised by bilateral stenosis or occlusion of arteries around circle of Willis with prominent collateral circulation. The term moyamoya (Japanese for ‘puff of smoke’) refers to the appearance on angiography of abnormal vascular collateral networks that develop adjacent to the stenotic vessels. Moyamoya disease was first described in Japan by Takeuchi and Shimizu in 1957.1 The prevalence and incidence of the disorder there has been reported to be 3.16 cases and 0.35 cases per 100 000 people, respectively. The incidence of moyamoya disease is highest in Japan.2 Moyamoya syndrome has now been observed throughout the world with increasing detection of this disease in American and European populations.3 4

Methods

32 years old gentleman with background of Rheumatoid arthritis (In remission) and asthma presented to hospital with confusion and word finding difficulty.

Results

Systemic examination was unremarkable except patient mentioned that he had difficulty in texting on his mobile phone. Blood tests showed raised inflammatory markers. Patient was treated on lines of meningoencephalitis. CT brain showed hypodensity in left temporal, parietal and occipital lobe. MRI brain with contrast showed confirmed these changes to be acute infarcts along with post contrast meningeal enhancement. CSF results came back normal including viral PCR.Patient referred to neurology who advised to continue treating as viral encephalitis. Vasculitic screen weakly positive P-ANCA. Stroke team was involved who organised MRA which showed generalised narrowing of left carotid siphon and left middle cerebral artery and its branches. It also showed loss of definition of M1 segment of right MCA and its branches. Changes initially though to be secondary to vasculitis and patient started on steroids. Patient seen by rheumatology team and possibility of vasculitis was ruled out. Neuroimaging was discussed in neuroradiology MDT after doing DSA and outcome was that changes on brain imaging were suggestive of moyamoya disease with extensive disease bilaterally with more on left side. Patient was seen in neurosurgery clinic and offered revascularisation surgery which patient refused. Patient is under surveillance by neurosurgical team.

Conclusion

Moyamoya is a rare cause of stroke which is diagnosed on basis of clinical and radiographic findings and patients can be offered revascularisation surgery which is the only recommended treatment.
Sphingosine 1-phosphate receptor modulation attenuate mechanical allodynia in mouse model of chronic complex regional pain syndrome by suppressing pathogenic astrocyte activation
Authors: Lee Byung Joo , Kim Jun Young , Cho Hyung-jung , Park Donghwi
Published: January 2020

Background and objectives

FTY720 ((2-amino-2-)2-[4-octylphenyl]ethyl)-1,3-propanediol) is an Food and Drug Administration (FDA)-approved immunomodulatory drug for treating multiple sclerosis. It inhibits lymphocyte egression from lymphoid tissues by downregulating sphingosine-1 phosphate receptor (S1PR). To date, there has been no study on the effects of FTY720 on the chronic stage of the complex regional pain syndrome (CRPS) rodent model, despite its antiallodynic effect in previous studies. Thus, the aim of this study is to investigate the effect of FTY720 in a chronic stage of the CRPS mouse model.

Method

The authors used a mouse model of CRPS, involving tibia fracture/cast immobilization, to test the efficacy of intrathecal FTY720 (2.5 or 25 ng daily; 6 days) or vehicle during the chronic (7 weeks after fracture) stage of CRPS.

Results

Intrathecal recombinant FTY720 administration was antiallodynic in the chronic stage of the CRPS mouse model, and such an effect of FTY720 developed by modulating astrocyte activation in the spinal cord. Additionally, according to the in vitro data, the FTY720 treatment inhibited S1P-induced increase in the nitric oxide production and suppression of the NF-κB pathway, by inhibiting the phosphorylation of NF-κB/p65 in astrocytes without toxic effect on astrocytes.

Conclusion

Collectively, these results demonstrate that intrathecally administered FTY720 attenuates mechanical allodynia in the chronic stage of the CRPS mouse model.
Tobacco manufacturer lobbying to undercut minimum price laws: an analysis of internal industry documents
Authors: Apollonio Dorie E , Glantz Stanton
Published: January 2020

Background

Increasing the price of tobacco products has the potential to reduce tobacco consumption. As other forms of promotion have been increasingly restricted over time, tobacco manufacturers have relied more on trade discounts. Minimum price laws that prevented the use of manufacturer promotions were once common; however in most US jurisdictions these discounts are now legally protected.

Methods

We collected tobacco industry documents, state legislation and court cases between 1987 and 2016 to review tobacco manufacturer strategies to change minimum price laws in the USA.

Results

Beginning in 2000, tobacco manufacturers lobbied to amend minimum price legislation after state regulators indicated that manufacturer promotions were illegal under existing laws. Companies viewed changing these laws as critical to maintaining tobacco sales, and after the initiation of an industry lobbying campaign, at least 20 states changed the way they calculated tobacco prices.

Conclusions

Modifying existing minimum price laws so that manufacturer discounts are no longer protected, and implementing new minimum price policies with comparable scope, would likely increase prices and reduce tobacco use.
Exogenous ubiquitin attenuates hypoxia/reoxygenation-induced cardiac myocyte apoptosis via the involvement of CXCR4 and modulation of mitochondrial homeostasis
Authors: Dalal Suman , Daniels Christopher R. , Li Ying , Wright Gary L. , Singh Mahipal , Singh Krishna
Published: January 2020

Exogenous ubiquitin (UB) plays a protective role in β-adrenergic receptor-stimulated and ischemia/reperfusion (I/R)-induced myocardial remodeling. Here, we report that UB treatment inhibits hypoxia/reoxygenation (H/R)-induced apoptosis in adult rat ventricular myocytes (ARVMs). The activation of Akt was elevated, whereas the activation of glycogen synthase kinase-3β was reduced in UB-treated cells post-H/R. The level of oxidative stress was lower, whereas the number of ARVMs with polarized mitochondria was significantly greater in the UB-treated samples. ARVMs express CXCR4 with majority of CXCR4 localized in the membrane fraction. CXCR4 antagonism using AMD3100, and siRNA-mediated knockdown of CXCR4 negated the protective effects of UB. Two mutated UB proteins (unable to bind CXCR4) had no effect on H/R-induced apoptosis, activation of Akt and GSK-3β, or oxidative stress. UB treatment enhanced mitochondrial biogenesis, and inhibition of mitochondrial fission using mdivi1 inhibited H/R-induced apoptosis. Ex vivo, UB treatment significantly decreased infarct size and improved functional recovery of the heart following global I/R. Activation of caspase-9, a key player of the mitochondrial death pathway, was significantly lower in UB-treated hearts post-I/R. UB, most likely acting via CXCR4, plays a protective role in H/R-induced myocyte apoptosis and myocardial I/R injury via modulation of mitochondrial homeostasis and the mitochondrial death pathway of apoptosis.
BCJ numerators from differential operator of multidimensional residue
Authors: Chen Gang , Wang Tianheng
Published: January 2020

In previous works, we devised a differential operator for evaluating typical integrals appearing in the Cachazo–He–Yuan (CHY) forms and in this paper we further streamline this method. We observe that at tree level, the number of free parameters controlling the differential operator depends solely on the number of external lines, after solving the constraints arising from the scattering equations. This allows us to construct a reduction matrix that relates the parameters of a higher-order differential operator to those of a lower-order one. The reduction matrix is theory-independent and can be obtained by solving a set of explicitly given linear conditions. The repeated application of such reduction matrices eventually transforms a given tree-level CHY-like integral to a prepared form. We also provide analytic expressions for the parameters associated with any such prepared form at tree level. We finally give a compact expression for the multidimensional residue for any CHY-like integral in terms of the reduction matrices. We adopt a dual basis projector which leads to the CHY-like representation for the non-local Bern–Carrasco–Johansson (BCJ) numerators at tree level in Yang–Mills theory. These BCJ numerators are efficiently computed by the improved method involving the reduction matrix.
Dynamics of general barotropic stellar fluid in the framework of R + 2αT gravity
Authors: Mosani Karim , Samanta Gauranga C.
Published: January 2020

Gravitational collapse of a spherically symmetric homogeneous perfect barotropic fluid with linear as well as polytropic-type Equation of State (EoS) has been investigated in the framework of a linear model of [Formula: see text] gravity. This modified gravity has the potential to explain the observed cosmic acceleration. The calculations have been done taking the transformed time coordinate [Formula: see text], where [Formula: see text] is the initial density of the fluid. For linear EoS [Formula: see text], the condition for being a true singularity, along with sufficient condition for the formation of apparent horizon covering the singularity has been derived. For a polytrope having the EoS [Formula: see text], the scale factor [Formula: see text] as a function of fluid density [Formula: see text] has been obtained which is then used to study the dynamics of the fluid. Role of the polytropic index [Formula: see text] and the constant of proportionality [Formula: see text] in the dynamics of the fluid is also studied. A new type of exotic matter field having varied dependence of scale factor on the density, and having the potential to give rise to bouncing cosmology, provided it is the dominating fluid in the universe, is obtained in this domain and is investigated. Energy conditions are discussed.
A new black hole solution in dilaton gravity inspired by power-law electrodynamics
Authors: Younesizadeh Younes , Ahmad Amir A. , Ahmed Ali Hassan , Younesizadeh Feyzollah , Ebrahimkhas Morad
Published: January 2020

In this work, a new class of slowly rotating black hole solutions in dilaton gravity has been obtained where dilaton field is coupled with nonlinear Maxwell invariant. The background space–time is a stationary axisymmetric geometry. Here, it has been shown that the dilaton potential can be written in the form of generalized three Liouville-type potentials. In the presence of these three Liouville-type dilaton potentials, the asymptotic behavior of the obtained solutions is neither flat nor (A)dS. One bizarre property of the electric field is that the electric field goes to zero when [Formula: see text] and diverges at [Formula: see text]. We show the validity of the first law of thermodynamics in thermodynamic investigations. The local and global thermodynamical stability are investigated through the use of heat capacity and Gibbs free energy. Also, the bounded, phase transition and the Hawking–Page phase transition points as well as the ranges of black hole stability have been shown in the corresponding diagrams. From these diagrams, we can say that the presence of the dilaton field makes the solutions to be locally stable near origin and vanishes the global stability of our solutions. In final thermodynamics analysis, we obtain the Smarr formula for our solution. We will show that the presence of dilaton field brings a new term in the Smarr formula. Also, we find that the dilaton field makes the black hole (AdS) mass to decrease for every fix values of [Formula: see text] (entropy).
There are no genuine Kähler–Codazzi manifolds
Authors: Etayo Fernando , deFrancisco Araceli , Santamaría Rafael
Published: January 2020

Nearly Kähler- and Kähler–Codazzi-type manifolds are defined in a very similar way. We prove that nearly Kähler-type manifolds make sense only in Hermitian and para-Hermitian contexts, and that Kähler–Codazzi-type manifolds reduce to Kähler-type manifolds in all the four Hermitian, para-Hermitian, Norden and product Riemannian geometries. Kähler–Codazzi condition is also studied on almost complex golden manifolds.
Classifying 3- and 4-designs on 28 points invariant under the group S6(2)
Authors: Rahimipour Ali Reza , Moshtagh Hossein
Published: January 2020

In this paper, we determine all simple block-transitive [Formula: see text]- and [Formula: see text]-designs on [Formula: see text] points admitting the group [Formula: see text] as the automorphism group. Thereby, we found 15 new [Formula: see text]-designs and two new [Formula: see text]-designs with the automorphism group [Formula: see text] up to isomorphism. Some of these designs are self-complementary and resolvable.
Domestic Sources of the US Trade War with China
Authors: STANGARONE Troy
Published: January 2020

The origins of the US–China trade war predate the Trump administration’s aggressive stance and have their roots in the economic impact of China’s entry into the WTO and China’s economic practices. The recently concluded phase one deal provides each side a chance to cool the tensions, but the politics in the United States likely preclude a full resolution in the near term. Another consequence of the trade war is the acceleration of production shifts out of China to Southeast Asia, but these opportunities are accompanied by greater US scrutiny of trade with the region.
Birth Control to Birth Promotion? China’s Population Policy at a Crossroads
Authors: ZHANG Min
Published: January 2020

China officially ended its one-child policy effective from 1 January 2016. Yet the effects of the relaxation of birth control policy have been limited thus far. Largely relying upon policy incentives, China’s policymakers also face pressure to take more direct measures to boost fertility rate. Whether the Chinese government is able to balance the needs of the nation and the citizens’ private rights remains a big question mark.
Macrophage modulation by polymerized hemoglobins: Potential as a wound-healing therapy
Authors: Krzyszczyk Paulina , Patel Kishan , Meng Yixin , O’Reggio Maurice , Richardson Kristopher , Acevedo Alison , Androulakis Ioannis P. , Yarmush Martin L. , Schloss Rene S. , Palmer Andre F. , Berthiaume François
Published: January 2020

Chronic skin wounds are hypoxic and are stalled in a pro-inflammatory state. Hemoglobin (Hb)-based oxygen carriers have shown potential in increasing oxygen delivery to aid wound healing. Macrophages also take up Hb, thus altering their phenotype and the regulation of inflammation. Herein, we compared the effect of Hb and polymerized Hbs (PolyHbs) on the phenotype of human macrophages. Macrophages were incubated with Hb or different forms of PolyHbs, and the inflammatory secretion profile was analyzed. PolyHbs were produced by polymerizing Hb in the relaxed (R) or tense (T) quaternary state and by varying the molar ratio of the glutaraldehyde crosslinking agent to Hb. Hb decreased the secretion of most measured factors. PolyHb treatment led to generally similar secretion profiles; however, Hb had more similar trends to R-state PolyHb. Ingenuity pathway analysis predicted positive outcomes in wound healing and angiogenesis for T-state PolyHb prepared with a 30:1 (glutaraldehyde:Hb) polymerization ratio. When tested in diabetic mouse wounds, T-state PolyHb resulted in the greatest epidermal thickness and vascular endothelial CD31 staining. Thus, the effects of PolyHb on macrophages are affected by the polymerization ratio and the quaternary state, and T-state PolyHb yields secretion profiles that are most beneficial in wound healing.
Fuzzing
Authors: Godefroid Patrice
Published: January 2020

Reviewing software testing techniques for finding security vulnerabilities.
Directions for professional social matching systems
Authors: Olsson Thomas , Huhtamäki Jukka , Kärkkäinen Hannu
Published: January 2020

Future PSM systems will require diversity-enhancing yet contextually sensitive designs.
PIV
Authors: Miri Pardis , Flory Robert , Uusberg Andero , Culbertson Heather , Harvey Richard H. , Kelman Agata , Peper Davis Erik , Gross James J. , Isbister Katherine , Marzullo Keith
Published: January 2020

We describe the design and evaluation of PIV, a personalizable and inconspicuous vibrotactile breathing pacer. Given the prevalence and adverse impact of anxiety and anxiety disorders, our goal is to develop a technology that helps people regulate their anxiety through paced breathing.

We examined two previously unstudied questions: What is an effective vibrotactile pattern for paced breathing, and where should the tactors be placed on the body to make the pacer most effective? We designed a series of personalized vibrotactile pacing patterns, and evaluated them on three body sites, in terms of self-reported and psychophysiological measures including skin conductance and breath wave parameters.

The results show that personalization plays an important role in PIV’s pattern and placement design choices. We concluded that the choice of frequency based, strong-exhale-phased patterns and abdomen placement are appropriate for future studies.
Opening up the baseboard management controller
Authors: Frazelle Jessie
Published: January 2020

If the CPU is the brain of the board, the BMC is the brain stem.
Dark web's doppelgängers aim to dupe antifraud systems
Authors: Marks Paul
Published: January 2020

Digital doppelgängers that fool online payment fraud detection systems are a threat to your bank balance.
Numbers are for computers, strings are for humans
Authors: Neville-Neil George V.
Published: January 2020

How and where software should translate data into a human-readable form.
Guiding students to develop essential skills
Authors: Kussmaul Clif
Published: January 2020

Students should interact with one another to practice skills and construct their own understanding, with assistance from a teacher acting as a coach and guide---not a lecturer.
Early angiogenic proteins associated with high risk for bronchopulmonary dysplasia and pulmonary hypertension in preterm infants
Authors: Arjaans Sanne , Wagner Brandie D. , Mourani Peter M. , Mandell Erica W. , Poindexter Brenda B. , Berger Rolf M. F. , Abman Steven H.
Published: January 2020

Early pulmonary vascular disease in preterm infants is associated with the subsequent development of bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH); however, mechanisms that contribute to or identify infants with increased susceptibility for BPD and/or PH are incompletely understood. Therefore, we tested if changes in circulating angiogenic peptides during the first week of life are associated with the later development of BPD and/or PH. We further sought to determine alternate peptides and related signaling pathways with the risk for BPD or PH. We prospectively enrolled infants with gestational age <34 wk and collected blood samples during their first week of life. BPD and PH were assessed at 36 wk postmenstrual age. Samples were assayed for each of the 1,121 peptides included in the SOMAscan scan technology, with subsequent pathway analysis. Of 102 infants in the study, 82 had BPD, and 13 had PH. Multiple angiogenic proteins (PF-4, VEGF121, ANG-1, bone morphogenetic protein 10 [BMP10], hepatocyte growth factor (HGF), ANG-2) were associated with the subsequent diagnosis of BPD; and FGF-19, PF-4, connective tissue activating peptide (CTAP)-III, and PDGF-AA levels were associated with BPD severity. Early increases in BMP10 was strongly associated with the late risk for BPD and PH. We found that early alterations of circulating angiogenic peptides and others were associated with the subsequent development of BPD. We further identified peptides that were associated with BPD severity and BPD-associated PH, including BMP10. We speculate that proteomic biomarkers during the first week of life may identify infants at risk for BPD and/or PH to enhance care and research.
Synthetic apolipoprotein A-I mimetic peptide 4F protects hearts and kidneys after myocardial infarction
Authors: Moreira Roberto S. , Irigoyen Maria C. , Capcha Jose M. C. , Sanches Talita R. , Gutierrez Paulo S. , Garnica Margoth R. , Noronha Irene de L. , Andrade Lucia
Published: January 2020

Patients undergoing coronary angiography after myocardial infarction (MI) often develop cardiac and renal dysfunction. We hypothesized that the apolipoprotein A-I mimetic peptide 4F (4F) would prevent those complications. Male Wistar rats were fed a high-cholesterol diet for 8 days. The rats were then anesthetized with isoflurane and randomly divided into five groups: a control group (sham-operated rats), and four groups of rats induced to MI by left coronary artery ligation, the rats in three of those groups being injected 6 h later, with the nonionic contrast agent iopamidol, 4F, and iopamidol plus 4F, respectively. At postprocedure hour 24, we performed the following experiments/tests ( n = 8 rats/group): metabolic cage studies; creatinine clearance studies; analysis of creatinine, urea, sodium, potassium, triglycerides, total cholesterol, very low-, low- and high-density lipoproteins (VLDL, LDL, and HDL); immunohistochemistry; histomorphometry; Western blot analysis; and transmission electron microscopy. In another set of experiments ( n = 8 rats/group), also performed at postprocedure hour 24, we measured mean arterial pressure, heart rate, heart rate variability, echocardiographic parameters, left ventricular systolic pressure, and left ventricular end-diastolic pressure. 4F protected against MI-induced increases in total cholesterol, triglycerides, and LDL; increased HDL levels; reversed autonomic and cardiac dysfunction; decreased the myocardial ischemic area; minimized renal and cardiac apoptosis; protected mitochondria; and strengthened endothelia possibly by minimizing Toll-like receptor 4 upregulation (thus restoring endothelial nitric oxide synthase protein expression) and by upregulating vascular endothelial growth factor protein expression. 4F-treated animals showed signs of cardiac neovascularization. The nitric oxide-dependent cardioprotection and renoprotection provided by 4F could have implications for post-MI treatment.
Neurokinin-1 receptor activation is sufficient to restore the hypercapnic ventilatory response in the Substance P-deficient naked mole-rat
Authors: Clayson Maxwell S. , Devereaux Maiah E. M. , Pamenter Matthew E.
Published: January 2020

Naked mole-rats (NMRs) live in large colonies within densely populated underground burrows. Their collective respiration generates significant metabolic carbon dioxide (CO2) that diffuses slowly out of the burrow network, creating a hypercapnic environment. Currently, the physiological mechanisms that underlie the ability of NMRs to tolerate environmental hypercapnia are largely unknown. To address this, we used whole-body plethysmography and respirometry to elucidate the hypercapnic ventilatory and metabolic responses of awake, freely behaving NMRs to 0%–10% CO2. We found that NMRs have a blunted hypercapnic ventilatory response (HCVR): ventilation increased only in 10% CO2. Conversely, metabolism was unaffected by hypercapnia. NMRs are insensitive to cutaneous acid-based pain caused by modified substance P (SP)-mediated peripheral neurotransmission, and SP is also an important neuromodulator of ventilation. Therefore, we re-evaluated physiological responses to hypercapnia in NMRs after an intraperitoneal injection of exogenous substance P (2 mg/kg) or a long-lived isoform of substance P {[pGlu5-MePhe8-MeGly9]SP(5-11), DiMe-C7; 40–400 μg/kg}. We found that both drugs restored hypercapnia sensitivity and unmasked an HCVR in animals breathing 2%–10% CO2. Taken together, our findings indicate that NMRs are remarkably tolerant of hypercapnic environments and have a blunted HCVR; however, the signaling network architecture required for a “normal” HCVR is retained but endogenously inactive. This muting of chemosensitivity likely suits the ecophysiology of this species, which presumably experiences hypercapnia regularly in their underground niche.
Self-motion trajectories can facilitate orientation-based figure-ground segregation
Authors: Dutta Arkadeb , Lev-Ari Tidhar , Barzilay Ouriel , Mairon Rotem , Wolf Alon , Ben-Shahar Ohad , Gutfreund Yoram
Published: January 2020

Segregation of objects from the background is a basic and essential property of the visual system. We studied the neural detection of objects defined by orientation difference from background in barn owls ( Tyto alba). We presented wide-field displays of densely packed stripes with a dominant orientation. Visual objects were created by orienting a circular patch differently from the background. In head-fixed conditions, neurons in both tecto- and thalamofugal visual pathways (optic tectum and visual Wulst) were weakly responsive to these objects in their receptive fields. However, notably, in freely viewing conditions, barn owls occasionally perform peculiar side-to-side head motions (peering) when scanning the environment. In the second part of the study we thus recorded the neural response from head-fixed owls while the visual displays replicated the peering conditions; i.e., the displays (objects and backgrounds) were shifted along trajectories that induced a retinal motion identical to sampled peering motions during viewing of a static object. These conditions induced dramatic neural responses to the objects, in the very same neurons that where unresponsive to the objects in static displays. By reverting to circular motions of the display, we show that the pattern of the neural response is mostly shaped by the orientation of the background relative to motion and not the orientation of the object. Thus our findings provide evidence that peering and/or other self-motions can facilitate orientation-based figure-ground segregation through interaction with inhibition from the surround.

NEW & NOTEWORTHY Animals frequently move their sensory organs and thereby create motion cues that can enhance object segregation from background. We address a special example of such active sensing, in barn owls. When scanning the environment, barn owls occasionally perform small-amplitude side-to-side head movements called peering. We show that the visual outcome of such peering movements elicit neural detection of objects that are rotated from the dominant orientation of the background scene and which are otherwise mostly undetected. These results suggest a novel role for self-motions in sensing objects that break the regular orientation of elements in the scene.
Single-unit activity in marmoset posterior parietal cortex in a gap saccade task
Authors: Ma Liya , Selvanayagam Janahan , Ghahremani Maryam , Hayrynen Lauren K. , Johnston Kevin D. , Everling Stefan
Published: January 2020

Abnormal saccadic eye movements can serve as biomarkers for patients with several neuropsychiatric disorders. The common marmoset ( Callithrix jacchus) is becoming increasingly popular as a nonhuman primate model to investigate the cortical mechanisms of saccadic control. Recently, our group demonstrated that microstimulation in the posterior parietal cortex (PPC) of marmosets elicits contralateral saccades. Here we recorded single-unit activity in the PPC of the same two marmosets using chronic microelectrode arrays while the monkeys performed a saccadic task with gap trials (target onset lagged fixation point offset by 200 ms) interleaved with step trials (fixation point disappeared when the peripheral target appeared). Both marmosets showed a gap effect, shorter saccadic reaction times (SRTs) in gap vs. step trials. On average, stronger gap-period responses across the entire neuronal population preceded shorter SRTs on trials with contralateral targets although this correlation was stronger among the 15% “gap neurons,” which responded significantly during the gap. We also found 39% “target neurons” with significant saccadic target-related responses, which were stronger in gap trials and correlated with the SRTs better than the remaining neurons. Compared with saccades with relatively long SRTs, short-SRT saccades were preceded by both stronger gap-related and target-related responses in all PPC neurons, regardless of whether such response reached significance. Our findings suggest that the PPC in the marmoset contains an area that is involved in the modulation of saccadic preparation.

NEW & NOTEWORTHY As a primate model in systems neuroscience, the marmoset is a great complement to the macaque monkey because of its unique advantages. To identify oculomotor networks in the marmoset, we recorded from the marmoset posterior parietal cortex during a saccadic task and found single-unit activities consistent with a role in saccadic modulation. This finding supports the marmoset as a valuable model for studying oculomotor control.
Vagus Nerve Stimulation Alleviates Hepatic Ischemia and Reperfusion Injury by Regulating Glutathione Production and Transformation
Authors: Xia Haoyang , Liu Zhongzhong , Liang Wenjin , Zeng Xianpeng , Yang Yi , Chen Pu , Zhong Zibiao , Ye Qifa
Published: January 2020

Inflammation and oxidative stress are pivotal mechanisms for the pathogenesis of ischemia and reperfusion injury (IRI). Vagus nerve stimulation (VNS) may participate in maintaining oxidative homeostasis and response to external stimulus or injury. We investigated whether the in vivo VNS can protect the liver from IRI. In this study, hepatic IRI were induced by ligating the vessels supplying the left and middle lobes of the liver, which underwent 1 h occlusion followed with 24 h reperfusion. VNS was initiated 15 min after ischemia and continued 30 min. Hepatic function, histology, and apoptosis rates were evaluated after 24 h reperfusion. Compared with the IRI group, VNS significantly improved hepatic function. The protective effect was accompanied by a reduction in histological damage in the ischemic area, and the apoptosis rate of hepatocytes has considerable reduction. To find the underlying mechanism, proteomic analysis was performed and differential expression of glutathione synthetase (GSS) and glutathione S-transferase (GST) was observed. Subsequently, test results indicated that VNS upregulated the expression of mRNA and protein of GSS and GST. Meanwhile, VNS increased the plasma levels of glutathione and glutathione peroxidases. We found that VNS alleviated hepatic IRI by upregulating the antioxidant glutathione via the GSS/glutathione/GST signaling pathway.
New Diagnosis Test under the Neutrosophic Statistics: An Application to Diabetic Patients
Authors: Aslam Muhammad , Arif Osama H. , Sherwani Rehan Ahmad Khan
Published: January 2020

The diagnosis tests (DT) under classical statistics are applied under the assumption that all observations in the data are determined. Therefore, these DT cannot be applied for the analysis of the data when some or all observations are not determined. The neutrosophic statistics (NS) which is the extension of classical statistics can be applied for the data having uncertain, unclear, and fuzzy observations. In this paper, we will present the DT, and gold‐standard tests under NS are called neutrosophic diagnosis tests (NDT). Therefore, the proposed NDT is the generalization of the existing DT and can be applied under the uncertainty environment. We will present the NDT table and present a real example from the medical field. The use of the proposed method will be more effective and adequate to be used in medical science, biostatistics, decision, and classification analysis.
Changes in Intestinal Microbiota Are Associated with Islet Function in a Mouse Model of Dietary Vitamin A Deficiency
Authors: Zhou Yunting , Zhou Junming , Zhang Yumin , Tang Jun , Sun Bo , Xu Wei , Wang Xiaohang , Chen Yang , Sun Zilin
Published: January 2020

Aims. The underlying mechanisms involved in Vitamin A- (VA-) related changes in glucose metabolic disorders remain unclear. Recent evidence suggests that intestinal microbiota is closely linked to the metabolic syndrome. Here, we explored whether and how intestinal microbiota affects glucose homeostasis in VA-deficient diet-fed mice. Methods. Six-week-old male C57BL/6 mice were randomly placed on either a VA-sufficient (VAS) or VA-deficient (VAD) diet for 10 weeks. Subsequently, a subclass of the VAD diet-fed mice was switched to a VA-deficient rescued (VADR) diet for an additional 8 weeks. The glucose metabolic phenotypes of the mice were assessed using glucose tolerance tests and immunohistochemistry staining. Changes in intestinal microbiota were assessed using 16S gene sequencing. The intestinal morphology, intestinal permeability, and inflammatory response activation signaling pathway were assessed using histological staining, western blots, quantitative-PCR, and enzyme-linked immunosorbent assays. Results. VAD diet-fed mice displayed reduction of tissue VA levels, increased area under the curve (AUC) of glucose challenge, reduced glucose-stimulated insulin secretion, and loss of β cell mass. Redundancy analysis showed intestinal microbiota diversity was significantly associated with AUC of glucose challenge and β cell mass. VAD diet-driven changes in intestinal microbiota followed the inflammatory response with increased intestinal permeability and higher mRNA expression of intestinal inflammatory cytokines through nuclear factor-κB signaling pathway activation. Reintroduction of dietary VA to VAD diet-fed mice restored tissue VA levels, endocrine hormone profiles, and inflammatory response, which are similar to those observed following VAS-controlled changes in intestinal microbiota. Conclusions. We found intestinal microbiota effect islet function via controlling intestinal inflammatory phenotype in VAD diet-fed mice. Intestinal microbiota influences could be considered as an additional mechanism for the effect of endocrine function in a VAD diet-driven mouse model.
Knowledge, Attitude, and Associated Factors towards Colostrum Feeding among Antenatal Care Attendant Mothers in Gununo Health Centre, Wolaita Zone, Ethiopia 2019: Cross-Sectional Study
Authors: Yeshambel Wassie Addisu , Atnafu Gebeyehu Natnael , Abebe Gelaw Kelemu
Published: January 2020

Background. The role of colostrum in promoting the growth and development of the newborn as well as fighting infections is widely acknowledged. In Ethiopia, there are differences in cultures in the acceptability of colostrum and the prevalence of colostrum feeding. Although breastfeeding is a common practice in Ethiopia, there is a difference in the awareness and attitude of pregnant mothers regarding colostrum feeding. Objectives. To assess knowledge, attitude, and associated factors towards colostrum feeding among antenatal care attendant mothers in Gununo Health Center, South Ethiopia, 2019. Methods. Facility-based cross-sectional study design was conducted among 342 ANC (antenatal care) attendant mothers in Gununo Health Center from April to May 2019. Data was collected by using structured interviewer questionnaires and the subjects were selected through systematic random sampling. Data template was prepared by Epi data-manger version 4.2 and SPSS version 23 was used for analysis. Bivariate and multivariate analysis with 95% CI was employed. Variables found to have a p-value < 0.2 in the binary logistic regression were entered into multivariate analysis and strength of association was declared at p-value < 0.05. Results. Among the study participants 226 (66.1%) were knowledgeable and 39 (11.4%) were not knowledgeable on colostrum feeding. From the respondents, 239 (69.9%) had a positive attitude and the rest 103 (30.1%) mothers had a negative attitude towards colostrum feeding. Respondents who had more than four children (AOR = 1.21, 95% CI [1.31, 2.47], ANC visit (four times and above) (AOR=2.8, 95% CI [2.23, 4.49]), and counseled about colostrum feeding (AOR = 2.29, 95% CI [2.34, 3.74]), were some variables that significantly associated with knowledge of colostrum feeding. Those who had been counseled about breastfeeding (AOR = 1.16, 95% CI [1.59–3.96]), ANC visit (AOR = 11.32, 95% CI [1.14, 112.64]), and multiparas (AOR = 5.68, 95% CI [1.57, 20.53]) were some variables that significantly associated with attitude. Conclusion and Recommendation. Even though the mothers’ knowledge and attitude seem higher than from previously conducted articles in Ethiopia, still gaps were seen clearly on colostrum feeding in the area. It is recommended to set strategies to promote colostrum feeding.