bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Bio-Inspired Pneumatic Valve Adapter for Soft Robotic Vasculature
Authors: Saunders Benjamin O. , Swensen John P.
Published: November 2020

This paper proposes a novel pneumatic valve adapter that decreases the size and quantity of pneumatic tubes and valves necessary for soft robotics by mimicking cardiovascular systems. Some cardiovascular systems, evolved to be powered by a single reservoir, the heart, which in turn powers the rest of the body by systematically opening and closing valves as needed. The presented valve adapter consists of a set of concentric tube, where both tubes have strategically patterned holes. The inner tube can be moved translationally and rotationally to align with designated hole positions in the outer tube, thus opening and closing pathways to chambers for pressure flow. The two-tube system can be used to either pressurize a chamber or depressurize a chamber or multiple chambers simultaneously.
Design of Revolute Joint With Bi-Stability Using Permanent Magnets
Authors: Yang Hyeon-Ho , Han Jae-Hung
Published: November 2020

Bi-stable mechanisms are systems with two distinct stable equilibrium positions within their range of operation. They are capable of steadily staying in positions without external power input and require less energy to move to the next stable state because of their snap-through behavior. Diverse applications including switches, deployable structures, and reconfigurable robots can benefit from bi-stability characteristics. However, the complexity of implementation and the limitation of structure configuration have made it difficult to apply conventional bi-stable mechanisms to the structures that require rotational bi-stability. Thus, in this paper, we proposed an implementation method using cylindrical magnets for the rotational bi-stable mechanism.

The proposed bi-stable mechanism consists of a revolute joint with two links; one is the rotational link and the other is the fixed link. It has rotational bi-stability through the magnetic force relationship between the array of magnets on each link. To identify the characteristics of the proposed bi-stable mechanism, a cylindrical permanent magnet is considered as an electromagnet model that consists of one ring with a virtual electric current. Consequently, the magnetic field of the cylindrical permanent magnet can be calculated using Biot-Savart law. Similarly, the magnetic force between two cylindrical permanent magnets of the electromagnet model is calculated using Lorentz force law.

The criteria of the magnet array for symmetric bi-stability are proposed and the potential energy diagram of the rotation link is considered as the performance criterion to identify the stable state.
Real-Time Model Updating Algorithm for Structures Experiencing High-Rate Dynamic Events
Authors: Hong Seong Hyeon , Drnek Claire , Downey Austin , Wang Yi , Dodson Jacob
Published: November 2020

Real-time model updating of active structures subject to unmodeled high-rate dynamic events require structural model updates on the timescale of 2 ms or less. Examples of active structures subjected to unmodeled high-rate dynamic events include hypersonic vehicles, active blast mitigation, and orbital infrastructure. Due to the unmodeled nature of the events of interest, the real-time model updating algorithm should circumvent any model pre-calculations. In this work, we present a methodology that updates the finite element analysis (FEA) model of a structure experiencing varying dynamics through online measurements. The algorithm is demonstrated for a testbed, comprised of a cantilever beam and a roller that serves as movable support. The structure’s state is updated (i.e. the position of the moving roller) by continuously updating the associated FEA model through an online adaptive meshing and search algorithm. The structure’s state is continuously estimated by comparing the measured signals with FEA models. New FEA models are built based on the enhanced estimate of the structure’s state through adaptive meshing for modal analysis and adaptive search space for the FEA model selection. The proposed methodology is verified experimentally in real-time using the testbed. It is demonstrated that the adaptive features can achieve accurate state estimations within the required 2 ms timescale.
Whole-Genome Analysis of a Shiga Toxin-Producing Escherichia coli O103:H2 Strain Isolated from Cattle Feces
Authors: Zhang Yujie , Liao Yen-Te , Wu Vivian C. H.
Published: November 2020

Shiga toxin-producing
Escherichia coli
(STEC) serotype O103 is one of the primary pathogenic contaminants of beef products, contributing to several foodborne outbreaks in recent years. Here, we report the whole-genome sequence of a STEC O103:H2 strain isolated from cattle feces that contains a locus of enterocyte effacement (LEE) pathogenicity island.
Genome Sequences of Microbacteriophages Zada and Ioannes
Authors: El Yaman Razan , Anderson Jayla S. , Anderson Tania M. , Avalos Michael A. , Bangurah Sheku K. , Dada Ken B. , Degener Kiefer R. , Hadeed Mohammad N. , Issa Leen H. , Jaeran Akhteyar S. , Kowalski Katelynn M. , Lloyd Yamere T. , Loucopoulos Demitra P. , Manzo Vanessa J. , Nunez Nicolas M. , Sandoval Andrea M. , Shelton Semaj , Taddei Steven M. , Zamat Ali A. , Conant Stephanie B. , Finkel Jonathan S. , Kagey Jacob D.
Published: November 2020

Microbacteriophages Zada and Ioannes were isolated from soil and characterized. Genomes were then sequenced and annotated. This was done using the host bacterium
Microbacterium foliorum
. Zada and Ioannes are both lytic phages with a
Siphoviridae
morphotype.
Draft Genome Sequences of Hazelnut-Associated
Pseudomonas
Strains Isolated in Ontario, Canada
Authors: Ellouze Walid , Nesbitt Darlene , Parcey Michael , Gayder Steven , Marchand Geneviève , Svircev Antonet M. , Tambong James T.
Published: November 2020

Two
Pseudomonas
strains (H346-M and H346-S) were isolated from hazelnut trees showing symptoms of shoot dieback and necrosis. The draft genome sequences of H346-M and H346-S consist of 66 and 51 contigs, respectively, with total sizes of 5,693,988 and 5,889,925 bp and 4,885 and 5,045 protein-coding sequences, respectively.
Genome Sequencing of Escherichia coli and Klebsiella pneumoniae Isolates That Harbor the FOX-5 β-Lactamase Gene
Authors: Hazen Tracy H. , Johnson J. Kristie , Harris Anthony D. , Rasko David A.
Published: November 2020

We generated draft genome assemblies of three
Escherichia coli
and seven
Klebsiella pneumoniae
isolates that harbor the FOX-5 β-lactamase-encoding gene.
A new glacial varve chronology along the southern Laurentide Ice Sheet that spans the Younger Dryas–Holocene boundary
Authors: Breckenridge A. , Lowell T.V. , Peteet D. , Wattrus N. , Moretto M. , Norris N. , Dennison A.
Published: November 2020

Glacial varves can detail ice-margin positions and provide a proxy for meltwater discharge at resolutions comparable to those of the Greenland ice core archives, and thus they can be critical paleorecords for assessing the response of both ancient and modern ice sheets to climate change. Here we provide an ∼1500 yr varve chronology straddling the Younger Dryas (YD)–Holocene boundary (11.65 cal. kyr B.P.), the first such chronology in North America. The varves are from glacial Lake Agassiz (central North America). The chronology is pinned on accelerator mass spectrometry radiocarbon-dated terrestrial macrofossils at the base of a widespread red-clay bed deposited during flooding from the Lake Superior basin. We illustrate the utility of this record by examining ice-margin retreat and melting through the late Younger Dryas and across the Holocene boundary. The ice margin receded at a constant rate, not only during the late YD, but for at least 300 yr after the onset of the Holocene. In contrast, varve thicknesses increased at the boundary, and a moraine formed over a 50 yr period, perhaps in response to the warming climate. Our expectation is that this time series will continue to be developed, expanded, and refined because it promises to be the longest and most geographically extensive glacial varve data set in North America.
Pulsed volcanic combustion events coincident with the end-Permian terrestrial disturbance and the following global crisis
Authors: Kaiho Kunio , Aftabuzzaman Md. , Jones David S. , Tian Li
Published: November 2020

Eruption of the Siberian Traps large igneous province (LIP) is thought to have triggered the Permian-Triassic biological crisis, the largest of the Phanerozoic mass extinctions. Mercury concentration enrichments have been widely used as a proxy for volcanic inputs to sediments, especially for ancient LIP eruptions. However, detailed correlations of magmatic pulses with extinction events in the terrestrial and marine realms are not fully resolved. Here we use paired coronene (a six-ring polycyclic aromatic hydrocarbon, a high-temperature combustion proxy) and mercury spikes as a refined proxy for LIP emplacement. In records from stratigraphic sections in south China and Italy, we identify two sets of paired coronene-mercury spikes accompanied by land plant biomarker spikes, followed by a rapid decrease coinciding with terrestrial ecological disturbance and extinction of marine metazoans. Each short-term episode is likely caused by high-temperature combustion of sedimentary hydrocarbons during initial sill emplacement of the Siberian Traps LIP. These data indicate that discrete volcanic eruptions could have caused the terrestrial ecosystem crisis followed by the marine ecosystem crisis in ∼60 k.y., and that the terrestrial ecosystem was disrupted by smaller global environmental changes than the marine ecosystem.
Melioidosis of the nervous system: atypical presentation of a rare disease in a 48-year-old man
Authors: Hamdoon Saif , Wilson Ian , Smith Simon , Gericke Christian
Published: November 2020

A 48-year-old man who worked in mining in remote, northern Australia was transferred from a rural hospital 5 days after the onset of headaches, subjective fevers and flaccid paralysis of the left upper limb. Initial investigations demonstrated inflammatory cerebrospinal fluid (CSF) changes and a longitudinally extensive cervical cord lesion. Given two serial negative blood and CSF cultures, he was treated as inflammatory myelitis with intravenous methylprednisolone. Despite the initial improvement in pain and left arm power, the patient’s neurological deficit plateaued and then deteriorated with worsening neck pain, diaphragmatic dysfunction and dysphagia requiring intubation and respiratory support. A third CSF culture isolatedBurkholderia pseudomalleiconfirming a diagnosis of neuro-melioidosis. Repeat imaging revealed the rostral extension of the original spinal cord lesion into the medulla and pons. Over the next 4 weeks, the patient’s neurological deficits slowly improved with continued intravenous antibiotic therapy with meropenem and oral trimethoprim/sulfamethoxazole.
Normal and abnormal foveal development
Authors: Thomas Mervyn G , Papageorgiou Eleni , Kuht Helen J , Gottlob Irene
Published: November 2020

Normal foveal development begins in utero at midgestation with centrifugal displacement of inner retinal layers (IRLs) from the location of the incipient fovea. The outer retinal changes such as increase in cone cell bodies, cone elongation and packing mainly occur after birth and continue until 13 years of age. The maturity of the fovea can be assessed invivo using optical coherence tomography, which in normal development would show a well-developed foveal pit, extrusion of IRLs, thickened outer nuclear layer and long outer segments. Developmental abnormalities of various degrees can result in foveal hypoplasia (FH). This is a characteristic feature for example in albinism, aniridia, prematurity, foveal hypoplasia with optic nerve decussation defects with or without anterior segment dysgenesis without albinism (FHONDA) and optic nerve hypoplasia. In achromatopsia, there is disruption of the outer retinal layers with atypical FH. Similarly, in retinal dystrophies, there is abnormal lamination of the IRLs sometimes with persistent IRLs. Morphology of FH provides clues to diagnoses, and grading correlates to visual acuity. The outer segment thickness is a surrogate marker for cone density and in foveal hypoplasia this correlates strongly with visual acuity. In preverbal children grading FH can help predict future visual acuity.
Exercise interventions in lateral elbow tendinopathy have better outcomes than passive interventions, but the effects are small: a systematic review and meta-analysis of 2123 subjects in 30 trials
Authors: Karanasios Stefanos , Korakakis Vasileios , Whiteley Rod , Vasilogeorgis Ioannis , Woodbridge Sarah , Gioftsos Georgios
Published: November 2020

Objective

To evaluate the effectiveness of exercise compared with other conservative interventions in the management of lateral elbow tendinopathy (LET) on pain and function.

Design

Systematic review and meta-analysis.

Methods

We used the Cochrane risk-of-bias tool 2 for randomised controlled trials (RCTs) to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation methodology to grade the certainty of evidence. Self-perceived improvement, pain intensity, pain-free grip strength (PFGS) and elbow disability were used as primary outcome measures.

Eligibility criteria

RCTs assessing the effectiveness of exercise alone or as an additive intervention compared with passive interventions, wait-and-see or injections in patients with LET.

Results

30 RCTs (2123 participants, 5 comparator interventions) were identified. Exercise outperformed (low certainty) corticosteroid injections in all outcomes at all time points except short-term pain reduction. Clinically significant differences were found in PFGS at short-term (mean difference (MD): 12.15, (95% CI) 1.69 to 22.6), mid-term (MD: 22.45, 95% CI 3.63 to 41.3) and long-term follow-up (MD: 18, 95% CI 11.17 to 24.84). Statistically significant differences (very low certainty) for exercise compared with wait-and-see were found only in self-perceived improvement at short-term, pain reduction and elbow disability at short-term and long-term follow-up. Substantial heterogeneity in descriptions of equipment, load, duration and frequency of exercise programmes were evident.

Conclusions

Low and very low certainty evidence suggests exercise is effective compared with passive interventions with or without invasive treatment in LET, but the effect is small.

PROSPERO registration number

CRD42018082703.
Telehealth: improving maternity services by modern technology
Authors: Fazal Nusrat , Webb Anne , Bangoura Jo , El Nasharty Mohamed
Published: November 2020

Hypertension is considered one of the most common medical disorders causing complexities in pregnancy. It could be a newly developed pregnancy-induced hypertension (PIH) or a pre-existing hypertension developing into superimposed pre-eclamptic toxaemia. PIH affects approximately 10% of pregnancies and can have a serious impact on both maternal and fetal well-being; hence requires frequent monitoring and timely intervention. National Institute for Health and Care Excellence (NICE) guidelines recommends once or twice weekly monitoring of blood pressure for such patients. The required frequent monitoring comes with certain implications for patients and healthcare services. An average patient with PIH would need to see her healthcare provider once or twice a week until delivery and 6 weeks thereafter. This certainly increases pressure on limited National Health Service (NHS) resources. Home-based monitoring using Telehealth technology can represent a potential solution for achieving good-quality care for the patient without increasing the workload for healthcare providers. We used ‘Florence’, a text-based technology platform to support home monitoring. We tested its acceptability, feasibility and safety to replace face-to-face appointments for blood pressure monitoring in selected patients with PIH. We implemented our project in three progressive phases using a plan, do, study, act methodology. Florence, telehealth technology was used for blood pressure monitoring instead of face-to-face appointments, and the effect of this innovative technology on the services and the patient experience was studied and necessary modifications were made before progression into the next phase. We recruited 75 patients over 12 months through the progressive phases and replaced around 800 face-to-face appointments by remotely supervised monitoring sessions with Florence successfully, with improved care and patient satisfaction. We also achieved better compliance with the NICE guidelines for blood pressure monitoring in PIH. Our project concluded that Telehealth can be a potential solution for improving care in maternity services, with lesser burden on NHS resources.
Home-related and work-related injuries in Makwanpur district, Nepal: a household survey
Authors: Pant Puspa Raj , Deave Toity , Banstola Amrit , Bhatta Sumiksha , Joshi Elisha , Adhikari Dhruba , Manandhar Sunil Raja , Joshi Sunil Kumar , Mytton Julie A
Published: November 2020

Objective

To describe the epidemiology of home-related and work-related injuries, their mechanisms, inequalities and costs associated with these injuries.

Methods

A household survey was undertaken in three palikas of Makwanpur district between April and June 2019. Data were collected electronically on non-fatal injuries that occurred in the previous 3 months and fatal injuries that occurred in the previous 5 years.

Findings

17 593 individuals were surveyed from 3327 households. Injury rates were 8.0 per 1000 population for home injuries and 6.4 per 1000 for work-related injuries; 61.0% of home injuries were among women and 69.9% of work-related injuries among men. Falls were the cause of 48% home injuries, affecting 50.9% of men and 46.5% of women. Burns/scalds were higher in women than men, affecting 17.4% of women reporting home injuries. Cuts and piercings accounted for 39.8% of all work-related injuries and 36.3% were falls. Injury incidence varied by ethnic group: home injuries were highest in Brahmin (12.0 per 1000) and work-related injuries highest in Rai groups (21.0 per 1000). The total mean costs (transport and treatment) of work-related injury was US$143.3 (SD 276.7), higher than for home injuries (US$130.4, SD 347.6). The number of home (n=74, 64.9%) and work-related (n=67, 77.9%) injuries were higher in families below the poverty line than families in the next income bracket (home: n=22, 19.3%; work: n=11, 12.8%).

Conclusions

Home-related and work-related fall injuries are common. The inequalities in injury identified in our study by rurality, age, sex, income level and ethnic group can help target injury prevention interventions for vulnerable groups.
Associations of APOE e2 genotype with cerebrovascular pathology: a postmortem study of 1275 brains
Authors: Goldberg Terry E , Huey Edward D , Devanand Davangere P
Published: November 2020

Objective

We assessed the association of apolipoprotein E (APOE) genotype with cerebrovascular disease (CVD) in a large neuropathological database maintained by the National Alzheimer’s Coordinating Center (NACC). Such a comprehensive investigation of APOE and CVD pathology has not heretofore been conducted. We focused on APOE e2, an established neuroprotective genetic variant against Alzheimer’s disease.

Methods

To implement these objectives APOE associations in the NACC database of 1275 brains with 11 CVD pathologies, including old and recent infarcts, haemorrhages, cerebral amyloid angiopathy (CAA) and arteriosclerosis, were examined. These pathologies were uniformly and semiquantitatively measured across 39 Alzheimer’s Disease Center sites. We used χ2 statistics and ordinal regression to assess the significance of associations and Bonferroni corrected for multiple comparisons.

Results

Of the cases, 98 were e2/e3 or e2/e2 genotypes (‘e2’ carriers), 621 were e3 homozygotes (‘e3’ group), and 556 were e4/e3 (442) or e4/e4 (114) genotypes (‘e4’ group). Results indicated that the APOE e4 allele significantly increased risk for CAA. After stratification by CAA presence/absence, we found that in those cases in which CAA was present, APOE e2 significantly increased risk for gross haemorrhage. All other associations were negative.

Conclusions

In this, the largest study of APOE e2 effects on pathologically verified CVD, e2 was not protective against any CVD pathology compared with e3 homozygotes, including CAA. Regarding the latter pathology, e4 was associated with increases in its severity. Furthermore, and perhaps unexpectedly, e2 significantly increased risk of acute/subacute gross haemorrhage in the presence of CAA. Thus, there were limits to e2 neuroprotection against amyloidosis, despite its known and large protective effects against diffuse and neuritic amyloid plaques compared with e3/e3 and e4 carriers in this very collection.
Prevalence, predictors and prognosis of incidental intracranial aneurysms in patients with suspected TIA and minor stroke: a population-based study and systematic review
Authors: Hurford Robert , Taveira Isabel , Kuker Wilhelm , Rothwell Peter M
Published: November 2020

Introduction

Unruptured intracranial aneurysms (UIAs) are common incidental imaging findings, but there are few data in patients with transient ischaemic attack (TIA)/stroke. The frequency of UIA might be higher due to shared risk factors, but rupture risk might be reduced by intensive secondary prevention. We determined the prevalence and prognosis of UIA in patients with suspected TIA/minor stroke.

Methods

All patients referred to the population-based Oxford Vascular Study (2011–2020) with suspected TIA/minor stroke and non-invasive angiography were included. We determined the prevalence of incidental asymptomatic UIA and the risk of subsequent subarachnoid haemorrhage (SAH) by follow-up on intensive medical treatment, with guideline-based monitoring/management. We also did a systematic review of UIA prevalence/prognosis in cohorts with TIA/stroke.

Findings

Among 2013 eligible patients, 95 (4.7%) had 103 previously unknown asymptomatic UIA. Female sex (OR 2.3, 95% CI 1.5 to 3.7), smoking (2.1, 1.2 to 3.6) and hypertension (1.6, 1.0 to 2.5) were independently predictive of UIA, with a prevalence of 11.1% in those with all three risk factors. During mean follow-up of 4.5 years, only one SAH occurred: 2.3 (95% CI 0.3 to 16.6) per 1000 person-years. We identified 19 studies of UIA in TIA/stroke cohorts (n=12 781), all with either symptomatic carotid stenosis or major acute stroke. The pooled mean UIA prevalence in patients with TIA/stroke was 5.1% (95% CI 4.8 to 5.5) and the incidence of SAH was 4.6 (95% CI 1.9 to 11.0) per 1000 person-years.

Interpretation

The 5% prevalence of UIA in patients with confirmed TIA/minor stroke is likely higher than that in the general population. However, the risk of SAH on intensive medical treatment and guideline-based management/monitoring is low.
Ethics of pursuing targets in public health: the case of voluntary medical male circumcision for HIV-prevention programs in Kenya
Authors: Rennie Stuart , Gilbertson Adam , Hallfors Denise , Luseno Winnie K
Published: November 2020

The use of targets to direct public health programmes, particularly in global initiatives, has become widely accepted and commonplace. This paper is an ethical analysis of the utilisation of targets in global public health using our fieldwork on and experiences with voluntary medical male circumcision (VMMC) initiatives in Kenya. Among the many countries involved in VMMC for HIV prevention, Kenya is considered a success story, its programmes having medically circumcised nearly 2 million men since 2007. We describe ethically problematic practices in Kenyan VMMC programmes revealed by our fieldwork, how the problems are related to the pursuit of targets and discuss possible approaches to their management. Although the establishment and pursuit of targets in public health can have many benefits, assessments of target-driven programmes tend to focus on quantifiable outcomes rather than the processes by which the outcomes are obtained. However, in order to speak more robustly about programmatic ‘success’, and to maintain community trust, it is vital to ethically evaluate how a public health initiative is actually implemented in the pursuit of its targets.
Emotional support animals are not like prosthetics: a response to Sara Kolmes
Authors: du Toit Jessica , Benatar David
Published: November 2020

Sara Kolmes has argued that the human ‘handlers’ of emotional support animals (ESAs) should have the sorts of body-like rights to those animals that people with prosthetics have to their prosthetics. In support of this conclusion, she argues that ESAs both function and feel like prosthetics, and that the disanalogies between ESAs and prosthetics are irrelevant to whether humans can have body-like rights to their ESAs. In response, we argue that Ms Kolmes has failed to show that ESAs are body-like in the ways that paradigmatic prostheses are and that, even if they were, these similarities would be outweighed by a crucial dissimilarity that she underestimates.
Roles of Very Fast Ripple (500–1000Hz) in the Hippocampal Network During Status Epilepticus
Authors: Hao Jianmin , Cui Yan , Niu Bochao , Yu Liang , Lin Yuhang , Xia Yang , Yao Dezhong , Guo Daqing
Published: November 2020

Very fast ripples (VFRs, 500–1000[Formula: see text]Hz) are considered more specific than high-frequency oscillations (80–500[Formula: see text]Hz) as biomarkers of epileptogenic zones. Although VFRs are frequent abnormal phenomena in epileptic seizures, their functional roles remain unclear. Here, we detected the VFRs in the hippocampal network and tracked their roles during status epilepticus (SE) in rats with pilocarpine-induced temporal lobe epilepsy (TLE). All regions in the hippocampal network exhibited VFRs in the baseline, preictal, ictal and postictal states, with the ictal state containing the most VFRs. Moreover, strong phase-locking couplings existed between VFRs and slow oscillations (1–12[Formula: see text]Hz) in the ictal and postictal states for all regions. Further investigation indicated that during VFRs, the build-up of slow oscillations in the ictal state began from the temporal lobe and then spread through the whole hippocampal network via two different pathways, which might be associated with the underlying propagation of epileptiform discharges in the hippocampal network. Overall, we provide a functional description of the emergence of VFRs in the hippocampal network during SE, and we also establish that VFRs may be the physiological representation of the pathological alterations in hippocampal network activity during SE in TLE.
Study of cosmic models in f(R,T) gravity with tilted observers
Authors: Dagwal V. J. , Pawar D. D. , Solanke Y. S.
Published: November 2020

In this work, we have studied LRS Bianchi type I cosmological models in [Formula: see text] gravity with tilted observers, where [Formula: see text] is the Ricci scalar and [Formula: see text] is the trace of the stress energy tensor. We have explored a tilted model and determined the solutions of the field equations by assuming special law of variation of Hubble’s parameter, proposed by Berman (1983) that yields constant deceleration parameter. In this scenario, we have used the equation of state [Formula: see text] and power law of velocity to describe the different anisotropic physical models such as Dust Universe, Radiation Universe, Hard Universe and Zedovich Universe. We have discussed graphical presentation of all parameters of the derived models with the help of MATLAB. Some physical and geometrical aspects of the models are also discussed.
The Paleoproterozoic porphyry copper–molybdenum deposit of Kourki (Liptako Province, western Niger)
Authors: Hallarou Mallam Mamane , Konaté Moussa , Olatunji Akinade Shadrach , Ahmed Yacouba
Published: November 2020

The Kourki porphyry Cu–Mo deposit is located in the southern part of the Gorouol greenstone belt in Western Niger. The potential Cu–Mo mineralization is hosted by granitoids (granodiorite and diorite) and veins, in Paleoproterozoic plutonic rocks, which are the main porphyry Cu–Mo system. The scientific objective of this study was to determine the characteristics of Kourki Cu–Mo mineralization and to compare them with other porphyry systems in the world and particularly with those of the West African Craton. The methods implemented consist of a field study and a polarizing microscope analysis in transmitted and reflected light on the rocks bearing Cu–Mo mineralization. The use of reference diagrams made it possible, on the one hand, to confirm the origin of the Cu–Mo mineralization and, on the other hand, to specify conditions of the formation of this mineralization. The geology of the study area shows a granodiorite–tonalite pluton in close contact with dioritic intrusions to the north, clastic sediments to the east, and volcano-sedimentary rocks to the SE. The pluton is crosscut by an intrusion of molybdenum porphyry dyke with irregular shape that can be observed in outcrop. The geochemical study shows that the granodiorite–tonalite pluton can be related to a calc-alkaline plutonic series which characterizes an arc type environment. Large areas of hydrothermal quartz breccia have been identified within the pluton. They were set up by hydraulic fracturing along the zones of weakness. Most of the Cu–Mo mineralization in the Kourki deposit occurs as hydrothermal breccia, filled with veins, and was disseminated in the porphyry diorite and quartz–diorite stockworks. The mineralogical assemblage is marked by a predominance of pyrite, molybdenite, chalcopyrite and quartz with some bornite and chalcocite. The alterations include potassic alteration, propylitic alteration, sericitization and epidotization. All of these data show that the Kourki porphyry represents a characteristic system of an environmental arc, quite comparable with that of the Andean Cordillera.
TNFα induces mitochondrial fragmentation and biogenesis in human airway smooth muscle
Authors: Delmotte Philippe , Marin Mathieu Natalia , Sieck Gary C.
Published: November 2020

In human airway smooth muscle (hASM), mitochondrial volume density is greater in asthmatic patients compared with normal controls. There is also an increase in mitochondrial fragmentation in hASM of moderate asthmatics associated with an increase in dynamin-related protein 1 (Drp1) and a decrease in mitofusin 2 (Mfn2) expression, mitochondrial fission, and fusion proteins, respectively. Proinflammatory cytokines such TNFα contribute to hASM hyperreactivity and cell proliferation associated with asthma. However, the involvement of proinflammatory cytokines in mitochondrial remodeling is not clearly established. In nonasthmatic hASM cells, mitochondria were labeled using MitoTracker Red and imaged in three dimensions using a confocal microscope. After 24-h TNFα exposure, mitochondria in hASM cells were more fragmented, evidenced by decreased form factor and aspect ratio and increased sphericity. Associated with increased mitochondrial fragmentation, Drp1 expression increased while Mfn2 expression was reduced. TNFα also increased mitochondrial biogenesis in hASM cells reflected by increased peroxisome proliferator-activated receptor-γ coactivator 1α expression and increased mitochondrial DNA copy number. Associated with mitochondrial biogenesis, TNFα exposure also increased mitochondrial volume density and porin expression, resulting in an increase in maximum O2 consumption rate. However, when normalized for mitochondrial volume density, O2 consumption rate per mitochondrion was reduced by TNFα exposure. Associated with mitochondrial fragmentation and biogenesis, TNFα also increased hASM cell proliferation, an effect mimicked by siRNA knockdown of Mfn2 expression and mitigated by Mfn2 overexpression. The results of this study support our hypothesis that in hASM cells exposed to TNFα mitochondria are more fragmented, with an increase in mitochondrial biogenesis and mitochondrial volume density resulting in reduced O2 consumption rate per mitochondrion.
Microvesicles in bronchoalveolar lavage as a potential biomarker of COPD
Authors: Bazzan Erica , Radu Claudia Maria , Tinè Mariaenrica , Neri Tommaso , Biondini Davide , Semenzato Umberto , Casara Alvise , Balestro Elisabetta , Simioni Paolo , Celi Alessandro , Cosio Manuel G. , Saetta Marina
Published: November 2020

Microvesicles (MVs) released from almost all cells are recognized as cell communication tools. MVs have been investigated in several inflammatory diseases but poorly in biological fluids like bronchoalveolar lavage (BAL) of smokers. The purpose of this study was to investigate the presence and source of MVs in BAL of smokers with and without chronic obstructive pulmonary disease (COPD) compared with nonsmoking controls. Using flow cytometry in BAL, we detected endothelial and alveolar macrophage (AM)-derived MVs and found a higher number of AM-MVs in the BAL of smokers with COPD than in smokers without COPD and nonsmokers, which correlated with the pack-years ( r = 0.46; P = 0.05) and with the degree of airway obstruction measured by the forced expiratory volume in 1 s percent predicted ( r = −0.56; P = 0.01). Endothelial and alveolar macrophage-derived MVs are present and measurable in human BAL fluid. In response to smoking and to the development of COPD, inflammatory signals in AM-derived MVs can be quantified, and their numbers are related to the pack-years and the decrease in lung function. These results open the opportunity for future investigation of these microvesicles as biomarkers and possible mechanistic guides in COPD.
Bladder underactivity induced by prolonged pudendal afferent activity in cats
Authors: Mohapatra Anand , Chen Jialiang , Zhao Jun , Zhong Yihua , Armann Kody , Shen Bing , Wang Jicheng , Beckel Jonathan , de Groat William C. , Tai Changfeng
Published: November 2020

The purpose of this study was to determine the effects of pudendal nerve stimulation (PNS) on reflex bladder activity and develop an animal model of underactive bladder (UAB). In six anesthetized cats, a bladder catheter was inserted via the urethra to infuse saline and measure pressure. A cuff electrode was implanted on the pudendal nerve. After determination of the threshold intensity (T) for PNS to induce an anal twitch, PNS (5 Hz, 0.2 ms, 2 T or 4 T) was applied during cystometrograms (CMGs). PNS (4-6 T) of 30-min duration was then applied repeatedly until bladder underactivity was produced. Following stimulation, control CMGs were performed over 1.5-2 h to determine the duration of bladder underactivity. When applied during CMGs, PNS (2 T and 4 T) significantly ( P < 0.05) increased bladder capacity while PNS at 4 T also significantly ( P < 0.05) reduced bladder contraction amplitude, duration, and area under contraction curve. Repeated application of 30-min PNS for a cumulative period of 3-8 h produced bladder underactivity exhibiting a significantly ( P < 0.05) increased bladder capacity (173 ± 14% of control) and a significantly ( P < 0.05) reduced contraction amplitude (50 ± 7% of control). The bladder underactivity lasted more than 1.5-2 h after termination of the prolonged PNS. These results provide basic science evidence supporting the proposal that abnormal afferent activity from external urethral/anal sphincter could produce central inhibition that underlies nonobstructive urinary retention (NOUR) in Fowler’s syndrome. This cat model of UAB may be useful to investigate the mechanism by which sacral neuromodulation reverses NOUR in Fowler’s syndrome.
Activity-dependent long-term potentiation of electrical synapses in the mammalian thalamus
Authors: Fricker Brandon , Heckman Emily , Cunningham Patrick C. , Wang Huaixing , Haas Julie S.
Published: November 2020

This work reveals a physiologically relevant form of activity pairing in coupled neurons that results in long-term potentiation of mammalian electrical synapses. These findings, in combination with previous work, allow the authors to propose a bidirectional calcium-based rule for plasticity of electrical synapses, similar to those demonstrated for chemical synapses. These new insights inform the field on how electrical synapse plasticity may modify the neural circuits that incorporate them.
Multilayer Network Risk Factor Pricing Model
Authors: Liu Yu , Hu Conglin , Wang Lei , Yang Kun
Published: November 2020

This paper proposes a multilayer network risk factor pricing model to depict the impact of interactions between stocks on excess stock returns by constructing the network risk factor based on the stock multilayer network and introducing it to the traditional three-factor pricing model. According to China’s stock market data, we find that compared with the traditional three-factor model, the multilayer network risk factor pricing model can achieve higher fitting degree. Meanwhile, the multilayer network risk factor has a significant positive impact on the excess stock returns in most cases.
Application of Artificial Intelligence Techniques for the Estimation of Basal Insulin in Patients with Type I Diabetes
Authors: Guzman Gómez Guillermo Edinson , Burbano Agredo Luis Eduardo , Martínez Veline , Bedoya Leiva Oscar Fernando
Published: November 2020

Artificial intelligence techniques have been positioned in the resolution of problems in various areas of healthcare. Clinical decision support systems developed from this technology have optimized the healthcare of patients with chronic diseases through mobile applications. In this study, several models based on this methodology have been developed to calculate the basal insulin dose in patients with type I diabetes using subcutaneous insulin infusion pumps. Methods. A pilot experimental study was performed with data from 56 patients with type 1 diabetes who used insulin infusion pumps and underwent continuous glucose monitoring. Several models based on artificial intelligence techniques were developed to analyze glycemic patterns based on continuous glucose monitoring and clinical variables in order to estimate the basal insulin dose. We used neural networks (NNs), Bayesian networks (BNs), support vector machines (SVMs), and random forests (RF). We then evaluated the agreement between predicted and actual values using several statistical error measurements: mean absolute error (MAE), mean square error (MSE), root-mean-square error (RMSE), Pearson’s correlation coefficient (R), and determination coefficient (R2). Results. Twenty-four different models were obtained, one for each hour of the day, with each chosen technique. Correlation coefficients obtained with RF, SVMs, NNs, and BNs were 0.9999, 0.9921, 0.0303, and 0.7754, respectively. The error increased between 06:00 and 07:00 and between 13:00 and 17:00. Conclusions. The performance of the RF technique was excellent and got very close to the actual values. Intelligence techniques could be used to predict basal insulin dose. However, it is necessary to explore the validity of the results and select the target population. Models that allow for more accurate levels of prediction should be further explored.
Wind Tunnel Test of the Icing Characteristics of Airfoil Rotating around a Vertical Axis
Authors: Li Yan , Shi Lei , Guo Wenfeng , Sun Ce , Jiang Yu
Published: November 2020

To determine the process of icing on the rotating machinery, an icing experiment on a rotating airfoil blade was carried out in this paper. First, an icing wind tunnel was fabricated, and its conditional parameters were calibrated. The calibration results showed that the performance of this icing wind tunnel was reliable and stable. The experimental temperature was -15°C, and the MVD was 50 μm. Then, an icing experiment on the rotating blade with the NACA0018 airfoil was carried out. The characteristics of icing, including icing distribution, growth rate of icing, and thickness of the ice layer, were defined and quantitatively analyzed under different tip speed ratios and setting angles. The results show that the type of icing changes from rime ice to glaze ice with an increase in the tip speed ratio. The dimensionless icing area and dimensionless thickness of the ice layer both increase with an increase in the icing time. The growth rate of icing increases rapidly at the initial icing stage and then decreases dramatically under each tip speed ratio condition.
A Case of Prolonged Catatonia Caused by Sjögren’s Syndrome
Authors: Inagaki Takahiko , Kudo Kotaro , Kurimoto Naoki , Aoki Takashi , Kuriyama Kenichi
Published: November 2020

Sjögren’s syndrome (SS) is a chronic autoimmune disorder, often associated with some neuropsychiatric symptoms as well as systemic lupus erythematosus. Although catatonia is frequently reported in patients with systemic lupus erythematosus, it has been rarely reported in patients with SS. Herein, we present a case of SS with catatonia effectively and safely treated with modified electroconvulsive therapy (ECT). A 58-year-old woman showed prolonged catatonia and depressive mood along with pathologically dried eye and mouth. Based on physical findings and blood tests, she was diagnosed with SS. Because of the presence of pressure sores, we were unable to perform lumbar puncture for the diagnosis of abacterial encephalitis. Alternatively, single-photon emission computed tomography of her brain revealed multifocal hypoperfused areas in the parietotemporal region. Consequently, we performed ECT for the treatment of catatonia comorbid with SS. Following 20 sessions of ECT, the catatonia was improved without obvious adverse effects. One week after the last ECT, elevated levels of interleukin-6 were identified in the cerebral fluid. After receiving steroid pulse therapy, she has not experienced catatonia for more than 5 years. SS can cause catatonia, and ECT is a safe and effective option for the treatment of catatonia with SS.
OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors
Authors: Gutierrez Martin , Moreno Victor , Heinhuis Kimberley M. , Olszanski Anthony J. , Spreafico Anna , Ong Michael , Chu Quincy , Carvajal Richard D. , Trigo José , Ochoa de Olza Maria , Provencio Mariano , De Vos Filip Yves , De Braud Filippo , Leong Stephen , Lathers Deanne , Wang Rui , Ravindran Palani , Feng Yan , Aanur Praveen , Melero Ignacio
Published: November 2020

Purpose:

This phase I/IIa study (NCT02737475) evaluated the safety and activity of BMS-986178, a fully human OX40 agonist IgG1 mAb, ± nivolumab and/or ipilimumab in patients with advanced solid tumors.

Patients and Methods:

Patients (with non–small cell lung, renal cell, bladder, other advanced cancers) received BMS-986178 (20–320 mg) ± nivolumab (240–480 mg) and/or ipilimumab (1–3 mg/kg). The primary endpoint was safety. Additional endpoints included immunogenicity, pharmacodynamics, pharmacokinetics, and antitumor activity per RECIST version 1.1.

Results:

Twenty patients received BMS-986178 monotherapy, and 145 received combination therapy in various regimens (including two patients receiving nivolumab monotherapy). With a follow-up of 1.1 to 103.6 weeks, the most common (≥5%) treatment-related adverse events (TRAEs) included fatigue, pruritus, rash, pyrexia, diarrhea, and infusion-related reactions. Overall, grade 3–4 TRAEs occurred in one of 20 patients (5%) receiving BMS-986178 monotherapy, six of 79 (8%) receiving BMS-986178 plus nivolumab, zero of two receiving nivolumab monotherapy, six of 41 (15%) receiving BMS-986178 plus ipilimumab, and three of 23 (13%) receiving BMS-986178 plus nivolumab plus ipilimumab. No deaths occurred. No dose-limiting toxicities were observed with monotherapy, and the MTD was not reached in either the monotherapy or the combination escalation cohorts. No objective responses were seen with BMS-986178 alone; objective response rates ranged from 0% to 13% across combination therapy cohorts.

Conclusions:

In this study, BMS-986178 ± nivolumab and/or ipilimumab appeared to have a manageable safety profile, but no clear efficacy signal was observed above that expected for nivolumab and/or ipilimumab.
Development of Highly Optimized Antibody–Drug Conjugates against CD33 and CD123 for Acute Myeloid Leukemia
Authors: Han Yoon-Chi , Kahler Jennifer , Piché-Nicholas Nicole , Hu Wenyue , Thibault Stephane , Jiang Fan , Leal Mauricio , Katragadda Madan , Maderna Andreas , Dushin Russell , Prashad Nadira , Charati Manoj B. , Clark Tracey , Tumey L. Nathan , Tan Xingzhi , Giannakou Andreas , Rosfjord Edward , Gerber Hans-Peter , Tchistiakova Lioudmila , Loganzo Frank , O'Donnell Christopher J. , Sapra Puja
Published: November 2020

Purpose:

Mortality due to acute myeloid leukemia (AML) remains high, and the management of relapsed or refractory AML continues to be therapeutically challenging. The reapproval of Mylotarg, an anti-CD33–calicheamicin antibody–drug conjugate (ADC), has provided a proof of concept for an ADC-based therapeutic for AML. Several other ADCs have since entered clinical development of AML, but have met with limited success. We sought to develop a next-generation ADC for AML with a wide therapeutic index (TI) that overcomes the shortcomings of previous generations of ADCs.

Experimental Design:

We compared the TI of our novel CD33-targeted ADC platform with other currently available CD33-targeted ADCs in preclinical models of AML. Next, using this next-generation ADC platform, we performed a head-to-head comparison of two attractive AML antigens, CD33 and CD123.

Results:

Our novel ADC platform offered improved safety and TI when compared with certain currently available ADC platforms in preclinical models of AML. Differentiation between the CD33- and CD123-targeted ADCs was observed in safety studies conducted in cynomolgus monkeys. The CD33-targeted ADC produced severe hematologic toxicity, whereas minimal hematologic toxicity was observed with the CD123-targeted ADC at the same doses and exposures. The improved toxicity profile of an ADC targeting CD123 over CD33 was consistent with the more restricted expression of CD123 in normal tissues.

Conclusions:

We optimized all components of ADC design (i.e., leukemia antigen, antibody, and linker-payload) to develop an ADC that has the potential to translate into an effective new therapy against AML.
PIPAC-OX: A Phase I Study of Oxaliplatin-Based Pressurized Intraperitoneal Aerosol Chemotherapy in Patients with Peritoneal Metastases
Authors: Kim Guowei , Tan Hon Lyn , Sundar Raghav , Lieske Bettina , Chee Cheng Ean , Ho Jingshan , Shabbir Asim , Babak Maria V. , Ang Wee Han , Goh Boon Cher , Yong Wei Peng , Wang Lingzhi , So Jimmy B.Y.
Published: November 2020

Purpose:

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel laparoscopic, intraperitoneal chemotherapy delivery technique aiming to improve drug distribution and tissue penetration to treat peritoneal metastases. Thus far, PIPAC oxaliplatin is conducted at an arbitrary dose of 92 mg/m2. We conducted a phase I study to establish safety and tolerability.

Patients and Methods:

We used a 3+3 dose-escalation design of PIPAC oxaliplatin for patients with peritoneal metastases from gastrointestinal tumors, after failure of at least first-line chemotherapy. Dose levels were planned at 45, 60, 90, and 120 mg/m2.

Results:

This study included 16 patients with 24 PIPAC procedures (8 gastric; 5 colorectal; and 1 gallbladder, pancreas, and appendix cancer each). Median age and peritoneal cancer index (PCI) score were 62 years and 17, respectively. Two patients developed pancreatitis (grade 2 and 3) at 45 mg/m2, necessitating cohort expansion. Another patient developed grade 2 pancreatitis at 90 mg/m2. There were no other dose-limiting toxicities, and the highest-dose cohort (120 mg/m2) tolerated PIPAC well. Pharmacokinetic analyses demonstrated good linearity between dose and maximum concentration (r2 = 0.95) and AUC (r2 = 0.99). On the basis of RECIST, 62.5% and 50% had stable disease after one and two PIPAC procedures, respectively. A total of 8 patients underwent two PIPAC procedures, with improvement of median PCI and peritoneal regression grade score from 15 to 12 and 2.5 to 2.0, respectively.

Conclusions:

The recommended phase II dose is 120 mg/m2. Future studies should further delineate the efficacy and role of PIPAC oxaliplatin for peritoneal metastases.

See related commentary by de Jong et al., p. 1830