bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanofiltration as a robust method contributing to viral safety of plasma‐derived therapeutics: 20 yearsʼ experience of the plasma protein manufacturers
Authors: Roth Nathan J. , Dichtelmüller Herbert O. , Fabbrizzi Fabrizio , Flechsig Eckhard , Gröner Albrecht , Gustafson Mary , Jorquera Juan I. , Kreil Thomas R. , Misztela Dominika , Moretti Elisa , Moscardini Mila , Poelsler Gerhard , More John , Roberts Peter , Wieser Andreas , Gajardo Rodrigo
Published: August 2020

Background

Nanofiltration entails the filtering of protein solutions through membranes with pores of nanometric sizes that have the capability to effectively retain a wide range of viruses.

Study Design and Methods

Data were collected from 754 virus validation studies (individual data points) by Plasma Protein Therapeutics Association member companies and analyzed for the capacity of a range of nanofilters to remove viruses with different physicochemical properties and sizes. Different plasma product intermediates were spiked with viruses and filtered through nanofilters with different pore sizes using either tangential or dead‐end mode under constant pressure or constant flow. Filtration was performed according to validated scaled‐down laboratory conditions reflecting manufacturing processes. Effectiveness of viral removal was assessed using cell culture infectivity assays or polymerase chain reaction (PCR).

Results

The nanofiltration process demonstrated a high efficacy and robustness for virus removal. The main factors affecting nanofiltration efficacy are nanofilter pore size and virus size. The capacity of nanofilters to remove smaller, nonenveloped viruses was dependent on filter pore size and whether the nanofiltration process was integrated and designed with the intention to provide effective parvovirus retention. Volume filtered, operating pressure, and total protein concentration did not have a significant impact on the effectiveness of virus removal capacity within the investigated ranges.

Conclusions

The largest and most diverse nanofiltration data collection to date substantiates the effectiveness and robustness of nanofiltration in virus removal under manufacturing conditions of different plasma‐derived proteins. Nanofiltration can enhance product safety by providing very high removal capacity of viruses including small non‐enveloped viruses.
Pharmacologic ciliary body ablation for chronic glaucoma in dogs: A retrospective review of 108 eyes from 2013 to 2018
Authors: Julien Martha E. , Schechtmann Simone A. , Michau Tammy M. , Welihozkiy Anja , Baldwin Terri L. , Stine Jessica M.
Published: August 2020

Objective

To evaluate the long‐term outcome and efficacy of intravitreal injection of gentamicin and dexamethasone sodium phosphate (IVGD) or triamcinolone in end‐stage glaucoma patients and determine pre‐procedure prognostic indicators of success and post‐operative complications.

Procedure

Medical records were reviewed for 108 dogs (108 eyes) treated with intravitreal gentamicin with or without dexamethasone sodium phosphate or triamcinolone for glaucoma between 2013 and 2018 with 3 months of minimum follow‐up. Signalment and clinical findings, including type of glaucoma, pre‐procedure intraocular pressure (IOP), chronicity, procedure protocol, and outcome were recorded. Success was defined as an intraocular pressure of ≤25 mm Hg at the time of last re‐examination or no ocular hypotensive medications at 3 months or longer post‐injection.

Results

The overall success rate for pharmacologic ablation was 95%. The success rate for dogs receiving no ocular hypotensive medications was 86%. Seventy‐six eyes (70.4%) had primary glaucoma, and 32 eyes (29.6%) had secondary glaucoma. Age at the time of injection had no effect on initial success but did in final success (P =‐.03) for dogs requiring repeat injections. Cocker Spaniels required the most repeat 2nd and 3rd injections (3/12 dogs) and (2/4 dogs), respectively. No preoperative variable significantly affected the success rate. The most common complications were phthisis bulbi (59.2%), corneal edema (25.9%), and ulcerative keratitis (22.3%). Uncontrolled IOP resulted in enucleation in two dogs (1.8%).

Conclusions

Pharmacologic ablation has a high overall success rate in lowering IOP to ≤25 mm Hg short‐term in blind, glaucomatous canine eyes. Type of glaucoma, pre‐procedure IOP, chronicity, and protocol did not affect success.
Risk factors for reluxation after toggle rod stabilization for treatment of coxofemoral luxation in 128 dogs
Authors: Mathews Megan E. , Barnhart Matthew D.
Published: August 2020

Objective

Evaluate the risk factors for reluxation and outcomes for dogs with a toggle rod construct.

Study design

Retrospective case series.

Animals

One hundred twenty‐eight client‐owned dogs.

Methods

Medical records from 2007 to 2018 were reviewed for signalment, history, surgery, and outcome for dogs with a coxofemoral luxation repaired with a commercial toggle rod and nylon monofilament suture construct. Univariate and multiple logistics regression analysis were performed to assess risk factors associated with postoperative luxation. Primary veterinarians and owners were contacted for follow‐up via telephone or electronic communication.

Results

The overall complication rate was 24.2%, and the reluxation rate was 14.8%. There was a decreased risk of reluxation when the cause was traumatic in origin (odds ratio [OR] 0.10) or when the lameness was severe at presentation (OR 0.42). Fifteen of 58 (25.9%) owners contacted completed a follow‐up survey.

Conclusion

Dogs with nontraumatic, low impact luxations were at a higher risk for reluxation.

Clinical significance

Dogs of any body condition with a traumatic coxofemoral luxation are at lowest risk for reluxation.
LEGITIMACY AND THE FIELD OF SCIENCE AND RELIGION
Authors: Jordan Peter N.
Published: August 2020

Prompted by the concerns about legitimacy that Josh Reeves expresses in his book Against Methodology in Science and Religion: Recent Debates on Rationality and Theology, this article considers how the field of science and religion, and the disciplines and scholars that comprise it, should think about the pursuit of legitimacy today. It begins by examining four features of any conferral of legitimacy on an object. It then looks more closely at distance and its effects on judgments of legitimacy. It first notes how longer distances can enable a wide range of factors other than the internal features or inherent merits of the object to influence judgments of its legitimacy. It then explores the factors that persons who have significant expertise in or experience with the object may consider when judging its legitimacy. It closes by posing three questions that anyone designing a strategy to increase the perceived legitimacy of an object might ask.
THE NUTS AND BOLTS OF TRANSFORMATION: SCIENCE FICTION'S IMAGINED TECHNOLOGIES AND THE CIVIC IMAGINATION
Authors: Burton Emanuelle
Published: August 2020

This is an introduction to the thematic section on Science Fiction's Imagined Technologies, which includes three articles that were presented at the annual meeting of the American Academy of Religion (AAR) in San Diego, CA on November 24, 2019.
I WALK THE LINE: COMMENT ON MIKAEL LEIDENHAG ON THEISTIC EVOLUTION AND INTELLIGENT DESIGN
Authors: Skogholt Christoffer
Published: August 2020

Is theistic evolution (TE) a philosophically tenable position? Leidenhag argues in his article “The Blurred Line between Theistic Evolution and Intelligent Design” that it is not, since it, Leidenhag claims, espouses a view of divine action that he labels “natural divine causation” (NDC), which makes God explanatory redundant. That is, in so far as TE does not invoke God as an additional cause alongside natural causes, it is untenable. Theistic evolutionists should therefore “reject NDC and affirm a more robust notion of divine agency.” However, this will, Leidenhag claims, have the effect that theistic evolutionists “will move their position significantly closer to Intelligent Design,” and so the line between TE and intelligent design is (or ought to be?) blurred. If successful, the criticism by Leidenhag would be bad news for theists who want to take science seriously and good news for those scientistic atheists according to whom there simply is no scientifically respectable way of combining theism and modern natural science in an overarching worldview. So, is TE stuck between a rock (of redundancy) and a hard place (of pseudo‐science)? No, at least not due to the criticism offered by Leidenhag—but maybe religious naturalism is?
THE PROBLEM OF NATURAL DIVINE CAUSATION AND THE BENEFITS OF PARTIAL CAUSATION: A RESPONSE TO SKOGHOLT
Authors: Leidenhag Mikael
Published: August 2020

In this article, I defend my previous argument that natural divine causation suffers under the problem of causal overdetermination and that it cannot serve as a line of demarcation between theistic evolution (TE) and intelligent design (ID). I do this in light of Christoffer Skogholt's critique of my article. I argue that Skogholt underestimates the naturalistic ambitions of some current thinkers in TE and fails, therefore, to adequately respond to my main argument. I also outline how partial causation better serves as a model for the relationship between God's providence and evolution.
IN ALGORITHMS WE TRUST: MAGICAL THINKING, SUPERINTELLIGENT AI AND QUANTUM COMPUTING
Authors: Schradle Nathan
Published: August 2020

This article analyzes current attitudes toward artificial intelligence (AI) and quantum computing and argues that they represent a modern‐day form of magical thinking. It proposes that AI and quantum computing are thus excellent examples of the ways that traditional distinctions between religion, science, and magic fail to account for the vibrancy and energy that surround modern technologies.
Dietary nitrate supplementation does not influence thermoregulatory or cardiovascular strain in older individuals during severe ambient heat stress
Authors: Cramer Matthew N. , Hieda Michinari , Huang Mu , Moralez Gilbert , Crandall Craig G.
Published: August 2020

New Findings

What is the central question of this study?

Does dietary nitrate supplementation with beetroot juice attenuate thermoregulatory and cardiovascular strain in older adults during severe heat stress?

What is the main finding and its importance?

A 7‐day nitrate supplementation regimen lowered resting mean arterial pressure in thermoneutral conditions. During heat stress, core and mean skin temperatures, vasodilatory responses, sweat loss, heart rate and left ventricular function were unchanged, and mean arterial pressure was only transiently reduced, post‐supplementation. These data suggest nitrate supplementation with beetroot juice does not mitigate thermoregulatory or cardiovascular strain in heat‐stressed older individuals.

This study tested the hypothesis that dietary nitrate supplementation with concentrated beetroot juice attenuates thermoregulatory and cardiovascular strain in older individuals during environmental heat stress. Nine healthy older individuals (six females, three males; aged 67 ± 5 years) were exposed to 42.5 ± 0.1°C and 34.0 ± 0.5% relative humidity conditions for 120 min before (CON) and after 7 days of dietary nitrate supplementation with concentrated beetroot juice (BRJ; 280 ml, ∼16.8 mmol of nitrate daily). Core and skin temperatures, body mass changes (indicative of whole‐body sweat loss), skin blood flow and cutaneous vascular conductance, forearm blood flow and vascular conductance, heart rate, arterial blood pressures and indices of cardiac function were measured. The 7‐day beetroot juice regimen increased plasma nitrate/nitrite levels from 27.4 ± 15.2 to 477.0 ± 102.5 μmol l−1 (P < 0.01) and lowered resting mean arterial pressure from 90 ± 7 to 83 ± 10 mmHg at baseline under thermoneutral conditions (P = 0.02). However, during subsequent heat stress, no differences in core and skin temperatures, skin blood flow and vascular conductance, forearm blood flow and vascular conductance, whole‐body sweat loss, heart rate, and echocardiographic indices of systolic function and diastolic filling were evident following nitrate supplementation (all P > 0.05). Mean arterial pressure was lower in BRJ vs. CON during heat stress (treatment‐by‐time interaction: P = 0.02). Overall, these findings suggest that dietary nitrate supplementation with concentrated beetroot juice does not attenuate thermoregulatory or cardiovascular strain in older individuals exposed to severe ambient heat stress.
Effects of elasticity and flow ramp up on kinetics of shear banding flow formation in wormlike micellar fluids
Authors: Rassolov Peter , Mohammadigoushki Hadi
Published: August 2020

We report experiments on spatiotemporal evolution of the velocity profiles in shear-banding wormlike micelles upon inception of the flow in a Taylor–Couette (TC) cell. Both moderately entangled and highly entangled solutions are considered over a broad range of fluid elasticity E. Fluid elasticity, E = Wi/Re, characterizes the relative importance of the elastic to inertial effects. For both moderately and highly entangled solutions, upon inception of the shear, and during the stress decay period, fluid moves in the opposite direction to that of the imposed motion in a subset of the gap beyond critical thresholds of elasticity and flow ramp up rate, which depend on the fluid entanglement density. Surprisingly, beyond a second critical threshold of the fluid elasticity, the transient backflow disappears in moderately entangled solutions, highlighting the importance of the micellar entanglement on transient evolution of the flow in shear banding systems. More interestingly, we report the formation of multibanded quasisteady velocity profiles under certain conditions of fluid elasticity and flow ramp up rate. The multibanded profiles are characterized by a low shear band near the inner cylinder, a high shear band in the middle of the TC gap, and another low shear band near the outer cylinder. Finally, we show that the apparent wall slip at the inner cylinder of the TC cell is more pronounced for highly entangled solutions and decreases as the fluid elasticity increases. Experimental observations are compared with the existing simulations of the Vasquez–Cook–McKinley model, and several suggestions are made for future simulations.
Interplay of edge fracture and shear banding in complex fluids
Authors: Hemingway Ewan J. , Fielding Suzanne M.
Published: August 2020

We explore theoretically the interplay between shear banding and edge fracture in complex fluids by performing a detailed simulation study within two constitutive models: the Johnson–Segalman model and the Giesekus model. We consider separately parameter regimes in which the underlying constitutive curve is monotonic and nonmonotonic, such that the bulk flow (in the absence of any edge effects) is, respectively, homogeneous and shear banded. Phase diagrams of the levels of edge disturbance and of bulk (or quasibulk) shear banding are mapped as a function of the surface tension of the fluid–air interface, the wetting angle where this interface meets the walls of the flow cell, and the imposed shear rate. In particular, we explore in more detail the basic result recently announced by Hemingway and Fielding [Phys. Rev. Lett. 120, 138002 (2018)]: that precursors to edge fracture can induce quasibulk shear banding. We also appraise analytical predictions that shear banding can induce edge fracture [S. Skorski and P. D. Olmsted, J. Rheol., 55, 1219 (2011)]. Although a study of remarkable early insight, Skorski and Olmsted [J. Rheol., 55, 1219 (2011)] made some strong assumptions about the nature of the “base state,” which we examine using direct numerical simulation. The basic prediction that shear banding can cause edge fracture remains valid but with qualitatively modified phase boundaries.
Fine Motor Skills and Unsystematic Spatial Binding in the Common Region Test: Under-Inclusivity in Autism Spectrum Disorder and Over-Inclusivity in Attention-Deficit Hyperactivity Disorder
Authors: Lange-Küttner Christiane , Kochhar Ridhi
Published: August 2020

Introduction:The Common Region Test (CRT) is useful for predicting children’s visual memory as individual object-place binding predicted better object memory while objects-region coding predicted better place memory.Aim:To test children with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) with regards to spatial binding in the CRT.Methods:19 children with ASD and 20 children with ADHD were gender-matched with 39 typically developing children by chronological age and with another 39 children by verbal mental age as control groups (N = 117) and tested with the CRT and Bender Gestalt test. Results:Children with ASD and ADHD showed more unsystematic coding than typically developing children. This was due to lower fine motor skills, and in children with ADHD also because of reduced verbal naming. Almost all children with ASD presented the less mature under-inclusive Type I unsystematic coding which included object-place binding, while children with ADHD showed the over-inclusive Type II unsystematic coding that was overriding the Gestalt-like properties of proximity and similarity.Conclusions:It was demonstrated that the CRT is a useful screening instrument for ASD and ADHD that shows that their spatial categorization varies in their unsystematic visuo-spatial classification due to fine motor skill deficiencies.
Accumulation of collagen molecular unfolding is the mechanism of cyclic fatigue damage and failure in collagenous tissues
Authors: Zitnay Jared L. , Jung Gang Seob , Lin Allen H. , Qin Zhao , Li Yang , Yu S. Michael , Buehler Markus J. , Weiss Jeffrey A.
Published: August 2020

Denatured collagen accumulates during cyclic fatigue loading and explains the micro-damage hypothesis of overuse tissue injury.
Processing Has Differential Effects on Microbiota-Accessible Carbohydrates in Whole Grains during
In Vitro
Fermentation
Authors: Smith Caroline , Van Haute Mallory J. , Rose Devin J.
Published: August 2020

Dietary nondigestible carbohydrates, or dietary fiber, have long been recognized for their beneficial health effects. However, recent studies have revealed that fermentation of nondigestible carbohydrates by gut bacteria is critical in mediating many of the health-promoting properties of dietary fibers. Whole grains are excellent candidates to supply the microbiome with a plentiful source of nondigestible carbohydrates, although unfortunately a majority of these carbohydrates in whole grains are not available to gut bacteria for fermentation. Processing is known to alter the structural characteristics of nondigestible carbohydrates in whole grains, yet the relationship between these effects and gut microbial fermentation is unknown. This research aimed to address this important research gap by identifying interactions between whole-grain processing and gut bacteria, with the ultimate goal of increasing the availability of nondigestible carbohydrates for fermentation to enhance host health.
SARS-CoV-2 Assays To Detect Functional Antibody Responses That Block ACE2 Recognition in Vaccinated Animals and Infected Patients
Authors: Walker Susanne N. , Chokkalingam Neethu , Reuschel Emma L. , Purwar Mansi , Xu Ziyang , Gary Ebony N. , Kim Kevin Y. , Helble Michaela , Schultheis Katherine , Walters Jewell , Ramos Stephanie , Muthumani Kar , Smith Trevor R. F. , Broderick Kate E. , Tebas Pablo , Patel Ami , Weiner David B. , Kulp Daniel W.
Published: August 2020

S
evere
a
cute
r
espiratory
s
yndrome
co
rona
v
irus
2
(SARS-CoV-2) has caused a global pandemic of COVID-19, resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >20 million people worldwide, with >5 million cases in the United States (11 August 2020). The development of diagnostic and research tools to determine infection and vaccine efficacy is critically needed.
Cystic fibrosis newborn screening: the importance of bloodspot sample quality
Authors: Doull Iolo , Course Christopher William , Hanks Ruth E , Southern Kevin W , Forton Julian T , Thia Lena P , Moat Stuart J
Published: August 2020

Objective

Wales has an immunoreactive trypsin (IRT)-DNA cystic fibrosis (CF) newborn screening (NBS) programme. Most CF NBS false negative cases are due to an IRT concentration below the screening threshold. The accuracy of IRT results is dependent on the quality of the dried bloodspot (DBS) sample. The aim of this study was to determine the cause of false negative cases in CF NBS and their relationship to DBS quality.

Design

Longitudinal birth cohort.

Setting

Wales 1996–2016.

Patients

Children with CF.

Interventions

Identification of all CF patients with triangulation of multiple data sources to detect false negative cases.

Main outcome measures

False negative cases.

Results

Over 20 years, 673 952 infants were screened and 239 were diagnosed with CF (incidence 1:2819). The sensitivity of the programme was 0.958, and positive predictive value was 0.476. Eighteen potential false negatives were identified, of whom eight were excluded: four screened outside Wales, two had complex comorbidities, no identified cystic fibrosis transmembrane conductance regulator (CFTR) variants on extended analysis and thus not considered to have CF and two were diagnosed after their 16th birthday. Of the 10 false negatives, 9 had a low DBS IRT and at least one common CFTR variant and thus should have received a sweat test under the programme. DBS cards were available for inspection for five of the nine false negative cases—all were classified as small/insufficient or poor quality.

Conclusions

The majority of false negatives had a low bloodspot IRT, and this was associated with poor quality DBS. The optimal means to improve the sensitivity of our CF NBS programme would be to improve DBS sample quality.
How to use the Bayley Scales of Infant and Toddler Development
Authors: Del Rosario Chelo , Slevin Marie , Molloy Eleanor J , Quigley Jean , Nixon Elizabeth
Published: August 2020

The Bayley Scales of Infant and Toddler Development—Third Edition (Bayley-III) is a gold standard series of behavioural assessments used by clinicians and researchers to assess the developmental functioning of young children. The rigorous psychometric properties of the tool are attributed to the carefully standardised normative sample and quantitative scoring system. It is a common end-point assessment used in neonatal trials and is routinely used in a clinical setting to assess the development of children at risk of delay. Incidence of developmental delay is higher in clinical populations such as those born preterm or with complications such as neonatal encephalopathy. Early identification of delay is critical as early intervention is most effective in minimising impairment; therefore, routine assessment of developmental outcomes is recommended, particularly among high-risk populations.
Atypical manifestations of COVID-19 in general practice: a case of gastrointestinal symptoms
Authors: Wahab Sardam Faraidon , Løgstrup Brian Bridal
Published: August 2020

During the previous months, we have seen the rapid pandemic spread of SARS-CoV-2. Despite being considered a respiratory virus, it has become clear that other clinical presentations are possible and some of these are quite frequent. In this paper, a case of a man in his late 70s showing atypical symptoms in general practice is presented. Apart from fever, the patient complained of diarrhoea, borborygmus, loss of appetite and nausea. He developed no respiratory symptoms during his disease. Due to his symptoms, malignant disease was suspected, and he was referred for further testing which revealed typical COVID-19 findings on a chest CT scan. The occurrence of atypical symptoms is discussed, including the importance of recognising these in an ongoing pandemic.
Survival of the fittest: phacoemulsification outcomes in four corneal transplants by Dr Ramon Castroviejo
Authors: Franco Jovany Jeomar , Reyes Luis Jose Luis , Rahim Salma , Greenstein Stephen , Pineda Roberto
Published: August 2020

Aim

To evaluate and report the outcomes following phacoemulsification on four eyes, 45 years or more after corneal transplantation.

Methods

A retrospective case series of four eyes in three patients (P1, P2, P3), undergoing phacoemulsification at least 45 years after corneal transplantation by Dr Ramon Castroviejo. Corneal graft survival outcome measures included central corneal thickness (CCT), best-corrected visual acuity (BCVA), corneal clarity and endothelial cell count (ECC).

Results

Phacoemulsification was successfully completed in all four cases with no instances of graft failure during the postoperative follow-up period, which ranged from 17 months to 76 months. At the conclusion of the follow-up period, all four grafts remained clear, and BCVA remained better than or similar to preoperative values. Long-term follow-up revealed no meaningful changes in CCT after phacoemulsification. All but one case experienced a decrease in ECC, with ECC values in the four cases ranging from 538 cells/mm2 to 1436 cells/mm2 at the conclusion of postoperative follow-up.

Conclusion

Limited data have been published on the long-term survival of corneal grafts after intraocular surgery, especially for extremely ‘mature’ corneal transplants. This case series demonstrates that with appropriate preoperative, intraoperative and postoperative measures, successful phacoemulsification can be performed in these cases with excellent long-term results.
Enhancing your scholarship as a family medicine junior faculty member
Authors: Rollins Lisa K
Published: August 2020

Family medicine faculty are often expected to produce some form of scholarship as members of academic departments. However, this can be challenging given a range of contextual factors, including limited research capacity in many departments, increased competition for funding and individual challenges around balancing multiple roles, unclear expectations and lack of mentorship, to name a few. The purpose of this reflection is to discuss seven content areas that might be addressed by faculty in order to promote scholarship, particularly among junior faculty. These include: 1) knowing your academic track and its associated expectations by rank, as well as the scholarship expectations within your department; 2) considering your personal goals, interests, professional development needs and the relationship between meaningful work and burnout; 3) starting small and building towards a niche content area; 4) finding collaborators and the benefits of collaboration; 5) seeking alignment between your scholarship and work that you already are performing; 6) educating yourself about available outlets for scholarship and 7) seeking mentorship.
Exposure to Chinese famine in early life and the risk of sensory impairment in adulthood
Authors: Rong Hongguo , Lai Xiaozhen , Mahmoudi Elham , Fang Hai
Published: August 2020

Background

Studies have shown that malnutrition in early life has a negative effect on midlife cognitive functions. Little is known, however, about the relationship between early-life malnutrition and visual, hearing or dual sensory impairments in adulthood. This study aims to investigate the association between exposure to the 1959–1961 Chinese famine in early life and sensory impairments in adulthood.

Methods

A total of 6347 adults born between 1952 and 1964 surveyed in the 2015 China Health and Retirement Longitudinal Study were included in this study. The presence of sensory impairments was identified by self-reported assessment of visual and hearing functions. The associations between multi-stage early-life famine exposure and sensory functions were estimated using the multiple generalised linear model.

Results

Compared with the unexposed group, respondents exposed to famine in the fetal period and late childhood had a significantly higher risk of hearing impairment (OR 1.54, 95% CI 1.06 to 2.24; OR 1.75, 95% CI 1.23 to 2.50) and dual sensory impairments (OR 1.45, 95% CI 1.00 to 2.11; OR 1.55, 95% CI 1.09 to 2.21), respectively. Furthermore, in severely famine-affected areas, the early, mid and late childhood-exposed groups were more likely to have hearing and dual sensory impairments than the unexposed group. Those associations were not observed in less famine-affected areas. However, no significant association was found between famine exposure and visual impairment in early-life famine-exposed group.

Conclusion

Exposure to Chinese famine in the fetal period and late childhood was linked to hearing and dual sensory impairments in adulthood.
Association between Acute Respiratory Failure Requiring Mechanical Ventilation and the Production of Advanced Glycation End Products
Authors: Edriss Hawa , Molehin Adebayo J , Gavidia Rocio , Selvan Kavitha , Nugent Kenneth
Published: August 2020

Patients with acute respiratory failure often have hyperglycemia. Elevated glucose levels could cause acute lung injury through the production of advanced glycation end products. We measured glucose, advanced glycation end products, glycated albumin, circulating glycated hemoglobin, and soluble receptor for advanced glycation end product (sRAGE) levels on admission, at 24 hours, and at 72 hours in 40 patients with acute respiratory failure requiring mechanical ventilation. We compared these values with healthy control subjects. The mean age was 63.3±11.2 years. Fifty percent of the patients were women. Thirteen patients (32.5%) died during this hospitalization. The mean maximum glucose level on the day of admission was 215.7±171.1 mg/dL. Compared with control subjects, there was a significant reduction in advanced glycation end product levels (p=0.0001) in the patients at all 3 time points. Circulating glycated hemoglobin levels were significantly higher in patients compared with control subjects. We also observed a moderate increase in glycated albumin levels on admission and at 24 hours when compared with the control samples. Overall sRAGE levels were similar to controls, but patients with dense infiltrates on chest X-ray had increased levels compared with patients who did not have these dense infiltrates on the day of admission. Patients with acute respiratory failure requiring mechanical ventilation have decreased levels of advanced glycation end products and increased levels of circulating glycated hemoglobin. The results from this pilot study suggest that the acute stress associated with respiratory failure might create glycated proteins which could contribute to disease pathogenesis.
Antigen processing and presentation in cancer immunotherapy
Authors: Lee Maxwell Y , Jeon Jun W , Sievers Cem , Allen Clint T
Published: August 2020

Background

Knowledge about and identification of T cell tumor antigens may inform the development of T cell receptor-engineered adoptive cell transfer or personalized cancer vaccine immunotherapy. Here, we review antigen processing and presentation and discuss limitations in tumor antigen prediction approaches.

Methods

Original articles covering antigen processing and presentation, epitope discovery, and in silico T cell epitope prediction were reviewed.

Results

Natural processing and presentation of antigens is a complex process that involves proteasomal proteolysis of parental proteins, transportation of digested peptides into the endoplasmic reticulum, loading of peptides onto major histocompatibility complex (MHC) class I molecules, and shuttling of peptide:MHC complexes to the cell surface. A number of T cell tumor antigens have been experimentally validated in patients with cancer. Assessment of predicted MHC class I binding and total score for these validated T cell antigens demonstrated a wide range of values, with nearly one-third of validated antigens carrying an IC50of greater than 500 nM.

Conclusions

Antigen processing and presentation is a complex, multistep process. In silico epitope prediction techniques can be a useful tool, but comprehensive experimental testing and validation on a patient-by-patient basis may be required to reliably identify T cell tumor antigens.
Constraints on range expansion of introduced red squirrels (Tamiasciurus hudsonicus) in an island ecosystem
Authors: McDermott Jenna P.B. , Whitaker Darroch M. , Warkentin Ian G.
Published: August 2020

Factors that limit the range expansion of introduced species can offer insights into the basic ecology of these species and inform conservation of associated endemic species. North American red squirrels (Tamiasciurus hudsonicus (Erxleben, 1777)) were recently introduced to the island of Newfoundland, Canada, where they have been implicated in the decline of two endemic bird subspecies. During the summers of 2016 (following conifer masting) and 2017 (following nonmasting), we conducted surveys with 1960 point counts and playback to assess red squirrel distribution and habitat use across a 257 km2montane landscape in western Newfoundland. We used generalized additive models with stepwise model selection to assess the relationship between land cover and red squirrel occurrence each summer. Red squirrels were most common at low elevations and were not detected at elevations above ∼500 m. Their occurrence was negatively associated with the presence of water, coniferous scrub, and 10- to 30-year-old fir–spruce but positively associated with the presence of 30- to 70-year-old fir–spruce and >70-year-old fir. Red squirrel presence was related to more land cover variables in 2016, after a masting year. The absence of red squirrels from forests at higher elevations apparently resulted from lack of suitable habitat rather than incomplete range expansion. Climate- or silviculture-induced changes in vegetation may alter mid- and upper-elevation habitat suitability.
Dark matter in inert doublet model with one scalar singlet and $$U(1)_X$$ gauge symmetry
Authors: Arroyo-Ureña M. A. , Gaitan R. , Martinez R. , Montes de Oca Yemha J. H.
Published: August 2020

We study dark matter (DM) abundance in the framework of the extension of the Standard Model (SM) with an additional $$U(1)_X$$U(1)X gauge symmetry. One complex singlet is included to break the $$U(1)_X$$U(1)X gauge symmetry, meanwhile one of the doublets is considered inert to introduce a DM candidate. The stability of the DM candidate is analyzed with a continuous $$U(1)_X$$U(1)X gauge symmetry as well as discrete $$Z_2$$Z2 symmetry. We find allowed regions for the free model parameters which are in agreement with the most up-to-date experimental results reported by CMS and ATLAS Collaborations, the upper limit on WIMP-nucleon cross section imposed by XENON1T Collaboration and the upper limit on the production cross-section of a $$Z^{\prime }$$Z′ gauge boson times the branching ratio of the $$Z^{\prime }$$Z′ boson decaying into $$\ell ^-\ell ^+$$ℓ-ℓ+. We also obtain allowed regions for the DM candidate mass from the relic density reported by the PLANCK Collaboration including light, intermediate and heavy masses; depending mainly on two parameters of the scalar potential, $$\lambda _{2x}$$λ2x and $$\lambda _{345}=\lambda _3+\lambda _4+2\lambda _5$$λ345=λ3+λ4+2λ5. We find that trough $$pp\rightarrow \chi \chi \gamma $$pp→χχγ production, it may only be possible for a future hadron–hadron circular collider (FCC-hh) to be able to detect a DM candidate within the range of masses 10–60 GeV.
Viability tests of f(R)-gravity models with Supernovae Type 1A data
Authors: Hough R. T. , Abebe A. , Ferreira S. E. S.
Published: August 2020

In this work, we will be testing four different general f(R)-gravity models, two of which are the more realistic models (namely the Starobinsky and the Hu–Sawicki models), to determine if they are viable alternative models to pursue a more vigorous constraining test upon them. For the testing of these models, we use 359 low- and intermediate-redshift Supernovae Type 1A data obtained from the SDSS-II/SNLS2 Joint Light-curve Analysis (JLA). We develop a Markov Chain Monte Carlo (MCMC) simulation to find a best-fitting function within reasonable ranges for each f(R)-gravity model, as well as for the Lambda Cold Dark Matter ($$\varLambda $$ΛCDM) model. For simplicity, we assume a flat universe with a negligible radiation density distribution. Therefore, the only difference between the accepted $$\varLambda $$ΛCDM model and the f(R)-gravity models will be the dark energy term and the arbitrary free parameters. By doing a statistical analysis and using the $$\varLambda $$ΛCDM model as our “true model”, we can obtain an indication whether or not a certain f(R)-gravity model shows promise and requires a more in-depth view in future studies. In our results, we found that the Starobinsky model obtained a larger likelihood function value than the $$\varLambda $$ΛCDM model, while still obtaining the cosmological parameters to be $$\varOmega _{m} = 0.268^{+0.027}_{-0.024}$$Ωm=0.268-0.024+0.027 for the matter density distribution and $${\bar{h}} = 0.690^{+0.005}_{-0.005}$$h¯=0.690-0.005+0.005 for the Hubble uncertainty parameter. We also found a reduced Starobinsky model that are able to explain the data, as well as being statistically significant.
Stationary Probability Vectors of Higher-Order Two-Dimensional Symmetric Transition Probability Tensors
Authors: Huang Zheng-Hai , Qi Liqun
Published: August 2020

In this paper, we investigate stationary probability vectors of higher-order two-dimensional symmetric transition probability tensors. We show that there are two special symmetric transition probability tensors of order [Formula: see text] dimension 2, which have and only have two stationary probability vectors; and any other symmetric transition probability tensor of order [Formula: see text] dimension 2 has a unique stationary probability vector. As a byproduct, we obtain that any symmetric transition probability tensor of order [Formula: see text] dimension 2 has a unique positive stationary probability vector, and that any symmetric irreducible transition probability tensor of order [Formula: see text] dimension 2 has a unique stationary probability vector.
Spatial dynamics in interacting systems with discontinuous coefficients and their continuum limits
Authors: Zanco Giovanni
Published: August 2020

We consider a discrete model in which particles are characterized by two quantities [Formula: see text] and [Formula: see text]; both quantities evolve in time according to stochastic dynamics and the equation that governs the evolution of [Formula: see text] is also influenced by mean-field interaction between the particles. We allow for discontinuous coefficients and random initial condition and, under suitable assumptions, we prove that in the limit as the number of particles grows to infinity the dynamics of the system is described by the solution of a Fokker–Planck partial differential equation. We provide the existence and uniqueness of a solution to the latter and show that such solution arises as the limit in probability of the empirical measures of the system.
Wave-like spatially homogeneous models of Stackel spacetimes (3.1) type in the scalar-tensor theory of gravity
Authors: Osetrin Evgeny , Osetrin Konstantin , Filippov Altair , Kirnos Ilya
Published: August 2020

All classes of spatially homogeneous spacetime models in the generalized scalar–tensor theory of gravitation are found to allow the integration of the equations of motion of test particles and the eikonal equation by the method of separation of variables by type (3.1). Three classes of exact solutions are obtained that relate to Shapovalov wave-like spacetime models. The resulting spacetime models are of types IV, VI and VII according to the Bianchi classification and type N according to Petrov classification.
On Finite Noncommutative Gröbner Bases
Authors: Diop Yatma , Sow Djiby
Published: August 2020

It is well known that in the noncommutative polynomial ring in serveral variables Buchberger’s algorithm does not always terminate. Thus, it is important to characterize noncommutative ideals that admit a finite Gröbner basis. In this context, Eisenbud, Peeva and Sturmfels defined a map γ from the noncommutative polynomial ring k⟨X1, …, Xn⟩ to the commutative one k[x1, …, xn] and proved that any ideal [Formula: see text] of k⟨X1, …, Xn⟩, written as [Formula: see text] = γ−1([Formula: see text]) for some ideal [Formula: see text] of k[x1, …, xn], amits a finite Gröbner basis with respect to a special monomial ordering on k⟨X1, …, Xn⟩. In this work, we approach the opposite problem. We prove that under some conditions, any ideal [Formula: see text] of k⟨X1, …, Xn⟩ admitting a finite Gröbner basis can be written as [Formula: see text] = γ−1([Formula: see text]) for some ideal [Formula: see text] of k[x1, …, xn].
Completed Tensor Product and Flatness
Authors: Tabaâ Mohamed
Published: August 2020

We give, in a more general case than the Noetherian case, an answer to the question posed by Shaul on the flatness of the completed tensor product.
The Category of Modules on an n-Trivial Extension: the Basic Properties
Authors: Benkhadra Dirar , Bennis Driss , García Rozas J.R.
Published: August 2020

In this paper we investigate a categorical aspect of n-trivial extension of a ring by a family of modules. Namely, we introduce the right (resp., left) n-trivial extension of a category by a family of endofunctors. Among other results, projective, injective and flat objects of this category are characterized, and two applications are presented at the end of this paper. We characterize when an n-trivial extension ring is k-perfect and establish a result on the self-injective dimension of an n-trivial extension ring.
Asymmetric voltage multiplying circuit coupled to sliding electrodes for biomass fractionation with high-voltage and high current pulsed electric fields
Authors: Levkov Klimentiy , Golberg Alexander
Published: August 2020

Pulsed electric field (PEF) is an emerging technology for biomass processing and fractionation by electroporation of cell membrane. Nevertheless, PEF technology and devices require tailoring and adaptation for each specific type of biomass. Such an optimization requires convenient and adaptable laboratory systems, which will enable both electrical and mechanical parameters determination before process upscaling. In this work, we report on the design and development of a laboratory PEF system that allows applying for up to 4[Formula: see text]kV, 1[Formula: see text]kA pulses with 1–100[Formula: see text][Formula: see text]s and total power dissipation of 20[Formula: see text]W and up to 25[Formula: see text]kg of mechanical load. The design of an asymmetric voltage multiplying circuit allows for controlling pulse parameters for each pulse in series. Such an approach enables precise adaptation of PEF to the changing conductivity of the biomass, minimizing the total invested energy in the process. The system was tested on highly conductive marine macroalgae Ulva sp, a promising but challenging feedstock for the biorefinery. This work provides a design of an adaptable PEF device, important for biomass processing with electroporation.
Molecular Mechanisms of CRISPR-Cas Immunity in Bacteria
Authors: Nussenzweig Philip M. , Marraffini Luciano A.
Published: August 2020

Prokaryotes have developed numerous defense strategies to combat the constant threat posed by the diverse genetic parasites that endanger them. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas loci guard their hosts with an adaptive immune system against foreign nucleic acids. Protection starts with an immunization phase, in which short pieces of the invader's genome, known as spacers, are captured and integrated into the CRISPR locus after infection. Next, during the targeting phase, spacers are transcribed into CRISPR RNAs (crRNAs) that guide CRISPR-associated (Cas) nucleases to destroy the invader's DNA or RNA. Here we describe the many different molecular mechanisms of CRISPR targeting and how they are interconnected with the immunization phase through a third phase of the CRISPR-Cas immune response: primed spacer acquisition. In this phase, Cas proteins direct the crRNA-guided acquisition of additional spacers to achieve a more rapid and robust immunization of the population.
Histone Variants: The Nexus of Developmental Decisions and Epigenetic Memory
Authors: Loppin Benjamin , Berger Frédéric
Published: August 2020

Nucleosome dynamics and properties are central to all forms of genomic activities. Among the core histones, H3 variants play a pivotal role in modulating nucleosome structure and function. Here, we focus on the impact of H3 variants on various facets of development. The deposition of the replicative H3 variant following DNA replication is essential for the transmission of the epigenomic information encoded in posttranscriptional modifications. Through this process, replicative H3 maintains cell fate while, in contrast, the replacement H3.3 variant opposes cell differentiation during early embryogenesis. In later steps of development, H3.3 and specialized H3 variants are emerging as new, important regulators of terminal cell differentiation, including neurons and gametes. The specific pathways that regulate the dynamics of the deposition of H3.3 are paramount during reprogramming events that drive zygotic activation and the initiation of a new cycle of development.
Editors’ Choice—Perspective—Challenges in Moving to Multiscale Battery Models: Where Electrochemistry Meets and Demands More from Math
Authors: Shah Krishna , Subramaniam Akshay , Mishra Lubhani , Jang Taejin , Bazant Martin Z. , Braatz Richard D. , Subramanian Venkat R.
Published: August 2020

There has been significant recent interest in studying multiscale characteristics of current and next-generation batteries, including lithium-metal and lithium-sulfur batteries. Advances in computing power make researchers believe that the detailed multiscale models can be efficiently simulated to arrive at the insights for the degradation and performance loss; however, this is not true and special attention needs to be paid to local singularities, boundary layers, moving boundaries, etc. This article presents 2D examples that illustrate the importance of grid convergence studies, provides well-defined detailed models to test the efficiency of numerical schemes, and discusses the associated simulation challenges.
Enhanced KCl-mediated contractility and Ca2+sensitization in porcine collateral-dependent coronary arteries persist after exercise training
Authors: Heaps Cristine L. , Bray Jeff F. , Parker Janet L.
Published: August 2020

Small coronary arteries distal to chronic occlusion displayed enhanced contractile responses, which were further augmented after exercise training and attributable to enhanced calcium sensitization without alterations in calcium channel current. The calcium sensitization mediators Rho-kinase and CaMKII significantly contributed to enhanced contraction in collateral-dependent arteries of exercise-trained, but not sedentary, pigs. Exercise-enhanced contractile responses may increase resting arterial tone, creating an enhanced coronary flow reserve that is accessible during periods of increased metabolic demand.