bluuebunny/crossref_metadata_2025 huggingface dataset:
Opportunities for sustainability improvement in aluminum industry
Authors: Pandey Ashok Kumar , Prakash Ravi
Published: April 2020

The aluminum consumption in India of 2.5 kg per capita is way below the global average of 11 kg per capita. In the future, India will require additional annual consumption of 16 million tons of aluminum. Due to the energy‐intensive nature of aluminum production coupled with its projected growth, there are sustainability concerns for this industrial sector. This paper examines some opportunities available for sustainability improvement in an existing aluminum plant using coal‐based electricity. An industrial sustainability index (ISI), as previously developed by the authors, is here to quantitatively evaluate the magnitude of sustainability improvement through a natural gas‐based combined cycle (NGCC) power generation. Two modes of sustainability improvement are examined: (a) NGCC with surplus power generation and (b) NGCC with doubling of production capacity. It is observed that the ISI values can be increased by 5 to 6 times through the above modes, as compared to the existing model. The investment required for such sustainability improvement is expected to be less than that required for setting up a totally new plant. The direct carbon emissions for the existing plant are nearly 6.4% of the total carbon emissions, which may be eliminated by adopting new smelting technology now available, with the further possibility of sustainability improvement.
Riverine large wood and recreation safety: A framework to discretize and contextualize hazard
Authors: Conley Will , Kramer Natalie
Published: April 2020

The importance of large wood (LW) to riverine functions is well established scientifically and increasingly recognized by river managers in many countries. However, public perceptions largely associate LW with elevated danger and/or need for intervention. Such perspectives are amplified amongst recreational river users (defined here as any individuals that recreate by floating on the water surface of a river) who interact more directly with rivers than the general public and commonly view wood in life‐or‐death terms. Given that human life occupies a highest‐order charge for river managers, they are left in a difficult position when safety appears to conflict with environmental services. LW deficits are perpetuated partly because wood removal, often in the name of safety, is far easier than placing wood in rivers. Further, river restoration practitioners are frequently burdened with expectations and liability unparalleled in built environments. A fundamentally different mindset is necessary to achieve desired ecologic outcomes when working with rivers. Based on two decades of experience as boaters, LW practitioners, and emergency responders, we (1) discuss LW hazard and risk from recreational and management viewpoints, (2) discretize objective and measurable physical properties of LW hazards, and (3) propose a decision framework that implicitly addresses risk by considering LW hazards relative to river use and ambient hazards. The approach is structured to increase objectivity in LW hazard mitigation and diminish asymmetric biases that favor LW removal. Our intent is to build understanding and rational flexibility among risk‐averse management, regulatory, and funding entities to facilitate implementation of scientific understanding without undue risk to river users. © 2020 John Wiley & Sons, Ltd.
Endocrine surgery in the Coronavirus disease 2019 pandemic: Surgical Triage Guidelines
Authors: Jozaghi Yelda , Zafereo Mark E. , Perrier Nancy D. , Wang Jennifer R. , Grubbs Elizabeth , Gross Neil D. , Fisher Sarah , Sturgis Erich M. , Goepfert Ryan P. , Lai Stephen Y. , Best Conor , Busaidy Naifa L. , Cabanillas Maria E. , Dadu Ramona , Gagel Robert F. , Habra Mouhammed A. , Hu Mimi I. , Jimenez Camilo , Sherman Steven I. , Thosani Sonali , Varghese Jeena , Waguespack Steven G. , Weitzman Steven , Ying Anita K. , Graham Paul H.
Published: April 2020

Background

In the face of the COVID‐19 pandemic, cancer care has had to adapt rapidly given the Centers for Disease Control and Prevention and the American College of Surgeons (ACS) issuing recommendations to postpone nonurgent surgeries.

Methods

An institutional multidisciplinary group of Head and Neck Surgical Oncology, Surgical Endocrinology, and Medical Endocrinology devised Surgical Triaging Guidelines for Endocrine Surgery during COVID‐19, aligned with phases of care published by the ACS.

Results

Phases of care with examples of corresponding endocrine cases are outlined. Most cases can be safely postponed with active surveillance, including most differentiated and medullary thyroid cancers. During the most acute phase, all endocrine surgeries are deferred, except thyroid tumors requiring acute airway management.

Conclusions

These guidelines provide context for endocrine surgery within the spectrum of surgical oncology, with the goal of optimal individualized multidisciplinary patient care and the expectation of significant resource diversion to care for patients with COVID‐19.
Managing head and neck cancer patients with tracheostomy or laryngectomy during the COVID‐19 pandemic
Authors: Kligerman Maxwell P. , Vukkadala Neelaysh , Tsang Raymond K. Y. , Sunwoo John B. , Holsinger F. Christopher , Chan Jason Y. K. , Damrose Edward J. , Kearney Ann , Starmer Heather M.
Published: April 2020

Head and neck cancer patients with tracheostomies and laryngectomies, as well as their healthcare providers, face unique challenges in the context of the current COVID‐19 pandemic. This document consolidates best available evidence to date and presents recommendations to minimize the risks of aerosolization and SARS‐CoV‐2 exposures in both the inpatient and outpatient settings. The cornerstones of these recommendations include the use of closed‐circuit ventilation whenever possible, cuffed tracheostomy tubes, judicious use of heat moisture exchange units, appropriate personal protective equipment for providers and patients, meticulous hand hygiene, and minimal manipulation of tracheostomy tubes.
Clinical Best Practice Advice for Hepatology and Liver Transplant Providers During the COVID‐19 Pandemic: AASLD Expert Panel Consensus Statement
Authors: Fix Oren K. , Hameed Bilal , Fontana Robert J. , Kwok Ryan M. , McGuire Brendan M. , Mulligan David C. , Pratt Daniel S. , Russo Mark W. , Schilsky Michael L. , Verna Elizabeth C. , Loomba Rohit , Cohen David E. , Bezerra Jorge A. , Reddy K. Rajender , Chung Raymond T.
Published: April 2020

Background and Aims

Coronavirus disease 2019 (COVID‐19), the illness caused by the SARS‐CoV‐2 virus, is rapidly spreading throughout the world. Hospitals and healthcare providers are preparing for the anticipated surge in critically ill patients, but few are wholly equipped to manage this new disease. The goals of this document are to provide data on what is currently known about COVID‐19, and how it may impact hepatologists and liver transplant providers and their patients. Our aim is to provide a template for the development of clinical recommendations and policies to mitigate the impact of the COVID‐19 pandemic on liver patients and healthcare providers.

Approach and Results

This article discusses what is known about COVID‐19 with a focus on its impact on hepatologists, liver transplant providers, patients with liver disease, and liver transplant recipients. We provide clinicians with guidance for how to minimize the impact of the COVID‐19 pandemic on their patients’ care.

Conclusions

The situation is evolving rapidly, and these recommendations will need to evolve as well. As we learn more about how the COVID‐19 pandemic impacts the care of patients with liver disease, we will update the online document available at https://www.aasld.org/about-aasld/covid-19-and-liver.
Perovskite: Name Puzzle and German‐Russian Odyssey of Discovery
Authors: Katz Eugene A.
Published: April 2020

Today the term ‘perovskite’ is used to designate the crystalline structure of a wide variety of ABX3 ionic compounds. However, historically this name was used for a specific material, having been coined for a mineral, calcium titanate (CaTiO3). This mineral was discovered in the Ural Mountains, Russia. The first sample of the mineral was transferred from Saint Petersburg to Berlin in 1839 by the Russian mineralogist Alexander Kämmerer, who gave the sample for further investigation to the German mineralogist and crystallographer Gustav Rose. Rose determined its properties and chemical composition and named the mineral after the Russian politician and mineralogist Lev Perovski. The present essay describes the background of this discovery as well as the life stories of the personalities involved.
In vivo studies on osteoinduction: A systematic review on animal models, implant site, and type and postimplantation investigation
Authors: Veronesi Francesca , Maglio Melania , Brogini Silvia , Fini Milena
Published: April 2020

Musculoskeletal diseases involving loss of tissue usually require management with bone grafts, among which autografts are still the gold standard. To overcome autograft disadvantages, the development of new scaffolds is constantly increasing, as well as the number of in vivo studies evaluating their osteoinductivity in ectopic sites. The aim of the present systematic review is to evaluate the last 10 years of osteoinduction in vivo studies. The review is focused on: (a) which type of animal model is most suitable for osteoinduction evaluation; (b) what are the most used types of scaffolds; (c) what kind of post‐explant evaluation is most used. Through three websites (www.pubmed.com, www.webofknowledge.com and www.embase.com), 77 in vivo studies were included. Fifty‐eight studies were conducted in small animal models (rodents) and 19 in animals of medium or large size (rabbits, dogs, goats, sheep, and minipigs). Despite the difficulty in establishing the most suitable animal model for osteoinductivity studies, small animals (in particular mice) are the most utilized. Intramuscular implantation is more frequent than subcutis, especially in large animals, and synthetic scaffolds (especially CaP ceramics) are preferred than natural ones, also in combination with cells and growth factors. Paraffin histology and histomorphometric evaluations are usually employed for postimplantation analyses.
Associations between estimated glomerular filtration rate and cardiac biomarkers
Authors: Pang Lu , Wang Zhe , Zhao Zi‐Long , Guo Qi , Huang Chen‐Wei , Du Jia‐Lin , Yang Hong‐Yun , Li Hai‐Xia
Published: April 2020

Background

Chronic kidney disease (CKD) is associated with an increased cardiovascular disease (CVD) mortality risk. Elevation of cardiac biomarkers in patients with renal dysfunction is ambiguous in the diagnosis of CVD. The purpose of this study was to investigate the associations between estimated glomerular filtration rate (eGFR) and cardiac biomarkers, and the influence of renal dysfunction on the cardiac biomarkers.

Methods

We examined the cross‐sectional associations of eGFR with cardiac troponin I (cTnI), creatine kinase (CK), CK‐MB, lactic dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), and brain natriuretic peptide (BNP) in 812 adults and 215 child. Spearman correlation and logistic regression analysis were performed to evaluate the associations.

Results

For adults, lower eGFR CKD‐EPI had significantly higher cTnI, CK‐MB, LDH, HBDH, and BNP. There were negative correlations between eGFRCKD‐EPI and cTnI, CK‐MB, LDH, HBDH, and BNP. After adjustment for potential confounders, as compared with eGFRCKD‐EPI ≥ 90 mL/min/1.73 m2, eGFRCKD‐EPI < 60 mL/min/1.73 m2 remained associated with a 2.83 (1.08‐7.41) [ratio (95% CI)] times higher cTnI and a 6.50 (2.32‐18.22) [ratio (95% CI)] times higher HBDH. For child, lower eGFRSchwartz had significant higher CK and CK‐MB. There were negative correlations between eGFRSchwartz and CK, and eGFRSchwartz and CK‐MB. After adjustment for potential confounders, as compared with eGFRSchwartz ≥ 90 mL/min/1.73 m2, eGFRSchwartz < 90 mL/min/1.73 m2 revealed no significant higher CVD biomarkers.

Conclusion

Reduced eGFR is associated with elevated cTnI and HBDH among adults without clinically evident CVD, but not child.
Greener gas? Impact of biosolids on carbon intensity of switchgrass ethanol
Authors: Brown Sally , Pannu Manmeet , Fransen Steven C.
Published: April 2020

Synthetic fertilizers make up a significant fraction of the energy required to grow switchgrass (Panicum virgatum L.) for ethanol production. A field study compared biosolids and synthetic fertilizers on biomass yield, ethanol production, and nitrous oxide (N2O) emissions of switchgrass to determine if using an alternative source of nutrient would lower the energy density of the fuel. Minimal N2O emissions were observed the first year of the study (0.99 ± 1.5 g N2O ha−1 d−1 for biosolids), with no difference between treatments. Biosolids were added in excess of agronomic rates, and gas samples were collected immediately after irrigation for the subsequent years to examine maximum N2O emissions. Mean Year 2 emissions increased for fertilizers to 1.8 ± 8 g N2O ha−1 d−1 (n = 131) and to 3.73 ± 10.2 g N2O ha−1 d−1 (n = 130) for biosolids‐amended soils. Emissions in Year 3 were similar to Year 2. Yield was similar and ranged from 3.7 ± 5 to 11 ± 1.1 and from 5.0 ± 0.2 to 13.4 ± 1.7 Mg ha−1 for biosolids and fertilizer, respectively. The potential ethanol yield was 365 ± 28 L Mg−1 and 374 ± 34 L Mg−1 for the biosolids‐ and fertilizer‐grown grass, respectively. Greenhouse gas emissions associated with fertilizer production were considered for N, P, and K and totaled 1,653 kg carbon dioxide equivalent (CO2e) ha−1. The equivalent credits for substitution of biosolids (18 Mg ha−1) were −2,492 kg CO2e ha−1. Nitrous oxide emissions were calculated based on 1% of total N applied for agronomic applications and were 8,600 and 3,500 g N2O ha−1 for the biosolids and fertilizer treatments, respectively. Total carbon costs associated with fertilization were 2,700 kg CO2e ha−1 for fertilizer and 60 kg CO2e ha−1 for biosolids. Using measured N2O data would have resulted in lower emissions for both treatments.
Significance of fecal hemoglobin concentration for predicting risk of colorectal cancer after colonoscopy
Authors: Kawamura Takuji , Inoue Takato , Shinomiya Ryo , Sakai Hiroaki , Amamiya Kana , Sakiyama Naokuni , Shirakawa Atsushi , Okada Yusuke , Sanada Kasumi , Nakase Kojiro , Mandai Koichiro , Suzuki Azumi , Kamaguchi Mai , Morita Atsushi , Nishioji Kenichi , Tanaka Kiyohito , Uno Koji , Yokota Isao , Kobayashi Masao , Yasuda Kenjiro
Published: April 2020

Background and Aim

As the significance of the quantitative fecal immunochemical test (FIT) in patients who previously underwent a colonoscopy is unknown, this study aimed at investigating the association between fecal hemoglobin concentration and the risk of colorectal cancer (CRC).

Methods and Results

We retrospectively analyzed FIT‐positive patients who underwent a colonoscopy through our opportunistic annual screening program from April 2010 to March 2017 at the Kyoto Second Red Cross Hospital. We stratified them into no colonoscopy and past colonoscopy (>5 years or ≤5 years) groups based on whether they had a history of undergoing a colonoscopy and analyzed the correlation between fecal hemoglobin concentration and advanced neoplasia or invasive cancer detection in each group. We analyzed 1248 patients with positive FIT results. There were 748 (59.9%), 198 (15.9%), and 302 (24.2%) patients in the no colonoscopy, past colonoscopy (>5 years), and past colonoscopy (≤5 years) groups, respectively. In the no colonoscopy group, the advanced neoplasia detection rate significantly increased with the fecal hemoglobin concentration (P < 0.001). However, no significant trend was observed in the past colonoscopy (both >5 years and ≤5 years) group (P = 0.982). No invasive cancer was detected in the past colonoscopy (≤5 years) group.

Conclusion

The risk of CRC might be low even if fecal hemoglobin concentration was high, especially in those who underwent colonoscopy within 5 years.
Epidemiology and persistence of cervical human papillomavirus infection among outpatient women in Heilongjiang province: A retrospective cohort study
Authors: Liu Jiaxin , Shi Yafeng , Wang Lishuang , Wang Jiao , Fan Dongxue , Han Shiyu , Wei Lanlan
Published: April 2020

As persistent carcinogenic human papillomavirus (HPV) infection is a prominent driver of cervical cancer, it is essential to explore HPV persistence and its associated factors for cancer screening and prevention. A retrospective cohort study was performed in outpatient women between March 2010 and 2019 in Heilongjiang, northeast China. HPV genotyping was performed by polymerase chain reaction‐membrane hybridization. An unconditional logistic regression model was used to analyze the association of factors with persistence. The overall prevalence of HPV at baseline was 27.1%, with a downward trend from 2010 to 2019 (P <  .0001). The most commonly observed high‐ and low‐risk HPVs were HPV16 (N = 1094, 5.9%) and HPV11 (N = 596, 3.2%), respectively. The probabilities of 6‐month persistence were high for women infected with HPV16 (P = .0001), HPV58 (P = .018), and HPV53 (P = .014), as well as for women with multiple infections (P = .009), and those who were 51 to 60 years old (P = .004) or more than  60 years old (P = .007). The probabilities of 12‐month persistence were high for women infected with HPV53 (P = .017) and 51‐ to 60‐year‐old women (P = .044). HPV16 is the dominant HPV type in Heilongjiang. An age in the range of 51 to 60 years and infection with HPV53 is associated with HPV infection persistence in the Heilongjiang population.
Direct separation of the enantiomers of ramosetron on a chlorinated cellulose‐based chiral stationary phase in hydrophilic interaction liquid chromatography mode
Authors: Colombo Marta , Ferretti Rosella , Zanitti Leo , Cirilli Roberto
Published: April 2020

Ramosetron is an enantiopure active pharmaceutical ingredient marketed in Japan since 1996 and later in a few Southeast Asian countries predominantly as an antiemetic for patients receiving chemotherapy. In this study, a simple and rapid high‐performance liquid chromoatography method for the separation of ramosetron and its related enantiomeric impurity by using hydrophilic interaction liquid chromatography mode is presented. Chiral resolution was performed on an analytical column (100 mm × 4.6 mm id) packed with 3 μm particles of cellulose‐based Chiralpak IC‐3 chiral stationary phase. Using a mobile phase containing acetonitrile–water–diethylamine (100:10:0.1, v/v/v) and setting the column temperature at 35°C, the resolution value was 7.35. At a flow rate of 1 mL/min, the enantioseparation was completed within 5 min. The proposed method was partially validated and it has proven to be sensitive with limit of detection and limit of quantitation of the (S)‐enantiomer impurity of 44.5 and 133.6 ng/mL.
Transvaginal Ultrasound‐Guided Fine‐Needle Aspiration of Adnexal Cysts With a Low Risk of Malignancy
Authors: Díaz de la Noval Begoña , Rodríguez Suárez Mª José , Fernández Ferrera Carmen Belén , Valdés Lafuente David , Arias Cailleau Rocío , Pérez Arias Héctor , Torrejón Becerra Juan Carlos , Suárez Gil Patricio , Lucio González Laura Rebeca
Published: April 2020

Objectives

The purpose of this study was to assess the effectiveness of ultrasound (US)‐guided aspiration for the management of low‐risk adnexal cysts.

Methods

A longitudinal cohort of women with a low‐risk adnexal cyst who underwent transvaginal US‐guided aspiration from January 2012 to April 2018 were included. All procedures were performed on an outpatient basis, without anesthesia, sedation, or antibiotics. The posttreatment follow‐up protocol included transvaginal US at 3 and 12 months. Potential risk factors for recurrence (ie, age, menopausal status, comorbidities, symptoms, cyst diameter, incomplete emptying, and location) were analyzed by multiple logistic regression.

Results

A total of 156 patients were included. The median (interquartile range) cyst diameter was 66 (58–80) mm. Fifty‐seven (36.5%) cases were resolved by US‐guided aspiration. The median follow‐up time was 556.5 (344–1070.25) days. The complication rate of the procedure was 2.6% (n = 4), with 3 cases of a major complication due to a pelvic abscess and 1 case of a minor complication due to self‐limited vaginal spotting. A larger cyst size (odds ratio, 1.01; 95% confidence interval, 1.04–1.07; P = .002) and an older age (odds ratio, 1.01; 95% confidence interval, 1.03–1.05; P = .007) at diagnosis were independent factors related to recurrence.

Conclusions

Based on the low resolution rate, US‐guided aspiration is not an effective option for the treatment of low‐risk adnexal cysts. Risk factors associated with recurrence were age and cyst size at diagnosis. Larger randomized studies are necessary to assess predictive factors for cyst recurrence.
Laser‐Triggered Writing and Biofunctionalization of Thiol‐Ene Networks
Authors: Romano Angelo , Angelini Angelo , Rossegger Elisabeth , Palmara Gianluca , Castellino Micaela , Frascella Francesca , Chiappone Annalisa , Chiadò Alessandro , Sangermano Marco , Schlögl Sandra , Roppolo Ignazio
Published: April 2020

The light responsivity of ortho‐nitrobenzyl esters (o‐NBE) is exploited to inscribe µ‐scale 2.5D patterns in thiol‐ene networks by direct laser writing. For this purpose, a multifunctional thiol and a photosensitive alkene with an o‐NBE chromophore are cured upon visible light exposure without inducing a premature photocleavage of the o‐NBE links. Once the network is formed, a laser beam source with a wavelength of 375 nm is used for selectively inducing the photocleavage reaction of the o‐NBE groups. Positive tone patterns are directly inscribed onto the sample surface without the requirement of a subsequent development step (removing soluble species in an appropriate organic solvent). Along with the realization of dry‐developable micropatterns, the chemical surface composition of the exposed areas can be conveniently adjusted since different domains with a tailored content of carboxylic groups are obtained simply by modulating the laser energy dose. In a following step, those are activated and exploited as anchor points for attaching an Alexa‐546 conjugated Protein A. Thus, the laser writable thiol‐ene networks do not only provide a convenient method for the fabrication of positive tone patterns but also open future prospectives for a wide range of biosensing applications.
Mittag‐Leffler stability and adaptive impulsive synchronization of fractional order neural networks in quaternion field
Authors: Pratap Anbalagan , Raja Ramachandran , Alzabut Jehad , Cao Jinde , Rajchakit Grienggrai , Huang Chuangxia
Published: April 2020

Fractional order quaternion‐valued neural networks are a type of fractional order neural networks for which neuron state, synaptic connection strengths, and neuron activation functions are quaternion. This paper is dealing with the Mittag‐Leffler stability and adaptive impulsive synchronization of fractional order neural networks in quaternion field. The fractional order quaternion‐valued neural networks are separated into four real‐valued systems forming an equivalent four real‐valued fractional order neural networks, which decreases the computational complexity by avoiding the noncommutativity of quaternion multiplication. Via some fractional inequality techniques and suitable Lyapunov functional, a brand new criterion is proposed first to ensure the Mittag‐Leffler stability for the addressed neural networks. Besides, the combination of quaternion‐valued adaptive and impulsive control is intended to realize the asymptotically synchronization between two fractional order quaternion‐valued neural networks. Ultimately, two numerical simulations are provided to check the accuracy and validity of our obtained theoretical results.
2H SOLCOR: A novel tool for reducing volume variation as a source of error in external standard quantitative NMR
Authors: Ewanicki Jason , Kim William , Wang Wei
Published: April 2020

Tube to tube volume difference presents a challenge in obtaining correct external standard quantitative NMR (esqNMR) results. Deuterium (2H) NMR is easily observable, intrinsically quantitative, present in all samples, free of interfering signals, and insensitive to probe tune/match and sample saltiness. These properties make 2H peak integral an ideal parameter in esqNMR for correcting volume differences between the reference standard and analyte. We demonstrate a novel and practical technique abbreviated as “2H SOLCOR” (2H SOLvent CORrected), where the 2H peak integral from the solvent is used as a universal internal standard to correct volume variations in NMR tubes, thereby improving accuracy and precision of esqNMR method. Herein, this simple yet effective technique is described, and practical considerations for successful implementation are presented. 2H SOLCOR can be applied anywhere esqNMR is used, including where precious samples need to be accurately quantified for qualification as an authentic analytical standard.
Gremlin 1 depletion in vivo causes severe enteropathy and bone marrow failure
Authors: Rowan Simon C , Jahns Hanne , Mthunzi Liberty , Piouceau Lucie , Cornwell Joanna , Doody Róisín , Frohlich Stephen , Callanan John J , McLoughlin Paul
Published: April 2020

The intestinal epithelium is perpetually renewed from a stem cell niche in the base of crypts to maintain a healthy bowel mucosa. Exit from this niche and maturation of epithelial cells requires tightly controlled gradients in BMP signalling, progressing from low BMP signalling at the crypt base to high signalling at the luminal surface. The BMP antagonist gremlin 1 (Grem1) is highly expressed by subepithelial myofibroblasts adjacent to the intestinal crypts but its role in regulating the stem cell niche and epithelial renewal in vivo has not been explored. To explore the effects of Grem1 loss in adulthood following normal growth and development, we bred mice (ROSA26CreER‐Grem1
flx/flx) in which Grem1 could be deleted by tamoxifen administration. While Grem1 remained intact, these mice were healthy, grew normally, and reproduced successfully. Following Grem1 depletion, the mice became unwell and were euthanised (at 7–13 days). Post‐mortem examination revealed extensive mucosal abnormalities throughout the small and large intestines with failure of epithelial cell replication and maturation, villous atrophy, and features of malabsorption. Bone marrow hypoplasia was also observed with associated early haematopoietic failure. These results demonstrate an essential homeostatic role for gremlin 1 in maintaining normal bowel epithelial function in adulthood, suggesting that abnormalities in gremlin 1 expression can contribute to enteropathies. We also identified a previously unsuspected requirement for gremlin 1 in normal haematopoiesis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Dosing: The key to precision plasma oncology
Authors: Dai Xiaofeng , Zhang Zhifa , Zhang Jianying , Ostrikov Kostya (Ken)
Published: April 2020

Cold atmospheric plasma (CAP) is an emerging oncotherapeutic approach with selectivity for cancer cells. It can induce different cell survival and death programs depending on the CAP dose, and it can function as a neo or adjuvant therapy against cancer. Establishing an evaluation system for precise CAP dosing is the key to make plasma therapy act alone or in combination with other therapeutic modalities for achieving desirable treatment responses. By classifying CAP‐induced effects and associating them with the dosing of plasma‐reactive agents, we identify opportunities for CAP to contribute to precision oncotherapy and discuss challenges en route to clinical applications. We emphasize the importance of dosing in plasma medicine and encourage cross‐disciplinary collaborations to develop suitable dosing metrics.
Two fatty acid‐binding proteins expressed in the intestine interact differently with endocannabinoids
Authors: Lai May Poh , Katz Francine S. , Bernard Cédric , Storch Judith , Stark Ruth E.
Published: April 2020

Two different members of the fatty acid‐binding protein (FABP) family are found in enterocyte cells of the gastrointestinal system, namely liver‐type and intestinal fatty acid‐binding proteins (LFABP and IFABP, also called FABP1 and FABP2, respectively). Striking phenotypic differences have been observed in knockout mice for either protein, for example, high fat‐fed IFABP‐null mice remained lean, whereas LFABP‐null mice were obese, correlating with differences in food intake. This finding prompted us to investigate the role each protein plays in directing the specificity of binding to ligands involved in appetite regulation, such as fatty acid ethanolamides and related endocannabinoids. We determined the binding affinities for nine structurally related ligands using a fluorescence competition assay, revealing tighter binding to IFABP than LFABP for all ligands tested. We found that the head group of the ligand had more impact on binding affinity than the alkyl chain, with the strongest binding observed for the carboxyl group, followed by the amide, and then the glycerol ester. These trends were confirmed using two‐dimensional 1H–15N nuclear magnetic resonance (NMR) to monitor chemical shift perturbation of the protein backbone resonances upon titration with ligand. Interestingly, the NMR data revealed that different residues of IFABP were involved in the coordination of endocannabinoids than those implicated for fatty acids, whereas the same residues of LFABP were involved for both classes of ligand. In addition, we identified residues that are uniquely affected by binding of all types of ligand to IFABP, suggesting a rationale for its tighter binding affinity compared with LFABP.
Stand ages adjust fluctuating patterns of soil respiration and decrease temperature sensitivity after revegetation
Authors: Tong Di , Xiao Haibing , Li Zhongwu , Nie Xiaodong , Huang Jinquan
Published: April 2020

Revegetation plays an essential role in controlling soil erosion and influencing soil respiration (Rs) by changing the vegetation coverage and soil biochemical characteristics. Soil respiration and its temperature sensitivity (Q10) have been studied comprehensively. However, the effect of stand age after revegetation on Rs and Q10 remains unclear. We selected four stands (i.e., eroded hillslopes [EBs] and 0‐ to 5‐yr, 5‐ to 10‐yr, and 10‐yr apple orchards) to investigate the changes in Rs and Q10 values. A soil CO2 flux system (Li‐8100) was used to measure Rs in situ from July 2018 to December 2018 in the Luoyugou watershed on the Chinese Loess Plateau. The average Rs rate showed decreased and increased periods with stand age. Changes in Rs were mainly induced by soil nutrient status, which accounted for 44.5% of the heavy weight in principal component analysis. The Q10 values decreased with stand age after revegetation and followed the order EB (4.96) > 0‐ to 5‐yr apple orchard (3.02) > 5‐ to 10‐yr apple orchard (2.25) > 10‐yr apple orchard (1.67). Our results suggest that Rs is substantially influenced by fungal richness and soil microbial biomass carbon (C), and the Q10 values are explained by the nonmetric multidimensional scaling ordinations of bacteria, which in turn are influenced by labile organic C. We demonstrate that converting EBs to apple orchards could be an effective way to decrease Rs and Q10 values. The fluctuating patterns of Rs with stand age should be considered when accurately evaluating the global C balance and predicting future climate change.
Safety and efficacy of intrarenal arterial autologous CD34+ cell transfusion in patients with chronic kidney disease: A randomized, open-label, controlled phase II clinical trial
Authors: Yang Chih-Chao , Sung Pei-Hsun , Cheng Ben-Chung , Li Yi-Chen , Chen Yi-Ling , Lee Mel S. , Yip Hon-Kan
Published: April 2020

Background

This was a randomized, open-label, controlled phase II clinical trial to investigate the safety, efficacy, and outcomes of intrarenal artery infusion of autologous peripheral-blood-derived CD34+ cells for patients with chronic kidney disease (CKD; ie, stage III or IV).

Materials and Methods

Between October 2016 and July 2018, 52 consecutive patients with CKD at stage III or IV were randomly allocated into a treatment group (TG; 2.5 × 107 cells for each intrarenal artery; n = 26) and a control group (CG; standardized pharmacotherapy only; n = 26). The primary endpoints included safety and change of creatinine level/creatinine clearance. The secondary endpoints were 12-month combined unfavorable clinical outcomes (defined as dialysis or death), improvement in proteinuria, and CD34+ cell-related adverse events.

Results

All patients were uneventfully discharged after CD34+ cell therapy. The baseline endothelial progenitor cell (EPC) populations did not differ between TG and CG (P > .5). Flow cytometric analysis showed increases in circulating EPC (ie, CD34+KDR+CD45dim/ CD34+CD133+CD45dim/CD31+CD133+CD45dim/CD34+CD133+KDR+/CD133+) and hematopoietic stem cell (CD34+) populations after granulocyte-colony stimulating factor treatment (all P < .001). Besides, Matrigel assay of angiogenesis was also significantly enhanced (all P < .001). Renal-venous blood samplings (ie, at 0, 5, 10, and 30 minutes after CD34+ cell infusion) demonstrated significant progressive increases in EPC level (P for trend <.001) among the TG patients. One-year combined unfavorable clinical outcomes were significantly lower in TG than those in CG (0% [0] vs 13.3% [4], P = .038). By 12 months after CD34+ cell therapy, circulating creatinine level, ratio of urine protein to urine creatinine, and creatinine clearance showed no difference between TG and CG (all P > .1).

Conclusion

CD34+ cell therapy was safe and improved 1-year outcome.

Significance statement The results of this phase II clinical trial provide important clinical information about the impact of intrarenal artery infusion of autologous peripheral-blood-derived CD34+ cells for patients with chronic kidney disease.
Multihazard fragility assessment of steel‐concrete composite frame structures with buckling‐restrained braces subjected to combined earthquake and wind
Authors: Li Hong‐Nan , Liu Yang , Li Chao , Zheng Xiao Wei
Published: April 2020

Engineering structures may inevitably be subjected to multiple natural hazards (such as earthquakes and winds) during their life cycles. This paper presents an efficient multihazard fragility methodology based on the structural demand models. The approach is applied to two steel‐concrete composite frame structures (SCCFSs), with and without buckling‐restrained braces (BRBs), aiming to evaluate the effect of BRBs on controlling the structural responses and fragilities under the combined earthquake and wind loads. In total, 120 earthquake records are selected, and 120 sets of wind drag force time histories are simulated by considering the spatial variation along the height of the exemplar building. The combined “earthquake–wind” events are stochastically assembled, in which the intensities of these two hazards are modeled using the Monte Carlo simulation. The OpenSees platform is employed to calculate the dynamic responses of the SCCFSs with and without BRBs under simultaneous earthquake and wind loads. The goodness of fits of the first‐, second‐, and third‐order polynomial in predicting the structural demand are evaluated, and the optimal polynomial is employed to generate the multihazard fragility surfaces at different damage states. The numerical results indicate that the structural responses and fragilities under the combined earthquake and wind are higher than those under an individual hazard, while the influencing extent varies with the relative intensities of these two hazards. The impact of multiple hazards and the control effect of BRBs on the structural responses and fragilities are systematically quantified and discussed in details.
Characterization of an HLA-restricted and human cytomegalovirus-specific antibody repertoire with therapeutic potential
Authors: Bewarder Moritz , Held Gerhard , Thurner Lorenz , Stilgenbauer Stephan , Smola Sigrun , Preuss Klaus-Dieter , Carbon Gabi , Bette Birgit , Christofyllakis Konstantinos , Bittenbring Joerg Thomas , Felbel Arne , Hasse Alexander , Murawski Niels , Kaddu-Mulindwa Dominic , Neumann Frank
Published: April 2020

With an infection rate of 60–90%, the human cytomegalovirus (HCMV) is very common among adults but normally causes no symptoms. When T cell-mediated immunity is compromised, HCMV reactivation can lead to increased morbidity and mortality. HCMV antigens are processed and presented as peptides on the cell surface via HLA I complexes to the T cell receptor (TCR) of T cells. The generation of antibodies against HCMV peptides presented on HLA complexes (TCR-like antibodies) has been described, but is without therapeutic applications to date due to the polygenic and polymorphic nature of HLA genes. We set out to obtain antibodies specific for HLA/HCMV-peptides, covering the majority of HLA alleles present in European populations. Using phage display technology, we selected 10 Fabs, able to bind to HCMV-peptides presented in the 6 different HLA class I alleles A*0101, A*0201, A*2402, B*0702, B*0801 and B*3501. We demonstrate specific binding of all selected Fabs to HLA-typed lymphoblastoid cell lines (EBV-transformed B cells) and lymphocytes loaded with HCMV-peptides. After infection with HCMV, 4/10 tetramerized Fabs restricted to the alleles HLA-A*0101, HLA-A*0201 and HLA-B*0702 showed binding to infected primary fibroblasts. When linked to the pseudomonas exotoxin A, these Fab antibodies induce highly specific cytotoxicity in HLA matched cell lines loaded with HCMV peptides. TCR-like antibody repertoires therefore represent a promising new treatment modality for viral infections and may also have applications in the treatment of cancers.
Prevention and control measures in radiology department for COVID-19
Authors: Ding Jinli , Fu Haihong , Liu Yaou , Gao Jianbo , Li Zhenlin , Zhao Xin , Zheng Junhui , Sun Wenge , Ni Hongyan , Ma Xinwu , Feng Ji , Wu Aiqin , Liu Jie , Wang Yun , Geng Pengfei , Chen Yong
Published: April 2020

Since a novel coronavirus was discovered from a cluster of patients with emerging pneumonia of unknown etiology in Wuhan, China, it has spread rapidly through droplet and contact transmission. Recently, the novel coronavirus pneumonia which was named COVID-19 by the World Health Organization (WHO) has been raised as a worldwide problem. Radiological examinations were confirmed as effective methods for the screening and diagnosis of COVID-19. It is reported that some radiologists and radiological technologists were infected when giving examinations to the patients with COVID-19. In order to reduce the infection risk of medical staff in radiology department, we summarized the experience on prevention and control measures in radiology department for COVID-19, aiming to guide the prevention and practical work for radiologists and radiological technologists.

Key Points

• The novel coronavirus spreads rapidly through droplet and contact transmission.

• Radiologists and radiological technologists were possibly infected by patients.

• Prevention and control measures in radiology department for COVID-19 are important.
The emerging role of sarcopenia as a prognostic indicator in patients undergoing abdominal wall hernia repairs: a systematic review of the literature
Authors: Clark S. T. , Malietzis G. , Grove T. N. , Jenkins J. T. , Windsor A. C. J. , Kontovounisios C. , Warren O. J.
Published: April 2020

Background

There is strong evidence suggesting that excessive fat distribution, for example, in the bowel mesentery or a reduction in lean body mass (sarcopenia) can influence short-, mid-, and long-term outcomes from patients undergoing various types of surgery. Body composition (BC) analysis aims to measure and quantify this into a parameter that can be used to assess patients being treated for abdominal wall hernia (AWH). This study aims to review the evidence linking quantification of BC with short- and long-term abdominal wall hernia repair outcomes.

Methods

A systematic review was performed according to the PRISMA guidelines. The literature search was performed on all studies that included BC analysis in patients undergoing treatment for AWH using Medline, Google Scholar and Cochrane databases by two independent reviewers. Outcomes of interest included short-term recovery, recurrence outcomes, and long-term data.

Results

201 studies were identified, of which 4 met the inclusion criteria. None of the studies were randomized controlled trials and all were cohort studies. There was considerable variability in the landmark axial levels and skeletal muscle(s) chosen for analysis, alongside the methods of measuring the cross-sectional area and the parameters used to define sarcopenia. Only two studies identified an increased risk of postoperative complications associated with the presence of sarcopenia. This included an increased risk of hernia recurrence, postoperative ileus and prolonged hospitalisation.

Conclusion

There is some evidence to suggest that BC techniques could be used to help predict surgical outcomes and allow early optimisation in AWH patients. However, the lack of consistency in chosen methodology, combined with the outdated definitions of sarcopenia, makes drawing any conclusions difficult. Whether body composition modification can be used to improve outcomes remains to be determined.
Does linear equating improve prediction in mapping? Crosswalking MacNew onto EQ-5D-5L value sets
Authors: Lamu Admassu N.
Published: April 2020

Purpose

Preference-based measures are essential for producing quality-adjusted life years (QALYs) that are widely used for economic evaluations. In the absence of such measures, mapping algorithms can be applied to estimate utilities from disease-specific measures. This paper aims to develop mapping algorithms between the MacNew Heart Disease Quality of Life Questionnaire (MacNew) instrument and the English and the US-based EQ-5D-5L value sets.

Methods

Individuals with heart disease were recruited from six countries: Australia, Canada, Germany, Norway, UK and the US in 2011/12. Both parametric and non-parametric statistical techniques were applied to estimate mapping algorithms that predict utilities for MacNew scores from EQ-5D-5L value sets. The optimal algorithm for each country-specific value set was primarily selected based on root mean square error (RMSE), mean absolute error (MAE), concordance correlation coefficient (CCC), and r-squared. Leave-one-out cross-validation was conducted to test the generalizability of each model.

Results

For both the English and the US value sets, the one-inflated beta regression model consistently performed best in terms of all criteria. Similar results were observed for the cross-validation results. The preferred model explained 59 and 60% for the English and the US value set, respectively. Linear equating provided predicted values that were equivalent to observed values.

Conclusions

The preferred mapping function enables to predict utilities for MacNew data from the EQ-5D-5L value sets recently developed in England and the US with better accuracy. This allows studies, which have included the MacNew to be used in cost-utility analyses and thus, the comparison of services with interventions across the health system.
QTL analysis of shoot elongation before winter in relation to vernalization requirement in the doubled haploid population L16 × Express617 (Brassica napus L.)
Authors: Ghanbari Mohammad , Paul Madhuri , Möllers Christian
Published: April 2020

In winter oilseed rape shoot elongation before winter is considered as a critical component of the complex trait winter hardiness. Genotypes with an enhanced shoot length before winter are very much prone to frost damage. However, it is not known to which extent shoot elongation before winter is related to vernalization requirement. Shoot length measured 3 months after sowing of winter oilseed rape in spring has been shown to be a good quantitative estimator for vernalization requirement. The main objective of this study was to analyze inheritance of shoot elongation before winter and in spring-sown field experiments using a doubled haploid population derived from the cross between two inbred lines. A SNP based molecular marker map was used to map QTL for shoot length and flowering time. Significant genotypic effects were detected for shoot length before winter and in the spring-sown environment, but there was no correlation between both traits. Six QTL for shoot length before winter contributed 49.2% to the phenotypic variance. For shoot length in the spring-sown environment three QTL were detected that explained 68% of the phenotypic variance. Flowering time genes CONSTANS (BnaC09g41980D), FLC (BnaC09g42060D) and FT (BnaA02g12130D) were identified within C09 and A02 QTL confidence intervals. No collocation of QTL for shoot length before winter and for shoot length in the spring-sown environment was found. Results show that selection for reduced shoot length before winter would be effective and that this trait is inherited largely independent of vernalization requirement.
Revealing cytotoxic substructures in molecules using deep learning
Authors: Webel Henry E. , Kimber Talia B. , Radetzki Silke , Neuenschwander Martin , Nazaré Marc , Volkamer Andrea
Published: April 2020

In drug development, late stage toxicity issues of a compound are the main cause of failure in clinical trials. In silico methods are therefore of high importance to guide the early design process to reduce time, costs and animal testing. Technical advances and the ever growing amount of available toxicity data enabled machine learning, especially neural networks, to impact the field of predictive toxicology. In this study, cytotoxicity prediction, one of the earliest handles in drug discovery, is investigated using a deep learning approach trained on a highly consistent in-house data set of over 34,000 compounds with a share of less than 5% of cytotoxic molecules. The model reached a balanced accuracy of over 70%, similar to previously reported studies using Random Forest. Albeit yielding good results, neural networks are often described as a black box lacking deeper mechanistic understanding of the underlying model. To overcome this absence of interpretability, a Deep Taylor Decomposition method is investigated to identify substructures that may be responsible for the cytotoxic effects, the so-called toxicophores. Furthermore, this study introduces cytotoxicity maps which provide a visual structural interpretation of the relevance of these substructures. Using this approach could be helpful in drug development to predict the potential toxicity of a compound as well as to generate new insights into the toxic mechanism. Moreover, it could also help to de-risk and optimize compounds.