bluuebunny/crossref_metadata_2025 huggingface dataset:
The major constituents of rye (Secale cereale L.) flour and their role in the production of rye bread, a food product to which a multitude of health aspects are ascribed
Authors: Deleu Lomme J. , Lemmens Elien , Redant Lore , Delcour Jan A.
Published: June 2020

Background

Rye (Secale cereale L.) is, second to wheat (Triticum aestivum L.), the most common cereal used for producing bread. Rye‐based breads are of great interest because of their high dietary fiber and lysine contents and because of their health effects. However, the bread‐making performance of rye flour is inferior to that of wheat flour.

Findings

This review summarizes the current knowledge about the major rye constituents (starch, proteins, and arabinoxylans), their role during bread making, and the potential health implications of rye bread consumption. Rye proteins play only a minor role during bread making, but their exact role remains insufficiently explored. In contrast to wheat proteins, they lack the ability to form a network with good gas‐retaining properties. The rye bread crumb structure is partly attributed to its starch and arabinoxylan polysaccharides. Both bind a lot of water, form networks, and bring about the rye bread structure.

Conclusions

Nevertheless, a better understanding of the role of rye starch, proteins, and arabinoxylans, their interactions, and their impact on dough structure or product quality still needs further exploration. In terms of health effects, EFSA has acknowledged that rye fiber contributes to normal bowel function. There are also indications that rye bread consumption has a number of positive effects such as reducing the risk of colon cancer and hunger feelings and cholesterol‐lowering effects. However, although beneficial health effects of rye‐bread consumption are shown, more research is needed.

Significance and novelty

A literature search with the terms “rye” and “review” in Web of Science in April 2020 resulted in only six manuscripts. Therefore, this review summarizes the current knowledge about the major rye constituents (starch, proteins, and arabinoxylans), their role during bread making, and the potential health implications of rye bread consumption.
Post‐thrombectomy intracranial blooming artifact
Authors: Coward John , Prier Jillian , Duda Julian , Yallapragada Anil
Published: June 2020

Mechanical thrombectomy is a procedure used for the treatment of acute ischemic stroke in patients with large vessel occlusions. Usually with a low complication rate, we present a case with a complication post‐thrombectomy not previously described in the literature noted on imaging as “blooming artifact”.
Oxygen‐Vacancy‐Abundant Ferrites on N‐Doped Carbon Nanosheets as High‐Performance Li‐Ion Battery Anodes
Authors: Yue Hailong , Ren Congying , Wang Guangming , Li Guihua , Jin Rencheng
Published: June 2020

Transition metal oxides, as one of the most promising anode materials for lithium‐ion batteries, often suffer from poor electronic conductivity and serious structural collapse. In this work, oxygen‐vacancy‐abundant CoFe2O4 and NiFe2O4 deposited on N‐doped carbon nanosheets are designed and fabricated through a calcination procedure and a solvothermal strategy using Zn‐hexamine coordination frameworks as precursors. The as‐prepared NC@CoFe2O4 and NC@NiFe2O4 hybrids display improved cycle performances and rate capacities compared with CoFe2O4, NiFe2O4, and Fe2O3. The enhanced lithium storage performances of NC@CoFe2O4 and NC@NiFe2O4 are attributed to the oxygen vacancies and conductive N‐doped carbon nanosheets, which increase the electronic conductivity and electrochemical reaction kinetics. The synthetic process in this work provides a new perspective for designing other high‐performance transition metal oxide anodes.
Dual‐Acting Small‐Molecule Inhibitors Targeting Mycobacterial DNA Replication
Authors: Singh Meenakshi , Ilic Stefan , Tam Benjamin , Ben‐Ishay Yesmin , Sherf Dror , Pappo Doron , Akabayov Barak
Published: June 2020

Mycobacterium tuberculosis (Mtb) is a pathogenic bacterium and a causative agent of tuberculosis (TB), a disease that kills more than 1.5 million people worldwide annually. One of the main reasons for this high mortality rate is the evolution of new Mtb strains that are resistant to available antibiotics. Therefore, new therapeutics for TB are in constant demand. Here, we report the development of small‐molecule inhibitors that target two DNA replication enzymes of Mtb, namely DnaG primase and DNA gyrase (Gyr), which share a conserved TOPRIM fold near the inhibitors’ binding site. The molecules were developed on the basis of previously reported inhibitors for T7 DNA primase that bind near the TOPRIM fold. To improve the physicochemical properties of the molecules as well as their inhibitory effect on primase and gyrase, 49 novel compounds have been synthesized as potential drug candidates in three stages of optimization. The last stage of chemical optimization yielded two novel inhibitors for both Mtb DnaG and Gyr that also showed inhibitory activity toward the fast‐growing non‐pathogenic model Mycobacterium smegmatis (Msmg).
Oxidized Hemithioindigo Photoswitches—Influence of Oxidation State on (Photo)physical and Photochemical Properties
Authors: Köttner Laura , Schildhauer Monika , Wiedbrauk Sandra , Mayer Peter , Dube Henry
Published: June 2020

The photophysical and photochemical properties of sulfoxide and sulfone derivatives of hemithioindigo photoswitches are scrutinized and compared to the unoxidized parent chromophores. Oxidation results in significantly blue‐shifted absorptions and mostly reduction of photochromism while thermal stabilities of individual isomers remain largely unaltered. Effective photoswitching takes place at shorter wavelengths compared to parent hemithioindigos and high isomeric yields can be obtained reversibly in the respective photostationary states. Reversible solid‐state photoswitching is observed for a twisted sulfone derivative accompanied by visible color changes. These results establish oxidized hemithioindigo photoswitches as promising and versatile tools for robust light‐control of molecular behavior for a wide range of applications.
Deoxygenation of Epoxides with Carbon Monoxide
Authors: Maulbetsch Theo , Jürgens Eva , Kunz Doris
Published: June 2020

The use of carbon monoxide as a direct reducing agent for the deoxygenation of terminal and internal epoxides to the respective olefins is presented. This reaction is homogeneously catalyzed by a carbonyl pincer‐iridium(I) complex in combination with a Lewis acid co‐catalyst to achieve a pre‐activation of the epoxide substrate, as well as the elimination of CO2 from a γ‐2‐iridabutyrolactone intermediate. Especially terminal alkyl epoxides react smoothly and without significant isomerization to the internal olefins under CO atmosphere in benzene or toluene at 80–120 °C. Detailed investigations reveal a substrate‐dependent change in the mechanism for the epoxide C−O bond activation between an oxidative addition under retention of the configuration and an SN2 reaction that leads to an inversion of the configuration.
Iridium‐Catalyzed Enantioselective C(sp3)–H Borylation of Cyclobutanes
Authors: Chen Xiang , Chen Lili , Zhao Hongliang , Gao Qian , Shen Zhenlu , Xu Senmiao
Published: June 2020

Summary of main observation and conclusion

We herein report the first example of iridium‐catalyzed enantioselective C(sp3)–H borylation of cyclobutanes using benzoxazoline as the directing group. The combination of a chiral bidentate boryl ligand and an iridium precursor has found to effectively catalyze C(sp3)–H borylation to afford a variety of cyclobutylboronates with good to excellent enantioselectivities. We also demonstrate the synthetic utility of the current method by converting the stereogenic C—B bond to other functionalities.
The effect of optic nerve section on form deprivation myopia in the guinea pig
Authors: McFadden Sally A , Wildsoet Christine
Published: June 2020

Myopia is induced when a growing eye wears a diffuser that deprives it of detailed spatial vision (form deprivation, FD). In chickens with optic nerve section (ONS), FD myopia still occurs, suggesting that the signals underlying myopia reside within the eye. As avian eyes differ from mammals, we asked whether local mechanisms also underlie FD myopia in a mammalian model. Young guinea pigs underwent either sham surgery followed by FD (SHAM + FD, n = 7); or ONS followed by FD (ONS + FD, n = 7); or ONS without FD (ONS, n = 9). FD was initiated 3 days after surgery with a diffuser that was worn on the surgically treated eye for 14 days. Animals with ONS + FD developed −8.9 D of relative myopia and elongated by 135 μm more than in their untreated eyes after 2 weeks of FD. These changes were significantly greater than those in SHAM + FD animals (−5.5 D and 40 μm of elongation after 14 days of FD), and reflected exaggerated elongation of the posterior vitreous chamber. The myopia reversed when FD was discontinued, despite ONS, but eyes did not recover back to normal (30 days after surgery, ONS + FD eyes still retained −3 D of relative myopia when SHAM+FD animals had returned to normal). No long‐term residual myopia was present after ONS alone, ruling out a surgical artifact. Although the gross mechanism signaling myopic ocular growth and its recovery in the young mammalian eye does not require an intact optic nerve, its fine‐tuning is disrupted by ONS.
Epidemiology of heart failure
Authors: Groenewegen Amy , Rutten Frans H. , Mosterd Arend , Hoes Arno W.
Published: June 2020

The heart failure syndrome has first been described as an emerging epidemic about 25 years ago. Today, because of a growing and ageing population, the total number of heart failure patients still continues to rise. However, the case mix of heart failure seems to be evolving. Incidence has stabilized and may even be decreasing in some populations, but alarming opposite trends have been observed in the relatively young, possibly related to an increase in obesity. In addition, a clear transition towards heart failure with a preserved ejection fraction has occurred. Although this transition is partially artificial, due to improved recognition of heart failure as a disorder affecting the entire left ventricular ejection fraction spectrum, links can be made with the growing burden of obesity‐related diseases and with the ageing of the population. Similarly, evidence suggests that the number of patients with heart failure may be on the rise in low‐income countries struggling under the double burden of communicable diseases and conditions associated with a Western‐type lifestyle. These findings, together with the observation that the mortality rate of heart failure is declining less rapidly than previously, indicate we have not reached the end of the epidemic yet. In this review, the evolving epidemiology of heart failure is put into perspective, to discern major trends and project future directions.
Synthesis of Isofagomine Derivatives as New Fluorescence pH Indicators/Glycosidase Inhibitors
Authors: Wang Bo , Bogh Sidsel Ammitzbøll , Poulsen Jens Christian Navarro , Laursen Bo W. , Bols Mikael
Published: June 2020

Inhibitor protonation of azasugars of the isofagomine type when bound to enzyme can be investigated using photon induced electron transfer (PET) quenching of an attached fluorophore. For this purpose, Isofagomine, iso‐d‐galacto‐fagomine, and iso‐l‐gulo‐fagomine were converted to N‐(10‐chloroanthracenenyl‐9‐alkyl) derivatives where the alkyl group contained one, two, or three methylene groups. The new derivatives displayed pH dependent fluorescence; as the ammonium forms they were fluorescent, while 90–99 % of the fluorescence was quenched in the amine forms. The 3 isofagomine derivatives were competitive inhibitors of T. Maritima Ι‐glucosidase with Ki values from 0.37–4.6ΤM. Similarly, the iso‐d‐galacto‐fagomines inhibited A. Niger Ι‐galactosidase with Ki values from 63–2000 nm. When bound to the enzymes the inhibitors displayed between 1–15 % fluorescence.
High bioreactor production and emulsifying activity of an unusual exopolymer by Chromohalobacter canadensis 28
Authors: Radchenkova Nadja , Boyadzhieva Ivanka , Hasköylü Merve Erginer , Atanasova Nikolina , Yıldız Songül Yaşar , Kuncheva Margarita J. , Panchev Ivan , Kisov Hristo , Vassilev Spasen , Oner Ebru Toksoy , Kambourova Margarita S.
Published: June 2020

Unusual composition of an exopolymer (EP) from an obligate halophilic bacterium Chromohalobacter canadensis 28 has triggered an interest in development of an effective bioreactor process for its production. Its synthesis was investigated in 2‐L bioreactor at agitation speeds at interval 600‐1000 rpm, at a constant air flow rate of 0.5 vvm; aeration rates of 0.5, 1.0, and 1.5 vvm were tested at constant agitation rate of 900 rpm. EP production was affected by both, agitation and aeration. As a result twofold increase of EP yield was observed and additionally increased up to 3.08 mg/mL in a presence of surfactants. For effective scale‐up of bioreactors mass transfer parameters were estimated and lowest values of KLa obtained for the highest productivity fermentation was established. Emulsification activity of EP exceeded that of trade hydrocolloids xanthan, guar gum, and cellulose. A good synergism between EP and commercial cellulose proved its potential exploration as an enhancer of emulsifying properties of trade emulsions. A pronounced lipophilic effect of EP was established toward olive oil and liquid paraffin. Cultivation of human keratinocyte cells (HaCaT) with crude EP and purified γ‐polyglutamic acid (PGA) showed higher viability than control group.
Theoretical foundations of the Programmatic Action Framework (PAF)
Authors: Bandelow Nils C. , Hornung Johanna , Smyrl Marc
Published: June 2020

This article introduces the Programmatic Action Framework (PAF) as a supplementary perspective in policy process research. It focuses on professional biographies of programmatic actors, policy programs, and programmatic identities as driving factors for policies. Programmatic actors are individuals in direct interaction with the state apparatus. Civil servants, politicians, and similar individuals under certain predictable circumstances form stable alliances called programmatic groups. These programmatic groups are bound by commitment to the creation and promotion of a specific policy program, a definable set of instruments intended to attain an explicit policy objective. This policy program, rather than more diffuse beliefs or preferences, provides the defining element of the social group and corresponding social identity for such programmatic groups. Programmatic groups compete with each other for legitimate authority within and across policy sectors by seeking to impose their preferred instruments. Homogenous career trajectories, continuous linkages, and a coherent and strong joint program are essential determinants for the formation and success of programmatic groups.
Exactly well‐balanced positivity preserving nonstaggered central scheme for open‐channel flows
Authors: Dong Jian , Fang Li Ding
Published: June 2020

In this paper, we construct and study an exactly well‐balanced positivity‐preserving nonstaggered central scheme for shallow water flows in open channels with irregular geometry and nonflat bottom topography. We introduce a novel discretization of the source term based on hydrostatic reconstruction to obtain the exactly well‐balanced property for the still water steady‐state solution even in the presence of wetting and drying transitions. The positivity‐preserving property of the cross‐sectional wet area is obtained by using a modified “draining" time‐step technique. The current scheme is also Riemann‐solver‐free. Several classical problems of open‐channel flows are used to test these properties. Numerical results confirm that the current scheme is robust, exactly well‐balanced and positivity‐preserving.
Outcomes after radiation therapy forT2N0/stageIIglottic squamous cell carcinoma
Authors: Al Feghali Karine A. , Youssef Bassem Y. , Mohamed Abdallah S. R. , Hilal Lara , Smith Blaine D. , Abu‐Gheida Ibrahim , Farha Georges , Gunn G. Brandon , Phan Jack , Lewin Jan , Thekdi Apurva , Morrison William H. , Garden Adam S. , Fuller Clifton David , Rosenthal David I.
Published: June 2020

Background

We report outcomes for patients with T2N0M0 glottic squamous cell carcinoma (SCC) treated with radiation therapy (RT).

Methods

Patients who received definitive RT for T2 glottic SCC from 2000 through 2013 were retrospectively reviewed.

Results

One hundred and thirteen patients were analyzed (median follow‐up time 91 months; 85 patients received three‐dimensional conformal radiotherapy [3D‐CRT] and 28 received intensity‐modulated radiation therapy [IMRT]). Fractionation was conventional (58%) or altered (42%); 20 patients (18%) received concurrent chemotherapy. Five‐year local control was 83% for the 3D‐CRT vs 81% for the IMRT group (P= .76). The ultimate locoregional control at 5 years was 100% for IMRT vs 91% for 3D‐CRT (P= .1). The 5‐year overall survival (OS) was 78% for 3D‐CRT vs 81% for IMRT (P= .83). On multivariate analysis, younger age was the only independent predictor of improved OS (P= .0002).

Conclusions

Oncologic and survival outcomes were excellent for patients with T2N0 glottic cancer. Patients treated with IMRT and 3D‐CRT had no statistically significant differences in all investigated endpoints.
Genetically driven CD39 expression shapes human tumor‐infiltrating CD8+ T‐cell functions
Authors: Gallerano Daniela , Ciminati Selina , Grimaldi Alessio , Piconese Silvia , Cammarata Ilenia , Focaccetti Chiara , Pacella Ilenia , Accapezzato Daniele , Lancellotti Francesco , Sacco Luca , Caronna Roberto , Melaiu Ombretta , Fruci Doriana , D'Oria Valentina , Manzi Emy , Sagnotta Andrea , Parrino Chiara , Coletta Diego , Peruzzi Giovanna , Terenzi Valentina , Battisti Andrea , Cassoni Andrea , Fadda Maria Teresa , Brozzetti Stefania , Fazzi Katia , Grazi Gian Luca , Valentini Valentino , Chirletti Piero , Polimeni Antonella , Barnaba Vincenzo , Timperi Eleonora
Published: June 2020

In our study, we investigated the role of CD39 on tumor‐infiltrating CD8+ T lymphocytes (CD8+ TILs) in colorectal, head and neck and pancreatic cancers. Partially confirming recent observations correlating the CD39 expression with T‐cell exhaustion, we demonstrated a divergent functional activity in CD39+CD8+ TILs. On the one hand, CD39+CD8+ TILs (as compared to their CD39− counterparts) produced significantly lower IFN‐γ and IL‐2 amounts, expressed higher PD‐1, and inversely correlated with perforin and granzyme B expression. On the other, they displayed a significantly higher proliferative capacity ex vivo that was inversely correlated with the PD‐1 expression. Therefore, CD39+CD8+ TILs, including those co‐expressing the CD103 (a marker of T resident memory [TRM] cells), were defined as partially dysfunctional T cells that correlate with tumor patients with initial progression stages. Interestingly, our results identified for the first time a single nucleotide polymorphism (SNP rs10748643 A>G), as a genetic factor associated with CD39 expression in CD8+ TILs. Finally, we demonstrated that compounds inhibiting CD39‐related ATPases improved CD39+CD8+ T‐cell effector function ex vivo, and that CD39+CD8+ TILs displayed effective suppression function in vitro. Overall these data suggest that the SNP analysis may represent a suitable predictor of CD39+CD8+ T‐cell expression in cancer patients, and propose the modulation of CD39 as a new strategy to restore partially exhausted CD8+ TILs.
Clinical pharmacy education and practice evolvement in Malta
Authors: Azzopardi Lilian M. , Serracino‐Inglott Anthony
Published: June 2020

Introduction

Malta, a member state in the European Union, provides an education in line with the requirements for professional registration in Europe including a unique pharmacy education program with patient‐focused practice and synergism between practice, research, and education. A postgraduate Doctorate in Pharmacy program, which runs in collaboration with the College of Pharmacy at the University of Illinois at Chicago provides an opportunity for advanced clinical pharmacy practice and innovative practice research.

Objective

This paper discusses how outcomes of pharmacy education developments have impacted pharmacy practice in Malta.

Methods

Pharmacy education at the University of Malta is examined through an analysis of the facilitators of change, the positiveness of this transformation in pharmacy education, and a critical description of the evolving pharmacy course changes. Objectives and strengths of the changes and how practice research influenced the development of collaborative clinical pharmacy services are described. The uniqueness of clinical pharmacy aspects in community pharmacy, as prompted through educational models, is highlighted. Inspirational aspects through international collaborations, including the establishment of a postgraduate doctorate in pharmacy, are described.

Results

The leveraging of education, practice, and research provided synergism for advancing pharmacy practice which puts the patient in the center. Transformative education models focusing on empowering graduates were developed and practice research was used to advance practice within health systems. Facilitators included particular settings such as the closeness of the family doctors in community pharmacies, the participation of academics in regulatory sciences leadership, and in international collaborations. The postgraduate professional doctorate in pharmacy program that was developed contributes to the advancement of clinical pharmacy both locally and internationally.

Conclusion

The characteristics of pharmacy education in Malta involve the absorption of change in a transformative process that produced positive pharmacy education outcomes and an impact on clinical pharmacy evolvements in both hospital and community practice.
Operating performance and long‐run stock returns following share repurchase: Evidence from an emerging market
Authors: Wang Huabing Barbara , Nguyen Cuong , Dinh Ngoc
Published: June 2020

This study examines the long‐term abnormal returns and operating performance following share repurchase announcements by Vietnamese listed firms. Applying matched control samples based on industry, exchange listing, size plus book‐to‐market, and pre‐event operating performance, we document significantly higher post‐repurchase buy‐and‐hold abnormal returns over the one‐year window. The outperformance becomes insignificant for most control samples with a longer horizon of 2 years after controlling for common pricing factors. Regarding operating performance, our results show improvement for repurchasing firms in the fiscal year concurrent with the repurchase announcements when we adopt the control sample based on pre‐event performance, but we do not find significant differences for the subsequent fiscal year. Examining the relation between the dual phenomena, we find some evidence of positive association in that firms with better post‐repurchase performance tend to have higher post‐event abnormal returns. This relation is stronger for firms with higher completion rates, consistent with the notion that actual repurchase is a stronger and more credible signal to the market.
Prognostic impact of myosteatosis in patients with colorectal cancer: a systematic review and meta‐analysis
Authors: Lee Chan Mi , Kang Jeonghyun
Published: June 2020

Background

Myosteatosis has been reported to be a novel biomarker that could predict survival outcomes in patients with colorectal cancer. However, results have been conflicting. This systematic review and meta‐analysis aimed to evaluate the long‐term impact of myosteatosis on the survival of these patients.

Methods

A systematic search of PubMed, Embase, and Cochrane up to 27 November 2019 generated 7022 records. Studies that reported hazard ratio (HR) for overall survival, cancer‐specific survival, or disease‐free survival based on myosteatosis or radiodensity were included. A total of 110 full‐text articles were considered for inclusion, and 14 were selected for qualitative analysis. Inverse variance method was used with random effects model for data analysis.

Results

The total number of enrolled patients included in the meta‐analysis was 6518 for univariate and 8572 for multivariate HR analysis, from 12 and 10 studies, respectively. Patients with myosteatosis had a significant increase in overall mortality compared with non‐myosteatosis patients by both univariate analysis [HR 1.38, 95% confidence interval (CI) 1.21 to 1.58, P < 0.00001] and multivariate analysis (HR 1.55, 95% CI 1.23 to 1.96, P < 0.00001). In subgroup analysis based on studies that reported HRs of both sarcopenia and myosteatosis, the negative effect of myosteatosis on overall survival was independent of sarcopenia using univariate values (sarcopenia HR 1.48, 95% CI 1.14 to 1.91, P = 0.003 vs. myosteatosis HR 1.51, 95% CI 1.17 to 1.96, P = 0.002) and multivariate values (sarcopenia HR 1.28, 95% CI 1.09 to 1.49, P = 0.002 vs. myosteatosis HR 1.38, 95% CI 1.07 to 1.80, P = 0.001).

Conclusions

This meta‐analysis demonstrates that myosteatosis is associated with worse overall survival in patients with colorectal cancer. More investigation is needed to standardize the measurement protocol for myosteatosis and to further optimize its prognostic power for colorectal cancer patients.
Removal of phosphate from wastewater by steel slag with high calcium oxide column filter system; efficiencies and mechanisms study
Authors: Ahmad Siti Zu Nurain , Hamdan Rafidah , Al‐Gheethi Adel , Alkhadher Sadeq , Othman Norzila
Published: June 2020

BACKGROUND

The discharge of wastewater with heavy loads of phosphorus (P) leads to eutrophication in natural water systems. The current work investigated the removal of P from synthetic wastewater via a slag filtration system with a high content calcium oxide (CaO) filter media (HCa) followed by treatment in an electric arc furnace (EAF). The pH, point of zero charge (PZC) and X‐ray fluorescence (XRF) of the HCa filter medium was studied. The removal of phosphorus was investigated in a designed vertical column filters in aerated HCa (AEF) and unaerated HCa (UEF) systems. Fourier transform infrared (FTIR), X‐ray diffraction (XRD) and scanning electron microscopy with energy dispersive X‐ray (SEM–EDX) analyses was implemented for studying the microstructure of HCa.

RESULTS

The results of XRF revealed that CaO ranged from 20.2 to 49.5%. The PZC for the HCa filter was recorded at pH 17.75. The highest efficiencies recorded were 94.65 ± 3.46% and 96.13 ± 2.75% at pH 3, and 93.70 ± 2.59% and 97.15 ± 1.59% at pH 5 for AEF and UEF, respectively. These findings indicated that AEF performed greater removal than UEF systems, possibly resulting from the presence of high Ca concentration in AEF, which plays an important role in the process of phosphorus removal. The main elements on the surface of HCa included oxygen, carbon, magnesium, Ca, aluminium and silicon. XRD analysis indicated that the precipitation of orthophosphate as Ca and Ca‐phosphates was the removal mechanism, which was confirmed by FTIR analysis.

CONCLUSION

These findings demonstrated the efficiency of HCa in removing P from wastewater. © 2020 Society of Chemical Industry
Early‐onset coenzyme Q10 deficiency associated with ataxia and respiratory chain dysfunction due to novel pathogenic COQ8A variants, including a large intragenic deletion
Authors: Cotta Ana , Alston Charlotte L. , Baptista‐Junior Sidney , Paim Julia F. , Carvalho Elmano , Navarro Monica M. , Appleton Marie , Ng Yi Shiau , Valicek Jaquelin , da‐Cunha‐Junior Antonio L. , Lima Maria I. , de la Rocque Ferreira Alessandra , Takata Reinaldo I. , Hargreaves Iain P. , Gorman Gráinne S. , McFarland Robert , Pierre Germaine , Taylor Robert W.
Published: June 2020

Coenzyme Q10 (CoQ10) deficiency is a clinically and genetically heterogeneous subtype of mitochondrial disease. We report two girls with ataxia and mitochondrial respiratory chain deficiency who were shown to have primary CoQ10 deficiency. Muscle histochemistry displayed signs of mitochondrial dysfunction—ragged red fibers, mitochondrial paracrystalline inclusions, and lipid deposits while biochemical analyses revealed complex II+III respiratory chain deficiencies. MRI brain demonstrated cerebral and cerebellar atrophy. Targeted molecular analysis identified a homozygous c.1015G>A, p.(Ala339Thr) COQ8A variant in subject 1, while subject 2 was found to harbor a single heterozygous c.1029_1030delinsCA variant predicting a p.Gln343_Val344delinsHisMet amino acid substitution. Subsequent investigations identified a large‐scale COQ8A deletion in trans to the c.1029_1030delinsCA allele. A skin biopsy facilitated cDNA studies that confirmed exon skipping in the fibroblast derived COQ8A mRNA transcript. This report expands the molecular genetic spectrum associated with COQ8A‐related mitochondrial disease and highlights the importance of thorough investigation of candidate pathogenic variants to establish phase. Rapid diagnosis is of the utmost importance as patients may benefit from therapeutic CoQ10 supplementation.
Tocilizumab challenge: A series of cytokine storm therapy experiences in hospitalized COVID‐19 pneumonia patients
Authors: Borku Uysal Betul , Ikitimur Hande , Yavuzer Serap , Ikitimur Baris , Uysal Harun , Islamoglu Mehmet Sami , Ozcan Erkan , Aktepe Emre , Yavuzer Hakan , Cengiz Mahir
Published: June 2020

To recognize the period of exaggerated cytokine response in patients with coronavirus disease 2019 (COVID‐19) pneumonia, and to describe the clinical outcomes of using tocilizumab as a treatment option. The data of 12 adult COVID‐19 pneumonia patients who were followed in the inpatient clinics of Biruni University Medical Faculty Hospital (Istanbul, Turkey) were retrospectively analyzed. Diagnostic tests, laboratory examinations, clinical findings, and computed tomography of the thorax imaging results were evaluated. A dramatic laboratory and clinical improvement was observed in 83% (10 out of 12) of patients after tocilizumab. In 17% (2 out of 12) of our patients, short‐term ventilator support was required in the intensive care unit. The longest hospital stay was 18 days. However, in the end, all of our patients were discharged home with good health. Although arterial oxygen saturations (87.58 ± 3.12%) dropped in room air in the pre‐tocilizumab period, post‐tocilizumab they normalized in all patients (94.42 ± 1%). None of them had fever after tocilizumab treatment and the levels of C‐reactive protein (13.08 ± 12.89) were almost within normal limits. Eosinophil values were quite low at the time of diagnosis (10 ± 17.06), but increased significantly post‐tocilizumab (155.33 ± 192.69). There is currently no proven treatment for COVID‐19 induced by novel coronavirus SARS‐CoV‐2. Based on our experience with twelve adult COVID‐19 pneumonia patients, we can say that tocilizumab, an IL‐6 inhibitor, is more beneficial in preventing the damage caused by excessive cytokine response in the body if administered at the right time and provides clinical and radiological recovery.
Unethical leadership and crimes of obedience: A moral awareness perspective
Authors: Javaid Muhammad Fahad , Raoof Rabeeya , Farooq Mariam , Arshad Muhammad
Published: June 2020

As illustrated by the outcomes of recent corporate scandals, crimes of obedience—an individuals' passive response to unethical requests from organizational leaders—can pose a significant threat. How can this threat be avoided? A study based on data collected from employees in public and private sector organizations in Pakistan shows how unethical leadership can influence crimes of obedience and how this effect can be moderated by a sense of moral awareness. The study showed that unethical leadership positively influences the tendency for employees to commit crimes of obedience, but that a sense of moral awareness dampened this effect. Through theoretical justification and empirical testing, the study offers guidance to employers concerning ways to prevent employees committing crimes of obedience and, in addition, contributes to the emerging debate about the influence of unethical leadership in organizations.
Functional characterization and reclassification of an enzyme previously proposed to be a limonoid UDP‐glucosyltransferase
Authors: Cui Youtian , Allmon Steven D , Siegel Justin B
Published: June 2020

BACKGROUND

A major problem in the orange industry is ‘delayed’ bitterness, which is caused by limonin, a bitter compound developing from its non‐bitter precursor limonoate A‐ring lactone (LARL) during and after extraction of orange juice. The glucosidation of LARL by limonoid UDP‐glucosyltransferase (LGT) to form non‐bitter glycosyl‐limonin during orange maturation has been demonstrated as a natural way to debitter by preventing the formation of limonin.

RESULT

Here, the debittering potential of heterogeneously expressed glucosyltransferase, maltose‐binding protein (MBP) fused to cuGT from Citrus unishiu Marc (MBP‐cuGT), which was previously regarded as LGT, was evaluated. A liquid chromatography – mass spectrometry (LC–MS) method was established to determine the concentration of limonin and its derivatives. The protocols to obtain its potential substrates, LARL and limonoate (limonin with both A and D ring open), were also developed. Surprisingly, MBP‐cuGT did not exhibit any detectable effect on limonin degradation when Navel orange juice was used as the substrate; MBP‐cuGT was unable to biotransform either LARL or limonoate as purified substrates. However, it was found that MBP‐cuGT displayed a broad activity spectrum towards flavonoids, confirming that the enzyme produced was active under the conditions evaluated in vitro.

CONCLUSION

Our results based on LC–MS demonstrated that cuGT functionality was incorrectly identified. Its active substrates, including various flavonoids but not limonoids, highlight the need for further efforts to identify the enzyme responsible for LGT activity to develop biotechnology‐based approaches for producing orange juice from varietals that traditionally have a delayed bitterness. © 2020 Society of Chemical Industry
Analysis of cerium oxide and copper oxide nanoparticles bioaccessibility from radish using SP‐ICP‐MS
Authors: Hayder Maria , Wojcieszek Justyna , Asztemborska Monika , Zhou Ying , Ruzik Lena
Published: June 2020

BACKGROUND

The transformation of nanoparticles (NPs) internalized in plant tissues is the human digestive system that can provide a better understanding of the impact of NPs on the human system. The presented methodology was developed to study the bioaccessibility of cerium oxide (CeO2) and copper oxide (CuO) NPs from radish after the in vitro simulation of gastrointestinal digestion using single‐particle inductively coupled plasma mass spectrometry (SP‐ICP‐MS).

RESULTS

Radish plants were cultivated hydroponically in a growth medium containing: (i) CeO2 NPs and (ii) CuO NPs. Both cerium (Ce) and copper (Cu) were found in all organs of the radish plants after analysis by standalone ICP‐MS. This confirms the bioaccumulation of CeO2 and CuO NPs and the translocation of their Ce and Cu to the aerial parts of the plant. Less Ce (4.095 μg g−1) has been detected in leaves than in roots (1.156 mg g−1) while Cu content in leaves was 5.245 μg g−1 and in roots was 10.41 μg g−1. Analysis of the digestive extracts obtained after the in vitro simulation of gastro (pepsin) and gastrointestinal (pancreatin) digestion showed that Ce has easy access to human system at least by 73%.

CONCLUSION

The size of CeO2 NPs in digestive extracts showed no significant changes. However, the results obtained for CuO NPs digestion were variable and suggested that CuO NPs dissolved during the digestion process. The CuO NPs were observed in roots after the gastrointestinal digestion concluding that CuO NPs recovered after the initial dissolution. © 2020 Society of Chemical Industry
Effect of partial replacement of meat by carrot on physicochemical properties and fatty acid profile of fresh turkey sausages: a chemometric approach
Authors: Rocchetti Gabriele , Pateiro Mirian , Campagnol Paulo CB , Barba Francisco J , Tomasevic Igor , Montesano Domenico , Lucini Luigi , Lorenzo Jose M
Published: June 2020

BACKGROUND

This study evaluated the modification of physicochemical characteristics and fatty acid composition of fresh turkey sausages manufactured including carrot (Daucus carota L.) as a vegetable source (i.e., 10%, 20% and 30%, w/w).

RESULTS

The results were compared with sausages used as controls (i.e., containing 100% turkey meat, w/w). Overall, significant differences were detected for all of the evaluated attributes. The inclusion of 20% and 30% carrot (w/w) in the sausages resulted in a reduction of the lipid content (by 5.42 and 5.26 g/100 g, respectively) and reduced energy value (−7.6%). The color parameters were strongly affected by the inclusion of carrot, recording a significant increase in both redness and yellowness. A reduction of Na content (−47.4% on average) was also observed when experimental carrot sausages were compared with control sausages. Interestingly, a significant reduction in the n‐6/n‐3 fatty acids ratio was also detected. A multivariate orthogonal projection to latent structures discriminant analysis (OPLS‐DA) applied to the parameters studied here suggested that the inclusion of carrot provided completely different nutritional and physicochemical profiles, with color parameters possessing the highest discrimination potential.

CONCLUSION

Including carrot in turkey sausages could represent a valuable tool to design healthier meat products. © 2020 Society of Chemical Industry
Development and quality evaluation of banana‐rice‐bean porridge as weaning food for older infants and young children
Authors: Borbi Makafui A. , Dolan Kirk D. , Siddiq Muhammad , Hooper Sharon , Sami Abdul
Published: June 2020

Among low‐income families in developing countries, foods fed to infants and young children are rich in carbohydrates but limiting in protein and important micronutrients. Our objective was to develop a high‐protein weaning food (porridge), with enhanced nutritional contents and acceptable sensory attributes. Cooked light red kidney beans and brown rice and semi‐ripe Cavendish bananas were air‐dried (60°C, 8–16 hr) and milled into flours to formulate seven banana‐rice‐bean (BRB) porridge premixes; 80:10:10, 70:10:20, 70:20:10, 60:25:15, 55:20:25, 50:30:20, and 45:40:15 BRBs, respectively. The premixes were analyzed for nutritional (protein, dietary fiber, resistant starch, minerals) and physical properties (moisture, color, density, water solubility, oil and water absorption capacity). Four prepared porridges were evaluated for selected sensory attributes by 31 African/Asian mothers. All BRB porridge premixes met the World Health Organization recommended levels of protein for complementary foods (5.70–8.52 g/100 g). Resistant starch and dietary fiber contents were 6.35–9.21 and 10.1–11.82 g/100 g, respectively. The oligosaccharide (raffinose, stachyose) ranged from 0.19 to 0.46 mg/g and 3.49–6.27 mg/g, respectively. The Tristimulus color values showed a mixed trend, with significant differences among porridges for CIE L*and a* values and Hue angle, whereas no differences were observed for CIE b* value and Chroma. The sensory quality of all prepared porridges was shown to be acceptable, with scores of 6.5–7.1, on a 9‐point Hedonic scale. Twenty‐nine panelists indicated that they would feed BRB porridge to a child under 5 years old. Overall, the results of this study demonstrated that the BRB porridge could be used as a nutritious weaning food.
Temperature Window for Encapsulation of an Enzyme into Thermally Shrunk, CaCO3 Templated Polyelectrolyte Multilayer Capsules
Authors: Van der Meeren Louis , Li Jie , Konrad Manfred , Skirtach Andre G. , Volodkin Dmitry , Parakhonskiy Bogdan V.
Published: June 2020

Encapsulation of enzymes allows to preserve their biological activities in various environmental conditions, such as exposure to elevated temperature or to proteases. This is particularly relevant for in vivo applications, where proteases represent a severe obstacle to maintaining the activity of enzymes. Polyelectrolyte multilayer capsules are suitable for enzyme encapsulation, where CaCO3 particles and temperature‐dependent capsule formation are the best templates and the most adequate method, respectively. In this work, these two areas are combined and, ALP (alkaline phosphatase), which is a robust and therapeutically relevant enzyme, is encapsulated into thermally shrunk polyelectrolyte multilayer (PDADMAC/PSS)4 capsules templated on calcium carbonate particles (original average diameter: ≈3.5 µm). The activity of the encapsulated enzyme and the optimal temperature range for encapsulation are investigated. The enzymatic activity is almost four times higher upon encapsulation when the temperature range for encapsulation is situated just above the glass transition temperature (40 °C), while its optimal conditions are dictated, on the one hand, by the enzyme activity (better at lower temperatures) and, on the other hand, by the size and mechanical properties of capsules (better at higher temperatures).
Hot corrosion studies of a salt‐coated Ni‐based superalloy under flowing wet air and sulfur vapor ambient
Authors: Liu Hongfei , Chen Shuting , Tan Dennis C. C. , Lee Coryl J. J. , Yao Kui
Published: June 2020

Corrosion of a salt‐coated Ni‐superalloy has been studied at 900°C under a wet air and sulfur vapor ambient. The corrosion thickness, after an incubation of ~60 hr, linearly increases with the corrosion time t and the onset of surface spallation occurred at t ≈ 60 hr. The corroded layer consists of a corrosion front dominated by Cr3S4 scales and linear precipitate structures, an inner corrosion layer dominated by Ni3S2 and NiO, and an outer corrosion layer dominated by Al2O3 networks surrounding the Ni3S2 and/or NiO scale structures. The corrosion mechanism is discussed based on the coexistence of H2O, sulfur, and oxygen.
Physicochemical studies of mild steel corrosion and atmospheric corrosivity mapping of Karachi: An important harbor city of modern Maritime Silk Route
Authors: Zafar Faiza , Bano Humaira , Mahmood Azhar , Corvo Francisco , Rodriguez Joelis
Published: June 2020

This paper has reported physicochemical features of mild steel's corrosion products and provided atmospheric corrosivity maps of Karachi harbor city, drafted on the basis of spatial distribution of corrosion data from July 2018 to June 2019 at 10 different urban, industrial, and marine test sites. Exposure tests have been performed to study atmospheric corrosivity, corrosion products, and corrodants including chloride, sulfur dioxide, time of wetness (TOW), and corrosion rate as per ISO and ASTM standards. Scanning electron microscope, Fourier‐transform infrared spectroscopy, and X‐ray diffraction have corroborated the presence of lepidocrocite, goethite, magnetite, and quartz phases at almost all the test sites, with slight variations in their morphologies and quantities. The data analysis has revealed that TOW is a major detrimental factor to accelerate corrosion of mild steel at Karachi city. The corrosivity category of all urban and marine test sites is found in C4–C5 range, whereas for industrial test sites, it is found in C3–C5 range. Resultant corrosivity maps have shown that the prevailing atmosphere is significantly corrosive at Karachi harbor city. This study has furnished a novel product of atmospheric corrosivity map, which is the first‐ever corrosivity map for Pakistan.
Identification and functional characterization of NAD(P)+‐dependent meso‐diaminopimelate dehydrogenase from Numidum massiliense
Authors: Akita Hironaga , Nakamichi Yusuke , Morita Tomotake , Matsushika Akinori
Published: June 2020

meso‐Diaminopimelate dehydrogenase (meso‐DAPDH) catalyzes the reversible NADP+‐dependent oxidative deamination of meso‐2,6‐diaminopimelate (meso‐DAP) to produce l‐2‐amino‐6‐oxopimelate. Moreover, d‐amino acid dehydrogenase (d‐AADHs) derived from protein‐engineered meso‐DAPDH is useful for one‐step synthesis of d‐amino acids with high optical purity. Here, we report the identification and functional characterization of a novel NAD(P)+‐dependent meso‐DAPDH from Numidum massiliense (NmDAPDH). After the gene encoding the putative NmDAPDH was expressed in recombinant Escherichia coli cells, the enzyme was purified 4.0‐fold to homogeneity from the crude extract through five purification steps. Although the previously known meso‐DAPDHs use only NADP+ as a coenzyme, NmDAPDH was able to use both NADP+ and NAD+ as coenzymes. When NADP+ was used as a coenzyme, NmDAPDH exhibited an approximately 2 times higher kcat/Km value toward meso‐DAP than that of meso‐DAPDH from Symbiobacterium thermophilum (StDAPDH). NmDAPDH also catalyzed the reductive amination of corresponding 2‐oxo acids to produce acidic d‐amino acids such as d‐aspartate and d‐glutamate. The optimum pH and temperature for the oxidative deamination of meso‐DAP were about 10.5 and 75°C, respectively. Like StDAPDH, NmDAPDH exhibited high stability: it retained more than 75% of its activity after 30 min at 60°C (pH 7.2) or at pHs ranging from 5.5 to 13.0 (50°C). Alignment of the amino acid sequences of NmDAPDH and the known meso‐DAPDHs suggested NmDAPDH has a hexameric structure. Given its specificity for both NADP+ and NAD+, high stability, and a broad range of reductive amination activity toward 2‐oxo acids, NmDAPDH appears to offer advantages for engineering a more effective d‐AADH.
Is viral E6 oncoprotein a viable target? A critical analysis in the context of cervical cancer
Authors: Kumar Avinash , Rathi Ekta , Hariharapura Raghu Chandrashekar , Kini Suvarna G.
Published: June 2020

An understanding of the pathology of cervical cancer (CC) mediated by E6/E7 oncoproteins of high‐risk human papillomavirus (HPV) was developed by late 80's. But if we look at the present scenario, not a single drug could be developed to inhibit these oncoproteins and in turn, be used specifically for the treatment of CC. The readers are advised not to presume the “viability of E6 protein” as mentioned in the title relates to just druggability of E6. The viability aspect will cover almost everything a researcher should know to develop E6 inhibitors until the preclinical stage. Herein, we have analysed the achievements and shortcomings of the scientific community in the last four decades in targeting HPV E6 against CC. Role of all HPV proteins has been briefly described for better perspective with a little detailed discussion of the role of E6. We have reviewed the articles from 1985 onward, reporting in vitro inhibition of E6. Recently, many computational studies have reported potent E6 inhibitors and these have also been reviewed. Subsequently, a critical analysis has been reported to cover the in vitro assay protocols and in vivo models to develop E6 inhibitors. A paragraph has been devoted to the role of public policy to fight CC employing vaccines and whether the vaccine against HPV has quenched the zeal to develop drugs against it. The review concludes with the challenges and the way forward.