bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening of surface exposed lipoproteins of Leptospira involved in modulation of host innate immune response
Authors: Kumar Ajay , Varma Vivek P. , Faisal Syed M.
Published: August 2021

Leptospira, a zoonotic pathogen is capable of causing both chronic and acute infection in susceptible host. Surface exposed lipoproteins play major role in modulating the host immune response by activating the innate cells like macrophages and DCs or evading complement attack and killing by phagocytes like neutrophils to favour pathogenesis and establish infection. In this study we screened some of surface exposed lipoproteins which are known to be involved in pathogenesis for their possible role in immune modulation (innate immune activation or evasion). Surface proteins of Len family (LenB, LenD, LenE), Lsa30, Loa22 and Lipl21 were purified in recombinant form and then tested for their ability to activate macrophages of different host (mouse, human and bovine). These proteins were tested for binding with complement regulators (FH, C4BP), host protease (plasminogen, PLG) and as nucleases to access their possible role in innate immune evasion. Our results show that of various proteins tested Loa22 induced strong innate activation and Lsa30 was least stimulatory as evident from production of pro-inflammatory cytokines (IL-6, TNF-a) and expression of surface markers (CD80, CD86, MHCII). All the tested proteins were able to bind to FH, C4BP and PLG, however Loa22 showed strong binding to PLG correlating to plasmin activity. All the proteins except Loa22 showed nuclease activity albeit with requirement of different metal ions. The nuclease activity of these proteins correlated to in vitro degradation of Neutrophil extracellular trap (NET). These results indicate that these surface proteins are involved in innate immune modulation and may play critical role in assisting the bacteria to invade and colonize the host tissue for persistent infection.
A nitrite-oxidizing bacterium constitutively consumes atmospheric hydrogen
Authors: Leung Pok Man , Daebeler Anne , Chiri Eleonora , Cordero Paul R. F. , Hanchapola Iresha , Gillett David L. , Schittenhelm Ralf B. , Daims Holger , Greening Chris
Published: August 2021

Chemolithoautotrophic nitrite-oxidizing bacteria (NOB) of the genus Nitrospira contribute to nitrification in diverse natural environments and engineered systems. Nitrospira are thought to be well-adapted to substrate limitation owing to their high affinity for nitrite and capacity to use alternative energy sources. Here, we demonstrate that the canonical nitrite oxidizer Nitrospira moscoviensis oxidizes hydrogen (H2) below atmospheric levels using a high-affinity group 2a nickel-iron hydrogenase [Km(app) = 32 nM]. Atmospheric H2 oxidation occurred under both nitrite-replete and nitrite-deplete conditions, suggesting low-potential electrons derived from H2 oxidation promote nitrite-dependent growth and enable survival during nitrite limitation. Proteomic analyses confirmed the hydrogenase was abundant under both conditions and indicated extensive metabolic changes occur to reduce energy expenditure and growth under nitrite-deplete conditions. Respirometry analysis indicates the hydrogenase and nitrite oxidoreductase are bona fide components of the aerobic respiratory chain of N. moscoviensis, though they transfer electrons to distinct electron carriers in accord with the contrasting redox potentials of their substrates. Collectively, this study suggests atmospheric H2 oxidation enhances the growth and survival of NOB in amid variability of nitrite supply. These findings also extend the phenomenon of atmospheric H2 oxidation to a seventh phylum (Nitrospirota) and reveal unexpected new links between the global hydrogen and nitrogen cycles.
Frequent Aneuploidy in Primary Human T Cells Following CRISPR-Cas9 cleavage
Authors: Nahmad A.D. , Reuveni E. , Goldschmidt E. , Tenne T. , Liberman M. , Horovitz-Fried M. , Khosravi R. , Kobo H. , Reinstein E. , Madi A. , Ben-David U. , Barzel A.
Published: August 2021

Multiple ongoing clinical trials use site-specific nucleases to disrupt T cell receptor (TCR) genes in order to allow for allogeneic T cell therapy1–5. In particular, the first U.S. clinical trial using CRISPR-Cas9 entailed the targeted disruption of the TCR chains and programmed cell death protein 1 (PDCD1) in T cells of refractory cancer patients6. Here, we used the same guide RNA sequences and applied single-cell RNA sequencing (scRNAseq) to more than 7000 primary human T cells, transfected with CRISPR-Cas9. Four days post-transfection, we found a loss of chromosome 14, harboring the TCRα locus, in up to 9% of the cells, and a chromosome 14 gain in up to 1.4% of the cells. We further identified truncations of chromosome 7, harboring the TCRβ locus, in 9.9% of the cells. Loss of heterozygosity (LOH) was further validated using fluorescencein situhybridization (FISH) and the temporal dynamics of cleavage and incomplete repair were monitored using digital droplet PCR (ddPCR). Aneuploidy was found among all T cell subsets and was associated with transcriptional signatures of reduced proliferation and metabolism as well as with induced p53 activation and cell death. We conclude that aneuploidy and chromosomal truncations are frequent outcomes of CRISPR-Cas9 cleavage in clinical protocols. Monitoring and minimizing these aberrant products is crucial for future applications of genome editing in T cell engineering and beyond.
Two crystallographic forms and the absolute structure of 5α,14α-androstane
Authors: Crittenden Christopher M. , DiPasquale Antonio G.
Published: August 2021

5α,14α-Androstane (C19H32) crystallizes in two different polymorphic forms in the same vapor diffusion experiment. The major form (Form I) crystallizes as thin plates in the space group P21, with Z = 4. These plates are twinned along a long c axis of length 43 Å and readily suffer from radiation damage when diffracted. The minor form (Form II) crystallizes as fine needles in the space group P212121, Z = 3. In the minor form, 5α,14α-androstane cocrystallizes with 5α,14α-androstan-17-one, an oxidation product of 5α,14α-androstane. The presence of 5α,14α-androstan-17-one in the minor form of the crystals was confirmed by HR-MS. Form II can be crystallized as a pure form without the ketone impurity using a different solvent system. High level density functional theory (DFT) lattice free energy calculations were performed and show that both pure forms are isoergic within the estimated error of the calculations.
Crystal structure of bis[cis-diaquabis(phenanthroline)cobalt(II)] bis(citrato)germanate(IV) dinitrate
Authors: Buchko Olha , Dyakonenko Viktoriya , Martsinko Elena , Chebanenko Elena
Published: August 2021

The asymmetric unit of the title compound, [Co(C12H8N2)2(H2O)2]2[Ge(C6H5O7)2](NO3)2, features two complex [(C12H8N2)2(H2O)2Co]2+ cations, two NO3
− anions as well as one centrosymmetric [(C6H5O7)2Ge]2− anion. Two HCit ligands (Cit = citrate, C6H4O7) each coordinate via three different oxygen atoms (hydroxylate, α-carboxylate, β-carboxylate) to the Ge atom, forming a slightly distorted octahedron. The coordination polyhedron of the Co atom is also octahedral, formed by coordination of four nitrogen atoms from two phenanthroline molecules and two water oxygen atoms. In the crystal, the cations and anions are linked by hydrogen bonds and form layers parallel to the bc plane. The structure exhibits disorder of the NO3
− anion [disorder ratio 0.688 (9) to 0.312 (9)]. There are also highly disordered solvent molecules (presumably water and/or ethanol) in the crystal structure; explicit refinement of these molecules was not possible, and the content of the voids was instead taken into account using reverse Fourier transform methods [SQUEEZE procedure in PLATON; Spek (2015). Acta Cryst. C71, 9–18]. The given chemical formula and other crystal data do not take into account the unknown solvent molecule(s).
Trends and characteristics of China's medical informatization policy from 1996 to 2020: a bibliometric analysis
Authors: Xu Man , Gan Dan , Pan Ting , Sun Xiaohan
Published: August 2021

Purpose

Qualitative methods are not suitable to process high volumes of policy texts for exploring policy evolution. Therefore, it is hard to use qualitative methods to systematically analyze the characteristics of complex policy networks. So the authors propose a bibliometric research study for exploring policy evolution from time–agency–theme perspectives to excavate the rules and existing problems of China's medical informatization policy and to provide suggestions for formulating and improving the future medical informatization policies.

Design/methodology/approach

Initially, 615 valid samples are obtained by retrieving related China's medical informatization policy documents, and the joint policy-making agency network and the co-occurrence network models of medical informatization policies are defined, and then the authors research China's medical informatization policies from single-dimension and multi-dimension view.

Findings

The analysis results reveal that China's medical informatization policy process can be divided into four stages; the policy-making agencies are divided into four subgroups by community detection analysis according to the fast unfolding algorithm; the core policy theme keywords are identified based on the eigenvector centrality of the nodes in those networks; the focuses of theme terms are varied in different stages and the correlations between agencies and themes are gradually decentralized.

Practical implications

These findings provide experience and evidence on leveraging informatics in the medical and healthcare field of China. Also, they can help scholars and practitioners better understand the current status and future directions of medical and healthcare informatics development in China and provide a reference to formulate and improve China's future medical informatization policies.

Originality/value

This study proposes a quantitative bibliometric-based research framework to describe transitions and trends of China's medical informatization policy.
Meta-frontier and measures of efficiency emphasising optimal corporate governance risk across countries
Authors: ElKelish Walaa Wahid , Zervopoulos Panagiotis
Published: August 2021

Purpose

This paper aims to investigate the internal and external determinants of firms’ efficiency and develop optimal corporate governance risk benchmarks for the manufacturing sector across different countries.

Design/methodology/approach

Corporate governance risk data were acquired from Institutional Shareholder Services Europe SA. Data on firms’ efficiency and for explanatory and control variables were taken from the DataStream database. The generalised directional distance function data envelopment analysis (GDDF-DEA) model and its stochastic extension provided corporate efficiency measures and optimal corporate governance benchmarks. The authors used ordinary least squares multiple regression analysis with wild bootstrapping to test the study hypotheses.

Findings

The authors found significant differences between firms’ optimal and actual efficiency input/output variables and corporate governance risks in the manufacturing sector across countries. Internal firm characteristics such as group affiliations, product market competition and insider ownership and external institutional factors such as the legal system, the rule of law, control of corruption, law enforcement and cultural values are vital determinants of firms’ efficiency.

Practical implications

This paper provides valuable guidance to enable corporate managers, regulators and policymakers to enhance firms’ efficiency and corporate governance practices.

Originality/value

This paper develops optimal corporate governance risk benchmarks and identifies the most critical internal and external factors affecting firms’ efficiency in the manufacturing sector in various countries. It also used a novel GDDF-DEA model, with the multi-parametric model for bias correction of efficiency estimator.
The internet of things in upscale hotels: its impact on guests’ sensory experiences and behavior
Authors: Pelet Jean-Éric , Lick Erhard , Taieb Basma
Published: August 2021

Purpose

This study bridges the gap between sensory marketing and the use of the internet of things (IoT) in upscale hotels. This paper aims to investigate how stimulating guests’ senses through IoT devices influenced their emotions, affective experiences, eudaimonism (well-being), and ultimately, guest behavior. The authors examined the potential moderating effects of gender.

Design/methodology/approach

Research conducted comprised an exploratory study, which consisted of interviews with hotel managers (Study 1) and an online confirmatory survey (n = 357) among hotel guests (Study 2).

Findings

The results showed that while the senses of smell, hearing and sight had an impact on guests’ emotions, the senses of touch, hearing and sight impacted guests’ affective experiences. The senses of smell and taste influenced guests’ eudaimonism. The sense of smell had a greater effect on eudaimonism and behavioral intentions among women compared to men.

Research limitations/implications

This study concentrated on upscale hotels located in Europe. Further research may explore the generalizability of the findings (e.g. in other cultures, comparison between high-end and low-end hotels).

Practical implications

Managers of upscale hotels should apply congruent sensory stimuli from all five senses. Stimuli may be customized (“SoCoIoT” marketing). IoT in hotels may be useful in the aftermath of the COVID pandemic, as voice commands help guests avoid touching surfaces.

Originality/value

IoT can be applied in creating customized multi-sensory hotel experiences. For example, hotels may offer unique and diverse ambiances in their rooms and suites to improve guest experiences.
Nonlinear modelling and finite element analysis on the load-bearing capacity of RC beams with considering the bond–slip effect
Authors: Pandimani Pandimani , Ponnada Markandeya Raju , Geddada Yesuratnam
Published: August 2021

Purpose

This paper aims to present nonlinear numerical simulations using the versatile finite element (FE) analysis tool ANSYS and theoretical analysis based on code provisions to assess the load-carrying capacity of reinforced concrete (RC) beams under two-point monotonic static loadings.

Design/methodology/approach

Four quarter-size FE models with load and geometry symmetry conditions were constructed, the load-bearing capacity and associated mid-span deflections at critical points are verified against the full-scale experimental RC beams available in the literature. These developed FE models incorporated the tension stiffening effects and bond–slip behaviour. Theoretical analyses based on Indian standard code IS: 456–2000 and ACI 318–19 were also carried to verify the experimental and numerical predicted moments at critical loading points.

Findings

The load-deflection curves predicted through FE models exhibit closer corroboration with the experimental curves throughout the loading history. The contour plots for deflections, concrete principal stresses, reinforcement yield stresses are satisfactorily predicted by the FE models, which reveal the complete information of nonlinear behaviour of RC beams. The developed model well captured the initial and progressive crack patterns at each load increments.

Practical implications

The FE modelling is an efficient, valid and economical tool that is an alternative to the expensive experimental program and can be used to explore, analyse and fully understand the nonlinear response of RC beams under static loadings.

Originality/value

The ultimate moment capacity evaluated based on ACI 318–19 code provision show a better correlation with the experimental data as compared to the IS: 456–2000 code provision. The ultimate loads and associated centre-span deflections predicted by RN-2, RN-3, RB-12 and RB-16 FE model show a discrepancy of 1.66 and –0.49%, –4.68 and –0.60%, –9.38 and –14.53% and –4.37 and 4.21%, respectively, against the experimental results, which reveals that the developed ANSYS FE models predict consistent results and achieved a reasonable agreement with the experimental data.
Influence of COVID-19 pandemic on local construction firms’ viability
Authors: Oladimeji Olubimbola
Published: August 2021

Purpose

This paper aims to assess COVID-19 (C-19) pandemic influence in the 37 factors identified from extant literature as factors influencing the viability of local construction firms (LCFs).

Design/methodology/approach

A sample size of 65 staff of 31 LCFs that were awarded construction projects contracts in institutions in Nigeria was purposefully selected and accessed based on relevant predetermined criteria. Respondents’ views on factors determining the viability of LCFs were obtained. Factors known to be influenced by C-19 are 25 of the 37 factors rated on a five-point Likert scale of importance by the respondents. Mean scores were used to rank the factors and principal component analysis was used to obtain key component factors (CFs) influenced by the C-19 pandemic.

Findings

Six of the first ten “extremely important” and “very important” factors are known to be influenced by C-19 pandemic. A total of 8 CFs having 20 variables with factor loadings of more than 0.5 each were known to be influenced by C-19. The C-19 pandemic influenced LCFs’ cash flow and management of construction labour, plant and equipment amidst variables that had above 0.8 factor loading.

Research limitations/implications

A limitation of this study is the inability to conduct close contact interview during this period to obtain personal views on the influence of C-19 on LCFs. However, this does not reduce the quality of findings of this study, as there are valid literature basis hinging this study findings.

Practical implications

The paper recommends that all stakeholders pay prompt attention to the factors adversely affected by the C-19 pandemic to improve or at the least sustain the viability of LCFs.

Originality/value

This paper fulfils a present pertinent need of assessing the influence of the C-19 pandemic on various factors influencing the viability of construction firms.
Viewpoint – a big opportunity for interactive marketing post-COVID-19
Authors: McDonald Malcolm
Published: August 2021

Purpose

The objective of this short research-informed, practitioner-orientated paper is to provide a viewpoint on interactive marketing pre and post COVID-19.

Design/methodology/approach

This is a conceptual article designed to articulate a viewpoint that despite COVID-19 the strategic considerations that marketers need to make remain unchanged.

Findings

As a result of the pandemic, there is much more obvious use of interactivity in other, aligned functions such as sales and customer services. The effectiveness of interactive marketing will only be increased by having focus on the fundamental roles of the marketing discipline, strategy and segmentation, and understanding customers at the individual level. We also need reminding briefly that the rules of competition had changed well before the COVID-19 pandemic. The traditional make and sell model has been substantially replaced by new technology-enabled organisations without the restrictions of high fixed costs and cloying bureaucracy. Customers can now search for and evaluate products and services independent of suppliers and now have as much information about suppliers as suppliers have of customers. This is the backcloth against which marketers face the challenges at the beginning of 2021. We conclude that there is a great future ahead. There is no reason why the best of interactive marketing will not be capable of building relationships that are great for customers, great for the people who create them, great for all stakeholders and great for the environment.

Originality/value

This is a practitioner viewpoint outlining the view that COVID-19 has not had as great of an impact on interactive marketing practice as technological change has and that interactive marketing will continue to develop after COVID-19 has receded.
Dialogic accounting through popular reporting and digital platforms
Authors: Grossi Giuseppe , Biancone Paolo Pietro , Secinaro Silvana , Brescia Valerio
Published: August 2021

Purpose

The purpose of this study is to explore the usefulness of popular reporting (PR) in an Italian city as a dialogic accounting tool for promoting citizens’ engagement with digital platforms. This study aims to contribute to the debate on democratic accounting technologies with a focus on PR and digital platforms, using the theoretical lens of dialogic accounting.

Design/methodology/approach

A longitudinal case study is used to analyse the implementation and evolution of PR in the city of Turin, Italy and explore how the city involved its citizens with digital platforms.

Findings

This study contributes to the debate on public accountability through dialogic accounting tools.

Research limitations/implications

Multiple sources (surveys, interviews and interventionist workshops) are used to analyse Turin, Italy as a longitudinal case study.

Practical implications

This study offers practical reflections for legislators, politicians and public managers who need new knowledge and empirical analysis of the effective implementation of the PR as a tool for dialogue and empowering public accounting to hold continuous dialogue with the citizens.

Originality/value

PR can be considered a useful dialogic accounting tool for politicians, managers and government experts to encourage citizens’ engagement in a pluralistic society.
Toward a taxonomy of dynamic capabilities – a systematic literature review
Authors: Leemann Niklaus , Kanbach Dominik K.
Published: August 2021

Purpose

This paper aims to categorize and organize dynamic capabilities that have been inductively identified in empirical research into a comprehensive taxonomy. Thus, it addresses calls in the literature for a better understanding of dynamic capabilities and integration of scattered empirical findings into theory.

Design/methodology/approach

A systematic literature review approach was adopted, with a total of 34 articles published between August 2007 and April 2020, from which 240 idiosyncratic dynamic capabilities were identified. The taxonomy was constructed using the Gioia-method.

Findings

The main finding is a three-level taxonomy of dynamic capabilities (DC). Level DC-1 is based on the existing triad of sensing, seizing and transforming. Level DC-2 is newly introduced to the literature by this study, consisting of 19 dynamic sub-capabilities that categorize and organize all 240 idiosyncratic dynamic capabilities in the sample (level DC-3). The taxonomy supports the existing claim that dynamic capabilities are common in key features and idiosyncratic in details. Moreover, theoretical connections to business model innovation and ambidexterity are indicated.

Practical implications

This study integrates scattered empirical findings of specific dynamic capabilities and translates them to a practitioner audience. The taxonomy allows the strategic manager to understand what they specifically are and, thus, assess the dynamic capability endowment of the firm which allows deploying, developing and fostering them.

Originality/value

The taxonomy provides a comprehensive and tangible picture of what dynamic capabilities look like in practice. It improves existing knowledge and understanding by bridging the rigor-relevance gap between rather rigorous conceptual literature and rather relevant empirical research as it integrates them. As such, it can serve as a “map” of dynamic capabilities for scholars and practitioners.
Novel study of using chitosan in gamma dose monitoring applications
Authors: Bekhit Mohamad , Fahim Essam , Sobhy Asmaa
Published: August 2021

Purpose

The purpose of this paper is to fall light on the possibility of using the biopolymer chitosan in gamma dose monitoring.

Design/methodology/approach

The chitosan films were irradiated to gamma rays in the range starting from 10 to 120 kGy at a dose rate of 1.4 kGy/h using 60Co gamma source. The ultra violet and visible (UV/Vis) spectrophotometry were used to examine the optical properties of chitosan film. Also, Fourier transform infrared (FTIR) analysis was used to detect and trace any change in structural bands that may take place upon irradiation.

Findings

Increase in optical density of the chitosan film was recorded at 298 nm that correlated with increasing in the absorbed doses. Change in color of the film from pale yellow to denser yellow was detected upon increasing the absorbed doses. The close investigation for UV/Vis and FTIR analysis nominates the chitosan film to be used as a label-dosimeter in the range of 10–120 kGy depending on chitosan concentrations. The chitosan film has an excellent stability in different environmental conditions with ±3.7% uncertainty in measurements (2σ, approximately equal to a 95% confidence level).

Research limitations/implications

Chitosan film may be used as a medium and high-dose monitor with an acceptable overall uncertainty in routine radiation processing

Originality/value

The useful dose range from 10 to 80 kGy was detected for different concentrations of chitosan (0.5, 1, 1.5 Wt%) that correlated with increasing the absorbed dose, which is assigned to the linear parts in the target response curves. For the dose range 10–120 kGy, the film may be used as label dosimeter with detected color change from pale yellow to dense yellow.
The informal culture of a direct care staff team supporting people with intellectual disabilities who present with behaviours that challenge: commentary
Authors: Beadle-Brown Julie
Published: August 2021

Purpose

The purpose of this paper is to provide a commentary on Banks et al. and sets the wider context.

Design/methodology/approach

It provides a brief narrative review of the literature on the factors that determine the quality of life of people with intellectual disabilities, including the impact of culture.

Findings

Key to ensuring good quality of life outcomes is support that is facilitative, enabling and empowering which can compensate for severity of disability and improve people’s experiences. This approach is called Active Support. Improving quality of life is a key part of preventing and responding to behaviours that challenge. Culture is an important factor in ensuring staff are motivated to work in such ways but is likely to be intertwined with many other factors.

Originality/value

This paper summarises the key literature on what is needed to improve outcomes for people with intellectual disabilities. It introduces the importance of exploring how the different dimensions of culture interact and how culture, practice, processes and structures might work in a much more complex and intertwined fashion than previously conceptualised.
Making the world a better place: achieving impact through innovation and an entrepreneurial ethos
Authors: Pepin John
Published: August 2021

Purpose

The purpose of this paper is to describe and evaluate the programme of philanthropy arising from the work of the Shirley Foundation, with particular reference to its impact in addressing issues related to autism.

Design/methodology/approach

The paper is based on the 2017 evaluation of The Shirley Foundation 1996–2016 by Aperio Group (Europe) Limited entitled 20 Years of Grant Making Autism and Information Technology: An Overview of The Foundation’s Impact (Pepin, 2017). The evaluation included interviews with Dame Stephanie Shirley CH (the Foundation’s founder), a documentation review and a survey of key grantees.

Findings

The evaluation concluded that the funding achieved both grantee purposes and those of The Shirley Foundation. The projects funded generally produced outcomes that made a difference and grant-making and monitoring processes were regarded, on the whole, as efficient.

Originality/value

The evaluation demonstrates the value of an innovative, catalytic, social entrepreneurial approach to funding to achieve impact.
Sleep disturbance in clients attending a specialist addiction clinic
Authors: Ogeil Rowan P. , Arunogiri Shalini , Petersen Vanessa , Gooden James R. , Lubman Dan I.
Published: August 2021

Background and Objectives

Sleep problems are common among clients attending alcohol and drug services, yet the specific components of sleep disturbed by primary drug of concern (PDOC), and their relationships to affective disorder symptoms are unclear.

Methods

We examined sleep problems in clients (n = 32) attending a specialist addiction clinic.

Results

Global sleep quality was rated poor by >90% of participants (particularly disturbances, latency and efficiency components), with significant associations (p < .05) between poor sleep quality and depression (r = .517), anxiety (r = .571) and stress (r = .503). Sleep quality was significantly poorer among those with a nonalcohol PDOC compared with alcohol as PDOC, t(22) = 3.09, p = .005.

Conclusion and Scientific Significance

Poor sleep is almost ubiquitous among clients attending alcohol and drug services. However, components of sleep quality disturbed differ in terms of PDOC, highlighting the need for individualised sleep interventions.
Impact of different levels of low‐fat dried distillers grains on performance of young Nellore bulls during the finishing phase
Authors: Alhadas Herlon M. , Valadares Filho Sebastião C. , Tedeschi Luis O. , Vilela Rizielly S. R. , Souza Gilyard A. P. , Lage Bruno C. , Silva Breno C. , Rennó Luciana N. , Paulino Mario F.
Published: August 2021

This study evaluated the effect of including low‐fat dried distillers grains (DDG) on young Nellore bulls performance, nutritional parameters, and nitrogen metabolism. Thirty‐five Nellore cattle were randomly divided into four diets: without dried distillers grains (D0) or with the inclusion of DDG at 150 g/kg (D150), 300 g/kg (D300), or 450 g/kg (D450). The evaluation period lasted 126 days, and three periods of collection of feces and urine were carried out. Final body weight (P = 0.099) and average daily gain (P = 0.097) tended to decrease linearly; the digestibility of dry matter (P < 0.001), organic matter (P < 0.001), ether extract (P < 0.001) and nonfiber carbohydrates (P < 0.001), and intakes of total digestible nutrients (TDN, P < 0.001) decreased linearly. The increase in crude protein intake (P < 0.001) did not result in an increase in the amount of nitrogen retained (P = 0.540). We concluded that the inclusion of low‐fat DDG in finishing diets up to the level of 450 g/kg tends to reduce animal performance and the intake of TDN.
Concentration‐QT modelling in early clinical oncology settings: Simulation evaluation of performance
Authors: Cantet Gael , Berges Alienor , O'Sullivan Rhianna , Cohen‐Rabbie Sarit , Dota Corina , Dubois Vincent , Benoist Guillemette E. , Tomkinson Helen , Rekić Dinko , Parkinson Joanna , Schalkwijk Stein
Published: August 2021

Aims

Concentration‐QT modelling (C‐QTc) of first‐in‐human data has been rapidly adopted as the primary evaluation of QTc interval prolongation risk. Here, we evaluate the performance of C‐QTc in early oncology settings (i.e., patients, no placebo or supratherapeutic dose, 3 + 3 designs).

Methods

C‐QTc performance was evaluated across three oncology scenarios using a simulation‐estimation approach: (scen1) typical dose‐escalation testing six dose levels (n = 21); (scen2) small dose‐escalation testing two dose levels (n = 9); (scen3) expansion cohorts at one dose level (n = 6–140). True ΔΔQTc effects ranged from 3 ms (“no effect”) to 20 ms (“large effect”). Performance was assessed based on the upper limit of the ΔQTc two‐sided 90% CI against a threshold of 10 or 20 ms.

Results

The performance against the 10 ms threshold was limited based on C‐QTc data from typical dose escalation (scen1) and acceptable performance was observed only for relatively large expansions (n ≥ 45; scen3). Performance against the 20 ms threshold was acceptable based on C‐QTc data from a typical dose escalation (scen1) or dose expansion cohort n > 10 (scen3). In general, pooling C‐QTc data from dose escalation and expansion cohorts substantially improved the performance and reduced the ΔQTc 90% CI width.

Conclusion

C‐QTc performance appeared limited using a 10 ms threshold, but acceptable against a 20 ms threshold. Selection of threshold may be informed by the benefit–risk balance in a specific disease area. Acceptable precision (i.e., confidence intervals) of the estimated ΔQTc, regardless of its magnitude, can be facilitated by pooling data from dose escalation and expansion cohorts.
Integrated source rock evaluation along the maturation gradient. Application to the Vaca Muerta Formation, Neuquén Basin of Argentina
Authors: Spacapan J. B. , Comerio M. , Brisson I. , Rocha E. , Cipollone M. , Hidalgo J. C.
Published: August 2021

The Vaca Muerta Formation (Tithonian–early Valanginian) is the main source rock in the Neuquén Basin and the most important unconventional shale resource in South America. In the present study, organic geochemistry, electron microscopy and basin and petroleum system modelling (BPSM) were combined to evaluate source rock properties and related processes along a transect from the early oil (east) to the dry gas (west) window. The unit is characterized by high present‐day (1%–8% average) and original (2%–16% average) total organic carbon contents, which increase towards the base of the unit and basinal (west) settings. Scanning electron microscopy shows that organic pores derived from the transformation of type II kerogen. Isolated bubble pores are typical of the oil window, whereas bubble and densely distributed spongy pores occur in the gas stage, indicating that the maturity gradient exerts strong control on organic porosity. Organic geochemistry, pressure and porosity data were incorporated into a 2D basin petroleum system model that includes the sequential restoration of tectonic events and calculation of compaction trends, kerogen transformation, hydrocarbon generation and estimation of pore pressure through geologic time. The W–E regional model extends from the Agrio Fold and Thrust Belts to the basin border and allows us to evaluate the relationship between thermal maturity and timing of hydrocarbon generation from highly deformed (west) to undeformed (east) regions. Modelling results show a clear decrease in maturity and organic matter (OM) transformation towards the eastern basin margin. Maximum hydrocarbon generation occurred in the inner sectors of the belt, at ca. 120 Ma; long before the first Andean compression phase, which started during the Late Cretaceous (ca. 70 Ma). Miocene compression (15–7 Ma) promoted tectonic uplift of the inner and outer sectors of the belt associated with a reduction in thermal stress and kerogen cracking, as well as massive loss of retained fluids and a decrease in pore pressure. The OM transformation impacted (a) the magnitude of effective porosity associated with organic porosity development, and (b) the magnitude and distribution of pore pressure within the unit controlled by hydrocarbon generation and compaction disequilibrium. BPSM shows a progressive increase in effective porosity from the top to the base and towards the west region related to the original organic carbon content and maturity increasing along the same trend. Overpressure intervals with high organic carbon contents are the most prone to develop organic pores. The latter represent favourable sites for the storage of hydrocarbons in the Vaca Muerta Formation.
Supporting preschoolers’ cognitive development: Short‐ and mid‐term effects of fluid reasoning, visuospatial, and motor training
Authors: Gizzonio Valentina , Bazzini Maria Chiara , Marsella Cosima , Papangelo Pamela , Rizzolatti Giacomo , Fabbri‐Destro Maddalena
Published: August 2021

Cognitive abilities are essential to children's overall growth; thus, the implementation of early and effective training interventions is a major challenge for developmental psychologists and teachers. This study explores whether an intervention simultaneously operating on fluid reasoning (FR), visuospatial, narrative, and motor abilities could boost these competencies in a group of Italian preschoolers (N = 108, 54 males 54 females, Agemean = 4.04). FR and visuospatial abilities showed training‐related increases at the end of the training and 1‐year follow‐up (moderate effect size). Interestingly, positive correlations with working memory and mathematical abilities were found. Beyond their scientific relevance, the short‐ and long‐term effects provide fundamental indications for designing and implementing educational programs dedicated to preschoolers.
Strontium‐incorporated titanium implant surfaces treated by hydrothermal treatment enhance rapid osseointegration in diabetes: A preclinical vivo experimental study
Authors: Xu Yangbo , Zhang Liefen , Xu Jiangang , Li Jia , Wang Hui , He Fuming
Published: August 2021

Objectives

The aim of the current study was to explore effects of strontium‐incorporated titanium implant surfaces by hydrothermal treatment on osseointegration in diabetic rats.

Materials and Methods

The surface characteristics of SLA and SLA‐Sr surfaces were detected by related instruments. Thirty‐six male Sprague‐Dawley rats were induced into diabetes, and thirty‐six rats were normal. SLA and SLA‐Sr implants were, respectively, inserted into bilateral tibial metaphysis of each rat. Percentage of bone‐to‐implant contact (BIC%) and percentage of bone area (BA%) were analyzed at 4 and 8 weeks after implantation. Immunohistochemistry of osteoprotegerin (OPG) and Wnt5a were conducted at 1 and 4 weeks. Gene expression levels of inflammatory cytokines and related signaling molecules in peri‐implant bone tissue were detected at 3 and 7 days.

Results

Strontium was uniformly distributed on SLA‐Sr surfaces, and it was released in an effective concentration range. SLA‐Sr surfaces showed significantly higher BIC% in diabetic rats at 4 (p < .05) and 8 weeks (p < .05). Besides, it displayed higher BIC% at 4 weeks (p < .05) in normal rats. Also, SLA‐Sr surfaces upregulated expression of OPG at 4 weeks (p < .05) in diabetic rats. What's more, SLA‐Sr surfaces downregulated inflammation (TNF‐α, IL‐1β, and IL‐6; p < .01) in diabetic rats at 3 days. In addition, expression of Wnt5a and ROR2 was upregulated (p < .05) at 7 days after implantation under diabetes.

Conclusion

It is suggested that strontium‐incorporated titanium implant surfaces by hydrothermal treatment could enhance implant osseointegration as compared with SLA implant surfaces in diabetic rats.
Kyoto classification risk scoring system and endoscopic grading of gastric intestinal metaplasia for gastric cancer: Multicenter observation study in Japan
Authors: Kawamura Masashi , Uedo Noriya , Koike Tomoyuki , Kanesaka Takashi , Hatta Waku , Ogata Yohei , Oikawa Tomoyuki , Iwai Wataru , Yokosawa Satoshi , Honda Junya , Asonuma Sho , Okata Hideki , Ohyauchi Motoki , Ito Hirotaka , Abe Yasuhiko , Ara Nobuyuki , Kayaba Shoichi , Shinkai Hirohiko , Shimokawa Toshio
Published: August 2021

Objectives

The usefulness of endoscopic and histological risk assessment for gastric cancer (GC) has not been fully investigated in Japanese clinical practice.

Methods

In this multicenter observation study, GC and non‐GC patients were prospectively enrolled in 10 Japanese facilities. The Kyoto classification risk scoring system, the Kimura–Takemoto endoscopic atrophy classification, the endoscopic grading of gastric intestinal metaplasia (EGGIM), the operative link on gastritis assessment (OLGA) and the operative link on gastric intestinal metaplasia assessment (OLGIM) were applied to all patients. The strength of an association with GC risk was compared. In addition, important endoscopic findings in the Kyoto classification were identified.

Results

Overall, 115 GC and 265 non‐GC patients were analyzed. Each risk stratification method had a significant association with GC risk in univariate analysis. In multivariate analysis, OLGIM stage III/IV (odds ratio [OR] 2.8 [95% CI 1.5–5.3]), high EGGIM score (OR 1.8 [1.0–3.1]) and opened‐type Kimura–Takemoto (OR 2.5 [1.4–4.5]) had significant associations with GC risk. In the Kyoto classification, opened‐type endoscopic atrophy, invisible regular arrangement of collecting venules (RAC), extensive (>30%) intestinal metaplasia in the corpus in image‐enhanced endoscopy, and map‐like redness in the corpus were independent high‐risk endoscopic findings. The modified Kyoto classification risk scoring system using these four findings demonstrated a better area under the receiver operating characteristic curve value (0.750, P = 0.052) than that of the original Kyoto classification (0.706).

Conclusions

The OLGIM stage III/IV, high EGGIM score and open‐typed Kimura–Takemoto had strong association with GC risk in Japanese patients. The modified Kyoto classification risk scoring system may be useful for GC risk assessment, which warrants further validation. (UMIN000027023).
Cerebrospinal fluid neopterin as a biomarker of treatment response to Janus kinase inhibition in Aicardi–Goutières syndrome
Authors: Han Velda X , Mohammad Shekeeb S , Jones Hannah F , Bandodkar Sushil , Crow Yanick J , Dale Russell C ,   AGS‐JAKi Study Group
Published: August 2021

Janus kinase (JAK) 1 inhibition represents a precision medicine approach in the treatment of Aicardi–Goutières syndrome (AGS), through targeting of type I interferon‐mediated cell signalling. Blood interferon mRNAseq has been proposed as a biomarker of disease with utility in therapeutic monitoring. Objective cerebrospinal fluid (CSF) biomarkers tracking treatment efficacy are currently lacking. Here, we report a retrospective case series of 13 patients (median age 6y, range 2y 6mo–17y; five females, eight males) with AGS demonstrating significantly elevated CSF neopterin levels at first sampling (median 200nmol/L, range 45–2024nmol/L), compared to 13 age‐matched controls with non‐inflammatory neurological conditions (median 23nmol/L, range 5–34nmol/L, p<0.001). Five patients with AGS treated with JAK inhibitors demonstrated a median 81.5% reduction of CSF neopterin (range –36% to –88% change from baseline), compared to eight untreated patients with AGS demonstrating a median 7% reduction in CSF neopterin (range –63% to +117% change) (p=0.047). Our data indicate a biological effect of JAK inhibitors, and the potential role of CSF neopterin as a biomarker of treatment response.
The relationship between meal carbohydrate quantity and the insulin to carbohydrate ratio required to maintain glycaemia is non‐linear in young people with type 1 diabetes: A randomized crossover trial
Authors: Cordon Natalie M. , Smart Carmel E. M. , Smith Grant J. , Davis Elizabeth A. , Jones Timothy W. , Seckold Rowen , Burckhardt Marie‐ Anne , King Bruce R.
Published: August 2021

Objective

To determine if the relationship between meal carbohydrate quantity and the insulin to carbohydrate ratio (ICR) required to maintain glycaemia is linear in people with type 1 diabetes.

Methods

We used an open labelled randomized four‐arm cross‐over study design. Participants (N = 31) aged 12–27 years, HbA1c ≤ 64 mmol/mol (8.0%) received insulin doses based on the individual's ICR and the study breakfast carbohydrate quantity and then consumed four breakfasts containing 20, 50, 100 and 150 g of carbohydrate over four consecutive days in randomized order. The breakfast fat and protein percentages were standardized. Postprandial glycaemia was assessed by 5 h continuous glucose monitoring.

The primary outcome was percent time in range (TIR) and secondary outcomes included hypoglycaemia, glucose excursion and incremental area under the curve. Statistical analysis included linear mixed modelling and Wilcoxon signed rank tests.

Results

The 20 g carbohydrate breakfast had the largest proportion of TIR (0.74 ± 0.29 p < 0.04). Hypoglycaemia was more frequent in the 50 g (n = 13, 42%) and 100 g (n = 15, 50%) breakfasts compared to the 20 g (n = 6, 20%) and 150 g (n = 7, 26%) breakfasts (p < 0.029). The 150 g breakfast glucose excursion pattern was different from the smaller breakfasts with the lowest glucose excursion 0–2 h and the highest excursion from 3.5 to 5 h.

Conclusions

A non‐linear relationship between insulin requirement and breakfast carbohydrate content was observed, suggesting that strengthened ICRs are needed for meals with ≤20 and ≥150 g of carbohydrate. Meals with ≥150 g of carbohydrate may benefit from dual wave bolusing.
My child's future mental health: Carer's engagement with risk identification in an intervention study for youth with at‐risk mental states
Authors: Tham Michael , Bendall Sarah , Carlyon‐Stewart Thomas , Polari Andrea , Hartmann Jessica , Kerr Melissa , Amminger Paul , McGorry Patrick , Nelson Barnaby , Ratheesh Aswin
Published: August 2021

Aim

Prevention and early intervention efforts of serious mental illnesses has yielded promising results. However, alongside benefits, several ethical concerns have been raised, including the effects of being identified as being at‐risk. In these debates, the voice of parents or carers is conspicuously absent. This is especially concerning as several at‐risk interventions are trialled in under‐age youth where parents consent on behalf of young people. Therefore, this study aimed to understand carer's experiences of their teenager being identified as at risk for psychosis.

Methods

Semi‐structured interviews were conducted with seven carers who had provided consent for their teenager to participate in a stepped intervention study for youth at‐risk for psychosis. Questions explored their experiences regarding having their teenager being identified as at‐risk. Transcripts were analysed using thematic analysis.

Results

We identified five main themes from seven female carers' experiences of risk identification including: (a) recall of risk information was limited, or variable, (b) goal of risk disclosure was perceived to be positive, (c) negative emotions were associated with knowledge of risk, (d) relief from uncertainty and helplessness and (e) effects of risk disclosure were mediated by individual circumstance.

Conclusion

Overall, the results demonstrate that carers' experience of risk disclosure varied with factors surrounding their individual circumstances, and the process of disclosure. Whilst participants acknowledged potential adverse effects associated with risk disclosure, many still adopted a positive outlook. Tailoring safe and effective disclosure of risk to suit the needs of youth and carers could outweigh the potential risks.