bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding p300-transcription factor interactions using sequence variation and hybridization
Authors: Hobor Fruzsina , Hegedus Zsofia , Ibarra Amaurys Avila , Petrovicz Vencel L. , Bartlett Gail J. , Sessions Richard B. , Wilson Andrew J. , Edwards Thomas A.
Published: December 2021

The hypoxic response is central to cell function and plays a significant role in the growth and survival of solid tumours. HIF-1 regulates the hypoxic response by activating over 100 genes responsible for adaptation to hypoxia, making it a potential target for anticancer drug discovery. Although there is significant structural and mechanistic understanding of the interaction between HIF-1α and p300 alongside negative regulators of HIF-1α such as CITED2, there remains a need to further understand the sequence determinants of binding. In this work we use a combination of protein expression, chemical synthesis, fluorescence anisotropy and isothermal titration calorimetry for HIF-1α sequence variants and a HIF-1α- CITED hybrid sequence which we term CITIF. We show the HIF-1α sequence is highly tolerant to sequence variation through reduced enthalpic and less unfavourable entropic contributions, These data imply backbone as opposed to side chain interactions and ligand folding control the binding interaction and that sequence variations are tolerated as a result of adopting a more disordered bound interaction or “fuzzy” complex.
ortho2align: a sensitive approach for searching for orthologues of novel lncRNAs
Authors: Mylarshchikov Dmitry Evgenevich , Mironov Andrey Alexandrovich
Published: December 2021

Background

Many novel long noncoding RNAs have been discovered in recent years due to advances in high-throughput sequencing experiments. Finding orthologues of these novel lncRNAs might facilitate clarification of their functional role in living organisms. However, lncRNAs exhibit low sequence conservation, so specific methods for enhancing the signal-to-noise ratio were developed. Nevertheless, current methods such as transcriptomes comparison approaches or searches for conserved secondary structures are not applicable to novel lncRNAs dy design.

Results

We present ortho2align — a versatile sensitive synteny-based lncRNA orthologue search tool with statistical assessment of sequence conservation. This tool allows control of the specificity of the search process and optional annotation of found orthologues. ortho2align shows similar performance in terms of sensitivity and resource usage as the state-of-the-art method for aligning orthologous lncRNAs but also enables scientists to predict unannotated orthologous sequences for lncRNAs in question. Using ortho2align, we predicted orthologues of three distinct classes of novel human lncRNAs in six Vertebrata species to estimate their degree of conservation.

Conclusions

Being designed for the discovery of unannotated orthologues of novel lncRNAs in distant species, ortho2align is a versatile tool applicable to any genomic regions, especially weakly conserved ones. A small amount of input files makes ortho2align easy to use in orthology studies as a single tool or in bundle with other steps that researchers will consider sensible.
Structure of human CST-pol-α/primase bound to a telomeric overhang poised for initiation of telomere C-strand synthesis
Authors: He Qixiang , Lin Xiuhua , Chavez Bianca L. , Lusk Benjamin L. , Lim Ci Ji
Published: December 2021

Telomere replication and regulation protect mammalian chromosome ends and promote genome stability. An essential step in telomere maintenance is the C-strand fill-in process, which is the de novo synthesis of the complementary strand of the telomere overhang. This step is catalyzed by polymerase-alpha/primase complex (pol-α/primase) and coordinated by an accessory factor, CTC1-STN1-TEN1 (CST). Using cryogenic-electron microscopy single-particle analysis, we report the structure of the human telomere C-strand fill-in preinitiation complex (PIC) at 3.9 Å resolution. The structure reveals a CST and a pol-α/primase co-bound to a single telomere overhang, poised for de novo RNA primer synthesis. Upon PIC assembly, the pol-α/primase undergoes large conformation change from its apo-state; CST partitions the DNA and RNA catalytic centers of pol-α/primase into two separate domains and positions the 3′ end of an extended telomere single-stranded DNA template towards the RNA catalytic center (PRIM1 or p49). The telomeric single-stranded DNA template is further positioned by the POLA1 (or p180) catalytically dead exonuclease domain. Together with CST, the exonuclease domain forms a tight-fit molecular tunnel for template direction. Given the structural homology of CST to Replication Protein A (RPA), our structure provides the structural basis for a new model of how pol-α/primase lagging-strand DNA synthesis is coordinated by single-stranded DNA-binding accessory factors.
Cancer metabolic subtypes and their association with molecular and clinical features
Authors: Moiso Enrico , Provero Paolo
Published: December 2021

Alterations of metabolic pathways in cancer have been investigated for many years, beginning way before the discovery of the role of oncogenes and tumor suppressors, and the last few years have witnessed a renewed interest in this topic. Large-scale molecular and clinical data on tens of thousands of samples allow us today to tackle the problem from a general point of view.

Here we show that transcriptomic profiles of tumors can be exploited to define metabolic cancer subtypes, which can be systematically investigated for association with other molecular and clinical data. We find thousands of significant associations between metabolic subtypes and molecular features such as somatic mutations, structural variants, epigenetic modifications, protein abundance and activation; and with clinical/phenotypic data including survival probability, tumor grade, and histological types.

Our work provides a methodological framework and a rich database of statistical associations, accessible from metaminer.unito.it, that will contribute to the understanding of the role of metabolic alterations in cancer and to the development of precision therapeutic strategies.
Chemoproteomics of microbiota metabolites reveals small-molecule agonists for orphan receptor GPRC5A
Authors: Zhao Xiaohui , Stein Kathryn R. , Chen Victor , Griffin Matthew E. , Hang Howard C.
Published: December 2021

The microbiota generates diverse metabolites that can engage multiple pathways to modulate host physiology and disease, but their protein targets and mechanism(s) of action have not been fully elucidated. To address this challenge, we focused on indole-3-acetic acid (IAA), a prominent microbiota metabolite, and developed IAA-based chemical reporters for proteomic studies. We discovered that IAA interacts with many proteins in host cells, including small-molecule transporters, receptors and metabolic enzymes. Notably, our functional studies revealed that IAA binds to orphan G protein-coupled receptors such as GPRC5A, but only aromatic monoamines were capable of inducing GPRC5A signaling. Functional profiling of microbiota uncovered specific bacterial species and enzymes that generate GPRC5A agonists. Finally, biochemical characterization of GPRC5A activation identified more potent synthetic agonists as well as key amino acid residues involved in ligand binding. These studies highlight the utility of chemoproteomics to dissect protein targets and mechanisms of action for microbiota metabolites.
Genomic epidemiological models describe pathogen evolution across fitness valleys
Authors: Cárdenas Pablo , Corredor Vladimir , Santos-Vega Mauricio
Published: December 2021

Genomics is fundamentally changing epidemiological research. However, systematically exploring hypotheses in pathogen evolution requires new modeling tools. Models intertwining pathogen epidemiology and genomic evolution can help understand processes such as the emergence of novel pathogen genotypes with higher transmissibility or resistance to treatment. In this work, we present Opqua, a flexible simulation framework that explicitly links epidemiology to sequence evolution and selection. We use Opqua to study determinants of evolution across fitness valleys. We confirm that competition can limit evolution in high transmission environments and find that low transmission, host mobility, and complex pathogen life cycles facilitate reaching new adaptive peaks through population bottlenecks and decoupling of selective pressures. The results show the potential of genomic epidemiological modeling as a tool in infectious disease research.
Evaluation of a phenotypic, point-of-care solution for the detection and quantitative antibiotic susceptibility testing for lower Urinary Tract Infection
Authors: Turner R. , Kirkby R. , Meader E. , Wain J.
Published: December 2021

Background

Urinary tract infections (UTIs) are one of the most common bacterial infections seen in primary care. The current standard for diagnosis is microbiological culture and antibiotic sensitivity testing of a mid-stream urine sample; however, this technique is costly, labour intensive and typically takes 2-3 days to yield a result.

Study design and Objective

This is a nonexperimental cross-sectional study. The aim of this study was to evaluate the efficacy of U-treat, a bioluminescent approach for rapid detection of bacteriuria and quantitative determination of the antimicrobial susceptibility profiles of uropathogens in clinical urine specimens - in under an hour.

Method

The evaluation was carried out in two UK-based Medical Centres using urine samples from patients presenting with symptoms of a UTI (n=249). The U-treat technology is a two test, two reagent process. Test 1 detects the presence of a bacterial UTI > 104 bacteria/mL (5-10 minutes). Test 2 produces quantitative antibiotic susceptibility (<50 minutes). Only urine samples testing positive for bacteria in Test 1 underwent Test 2 (n=82). U-treat results were compared retrospectively against reference laboratory culture and sensitivity findings. The influence of the technology on patient treatment outcomes was also analysed.

Results

Relative to reference laboratory analysis, Test 1 showed a sensitivity of 97.1% and specificity of 92.0%. (PPV: 89.3%; NPV: 97.8%). Test 2 produced an overall sensitivity (measurement of true susceptibility) of 94.1% (Predictive value: 96%) and an overall specificity (measurement of true resistance) of 90.5% (Predictive value 86.4%). Analysis of treatment data demonstrated that had the physicians had access to U-treat results at the point of care, the percentage of patients treated successfully would have risen from 68.3% to 92.7%.

Conclusion

U-treat represents the first technology, world-wide, capable of providing UTI treatment data to physicians at the point of care, in less than 60 minutes.
Matrix metalloproteinase 2 and 9 enzymatic activities are selectively increased in the myocardium of Chronic Chagas Disease cardiomyopathy patients: role of TIMPs
Authors: Baron Monique Andrade , Ferreira Ludmila Rodrigues Pinto , Teixeira Priscila Camillo , Moretti Ana Iochabel Soares , Santos Ronaldo Honorato Barros , Frade Amanda Farage , Kuramoto Andréia , Debbas Victor , Benvenuti Luiz Alberto , Gaiotto Fabio Antônio , Bacal Fernando , Pomerantzeff Pablo , Chevillard Christophe , Kalil Jorge , Cunha-Neto Edecio
Published: December 2021

Chronic Chagas disease (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis compared to other cardiomyopathies. We show the expression and activity of Matrix Metalloproteinases (MMP) and of their inhibitors TIMP (tissue inhibitor of metalloproteinases) in myocardial samples of end stage CCC, idiopathic dilated cardiomyopathy (DCM) patients, and from organ donors. Our results showed significantly increased mRNA expression of several MMPs, several TIMPs and EMMPRIN in CCC and DCM samples. MMP-2 and TIMP-2 protein levels were significantly elevated in both sample groups, while MMP-9 protein level was exclusively increased in CCC. MMPs 2 and 9 activities were also exclusively increased in CCC. Results suggest that the balance between proteins that inhibit the MMP-2 and 9 is shifted toward their activation. Inflammation-induced increases in MMP-2 and 9 activity and expression associated with imbalanced TIMP regulation could be related to a more extensive heart remodeling and poorer prognosis in CCC patients.
A dual reporter system identifies an intermediate state and sequential regulators of 2-cell-like-to-pluripotent state transition
Authors: Zhang Chao , Hao Jing , Shi Ming , Li Yu-Xuan , Yao Wang , Wang Yangming
Published: December 2021

Mouse embryonic stem cells (ESCs) cycle in and out of 2-cell-like (2C-like) state in culture. The molecular mechanism governing the exit of 2C-like state remains obscure, partly due to the lack of a reporter system that can genetically mark intermediate states during exiting process. Here, we identify an intermediate state that is marked by the co-expression ofMERVL::tdTomato andOCT4-GFP (MERLOT) during2C-like-to-pluripotent state transition (2CLPT). Transcriptome and epigenome analyses demonstrate that MERLOT cells cluster closely with 8-16 cell stage mouse embryos, suggesting that 2CLPT partly mimics early preimplantation development. Through a CRISPRa screen, we identify an ARRDC3-NEDD4-OCT4 regulatory axis that plays an essential role in controlling 2CLPT. Furthermore, re-evaluating previously reported 2C-like state regulators reveals dual function of Chaf1a in regulating the entry and exit of 2C-like state. Finally, ATAC-Seq footprinting analysis uncovers Klf3 as an essential transcription factor required for efficient 2CLPT. Together, our study identifies a genetically traceable intermediate state during 2CLPT and provides a valuable tool to study molecular mechanisms regulating this process.
Crystal structures of FolM alternative dihydrofolate reductase 1 from Brucella suis and Brucella canis
Authors: Porter Imani , Neal Trinity , Walker Zion , Hayes Dylan , Fowler Kayla , Billups Nyah , Rhoades Anais , Smith Christian , Smith Kaelyn , Staker Bart L. , Dranow David M. , Mayclin Stephen J. , Subramanian Sandhya , Edwards Thomas E. , Myler Peter J. , Asojo Oluwatoyin A.
Published: December 2021

Members of the bacterial genus Brucella cause brucellosis, a zoonotic disease that affects both livestock and wildlife. Brucella are category B infectious agents that can be aerosolized for biological warfare. As part of the structural genomics studies at the Seattle Structural Genomics Center for Infectious Disease (SSGCID), FolM alternative dihydrofolate reductases 1 from Brucella suis and Brucella canis were produced and their structures are reported. The enzymes share ∼95% sequence identity but have less than 33% sequence identity to other homologues with known structure. The structures are prototypical NADPH-dependent short-chain reductases that share their highest tertiary-structural similarity with protozoan pteridine reductases, which are being investigated for rational therapeutic development.
CEO beauty and management guidance
Authors: Guo Jun , Kim Jung Yeun , Kim Sungsoo , Zhou Nan
Published: December 2021

Purpose

The authors study whether CEO beauty influences management guidance.

Design/methodology/approach

The authors calculate an attractiveness score based on facial symmetry and perform regression analyses to examine the relation between CEO beauty and management guidance.

Findings

The authors find that attractive CEOs are more likely to issue voluntary management earnings guidance. After controlling for this appearance-based self-selection, the authors document that management forecasts provided by attractive CEOs are more optimistic yet less precise. Consistent with this result, the authors find that analysts' consensus forecast error following management forecasts made by attractive CEOs is larger than such error following management forecasts made by unattractive CEOs. The authors further find that the perceived credibility of management forecasts by attractive CEOs is not different from that by unattractive CEOs.

Originality/value

These findings suggest that attractive CEOs are more active but less skillful in issuing management forecasts. This adds to the emerging accounting literature on the relation between facial appearance and information delivery.
The effect of porosity and number of unit cell on applicability of volume average approach in closed cell porous media
Authors: Wang Chunyang , Zheng Xinghua , Zhang Ting , Chen Haisheng , Mobedi Moghtada
Published: December 2021

Purpose

The purpose of this study is to investigate the applicability of volume average which is extensively used for analyzing the heat and fluid flow (both for single-phase and solid/liquid-phase change) in a closed cell porous medium numerically.

Design/methodology/approach

Heat conduction equations for the solid frame and fluid (or phase change material) are solved for pore scale and volume average approaches. The study mainly focuses on the effect of porosity and the number of porous media unit cell on the agreement between the results of the pore scale and volume average approaches.

Findings

It is observed for the lowest porosity values such as 0.3 and the number of porous media unit cell as 4 in heat transfer direction, the results between two approaches may be questionable for the single-phase fluid. By increasing the number of porous media unit cell in heat transfer direction, the agreement between two approaches becomes better. In general, for high porosity values (such as 0.9) the agreement between the results of two approaches is in the acceptable range both for single-phase and solid/liquid-phase change. Two charts on the applicability of volume average method for single-phase and solid/liquid-phase change are presented.

Originality/value

The authors’ literature survey shows that it is the first time the applicability of volume average which is extensively used for analyzing the heat and fluid flow in a closed cell porous medium is investigated numerically.
Residents’ perceptions of environmental certification, environmental impacts and support for the world expo 2015: the moderating effect of place attachment
Authors: Prayag Girish , Chowdhury Mesbahuddin , Prajogo Daniel , Mariani Marcello , Guizzardi Andrea
Published: December 2021

Purpose

Based on social exchange theory (SET) and signaling theory (ST), this study aims to evaluate how an event’s perceived environmental certification (PEC) by residents, affect their evaluations of environmental impacts and subsequent event support (ES). The moderating role of place attachment (PA) on some of these relationships is also evaluated.

Design/methodology/approach

Using partial least square structural equation modeling (PLS-SEM), a theoretical model is tested on a sample of 450 residents who attended the 2015 Milan World Expo.

Findings

PEC positively affects evaluations of positive environmental impacts (PEI) but negatively affects evaluations of negative environmental impacts (NEI). PEC positively affects ES while the relationship between PEC and NEI is moderated by PA.

Research limitations/implications

Items used to measure PEC, PEI and NEI are not exhaustive. SET has its own limitations in explaining residents’ ES, which the authors have attempted to attenuate by using ST.

Practical implications

Using environmental certification as a communication tool must demonstrate to residents how it reduces negative externalities, rather than focusing only on its positive community benefits. Less well-educated residents had the lowest ES, suggesting the need to use social media to increase ES.

Originality/value

This study contributes to understandings of the perceptions of the benefits of event certification by residents, and how this affects their ES. PA moderates the relationship between PEC and NEI.
Effects of emotional healing on organisational learning and radical innovation: a leadership-based approach
Authors: Domínguez-Escrig Emilio , Mallén-Broch Francisco Fermín , Chiva Ricardo , Lapiedra Alcamí Rafael
Published: December 2021

Purpose

The objective of this study was to provide empirical evidence of the relationship between emotional healing, analysed as a leader behaviour and radical innovation.

Design/methodology/approach

To test the hypotheses, structural equations were used, with organisational learning capability as an explanatory variable. The study was conducted in a population of 402 Spanish companies. A sample frame of 292 questionnaires was obtained from 146 different organisations. The fieldwork took place in two stages, in 2010 and again in 2015.

Findings

Results confirm the hypotheses proposed in the model. Emotional healing promotes organisational learning capability and, in turn, radical innovation.

Practical implications

Our results provide some guidelines for companies that are trying to develop radical innovations by improving the workplace conditions.

Originality/value

To our knowledge, there are no previous studies which studied the relationship between emotional healing and its effect on radical innovation. Therefore, providing empirical evidence of such a relationship is the main contribution of this paper.
Supreme audit institutions in Europe: synergies, institutional transparency, gender equality and sustainability engagement
Authors: Hancu-Budui Andreea , Zorio-Grima Ana
Published: December 2021

Purpose

Supreme audit institutions (SAIs) examine and supervise the activity of public institutions. The study aims at contributing to the existing literature on public sector audit by providing a classification of 29 European SAIs – 28 national SAIs and the European Court of Auditors (ECA) – based on a broad range of attributes varying from the SAIs' environment to its structure, activity, resources or transparency.

Design/methodology/approach

The authors apply quantitative methodology for clustering by means of multidimensional scaling and regressive ordinary least square (OLS) and logistic models.

Findings

The authors' results show that SAIs from veteran EU member states (MSs) are more similar amongst them and the same applies to SAIs from Nordic countries, Baltic countries, Western Mediterranean countries and Eastern countries. The authors also perform additional analysis focussing on currently relevant issues such as gender equality, age, environment or the sustainable development goals (SDGs), concluding that the younger the institutions' staff, the more transparent the institutions are. The authors also find that more transparent SAIs report on environmental audits, more prone to cover the SDGs in their audits.

Research limitations/implications

The research is limited in purpose and scope because data cover only Europe. Given the limited number of observations (29), it does not have prospective purposes but only explanatory ones. The authors' findings are interesting for researchers because they offer original insights on public audit in Europe and cover matters of current interest such as environment, transparency or gender equality.

Practical implications

The research is also of interest for public auditors because it offers them information that may help them improve their activity and find institutional synergies, as the dataset is available to public auditors.

Social implications

From a social view point, the paper shows that public auditors perform work on topics of interest for the citizens.

Originality/value

The dataset compiled for the research offers extensive data and a wide variety of attributes defining European SAIs and may offer future opportunities for research from different perspectives.
Who is likely to hide knowledge after peer ostracism? An exchange-based perspective of contact quality and need to belong
Authors: Fatima Tehreem , Bilal Ahmad Raza , Imran Muhammad Kashif , Ayub Arslan , Arshad Hira
Published: December 2021

Purpose

The purpose of this study is to uncover how peer ostracism (POS) elicits knowledge hiding directed towards ostracizing peers through the intervening role of peer contact quality (PCQ). Moreover, the authors aim to highlight the role of the need to belong (NTB) as a first-order boundary condition in direct and indirect hypothesized paths.

Design/methodology/approach

The research opted for a three-wave time-lagged survey design. The data were obtained from the 234 teaching and non-teaching employees working in Higher Educational Sector in Pakistan through random sampling. Mediation and moderated mediation analysis was done by using PROCESS Models 4 and 7.

Findings

The results embraced the mediation, moderation and moderated mediation hypotheses. It was noted that POS creates negative exchange relationships. As a result, the ostracized employees withhold knowledge from the predating peer. NTB served as a buffering agent between POS and PCQ, as well as, in the indirect POS, PCQ and peer-directed knowledge hiding relationship.

Practical implications

This research serves as a guideline for management and faculty of Higher Educational Institutions for minimization of POS to promote effective collegial contact quality and curb knowledge hiding.

Originality/value

Although the research in workplace ostracism and knowledge hiding is not new, yet how this association emerges from the viewpoint of peers is not known. This study has added to the literature by answering who is more likely to reciprocate ostracism from peers by having poor quality contact and directing knowledge hiding towards the predator. By this, the authors have added to the limited stream of moderated mediation mechanisms underlying ostracism and knowledge hiding behaviour. In addition, the authors have drawn attention to the importance of peer relationships in higher educational settings.
Stroke survivors' perspectives on recovering in rural and remote Australia: A systematic mixed studies review
Authors: Jackson Sarah M. , Neibling Bridee A. , Barker Ruth N.
Published: December 2021

Introduction

Stroke survivors recovering in rural and remote locations often have little or no access to rehabilitation services. The purpose of this study was to review the literature on recovering in rural and remote Australia, from the perspective of stroke survivors. Use of technology to support recovery was also explored.

Methods

A systematic mixed studies review was conducted and reported according to the ENTREQ and PRISMA statements. MEDLINE (Ovid), CINAHL (EBSCOhost), Scopus, PsycINFO (ProQuest), Cochrane Library and Google Scholar were searched from inception to May 2021 for studies investigating stroke survivors' perspectives on recovering in rural or remote Australia. Qualitative, quantitative or mixed methods studies were included. Methodological quality was assessed using the Mixed Methods Appraisal Tool. Studies were not excluded or weighted according to methodological quality. To review the perspectives of stroke survivors on recovering, findings of included studies were mapped to the Living My Life framework and integrated using a convergent qualitative synthesis. The review protocol was registered on PROSPERO (CRD42017064990).

Results

Eight studies met the inclusion criteria: six qualitative, one quantitative and one mixed methods. Methodological quality of the small number of studies ranged from low to high, indicating further high‐quality research is needed. Included studies involved 152 stroke survivors in total. Review findings indicated that recovering was driven by working towards what mattered to stroke survivors, in ways that matched their beliefs and preferences and that worked for them in their world, including use of technology.

Conclusion

Stroke survivors recovering in rural and remote locations want to live their life by doing what matters to them, despite the challenges they face. They want support in ways that work for them in their environment. Further research is required to tailor support for stroke survivors that is specific to their life in rural and remote locations.
Tensions between (Post)Bureaucratic and Neo‐normative Demands: Investigating Employees’ Subjective Positions at EurAirport
Authors: Bardon Thibaut , Josserand Emmanuel , Sferrazzo Roberta , Clegg Stewart
Published: December 2021

The introduction of a neo‐normative discourse in a (post)bureaucratic organization can result in tensions between the neo‐normative injunction to be authentic and exhortations to fit with the ideal (post)bureaucratic organizational subject. Focusing on how shopfloor workers subjectively experience the tensions between neo‐normative and (post)bureaucratic demands, this empirical investigation yielded three major contributions. First, it pinpointed and addressed significant gaps in existing studies of normative and neo‐normative discourse. Second, the study better distinguished normative and neo‐normative control on the basis of two tensions: (1) authenticity versus conformity; and (2) conflation versus differentiation between life and work. Third, the study identified four distinct subject positions that demonstrated how organizational participants creatively appropriate and strive to resolve these two tensions in a work setting that mixes normative and neo‐normative control.
Predictive performance for placental dysfunction related stillbirth of the competing risks model for small‐for‐gestational‐age fetuses
Authors: Nicolaides Kypros H. , Papastefanou Ioannis , Syngelaki Argyro , Ashoor Ghalia , Akolekar Ranjit
Published: December 2021

Objectives

To examine the predictive performance for placental dysfunction related stillbirths of the competing risks model for small‐for‐gestational‐age (SGA) fetuses based on a combination of maternal risk factors, estimated fetal weight (EFW) and uterine artery pulsatility index (UtA‐PI); and second, to compare the performance of this model with that of a stillbirth‐specific model using the same biomarkers and with the Royal College of Obstetricians and Gynecologists (RCOG) guideline for the investigation and management of the SGA fetus.

Design

Prospective observational study.

Setting

Two UK maternity hospitals.

Population

A total of 131 514 women with singleton pregnancies attending for routine ultrasound examination at 19–24 weeks of gestation.

Methods

The predictive performance for stillbirth achieved by three models was compared.

Main Outcome Measure

Placental dysfunction related stillbirth.

Results

At 10% false‐positive rate, the competing risks model predicted 59%, 66% and 71% of placental dysfunction related stillbirths, at any gestation, at <37 weeks and at <32 weeks, respectively, which were similar to the respective figures of 62%, 70% and 73% for the stillbirth‐specific model. At a screen positive rate of 21.8%, as defined by the RCOG guideline, the competing risks model predicted 71%, 76% and 79% of placental dysfunction related stillbirths at any gestation, at <37 weeks and at <32 weeks, respectively, and the respective figures for the RCOG guideline were 40%, 44% and 42%.

Conclusion

The predictive performance for placental dysfunction related stillbirths by the competing risks model for SGA was similar to that of the stillbirth‐specific model and superior to that of the RCOG guideline.

Tweetable Abstract

The competing risks approach for SGA is superior to the RCOG guideline in the prediction of placental dysfunction related stillbirths.
Chickpea protein ingredients: A review of composition, functionality, and applications
Authors: Grasso Nadia , Lynch Nicola L. , Arendt Elke K. , O'Mahony James A.
Published: December 2021

Chickpea (Cicer arietinum L.) is a pulse consumed all over the world, representing a good source of protein, as well as fat, fiber, and other carbohydrates. As a result of the growing global population the demand for the protein component of this pulse is increasing and various approaches have been proposed and developed to extract same. In this review the composition, functionality, and applications of chickpea protein ingredients are described. Moreover, methods to enhance protein quality have been identified, as well as applications of the coproducts resulting from protein extraction and processing. The principal dry and wet protein enrichment approaches, resulting in protein concentrates and isolates, include air classification, alkaline/acid extraction, salt extraction, isoelectric precipitation, and membrane filtration. Chickpea proteins exhibit good functional properties such as solubility, water and oil absorption capacity, emulsifying, foaming, and gelling. During protein enrichment, the functionality of protein can be enhanced in addition to primary processing (e.g., germination and dehulling, fermentation, enzymatic treatments). Different applications of chickpea protein ingredients, and their coproducts, have been identified in research, highlighting the potential of these ingredients for novel product development and improvement of the nutritional profile of existing food products. Formulations to meet consumer needs in terms of healthy and sustainable foods have been investigated in the literature and can be further explored. Future research may be useful to improve applications of the specific coproducts that result from the extraction of chickpea proteins, thereby leading to more sustainable processes.
Characterizing changes in Maillard reaction indicators in whole milk powder and reconstituted low‐temperature pasteurized milk under different preheating conditions
Authors: Li Yong , Jia Xiaodi , Wang Zhaojun , He Zhiyong , Zeng Maomao , Chen Jie
Published: December 2021

The chemical properties and quality of milk powder and reconstituted milk can be changed by preheating treatment during milk powder processing. The effect of preheating conditions (low‐temperature pasteurization [LT], high‐temperature pasteurization [HT], extended shelf‐life [ESL], ultra‐high‐temperature [UHT], and in‐container sterilization [CS]), on furosine, furfural compounds, and advanced glycation end products were investigated in milk powders and reconstituted milk. The results revealed that Maillard reaction indicators were affected by preheating intensity; contents of furosine, 5‐hydroxymethylfurfural (HMF), 2‐furfural, Nε‐(carboxymethyl)lysine (CML), and Nε‐(carboxyethyl)lysine (CEL) increased, whereas lysine and 5‐methyl‐furfural (MF) decreased in both milk powder and reconstituted milk with an increase in the intensity of preheating. CML and CEL contents in reconstituted milk increased by 1.7‐ to 2.4‐fold and 1.3‐ to 1.6‐fold, respectibely. The content of CML and CEL in high‐preheating powders was 11%–34% and 18%–123% higher than that in LT samples, respectively. Compared with milk powder, furosine was reduced by 22%–55% and MF by 57%–69% in reconstituted milk; HMF increased by 12%–52%, CML and CEL increased 1.7–2.4 times and 1.3–1.6 times, respectively. A superposition effect was observed between preheating intensity and heat process times, which increased the content of Maillard reaction products.

Practical Application

Our findings revealed the promotion effect of higher preheating conditions on Maillard reaction indicators in milk powder and reconstituted low‐temperature pasteurized milk. The results will help reduce some of the harmful Maillard reaction indicators (e.g., advanced glycation end products) formed during heat processing and assist customers in selecting dairy products with low amounts of Maillard reaction products.
A systematic review of instruments to measure health literacy of patients in emergency departments
Authors: Hesselink Gijs , Cheng Joey , Schoon Yvonne
Published: December 2021

Objectives

Knowledge of patient's health literacy (HL) in the emergency department (ED) can facilitate care delivery and reduce poor health outcomes. This systematic review investigates HL measurement instruments used in the ED and their psychometric properties, accuracy in detecting limited HL, and feasibility.

Methods

We searched in five biomedical databases for studies published between 1990 and January 2021, evaluating HL measurement instruments tested in the ED on internal consistency, criterion validity, diagnostic accuracy, or feasibility. Reviewers screened studies for relevance and assessed methodologic quality with published criteria. Data were synthesized around study and instrument characteristics and outcomes of interest.

Results

Of the 2,376 references screened, seven met our inclusion criteria. Studied instruments varied in objective (n = 5) and subjective (n = 6) measurement of HL skills, and in HL constructs measured. The Brief Health Literacy Screen (BHLS) and the Subjective Numeracy Scale demonstrate acceptable and good internal consistency across studies. None of the instruments perform consistently well on criterion validity. The Rapid Estimate of Adult Literacy in Medicine–Revised and the Newest Vital Sign, both objective tests with short administration times, demonstrate good accuracy in one study with high risk of bias. The BHLS, a short subjective measure, shows moderate accuracy across studies including one with low risk of bias.

Conclusions

Several short instruments seem valid in measuring HL and accurate in detecting limited HL among ED patients, each with its practical advantages and disadvantages and specific measurement of HL. Additional research is necessary to develop a robust evidence base supporting these instruments.
Confocal laser scanning microscopy evaluation of roots subjected to activation protocol in endodontic microsurgery
Authors: Iandolo Alfredo , Abdellatif Dina , Barbosa Ana Flávia A. , Scelza Giuseppe , Gasparro Roberta , Sammartino Pasquale , Silva Emmanuel J. N. L.
Published: December 2021

This study evaluated the penetration of the irrigant subject to activation after performing retro‐preparation in endodontic microsurgery. Forty mandibular premolars were prepared and filled. Subsequently, 1 mm from the root apex was cut using a multi‐blade bur and the retro‐preparation was performed. In group 1, the retro‐cavity was cleaned with 2 mL of saline and then with 2 mL of 5.25% NaOCl gel mixed with 0.1% Rhodamine B. In group 2, the retro‐cavity was cleaned with 2 mL of saline, 17% EDTA gel was activated ultrasonically for 30 s and 5.25% NaOCl gel was mixed with 0.1% Rhodamine B and activated for 30 s. After 7 days, the roots were cut at 1mm from the apex and the slices were evaluated with confocal laser scanning microscopy. The samples of group 2 showed statistically better results. The activation protocol proposed resulted in enhanced irrigant penetration when compared to the traditional.
Efficiency of forest carbon policies at intensive and extensive margins
Authors: Li Rong , Sohngen Brent , Tian Xiaohui
Published: December 2021

The economic potential of forest carbon sequestration is widely acknowledged. However, no consensus has been reached regarding the appropriate policy instrument for promoting carbon sequestration. In this study, we develop a dynamic framework to measure the effects and efficiencies of alternative carbon policies. A stylized optimal control model of the timber market is first employed to illustrate the mechanisms through which different policies affect the decision making of the forest sector at the extensive margin (i.e., changing forest areas) and the intensive margin (i.e., changing harvest ages). We then introduce carbon price projections and species‐specific production information into a multi‐age dynamic timber market model. Different carbon policies are simulated numerically. Our results reveal that a carbon tax on forest emissions without compensating for sequestration leads to net carbon emissions and, thus, is the least efficient policy choice. Further, policies that do not increases carbon uptake at the intensive margin result in very high efficiency losses. A per‐hectare land subsidy may be more than 10 times more expensive than a per‐ton carbon tax and subsidy policy or a carbon subsidy policy.
Human skin microbiota in health and disease
Authors: Bay Lene , Ring Hans Christian
Published: December 2021

Cutaneous microbial composition is driven by the microenvironment of the skin, as well as by internal and external factors. Local changes in the microenvironment can affect the configuration of the community, which may lead toward an imbalance of microbiota. Alterations in the microbial profile are common in both inflammatory skin diseases and chronic infections. A shift in balance within the microbiota, toward limited variation and a greater abundance of specific pathogens, may further worsen the pathogenicity of the diseases. These alterations may be prevented by topical treatment of probiotic solutions stimulating a balanced multispecies community. Compositional variations may further constitute potential biomarkers to predict flares or monitor efficacy during therapy. New approaches such as machine learning may contribute to this prediction of microbial alterations prior to the development of chronic infections and flares. This review provides insight into the composition and distribution of a healthy community of microorganisms in the skin and draws parallels with the community in chronic infections and chronic inflammatory skin diseases such acne vulgaris and Hidradenitis Suppurativa. We discuss the potential role of specific species in the pathogenesis and the possible prevention of disease exacerbation.
Latent variable selection in multidimensional item response theory models using the expectation model selection algorithm
Authors: Xu Ping‐Feng , Shang Laixu , Zheng Qian‐Zhen , Shan Na , Tang Man‐Lai
Published: December 2021

The aim of latent variable selection in multidimensional item response theory (MIRT) models is to identify latent traits probed by test items of a multidimensional test. In this paper the expectation model selection (EMS) algorithm proposed by Jiang et al. (2015) is applied to minimize the Bayesian information criterion (BIC) for latent variable selection in MIRT models with a known number of latent traits. Under mild assumptions, we prove the numerical convergence of the EMS algorithm for model selection by minimizing the BIC of observed data in the presence of missing data. For the identification of MIRT models, we assume that the variances of all latent traits are unity and each latent trait has an item that is only related to it. Under this identifiability assumption, the convergence of the EMS algorithm for latent variable selection in the multidimensional two‐parameter logistic (M2PL) models can be verified. We give an efficient implementation of the EMS for the M2PL models. Simulation studies show that the EMS outperforms the EM‐basedL1regularization in terms of correctly selected latent variables and computation time. The EMS algorithm is applied to a real data set related to the Eysenck Personality Questionnaire.
Irreversible inhibitors of the proline racemase unveil innovative mechanism of action as antibacterial agents against Clostridioides difficile
Authors: Gateau Cécile , Melo Guilherme D. , Uriac Philippe , Tasseau Olivier , Renault Jacques , Blondel Arnaud , Gouault Nicolas , Barbut Frédéric , Minoprio Paola
Published: December 2021

Proline racemases (PRAC), catalyzing the l‐proline and d‐proline interconversion, are essential factors in eukaryotic pathogens such as Trypanosoma cruzi, Trypanosoma vivax, and Clostridioides difficile. If the discovery of irreversible inhibitors of T. cruzi PRAC (TcPRAC) led to innovative therapy of the Chagas disease, no inhibitors of CdPRAC have been discovered to date. However, C. difficile, due to an increased incidence in recent years, is considered as a major cause of health threat. In this work, we have taken into account the similarity between TcPRAC and CdPRAC enzymes to design new inhibitors of CdPRAC. Starting from (E) 4‐oxopent‐2‐enoic acid TcPRAC irreversible inhibitors, we synthesized 4‐aryl substituted analogs and evaluated their CdPRAC enzymatic inhibition against eleven strains of C. difficile. This study resulted in promising candidates and allowed for identification of (E)‐4‐(3‐bromothiophen‐2‐yl)‐4‐oxobut‐2‐enoic acid 20 that was chosen for complementary in vivo studies and did not reveal in vivo toxicity.
Multiple function of lncRNA MALAT1 in cancer occurrence and progression
Authors: Malakoti Faezeh , Targhazeh Niloufar , Karimzadeh Haniye , Mohammadi Erfan , Asadi Milad , Asemi Zatollah , Alemi Forough
Published: December 2021

Long non‐coding RNAs (lncRNAs) have received particular attention in the last decade due to its engaging in carcinogenesis and tumorigenesis. Metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) is a lncRNA that plays physiological and pathological roles in many aspects of genome function as well as biological processes involved in cell development, differentiation, proliferation, invasion, and migration. In this article, we will review the effects of lncRNA MALAT1 on the progression of six prevalent human cancers by focusing on MALAT1 ability to regulate post‐transcriptional modification and signaling pathways.
Effects of vitamin D receptor gene polymorphisms on the prognosis of COVID‐19
Authors: Apaydin Tugce , Polat Hamza , Dincer Yazan Ceyda , Ilgin Can , Elbasan Onur , Dashdamirova Saida , Bayram Feyza , Tukenmez Tigen Elif , Unlu Ozan , Tekin Ahmet F. , Arslan Ebru , Yilmaz Ipek , Haklar Goncagul , Ata Pınar , Gozu Hulya
Published: December 2021

Purpose

Vitamin D deficiency has emerged as another potential risk factor for coronavirus disease (COVID‐19) due to the immunomodulatory effects of 25 hydroxyvitamin D [25 (OH)D]. Vitamin D receptor (VDR) gene polymorphisms such as Fok I, Bsm I, Apa I, and Taq I are also associated with different courses of viral infections. This study aimed to evaluate the association between the VDR gene polymorphism at Fok I, Taq I, Bsm I, and Apa I genotypes and the prognosis of COVID‐19 in respect to vitamin D deficiency.

Methods

Two‐hundred ninety‐seven patients with COVID‐19 were enrolled. Serum 25 (OH)D levels were measured. Four variant regions of the VDR gene, FokI, BsmI, ApaI, and TaqI were determined.

Results

Eighty‐three percent of subjects had vitamin D deficiency, and 40.7% of the whole group had severe deficiency. Median 25 (OH)D level was 11.97 ng/ml. Vitamin D levels were not related to inflammatory markers, disease severity, admission to intensive care unit (ICU), and mortality. While disease severity was related to Fok I Ff genotype, it was Taq TT genotype for ICU admission. Moreover, the ApaI aa genotype was common among the patients who were died. None of the deceased subjects had the Fok I FF genotype.

Conclusion

25 (OH)D levels were not related to the severity and mortality of COVID‐19. VDR gene polymorphisms are independently associated with the severity of COVID‐19 and the survival of patients.
Research progress on the hedgehog signalling pathway in regulating bone formation and homeostasis
Authors: Zhou Huan , Zhang Lei , Chen Yue , Zhu Chun‐Hui , Chen Fa‐Ming , Li Ang
Published: December 2021

Bone formation is a complex regeneration process that was regulated by many signalling pathways, such as Wnt, Notch, BMP and Hedgehog (Hh). All of these signalling have been demonstrated to participate in the bone repair process. In particular, one promising signalling pathway involved in bone formation and homeostasis is the Hh pathway. According to present knowledge, Hh signalling plays a vital role in the development of various tissues and organs in the embryo. In adults, the dysregulation of Hh signalling has been verified to be involved in bone‐related diseases in terms of osteoarthritis, osteoporosis and bone fracture; and during the repair processes, Hh signalling could be reactivated and further modulate bone formation. In this chapter, we summarize our current understanding on the function of Hh signalling in bone formation and homeostasis. Additionally, the current therapeutic strategies targeting this cascade to coordinate and mediate the osteogenesis process have been reviewed.