bluuebunny/crossref_metadata_2025 huggingface dataset:
The CDK7 inhibitor CT7001 (Samuraciclib) targets proliferation pathways to inhibit advanced prostate cancer
Authors: Constantin Theodora A. , Varela-Carver Anabel , Greenland Kyle K. , de Almeida Gilberto Serrano , Penfold Lucy , Ang Simon , Ormrod Alice , Ainscow Edward K. , Bahl Ash K. , Carling David , Fuchter Matthew J. , Ali Simak , Bevan Charlotte L.
Published: June 2022

Background

Current strategies to inhibit the androgen receptor (AR) are circumvented in castration-resistant prostate cancer (CRPC). Cyclin-dependent kinase 7 (CDK7) promotes AR signalling, in addition to established roles in cell cycle and global transcription regulation, together, providing a rationale for its therapeutic targeting in CRPC.

Methods

The antitumour activity of CT7001, an orally bioavailable CDK7 inhibitor, was investigated across CRPC models in vitro and in xenograft models in vivo. Cell-based assays and transcriptomic analyses of treated xenografts were employed to investigate the mechanism driving activity of CT7001, alone and in combination with the antiandrogen enzalutamide.

Results

CT7001 selectively engages with CDK7 in prostate cancer cells, causing inhibition of proliferation and cell cycle arrest. Activation of p53, induction of apoptosis, and suppression of transcription mediated by full-length and constitutively active AR splice variants contribute to antitumour efficacy in vitro. Oral administration of CT7001 represses growth of CRPC xenografts and significantly augments growth inhibition achieved by enzalutamide. Transcriptome analyses of treated xenografts indicate cell cycle and AR inhibition as the mode of action of CT7001 in vivo.

Conclusions

This study supports CDK7 inhibition as a strategy to target deregulated cell proliferation and demonstrates CT7001 is a promising CRPC therapeutic, alone or in combination with AR-targeting compounds.
Insights into the microevolution of SARS-ACE2 Interactions: In-silico analysis of glycosylation and SNP pattern
Authors: Madasu Pavan K , Maity Arpita , Ghosh Surya K. , Chandran Thyageshwar
Published: June 2022

The prefatory protein-glycan interaction and stabilizing protein-protein interaction of severe acute respiratory syndrome viruses with angiotensin-converting enzyme 2 play a significant role in complex formation thereby promoting endocytosis. The microevolution of SARS-CoV-2 over a period of time has a significant role in increasing the affinity of receptor-binding domain against angiotensin converting-enzyme 2. In the current study, we have corroborated the vitality of acquired SNPs over a period of time with increased affinity by using docking studies. The results indicate that the virus modulates the undesirable glycosylation sites by a series of substitution and deletion mutations. It uses bulky residues such as Tyr/Phe for dynamic arrest for quick stabilization of the complex, and Lys residues for stabilizing via hydrogen bond formation besides increasing the binding affinity to ease the cell entry.
Identifying and quantifying isoforms from accurate full-length transcriptome sequencing reads with Mandalorion
Authors: Volden Roger , Schimke Kayla , Byrne Ashley , Dubocanin Danilo , Adams Matthew , Vollmers Christopher
Published: June 2022

The Mandalorion tool, which we have continuously developed over the last 5 years, identifies and quantifies high-confidence isoforms from accurate full-length transcriptome sequencing reads produced by methods like PacBio Iso-Seq and ONT-based R2C2. In this manuscript, we introduce and benchmark Mandalorion v4 which further improves upon the already strong performance of Mandalorion v3.6 used in the LRGASP consortium challenge. By processing real and simulated accurate full-length transcriptome sequencing data sets, we show three main features of Mandalorion: First, Mandalorion-based isoform identification has very high Precision and maintains high Recall even when used in the absence of any genome annotation. Second, isoform read counts as quantified by Mandalorion show high correlation with simulated read counts. Third, isoforms identified by Mandalorion closely reflect the full-length transcriptome sequencing data sets they are based on.
Chloroplast activity provides in vitro regeneration capability in contrasting cultivars
Authors: Sirohi Parul , Chaudhary Chanderkant , Baliyan Suchi , Vishnoi Ritika , Mishra Sumit Kumar , Chaudhary Reeku , Waghmode Bhairavnath , Poonia Anuj Kumar , Germain Hugo , Sircar Debabrata , Chauhan Harsh
Published: June 2022

Existence of potent in vitro regeneration system is a prerequisite for efficient genetic transformation and functional genomics of crop plants. We know little about why only some cultivars in crop plants are tissue culture friendly. In this study, tissue culture friendly cultivar Golden Promise (GP) and tissue culture resistant DWRB91(D91) were selected as contrasting cultivars to investigate the molecular basis of regeneration efficiency. Multiomics studies involving transcriptomics, proteomics, metabolomics, and biochemical analysis were performed using GP and D91 callus to unravel the regulatory mechanisms. Transcriptomics analysis revealed 1487 differentially expressed genes (DEGs), in which 795 DEGs were upregulated and 692 DEGs were downregulated in the GP-D91 transcriptome. Genes encoding proteins localized in chloroplast and involved in ROS generation were upregulated in the embryogenic calli of GP. Moreover, proteome analysis by LC-MSMS revealed 3062 protein groups and 16989 peptide groups, out of these 1586 protein groups were differentially expressed proteins (DEPs). Eventually, GC-MS based metabolomics analysis also revealed the higher activity of plastids and alterations in key metabolic processes such as sugar metabolism, fatty acid biosynthesis, and secondary metabolism. Higher accumulation of sugars, amino acids and metabolites corresponding to lignin biosynthesis were observed in GP as compared to D91.

Highlights:

Multi omics analysis revealed chloroplast play crucial role in providing in vitro regeneration capability in contrasting genotypes
Exploring key factors sustaining micro and small food, wine and hospitality firms through the COVID-19 crisis
Authors: Bressan Alessandro , Duarte Alonso Abel , Vu Oanh Thi Kim , O'Brien Seamus
Published: June 2022

Purpose

The purpose of this study is to contribute to the understanding of how micro and small firm owners/managers cope with an extreme event, as this has implications on how firms make decisions. The study considers self-efficacy and stakeholder theory as tools to gain more in-depth knowledge.

Design/methodology/approach

The perspectives of owners/managers of 308 micro and small firms operating in the food, wine and hospitality industries in Italy, one of the most affected nations, were drawn through an online questionnaire.

Findings

The importance of determination, passion, family support and a sense of responsibility towards internal and external stakeholders emerged as fundamental factors helping firms confront the crisis. Five theoretical dimensions that help explain how firm owners/managers make decisions to safeguard their firms during the COVID-19 crisis are identified. Three of these, “motivational”, “stepping up” and “firm-based”, are directly associated with tenets of self-efficacy theory, and two, “human-moral” and “entity-based”, with stakeholder theory. Further complementing this second contribution, a theoretical framework underlining conceptual and practical implications is proposed.

Originality/value

The study delves into the challenges and survival of a key group of firms facing an extreme crisis. The identified dimensions provide useful conceptual depth and practical insights that, together, form part of a proposed framework. For instance, the “human-moral” dimension reflects upon aspects that have wider implications, notably, for firms' employees and the wider society.
How do foodservice companies organize for inbound open innovation? Empirical evidence from a Dutch organization
Authors: Annosi Maria Carmela , Casprini Elena , Parra Hector
Published: June 2022

Purpose

The aim of the paper is to analyze how actors in foodservice companies organize for inbound open innovation (OI).

Design/methodology/approach

This paper conducted a case analysis of a large and successful foodservice company operating in the Dutch market. Furthermore, drawing on 18 interviews and archive data, we identified the main organizational practices involved in the implementation of inbound innovation activities and the ways they are embraced are defined.

Findings

The results provide a holistic view of the main organizational practices a foodservice company implemented at different organizational levels, to exploit external knowledge coming from third parties and to promote the sharing and recombination of knowledge resources within the organization. The identified organizational practices reveal the main interaction patterns between relevant internal actors and other external parties in the company network, as well as between actors on different hierarchical organizational levels which allows processing relevant innovation information and make relevant decisions about it.

Research limitations/implications

Implications are provided in terms of both theory and practice. This paper helps foodservice companies to create an internal organizational environment that supports the exploitation of customer knowledge.

Originality/value

There are few studies on how companies organize themselves for OI in general, and especially in the foodservice sector.
How A/E/C professionals accept BIM technologies in China: a technology acceptance model perspective
Authors: Zhao Yiwei , Sun Yindong , Zhou Qianqian , Cui Caiyun , Liu Yong
Published: June 2022

Purpose

The aim of this paper is to research the acceptance mechanism of building information modeling (BIM) technology and to explore the differences among Architecture/Engineering/Construction (A/E/C) professionals with different individual characteristics. The proposed acceptance mechanism of BIM technology is intended to be used by industry stakeholders to propose decisions and measures, and improve the degree of BIM adoption.

Design/methodology/approach

Traditional hypothesis testing is adopted by the current study to empirically research the specific mechanism of A/E/C professionals accepting BIM technologies. In the one phase, a conceptual model based on technology acceptance model (TAM) and technology organization environment (TOE) theory was established and a large-scale questionnaire survey was conducted. In the other phase, structural equation modeling (SEM) was used to analyze acquired sample data, so as to empirically test the validity of the proposed linkage.

Findings

The results show first that perceived ease of use has no significant influence on perceived usefulness, and perceived usefulness has no significant effect on behavior intention as well. Second, BIM technical features and government BIM policies have positive effects on perceived usefulness, BIM technical features and organization supports have positive effects on perceived ease of use. Third, the BIM acceptance mechanism of A/E/C professionals is diverse from respondents with different characteristics, e.g. regions and working time.

Originality/value

The authors highlight the large sample size, as well as the nationwide context, of the questionnaire survey. Meanwhile, acceptance differences among A/E/C professionals with different demographic characteristics have been clarified using profound data and t-test. The findings of this study enrich the research on the acceptance mechanism of BIM technology, and contribute to relevant stakeholders taking targeted measures to promote the effective application of BIM technology nationwide.
Legal regulation of the state financial guarantees of medical services for the population: domestic and international experience
Authors: Lytvyn Nataliia A. , Berlach Anatolii I. , Kovalko Nataliia M. , Melnyk Alla A. , Berlach Hanna V.
Published: June 2022

Purpose

The research topicality is stipulated by the need to study the legal regulation problems of the state financial guarantees of medical services for the population in Ukraine and to consider positive experience of the developed countries in this area. The aim of the article is to define the main trends in the legal regulation of healthcare in Ukraine; analyze the state financial guarantees of medical services for the population, and positive and negative aspects of the healthcare reform; to explore the international experience in medical services for its implementation to national law enforcement in the sphere of healthcare.

Design/methodology/approach

During the research, systematization and generalization of the positive international experience in the legal regulation of the state financial guarantees of medical services for the population were realized.

Findings

The analysis of the population's perception of healthcare innovations was carried out. The level of medical service was assessed. The results showed that in order to improve Ukrainian legislation on healthcare, it is necessary to remove absolute conflicts of normative legal acts; to establish public confidence in innovations and changes; to take into account international experience adapting it to specific features of Ukrainian legislation.

Originality/value

The defined theoretical and applied provisions constitute the practical significance for scholars and practicians, who deal with the legal regulation problems of the state financial guarantees of medical services for the population, university professors training highly qualified personnel, and all interested people concerned with healthcare.
Rebuilding disrupted supply chains: How can a self-organised social group facilitate supply chain resilience?
Authors: Lusiantoro Luluk , Pradiptyo Rimawan
Published: June 2022

Purpose

This paper seeks to explore how a self-organised social group (SOSG) can facilitate supply chain resilience (SCRES) during an emergency condition.

Design/methodology/approach

A netnographic research was conducted on SONJO, an online SOSG emerging in response to problems in personal protective equipment (PPE) and food small businesses' supply chains (SCs) during the state of COVID-19 emergency in Yogyakarta, Indonesia. Qualitative data of 237,010 words were extracted from the group chats among 223 SONJO WhatsApp Group (WAG) members and were analysed using template analysis.

Findings

This paper reveals five communicative acts through which the SOSG facilitates SCRES, namely supply chain (SC) knowledge sharing, networking, bridging, mapping, and mindfulness. The enactment of these communicative acts could foster SC collaboration and help rebuild and sustain the SC operations during the critical period of the pandemic. The SOSG also facilitates the SC actors to be heedful of their responsive actions and risky operations.

Practical implications

This paper emphasises the need for organisations to build and maintain relationships with social communities and to extend their social capital beyond their existing SC linkages as an alternative way to survive unexpected disruptions.

Originality/value

This paper offers a novel perspective to understand SCRES from an external force. It proposes that, in the face of a devastating disruption, SCRES is not a self-induced process and that the SOSG could play a pivotal role in rebuilding the disrupted SCs. It also shows how a humanitarian effort could help rebuild commercial SCs.
Is supplier involvement always beneficial for financial performance? The roles of ambidextrous innovations and product smartness
Authors: Wang Yu , Jia Tao , Chen Jinliang
Published: June 2022

Purpose

The purpose of this paper is to investigate the performance impact of supplier involvement, based on the knowing processes and contingencies of knowledge-based view. Ambidextrous innovations (i.e. exploitative innovation and exploratory innovation) are taken as intermediary processes. Furthermore, product smartness is considered to clarify boundary conditions.

Design/methodology/approach

The ordinary least squares regression was conducted, based on the two-source data collected from 125 high-tech firms in China.

Findings

Ambidextrous innovations positively mediate the relationship between supplier involvement and financial performance. Product smartness weakens the indirect impact via exploratory innovation but not exploitative innovation.

Originality/value

This study reveals the knowledge application and recombination mechanisms of ambidextrous innovations to mediate between supplier involvement and financial performance. It also highlights digital encapsulation function of product smartness as a contingent factor.
Community structure determines the predictability of population collapse
Authors: Baruah Gaurav , Ozgul Arpat , Clements Christopher F.
Published: June 2022

Early warning signals (EWS) are phenomenological tools that have been proposed as predictors of the collapse of biological systems. Although a growing body of work has shown the utility of EWS based on either statistics derived from abundance data or shifts in phenotypic traits such as body size, so far this work has largely focused on single species populations.

However, to predict reliably the future state of ecological systems, which inherently could consist of multiple species, understanding how reliable such signals are in a community context is critical.

Here, reconciling quantitative trait evolution and Lotka–Volterra equations, which allow us to track both abundance and mean traits, we simulate the collapse of populations embedded in mutualistic and multi‐trophic predator–prey communities. Using these simulations and warning signals derived from both population‐ and community‐level data, we showed the utility of abundance‐based EWS, as well as metrics derived from stability‐landscape theory (e.g. width and depth of the basin of attraction), were fundamentally linked. Thus, the depth and width of such stability‐landscape curves could be used to identify which species should exhibit the strongest EWS of collapse.

The probability a species displays both trait and abundance‐based EWS was dependent on its position in a community, with some species able to act as indicator species. In addition, our results also demonstrated that in general trait‐based EWS were less reliable in comparison with abundance‐based EWS in forecasting species collapses in our simulated communities. Furthermore, community‐level abundance‐based EWS were fairly reliable in comparison with their species‐level counterparts in forecasting species‐level collapses.

Our study suggests a holistic framework that combines abundance‐based EWS and metrics derived from stability‐landscape theory that may help in forecasting species loss in a community context.
Assessment of screen‐recalled abnormalities for digital breast tomosynthesis versus digital mammography screening in the BreastScreen Maroondah trial
Authors: Li Tong , Lockie Darren , Clemson Michelle , Houssami Nehmat
Published: June 2022

Introduction

Australia's first population‐based pilot trial comparing digital breast tomosynthesis (DBT) and digital mammography (DM) screening reported detection measures in 2019. This study describes the trial's secondary outcomes pertaining to the assessment process in women screened with DBT or DM, including the type of recalled abnormalities and the procedures performed.

Methods

Women with suspected abnormalities at screening were recalled for further investigation. Outcome measures were number of lesions assessed, types of imaging findings recalled to assessment, and data on testing and assessment outcomes; these were reported using descriptive analyses of lesion‐specific data.

Results

A total of 274 lesions and 203 lesions were reported in the DBT‐screened and DM‐screened groups, respectively. There were a higher proportion of lesions depicted as calcifications (32.4% vs 21.3%), and a lower proportion of lesions depicted as asymmetrical densities (3.2% vs 15.7%) for DBT recalls than DM recalls. A lower proportion of DBT‐recalled lesions was assessed with additional mammography than DM‐recalled lesions (49.3% vs 93.1%). Higher proportions of DBT‐recalled lesions than DM‐recalled lesions were investigated with clinical breast examination (50.4% vs 39.9%), core needle biopsy (45.6% vs 28.6%) and open biopsy (4.0% vs 1.0%). Similar proportions of DBT‐ and DM‐recalled lesions were assessed using ultrasound (76.3% vs 71.4%).

Conclusion

Assessment of screen‐recalled lesions showed that, compared with DM, DBT found more benign and more malignant lesions, and generally required more procedures except for less additional mammography workup. These findings show that a transition to DBT screening changes the assessment workload.
Gamma knife radiosurgery for patients with brain metastases from non–small cell lung cancer: Comparison of survival between <5 and ≥5 metastases
Authors: Zhao Xu , Ding Shouluan , Zhang Ming , Wang Chengwei
Published: June 2022

Background

Current evidence‐based guidelines support stereotactic radiosurgery (SRS) for patients with up to four brain metastases (BMs). However, debate continues about how many tumors may be treated by SRS alone.

Methods

This retrospective study included non–small cell lung cancer (NSCLC) patients with BMs treated with gamma knife as the initial treatment for cerebral lesions. The patients were followed up to obtain their survival information. The outcomes were statistically analyzed to compare the differences in survival between the <5 BMs and ≥5 BMs groups and to identify prognostic factors.

Results

A total of 77 patients were divided into two groups (54 patients with <5 BMs and 23 patients with ≥5 BMs). The median overall survival (OS) was 18.3 months in the <5 BMs group and 17.7 months in the ≥5 BMs group. The median intracranial progression‐free survival (IPFS) was 9.0 months in the <5 BMs group and 9.9 months in the ≥5 BMs group. There was no significant difference in OS and IPFS between the two groups. The multivariate analysis demonstrated that adenocarcinoma, controlled primary cancer, higher Karnofsky Performance Scale (KPS), and salvage treatment were independent prognostic factors favoring longer OS.

Conclusion

SRS alone as the initial treatment for NSCLC patients with more than four BMs was non‐inferior to SRS for those with one to four BMs in terms of OS and IPFS.
Association of topiramate prescribed for any indication with reduced alcohol consumption in electronic health record data
Authors: Kranzler Henry R. , Leong Shirley H. , Naps Michelle , Hartwell Emily E. , Fiellin David A. , Rentsch Christopher T.
Published: June 2022

Background and Aims

Topiramate is a medication that is widely prescribed to treat a variety of conditions, including alcohol use disorder (AUD). We used electronic health record (EHR) data to measure topiramate's effects on drinking in individuals differentiated by a history of AUD.

Design

Parallel‐groups comparison of patients prescribed topiramate and a propensity score‐matched comparison group.

Setting

A large US integrated health‐care system.

Participants

Patients with Alcohol Use Disorders Identification Test–Consumption (AUDIT‐C) scores prior to and after a minimum of 180 days of topiramate prescription for any indication and a propensity score‐matched group. The sample included 5918 patients with an electronic health record diagnosis of alcohol use disorder at any time (AUD‐hx‐pos) (1738 topiramate‐exposed and 4180 controls) and 23 614 patients with no EHR diagnosis of AUD (AUD‐hx‐neg) (6324 topiramate‐exposed and 17 290 controls).

Measurements

Regression analyses compared difference‐in‐difference (DiD) estimates, separately by AUD history. DiD estimates represent exposure‐group (i.e. topiramate versus control) differences on the pre–post difference in AUDIT‐C score. Effects of baseline AUDIT‐C score and daily topiramate dosage were also tested.

Findings

AUD‐hx‐neg patients who received topiramate had a greater reduction in AUDIT‐C score (−0.11) than matched controls (−0.04). This yielded a DiD score of −0.07 [95% confidence interval (CI) = −0.11,‐0.03; P = 0.002], with the greatest effect among AUD‐hx‐neg patients with a baseline AUDIT‐C score of 4+ (DiD = −0.35, 95% CI = –0.49, −0.21; P < 0.0001) and those prescribed > 150 mg/day of the medication (DiD = −0.15, 95%CI = –0.23, −0.07; P < 0.001).

Discussion

Among individuals with no history of alcohol use disorder, topiramate appears to be associated with reduced drinking. This small effect is most evident among patients with higher baseline drinking levels and at a higher average daily topiramate dosage.
Familial associations in adolescent substance use disorder: a population‐based cohort study
Authors: Hamad Amani F. , Roos Leslie L. , Bolton James M. , Wall‐Wieler Elizabeth
Published: June 2022

Background and aims

Family history of substance use disorder (SUD) affects a child's risk of the disorder through both genetic and shared environmental factors. We aimed to estimate the association between parental or older sibling SUD history with the risk of adolescent SUD diagnosis.

Design, setting and participants

We conducted a population‐based cohort study using administrative health‐care databases in the Province of Manitoba, Canada, which has a universal and publicly funded health‐care system. We included all children born from 1984 to 2000 who have linkages to both parents and were followed until age 18 years. We used generalized estimating equation models to produce unadjusted and adjusted relative risk (RR) estimates of adolescent SUD risk. The study cohort included 134 389 children and 31 307 full sibling pairs; 51.3% were male and 35.4% first‐born.

Measurements

The exposure was SUD diagnosis in a mother or father in either hospitalization or outpatient physician visit records before the children's age of 13 years. The secondary exposure was an adolescent SUD diagnosis in an older full sibling. The outcome was SUD diagnosis during adolescence (13 and 18 years of age) identified in either hospitalization or physician visit records. Children demographics and characteristics associated with SUD diagnosis were included in the models.

Findings

Of the 134 389 children, 9.5% had a mother with a history of SUD, 11.3% had a father and 1.3% had an older sibling with a history of SUD diagnosis; 2566 (1.9%) had an adolescent SUD diagnosis. An increased risk of adolescent SUD was observed with SUD history in mothers [adjusted RR (aRR) = 2.50; 95% confidence interval (CI) = 2.26, 2.79], fathers (aRR = 2.15; 95% CI = 1.95, 2.37), both parents (aRR = 3.74; 95% CI = 3.24, 4.31) and older sibling (aRR = 3.85; 95% CI = 2.53, 5.87).

Conclusions

A family history of substance use disorder in parents or older siblings appears to be associated with increased SUD risk in adolescents.
Peyronie's disease development and management in diabetic men
Authors: Gianazza Simone , Belladelli Federico , Leni Riccardo , Masci Federica , Rossi Piercarlo , Gianesini Giuseppe , Maggio Paolo , Zaffuto Emanuele , Salonia Andrea , Carcano Giulio , Dehò Federico , Capogrosso Paolo
Published: June 2022

Background

Peyronie's disease (PD) is a fibrosing disorder of the penis resulting in plaque formation and penile deformity that negatively affect sexual and psychosocial function of patients. A multifactorial etiology of PD is assumed with diabetes mellitus (DM) being a potential risk factor.

Objectives

The aim of this narrative review was to investigate diabetes role in PD pathophysiology, diagnosis, and treatment.

Materials and methods

A non‐systematic narrative review of original articles, meta‐analyses, and randomized trials was conducted, including articles in the pre‐clinical setting to support relevant findings.

Results

Diabetes is one of the most common comorbidity observed in PD patients, with a prevalence of about 11% and a strong association with erectile dysfunction (ED). DM is associated with both a higher risk of developing PD and has also an impact on the outcomes of PD's treatments.

Discussion

Evidence from literature underlines that metabolic alterations typical of DM are pivotal factors in the development of PD and resistance to its medical treatment.

Conclusion

The role of DM in development of PD is still debated, while its role in PD development is not completely clear, there is a clear impact of DM on PD treatment outcomes.
Review article: novel biomarkers in hepatitis B infection
Authors: Lok James , Dusheiko Geoffrey , Carey Ivana , Agarwal Kosh
Published: June 2022

Background

Chronic hepatitis B remains a global health problem with an estimated 296 million people affected worldwide. Individuals are at risk of serious complications such as cirrhosis and hepatocellular carcinoma and accurately predicting these clinical endpoints has proven difficult. However, several viral biomarkers have recently been developed, including quantitative HBV surface antigen (qHBsAg), hepatitis B RNA (HBV RNA) and core‐related antigen (HBcrAg), and shown promise in a range of clinical settings.

Aims

To critically appraise these novel biomarkers, exploring their potential uses, availability of assays and areas for future development.

Methods

We performed a literature search of PubMed, identifying articles published in the field of hepatitis B biomarkers between 2010 and 2022.

Results

Novel biomarkers such as HBcrAg, HBV RNA and qHBsAg may be useful in predicting treatment outcomes, stratifying the risk of future complications and estimating off‐treatment viral reactivation. Furthermore, HBV RNA and HBcrAg titres may accurately reflect cccDNA transcriptional activity, and this is particularly informative in the context of nucleoside analogue therapy. On a cautionary note, most studies have been performed in Caucasian or Asian populations, and methods for detecting HBV RNA lack standardisation.

Conclusion

Novel viral biomarkers have the potential to provide additional insights into the natural history of infection and allow a more bespoke, cost‐effective framework of care. However, access remains limited, and further efforts are needed to validate their use in ethnically diverse populations, confirm predictive cut‐off values, and establish their role in the era of novel antiviral therapies.
Pharmacokinetics, safety, and tolerability of gepotidacin administered as single or repeat ascending doses, in healthy adults and elderly subjects
Authors: Tiffany Courtney , Dumont Etienne F. , Hossain Mohammad , Srinivasan Meenakshi , Swift Brandon
Published: June 2022

Gepotidacin, a novel, first‐in‐class triazaacenaphthylene antibiotic, inhibits bacterial DNA replication by a distinct mechanism of action. We report the pharmacokinetics (PKs), safety, and tolerability of gepotidacin following single or multiple ascending doses. Studies 1 and 2 were randomized, single‐blind, placebo‐controlled trials in healthy adults aged 18–60 years, who received single (study 1 [NCT02202187]; 100–3000 mg) or repeat (study 2 [NCT01706315]; 400 mg twice daily to 2000 mg thrice daily) ascending doses of gepotidacin. Study 3 (NCT02045849) was an open‐label, three‐part, study in healthy adults; here, we report on part 3, a two‐period, repeat‐dose, crossover study. Healthy elderly participants received repeat 1500 mg gepotidacin twice daily with or without a moderate‐fat meal. Primary end points were PKs (studies 1 and 2) and safety (studies 1 and 3 part 3). Gepotidacin PK parameters were comparable across all ages and were dose proportional. In all studies, gepotidacin was readily absorbed with median time to maximum concentration observed ranging from 1.0 to 4.0 h across all doses. Median apparent terminal phase half‐life was consistent across studies and doses (range: 5.97–19.2 h). Steady‐state was achieved following repeated dosing for 3–5 days; gepotidacin PK parameters were time invariant after repeated oral dosing. A moderate‐fat meal did not affect gepotidacin PK parameters. Gepotidacin was generally well‐tolerated, with no drug‐related serious adverse events reported. Collectively, these PK and safety data across a wide range of doses in healthy participants aged greater than or equal to 18 years support the development of gepotidacin in further clinical studies.
Case of superficial esophageal cancer resected by modified gel immersion endoscopic submucosal dissection technique
Authors: Yamada Keisaku , Tajika Masahiro , Niwa Yasumasa
Published: June 2022

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Polyploidization as an opportunistic mutation: The role of unreduced gametes formation and genetic drift in polyploid establishment
Authors: Clo Josselin , Padilla‐García Nélida , Kolář Filip
Published: June 2022

It is broadly assumed that polyploidy success reflects an increase in fitness associated with whole‐genome duplication (WGD), due to higher tolerance to stressful conditions. Nevertheless, WGD also arises with several costs in neo‐polyploid lineages, like genomic instability, or cellular mis‐management. In addition to these costs, neo‐polyploid individuals also face frequency dependent selection because of frequent low‐fitness triploids formed by cross‐ploidy pollinations when tetraploids are primarily rare in the population. Interestingly, the idea that polyploidy can be fixed by genetic drift as a neutral or deleterious mutation is currently underexplored in the literature. To test how and when polyploidy can fix in a population by chance, we built a theoretical model in which autopolyploidization occurs through the production of unreduced gametes, a trait modelled as a quantitative trait that is allowed to vary through time. We found that when tetraploid individuals are less or as fit as their diploid progenitors, fixation of polyploidy is only possible when genetic drift is stronger than natural selection. The necessity of drift for tetraploid fixation holds even when polyploidy confers a selective advantage, except for scenarios where tetraploids are much fitter than diploids. Finally, we found that self‐fertilization is less beneficial for tetraploid establishment than previously thought, notably when polyploids harbour an initial decrease in fitness. Our results bring a novel, non‐exclusive explanation for the unequal temporal and spatial distribution of polyploid species.
Prioritizing nursing home staff and leadership consistency to improve quality
Authors: Carnahan Jennifer L. , Unroe Kathleen T.
Published: June 2022

This Editorial comments on the article by Zheng et al. in this issue.
Comparative clinical study for the efficacy and safety of two different hyaluronic acid‐based fillers with Tri‐Hyal versus Vycross technology: A long‐term prospective randomized clinical trial
Authors: Braccini Frederic , Fanian Ferial , Garcia Philippe , Delmar Henry , Loreto Federico , Benadiba Laurent , Nadra Karim , Kestemont Philippe
Published: June 2022

Background

Hyaluronic acid‐based fillers have an immediate volumizing effect for the treatment of dermal contour deformities and to smooth dermal depressions formed by the loss of volume. A previous study on 2016–2018 has shown the efficacy and safety of the HA‐based filler ART FILLER® Volume on the midface only, but not in a comparative manner.

Methods

In this context, an 18 months prospective randomized single‐blind study of the non‐inferiority of ART FILLER® Volume versus the reference product Juvéderm Voluma® was performed on the midface, temple, and jawline, and non‐comparative study on the chin. The efficacy and the longevity were evaluated for the selected face areas via dedicated clinical scoring systems after a single filler injection without any re‐touch or re‐injection. The short‐ and long‐term adverse effects were also recorded.

Results

The observations confirmed the non‐inferiority of ART FILLER® Volume versus the reference product on the different injected areas. For both fillers, the beneficial effects on volumes restoration were maintained 18 months post‐injection; however, these effects were diminished among the time. Furthermore, injections of Art Filler® Volume were well tolerated by the subjects and showed less acute side effects compared with the reference product that may be explained by a lower induction of inflammation.
“You're biracial but…”: Multiracial socialization discourse among mommy bloggers with Black and non‐Black multiracial children
Authors: Reyna Chandra V.
Published: June 2022

Objective

This study examines thematic content and discourse surrounding multiracial socialization between Black and non‐Black multiracial families on multiracial mommy blogs.

Background

Mommy blogs have been recognized as a medium through which mothers challenge dominant representations of motherhood, create community with other mothers, and seek out advice. But little is known about how mothers write about and discuss race, racism, and multiracial socialization online. This study addresses this knowledge gap by analyzing how a niche of bloggers—mothers to multiracial children—construct narratives surrounding race, multiraciality, and multiracial socialization online and how their narratives differ by the racial makeup of the blogger's family.

Method

Using a MultiCrit framework, this study analyzes 13 mommy blogs written by mothers of color with multiracial children. Blogs were analyzed for thematic content related to race, racial identification, multiraciality, and multiracial socialization.

Results

The findings demonstrate that mothers' orientations to multiracial socialization vary depending on whether the blogger has Black or non‐Black multiracial children. Bloggers who are mothers to Black multiracial children blogged frequently about their engagement insafety socialization, whereas mothers with non‐Black multiracial children did not.

Conclusion

The stark difference between thematic content from bloggers with and without Black multiracial children highlights the differing experiences among Black and non‐Black multiracial people, for mothers of Black multiracial children, and the implications anti‐Black racism has on family processes.
Morphology of Peri‐Implant Tissues Around Permanent Prostheses With Various Emergence Angles Following Free Gingival Grafting
Authors: Lin I‐Ping , Chen Szu‐Han , Chang Chung‐Chieh , Chang Jenny Zwei‐Chieng , Sun Jui‐Sheng , Chang Chih‐Hao
Published: June 2022

Purpose

To analyze the tissue morphology around implant‐supported prostheses by digital technology and to evaluate the effect of prosthetic contours on the changes in tissues following the free gingiva graft procedure.

Material and methods

A total of 53 implants in 32 patients receiving free gingiva grafts were selected. These had previously presented insufficient keratinized mucosa width (KMW). At the follow‐up visits (mean: 16.66 ± 9.97 months), the implant position and tissue condition were documented with an oral scanner. Vertical soft tissue thickness (VT), measured from the implant‐abutment connection to the marginal tissues, and horizontal soft tissue thickness (HT), at the level of the platform, were calculated. The VT, HT, and emergence angle (EA) of prostheses were assessed by 3Shape analyzing software. The final KMW was measured by clinical assessment. Marginal bone loss (MBL) was calculated in the follow‐up bitewing radiographs.

Results

The mean VT in the study was 2.65 ± 0.75 mm at the mid‐buccal sites, 3.74 ± 1.22 mm at the mesial, 3.16 ± 1.08 mm at the distal, and 2.53 ± 0.92 at the mid‐lingual aspects. The mid‐buccal HT was 1.45 ± 0.53 mm while the mid‐lingual was 1.05 ± 0.43 mm (p = 0.008). Interestingly, prostheses with mid‐buccal EA30° exhibited slightly lower VT, but higher HT, than the ones with EA30°. Prostheses with proximal EA > 30° displayed slightly more MBL, compared to prostheses with EA30°. The mean KMW was 4.08 ± 1.10 mm.

Conclusions

Free gingival grafting is a predictable treatment approach to augmenting soft tissue 3‐dimensionally. Prostheses with EA30° were preferable for preserving the maximal VT and maintaining crestal bone stability.
Halotolerant native bacteria Enterobacter 64S1 and Pseudomonas 42P4 alleviate saline stress in tomato plants
Authors: Pérez‐Rodriguez María Micaela , Pontin Mariela , Piccoli Patricia , Lobato Ureche Miguel Andrés , Gordillo María G. , Funes‐Pinter Iván , Cohen Ana Carmen
Published: June 2022

Salinity is one of the principal abiotic stresses that limit the growth and productivity of crops. The use of halotolerant plant growth‐promoting rhizobacteria (PGPR) that increase the growth of salt‐stressed crops is an environmentally friendly alternative to promote plant yield under salinity. The aim of this study was to test native PGPR, isolated according to their tolerance to NaCl, and to evaluate their influence on morphological, physiological, and biochemical traits promoted by salt stress in tomato plants. Enterobacter 64S1 and Pseudomonas 42P4 were selected as the most efficient strains in terms of salt tolerance. Both strains were classified as moderately resistant to salinity (NaCl) and maintained their plant growth‐promoting activities, such as nitrogen fixation and phosphate solubilization, even in the presence of high levels of salt. The results of a greenhouse experiment demonstrated that PGPR inoculation increased root and shoot dry weight, stem diameter, plant height, and leaf area compared to control noninoculated plants under nonsaline stress conditions, reversing the effects of salinity. Inoculated plants showed increased tolerance to salt conditions by reducing electrolyte leakage (improved membrane stability) and lipid peroxidation and increasing chlorophyll quantum efficiency (Fv/Fm) and the performance index. Also, inoculation increased the accumulation of proline and antioxidant nonenzymatic compounds, such as carotenes and total phenolic compounds. The catalase and peroxidase activities increased with salinity, but the effect was reversed by Enterobacter 64S1. In conclusion, Enterobacter 64S1 and Pseudomonas 42P4 isolated from salt‐affected regions have the potential to alleviate the deleterious effects of salt stress in tomato crops.
Numerical Simulation of Biogas Combustion by Using a Finite Volume Based-Multispecies Transport Model
Authors: Stéphane Kenfack Lontsi , Charles Chelem Mayigué , Paul Pountounynyi , Brice Obounou Akong Marcel , Sylvain Zekeng Serge
Published: June 2022

In this paper, we advocate the use of multispecies transport model coupled to global mechanisms instead of using detailed mechanisms, which are still not yet computational affordable for the majority of the research groups in Africa. The open-source sofware openFOAM® is used as the calculation platform. The obtained algorithm is validated by comparing its simulation results to the full Gas Research Institut (GRI)-3.0 mechanism-based simulations of Charest et al. (2014, “Numerical and Experimental Study of Soot Formation in Laminar Diffusion Flames Burning Simulated Biogas Fuels at Elevated Pressures,” Combust. Flame, 161, pp. 2678–2691) with quite satisfactory agreement for methane flames diluted with CO2. The new code is then used to investigate the axial flame temperature of locally produced biogases from pig slurry and cow dung respectively named BG L1, BG L2, BG B1, and BG B2. These biogases differ from each other in their composition. Methane proportion in the mixture ranges from 46% to 52%.
Effect of Polyurethane Stabilization and Coal Fouling on Drainage Behaviour of Railroad Ballast
Authors: Gundavaram Dinesh , Hussaini Syed Khaja Karimullah
Published: June 2022

Contamination of ballast not only adversely affects the track stability but also impedes the track drainage. While the use of polyurethane in ballast enhances the track stability due to polyurethane bond between the aggregates, but it may reduce the permeability of ballast. In this context, the drainage characteristics of the polyurethane-stabilized and unstabilized ballast under fresh and coal fouled conditions were assessed by using large-scale permeability apparatus. The test results highlighted that the hydraulic conductivity of ballast (k) decreased slightly from 43 mm/s to 37 mm/s upon polyurethane treatment. However, the coal fines have drastically decreased the value of k for both stabilized and unstabilized ballast. For unstabilized ballast, as the fouling content (Pf) is increased from 0 to 21.2%, the value of k reduced from 43 to 0.18 mm/s. The relative hydraulic conductivity ratio (kcb/kfb), computed as the fraction of hydraulic conductivity of clean ballast to that of fouled ballast was found to increase from 1 (one) to 29 and 239 as fouling content increased from 0 to 4.24% and 21.2%, respectively. Moreover, tortuosity (T) defined as the ratio of the actual flow path length to the length of porous sample increased from 1.59 in case of clean ballast to 1.98 due to fouling (Pf:21.2%). The corresponding values of T upon polyurethane stabilization increases to 1.64 and 2.08, respectively. In addition, a nonlinear empirical relationship was established between the k and T of ballast.
A Method for High Fidelity Simulations of Railway Virtual Coupling
Authors: Wu Qing , Ge Xiaohua , Cole Colin , Spiryagin Maksym
Published: June 2022

Virtual coupling uses wireless communications between railway trains to significantly reduce headways. Current train dynamics simulation methods in this topic model a whole trainset as a single mass neglecting inter-vehicle actions (in-train forces) as well as nonlinearities in traction, braking, suspension, and wheel-rail contact. This paper presents a better simulation method for railway virtual coupling by using high fidelity models to consider the previously neglected factors. The simulated train platoon is coordinated by using a detailed train control algorithm to safely keep the designed headway. Train dynamics simulations are then solved by using a parallel computing technique in which the Vehicle System Dynamics (VSD) simulation of each individual vehicle is assigned to an independent computer core. All used computer cores communicate via the parallel computing technique to exchange information to proceed with the simulations collaboratively. This new simulation method allows a better validation of the virtual coupling control algorithm and detailed assessments of train safety and general performance.
Advances in Railway Mechanical Engineering 2020 – 2021 Survey – Locomotives
Authors: Mast Timothy
Published: June 2022

This survey reports on motive power development for the previous year ending in August 2021. Invitations to participate were sent to a number of locomotive builders. Railway industry trade journals and other rail magazines were also consulted for additional input. Similar to the previous year, new locomotive production has been very low with a strong emphasis placed on locomotive overhauls and modernizations. Of the few new locomotives constructed in North America, Progress Rail and Wabtec have both continued working on new power sources for locomotives including battery electric, biodiesel and hydrogen. In Sweden, Alstom operated the first train running on hydrogen. For the first time since 2001, Amtrak received new diesel road locomotives for its non-electrified routes with VIA Rail’s new locomotives and trainsets not far behind. Finally, the survey will look at a motive power development of an 80-year-old locomotive as UP implements I-ETMS as Positive Train Control on their operational Big Boy steam engine using a trailing diesel locomotive. General information will be provided. For further details on any of the developments in the design of railway locomotives the reader is encouraged to reach out the original equipment manufacturers.