bluuebunny/crossref_metadata_2025 huggingface dataset:
National diagnostic reference levels: What they are, why we need them and what’s next
Authors: Thomas Peter
Published: March 2022

Diagnostic reference levels (DRLs) are an optimisation tool for medical imaging procedures using ionising radiation. They give an indication of the expected radiation dose received by an average‐sized patient undergoing a given imaging procedure. Comparison of typical (median) exposure levels for common imaging procedures with DRLs helps imaging facilities identify procedures that may be amenable to further optimisation. Undertaking comparisons with published DRLs is a requirement for medical imaging facilities under the Code for Radiation Protection in Medical Exposure and for their access to Medicare rebates under the Diagnostic Imaging Accreditation Scheme (DIAS). The Australian Radiation Protection and Nuclear Safety Agency has created the National Diagnostic Reference Level Service to facilitate the collection of data for the establishment of national DRLs in Australia and to assist imaging facilities in comparing their typical doses with the national DRLs. National DRLs have been established in computed tomography, nuclear medicine, and for image‐guided and interventional procedures. DRLs must be subject to ongoing review and revision by the national authority to ensure they reflect current practice. This ongoing cycle of assessment and review helps to ensure that the ratio of benefit to risk for patients is maximised.
‘With great power comes great responsibility’: An impetus for quality and safety in radiation oncology
Authors: Chilkuri Madhavi , Millar Jeremy , Adams Gerard
Published: March 2022

Strict quality control and vigilance at every step is essential to maintain rigour and ensure quality and safety in radiation oncology. The scientific knowledge and technological capabilities we possess give us enormous power to deliver specialised and complex treatments and improve health outcomes for our cancer patients. However, this requires development of whole system performance and its evaluation against established standards and benchmarks. It calls for organisational commitment and active participation of managers and clinical teams in quality improvement initiatives. In addition to medical physicists and radiation therapist, radiation oncologists, including trainees, must accept important leadership responsibilities to maintain a positive safety culture.
Quality use of artificial intelligence in medical imaging: What do radiologists need to know?
Authors: Goergen Stacy K , Frazer Helen ML , Reddy Sandeep
Published: March 2022

The application of artificial intelligence, and in particular machine learning, to the practice of radiology, is already impacting the quality of imaging care. It will increasingly do so in the future. Radiologists need to be aware of factors that govern the quality of these tools at the development, regulatory and clinical implementation stages in order to make judicious decisions about their use in daily practice.
Prognostic significance of albumin–bilirubin score in patients with unresectable hepatocellular carcinoma undergoing combined immunotherapy and radiotherapy
Authors: Dong Dezuo , Zhu Xianggao , Wang Hongzhi , Li Lijuan , Wan Meng , Li Shuai , Zhang Yangzi , Geng Jianhao , Li Yongheng , Wang Weihu
Published: March 2022

Introduction

We aimed to explore the prognostic value of albumin–bilirubin (ALBI) scores in unresectable hepatocellular carcinoma (HCC) treated with combined immune checkpoint inhibitors (ICIs) and radiotherapy (RT).

Methods

Patients with unresectable HCC receiving combined ICI and RT (July 2018 to February 2021) were retrospectively enrolled and analysed. Cox regression modelling was implemented to identify prognostic factors. Survival analysis was performed using the Kaplan–Meier method. Survival was compared using log‐rank tests.

Results

A total of 38 patients were enrolled. The median follow‐up was 16.5 months (range: 6.7–29.9). The objective response rate (ORR) was 28.9%, including complete response in three (7.9%) patients. The median progression‐free survival (PFS) was 5.6 months (95% confidence interval (CI): 3.2–8.0), and the median overall survival (OS) was 12.9 months (95% CI: 8.3–17.6). In the multivariate Cox regression analysis, ALBI score and age were identified as independent prognostic factors for PFS and OS. Patients with grade 1 ALBI scores who were ≥53 years of age (the low‐risk group) had statistically significantly higher ORRs (50.0% vs. 13.6%) and prolonged median PFS (15.3 vs. 2.7 months) and OS (not reached vs. 10.1 months). Grade 3 haematological toxicities and/or liver function abnormalities occurred in 15 (39.5%) patients; treatment was not interrupted. No grade 4 or higher side effects were observed.

Conclusion

Combined ICI and RT is an effective modality for treating unresectable HCC with moderate side effects. ALBI scores merits consideration when applying this combined treatment modality. These results should be validated within large cohort studies.
Childhood trauma and treatment outcomes during mood‐stabilising treatment with lithium or quetiapine among outpatients with bipolar disorder
Authors: Wrobel Anna L. , Köhler‐Forsberg Ole , Sylvia Louisa G. , Russell Samantha E. , Dean Olivia M. , Cotton Sue M. , Thase Michael , Calabrese Joseph R. , Deckersbach Thilo , Tohen Mauricio , Bowden Charles L. , McInnis Melvin G. , Kocsis James H. , Friedman Edward S. , Ketter Terence A. , Shelton Richard C. , Ostacher Michael J. , Iosifescu Dan V. , Berk Michael , Turner Alyna , Nierenberg Andrew A.
Published: March 2022

Background

Childhood trauma affects the course of mood disorders. Researchers are now considering childhood trauma as an influential factor in the treatment of mood disorders. However, the role of childhood trauma in the treatment of bipolar disorder remains understudied.

Methods

The effect of childhood trauma on treatment outcomes was evaluated among participants randomised to treatment with lithium or quetiapine in the Clinical and Health Outcomes Initiatives in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE) study by clinician assessment. Mixed effects linear regression models were used to analyse rates of improvement in symptom severity (assessed with the Bipolar Inventory of Symptoms Scale and the Clinical Global Impression Scale for Bipolar Disorder) and functional impairment (assessed with the Longitudinal Interval Follow‐up Evaluation‐Range of Impaired Functioning Tool).

Results

A history of any childhood trauma was reported by 52.7% of the sample (N = 476). Although participants with a history of any childhood trauma presented with greater symptom severity and functional impairment at most study visits, participants with and without a history of any childhood trauma showed similar rates of improvement in symptom severity and functional impairment over the 24 weeks of treatment.

Conclusion

This is the first study to explore the association between childhood trauma and treatment outcomes during treatment with lithium or quetiapine in the context of a randomised trial. In Bipolar CHOICE, a history of childhood trauma did not inhibit improvement in symptom severity or functional impairment. Nevertheless, these findings need replication across different settings.
Impact of state and trait anxiety severity on retention and phase advancement in an outpatient buprenorphine treatment program
Authors: Gokarakonda Srinivasa B. , Boydstun Jacob M. , Yilanli Musa , Han Xiaotong , Kumar Nihit , Oliveto Alison H. , Mancino Michael J.
Published: March 2022

Background and Objectives

Comorbid anxiety is common among buprenorphine patients and may lead to poorer outcomes. This study aimed to examine the prevalence and impact of anxiety severity, measured by the State‐Trait Anxiety Inventory (STAI) form Y‐1 & Y2 scale, on treatment outcomes (retention and phase advancement) among outpatient buprenorphine‐treated patients.

Methods

A retrospective chart review of 94 patients admitted to an outpatient buprenorphine treatment program was conducted. Patients were dichotomized into high and low severity groups based upon an STAI State Anxiety (S‐Anxiety) and STAI Trait Anxiety (T‐Anxiety) score ≥60 and <60, respectively. Associations of anxiety severity on successful phase advancement and retention during the first 90 days of treatment were assessed.

Results

Twenty‐one of 94 (22%) participants reported high S‐Anxiety and had a significantly greater likelihood of phase advancement (OR = 12.80, 95% CI = [1.19, 136.71]) than those with low S‐Anxiety. No significant associations were found between either S‐Anxiety or T‐Anxiety and treatment retention. Current alcohol use and UDS negative test results for THC or amphetamines were each associated with phase advancement. THC negative UDS test results were associated with 90‐day treatment retention.

Discussion and Conclusions

Contrary to prior reports, buprenorphine patients with higher state anxiety severity demonstrated similar retention and more rapid phase advancement than those with lower state anxiety severity.

Scientific Significance

To our knowledge, this is the first study to quantify current anxiety severity using the STAI scale and evaluate its impact on treatment outcomes among buprenorphine‐treated patients.
Letter: the potential link between oesophageal hypervigilance, visceral anxiety, increased swallow rate and oesophageal mucosal integrity
Authors: Ribolsi Mentore , Savarino Edoardo
Published: March 2022

LINKED CONTENT

This article is linked to Wong et al papers. To view these articles, visit https://doi.org/10.1111/apt.16561 and https://doi.org/10.1111/apt.16801
Editorial: infections and hepatic encephalopathy–does the chicken or the egg come FIRST? A novel perspective at the horizon
Authors: Riggio Oliviero , Ridola Lorenzo
Published: March 2022

LINKED CONTENT

This article is linked to Alabsawy et al papers. To view these articles, visit https://doi.org/10.1111/apt.16790 and https://doi.org/10.1111/apt.16829
Editorial: infections and hepatic encephalopathy—does the chicken or the egg come first? A novel perspective at the horizon. Authors’ reply
Authors: Alabsawy Eman , Shalimar  , Jalan Rajiv
Published: March 2022

LINKED CONTENT

This article is linked to Alabsawy et al papers. To view these articles, visit https://doi.org/10.1111/apt.16790 and https://doi.org/10.1111/apt.16809
Justice and the racial dimensions of health inequalities: A view from COVID‐19
Authors: Ganguli‐Mitra Agomoni , Qureshi Kaveri , Curry Gwenetta D. , Meer Nasar
Published: March 2022

In this paper, we take up the call to further examine structural injustice in health, and racial inequalities in particular. We examine the many facets of racism: structural, interpersonal and institutional as they appeared in the COVID‐19 pandemic in the UK, and emphasize the relevance of their systemic character. We suggest that such inequalities were entirely foreseeable, for their causal mechanisms are deeply ingrained in our social structures. It is by recognizing the conventional, un‐extraordinary nature of racism within social systems that we can begin to address socially mediated health inequalities.
Reading with induced worry: The role of physiological self‐regulation and working memory updating in text comprehension
Authors: Zaccoletti Sonia , Raccanello Daniela , Burro Roberto , Mason Lucia
Published: March 2022

Background

An interplay of emotional and cognitive aspects underlies academic performance. We focused on the contribution of such interplay to text comprehension.

Aims

We investigated the effect of worry on comprehension and the role of two potential moderators of this effect: physiological self‐regulation as resting heart rate variability (HRV) and working memory updating.

Sample

Eighty‐two seventh graders were involved in a quasi‐experimental design.

Methods

Students read an informational text in one of two reading conditions: to read for themselves to know more (n = 46; low‐worry condition) or to gain the highest score in a ranking (n = 36; high‐worry condition). Students’ resting HRV was recorded while watching a video of a natural scenario. The executive function of working memory updating was also assessed. After reading, students completed a comprehension task.

Results

Findings revealed the moderating role of HRV in the relationship between induced worry and text comprehension. In the high‐worry condition, students with higher resting HRV performed better than students who read under the same instructions but had lower HRV. In contrast, in the low‐worry condition, students with higher resting HRV showed a lower performance as compared to students with lower HRV. Finally, working memory updating was positively related to text comprehension.

Conclusions

Our findings indicate that the cognitive component of anxiety, that is, worry, plays a role in performing a fundamental learning activity like text comprehension. The importance of physiological self‐regulation emerges clearly. In a condition of high worry, higher ability to regulate emotions and thoughts acts as a protective factor.
Comorbidities in women living with HIV: A systematic review
Authors: Raffe Sonia , Sabin Caroline , Gilleece Yvonne ,   Women Against Viruses in Europe (WAVE), European AIDS Clinical Society
Published: March 2022

Objectives

Effective antiretroviral therapy (ART) has improved the life expectancy of women living with HIV (WLWH). This population is now experiencing age‐related comorbidities. This systematic review presents the current understanding of the prevalence and impact of comorbidities in WLWH in the modern ART era.

Methods

MEDLINE and Embase were searched for studies (1 January 2010 to 1 September 2020) reporting the prevalence of cardiovascular, bone, renal and neurocognitive disease in WLWH aged > 18 years. Studies were included if at least 100 participants (or > 50%) were female and data analysis included prevalence by sex.

Results

In all, 3050 articles were identified and screened; 153 full‐text articles were assessed for eligibility and 38 were included in the final review. Significant gaps in the literature were identified, notably a lack of data on WLWH aged > 50 years. The data suggest a high burden of cardiovascular, bone, renal and neurocognitive disease in WLWH compared with HIV negative women. Traditional risk factors, such as hypertension, diabetes and dyslipidaemia, were common and often poorly managed. Generalizability of the results was limited, as many studies were conducted in the USA. Comparisons between WLWH and men with HIV were limited by marked differences in demographic and socioeconomic factors.

Conclusions

Women living with HIV experience a high burden of comorbid disease. Traditional risk factors are common and often poorly managed. This review also highlights the magnitude of differences between women and men living with HIV beyond the pathophysiological. Future research must unpick the complex drivers of morbidity in WLWH, to improve the holistic management of this population.
Exploring compounds to be used as cosmetic agents that activate peroxisome proliferator‐activated receptor alpha
Authors: Tachibana Keisuke , Fukuda Syohei , Fukushima Jun , Ishimoto Kenji , Sakata Masahiro , Nishimori Yasutomo , Doi Takefumi
Published: March 2022

Objective

The human epidermis is formed by the proliferation and differentiation of keratinocytes adjacent to the basement membrane. The outermost layer, the stratum corneum, is equipped with a barrier function that prevents water evaporation, and intercellular lipids play an important role in this barrier function. When the barrier is functioning normally, evaporation is prevented; however, when barrier function is impaired, moisture evaporates, resulting in dry and rough skin. Therefore, maintenance of normal barrier function is critical for maintaining normal skin function. Peroxisome proliferator‐activated receptor α (PPARα) is mainly not only involved in lipid metabolism in the liver but is also expressed in the epidermis and is involved in inducing keratinocyte differentiation, promoting lipid production, maintaining barrier function and suppressing skin inflammation. Hence, compounds that activate PPARα are expected to control skin function. Therefore, we identified PPARα activators from among extracts of natural resources that have been approved for use in humans and analysed the effects of these extracts on skin function.

Methods

First, extracts of 474 natural resources were screened using a PPARα activator screening cell line independently constructed in our laboratory. Next, reporter assays were performed using the Gal4‐chimera system to evaluate whether these extracts act as ligands for PPARα. We then analysed their effect on primary normal human epidermal keratinocyte cells by using real‐time RT‐PCR. Finally, we evaluated PPARα activation effect by the combination of these extracts.

Results

We identified 36 extracts having the effect of activating PPARα. In particular, #419, a Typha angustifolia spike extract, showed concentration‐dependent transcriptional activation through PPARα‐LBD and was considered to be likely to contain a compound that is a ligand of PPARα. #419 increased the expression of PPARα target genes and genes related to skin function in primary cultured human epidermal keratinocytes. Finally, the use of #419 in combination with nine extracts increased PPAR activity more than twice as much as #419 alone treatment.

Conclusions

These results showed that the reporter cell line could be useful for discovering extracts of natural resources and that the identified Typha angustifolia spike extract could be used in cosmetics that activate PPARα, which expected to improve skin function.
External cervical resorption – Treatment outcomes and determinants: A retrospective cohort study with up to 10 years of follow‐up
Authors: Irinakis Eleni , Haapasalo Markus , Shen Ya , Aleksejuniene Jolanta
Published: March 2022

Aim

To assess long‐term external cervical resorption (ECR) treatment outcomes in relation to both local and treatment‐related determinants.

Methodology

Information was available for 76 patients (98 teeth) who were diagnosed with ECR during the period from 2008 to 2018 at the University of British Columbia graduate endodontics clinic. The ECR patients were followed up, and a clinical and radiographic examination was conducted. Chi‐square test compared failure rates amongst different subgroups. The survival analysis was used to evaluate the overall ECR survival/failure rates in relation to several local and treatment‐related determinants.

Results

Overall, 67 patients (89 teeth) were followed up. The mean follow‐up time was 3.9 years, and the minimum was 1 year. Twenty‐four teeth failed (19 extracted, 5 not functional), and the overall probability of failure was 50.0% 8 years after the diagnosis. Significant (p < .05) local ECR determinants were tooth location and the Heithersay classification, and treatment‐related determinants were root canal treatment (RCT) and the ECR repair combined with RCT. Treatment outcomes for Heithersay class 1 and 2 cases were better than for class 3 and 4 cases.

Conclusions

Higher failure rates were associated with posterior tooth location and higher Heithersay class, whilst RCT and ECR repair combined with RCT were associated with lower failure rates.
PCAOB international inspections: Updates and extensions
Authors: Hong Philip Keejae , Kerr David S. , Wiggins Casper E.
Published: March 2022

Based on data from 760 PCAOB inspection reports issued between December 2006 and April 2021 for 305 non‐U.S. audit firms, this paper analyses changes and trends in PCAOB inspection traits, inspection outcomes, audit firm characteristics and firms' reactions to those inspections. We find significant changes have occurred in several areas, including changes in audit quality for both principal‐auditor engagements and referred‐work (i.e., other auditor) engagements, audit deficiency rates for both Big‐4 affiliated firms and unaffiliated firms, firms' responses to inspections and several other changes. We also find a significant iteraction between the firm's network affiliation and the firm's role in the engagement (i.e., principal auditor vs. referred work). Further analysis of this interaction reveals that when unaffiliated firms perform referred‐work engagements, they have better PCAOB inspection outcomes than when performing principal‐auditor engagements. However, affiliation with a network mitigates this outcome.
Effectiveness and safety of electrical stimulation for treating pressure ulcers: A systematic review and meta‐analysis
Authors: Chen Lian , Ruan Yue , Ma Yuxia , Ge Long , Han Lin
Published: March 2022

Aim

This study aims to synthesize qualitative evidence on the effectiveness and safety of electrical stimulation for treating pressure ulcers.

Background

Electrical stimulation is often used clinically to treat pressure ulcers, but its effectiveness and safety and some potential problems are not clear.

Design

This is a qualitative systematic review.

Data Sources

The data sources are four English databases (PubMed, EMBASE, The Cochrane Library and Web of Science) and four Chinese databases (CNKI, SinoMed, VIP and WANFANG).

Methods

Two reviewers independently examined the records according to the eligibility criteria and extracted the data of each included study. We used the Review Manager 5.3 software to perform data analysis.

Results

Seventeen randomized controlled trials including 740 patients were included in this study. Meta‐analysis of eight randomized controlled trials demonstrated that electrical stimulation significantly reduced the ulcer surface in contrast with standard wound care alone or pulsed sham electrical stimulation. Nine studies showed that electrical stimulation increased the risk of pressure ulcers being completely healed than the controlled group. Three studies reported that adverse reactions were rare.

Conclusions

This study demonstrated that electrical stimulation was a relatively effective and safe adjunctive therapy for pressure ulcers treatment.
Predictors of COVID‐19 preventive behaviours in a sample of the Turkish population
Authors: Savci Cemile , Cil Akinci Ayse
Published: March 2022

Aim

This research aimed to determine predictors of COVID‐19 preventive behaviours in a sample of the Turkish population.

Methods

The study was conducted with 575 individuals. COVID‐19 preventive behaviours were evaluated with a 19‐item scale scored from 19 to 95. Knowledge on COVID‐19 was evaluated with a 22‐item scale scored from 0 to 22. General health literacy was evaluated with the Turkey Health Literacy Scale (THLS), which was scored from 0 to 50.

Results

The average COVID‐19 preventive behaviours score was moderately high in this sample of the Turkish population. Being female, having a higher level of education, better economic status, being a non‐smoker, having a higher level of COVID‐19 knowledge and better general health literacy score were significant predictors of COVID‐19 preventive behaviours (P < 0.05).

Conclusion

Sociodemographic characteristics, knowledge of COVID‐19 and general health literacy are crucial in preventing COVID‐19 infections in a sample of the Turkish population.
How does informalisation encourage or inhibit collective action by migrant workers? A comparative analysis of logistics warehouses in Italy and hand car washes in Britain
Authors: Cioce Gabriella , Clark Ian , Hunter James
Published: March 2022

Cross‐national research is key to understanding the global presence of informal and non‐compliant workplaces. This article comparatively examines how informalisation encourages or inhibits collective action led by migrant workers employed in Italian logistics warehouses (LWs) and the British hand car washes (HCWs). The term collective action derives from mobilisation theory and refers to joint resistance initiatives developed by workers and labour organisations to improve work conditions. The article argues that migrant labour does not necessarily lead to informal practices and claims that labour market regulatory agencies and trade unions play an important but dialectical role in responding to labour market non‐compliance and informality. Finally, it notes that sector‐based specificities contribute to and potentially inhibit the emergence of collective dynamics in such workplaces.
Novel fabrication of bi‐metal oxide hybrid nanocomposites for synergetic enhancement of in vivo healing and wound care after caesarean section surgery
Authors: Gao Yan , Wang Xiaorui , Zhang Yongai , Li Jing , Zhang Haimiao , Li Jinlian
Published: March 2022

In the current study, bi‐metal oxide hybrid nanocomposites prepared by cerium oxide (CeO2) nanoparticles are included into chitosan‐ZnO composites for developing the potential materials of dressing the wound. The wound healing effect of prepared hybrid nanocomposites was evaluated regarding the surface morphology, functional groups, thermal degradation and composite size. The antimicrobial activity of chitosan‐ZnO/CeO2 hybrid nano composites was tested against the pathogens of Staphylococcus aureus and Escherichia coli. The hybrid nanocomposites containing CeO2‐based chitosan and ZnO nanoparticles were taken for optimum dressing included in the vivo studies on the excisional wounds in wistar rats. After 2 weeks, it is seen that the wound treated with CS‐ZnO/CeO2 hybrid nano composites consists of the significant dressing of nearly 100% compared with control which showed nearly 65% of wound closure. Finally, our reported results gave the proof in supporting the availability of CS‐ZnO/CeO2 hybrid nanocomposites contains the dressing of the wounds for the treatment.
Bacillus altitudinis HNH7 and Bacillus velezensis HNH9 promote plant growth through upregulation of growth-promoting genes in upland cotton
Authors: Hasan Nadeem , Khan Irfan Ullah , Farzand Ayaz , Heng Zhou , Moosa Anam , Saleem Muhammad , Canming Tang
Published: March 2022

Aims

The potential of endophytic Bacillus strains to improve plant growth and yield was evaluated.

Methods and results

Endophytic Bacillus altitudinis HNH7 and Bacillus velezensis HNH9 were evaluated for their growth-promoting traits. In an in vitro plate assay, HNH7 and HNH9 exhibited proteolytic, amylolytic, lipolytic and cellulolytic activity. HNH7 and HNH9 were able to solubilize iron by producing siderophores but were unable to solubilize insoluble phosphate. PCR confirmed the presence of four growth-promoting genes viz. pvd, budA, asbA and satA in the genome of HNH7, while HNH9 also possessed the same genes except for budA. In a greenhouse experiment, HNH7 and HNH9 promoted the growth of upland cotton plants by upregulating the expression of growth-linked genes, EXP6, ARF1, ARF18, IAA9, CKX6 and GID1b. However, the expression of genes involved in ethylene biosynthesis, that is ERF and ERF17 was downregulated after treating the plants with HNH7 and HNH9 compared to the control. Furthermore, cotton plants treated with HNH7 and HNH9 exhibited a significantly higher rate of photosynthesis and stomatal conductance.

Conclusion

HNH7 and HNH9 showed a promising potential to promote the growth of cotton plants.

Significance and impact of study

Research on plant growth-promoting Bacillus strains can lead to the formation of biofertilizers.
Pseudocongruent phylogeography reflects unique responses to environmental perturbations in a biodiversity hotspot
Authors: Busschau Theo , Jordaan Adriaan , Conradie Werner , Daniels Savel R.
Published: March 2022

Aim

Comparative phylogeographic studies provide important insights into the biogeographic processes shaping regional patterns of diversity. Yet, comparative studies are lacking for southern African herpetofauna, despite their high diversity. We statistically compare phylogeographic structure and divergence‐time estimates among five co‐distributed forest‐living herpetofaunal taxa to assess rivers, climatic refugia and climatic gradients as congruent drivers of phylogeographic diversity.

Location

Maputoland‐Pondoland‐Albany biodiversity hotspot, Southern Africa.

Taxon

herpetofauna (reptiles and amphibians).

Methods

Phylogeographic structure and divergence‐times within species were estimated from mitochondrial and nuclear DNA sequence data. Phylogeographic concordance factors were used to estimate the degree of phylogeographic congruence among sympatric localities. Full‐likelihood Bayesian comparisons were used to estimate synchronous divergence between phylogeographic regions and across a putative river barrier. Palaeoclimatic niche models were compared among taxa to identify congruent climatic refugia. Nonparametric statistics were used to identify climatic differences between regions and among populations within each species. Finally, redundancy analyses were used to assess geographic distance, climate and the putative river barrier as explanatory variables to genetic diversity.

Results

There is comprehensive phylogeographic structuring within each species, comprising distinct northerly and southerly clades. Phylogeographic concordance factors generally support co‐diversification in a north/south axis. Yet, analyses of the divergence‐time estimates through the Mio/Plio/Pleistocene indicate asynchronous phylogeographic histories. Climatic niche models identified idiosyncratic responses to palaeoclimatic change. Climatic variables are significantly different among populations in all species and correlated with latitude. A combined model of distance, climate and rivers explained the greatest proportion of genetical diversity in most taxa, of which climate explained the highest variance.

Main Conclusions

Ancient and recent species‐specific responses to climatic and geological processes resulted in pseudo congruent phylogeographic histories among the five co‐distributed species. The presence of a congruent north/south pattern in multiple taxonomic groups occupying different forested microhabitats, from fossorial to arboreal, supports latitudinal gradients as global drivers of phylogeographic diversity along the east coast of South Africa.
Association of body mass index with risk of prediabetes in Chinese adults: A population‐based cohort study
Authors: Chai Yuliang , Liu Yuanqing , Yang Ruijuan , Kuang Maobin , Qiu Jiajun , Zou Yang
Published: March 2022

Aims/Introduction

Overweight and obesity in adults are strongly associated with an increased risk of prediabetes, and this study set out to gain a better understanding of the optimal body mass index (BMI) range for assessing the risk of prediabetes in the Chinese population.

Materials and Methods

The cohort study included 100,309 Chinese adults who underwent health screening. Participants were divided into six groups based on the cut‐off point for BMI recommended by the World Health Organization (underweight: <18.5 kg/m2, normal‐weight: 18.5–24.9 kg/m2, pre‐obese: 25.0–29.9 kg/m2, obese class I: 30.0–34.9 kg/m2, obese class II: 35.0–39.9 kg/m2, and obese class III ≥40 kg/m2). The association of BMI with prediabetes and the shape of the correlation were modeled using multivariate Cox regression and restricted cubic spline regression, respectively.

Results

In the multivariate Cox regression model, with normal weight as the control group, underweight people had a lower risk of developing prediabetes, whereas obese and pre‐obese people had a higher risk of prediabetes. Additionally, in the restricted cubic spline model, we found that the association of BMI with prediabetes follows a positive dose–response relationship, but does not conform to the pattern of obesity paradox. Among the general population in China, a BMI of 23.03 kg/m2 might be a potential intervention threshold for prediabetes.

Conclusions

The national cohort study found that the association of BMI with prediabetes follows a positive dose–response relationship, rather than a pattern of obesity paradox. For Chinese people with normal weight, more attention should be paid to glucose metabolism when BMI exceeds 23.03 kg/m2.
Childhood pneumonia in New Zealand
Authors: Loto‐Aso Eseta , Howie Stephen RC , Grant Cameron C
Published: March 2022

While deaths from pneumonia during childhood in New Zealand (NZ) are now infrequent, childhood pneumonia remains a significant cause of morbidity. In this viewpoint, we describe pneumonia epidemiology in NZ and identify modifiable risk factors. During recent decades, pneumonia hospitalisation rates decreased, attributable in part to inclusion of pneumococcal conjugate vaccine in NZ's immunisation schedule. Irrespective of these decreases, pneumonia hospitalisation rates are four times higher for Pacific and 60% higher for Māori compared with children of other ethnic groups. Consistent with other developed countries, hospitalisation rates for pneumonia with pleural empyema increased in NZ during the 2000s. Numerous factors contribute to childhood pneumonia acquisition, hospitalisation and morbidity in NZ include poor quality living environments, malnutrition during pregnancy and early childhood, incomplete and delayed vaccination during pregnancy and childhood and variable primary and secondary care management. To reduce childhood pneumonia disease burden, interventions should focus on addressing modifiable risk factors for pneumonia. These include using non‐polluting forms of household heating; decreasing cigarette smoke exposure; reducing household acute respiratory infection transmission; improving dietary nutritional content and nutrition during pregnancy and early childhood; breastfeeding promotion; vaccination during pregnancy and childhood and improving the quality of and decreasing the variance in primary and secondary care management of pneumonia.
Development and application of a physiologically based pharmacokinetic model for orbifloxacin in crucian carp (Carassius auratus)
Authors: Yang Fang , Liu Dan , Yang Chao , Song Zhe‐Wen , Shao Hao‐Tian , Zhang Mei , Zhang Chao‐Shuo , Zhang Zhen‐Dong , Yang Fan
Published: March 2022

A flow‐limited physiologically based pharmacokinetic (PBPK) model consisting of seven compartments was established for orbifloxacin in crucian carp to predict drug concentrations after intravenous or intramuscular injections. Physiological and anatomical parameters, including tissue weights and blood flow through different tissues, were obtained from previous literature. The tissue/plasma partition coefficients for orbifloxacin were calculated using the area method or parameter optimization. In addition, their values were 0.9326, 1.1204, 1.1644, 1.3514, and 2.0057 in the liver, skin, muscle, kidney, and the rest of the body compartment, respectively. Based on the current PBPK model, orbifloxacin concentrations were predicted and compared with those previously reported for further validation. In addition, the mean absolute percentage error (MAPE) values were also calculated, with values ranging from 10.21% in plasma to 42.37% in kidneys, indicating acceptable predictions for all tissues and plasma. A local sensitivity analysis was performed, which showed that the parameters related to elimination and distribution were most influential on orbifloxacin concentrations in muscle. This model was finally used to predict plasma and tissue concentrations after multiple intramuscular dosing. The current PBPK model provided a valuable tool for predicting the tissue residues of orbifloxacin in crucian carp following intramuscular injection.
Long non‐coding RNA H19 as a biomarker for hepatocellular carcinoma
Authors: Rojas Ángela , Gil‐Gómez Antonio , de la Cruz‐Ojeda Patricia , Muñoz‐Hernández Rocío , Sánchez‐Torrijos Yolanda , Gallego‐Durán Rocío , Millán Raquel , Rico María Carmen , Montero‐Vallejo Rocío , Gato‐Zambrano Sheila , Maya‐Miles Douglas , Ferrer M. Teresa , Muntané Jordi , Robles‐Frías María José , Ampuero Javier , Padillo Francisco J. , Romero‐Gómez Manuel
Published: March 2022

Background and Aims

Liver cancer stem cells (CSCs) could be involved in the carcinogenesis, recurrence, metastasis and chemoresistance of hepatocellular carcinoma (HCC). The aim of this study was to explore the role of lncRNA‐H19 as a biomarker for liver cancer.

Methods

LncRNA‐H19 expression levels and the functional assays were conducted in EpCAM+CD133+ CSCs and C57BL/6J mice fed with a high‐fat high‐cholesterol carbohydrate (HFHCC) or standard diet for 52 weeks. Liver tissue and plasma samples from patients with cirrhosis, with or without HCC, were used for the analyses of gene expression and circulating lncRNA‐H19 levels in an estimation and validation cohort.

Results

EpCAM+CD133+ cells showed a stem cell‐like phenotype, self‐renewal capacity, upregulation of pluripotent gene expression and overexpressed lncRNA‐H19 (p < .001). Suppression of lncRNA‐H19 by antisense oligonucleotide treatment significantly reduced the self‐renewal capacity (p < .001). EpCAM, CD133 and lncRNA‐h19 expression increased accordingly with disease progression in HFHCC‐fed mice (p < .05) and also in liver tissue from HCC patients (p = .0082). Circulating lncRNA‐H19 levels were significantly increased in HCC patients in both cohorts (p = .013; p < .0001). In addition, lncRNA‐H19 levels increased accordingly with BCLC staging (p < .0001) and decreased after a partial and complete therapeutic response (p < .05). In addition, patients with cirrhosis who developed HCC during follow‐up showed higher lncRNA‐H19 levels (p = .0025).

Conclusion

LncRNA‐H19 expression was increased in CSCs, in liver tissue and plasma of patients with HCC and decreased after partial/complete therapeutic response. Those patients who developed HCC during the follow‐up showed higher levels of lncRNA‐H19. LncRNA‐H19 could constitute a new biomarker of HCC.
Predicting microvascular invasion in hepatocellular carcinoma: A dual‐institution study on gadoxetate disodium‐enhanced MRI
Authors: Jiang Hanyu , Wei Jingwei , Fu Fangfang , Wei Hong , Qin Yun , Duan Ting , Chen Weixia , Xie Kunlin , Lee Jeong Min , Bashir Mustafa R. , Wang Meiyun , Song Bin , Tian Jie
Published: March 2022

Background & Aims

Microvascular invasion (MVI) is an important risk factor in hepatocellular carcinoma (HCC), but its diagnosis mandates postoperative histopathologic analysis. We aimed to develop and externally validate a predictive scoring system for MVI.

Methods

From July 2015 to November 2020, consecutive patients underwent surgery for HCC with preoperative gadoxetate disodium (EOB)‐enhanced MRI was retrospectively enrolled. All MR images were reviewed independently by two radiologists who were blinded to the outcomes. In the training centre, a radio‐clinical MVI score was developed via logistic regression analysis against pathology. In the testing centre, areas under the receiver operating curve (AUCs) of the MVI score and other previous MVI schemes were compared. Overall survival (OS) and recurrence‐free survival (RFS) were analysed by the Kaplan–Meier method with the log‐rank test.

Results

A total of 417 patients were included, 195 (47%) with pathologically‐confirmed MVI. The MVI score included: non‐smooth tumour margin (odds ratio [OR] = 4.4), marked diffusion restriction (OR = 3.0), internal artery (OR = 3.0), hepatobiliary phase peritumoral hypointensity (OR = 2.5), tumour multifocality (OR = 1.6), and serum alpha‐fetoprotein >400 ng/mL (OR = 2.5). AUCs for the MVI score were 0.879 (training) and 0.800 (testing), significantly higher than those for other MVI schemes (testing AUCs: 0.648–0.684). Patients with model‐predicted MVI had significantly shorter OS (median 61.0 months vs not reached, P < .001) and RFS (median 13.0 months vs. 42.0 months, P < .001) than those without.

Conclusions

A preoperative MVI score integrating five EOB‐MRI features and serum alpha‐fetoprotein level could accurately predict MVI and postoperative survival in HCC. Therefore, this score may aid in individualized treatment decision making.
Microbial Kin: Relations of Environment and Time
Authors: Benezra Amber
Published: March 2022

Microbiome science considers human beings supraorganisms: single ecological units made up of symbiotic assemblages of human cells and microorganisms. Microbes co‐evolve with humans, and microbial populations in human bodies are determined by environments/exposures including family, food and place, health care, race and gender inequities, and toxic pollution. Microbiomes are transgenerational links, disarrangements between different bodies and the outside world. This article asserts that microbes are kin—kin that are made of and making environments, across generations. Post/nonhuman theories have debated the agency, sociality, and ontologies of microbes and things like microbes, all the while appropriating and eliding Indigenous scholarship that directly address the nonhuman world. Microbial kin evokes Indigenous formulations that necessitate reciprocal, ethical accountability to more‐than‐human relations. This article uses fieldwork in a transnational microbiome malnutrition project in Bangladesh to explore what develops for both the biological and social sciences if we call human–microbe relations kinships, and call microbes our kin.
Biogeography and character‐mapping of Hiptage (Malpighiaceae) corroborate Indochina's rainforests as one of the main sources of plant diversity in southeastern Asia
Authors: de Almeida Rafael Felipe , van den Berg Cássio
Published: March 2022

In Malpighiaceae, Hiptage represents one of the seven past dispersal events from the Neotropics to the Paleotropical region, being by far the most widely diversified and distributed genus of Paleotropical Malpighiaceae. In this study, we tested the current infrageneric classification of Hiptage with a dated and calibrated molecular phylogeny. We also reconstructed ancestral areas to elucidate which route led to the colonization of southeast Asia by the most recent common ancestor (MRCA) of this genus. The pre‐existing infrageneric classification of Hiptage was incompatible with monophyly being based solely on homoplasic morphological characters, such as the presence and number of sepal glands. The MRCA of Hiptage arose in the rainforests of southeast Asia ca 24.0 Mya and greatly diversified in this region. Few lineages have dispersed eastward to the pacific islands or westwards to India. Based on our results, we hypothesize that the MRCA of Hiptage did not take the Indian route to reach southeastern Asia. Instead, it reached this region by past mainland forest connections between North America–Europe (Boreotropical hypothesis) and southeast Asia. Nonetheless, distribution ranges for the species of Hiptage must be carefully revised, and the five species of Hiptage endemic to India must also be sampled so we can properly test which route led the MRCA of Hiptage to reach southeast Asia in the early Miocene.
Mycorrhizal symbiosis pathway and edaphic fertility frame root economics space among tree species
Authors: Yan Han , Freschet Grégoire T. , Wang Huimin , Hogan James Aaron , Li Shenggong , Valverde‐Barrantes Oscar J. , Fu Xiaoli , Wang Ruili , Dai Xiaoqin , Jiang Lei , Meng Shengwang , Yang Fengting , Zhang Miaomiao , Kou Liang
Published: March 2022

The root economics space (RES) is multidimensional and largely shaped by belowground biotic and abiotic influences. However, how root–fungal symbioses and edaphic fertility drive this complexity remains unclear.

Here, we measured absorptive root traits of 112 tree species in temperate and subtropical forests of China, including traits linked to functional differences between arbuscular mycorrhizal (AM) and ectomycorrhizal (ECM) hosts.

Our data, from known mycorrhizal tree species, revealed a ‘fungal‐symbiosis’ dimension distinguishing AM from ECM species. This divergence likely resulted from the contrasting mycorrhizal evolutionary development of AM vs ECM associations. Increased root tissue cortical space facilitates AM symbiosis, whereas increased root branching favours ECM symbiosis. Irrespective of mycorrhizal type, a ‘root‐lifespan’ dimension reflecting aspects of root construction cost and defence was controlled by variation in specific root length and root tissue density, which was fully independent of root nitrogen content. Within this function‐based RES, we observed a substantial covariation of axes with soil phosphorus and nitrate levels, highlighting the role played by these two axes in nutrient acquisition and conservation.

Overall, our findings demonstrate the importance of evolved mycorrhizal symbiosis pathway and edaphic fertility in framing the RES, and provide theoretical and mechanistic insights into the complexity of root economics.
A systematic review of inequalities in the uptake of, adherence to, and effectiveness of behavioral weight management interventions in adults
Authors: Birch Jack M. , Jones Rebecca A. , Mueller Julia , McDonald Matthew D. , Richards Rebecca , Kelly Michael P. , Griffin Simon J. , Ahern Amy L.
Published: March 2022

The extent to which behavioral weight management interventions affect health inequalities is uncertain, as is whether trials of these interventions directly consider inequalities. We conducted a systematic review, synthesizing evidence on how different aspects of inequality impact uptake, adherence, and effectiveness in trials of behavioral weight management interventions. We included (cluster‐) randomized controlled trials of primary care‐applicable behavioral weight management interventions in adults with overweight or obesity published prior to March 2020. Data about trial uptake, intervention adherence, attrition, and weight change by PROGRESS‐Plus criteria (place of residence, race/ethnicity, occupation, gender, religion, education, socioeconomic status, social capital, plus other discriminating factors) were extracted. Data were synthesized narratively and summarized in harvest plots. We identified 91 behavioral weight loss interventions and 12 behavioral weight loss maintenance interventions. Fifty‐six of the 103 trials considered inequalities in relation to at least one of intervention or trial uptake (n = 15), intervention adherence (n = 15), trial attrition (n = 32), or weight outcome (n = 34). Most trials found no inequalities gradient. If a gradient was observed for trial uptake, intervention adherence, and trial attrition, those considered “more advantaged” did best. Alternative methods of data synthesis that enable data to be pooled and increase statistical power may enhance understanding of inequalities in behavioral weight management interventions.
Oral carcinogenesis triggers a nociceptive behavior and c‐Fos expression in rats’ trigeminal pathway
Authors: Alves Joana Maria dos Santos , Viana Khalil Fernandes , Pereira Anamaria Falcão , Lima Júnior Roberto César Pereira , Vale Mariana Lima , Pereira Karuza Maria Alves , Gondim Delane Viana
Published: March 2022

Objective

To recognize changes that occur along the trigeminal pathway in oral cancer in order to establish an effective approach to pain control.

Methods

Wistar rats were divided into control and 4‐NQO groups for 8, 12, 16, or 20 weeks. 4‐NQO suspension was administered on the animals’ tongues. Mechanical hyperalgesia, assessment of facial expressions, and an open‐field test were performed. After euthanasia, the animals’ tongues were removed for macro‐ and microscopic analysis. c‐Fos expression was analyzed in the trigeminal pathway structures.

Results

4‐NQO induced time‐dependent macroscopic lesions that were compatible with neoplastic tumors. Histopathological analysis confirmed oral squamous cell carcinoma in 50% of the animals on the 20th week. There was a significant nociceptive threshold reduction during the first two weeks, followed by a threshold return to the baseline levels, decreasing again from the 12th week. Facial nociceptive expression scores were observed on the 20th week, while increased grooming and exploratory activity were observed on the 8th week. Trigeminal ganglion showed an increased c‐Fos immunoexpression on the 20th week, and in the trigeminal subnucleus caudalis, it occurred on the 16th and 20th. The long‐term carcinogenic exposure caused changes in the nociceptive behavior and c‐Fos expression in the rats’ trigeminal pathway.