bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing researchers’ capabilities, opportunities, and motivation to conduct equity-oriented dissemination and implementation research, an exploratory cross-sectional study
Authors: Baumann Ana A. , Woodward Eva N. , Singh Rajinder Sonia , Adsul Prajakta , Shelton Rachel C.
Published: June 2022

Background

A recent paradigm shift has led to an explicit focus on enhancing health equity through equity-oriented dissemination and implementation (D&I) research. However, the integration and bidirectional learning across these two fields is still in its infancy and siloed. This exploratory study aimed to examine participants’ perceived capabilities, opportunities, and motivations to conduct equity-oriented D&I research.

Methods

We conducted an exploratory cross-sectional survey distributed online from December 2020 to April 2021. Participants were recruited at either D&I or health disparities-oriented conferences, meetings, through social media, or personal outreach via emails. Informed by the Capability, Opportunity, and Motivation Model (COM-B), the survey queried respondents about different aspects of engaging in and conducting equity-oriented D&I research. All analyses were conducted in SPSS Version 27.0.

Results

A total of 180 participants responded to the survey. Most participants were women (81.7%), white (66.1%), academics (78.9%), and faculty members (53.9%). Many reported they were advanced (36.7%) or advanced beginners (27.8%) in the D&I field, and a substantial proportion (37.8%) reported being novice in D&I research that focused on health equity. Participants reported high motivation (e.g., 62.8% were motivated to apply theories, models, frameworks for promoting health equity in D&I research), but low capability to conduct equity-oriented D&I research (e.g., 5% had the information needed for promoting health equity in D&I research). Most participants (62.2%) reported not having used measures to examine equity in their D&I projects, and for those who did use measures, they mainly used individual-level measures (vs. organizational- or structural-level measures). When asked about factors that could influence their ability to conduct equity-oriented D&I research, 44.4% reported not having the skills necessary, and 32.2% stated difficulties in receiving funding for equity-oriented D&I research.

Conclusions

Study findings provide empirical insight into the perspectives of researchers from different backgrounds on what is needed to conduct equity-oriented D&I research. These data suggest the need for a multi-pronged approach to enhance the capability and opportunities for conducting equity-oriented D&I work, such as: training specifically in equity-oriented D&I, collaboration between D&I researchers with individuals with expertise and lived experience with health equity research, funding for equity-oriented D&I research, and recognition of the value of community engaged research in promotion packages.
Experiences of hospital allied health professionals in collaborative student research projects: a qualitative study
Authors: Angus Rebecca L. , Hattingh H. Laetitia , Weir Kelly A.
Published: June 2022

Background

Active engagement in research by healthcare organisations and clinicians is associated with improvements in healthcare performance. Barriers to research engagement by clinician allied health (AH) professionals include competing priorities from high clinical workloads, lack of research skills and confidence, and lack of supportive research relationships. Collaboration with universities on joint clinical research projects is well recognised as a means of building health service research capacity. Research projects undertaken by students as part of their qualifying degree represent one such opportunity. However, there are few reports evaluating these collaborations from the health service perspective.

Methods

A qualitative study using semi-structured interviews and thematic analysis to explore the experiences of AH professionals in the co-supervision of students completing research placements as part of their professional degree course.

Results

Fourteen health service employees from six allied health disciplines described collaborations on research projects with 24 students from four different universities. Student placements and projects varied widely in length of placement, extent of collaboration, supervision structure and study design. Three overarching themes were identified in the AH professional co-supervision experience: 1) Professional growth; 2) Mismatch with expectations; and 3) Focus on the student. Project outcomes were categorised from the health system perspective. These were 1) Healthcare performance improvements, including local increases in staff clinical practice knowledge and wider contributions to the evidence base; 2) Research capacity gains within the health service, including research knowledge and skill development, collaborative linkages and opportunity for future research; and 3) Staff-centred outcomes including increased job satisfaction.

Conclusions

This study demonstrates the potential for AH professional supervision of students on research placements to contribute to healthcare performance improvements and research capacity gains within health services, alongside providing personal benefits for the AH professionals involved. Early consultation with a health service-employed research specialist may support health professional and student learning, team collaboration and project coordination for these student projects.
Intelligence outcome of pediatric intensive care unit survivors: a systematic meta-analysis and meta-regression
Authors: de Sonnaville Eleonore S. V. , Kӧnigs Marsh , van Leijden Ouke , Knoester Hennie , van Woensel Job B. M. , Oosterlaan Jaap
Published: June 2022

Background

Long-term morbidity after pediatric intensive care unit (PICU) admission is a growing concern. Both critical illness and accompanying PICU treatments may impact neurocognitive development as assessed by its gold standard measure; intelligence. This meta-analysis and meta-regression quantifies intelligence outcome after PICU admission and explores risk factors for poor intelligence outcome.

Methods

PubMed, Embase, CINAHL and PsycINFO were searched for relevant studies, published from database inception until September 7, 2021. Using random-effects meta-analysis, we calculated the standardized mean difference in full-scale intelligence quotient (FSIQ) between PICU survivors and controls across all included studies and additionally distinguishing between PICU subgroups based on indications for admission. Relation between demographic and clinical risk factors and study’s FSIQ effect sizes was investigated using random-effects meta-regression analysis.

Results

A total of 123 articles was included, published between 1973 and 2021, including 8,119 PICU survivors and 1,757 controls. We found 0.47 SD (7.1 IQ-points) lower FSIQ scores in PICU survivors compared to controls (95%CI -0.55 to -0.40, p < .001). All studied PICU subgroups had lower FSIQ compared to controls (range 0.38–0.88 SD). Later year of PICU admission (range 1972–2016) and longer PICU stay were related to greater FSIQ impairment (R2 = 21%, 95%CI -0.021 to -0.007, p < .001 and R2 = 2%, 95%CI -0.027 to -0.002, p = .03, respectively), whereas male sex and higher rate of survivors were related to smaller FSIQ impairment (R2 = 5%, 95%CI 0.001 to 0.014, p = .03 and R2 = 11%, 95%CI 0.006 to 0.022, p < .001, respectively). Meta-regression in PICU subgroups showed that later year of PICU admission was related to greater FSIQ impairment in children admitted after cardiac surgery and heart- or heart–lung transplantation. Male sex was related to smaller FSIQ impairment in children admitted after cardiac surgery. Older age at PICU admission and older age at follow-up were related to smaller FSIQ impairment in children admitted after heart- or heart–lung transplantation.

Conclusions

PICU survivors, distinguished in a wide range of subgroups, are at risk of intelligence impairment. Length of PICU stay, female sex and lower rate of survivors were related to greater intelligence impairment. Intelligence outcome has worsened over the years, potentially reflecting the increasing percentage of children surviving PICU admission.
Comprehensive analysis of the expression, prognostic significance, and function of FAM83 family members in breast cancer
Authors: Jin Yi , Yu Jiahui , Jiang Yi , Bu Jiawen , Zhu Tong , Gu Xi , Zhu Xudong
Published: June 2022

Background

TheFAM83family plays a key role in tumorigenesis and cancer progression. However, the role of theFAM83family in the development of breast tumors is unclear to date. This report explores the expression, prognostic significance, and function of theFAM83family members in breast cancer using public databases.

Methods

UALCAN database was used to explore the expression ofFAM83family members in breast cancer. Furthermore, we validated the expression ofFAM83family members in twenty pairs of breast cancer and normal tissues by RT-PCR. Kaplan–Meier plotter database was used to explore the prognostic significance ofFAM83family members in breast cancer. GeneMANIA and DAVID databases were used for functional and pathway enrichment analysis of genes co-expressed with FAM83A, FAM83D, FAM83F, and FAM83G. MEXPRESS and UALCAN databases were used to analyze the level of DNA promoter methylation of FAM83A, FAM83D, FAM83F, and FAM83G in breast cancer. TIMER database was utilized to explore the relationships between immune cell infiltration and FAM83A, FAM83D, FAM83F, and FAM83G expression.

Results

AmongFAM83family members, FAM83A, FAM83D, FAM83F, and FAM83G were higher expressed in breast cancer than in normal tissues. We also validated the significant high expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA in breast cancer than in normal samples. Their increased expression has an adverse prognostic effect on breast cancer patients. These genes co-expressed with FAM83A, FAM83D, FAM83F, and FAM83G might take part in cell proliferation, G2/M transition of the mitotic cell cycle, regulation of apoptosis process and other cancer-related biological processes. In addition, they were mainly enriched in the Hippo signaling pathway, Hedgehog signaling pathway, PI3K/AKT signaling pathway, and other cancer-related pathways. We also found that promoter DNA methylation might regulate the expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA in most CpG islands. At last, we found the expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA was significantly related to immune cell infiltration.

Conclusions

FAM83A, FAM83D, FAM83F, and FAM83G were highly expressed in breast cancer tissues and had an adverse effect on the survival outcomes of breast cancer patients. Also, they were involved in breast cancer-related signal pathways. Therefore, they might serve as potential therapeutic targets for breast cancer clinical treatment.
Altered transcriptional responses in the lungs of aged mice after influenza infection
Authors: Hernandez Ana M. , Mossman Jim A. , Toapanta Franklin R. , Previte Dana M. , Ross Ted M. , Nau Gerard J.
Published: June 2022

Background

Influenza causes a serious infection in older individuals who are at the highest risk for mortality from this virus. Changes in the immune system with age are well known. This study used transcriptomic analysis to evaluate how aging specifically affects the functional host response to influenza in the lung. Adult (12–16 weeks) and aged (72–76 weeks) mice were infected with influenza and lungs were processed for RNA analysis.

Results

Older mice demonstrated a delayed anti-viral response on the level of transcription compared to adults, similar to the immunologic responses measured in prior work. The transcriptional differences, however, were evident days before observable differences in the protein responses described previously. The transcriptome response to influenza in aged mice was dominated by immunoglobulin genes and B cell markers compared to adult animals, suggesting immune dysregulation. Despite these differences, both groups of mice had highly similar transcriptional responses involving non-immune genes one day after inoculation and T cell genes during resolution.

Conclusions

These results define a delayed and dysregulated immune response in the lungs of aged mice infected with influenza. The findings implicate B cells and immunoglobulins as markers or mechanisms of immune aging. In addition to discovering new therapeutic targets, the findings underscore the value of transcription studies and network analysis to characterize complex biological processes, and serve as a model to analyze the susceptibility of the elderly to infectious agents.
Blood–brain barrier: emerging trends on transport models and new-age strategies for therapeutics intervention against neurological disorders
Authors: Alajangi Hema Kumari , Kaur Mandeep , Sharma Akanksha , Rana Sumedh , Thakur Shipali , Chatterjee Mary , Singla Neha , Jaiswal Pradeep Kumar , Singh Gurpal , Barnwal Ravi Pratap
Published: June 2022

The integrity of the blood–brain barrier (BBB) is essential for normal central nervous system (CNS) functioning. Considering the significance of BBB in maintaining homeostasis and the neural environment, we aim to provide an overview of significant aspects of BBB. Worldwide, the treatment of neurological diseases caused by BBB disruption has been a major challenge. BBB also restricts entry of neuro-therapeutic drugs and hinders treatment modalities. Hence, currently nanotechnology-based approaches are being explored on large scale as alternatives to conventional methodologies. It is necessary to investigate the in-depth characteristic features of BBB to facilitate the discovery of novel drugs that can successfully cross the barrier and target the disease effectively. It is imperative to discover novel strategies to treat life-threatening CNS diseases in humans. Therefore, insights regarding building blocks of BBB, activation of immune response on breach of this barrier, and various autoimmune neurological disorders caused due to BBB dysfunction are discussed. Further, special emphasis is given on delineating BBB disruption leading to CNS disorders. Moreover, various mechanisms of transport pathways across BBB, several novel strategies, and alternative routes by which drugs can be properly delivered into CNS are also discussed.
The molecular mechanism of circRHOBTB3 inhibits the proliferation and invasion of epithelial ovarian cancer by serving as the ceRNA of miR-23a-3p
Authors: Fu Yihan , Sun Hong
Published: June 2022

Rising evidences bespeak that circular RNAs are indispensable in regulating cellular biological behaviors and engaging in diseases' occurrence. CircRHOBTB3 has been reported to participate intimately in the progression of some cancers. Nevertheless, the mechanism by which circRHOBTB3 regulates tumorigenesis in epithelial ovarian cancer (EOC) remains ill-defined. The present study determined the expression pattern and bio-effects of circRHOBTB3 in EOC. Furthermore, it revealed that circRHOBTB3 could serve as the ceRNA of miR‑23a-3p to facilitate PTEN expression, suppress proliferation, G1/S transition, invasion, and promote apoptosis in EOC. Summarily, our findings provided a primary research foundation that circRHOBTB3 might be typified as a neoteric biomarker and a promising target of EOC, which is essential for improving the early diagnosis and precision treatment, so as to cut down EOC's mortality finally.
Effectiveness and cost-effectiveness of sector-independent treatment coordination for people with substance-related disorders following an online assessment (ASSIST): study protocol for a randomized controlled trial
Authors: Mueller-Stierlin Annabel S. , Röhrig Jeanette , Goetzl Christian , Krausz Michael , Lehle Jutta , Prestin Elke , Schoch Vanessa-Emily , Sutter Lorenz , Westenberg Jean , Cabanis Maurice
Published: June 2022

Background

The implementation of person-centred, need-oriented and flexible care for people with substance-related problems is often insufficient, in large part due to the complexity of addiction support services among different providers. A standardized online assessment and subsequent sector-independent treatment coordination could provide individuals with more appropriate services, thereby making better use of individual services and leading to a more effective addiction support system as a whole. The aim of this study is to determine the effectiveness and cost-effectiveness of sector-independent treatment coordination following an online assessment, in comparison with the current standard of care and treatment process in Germany.

Methods

The sample size of this randomized, controlled trial has been set to a total of 400 participants with substance-related problems. Participants living in Stuttgart, Germany, will be randomly allocated to (1) the intervention group with immediate online assessment and subsequent sector-independent treatment coordination (ASSIST) or (2) the waitlist group. Participants in the waitlist group will initially remain in usual care and only be provided with the online assessment 6 months later. Short-term effects (over 2 months) and medium-term effects (over 6 months) of ASSIST will be compared between the intervention and the waitlist groups. The primary outcome is improved treatment satisfaction. Secondary outcomes include improved subjective quality of life and empowerment, reductions in patients’ substance use, unmet needs and illness-related clinical and social impairment. Health economic evaluation as well as quantitative and qualitative process evaluations will be conducted.

Discussion

The results of this study are expected to provide information on whether sector-independent treatment coordination following an online assessment contributes to improved health care service provision for people with substance-related problems. This randomized controlled trial will help identify facilitators and barriers to the sustainable implementation of a cross-sectoral care concept in substance abuse services.

Trial registration

German Clinical Trial Register DRKS00026996. Registered on 29 October 2021
Mapping the genetic landscape of early-onset Alzheimer’s disease in a cohort of 36 families
Authors: Mol Merel O. , van der Lee Sven J. , Hulsman Marc , Pijnenburg Yolande A. L. , Scheltens Phillip ,   Netherlands Brain Bank, Seelaar Harro , van Swieten John C. , Kaat Laura Donker , Holstege Henne , van Rooij Jeroen G. J.
Published: June 2022

Background

Many families with clinical early-onset Alzheimer’s disease (EOAD) remain genetically unexplained. A combination of genetic factors is not standardly investigated. In addition to monogenic causes, we evaluated the possible polygenic architecture in a large series of families, to assess if genetic testing of familial EOAD could be expanded.

Methods

Thirty-six pedigrees (77 patients) were ascertained from a larger cohort of patients, with relationships determined by genetic data (exome sequencing data and/or SNP arrays). All families included at least one AD patient with symptom onset <70 years. We evaluated segregating rare variants in known dementia-related genes, and other genes or variants if shared by multiple families.APOEwas genotyped and duplications inAPPwere assessed by targeted test or using SNP array data. We computed polygenic risk scores (PRS) compared with a reference population-based dataset, by imputing SNP arrays or exome sequencing data.

Results

In eight families, we identified a pathogenic variant, including the genesAPP,PSEN1,SORL1, and an unexpectedGRNframeshift variant.APOE-ε4 homozygosity was present in eighteen families, showing full segregation with disease in seven families. Eight families harbored a variant of uncertain significance (VUS), of which six includedAPOE-ε4 homozygous carriers. PRS was not higher in the families combined compared with the population mean (beta 0.05,P= 0.21), with a maximum increase of 0.61 (OR = 1.84) in theGRNfamily. Subgroup analyses indicated lower PRS in sixAPP/PSEN1families compared with the rest (beta −0.22 vs. 0.10;P= 0.009) and lowerAPOEburden in all eight families with monogenic cause (beta 0.29 vs. 1.15,P= 0.010). Nine families remained without a genetic cause or risk factor identified.

Conclusion

Besides monogenic causes, we suspect a polygenic disease architecture in multiple families based onAPOEand rare VUS. The risk conveyed by PRS is modest across the studied families. Families without any identified risk factor render suitable candidates for further in-depth genetic evaluation.
Autism-associated protein POGZ controls ESCs and ESC neural induction by association with esBAF
Authors: Sun Xiaoyun , Cheng Linxi , Sun Yuhua
Published: June 2022

Background

The POGZ gene has been found frequently mutated in neurodevelopmental disorders (NDDs), particularly autism spectrum disorder (ASD) and intellectual disability (ID). However, little is known about its roles in embryonic stem cells (ESCs), neural development and diseases.

Methods

We generated Pogz−/− ESCs and directed ESC differentiation toward a neural fate. We performed biochemistry, ChIP-seq, ATAC-seq, and bioinformatics analyses to understand the role of POGZ.

Results

We show that POGZ is required for the maintenance of ESC identity and the up-regulation of neural genes during ESC differentiation toward a neural fate. Genome-wide binding analysis shows that POGZ is primarily localized to gene promoter and enhancer regions. POGZ functions as both a transcriptional activator and repressor, and its loss leads to deregulation of differentiation genes, including neural genes. POGZ physically associates with the SWI-SNF (esBAF) chromatin remodeler complex, and together they modulate enhancer activities via epigenetic modifications such as chromatin remodeling and histone modification. During ESC neural induction, POGZ-mediated recruitment of esBAF/BRG1 and H3K27ac are important for proper expression of neural progenitor genes.

Limitations

The genotype and allele relevant to human neurodevelopmental disorders is heterozygous loss of function. This work is designed to study the effects of loss of POGZ function on ESCs and during ESC neural induction. Also, this work lacks of in vivo validation using animal models.

Conclusions

The data suggest that POGZ is both a transcription factor and a genome regulator, and its loss leads to defects in neural induction and neurogenesis.
The inhibition of tamoxifen on UGT2B gene expression and enzyme activity in rat liver contribute to the estrogen homeostasis dysregulation
Authors: Hao Zhixiang , Xu Jiahao , Zhao Han , Zhou Wei , Liu Zhao , He Shiqing , Yin Xiaoxing , Zhang Bei , Wang Zhongjian , Zhou Xueyan
Published: June 2022

Background

Tamoxifen treatment may induce dysregulation of estrogen homeostasis, leading to the occurrence of related adverse reactions. However, the potential mechanisms are still unclear. The purpose of the present study was to uncover whether tamoxifen treatment would act on estrogen metabolism-related biological enzymes and the regulatory effect on estrogen homeostasis to clarify the key factors and potential mechanisms of adverse reactions caused by long-term use of tamoxifen.

Method

Female SD rats were administrated with tamoxifen CMC-Na solution (p.o.) once daily for four weeks and then housed at room temperature. Serum, breast, liver, uterus, and ovarian tissues were obtained, and the effects of tamoxifen administration on estrogen homeostasis, the expression, and activity of estrogen metabolic enzyme were evaluated.

Results

Compared with the control group, the estrogen homeostasis was disturbed and the expression and activity of UGT2B1 (homology with human UGT2B7) were significantly reduced in the rats administrated with tamoxifen. The inhibitory effect of tamoxifen on UGT2B7 was dominated by hydrophobic and π-π stacking interactions, resulting in a concentration-dependent inhibition of UGT2B7 activity by tamoxifen and the imbalance of ligand-activated transcription factors, leading to abnormal regulation of UGT2B and disturbance of estrogen homeostasis, which in turn led to adverse reactions of tamoxifen.

Conclusion

We established links between estrogen metabolism and tamoxifen administration and we proposed that the UGT2B inhibition was involved in the disturbance of estrogen homeostasis and the occurrence of tamoxifen-related adverse reactions.
Fairness in assessment practices in online education: Iranian University English teachers’ perceptions
Authors: Azizi Zeinab
Published: June 2022

Although fairness in assessment practices (APs) in traditional classes has gained noticeable attention in recent years, it has remained unexplored in online education (OE). Thus, this study explores Iranian university English teachers’ perceptions of fair APs in OE. For this purpose, 21 university English teachers from Lorestan University and Ayatollah Borujerdi University, Iran, were selected using a purposive sampling method. They were invited to express their conceptions of fair APs by completing a reflective written statement questionnaire. The collected data were subjected to a thematic coding analysis. The results yielded three overarching categories: distributive justice (i.e., equality should be considered, equity is of paramount importance, and assessment practices should be tied with students’ needs), procedural justice (i.e., voices of students should be heard, both consistency and flexibility are required, and assessment procedures should be transparent), and interactional justice (i.e., interpersonal justice is crucial and informational justice should be considered). The study concludes by proposing a range of implications for different testing stakeholders.
Breakfast skipping and its relationship with academic performance in Ethiopian school-aged children, 2019
Authors: Abebe Lulu , Mengistu Nebiyu , Tesfaye Tinsae Shemelise , Kabthymer Robel Hussen , Molla Wondwosen , Tarekegn Desalegn , Wudneh Aregahegn , Shonor Misrak Negash , Yimer Solomon
Published: June 2022

Breakfast skipping and its relationship with academic achievement among primary school children were investigated in this study. A cross-sectional study was conducted among 848 primary school children. Breakfast skipping was analyzed using a 2-item questionnaire. A 19-item Social Academic and Emotional Behavior Risk Screening questionnaire was used to collect data on children’s behavior. The prevalence of breakfast skipping was found to be 38.1%. Living in a rural area (AOR = 5.2; 95% CI: 3.54, 7.71); having illiterate parents (AOR = 6.66; 95% CI 3.0, 14.7); having parents with a primary education level (AOR 5.18, 95% CI: 2.25, 11.94); living with guardians or other relatives (AOR = 4.06; 95%CI: 2.1, 7.9); and having lower academic achievement (AOR = 2.76; 95% CI: 1.44, 5.29) were factors associated with skipping breakfast.

In conclusion, breakfast skipping has been identified as a significant public health concern that requires an immediate response from stakeholders. It is recommended to intervene based on the identified factors.
Comparing self-reported and measured hypertension and hypercholesterolaemia at standard and more stringent diagnostic thresholds: the cross-sectional 2010–2015 Busselton Healthy Ageing study
Authors: Burvill Angela J , Murray Kevin , Knuiman Matthew W , Hung Joseph
Published: June 2022

Background

Population health behaviour and risk factor surveys most often rely on self-report but there is a lack of studies assessing the validity of self-report using Australian data. This study investigates the sensitivity, specificity and agreement of self-reported hypertension and hypercholesterolaemia with objective measures at standard and more stringent diagnostic thresholds; and factors associated with sensitivity and specificity of self-report at different thresholds.

Methods

This study was a secondary analysis of a representative community-based cross-sectional sample of 5,092 adults, aged 45–69 years, residing in Busselton, Western Australia, surveyed in 2010–2015. Participants completed a self-administered questionnaire. Blood pressure and serum cholesterol levels were measured.

Results

At currently accepted diagnostic thresholds, sensitivities of self-reported hypertension and hypercholesterolaemia were 58.5% and 39.6%, respectively and specificities were >90% for both. Agreement using Cohen’s kappa coefficient was 0.562 and 0.223, respectively. At two higher diagnostic thresholds, sensitivities of self-reported hypertension and hypercholesterolaemia improved by an absolute 14–23% and 15–25%, respectively and specificities remained >85%. Agreement was substantial for hypertension (kappa = 0.682–0.717) and moderate for hypercholesterolaemia (kappa = 0.458–0.533). Variables that were independently associated with higher sensitivity and lower specificity of self-report were largely consistent across thresholds and included increasing age, body mass index, worse self-rated health, diabetes and family history of hypertension.

Conclusions

Self-reported hypertension and hypercholesterolaemia often misclassify individuals’ objective status and underestimate objective prevalences, at standard diagnostic thresholds, which has implications for surveillance studies that rely on self-reported data. Self-reports of hypertension, however, may be reasonable indicators of those with blood pressures ≥160/100 mmHg or those taking anti-hypertensive medications. Self-reported hypercholesterolaemia data should be used with caution at all thresholds.
Effect of carbohydrate-restricted diets and intermittent fasting on obesity, type 2 diabetes mellitus, and hypertension management: consensus statement of the Korean Society for the Study of obesity, Korean Diabetes Association, and Korean Society of Hypertension
Authors: Choi Jong Han , Cho Yoon Jeong , Kim Hyun-Jin , Ko Seung-Hyun , Chon Suk , Kang Jee-Hyun , Kim Kyoung-Kon , Kim Eun Mi , Kim Hyun Jung , Song Kee-Ho , Nam Ga Eun , Kim Kwang Il ,   Committee of Clinical Practice Guidelines, Korean Society for the Study of Obesity (KSSO), Committee of Clinical Practice Guidelines and Committee of Food and Nutrition, Korean Diabetes Association (KDA), Policy Committee of Korean Society of Hypertension (KSH), Policy Development Committee of National Academy of Medicine of Korea (NAMOK)
Published: June 2022

Background

Carbohydrate-restricted diets and intermittent fasting (IF) have been rapidly gaining interest among the general population and patients with cardiometabolic disease, such as overweight or obesity, diabetes, and hypertension. However, there are limited expert recommendations for these dietary regimens. This study aimed to evaluate the level of scientific evidence on the benefits and harms of carbohydrate-restricted diets and IF to make responsible recommendations.

Methods

A meta-analysis and systematic literature review of 66 articles on 50 randomized controlled clinical trials (RCTs) of carbohydrate-restricted diets and ten articles on eight RCTs of IF was performed.

Results

Based on the analysis, the following recommendations are suggested. In adults with overweight or obesity, a moderately-low carbohydrate or low carbohydrate diet (mLCD) can be considered as a dietary regimen for weight reduction. In adults with type 2 diabetes, mLCD can be considered as a dietary regimen for improving glycemic control and reducing body weight. In contrast, a very-low carbohydrate diet (VLCD) and IF are recommended against in patients with diabetes. Furthermore, no recommendations are suggested for VLCD and IF in adults with overweight or obesity, and carbohydrate-restricted diets and IF in patients with hypertension.

Conclusion

Here, we describe the results of our analysis and the evidence for these recommendations.
Character strengths as protective factors against behavior problems in early adolescent
Authors: Qin Cheng , Cheng Xiaotong , Huang Yuyan , Xu Shuang , Liu Kezhi , Tian Mingyuan , Liao Xiaoyuan , Zhou Xinyi , Xiang Bo , Lei Wei , Chen Jing
Published: June 2022

Character strengths could effectively prevent negative psychological outcomes in adults. However, there was little research conducted among early adolescents. The present study aimed to explore character strengths that were independently related to fewer behavior problems in early adolescents. In total, 521 early adolescents (mean age 10.92 ± 0.04, range 10–12 years) were recruited from primary schools in Sichuan, China. Character strengths were measured using the Values in Action Inventory of Strengths for Youth (VIA-Youth). Behavior problems were measured using the Conners Parent Symptom Questionnaire (PSQ). The results showed that behavior problems were negatively correlated with character strengths (r= −0.14 to −0.3,p< 0.05 Bonferroni corrected). Character strengths explained a significant proportion of additional variance (14–22%) in five types of behavior problems after controlling the effect of demographic factors (residence, left-behind experiences, maternal education level). Moreover, several specific character strengths showed an independent contribution (β= −0.34 to −0.14 for self-regulation, perseverance, zest, humility, and leadership;β= 0.21 to 0.34, for hope; allp< 0.05) to behavior problems. Our study revealed that character strengths were protective factors against behavior problems in early adolescents.
Adaptive local discontinuous Galerkin methods with semi-implicit time discretizations for the Navier-Stokes equations
Authors: Meng Xiangyi , Xu Yan
Published: June 2022

In this paper, we present a mesh adaptation algorithm for the unsteady compressible Navier-Stokes equations under the framework of local discontinuous Galerkin methods coupled with implicit-explicit Runge-Kutta or spectral deferred correction time discretization methods. In both of the two high order semi-implicit time integration methods, the convective flux is treated explicitly and the viscous and heat fluxes are treated implicitly. The remarkable benefits of such semi-implicit temporal discretizations are that they can not only overcome the stringent time step restriction compared with time explicit methods, but also avoid the construction of the large Jacobian matrix as is done for fully implicit methods, thus are relatively easy to implement. To save computing time as well as capture the flow structures of interest accurately, a local mesh refinement (h-adaptive) technique, in which we present detailed criteria for selecting candidate elements and complete strategies to refine and coarsen them, is also applied for the Navier-Stokes equations. Numerical experiments are provided to illustrate the high order accuracy, efficiency and capabilities of the semi-implicit schemes in combination with adaptive local discontinuous Galerkin methods for the Navier-Stokes equations.
Engaging TEAM Medicine in Patient Care: Redefining Cancer Survivorship From Diagnosis
Authors: Alfano Catherine M. , Oeffinger Kevin , Sanft Tara , Tortorella Brooke
Published: June 2022

New approaches to cancer survivorship care must address the rising number of survivors who need complex care; the need to personalize care to improve health equity; workforce shortages and clinician knowledge deficits about the long-term and late effects of cancer; the need to engage and coordinate oncology, primary care, and a large multidisciplinary team of subspecialists and programs to meet survivors’ needs; and the need to control costs and deliver better value. This review proposes eight core tenets of an evolved standard of care to meet these needs by starting at diagnosis and continuing throughout oncology and into follow-up to: (1) facilitate team medicine by connecting oncology, primary care, subspecialists and programs, researchers, and patients and caregivers; (2) educate patients and support them in self-management; (3) mitigate toxicities; (4) manage comorbidities; (5) promote healthy behaviors and wellness; (6) improve health equity; (7) provide clear personalized follow-up; and (8) provide ongoing opportunities for participation in research as the standard of care. Strategies to successfully implement this care are discussed from the perspectives of oncology, primary care, and health care administration.
Social Justice and Equity: Why Older Adults With Cancer Belong—A Life Course Perspective
Authors: Yilmaz Sule , Sanapala Chandrika , Schiaffino Melody K. , Schumacher Jessica R. , Wallington Sherrie F. , McKoy June M. , Canin Beverly , Tang Weizhou , Tucker-Seeley Reginald D. , Simmons John , Gilmore Nikesha
Published: June 2022

The population of older adults with cancer in the United States is rapidly increasing, which will have a substantial impact on the oncology and public health workforces across the cancer continuum, from prevention to end of life. Unfortunately, inequities in existing social structures that cause increased psychosocial stressors have led to disparities in the incidence of cancer and the morbidity and mortality of cancer for individuals from marginalized backgrounds. It is imperative that older adults, especially those from historically marginalized backgrounds, be adequately represented in all stages of cancer research to address health inequities. Continued efforts and progress toward achieving social justice and health equity require a deeper commitment to and better understanding of the impact of social determinants of health within the cancer domain. Undoubtedly, a more holistic and integrated view that extends beyond the biologic and genetic factors of health must be adopted for health entities to recognize the critical role of environmental, behavioral, and social determinants in cancer health disparities. Against this backdrop, this paper uses a life course approach to present a multifactorial framework for understanding and addressing cancer disparities in an effort to advance social justice and health equity for racially and ethnically diverse older adults.
Microaggressions, Bias, and Equity in the Workplace: Why Does It Matter, and What Can Oncologists Do?
Authors: Velazquez Ana I. , Gilligan Timothy D. , Kiel Lauren L. , Graff Julie , Duma Narjust
Published: June 2022

Despite efforts to embrace diversity, women and members of racial, ethnic, and gender minority groups continue to experience bias, inequities, microaggressions, and unwelcoming atmospheres in the workplace. Specifically, women in oncology have lower promotion rates and less financial support and mentorship, and they are less likely to hold leadership positions. These experiences are exceedingly likely at the intersection of identities, leading to decreased satisfaction, increased burnout, and a higher probability of leaving the workforce. Microaggressions have also been associated with depression, suicidal thoughts, and other health and safety issues. Greater workplace diversity and equity are associated with improved financial performance; greater productivity, satisfaction, and retention; improved health care delivery; and higher-quality research. In this article, we provide tools and steps to promote equity in the oncology workplace and achieve cultural change. We propose the use of tailored approaches and tools, such as active listening, for individuals to become microaggression upstanders; we also propose the implementation of education, evaluation, and transparent policies to promote a culture of equity and diversity in the oncology workplace.
Regional Therapy for Colorectal Cancer Liver Metastases: Which Modality and When?
Authors: Raphael Michael J. , Karanicolas Paul J.
Published: June 2022

For patients with unresectable colorectal liver metastases (uCRLM), regional therapies leverage the unique, dual blood supply to the liver; the hepatic artery is the main blood supply for liver tumors, whereas the portal vein supplies most normal hepatic parenchyma. Infusion of cancer therapies via the hepatic artery allows selective delivery to the tumors with relative sparing of normal liver tissue and little extrahepatic exposure, thus limiting systemic side effects. There is a paucity of randomized controlled trial evidence to inform the optimal integration of regional therapies into the management of CRLM. Hepatic arterial infusion pump (HAIP) chemotherapy has a potential survival benefit when used in the adjuvant setting after resection of CRLM. HAIP chemotherapy can be safely given with contemporary systemic therapies and is associated with a high objective response and rate of conversion to resectability in patients with uCRLM. Drug-eluting beads coated with irinotecan transarterial chemoembolization is associated with high objective response rates within the liver and has a well-established safety profile in patients with uCRLM. Transarterial radioembolization achieves high rates of response within the liver but is not associated with improvements in overall survival or quality of life in the first- or second-line setting for uCRLM. The best treatment approach is the one that most aligns with a given patients' values, preferences, and philosophy of care. In the first-line setting, HAIP could be offered to motivated patients who hope to achieve conversion to resectability. After progression on chemotherapy, HAIP, transarterial chemoembolization, and transarterial radioembolization are valuable treatment options to consider for patients with liver-limited or liver-predominant CRLM who seek to optimize response rates and regional control.
Hepatocellular Carcinoma: Pick the Winner—Tyrosine Kinase Inhibitor Versus Immuno-oncology Agent–Based Combinations
Authors: Bejjani Anthony C. , Finn Richard S.
Published: June 2022

The treatment landscape for advanced hepatocellular carcinoma has changed dramatically over the past 4 years. We now have numerous options for patients in frontline, second-line, and beyond. The most significant impact has been the introduction of immunotherapy into our treatment paradigms. We now have regimens that induce consistent double-digit objective response rates and markedly improve overall survival (OS) with favorable side effect profiles. The combination of atezolizumab and bevacizumab has demonstrated that the combination of targeting programmed death-ligand 1 and the vascular endothelial growth factor axis can improve outcomes versus sorafenib in the IMBrave150 study. Results from the COSMIC-312 study evaluating the multikinase vascular endothelial growth factor receptor, hepatocyte growth factor receptor, and AXL tyrosine kinase receptor inhibitor cabozantinib in combination with atezolizumab improved progression-free survival versus sorafenib, but at this time, there is no improvement in OS and response rates were lower than expected. Additional data with similar combinations are awaited on the basis of encouraging early-phase data. In addition, the combination of cytotoxic T-lymphocyte–associated protein 4 and programmed cell death-1/programmed death-ligand 1 targeting is yielding similar promising early results, and the phase III HIMALAYA study met its primary end points of improving OS versus sorafenib for durvalumab plus tremelimumab and demonstrated noninferiority for single-agent durvalumab as well. However, this combination did not improve progression-free survival and objective response rates with this combination did not seem significantly different from that with single-agent durvalumab. Although there are still knowledge gaps in this rapidly changing landscape, we will address some of the important questions relevant to making therapeutic decisions in the management of advanced hepatocellular carcinoma in the modern era on the basis of our current knowledge of the safety and efficacy of these evolving regimens. The goal is to provide clinicians with the knowledge needed to optimize outcomes for their patients.
Neuroendocrine Tumors and Peptide Receptor Radionuclide Therapy: When Is the Right Time?
Authors: Hope Thomas A. , Pavel Marianne , Bergsland Emily K.
Published: June 2022

Since its approval in 2018 by the US Food and Drug Administration, peptide receptor radionuclide therapy (PRRT) has become a mainstay in the treatment of neuroendocrine tumors. Lutetium-177-DOTATATE, the only approved agent, is indicated for the treatment of gastroenteropancreatic-neuroendocrine tumors. Although patient selection appears straightforward with somatostatin receptor-positron emission tomography, there is considerable complexity when deciding which patients to treat and when to start PRRT. Herein, we review the many factors that affect patient selection, focusing on the optimal patients to treat. Although significant effort has been expended to determine which patients benefit the most from PRRT, a validated predictive biomarker remains elusive. Although PRRT has been used for more than 2 decades in Europe and standards of care exist for safe treatment, there remain numerous questions regarding when PRRT should be used relative to other treatments. It is important to remember that multidisciplinary discussions are essential. Currently, there are a number of ongoing studies looking to assess the efficacy of PRRT compared with other treatment options and to optimize treatment through combination therapy, different dosing strategies, or use of different radionuclides and radioligands.
Opportunities and Challenges for PBPK Model of mAbs in Paediatrics and Pregnancy
Authors: Gill Katherine L. , Jones Hannah M.
Published: June 2022

New drugs may in some cases need to be tested in paediatric and pregnant patients. However, it is difficult to recruit such patients and there are many ethical issues around their inclusion in clinical trials. Modelling and simulation can help to plan well-designed clinical trials with a reduced number of participants and to bridge gaps where recruitment is difficult. Physiologically based pharmacokinetic (PBPK) models for small molecule drugs have been used to aid study design and dose adjustments in paediatrics and pregnancy, with several publications in the literature. However, published PBPK models for monoclonal antibodies (mAb) in these populations are scarce. Here, the current status of mAb PBPK models in paediatrics and pregnancy is discussed. Seven mAb PBPK models published for paediatrics were found, which report good prediction accuracy across a wide age range. No mAb PBPK models for pregnant women have been published to date. Current challenges to the development of such PBPK models are discussed, including gaps in our knowledge of relevant physiological processes and availability of clinical data to verify models. As the availability of such data increases, it will help to improve our confidence in the PBPK model predictive ability. Advantages for using PBPK models to predict mAb PK in paediatrics and pregnancy are discussed. For example, the ability to incorporate ontogeny and gestational changes in physiology, prediction of maternal, placental and foetal exposure and the ability to make predictions fromin vitroand preclinical data prior to clinical data being available.
Enhanced ferroelectricity by strain gradient in few-layer HfO2thin films
Authors: Chen Jianwen , Zhao Wei , Song Wenjing , Cao Wang , Ding Jianwen
Published: June 2022

Due to the great potential in reducing the size of ferroelectric memory cells and the good compatibility with traditional silicon process, the ferroelectricity of few-layer HfO2 thin films has received huge attention, but its microscopic mechanism is still unclear. Based on first-principles calculations, the ferroelectricity of few-layer HfO2 thin films in the presence of both strain and strain gradient has been investigated systematically. It is shown that the orthorhombic ferroelectric phase exists stably with the strain between −7% and 3%, and the ferroelectric polarization decreases monotonically with the strain increasing, which is consistent with previous studies. In particular, the ferroelectric polarization increases monotonically with the strain gradient increasing within the strain less than −2.5%, which is due to the fact that the strain gradient further separates the positive and negative centers. Our findings provide possible theoretical explanations for recent experimental results and technical guidance for the design of ultra-thin ferroelectric devices.