bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the effectiveness of the Play Active policy intervention and implementation support in early childhood education and care: a pragmatic cluster randomised trial protocol
Authors: Nathan Andrea , Adams Emma , Trost Stewart , Cross Donna , Schipperijn Jasper , McLaughlin Matthew , Thornton Ashleigh , Trapp Georgina , Lester Leanne , George Phoebe , Wenden Elizabeth , Christian Hayley
Published: February 2022

Background

Daily physical activity is critical during the early years of life for facilitating children’s health and development. A large proportion of preschool children do not achieve the recommended 3 h of daily physical activity. Early childhood education and care (ECEC) services are a key setting to intervene to increase physical activity. There is a significant need for ECEC specific physical activity policy, including clearer guidelines on the amount of physical activity children should do during care, and strategies for implementation of these guidelines.

Methods

This study is a pragmatic cluster randomised trial to evaluate the effectiveness of the Play Active physical activity policy intervention to improve early childhood education and care educator’s physical activity-related practices. The central component of Play Active is an evidence-informed physical activity policy template which includes 25 practices to support nine age-specific recommendations on the amount of physical activity and sedentary time, including screen time, young children should do while in care. There are six implementation support strategies to facilitate physical activity policy implementation: (i) personalise policy (services select at least five of the 25 practices to focus on initially); (ii) policy review and approval; (iii) a resource guide; (iv) a brief assessment tool for monitoring children’s energetic play; (v) professional development; and (vi) Project Officer implementation support (phone calls). A total of 60 early childhood education and care services will be recruited from metropolitan Perth, Western Australia. After baseline assessment, services will be randomly allocated to either intervention or wait-listed comparison conditions. Primary (educator-reported frequency and amount of daily time provided for children’s physical activity, sedentary and screen time) and secondary (educator physical activity-related practices, self-efficacy, motivation, attitudes and beliefs, social support, and supportive physical environment) outcomes will be assessed at baseline and post-intervention, after intervention services have had a minimum 3 months of policy implementation within their service.

Discussion

The Play Active trial will rigorously evaluate a novel physical activity policy intervention with implementation support that promotes positive physical activity behaviours in educators and children attending ECEC. If effective, the program could be adapted, scaled-up and delivered in ECEC services nationally.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12620001206910 (date of registration 13/11/2020).
Advance care planning in primary care: a retrospective medical record study among patients with different illness trajectories
Authors: Bekker Yvonne A. C. , Suntjens Ankie F. , Engels Y. , Schers H. , Westert Gert P. , Groenewoud A. Stef
Published: February 2022

Background

Advance Care Planning (ACP) enables physicians to align healthcare with patients’ wishes, reduces burdensome life-prolonging medical interventions, and potentially improves the quality of life of patients in the last phase of life. However, little objective information is available about the extent to which structured ACP conversations are held in general practice.

Our aim was to examine the documentation of ACP for patients with cancer, organ failure and multimorbidity in medical records (as a proxy for ACP application) in Dutch general practice.

Methods

We chose a retrospective medical record study design in seven primary care facilities. Medical records of 119 patients who died non-suddenly (55 cancer, 28 organ failure and 36 multimorbidity) were analysed. Other variables were: general characteristics, data on ACP documentation, correspondence between medical specialist and general practitioner (GP), and healthcare utilization in the last 2 years of life.

Results

In 65% of the records, one or more ACP items were registered by the GP. Most often documented were aspects regarding euthanasia (35%), the preferred place of care and death (29%) and concerns and hopes towards the future (29%). Median timing of the first ACP conversation was 126 days before death (inter-quartile range (IQR) 30–316). ACP was more often documented in patients with cancer (84%) than in those with organ failure (57%) or multimorbidity (42%) (p = 0.000). Patients with cancer had the most frequent (median 3 times, IQR 2–5) and extensive (median 5 items, IQR 2–7) ACP consultations.

Conclusion

Documentation of ACP items in medical records by GPs is present, however limited, especially in patients with multimorbidity or organ failure. We recommend more attention for – and documentation of – ACP in daily practice, in order to start anticipatory conversations in time and address the needs of all people living with advanced conditions in primary care.
Addressing health disparities in hispanic communities through an innovative team-based medical spanish program at the medical school level – a single-institution study
Authors: Oliver Michael , Fernberg Taylor , Lyons Paul , Elango Sambandam , Green Gordon J. , Talib Zohray M.
Published: February 2022

Background

There are insufficient Spanish-speaking physicians to effectively serve a large and rapidly growing Spanish-speaking patient population.

Methods

A team-based hybrid medical Spanish program was designed and implemented at a single medical school in Southern California. This pilot program consisted of a weekly in-person portion where students reviewed Spanish vocabulary and grammar and practiced clinical encounters in teams through active role play. Students supplemented in-class learning with online coursework. Program success was measured through physician-evaluated clinical encounters with Spanish-speaking standardized patients, a 100-question multiple-choice exam, and pre- and post-program surveys.

Results

97% of students in the program (n = 32) received a passing grade at program completion. Student surveys demonstrated enthusiasm and engagement in weekly sessions (95% overall attendance, 97% reported feeling either excited or ready to learn prior to class). In a post-program survey, 100% of students felt better suited and increased desire to treat Hispanic patients. Additionally, all students indicated an interest in the continued use of Spanish in both their schooling and future practice. In a follow-up survey after three months of clinical experience in their 3rd year of medical school, 100% of students reported that medical Spanish is "very beneficial" in patient care and that students with medical Spanish proficiency have advantages over non-speaking students when it comes to patient care opportunities. 100% felt that time spent learning medical Spanish during pre-clinical years was time well spent and that the medical Spanish program enhanced their care of Spanish-speaking students.

Conclusions

The results of the pilot program show a significant increase in the ability of students to engage in clinical interaction in Spanish. The results of our study demonstrate a significant increase in the knowledge, clinical skills, and self-reported confidence of students to treat Hispanic patients. Furthermore, all students not only felt better equipped and more confident to treat Hispanic patients, but they also had an increased desire to do so moving forward in their careers. We conclude that an effective medical Spanish program can be executed simultaneously with a pre-clinical medical school curriculum.
The ambiguous role of obesity in oncology by promoting cancer but boosting antitumor immunotherapy
Authors: Assumpção José Antônio Fagundes , Pasquarelli-do-Nascimento Gabriel , Duarte Mariana Saldanha Viegas , Bonamino Martín Hernan , Magalhães Kelly Grace
Published: February 2022

Obesity is nowadays considered a pandemic which prevalence’s has been steadily increasingly in western countries. It is a dynamic, complex, and multifactorial disease which propitiates the development of several metabolic and cardiovascular diseases, as well as cancer. Excessive adipose tissue has been causally related to cancer progression and is a preventable risk factor for overall and cancer-specific survival, associated with poor prognosis in cancer patients. The onset of obesity features a state of chronic low-grade inflammation and secretion of a diversity of adipocyte-derived molecules (adipokines, cytokines, hormones), responsible for altering the metabolic, inflammatory, and immune landscape. The crosstalk between adipocytes and tumor cells fuels the tumor microenvironment with pro-inflammatory factors, promoting tissue injury, mutagenesis, invasion, and metastasis. Although classically established as a risk factor for cancer and treatment toxicity, recent evidence suggests mild obesity is related to better outcomes, with obese cancer patients showing better responses to treatment when compared to lean cancer patients. This phenomenon is termed obesity paradox and has been reported in different types and stages of cancer. The mechanisms underlying this paradoxical relationship between obesity and cancer are still not fully described but point to systemic alterations in metabolic fitness and modulation of the tumor microenvironment by obesity-associated molecules. Obesity impacts the response to cancer treatments, such as chemotherapy and immunotherapy, and has been reported as having a positive association with immune checkpoint therapy. In this review, we discuss obesity’s association to inflammation and cancer, also highlighting potential physiological and biological mechanisms underlying this association, hoping to clarify the existence and impact of obesity paradox in cancer development and treatment.
Diabetes and restenosis
Authors: Wilson Scott , Mone Pasquale , Kansakar Urna , Jankauskas Stanislovas S. , Donkor Kwame , Adebayo Ayobami , Varzideh Fahimeh , Eacobacci Michael , Gambardella Jessica , Lombardi Angela , Santulli Gaetano
Published: February 2022

Restenosis, defined as the re-narrowing of an arterial lumen after revascularization, represents an increasingly important issue in clinical practice. Indeed, as the number of stent placements has risen to an estimate that exceeds 3 million annually worldwide, revascularization procedures have become much more common. Several investigators have demonstrated that vessels in patients with diabetes mellitus have an increased risk restenosis. Here we present a systematic overview of the effects of diabetes on in-stent restenosis. Current classification and updated epidemiology of restenosis are discussed, alongside the main mechanisms underlying the pathophysiology of this event. Then, we summarize the clinical presentation of restenosis, emphasizing the importance of glycemic control in diabetic patients. Indeed, in diabetic patients who underwent revascularization procedures a proper glycemic control remains imperative.
Circular RNA circ_IRAK3 contributes to tumor growth through upregulating KIF2A via adsorbing miR-603 in breast cancer
Authors: Wang Fang , Li Jingruo , Li Lin , Chen Zhuo , Wang Nan , Zhu Mingzhi , Mi Hailong , Xiong Youyi , Guo Guangcheng , Gu Yuanting
Published: February 2022

Background

Breast cancer (BC) threatens the health of women around the world. Researchers have proved that hsa_circ_0005505 (circ_IRAK3) facilitates BC cell invasion and migration, but the regulatory mechanisms of circ_IRAK3 in BC remain mostly unknown. We aim to explore a new mechanism by which circ_IRAK3 promotes BC progression.

Methods

Levels of circ_IRAK3, microRNA (miR)-603, and kinesin family member 2A (KIF2A) mRNA in BC tissues and cells were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle progression, colony formation, and proliferation of BC cells were evaluated by flow cytometry, plate clone, or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assays. The migration, invasion, and apoptosis of BC cells were determined by transwell or flow cytometry assays. Several protein levels were detected using western blotting. The targeting relationship between circ_IRAK3 or KIF2A and miR-603 was verified via dual-luciferase reporter assay. The role of circ_IRAK3 in vivo was verified by xenograft assay.

Results

We observed higher levels of circ_IRAK3 in BC tissues and cell lines than their respective controls. Functional experiments presented that circ_IRAK3 silencing induced BC cell apoptosis, curbed cell proliferation, migration, and invasion in vitro, and decreased tumor growth in vivo. Mechanistically, circ_IRAK3 could modulate kinesin family member 2A (KIF2A) expression through acting as a microRNA (miR)-603 sponge. miR-603 silencing impaired the effects of circ_IRAK3 inhibition on the malignant behaviors of BC cells. Also, the repressive effects of miR-603 mimic on the malignant behaviors of BC cells were weakened by KIF2A overexpression.

Conclusions

circ_IRAK3 exerted a promoting effect on BC progression by modulating the miR-603/KIF2A axis, providing a piece of novel evidence for circ_IRAK3 as a therapeutic target for BC.
Dry-season transmission and determinants of Plasmodium infections in Jawi district, northwest Ethiopia
Authors: Amare Andualem , Eshetu Tegegne , Lemma Wossenseged
Published: February 2022

Background

Malaria remains a serious global public health problem, and continues to have a devastating impact on people’s health worldwide. Continuous monitoring and evaluation of current malaria transmission status in different seasons is a mainstay for the success of ongoing intervention strategies for malaria. The purpose of this study was to assess the dry-season transmission and determinants of malaria in Jawi district, northwest Ethiopia.

Methods

A community-based cross-sectional study was conducted from January 13 to February 11, 2020; among selected Kebeles in the Jawi district. A multistage sampling technique was used in this study. Random and systematic sampling techniques were carried out to selectKebelesand each household, respectively. Light microscopy and CareStart™ Malaria HRP2/pLDH (Pf/Pv) Combo RDT were implemented to determine the prevalence of malaria. Moreover, associated risk factors in the prevalence of malaria were assessed by using a bivariate and multivariate logistic regression model.

Results

A total of 219 study participants were enrolled in this study. Of the total enrolled individuals, malaria cases were found among 36 individuals with a positivity rate of 16.4% (95% CI 11.4–21.5).Plasmodium falciparumwas the predominant species with an estimated prevalence of 87.0% in the study areas. Interrupted utilization of ITN (AOR = 4.411, 95% CI 1.401–13.880), using over 3 years older ITNs (AOR = 9.622, 95% CI 1.881–49.214), travel history (AOR = 12.703, 95% CI 2.441–66.114), living in a house with holes on the wall (AOR = 3.811, 95% CI 1.010–14.384), and living in a house with an eave (AOR = 4.23, 95% CI 1.065–16.801) significantly increased the probability of malaria positivity rate.

Conclusion

Malaria is still an important public health burden among individuals in the Jawi district. Interrupted utilization of ITNs, using over 3 years older ITNs, living in a house with holes on the wall, living in a house with an eave, and travel history were identified as the risk factors of malaria. Therefore, the District health office and Health extension workers should promote daily utilization of good ITNs and improve housing conditions to reduce malaria prevalence.
The impact of Covid-19 on malaria services in three high endemic districts in Rwanda: a mixed-method study
Authors: Hakizimana Dieudonne , Ntizimira Christian , Mbituyumuremyi Aimable , Hakizimana Emmanuel , Mahmoud Hani , Birindabagabo Pascal , Musanabaganwa Clarisse , Gashumba Diane
Published: February 2022

Background

Rwanda has achieved impressive reductions in malaria morbidity and mortality over the past two decades. However, the disruption of essential services due to the current Covid-19 pandemic can lead to a reversal of these gains in malaria control unless targeted, evidence-based interventions are implemented to mitigate the impact of the pandemic. The extent to which malaria services have been disrupted has not been fully characterized. This study was conducted to assess the impact of Covid-19 on malaria services in Rwanda.

Methods

A mixed-methods study was conducted in three purposively selected districts in Rwanda. The quantitative data included malaria aggregated data reported at the health facility level and the community level. The data included the number of malaria tests, uncomplicated malaria cases, severe malaria cases, and malaria deaths. The qualitative data were collected using focus group discussions with community members and community health workers, as well as in-depth interviews with health care providers and staff working in the malaria programme. Interrupted time series analysis was conducted to compare changes in malaria presentations between the pre-Covid-19 period (January 2019 to February 2020) and Covid-19 period (from March 2020 to November 2020). The constant comparative method was used in qualitative thematic analysis.

Results

Compared to the pre-Covid-19 period, there was a monthly reduction in patients tested in health facilities of 4.32 per 1000 population and a monthly increase in patients tested in the community of 2.38 per 1000 population during the Covid-19 period. There was no change in the overall presentation rate for uncomplicated malaria. The was a monthly reduction in the proportion of severe malaria of 5.47 per 100,000 malaria cases. Additionally, although healthcare providers continued to provide malaria services, they were fearful that this would expose them and their families to Covid-19. Covid-19 mitigation measures limited the availability of transportation options for the community to seek care in health facilities and delayed the implementation of some key malaria interventions. The focus on Covid-19-related communication also reduced the amount of health information for other diseases provided to community members.

Conclusion

The Covid-19 pandemic resulted in patients increasingly seeking care in the community and poses challenges to maintaining delivery of malaria services in Rwanda. Interventions to mitigate these challenges should focus on strengthening programming for the community and home-based care models and integrating malaria messages into Covid-19-related communication. Additionally, implementation of the interrupted interventions should be timed and overlap with the malaria transmission season to mitigate Covid-19 consequences on malaria.
Protothecosis in the mucosa of the pharynx mimicking pharyngeal cancer in an immunocompetent individual: a case report
Authors: Yamashita Marie , Ikeda Mahoko , Kato Ito , Ohama Yuki , Ando Mizuo , Ikemura Masako , Jubishi Daisuke , Kanno Yoshiaki , Okamoto Koh , Umeyama Takashi , Nakamura Shigeki , Miyazaki Yoshitsugu , Okugawa Shu , Moriya Kyoji
Published: February 2022

Background

Protothecosis is a rare infection in humans and animals caused by the achlorophyllic algae Prototheca species. More than half of the protothecosis cases are cutaneous infections, and most cases are observed in immunocompromised individuals.

Case presentation

We report a case of Prototheca wickerhamii infection in the mucosa of the pharynx in a 53-year-old immunocompetent woman with an incidentally found mass lesion at the left tongue base. Histopathological findings of the mass lesion suggested cryptococcosis, but P. wickerhamii was identified from the oropharynx scrape culture based on DNA sequencing. After surgical resection, fosfluconazole treatment was initiated, and subsequently, treatment was switched to topical amphotericin B. The residual mass lesion did not deteriorate during the 4-month antifungal treatment and 1-year observational period.

Conclusions

Prototheca species can be easily misdiagnosed as yeasts because of their morphological and pathological similarities. Prototheca, in addition to Cryptococcus should be considered if slow-growing, large Gram-positive organisms are encountered. Lactophenol cotton blue staining of the colony helps distinguish these organisms. Further study is needed to determine the appropriate treatment according to the infection focus.
Exosomal circLPAR1 functions in colorectal cancer diagnosis and tumorigenesis through suppressing BRD4 via METTL3–eIF3h interaction
Authors: Zheng Rui , Zhang Ke , Tan Shanyue , Gao Fang , Zhang Yajie , Xu Wenxia , Wang Huabin , Gu Dongying , Zhu Lingjun , Li Shuwei , Chu Haiyan , Zhang Zhengdong , Liu Lingxiang , Du Mulong , Wang Meilin
Published: February 2022

Background

Exosomes have emerged as vital biomarkers of multiple cancers and contain abundant circular RNAs (circRNAs). However, the potential for exosomal circRNAs to be used in diagnostics and their molecular mechanism of action in colorectal cancer (CRC) remain unclear.

Methods

CRC-specific exosomal circRNAs were identified by RNA sequencing, exoRBase database and a tissue microarray. The diagnostic performance of plasma exosomal circRNAs was evaluated among cancer-free controls, precancer individuals, CRC patients, and patients with other types of cancer. The corresponding biological functions were mainly assessed using circRNA pull-down, proteomic analysis, and RNA immunoprecipitation assay underlying cellular and mouse models.

Results

CircLPAR1 was encapsulated in exosomes with high stability and detectability, and its expression in plasma exosomes was remarkably decreased during CRC development but recovered after surgery. Exosomal circLPAR1 showed cancer specificity in CRC diagnosis and increased the diagnostic performance to an area under the receiver operating characteristic curve of 0.875, as determined by analysing its performance in combination with common clinical biomarkers CEA and CA19–9. Additionally, circLPAR1 was downregulated in CRC tissues and was associated with overall survival. Mechanistically, exosomal circLPAR1 was internalized by CRC cells, and it suppressed tumor growth, likely because exosomal circLPAR1 directly bound with eIF3h specifically suppressed the METTL3-eIF3h interaction, decreasing the translation of oncogene BRD4.

Conclusions

This comprehensive study highlights plasma exosomal circLPAR1 as a promising predictor in CRC diagnosis and describes its biological regulation of colorectal tumorigenesis. This study provides a new perspective on early diagnosis in the clinic and pathogenesis in disease development.
m6A modification: recent advances, anticancer targeted drug discovery and beyond
Authors: Deng Li-Juan , Deng Wei-Qing , Fan Shu-Ran , Chen Min-Feng , Qi Ming , Lyu Wen-Yu , Qi Qi , Tiwari Amit K. , Chen Jia-Xu , Zhang Dong-Mei , Chen Zhe-Sheng
Published: February 2022

Abnormal N6-methyladenosine (m6A) modification is closely associated with the occurrence, development, progression and prognosis of cancer, and aberrant m6A regulators have been identified as novel anticancer drug targets. Both traditional medicine-related approaches and modern drug discovery platforms have been used in an attempt to develop m6A-targeted drugs. Here, we provide an update of the latest findings on m6A modification and the critical roles of m6A modification in cancer progression, and we summarize rational sources for the discovery of m6A-targeted anticancer agents from traditional medicines and computer-based chemosynthetic compounds. This review highlights the potential agents targeting m6A modification for cancer treatment and proposes the advantage of artificial intelligence (AI) in the discovery of m6A-targeting anticancer drugs.

Graphical abstract

Three stages of m6A-targeting anticancer drug discovery: traditional medicine-based natural products, modern chemical modification or synthesis, and artificial intelligence (AI)-assisted approaches for the future.
METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis
Authors: Fan Hui-Ning , Chen Zhao-Yu , Chen Xiao-Yu , Chen Ming , Yi You-Cai , Zhu Jin-Shui , Zhang Jing
Published: February 2022

Background

N6-methyladenosine (m6A) RNA methylation and circular RNAs (circRNAs) have been shown to act vital roles in multiple malignancies including gastric cancer (GC). However, there is little knowledge about how m6A modification of circRNAs contributes to GC progression.

Methods

The association of METTL14 expression with the clinicopathological characteristics and prognosis in patients with GC was assessed by Western blot, Immunohistochemistry and public datasets. In vitro and vivo function experiments were conducted to investigate the role of METTL14 in GC. Furthermore, m6A-circRNA epitranscriptomic microarray was utilized to identify METTL14-mediated m6A modification of circRNAs, which were validated by methylated RNA immunoprecipitation (Me-RIP), RT-qPCR and rescue experiments in GC cells. The sponge of circORC5 with miR-30c-2-3p was confirmed by luciferase gene report and RNA immunoprecipitation assays. The expression, localization and prognosis of circORC5 in GC were evaluated by fluorescence in situ hybridization. The effects of METTL14 and (or) circORC5 on miR-30c-2-3p-mediated AKT1S1 and EIF4B were estimated by RT-qPCR and Western blot analyses.

Results

We found that METTL14 was downregulated in GC tissue samples and its low expression acted as a prognostic factor of poor survival in patients with GC. Ectopic expression of METTL14 markedly repressed growth and invasion of GC cellsin vitroandin vivo, whereas knockdown of METTL14 harbored the opposite effects. Mechanically, m6A-circRNA epitranscriptomic microarray and Me-RIP identified circORC5 as the downstream target of METTL14. Silencing of METTL14 reduced the m6A level of circORC5, but increased circORC5 expression. Moreover, circORC5 could sponge miR-30c-2-3p, and reverse METTL14-caused upregulation of miR-30c-2-3p and downregulation of AKT1S1 and EIF4B. In addition, circORC5 possessed a negative correlation with miR-30c-2-3p and indicated a poor survival in GC.

Conclusion

Our findings demonstrate that METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis.
The effects and mechanism of paeoniflorin in promoting osteogenic differentiation of MC3T3-E1
Authors: Guo Wei , Yang Xiao-guang , Shi Yu-lin , Wang Hong
Published: February 2022

Background

The incidence of osteoporosis and osteoporotic fractures is increasing every year. Traditional Chinese Medicine (TCM) can shed new light on the treatment of osteoporosis. This study aimed to explore the role and mechanism of paeoniflorin in promoting osteogenic differentiation of an osteoblast precursor cell line (MC3T3-E1).

Methods

MC3T3-E1 cells were cultured in osteogenic induction medium (OIM) and OIM combined with different concentrations of paeoniflorin. The optimal dose of paeoniflorin was assessed by a cell counting kit-8 (CCK-8) assay. Then, alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining were performed to assess the osteogenic capacity of paeoniflorin. The transcription of osteogenic genes and the expression of osteogenic proteins were assessed by RT-PCR and Western blotting, respectively. The transcription of Wnt/β-catenin signaling pathway genes and proteins was assessed by RT-PCR and Western blotting, respectively. Finally, Dickkopf-1 (DKK-1), a Wnt/β-catenin signaling pathway inhibitor, was used to identify whether the Wnt/β-catenin signaling pathway was involved in the osteogenic differentiation of paeoniflorin. Osteoclastogenesis in RAW264.7 cells was identified by tartrate-resistant acid phosphatase (TRAP) staining.

Results

At concentrations ranging from 0.1 to 100 μM, paeoniflorin was not cytotoxic to MC3T3-E1 cells. Paeoniflorin significantly increased the osteogenic differentiation of MC3T3-E1 cells in a dose-dependent manner. Moreover, paeoniflorin significantly increased osteogenic differentiation gene and protein expression. Through bioinformatic analysis, paeoniflorin-affected genes were found to be involved in different signaling pathways, such as the Wnt/β-catenin signaling pathway. Paeoniflorin enhanced β-catenin and CyclinD1 expression compared with that of the control groups. DKK-1 partially reversed the promoting effects of paeoniflorin in promoting osteogenic differentiation of MC3T3-E1 cells. Moreover, paeoniflorin inhibited the osteoclastogenesis of RAW264.7 cells.

Conclusion

Paeoniflorin promotes osteogenic differentiation in MC3T3-E1 cells by regulating the Wnt/β-catenin pathway. Paeoniflorin is a potential therapeutic agent for the treatment of osteoporosis.
Shifting to Tele-Mental Health in humanitarian and crisis settings: an evaluation of Médecins Sans Frontières experience during the COVID-19 pandemic
Authors: Ibragimov Khasan , Palma Miguel , Keane Gregory , Ousley Janet , Crowe Madeleine , Carreño Cristina , Casas German , Mills Clair , Llosa Augusto ,   M. S. F. Mental Health Working Group, Marques Ana , Tijerino Ana-Maria , Droste Anneli , Echeverri Carolina , Fredj Nadja , Sleit Raghda , Sultan Sylvie Fagard
Published: February 2022

Background

‘Tele-Mental Health (MH) services,’ are an increasingly important way to expand care to underserved groups in low-resource settings. In order to continue providing psychiatric, psychotherapeutic and counselling care during COVID-19-related movement restrictions, Médecins Sans Frontières (MSF), a humanitarian medical organization, abruptly transitioned part of its MH activities across humanitarian and resource-constrained settings to remote format.

Methods

From June–July of 2020, investigators used a mixed method, sequential explanatory study design to assess MSF staff perceptions of tele-MH services. Preliminary quantitative results influenced qualitative question guide design. Eighty-one quantitative online questionnaires were collected and a subset of 13 qualitative follow-up in-depth interviews occurred.

Results

Respondents in 44 countries (6 geographic regions), mostly from Sub-Saharan Africa (39.5%), the Middle East and North Africa (18.5%) and Asia (13.6%) participated. Most tele-MH interventions depended on audio-only platforms (80%). 30% of respondents reported that more than half of their patients were unreachable using these interventions, usually because of poor network coverage (73.8%), a lack of communication devices (72.1%), or a lack of a private space at home (67.2%). Nearly half (47.5%) of respondents felt their staff had a decreased ability to provide comprehensive MH care using telecommunication platforms. Most respondents thought MH staff had a negative (46%) or mixed (42%) impression of remote care. Nevertheless, almost all respondents (96.7%) thought tele-MH services had some degree of usefulness, notably improved access to care (37.7%) and time efficiency (32.8%). Qualitative results outlined a myriad of challenges, notably in establishing therapeutic alliance, providing care for vulnerable populations and those inherent to the communications infrastructure.

Conclusion

Tele-MH services were perceived to be a feasible alternative solution to in-person therapeutic interventions in humanitarian settings during the COVID-19 pandemic. However, they were not considered suitable for all patients in the contexts studied, especially survivors of sexual or interpersonal violence, pediatric and geriatric cases, and patients with severe MH conditions. Audio-only technologies that lacked non-verbal cues were particularly challenging and made risk assessment and emergency care more difficult. Prior to considering tele-MH services, communications infrastructure should be assessed, and comprehensive, context-specific protocols should be developed.
Genetic variation at mouse and human ribosomal DNA influences associated epigenetic states
Authors: Rodriguez-Algarra Francisco , Seaborne Robert A. E. , Danson Amy F. , Yildizoglu Selin , Yoshikawa Harunori , Law Pui Pik , Ahmad Zakaryya , Maudsley Victoria A. , Brew Ama , Holmes Nadine , Ochôa Mateus , Hodgkinson Alan , Marzi Sarah J. , Pradeepa Madapura M. , Loose Matthew , Holland Michelle L. , Rakyan Vardhman K.
Published: February 2022

Background

Ribosomal DNA (rDNA) displays substantial inter-individual genetic variation in human and mouse. A systematic analysis of how this variation impacts epigenetic states and expression of the rDNA has thus far not been performed.

Results

Using a combination of long- and short-read sequencing, we establish that 45S rDNA units in the C57BL/6J mouse strain exist as distinct genetic haplotypes that influence the epigenetic state and transcriptional output of any given unit. DNA methylation dynamics at these haplotypes are dichotomous and life-stage specific: at one haplotype, the DNA methylation state is sensitive to the in utero environment, but refractory to post-weaning influences, whereas other haplotypes entropically gain DNA methylation during aging only. On the other hand, individual rDNA units in human show limited evidence of genetic haplotypes, and hence little discernible correlation between genetic and epigenetic states. However, in both species, adjacent units show similar epigenetic profiles, and the overall epigenetic state at rDNA is strongly positively correlated with the total rDNA copy number. Analysis of different mouse inbred strains reveals that in some strains, such as 129S1/SvImJ, the rDNA copy number is only approximately 150 copies per diploid genome and DNA methylation levels are < 5%.

Conclusions

Our work demonstrates that rDNA-associated genetic variation has a considerable influence on rDNA epigenetic state and consequently rRNA expression outcomes. In the future, it will be important to consider the impact of inter-individual rDNA (epi)genetic variation on mammalian phenotypes and diseases.
Efficacy and safety of modified Bushen Yiqi formulas (MBYF) as an add-on to formoterol and budesonide in the management of COPD: study protocol for a multicentre, double-blind, placebo-controlled, parallel-group, randomized clinical trial: FB-MBYF Trial
Authors: Kong Qing , Cao Yuxue , Gao Zhen , Sun Jing , Zhang Hongying , Du Yijie , Lv Yubao , Zhou Sihan , Tang Zihui , Liu Baojun , Dong Jingcheng
Published: February 2022

Background

Inhaled glucocorticoid corticosteroid (ICS), long-acting β2-adrenoceptor agonist (LABA), and other drugs have limited therapeutic effects on COPD with significant individual differences. Traditional Chinese medicine (TCM)-modified Bushen Yiqi formula (MBYF) demonstrates advantages in COPD management in China. This study aims to evaluate the efficacy and safety of MBYF as an add-on to budesonide/formoterol in COPD patients and confirm the related genes affecting the therapeutic effect in the treatment of COPD.

Methods

In this multicentre, randomised, double-blind, placebo-controlled, parallel-group study, eligible patients with COPD will randomly receive a 360-day placebo or MBYF as an adjuvant to budesonide/formoterol in a 1:1 ratio and be followed up with every 2 months. The primary outcomes will be the frequency, times, and severity of acute exacerbation of COPD (AECOPD), COPD assessment test (CAT) score, and pulmonary function tests (PFTs). The secondary outcomes will include the modified Medical Research Council (mMRC) dyspnoea scale, 6-min walking test (6MWT), BODE index, quantitative scores of syndromes classified in TCM, inflammation indices, and hypothalamic-pituitary-adrenaline (HPA) axis function. We will also test the genotype to determine the relationship between drugs and efficacy. All the data will be recorded in case report forms (CRFs) and analysed by SPSS V.20.0.

Discussion

A randomized clinical trial design to evaluate the efficacy and safety of MBYF in COPD is described. The results will provide evidence for the combination therapy of modern medicine and TCM medicine, and individual therapy for COPD.Trial registration.

Trial registration

ID: ChiCTR1900026124, Prospective registration.
Diet or additional supplement to increase potassium intake: protocol for an adaptive clinical trial
Authors: Hiremath Swapnil , Fergusson Dean , Knoll Greg , Ramsay Tim , Kong Jennifer , Ruzicka Marcel
Published: February 2022

Background

High blood pressure is the leading cause of cardiovascular disease worldwide. The prevalence of high blood pressure is steadily rising as the population grows amongst older adults with the ageing population. Therapeutical treatments are widely available to decrease blood pressures, in addition to many lifestyle options, such as dietary changes and exercise. There is a marked preference amongst patients, as reiterated by Hypertension Canada, for more research into non-therapeutic methods for controlling blood pressure or to reduce the burden of taking many pills to control high blood pressure. Indeed, effective options do exist, especially with diet, specifically decreasing sodium and increasing potassium intake. Current public health outreach primarily focusses on sodium intake, even though potassium intake remains low in the Western world. Excellent data exist in published research that increasing potassium intake, either via dietary modification or supplements, reduces blood pressure and reduces risk of cardiovascular outcomes such as stroke. However, the advice most often provided by medical professionals is to ‘eat more fruits and vegetables’ which has little impact on patient outcomes.

Methods

We propose to do a clinical trial in two stages with an adaptive trial design. In the first stage, participants with high blood pressure and proven low potassium intake (measured on the basis of a 24-h urine collection) will get individually tailored dietary advice, reinforced by weekly supportive phone/email support. At 4 weeks, if there has not been a measured increase in potassium intake, participants will be prescribed an additional potassium supplement. Testing will be conducted again at 8 weeks, to confirm the efficacy of the potassium supplement. Final measurements will be planned at 52 weeks to observe and measure the persistence of the effect of diet or additional supplement. Concurrent measurements of sodium intake, blood pressure, participant satisfaction, and safety measures will also be done.

Discussion

The results of the study will help determine the most effective method of increasing potassium intake, thus reducing blood pressure and need for blood pressure-lowering medicines, and at the same time potentially increasing participant satisfaction. The current guidelines recommend changes in diet, not a potassium supplement, to increase potassium intake; hence, the two-stage design will only add supplements if the most rigorous dietary advice does not work.

Trial registration

This study has been registered on ClinicalTrials.govNCT03809884. Registered on January 18, 2019
What Kigali’s open-air markets reveal about achieving food and nutrition security: the role of African indigenous crops
Authors: Baraka Eugene , Willis Mary S. , Ishimwe Brice A.
Published: February 2022

Background

Household dietary diversity in Rwanda remains low and significantly contributes to the double burden of malnutrition. Rwanda has one of the highest under five stunting rates globally, and malnutrition remains one of the most pressing public health issues; therefore, factors that shape food and nutrition security are of utmost concern. Globally, the variety of foods available in open-air markets has been shown to affect dietary diversity. Furthermore, the consumption of indigenous foods can contribute to a diverse diet and improve nutrition status. At present, there are limited data on foods available for purchase in open-air markets in Africa. Therefore, this study was designed to provide data on food availability in the largest open-air markets of Rwanda’s most populated city, Kigali, and to highlight which foods indigenous to Africa can be purchased.

Methods

All consumables were inventoried between October and December of 2020 in three open-air markets of Kigali, the capital city of Rwanda. Consumables were organized by the site of domestication and the nutritional contents of some African indigenous crops were compared to similar non-indigenous items.

Results

A variety of raw and processed consumables was available in the open-air markets inventoried; however, only 25.8% of available species are indigenous to Africa. All Rwanda’s staples, including sweet potatoes, plantains, beans, maize, banana, and cassava, are endemic to other continents. Indigenous plant species, which are often drought-resistant and more nutritious, for example, Africa’s pineapple fruits (Myrianthus holstii), could not be purchased in Kigali’s open-air markets. Pineapple fruits are richer in iron, vitamin C, protein, and vitamin A than banana, which is the most consumed fruit in Rwanda.

Conclusions

Given rapid population growth, limited arable land, and erratic climate patterns, policies to conserve and promote indigenous species, especially those already adapted to harsh environmental conditions, should be enacted in Rwanda. The cultivation of native vegetables and fruits in home gardens, and the conservation of edible wild species, can improve dietary diversity and enhance food and nutrition security across the entire country.
CAF indices and human ratings of oral performances in an opinion-based monologue task
Authors: Ogawa Chie
Published: February 2022

This study explored two assessment approaches to oral performances: analytical complexity, accuracy, and fluency (CAF) indices and human raters’ evaluations. CAF indices are frequently used in second-language speaking (L2) research; however, because tasks are communicative and goal-oriented, the degree to which students achieve such communicative goals must also be included. By incorporating human ratings of monologue organization and perceived CAF into speaking assessments, researchers can better understand the relationship between the analytical CAF indices and human ratings of a monologue task. The participants consisted of 48 English as a Foreign Language (EFL) students in a Japanese university. Their oral performances of 2-min opinion-based monologues were audio-recorded and then transcribed and analyzed using CAF measures. In addition, 11 human raters evaluated the same recordings in terms of the following criteria: topic organization, complexity, accuracy, and fluency. These ratings were then analyzed using the many-facet Rasch measurement (MFRM). Multiple linear regression results showed that fluency accounted for a significant amount of the human ratings, but other measures (lexis, complexity, accuracy) explained only a small portion of the variance. This study concluded with implications regarding L2 testing in speaking assessments.
What does it mean to “go beyond race”?
Authors: Osanami Törngren Sayaka , Suyemoto Karen L.
Published: February 2022

In this commentary piece, we argue that we must interrogate the meaning of race and examine why and how racedoesmatter in different societies across contexts before we can even consider moving “beyond race.” We understand race as fundamentally related to power, privilege, and oppression; we discuss how we cannot go “beyond race” in the face of persistent racisms, hierarchies and maintenance of power and privilege. We address that demographic changes in itself does not bring us “beyond race” and the importance of active policies and political mobilization through addressing race as an analytical category is necessary to go “beyond racism.”
PPP–RTK functional models formulated with undifferenced and uncombined GNSS observations
Authors: Zhang Baocheng , Hou Pengyu , Zha Jiuping , Liu Teng
Published: February 2022

Technique PPP–RTK combines the advantages of both the Precise Point Positioning (PPP) and the Real-Time Kinematic (RTK) positioning. With the emergence of multi-frequency Global Navigation Satellite System (GNSS) observations, it is preferable to formulate PPP–RTK functional models based on original (undifferenced and uncombined) observations. While there exist many variants of the undifferenced and uncombined PPP–RTK models, a unified theoretical framework needs developing to link these variants. In this contribution, we formulate a class of undifferenced and uncombined PPP–RTK functional models in a systematic way and cast them in a unified framework. This framework classifies the models into a code-plus-phase category and a phase-only category. Each category covers a variety of measurement scenarios on the network side, ranging from small-, medium- to large-scale networks. For each scenario, special care has been taken of the distinct ionospheric constraints and the difference between Code Division Multiple Access (CDMA) and Frequency Division Multiple Access (FDMA) signals. The key to systematically formulating these models lies in how to deal with the rank deficiency problems encountered. We opt for the Singularity-basis (S-basis) theory, giving rise to the full-rank observation equations in which the estimable parameters turn out to be the functions of original parameters and those selected as the S-basis. In the sequel, it becomes straightforward to derive for each scenario the user model as it, more or less, amounts to the single-receiver network model. Benefiting from the presented theoretical framework, the relationships and differences between various undifferenced and uncombined PPP–RTK models become clear, which can lead to the better use of these models in a specific situation.
Effect of an Antiracism Intervention on Racial Disparities in Time to Lung Cancer Surgery
Authors: Charlot Marjory , Stein Jacob Newton , Damone Emily , Wood Isabella , Forster Moriah , Baker Stephanie , Emerson Marc , Samuel-Ryals Cleo , Yongue Christina , Eng Eugenia , Manning Matthew , Deal Allison , Cykert Samuel
Published: February 2022

PURPOSE

Timely lung cancer surgery is a metric of high-quality cancer care and improves survival for early-stage non–small-cell lung cancer. Historically, Black patients experience longer delays to surgery than White patients and have lower survival rates. Antiracism interventions have shown benefits in reducing racial disparities in lung cancer treatment.

METHODS

We conducted a secondary analysis of Accountability for Cancer Care through Undoing Racism and Equity, an antiracism prospective pragmatic trial, at five cancer centers to assess the impact on overall timeliness of lung cancer surgery and racial disparities in timely surgery. The intervention consisted of (1) a real-time warning system to identify unmet care milestones, (2) race-specific feedback on lung cancer treatment rates, and (3) patient navigation. The primary outcome was surgery within 8 weeks of diagnosis. Risk ratios (RRs) and 95% CIs were estimated using log-binomial regression and adjusted for clinical and demographic factors.

RESULTS

A total of 2,363 patients with stage I and II non–small-cell lung cancer were included in the analyses: intervention (n = 263), retrospective control (n = 1,798), and concurrent control (n = 302). 87.1% of Black patients and 85.4% of White patients in the intervention group ( P = .13) received surgery within 8 weeks of diagnosis compared with 58.7% of Black patients and 75.0% of White patients in the retrospective group ( P < .01) and 64.9% of Black patients and 73.2% of White patients ( P = .29) in the concurrent group. Black patients in the intervention group were more likely to receive timely surgery than Black patients in the retrospective group (RR 1.43; 95% CI, 1.26 to 1.64). White patients in the intervention group also had timelier surgery than White patients in the retrospective group (RR 1.10; 95% CI, 1.02 to 1.18).

CONCLUSION

Accountability for Cancer Care through Undoing Racism and Equity is associated with timelier lung cancer surgery and reduction of the racial gap in timely surgery.