bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoscale characterization of drug-induced microtubule filament dysfunction using super-resolution microscopy
Authors: Rozario Ashley M. , Duwé Sam , Elliott Cade , Hargreaves Riley B. , Moseley Gregory W. , Dedecker Peter , Whelan Donna R. , Bell Toby D. M.
Published: December 2021

Background

The integrity of microtubule filament networks is essential for the roles in diverse cellular functions, and disruption of its structure or dynamics has been explored as a therapeutic approach to tackle diseases such as cancer. Microtubule-interacting drugs, sometimes referred to as antimitotics, are used in cancer therapy to target and disrupt microtubules. However, due to associated side effects on healthy cells, there is a need to develop safer drug regimens that still retain clinical efficacy. Currently, many questions remain open regarding the extent of effects on cellular physiology of microtubule-interacting drugs at clinically relevant and low doses. Here, we use super-resolution microscopies (single-molecule localization and optical fluctuation based) to reveal the initial microtubule dysfunctions caused by nanomolar concentrations of colcemid.

Results

We identify previously undetected microtubule (MT) damage caused by clinically relevant doses of colcemid. Short exposure to 30–80 nM colcemid results in aberrant microtubule curvature, with a trend of increased curvature associated to increased doses, and curvatures greater than 2 rad/μm, a value associated with MT breakage. Microtubule fragmentation was detected upon treatment with ≥ 100 nM colcemid. Remarkably, lower doses (< 20 nM after 5 h) led to subtle but significant microtubule architecture remodelling characterized by increased curvature and suppression of microtubule dynamics.

Conclusions

Our results support the emerging hypothesis that microtubule-interacting drugs induce non-mitotic effects in cells, and establish a multi-modal imaging assay for detecting and measuring nanoscale microtubule dysfunction. The sub-diffraction visualization of these less severe precursor perturbations compared to the established antimitotic effects of microtubule-interacting drugs offers potential for improved understanding and design of anticancer agents.
Expanding the application of non-invasive prenatal testing in the detection of foetal chromosomal copy number variations
Authors: Wang Chaohong , Tang Junxiang , Tong Keting , Huang Daoqi , Tu Huayu , Li Qingnan , Zhu Jiansheng
Published: December 2021

Purpose

The aim of this study was to assess the detection efficiency and clinical application value of non-invasive prenatal testing (NIPT) for foetal copy number variants (CNVs) in clinical samples from 39,002 prospective cases.

Methods

A total of 39,002 pregnant women who received NIPT by next-generation sequencing (NGS) with a sequencing depth of 6 M reads in our centre from January 2018 to April 2020 were enrolled. Chromosomal microarray analysis (CMA) was further used to diagnose suspected chromosomal aneuploidies and chromosomal microdeletion/microduplication for consistency assessment.

Results

A total of 473 pregnancies (1.213%) were positive for clinically significant foetal chromosome abnormalities by NIPT. This group comprised 99 trisomy 21 (T21, 0.254%), 30 trisomy 18 (T18, 0.077%), 25 trisomy 13 (T13, 0.064%), 155 sex chromosome aneuploidy (SCA, 0.398%), 69 rare trisomy (0.177%), and 95 microdeletion/microduplication syndrome (MMS, 0.244%) cases. Based on follow-up tests, the positive predictive values (PPVs) for the T21, T18, T13, SCA, rare trisomy, and MMS cases were calculated to be 88.89%, 53.33%, 20.00%, 40.22%, 4.88%, and 49.02%, respectively. In addition, the PPVs of CNVs of < 5 Mb, 5–10 Mb, and > 10 Mb were 54.55%, 38.46%, and 40.00%, respectively. Among the 95 cases with suspected CNVs, 25 were diagnosed as true positive and 26 cases as false positive; follow-up prenatal diagnosis by CMA was not performed for 44 cases. Moreover, among the 25 true positive cases, 10 were pathogenic, 3 were likely pathogenic, and 12 were of uncertain significance.

Conclusion

NIPT is not only suitable for screening T21, T18, T13, and SCA but also has potential significance for CNV detection. As combined with ultrasound, extended NIPT is effective for screening MMS. However, NIPT should not be recommended for whole-chromosome aneuploidy screening.
Transcriptome sequencing reveals a lncRNA–mRNA interaction network in extramammary Paget’s disease
Authors: Zheng Da-chao , Shen Yan-ting , Wei Zi-wei , Wan Xiang , Xie Min-kai , Yao Hai-jun , Wang Zhong
Published: December 2021

Background

Extramammary Paget’s disease (EMPD) is a rare malignant intraepidermal adenocarcinoma that is poorly understood. Regulatory long noncoding RNAs (lncRNAs) are characterized in many species and shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in different diseases, especially in cancer studies. In the present study, we used high-throughput sequencing to reveal the lncRNA–mRNA interaction network in extramammary Paget’s disease.

Methods

High-throughput sequencing was used to identify differentially expressed lncRNA and mRNA profiles between EMPD patients and healthy controls. Then, a series of bioinformatics analyses were conducted to construct the lncRNA–mRNA interaction network, which was finally confirmed in vitro.

Results

Six pairs of EMPD tumor and normal skin samples were collected and sequenced to identify the differentially expressed lncRNA and mRNA profiles between EMPD and healthy controls. A total of 997 differentially expressed mRNAs and 785 differentially expressed lncRNAs were identified. The GO and KEGG analyses show that epidermal development and cell adhesion play important roles in EMPD. The results of the lncRNA–mRNA interaction network analysis suggested that NEAT1, PGAP1, FKBP5 and CDON were the pivotal nodes of the network and that lncRNA NEAT1 might regulate mRNA PGAP1, FKBP5 and CDON. The results of the quantitative real-time RT–PCR performed in ten other patients for NEAT1, PGAP1, FKBP5 and CDON were consistent with those of the sequencing analysis. Moreover, an in vitro experiment confirmed the interactions between NEAT1 and PGAP1, FKBP5 and CDON in human immortalized keratinocytes.

Conclusion

These findings suggest that the lncRNA–mRNA interaction network based on four pivotal nodes, NEAT1, PGAP1 FKBP5 and CDON, may play an important role in EMPD, which will contribute to a deeper understanding of the pathogenesis of EMPD.
Changes in the role of explanatory factors for socioeconomic inequalities in physical performance: a comparative study of three birth cohorts
Authors: Klokgieters Silvia S. , Kok Almar A. L. , Visser Marjolein , van Groenou Marjolein I. Broese , Huisman Martijn
Published: December 2021

Background

Due to societal changes and changes in the availability of health promoting factors, explanatory factors of socioeconomic inequalities in health (SIH) may change with time. We investigate differences in the relative importance of behavioural, social and psychological factors for explaining inequalities in physical performance between three birth cohorts.

Methods

Data came from N = 988, N = 1002, and N = 1023 adults aged 55–64 years, collected in 1992, 2002 and 2012 as part of the Longitudinal Aging Study Amsterdam. Physical performance was measured by three performance tests. We included lifestyle factors (physical activity, smoking, alcohol use and Body Mass Index (BMI)); social factors (network size, network complexity, divorce, social support); and psychological factors (mastery, self-efficacy and neuroticism). In multi-group mediation models, we tested whether the strength of indirect effects from socioeconomic position (SEP) via the explanatory factors to health differed between birth cohorts. Stronger indirect effects indicate an increase in the importance; weaker indirect effects indicate a decrease in importance.

Results

Absolute SIH were present and similar across cohorts. The strength of indirect effects of SEP on physical performance through smoking, binge alcohol use, emotional support and mastery increased across cohorts. The indirect effects of BMI, network size, self-efficacy and neuroticism were similar across cohorts.

Conclusions

Inequalities in smoking, binge alcohol use, emotional support and mastery may have become more important for explaining SIH in recent cohorts of middle-aged adults. Policies that aim to reduce socioeconomic inequalities may need to adapt their targets of intervention to changing mechanisms in order to reduce SIH.
Access to primary healthcare Services in Conflict-Affected Fragile States: a subnational descriptive analysis of educational and wealth disparities in Cameroon, Democratic Republic of Congo, Mali, and Nigeria
Authors: Ramadan Marwa , Tappis Hannah , Uribe Manuela Villar , Brieger William
Published: December 2021

Background

Measuring and improving equitable access to care is a necessity to achieve universal health coverage. Pre-pandemic estimates showed that most conflict-affected and fragile situations were off-track to meet the Sustainable Development Goals on health and equity by 2030. Yet, there is a paucity of studies examining health inequalities in these settings. This study addresses the literature gap by applying a conflict intensity lens to the analysis of disparities in access to essential Primary Health Care (PHC) services in four conflict-affected fragile states: Cameroon, Democratic Republic of Congo, Mali and Nigeria.

Methods

For each studied country, disparities in geographic and financial access to care were compared across education and wealth strata in areas with differing levels of conflict intensity. The Demographic Health Survey (DHS) and the Uppsala Conflict Data Program were the main sources of information on access to PHC and conflict events, respectively. To define conflict intensity, household clusters were linked to conflict events within a 50-km distance. A cut-off of more than two conflict-related deaths per 100,000 population was used to differentiate medium or high intensity conflict from no or low intensity conflict. We utilized three measures to assess inequalities: an absolute difference, a concentration index, and a multivariate logistic regression coefficient. Each disparity measure was compared based on the intensity of conflict the year the DHS data was collected.

Results

We found that PHC access varied across subnational regions in the four countries studied; with more prevalent financial than geographic barriers to care. The magnitude of both educational and wealth disparities in access to care was higher with geographic proximity to medium or high intensity conflict. A higher magnitude of wealth rather than educational disparities was also likely to be observed in the four studied contexts. Meanwhile, only Nigeria showed statistically significant interaction between conflict intensity and educational disparities in access to care.

Conclusion

Both educational and wealth disparities in access to PHC services can be exacerbated by geographic proximity to organized violence. This paper provides additional evidence that, despite limitations, household surveys can contribute to healthcare assessment in conflict-affected and fragile settings.
Political economy analysis of universal health coverage and health financing reforms in low- and middle-income countries: the role of stakeholder engagement in the research process
Authors: Loffreda Giulia , Bello Kéfilath , Kiendrébéogo Joël Arthur , Selenou Isidore , Ahmed Mohamed Ali Ag , Dossou Jean Paul , Witter Sophie , Bertone Maria Paola
Published: December 2021

Background

Progress towards universal health coverage (UHC) is an inherently political process. Political economy analysis (PEA) is gaining momentum as a tool to better understand the role of the political and economic dimensions in shaping and achieving UHC in different contexts. Despite the acknowledged importance of actors and stakeholders in political economy considerations, their role in the PEA research process beyond “study subjects” as potential cocreators of knowledge and knowledge users has been overlooked so far. We therefore aimed to review the approaches with reference to stakeholder engagement during the research process adopted in the current published research on the political economy of UHC and health financing reforms, and the factors favouring (or hindering) uptake and usability of PEA work.

Methods

We reviewed the literature to describe whether, when and how stakeholders were involved in the research process of studies looking at the political economy of UHC and health financing reforms, and to identify challenges and lessons learned on effective stakeholder engagement and research uptake. We used a standardized search strategy with key terms across several databases; we screened and included articles that focused on PEA and UHC. Additionally, we conducted a short survey of the authors of the included studies to complement the information retrieved.

Results

Fifty articles met the inclusion criteria and were included in the analysis. We found overall little evidence of systematic engagement of stakeholders in the research process, which focused mostly on the data collection phase of the research (i.e., key informant interviews). Our study identifies some reasons for the varying stakeholder engagement. Challenges include PEA requiring specific skills, a focus on sensitive issues, and the blurriness in researchers’ and stakeholders’ roles and the multiple roles of stakeholders as research participants, study subjects and research users. Among the approaches that might favour usability of PEA work, we identified early engagement, coproduction of research questions, local partners and personal contact, political willingness, and trust and use of prospective analysis.

Conclusions

Stakeholder engagement and research uptake are multifaceted concepts and complex processes, particularly when applied to PEA. As such, stakeholder engagement in the research process of PEA of UHC and health financing reforms is limited and underreported. Despite the challenges, however, stakeholder engagement remains key to ensuring relevance, usability and research uptake of PEA studies. More efforts are required to ensure engagement at different stages of the research process and better reporting in published articles.
Is value-based payment for healthcare feasible under Ghana’s National Health Insurance Scheme?
Authors: Issahaku Yussif , Thoumi Andrea , Abiiro Gilbert Abotisem , Ogbouji Osondu , Nonvignon Justice
Published: December 2021

Background

Effective payment mechanisms for healthcare are critical to the quality of care and the efficiency and responsiveness of health systems to meet specific population health needs. Since its inception, Ghana’s National Health Insurance Scheme (NHIS) has adopted fee-for-service, diagnostic-related groups and capitation methods, which have contributed to provider reimbursement delays, rising costs and poor quality of care rendered to the scheme’s clients. The aim of this study was to explore stakeholder perceptions of the feasibility of value-based payment (VBP) for healthcare in Ghana. Value-based payment refers to a system whereby healthcare providers are paid for the value of services rendered to patients instead of the volume of services.

Methods

This study employed a cross-sectional qualitative design. National-level stakeholders were purposively selected for in-depth interviews. The participants included policy-makers (n = 4), implementers (n = 5), public health insurers (n = 3), public and private healthcare providers (n = 7) and civil society organization officers (n = 1). Interviews were audio-recorded and transcribed. Data analysis was performed using both deductive and inductive thematic analysis. The data were analysed using QSR NVivo 12 software.

Results

Generally, participants perceived VBP to be feasible if certain supporting systems were in place and potential implementation constraints were addressed. Although the concept of VBP was widely accepted, study participants reported that efficient resource management, provider motivation incentives and community empowerment were required to align VBP to the Ghanaian context. Weak electronic information systems and underdeveloped healthcare infrastructure were seen as challenges to the integration of VBP into the Ghanaian health system. Therefore, improvement of existing systems beyond healthcare, including public education, politics, data, finance, regulation, planning, infrastructure and stakeholder attitudes towards VBP, will affect the overall feasibility of VBP in Ghana.

Conclusion

Value-based payment could be a feasible policy option for the NHIS in Ghana if potential implementation challenges such as limited financial and human resources and underdeveloped health system infrastructure are addressed. Governmental support and provider capacity-building are therefore essential for VBP implementation in Ghana. Future feasibility and acceptability studies will need to consider community and patient perspectives.
Sixteen years of eHealth experiences in Iran: a qualitative content analysis of national policies
Authors: Mousavi Seyyed Meysam , Takian Amirhossein , Tara Mahmood
Published: December 2021

Introduction

As a building block of all health systems and a multi-sectoral domain, eHealth has a critical role to accelerate the achievement of sustainable development goals (SDGs), particularly universal health coverage (UHC). Our objective was to provide a better understanding of the recent experiences on eHealth policy, particularly in framing process of the policies and strategies, in an attempt to develop evidence-based recommendations that can inform future eHealth policy formulation, implementation, and development in Iran.

Methods

We undertook an exploratory, descriptive, comparative, retrospective and longitudinal analysis of eHealth policies by using content analysis of upstream and other key national policy documents, guided by criteria for reporting qualitative research (COREQ). A systematic and purposive search was conducted to identify publicly-accessible documents related to eHealth policies in Iran, followed by in-depth, semi-structured, open-ended interviews with purposefully identified national key informants in the field of eHealth. MAXQDA® 12 was used to assist with qualitative data analysis.

Findings

We retrieved and included 13 national policy documents demonstrating 16 years experiences of recorded eHealth policy in Iran, from 2004–2020. Our analysis revealed seven main categories as challenges of eHealth policies in Iran: (1) lack of comprehensive and big picture of all eHealth components; (2) lack of long-term and strategic plans on eHealth; (3) poor consistency among national policy documents; (4) unrealistic and non-operational timing of policy documents; (5) inappropriate identification and lack of involvement of key actors in development and implementation of eHealth policies; (6) low priority of eHealth in the national health system, and (7) unconventional focus and attention to Electronic Health Record (EHR).

Conclusion

The findings reveal almost two decades history of eHealth initiatives at the national and upstream policy level in Iran, with noticeable gaps between desired policies and achieved expectations. The inclusion of eHealth solutions in the policy documents has been controversial and challenging. eHealth seems to have not been meaningfully established in the minds and views of policy makers and senior manager, which might have led to the development of incomplete and contradictory policies. The health system in Iran needs, we advocate, the design of an evidence-informed eHealth roadmap, as well as continuous, systematic, and reasonably time-bounded strategic plans to establish eHealth as the building block of health system along the pathway towards sustainable health development.
A new experimental design to study inflammation-related versus non-inflammation-related depression in mice
Authors: Cardinal Pierre , Monchaux de Oliveira Camille , Sauvant Julie , Foury Aline , Darnaudéry Muriel , Vancassel Sylvie , Castanon Nathalie , Capuron Lucile
Published: December 2021

Background

Major depressive disorder (MDD) represents a major public health concern, particularly due to its steadily rising prevalence and the poor responsiveness to standard antidepressants notably in patients afflicted with chronic inflammatory conditions, such as obesity. This highlights the need to improve current therapeutic strategies, including by targeting inflammation based on its role in the pathophysiology and treatment responsiveness of MDD. Nevertheless, dissecting the relative contribution of inflammation in the development and treatment of MDD remains a major issue, further complicated by the lack of preclinical depression models suitable to experimentally dissociate inflammation-related vs. inflammation-unrelated depression.

Methods

While current models usually focus on one particular MDD risk factor, we compared in male C57BL/6J mice the behavioral, inflammatory and neurobiological impact of chronic exposure to high-fat diet (HFD), a procedure known to induce inflammation-related depressive-like behaviors, and unpredictable chronic mild stress (UCMS), a stress-induced depression model notably renowned for its responsivity to antidepressants.

Results

While both paradigms induced neurovegetative, depressive-like and anxiety-like behaviors, inflammation and downstream neurobiological pathways contributing to inflammation-driven depression were specifically activated in HFD mice, as revealed by increased circulating levels of inflammatory factors, as well as brain expression of microglial activation markers and enzymes from the kynurenine and tetrahydrobiopterin (BH4) pathways. In addition, serotoninergic and dopaminergic systems were differentially impacted, depending on the experimental condition.

Conclusions

These data validate an experimental design suitable to deeply study the mechanisms underlying inflammation-driven depression comparatively to non-inflammatory depression. This design could help to better understand the pathophysiology of treatment resistant depression.
A simulation study of regression approaches for estimating risk ratios in the presence of multiple confounders
Authors: Fuyama Kanako , Hagiwara Yasuhiro , Matsuyama Yutaka
Published: December 2021

Background

Risk ratio is a popular effect measure in epidemiological research. Although previous research has suggested that logistic regression may provide biased odds ratio estimates when the number of events is small and there are multiple confounders, the performance of risk ratio estimation has yet to be examined in the presence of multiple confounders.

Methods

We conducted a simulation study to evaluate the statistical performance of three regression approaches for estimating risk ratios: (1) risk ratio interpretation of logistic regression coefficients, (2) modified Poisson regression, and (3) regression standardization using logistic regression. We simulated 270 scenarios with systematically varied sample size, the number of binary confounders, exposure proportion, risk ratio, and outcome proportion. Performance evaluation was based on convergence proportion, bias, standard error estimation, and confidence interval coverage.

Results

With a sample size of 2500 and an outcome proportion of 1%, both logistic regression and modified Poisson regression at times failed to converge, and the three approaches were comparably biased. As the outcome proportion or sample size increased, modified Poisson regression and regression standardization yielded unbiased risk ratio estimates with appropriate confidence intervals irrespective of the number of confounders. The risk ratio interpretation of logistic regression coefficients, by contrast, became substantially biased as the outcome proportion increased.

Conclusions

Regression approaches for estimating risk ratios should be cautiously used when the number of events is small. With an adequate number of events, risk ratios are validly estimated by modified Poisson regression and regression standardization, irrespective of the number of confounders.
Freshwater crabs could act as vehicles of spreading avian influenza virus
Authors: Ma Weiwei , Ren Chenyang , Hu Qingbiao , Li Xiaodong , Feng Yali , Zhang Ying
Published: December 2021

Avian influenza virus (AIV) possessed significant risk to various animals and human health. Wild birds, especially waterfowls are considered to be the natural reservoir of AIVs. The ecology of AIV is still far from being fully understood. Freshwater crabs are nonnegligible biotic factor in AIV ecosystem. We analyzed the ability of freshwater crabs accumulate and spread AIV. We found that AIV remain infectious in water only for 36 h but persist in crabs for 48 h. Crabs could accumulate AIV in their gills and gastrointestinal tracts. The AIV titers in crabs were higher than the surrounding contaminated water. Crabs could accumulate AIV from contaminated water, carry the virus and spread to naïve crabs via surrounding water. Our study identified freshwater crab as a novel transmission vehicle in AIV ecosystem.
Species perceived to be dangerous are more likely to have distinctive local names
Authors: Farooq Harith , Bero Cláudio , Guilengue Yolanda , Elias Clementina , Massingue Yasalde , Mucopote Ivo , Nanvonamuquitxo Cristóvão , Marais Johan , Antonelli Alexandre , Faurby Søren
Published: December 2021

Background

Species with direct uses, such as sources of food, shelter, building material and medicine tend to have more specific local names. But could the same apply for species that people fear?

Methods

To address this question, here we explore the behavior and perception of species diversity and dangerousness through a survey of 1037 households in nine villages in Cabo Delgado, northern Mozambique. We compare people’s knowledge of snakes with that of lizards and amphibians.

Results

We find that northern Mozambicans know four to five times more local names for snakes than for lizards and frogs, despite the local species richness of snakes being comparable to the diversity of lizards and frogs. We further find that local knowledge was on par with the academic literature regarding snakebite symptoms.

Conclusions

Our results suggest that fear can increase the level of specificity in naming species among indigenous communities, which could lead to biases in the mapping and protection of species that include data from citizen reports.
Comparative efficacy of 5 suture configurations for arthroscopic rotator cuff tear repair: a network meta-analysis
Authors: Wang Wei , Kang Hui , Li Hongchuan , Li Jian , Meng Yibin , Li Peng
Published: December 2021

Background

Rotator cuff tear is one of the most common complaint with shoulder pain, disability, or dysfunction. So far, different arthroscopic techniques including single row (SR), double row (DR), modified Mason–Allen (MMA), suture bridge (SB) and transosseous (TO) have been identified to repair rotator cuff. However, no study has reported the comparative efficacy of these 5 suture configurations. The overall aim of this network meta-analysis was to analyze the clinical outcomes and healing rate with arthroscopy among SR, DR, MMA, SB and TO.

Methods

A systematic literature was searched from PubMed, EBSCO-MEDLINE, Web of Science, google scholar and www.dayi100.com, and checked for the inclusion and exclusion standards. The network meta-analysis was conducted using Review Manager 5.3 and SATA 15.0 software.

Results

Thirty-four studies were eligible for inclusion, including 15 randomized controlled trials, 17 retrospective and 2 prospective cohort studies, with total 3250 shoulders. Two individual reviewers evaluated the quality of the 34 studies, the score form 5 and 9 of 10 were attained according to the Newcastle–Ottawa Scale for the 17 retrospective and 2 prospective studies. There was no significant distinction for the Constant score among 5 groups in the 16 studies with 1381 shoulders. The treatment strategies were ranked as MMA, DR, SB, SR and TO. In ASES score, 14 studies included 1464 shoulders showed that no significant differences was showed among all 5 groups after surgery. Whereas the efficacy probability was TO, MMA, DR, SB and SR according to the cumulative ranking curve. The healing rate in 25 studies include 2023 shoulders was significant in both SR versus DR [risk ratio 0.45 with 95% credible interval (0.31, 0.65)], and SR versus SB [risk ratio 0.45 (95% credible interval 0.29, 0.69)], and no significant in the other comparison, the ranking probability was MMA, SB, DR, TO and SR.

Conclusion

Based on the clinical results, this network meta-analysis revealed that these 5 suture configurations shows no significant difference. Meanwhile, suture bridge may be the optimum treatment strategy which may improve the healing rate postoperatively, whereas the DR is a suboptimal option for arthroscopic rotator cuff repairs.
The default methods in the 2019 Refinement drastically reduce estimates of global carbon sinks of harvested wood products
Authors: Kayo Chihiro , Kalt Gerald , Tsunetsugu Yuko , Hashimoto Seiji , Komata Hirotaka , Noda Ryu , Oka Hiroyasu
Published: December 2021

Background

The stock dynamics of harvested wood products (HWPs) are a relevant component of anthropogenic carbon cycles. Generally, HWP stock increases are treated as carbon removals from the atmosphere, while stock decreases are considered emissions. Among the different approaches suggested by the Intergovernmental Panel on Climate Change (IPCC) for accounting HWPs in national greenhouse gas inventories, the production approach has been established as the common approach under the Kyoto Protocol and Paris Agreement. However, the 24th session of the Conference of the Parties to the United Nations Framework Convention on Climate Change decided that alternative approaches can also be used. The IPCC has published guidelines for estimating HWP carbon stocks and default parameters for the various approaches in the 2006 Guidelines, 2013 Guidance, and 2019 Refinement. Although there are significant differences among the default methods in the three IPCC guidelines, no studies have systematically quantified or compared the results from the different guidelines on a global scale. This study quantifies the HWP stock dynamics and corresponding carbon removals/emissions under each approach based on the default methods presented in each guideline for 235 individual countries/regions.

Results

We identified relatively good consistency in carbon stocks/removals between the stock-change and the atmospheric flow approaches at a global level. Under both approaches, the methodological and parameter updates in the 2019 Refinement (e.g., considered HWPs, starting year for carbon stocks, and conversion factors) resulted in one-third reduction in carbon removals compared to the 2006 Guidelines. The production approach leads to a systematic underestimation of global carbon stocks and removals because it confines accounting to products derived from domestic harvests and uses the share of domestic feedstock for accounting. The 2013 Guidance and the 2019 Refinement reduce the estimated global carbon removals under the production approach by 15% and 45% (2018), respectively, compared to the 2006 Guidelines.

Conclusions

Gradual refinements in the IPCC default methods have a considerably higher impact on global estimates of HWP carbon stocks and removals than the differences in accounting approaches. The methodological improvements in the 2019 Refinement halve the global HWP carbon removals estimated in the former version, the 2006 Guidelines.
Integrated proteogenomic analysis revealed the metabolic heterogeneity in noncancerous liver tissues of patients with hepatocellular carcinoma
Authors: Liao Haotian , Du Jinpeng , Wang Haichuan , Lan Tian , Peng Jiajie , Wu Zhenru , Yuan Kefei , Zeng Yong
Published: December 2021

Understanding the adjacent liver microenvironment of hepatocellular carcinoma (HCC) with possible metastasis tendency might provide a strategy for risk classification of patients and potential therapies by converting the unique metastasis-inclined microenvironment to a metastasis-averse one. In this study, we performed an integrated proteogenomic analysis to have a comprehensive view on the heterogeneity of hepatic microenvironment contributing to HCC metastasis. Pairing mRNA-protein analysis revealed consistent and discordant mRNA-protein expressions in metabolism regulations and cancer-related pathways, respectively. Proteomic profiling identified three subgroups associated with the recurrence-free survival of patients. These proteomic subgroups demonstrated distinct features in metabolic reprogramming, which was potentially modified by epigenetic alterations. This study raises the point of metabolic heterogeneity in HCC noncancerous tissues and may offer a new perspective on HCC treatment.
Ovarian reserve in nigerian women with sickle cell anaemia: a cross- sectional study
Authors: Garba Sunusi Rimi , Makwe Christian Chigozie , Osunkalu Vincent Oluseye , Kalejaiye Olufunto Olufela , Soibi-Harry Adaiah Priscillia , Aliyu Amina Umar , Afolabi Bosede Bukola
Published: December 2021

Introduction

Sickle cell disease is the most common monogenetic disorder worldwide. There have been reports of endocrine dysfunction and gonadal failure among affected individuals, especially in males. The findings on ovarian reserve and failure in women with sickle anaemia have been inconsistent.

Aim and objective

The aim of this study was to determine and compare the ovarian reserve of Nigerian women with and without sickle cell anaemia attending a University Teaching Hospital.

Study Design

This cross-sectional study was carried out at the Adult Sickle Cell Clinic and the Community Health Clinic of the Lagos University Teaching Hospital.

Methodology

A total of 166 participants who met the selection criteria, were recruited for the study. The study population consisted of two groups of women matched for age: 83 women with HbSS and 83 women with HbAA. The haemoglobin phenotype of each participant was determined on alkaline electrophoresis (pH 8.4) before analysis. Serum Anti-Mullerian Hormone (AMH) was determined using Enzyme-linked immunosorbent assay (ELISA) method (Calbiotech Inc. USA, Catalog no AM448T).

Results

The mean ± SD of serum AMH level in women with HbSS was 3.64 ± 0.65 ng/mL and was lower than that of women with HbAA 7.35 ±1.19 ng/mL (p < 0.001). Serum AMH negatively correlated with age in both study groups (HbAA and HbSS). Also, a significant negative correlation was found between serum AMH and BMI in women with HbAA.

Conclusion

The study showed diminished ovarian reserve in women with HbSS when compared to age-matched women with HbAA.
Comparison of the number of oocytes obtained after ovarian stimulation between Chinese and Caucasian women undergoing in vitro fertilization using a standardized stimulation regime
Authors: Ko Jennifer K. Y. , Kan Andrew , Leung Peter , Lee Vivian C. Y. , Li Raymond H. W. , Ledger William , Ng Ernest H. Y.
Published: December 2021

Background

In vitro fertilization (IVF) is a well-established method to treat various causes of infertility. Some previous retrospective studies suggested a lower ovarian response in Asian women compared to Caucasian women. However, the ovarian stimulation regimens were not standardized, potentially confounding the findings. The objective of this study is to compare the number of oocytes obtained after ovarian stimulation between Chinese and Caucasian women undergoing IVF using a standardized stimulation regimen.

Methods

This is a prospective cohort study conducted in two tertiary IVF units in Hong Kong, China and Sydney, Australia from October 2016 to August 2019. A total of 192 women aged 18–42 years with a body weight > 60 kg underwent IVF with a standard ovarian stimulation regimen of 150 micrograms corifollitropin alfa (Elonva®) followed by 200 IU follitropin beta (Puregon®) per day. The number of oocytes retrieved in Chinese women treated in the Hong Kong center was compared to that of Caucasian women treated in the Australian center.

Results

Serum AMH levels were similar between the two groups. Although women in the Chinese cohort were older and had a higher body mass index (BMI), longer duration of infertility and lower antral follicle count (AFC) than those in the Caucasian cohort in this study, no differences in the number of oocytes retrieved [11 (8–17) vs. 11 (6–17), p=0.29], total dosage and duration of stimulation and number of follicles aspirated were noted between the two ethnic cohorts. The peak estradiol level was greater in Chinese women than in Caucasian women. After controlling for age, BMI and AFC, ethnicity was a significant independent determinant of the number of oocytes obtained.

Conclusions

Chinese women had a higher number of oocytes after ovarian stimulation using a standardized stimulation regimen compared with Caucasian women undergoing IVF after controlling for age, BMI, AFC and AMH despite presenting later after a longer duration of infertility. Trial registration number: NCT02748278
Dietary diversity and associated factors among children (6–23 months) in Gedeo zone, Ethiopia: cross - sectional study
Authors: Molla Wondwosen , Adem Dirshaye Argaw , Tilahun Ruth , Shumye Seid , Kabthymer Robel Hussen , Kebede Daniel , Mengistu Nebiyu , Ayele Getnet Melaku , Assefa Dawit Getachew
Published: December 2021

Introduction

Different foods and food groups are good sources for various macro- and micronutrients. Diversified diet play an important role in both physical and mental growth and development of children. However, meeting minimum standards of dietary diversity for children is a challenge in many developing countries including Ethiopia.

Objective

To assess dietary diversity and associated factors among children (6–23 months) in Gedieo Zone, Ethiopia.

Method

Community based cross-sectional study was carried out at Gedieo Zone, Ethiopia, from January to March 15, 2019. Multi-stage sampling technique was used to get a total of 665 children with the age of between 6 and 23 months from their kebeles. Data was collected by using face-to-face interview with structured questionnaire. Data was entered into Epidata version 3.1 and exported to Statistical Package for the Social Sciences (SPSS) version 23.0 for analyses. Variables having p < 0.25 at bivariate analysis were fitted to multivariable analysis. Multivariable logistic regression model was used at 95% confidence interval and with P-Value < 0.05. Bivariate.

Result

A total of 665 children were participated with response rate of 96.2%. Only 199(29.9%) of children were met the minimum requirements for dietary diversity. Age of children [AOR 4.237(1.743–10.295))], Educational status [AOR 2.864(1.156–7.094)], Number of families [AOR 2.865(1.776–4.619))] and household wealth index [AOR4.390(2.300–8.380)] were significantly associated with Dietary Diversity of children.

Conclusion

Only, one out of four children aged of 6–23 months attained the minimum dietary diversity score. Children from low socioeconomic status and mothers with no formal educational attainment need special attention to improve the practice of appropriate feeding of children.
Clinical validation of a combinatorial PharmAcogeNomic approach in major Depressive disorder: an Observational prospective RAndomized, participant and rater-blinded, controlled trial (PANDORA trial)
Authors: Minelli Alessandra , Barlati Stefano , Vitali Erika , Bignotti Stefano , Dattilo Vincenzo , Tura Giovanni Battista , Maffioletti Elisabetta , Giacopuzzi Edoardo , Santoro Vincenza , Perusi Giulia , Cobelli Chiara , Magri Chiara , Bonizzato Silvia , Bocchio-Chiavetto Luisella , Spina Edoardo , Vita Antonio , Gennarelli Massimo
Published: December 2021

Background

Major depressive disorder (MDD) is a common, chronic, debilitating mood disorder that causes serious functional impairment and significantly decreased quality of life. Pharmacotherapy represents the first-line treatment option; however, only approximately one third of patients respond to the first treatment because of the ineffectiveness or side effects of antidepressants. Precision medicine in psychiatry might offer clinicians the possibility to tailor treatment according to the best possible evidence of efficacy and tolerability for each subject. In this context, our study aims to carry out a clinical validation of a combinatorial pharmacogenomics (PGx) test in an Italian MDD patient cohort with advocacy license independence.

Methods

Our study is a prospective participant- and rater-blinded, randomized, controlled clinical observational trial enrolling 300 MDD patients who are referred to psychiatric services to receive a new antidepressant due to the failure of their current treatment and/or the onset of adverse effects. Eligible participants are randomized to the TGTG group (Treated with Genetic Test Guide) or TAU group (Treated as Usual). For all subjects, DNA is collected with a buccal brush. The primary outcome is the reduction in depressive symptomatology. The secondary outcomes involve a range of scales that assess MDD symptoms and social functioning outcomes. The assessment is performed at four timepoints: baseline and 4, 8, and 12 weeks.

Discussion

This project represents the first randomized controlled clinical trial to investigate whether a non-commercial PGx test improves outcomes in an MDD naturalistic cohort. Moreover, the identification of new genetic variants associated with non-response or side effects will improve the efficacy of the test, leading to further cost-saving.

Trial registration number

ClinicalTrials.gov NCT04615234. Registered on November 4, 2020.
Effects of immunoglobulin plus prednisolone in reducing coronary artery lesions in patients with Kawasaki disease: study protocol for a phase III multicenter, open-label, blinded-endpoints randomized controlled trial
Authors: Lin Si-Yuan , He Lan , Xie Li-Ping , Wang Yin , Lin Yi-Xiang , Cao Yin-Yin , Yan Wei-Li , Liu Fang , Huang Guo-Ying
Published: December 2021

Background

Kawasaki disease (KD) is an acute systemic vasculitis of unclear etiology that mainly affects infants and young children. Strategies to reduce the incidence and severity of coronary artery lesions (CALs), the determinant factor in the long-term prognosis of KD, are currently a focus of studies on KD. Corticosteroids, preferred in the treatment of the majority of vasculitides, are controversial in the treatment of acute KD. In this trial, we will evaluate whether the addition of prednisolone to standard intravenous immunoglobulin (IVIG) plus aspirin therapy can reduce the occurrence of CAL in Chinese patients with KD.

Methods

This is a multicenter, prospective, open-label, randomized controlled trial, which is expected to be conducted in more than 20 hospitals in China and aims to assess the efficacy and safety of IVIG + prednisolone treatment versus standard treatment. Patients with KD who fulfill the inclusion and exclusion criteria will be recruited and randomized (1:1) to receive either a large dose of IVIG (2 g/kg over 12–24 h with a maximum dose of 60 g) + aspirin 30 mg/kg/d or IVIG (2 g/kg over 12–24 h) + aspirin 30 mg/kg/d + prednisolone (2 mg/kg/d with a maximum dose of 60 mg tapered over 15 days after normalization of C-reactive protein concentration). The primary outcome will be the occurrence of CAL at 1 month of illness. The follow-up duration for each participant will be set as 1 year. Patients and treating physicians will be unmasked to group allocation.

Discussion

This will be the first multicenter randomized controlled trial to evaluate the efficacy of IVIG + aspirin + prednisolone in Chinese pediatric patients with KD, which may provide high-level evidence for improving the initial treatment for acute KD.

Trial registration

ClinicalTrials.govNCT04078568. Registered on 16 August 2018.
The Moo’D Study: protocol for a randomised controlled trial of A2 beta-casein only versus conventional dairy products in women with low mood
Authors: Hockey Meghan , Aslam Hajara , Berk Michael , Pasco Julie A. , Ruusunen Anu , Mohebbi Mohammadreza , Macpherson Helen , Chatterton Mary Lou , Marx Wolfgang , O’Neil Adrienne , Rocks Tetyana , McGuinness Amelia J. , Young Lauren M. , Jacka Felice N.
Published: December 2021

Background

Beta-casein is a major protein in cow’s milk, of which A1 and A2 are the most frequent variants. Recent evidence implicates A1 beta-casein consumption in mechanisms that are of potential importance to mental health, yet its possible effects on psychological endpoints remains unknown. The primary aim of the study is to evaluate the comparative effects of consumption of dairy products containing A2 beta-casein versus conventional dairy (i.e. containing both A1 and A2 beta-casein) on symptoms of psychological distress in women with low mood.

Methods

‘The Moo’D Study’ is a 16-week, superiority, 1:1 parallel group, triple-blinded, randomised controlled trial. Ninety women with low mood (Patient Health Questionnaire score ≥ 5) will be randomised to consume either A2 beta-casein only or conventional dairy products. The primary outcome, symptoms of psychological distress, will be measured by the 21-item Depression, Anxiety and Stress Scale. Secondary outcomes will include symptoms of depression, anxiety and stress, severity of low mood, cognition, gut microbiota composition, gut symptomatology, markers of immune function, gut inflammation, systemic metabolites, endothelial integrity and oxidative stress, body composition, perceived wellbeing, sleep, quality of life, resource use and cost-effectiveness.

Discussion

This study will advance our understanding of the possible impact of milk proteins on psychological distress in women as well as elucidate mechanisms underpinning any association. Given dairy products form a substantial component of traditional and Western diets, the implications of these findings are likely to be of clinical and public health importance.

Trial registration

The trial protocol has been prospectively registered with the Australia and New Zealand Clinical Trials Registry, ACTRN12618002023235. Registered on 17 December 2018.