bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating surveillance definitions of HIV viral suppression 2015–2019: Which definition best detected barriers to care?
Authors: Erly Steven , Campos Leticia , Buskin Susan , Reuer Jennifer
Published: June 2023

Background:

People living with HIV (PLWH) who have not achieved or maintained viral suppression post-diagnosis likely face multiple barriers to HIV care. To identify these barriers a universally accepted definition of viral suppression is needed. The most common definition, the Center for Disease Control and Prevention (CDC) definition, contains simplifying assumptions that may misclassify individuals and attenuate associations. In this study, we evaluated alternative definitions of viral suppression on their ability to identify barriers to care.

Design and methods:

We used HIV surveillance data to classify participants of the 2015–2019 Washington Medical Monitoring Project (MMP) as virally suppressed or not using the CDC definition and two definitions that assess viral suppression over a longer period (“Enriched” and “Durable”). We identified barriers to suppression from literature (unstable housing, illicit drug use, poor mental health, heavy drinking, recent incarceration, racism, and poverty) and measured them using interview questions from MMP. We compared the rate ratios (RR) of being not virally suppressed using each definition for each barrier.

Results:

There were 858 PLWH in our study. All viral suppression definitions classified a similar proportion of people as suppressed (85%–89%). The durable viral suppression definition consistently yielded the largest rate ratios (e.g. unstable housing: CDC RR = 1.3, 95% CI 0.9–1.8; Enriched 1.5, 95% CI 1.0–2.2; Durable 2.2, 95% CI 1.6–3.1) and reclassified 10% of the population relative to the CDC definition.

Conclusions:

Longitudinal definitions for viral suppression may yield less misclassification and serve as superior tools for identifying and curtailing barriers to HIV care.
Translational predictions of phase 2a first-in-patient efficacy studies for antituberculosis drugs
Authors: Ernest Jacqueline P. , Goh Janice Jia Ni , Strydom Natasha , Wang Qianwen , van Wijk Rob C. , Zhang Nan , Deitchman Amelia , Nuermberger Eric , Savic Rada M.
Published: June 2023

Background:

Phase 2a trials in tuberculosis typically use early bactericidal activity (EBA), the decline in sputum CFU over 14 days, as the primary end-point for testing the efficacy of drugs as monotherapy. However, the cost of phase 2a trials can range from USD 7 million to USD 19.6 million on average, while >30% of drugs fail to progress to phase 3. Better utilising pre-clinical data to predict and prioritise the most likely drugs to succeed will thus help to accelerate drug development and reduce costs. We aim to predict clinical EBA using pre-clinicalin vivopharmacokinetic (PK)-pharmacodynamic (PD) data and a model-based translational pharmacology approach.

Methods and findings:

First, mouse PK, PD and clinical PK models were compiled. Second, mouse PK-PD models were built to derive an exposure–response relationship. Third, translational prediction of clinical EBA studies was performed using mouse PK-PD relationships and informed by clinical PK models and species-specific protein binding. Presence or absence of clinical efficacy was accurately predicted from the mouse model. Predicted daily decreases of CFU in the first 2 days of treatment and between day 2 and day 14 were consistent with clinical observations.

Conclusion:

This platform provides an innovative solution to inform or even replace phase 2a EBA trials, to bridge the gap between mouse efficacy studies and phase 2b and phase 3 trials, and to substantially accelerate drug development.
Nasal airway microRNA profiling of infants with severe bronchiolitis and risk of childhood asthma: a multicentre prospective study
Authors: Zhu Zhaozhong , Freishtat Robert J. , Harmon Brennan , Hahn Andrea , Teach Stephen J. , Pérez-Losada Marcos , Hasegawa Kohei , Camargo Carlos A.
Published: June 2023

Background

Severe bronchiolitis (i.e.bronchiolitis requiring hospitalisation) during infancy is a major risk factor for childhood asthma. However, the exact mechanism linking these common conditions remains unclear. We examined the longitudinal relationship between nasal airway miRNAs during severe bronchiolitis and the risk of developing asthma.

Methods

In a 17-centre prospective cohort study of infants with severe bronchiolitis, we sequenced their nasal microRNA at hospitalisation. First, we identified differentially expressed microRNAs (DEmiRNAs) associated with the risk of developing asthma by age 6 years. Second, we characterised the DEmiRNAs based on their association with asthma-related clinical features, and expression level by tissue and cell types. Third, we conducted pathway and network analyses by integrating DEmiRNAs and their mRNA targets. Finally, we investigated the association of DEmiRNAs and nasal cytokines.

Results

In 575 infants (median age 3 months), we identified 23 DEmiRNAs associated with asthma development (e.g.hsa-miR-29a-3p; false discovery rate (FDR) <0.10), particularly in infants with respiratory syncytial virus infection (FDR for the interaction <0.05). These DEmiRNAs were associated with 16 asthma-related clinical features (FDR <0.05),e.g.infant eczema and corticosteroid use during hospitalisation. In addition, these DEmiRNAs were highly expressed in lung tissue and immune cells (e.g.T-helper cells, neutrophils). Third, DEmiRNAs were negatively correlated with their mRNA targets (e.g.hsa-miR-324-3p/IL13), which were enriched in asthma-related pathways (FDR <0.05),e.g.toll-like receptor, PI3K-Akt and FcɛR signalling pathways, and validated by cytokine data.

Conclusion

In a multicentre cohort of infants with severe bronchiolitis, we identified nasal miRNAs during illness that were associated with major asthma-related clinical features, immune response, and risk of asthma development.
Causal analysis between gastro-oesophageal reflux disease and obstructive sleep apnoea
Authors: Chen Gui , Gong Xin , Liu Shenrong , Xie Junyang , Wang Yingqi , Guo Wucheng , Liao Wenjing , Song Lijuan , Zhang Xiaowen
Published: June 2023

Background

Based on evidence from existing observational research, clarifying the causal relationship between gastro-oesophageal reflux disease (GORD) and obstructive sleep apnoea (OSA) is challenging. Here, Mendelian randomisation, a method based on genetics, was used to provide new evidence for causality.

Methods

Summary statistics from two publicly available genome-wide association studies were used to evaluate the causal relationship between GORD and OSA (the GORD database was used as an exposure variable and the OSA database as an outcome). Inverse variance weighting was used as the main analytical tool in Mendelian randomisation to estimate causal effects. The robustness of the results was evaluated by sensitivity analysis. Possible mediators were evaluated using multivariate Mendelian randomisation.

Results

A statistically significant causal relationship was observed between GORD and OSA (OR 1.597, 95% CI 1.401–1.821, p<0.001), and similar results were observed in weighted median and Mendelian randomisation–Egger regression analyses. No bias was found in the sensitivity analysis of Mendelian randomisation estimation. Multivariate Mendelian randomisation showed that GORD significantly increased the risk of developing OSA, even when the possible mediator was excluded (OR 1.107, 95% CI 1.101–1.212, p<0.001).

Conclusion

Our study confirmed a causal relationship between GORD and OSA and suggests that intervention measures should be taken for patients with GORD to prevent the occurrence of OSA.
Modified-release morphine or placebo for chronic breathlessness: the MABEL trial protocol
Authors: Date Kathryn , Williams Bronwen , Cohen Judith , Chaudhuri Nazia , Bajwah Sabrina , Pearson Mark , Higginson Irene , Norrie John , Keerie Catriona , Tuck Sharon , Hall Peter , Currow David , Fallon Marie , Johnson Miriam
Published: June 2023

Chronic breathlessness, a persistent and disabling symptom despite optimal treatment of underlying causes, is a frightening symptom with serious and widespread impact on patients and their carers. Clinical guidelines support the use of morphine for the relief of chronic breathlessness in common long-term conditions, but questions remain around clinical effectiveness, safety and longer term (>7 days) administration. This trial will evaluate the effectiveness of low-dose oral modified-release morphine in chronic breathlessness.

This is a multicentre, parallel group, double-blind, randomised, placebo-controlled trial. Participants (n=158) will be opioid-naïve with chronic breathlessness due to heart or lung disease, cancer or post-coronavirus disease 2019. Participants will be randomised 1:1 to 5 mg oral modified-release morphine/placebo twice daily and docusate/placebo 100 mg twice daily for 56 days. Non-responders at Day 7 will dose escalate to 10 mg morphine/placebo twice daily at Day 15.

The primary end-point (Day 28) measure will be worst breathlessness severity (previous 24 h). Secondary outcome measures include worst cough, distress, pain, functional status, physical activity, quality of life, and early identification and management of morphine-related side-effects. At Day 56, participants may opt to take open-label, oral modified-release morphine as part of usual care and complete quarterly breathlessness and toxicity questionnaires.

The study is powered to be able to reject the null hypothesis and an embedded normalisation process theory-informed qualitative substudy will explore the adoption of morphine as a first-line pharmacological treatment for chronic breathlessness in clinical practice if effective.
Mental health: the new frontier for labour economics
Authors: Layard Richard
Published: June 2023

This lecture argues that mental health is a major factor of production. It is the biggest single influence on life satisfaction, with mental health eight years earlier a more powerful explanatory factor than current income. Mental health also affects earnings and educational success. But, most strikingly, it affects employment and physical health.

In advanced countries mental health problems are the main illness of working age – amounting to 40% of all illness under 65. They account for over one third of disability and absenteeism in advanced countries. They can also cause or exacerbate physical illness. It is estimated that in the absence of mental illness, the costs of physical healthcare for chronic diseases would be one third lower.

The good news is that cost-effective treatments for the most common mental illnesses now exist (both drugs and psychological therapy). But only a quarter of those who suffer are in treatment. Yet psychological therapy, such as cognitive behavioural therapy, if more widely available would pay for itself in savings on benefits and lost taxes.

The lecture ends by illustrating how rational policy can be made using life-course models of wellbeing. Such policies should include a much greater role for the treatment and prevention of mental illness.

Jel codes

I30, J30
eSPRESSO: topological clustering of single-cell transcriptomics data to reveal informative genes for spatio–temporal architectures of cells
Authors: Mori Tomoya , Takase Toshiro , Lan Kuan-Chun , Yamane Junko , Alev Cantas , Kimura Azuma , Osafune Kenji , Yamashita Jun K. , Akutsu Tatsuya , Kitano Hiroaki , Fujibuchi Wataru
Published: June 2023

Background

Bioinformatics capability to analyze spatio–temporal dynamics of gene expression is essential in understanding animal development. Animal cells are spatially organized as functional tissues where cellular gene expression data contain information that governs morphogenesis during the developmental process. Although several computational tissue reconstruction methods using transcriptomics data have been proposed, those methods have been ineffective in arranging cells in their correct positions in tissues or organs unless spatial information is explicitly provided.

Results

This study demonstrates stochastic self-organizing map clustering with Markov chain Monte Carlo calculations for optimizing informative genes effectively reconstruct any spatio–temporal topology of cells from their transcriptome profiles with only a coarse topological guideline. The method, eSPRESSO (enhanced SPatial REconstruction by Stochastic Self-Organizing Map), provides a powerful in silico spatio–temporal tissue reconstruction capability, as confirmed by using human embryonic heart and mouse embryo, brain, embryonic heart, and liver lobule with generally high reproducibility (average max. accuracy = 92.0%), while revealing topologically informative genes, or spatial discriminator genes. Furthermore, eSPRESSO was used for temporal analysis of human pancreatic organoids to infer rational developmental trajectories with several candidate ‘temporal’ discriminator genes responsible for various cell type differentiations.

Conclusions

eSPRESSO provides a novel strategy for analyzing mechanisms underlying the spatio–temporal formation of cellular organizations.
Use, satisfaction, and preference of online health services among older adults with multimorbidity in Hong Kong primary care during COVID-19
Authors: Xu Zijun , Zhang Dexing , Zheng Xiaoxiang , Lee Rym C.M. , Wong Samuel Y.S. , Wong Carmen K.M.
Published: June 2023

Background

The use of online and mobile internet and social media has been increasing in healthcare service delivery. However, there is limited literature on the acceptance and use of online health services for older adults with multimorbidity who require more medical care and assistance. This study aims to explore the use of social media in older adults with multimorbidity in Hong Kong primary care and to assess the feasibility and usage of online health services in this population, including satisfaction, preference, and problems encountered.

Methods

This is a cross-sectional study among older adults with multimorbidity conducted between November 2020 and March 2021 in a Hong Kong primary care programme. Online and face-to-face services were offered based on the needs of the participants. Demographic characteristics and health conditions were assessed at baseline. Participants using online services were invited to complete a feedback questionnaire.

Results

The study included 752 participants, of which 66.1% use social media every day. Participants who declined to use online services were found to be significantly older, live alone, have lower income, have social security assistance, have greater cognitive decline, and be less depressed (p < 0.05). Non-responders to the online questionnaire had fewer years of education and greater cognitive decline (p < 0.05). The median satisfaction with the online services was 8 (interquartile range: 7, 9), and 14.6% of the participants preferred online more than face-to-face services. Lower education levels, fewer internet connection issues, and more self-efficacy on mobile apps were associated with a higher level of online satisfaction after adjustment (p < 0.05). Fewer internet connection issues and more self-efficacy on mobile apps were associated with participants’ preference for online services (p < 0.05).

Conclusions

More than half of Hong Kong older adults with multimorbidity in primary care use social media daily. Internet connection issues can be a significant barrier to the usage of online services in this population. Prior use and training can be beneficial to enhance use and satisfaction in older adults.
Eukaryotic initiation factor 4 A-3 promotes glioblastoma growth and invasion through the Notch1-dependent pathway
Authors: Wei Lei , Pan Mika , Jiang Qiulan , Hu Beiquan , Zhao Jianyi , Zou Chun , Chen Liechun , Tang Chunhai , Zou Donghua
Published: June 2023

Background

As an adult tumor with the most invasion and the highest mortality rate, the inherent heterogeneity of glioblastoma (GBM) is the main factor that causes treatment failure. Therefore, it is important to have a deeper understanding of the pathology of GBM. Some studies have shown that Eukaryotic Initiation Factor 4A-3 (EIF4A3) can promote the growth of many people’s tumors, and the role of specific molecules in GBM remains unclear.

Methods

The correlation between the expression of EIF4A3 gene and its prognosis was studied in 94 GBM patients using survival analysis. Further in vitro and in vivo experiments, the effect of EIF4A3 on GBM cells proliferation, migration, and the mechanism of EIF4A3 on GBM was explored. In addition, combined with bioinformatics analysis, we further confirmed that EIF4A3 contributes to the progress of GBM.

Results

The expression of EIF4A3 was upregulated in GBM tissues, and high expression of EIF4A3 is associated with poor prognosis in GBM. In vitro, knockdown of EIF4A3 significantly reduced the proliferation, migration, and invasion abilities of GBM cells, whereas overexpression of EIF4A3 led to the opposite effect. The analysis of differentially expressed genes related to EIF4A3 indicates that it is involved in many cancer-related pathways, such as Notch and JAK-STAT3 signal pathway. In Besides, we demonstrated the interaction between EIF4A3 and Notch1 by RNA immunoprecipitation. Finally, the biological function of EIF4A3-promoted GBM was confirmed in living organisms.

Conclusion

The results of this study suggest that EIF4A3 may be a potential prognostic factor, and Notch1 participates in the proliferation and metastasis of GBM cells mediated by EIF4A3.
Comparison of cardiovascular disease risk in women with and without breast cancer: secondary data analysis with the 2014–2018 korean national health and nutrition examination survey
Authors: Choi Seongmi , Park Na-Jin , Kim Mihui , Song Kijun , Choi JiYeon
Published: June 2023

Background

Aging breast cancer survivors may be at an elevated risk of cardiovascular disease (CVD), but little is known about CVD risk assessment and breast cancer in Korean women. We hypothesized that Korean breast cancer survivors would have higher risks of future CVD within the next 10 years (i.e., Framingham Risk Score [FRS]) than women without cancer.

Objectives

(1) To compare FRS-based CVD risks in women with and without breast cancer based on propensity score matching; and (2) To explore adiposity-related measures in relation to FRS in Korean women with breast cancer.

Methods

Using the cross-sectional data from the 2014–2018 Korean National Health and National Survey (KNHANES), we identified 136 women with breast cancer aged 30–74 years who had no other cancer and no CVD. The comparison group of 544 women with no cancer were selected by 1:4 nearest-neighbor propensity score matching based on breast cancer diagnosis. CVD risk was assessed by FRS based on multiple traditional risk factors (e.g., cholesterol, blood pressure, diabetes, and smoking). Adiposity was measured by physical examination, including body mass index (BMI) and waist-to-height ratio (WHtR). Physical activity and health behaviors were assessed by self-reports.

Results

Women with breast cancer (mean age of 57 years) had similar FRS levels at a low-risk category (< 10%) to women with no cancer (4.9% vs. 5.5%). Breast cancer survivors (mean 8.5 survival years) presented at significantly lower levels of total cholesterol, BMI, and WHtR (all p values < 0.05) than their counterpart. Within the breast cancer group, WHtR ≥ 0.5 was associated with higher FRS, compared to WHtR < 0.5. FRS was not different by survival < 5 years or ≥ 5 years after breast cancer diagnosis.

Conclusions

FRS-based CVD risks were not different in Korean, mostly postmenopausal, women by breast cancer status. Whereas breast cancer survivors had even lower levels of lipid and adiposity measures than women without cancer, those values indicating borderline cardiometabolic risk suggest continued screening and management efforts for these aging women. Future studies are needed to examine longitudinal trajectories of CVD risk factors and CVD outcomes among Korean breast cancer survivors.
The causal effect of family physician program on the prevalence, screening, awareness, treatment, and control of hypertension and diabetes mellitus in an Eastern Mediterranean Region: a causal difference-in-differences analysis
Authors: Mohammadi Neda , Alizadeh Ahad , Moghaddam Sahar Saeedi , Ghasemi Erfan , Ahmadi Naser , Yaseri Mehdi , Rezaei Negar , Mansournia Mohammad Ali
Published: June 2023

Background

Hypertension (HTN) and diabetes mellitus (DM) as part of non-communicable diseases are among the most common causes of death worldwide, especially in the WHO’s Eastern Mediterranean Region (EMR). The family physician program (FPP) proposed by WHO is a health strategy to provide primary health care and improve the community’s awareness of non-communicable diseases. Since there was no clear focus on the causal effect of FPP on the prevalence, screening, and awareness of HTN and DM, the primary objective of this study is to determine the causal effect of FPP on these factors in Iran, which is an EMR country.

Methods

We conducted a repeated cross-sectional design based on two independent surveys of 42,776 adult participants in 2011 and 2016, of which 2301 individuals were selected from two regions where the family physician program was implemented (FPP) and where it wasn't (non-FPP). We used an Inverse Probability Weighting difference-in-differences and Targeted Maximum Likelihood Estimation analysis to estimate the average treatment effects on treated (ATT) using R version 4.1.1.

Results

The FPP implementation increased the screening (ATT = 36%, 95% CI: (27%, 45%), P-value < 0.001) and the control of hypertension (ATT = 26%, 95% CI: (1%, 52%), P-value = 0.03) based on 2017 ACC/AHA guidelines that these results were in keeping with JNC7. There was no causal effect in other indexes, such as prevalence, awareness, and treatment.

The DM screening (ATT = 20%, 95% CI: (6%, 34%), P-value = 0.004) and awareness (ATT = 14%, 95% CI: (1%, 27%), P-value = 0.042) were significantly increased among FPP administered region. However, the treatment of HTN decreased (ATT = -32%, 95% CI: (-59%, -5%), P-value = 0.012).

Conclusion

This study has identified some limitations related to the FPP in managing HTN and DM, and presented solutions to solve them in two general categories. Thus, we recommend that the FPP be revised before the generalization of the program to other parts of Iran.
Technical complications with tooth-supported fixed dental prostheses (FDPs) of different span lengths: an up to 15-year retrospective study
Authors: Alenezi Ali , Aloqayli Sarah
Published: June 2023

Backgrounds

Long-span dental bridges may cause excessive load on abutment teeth and the periodontal area, which may lead to bridge fractures or periodontal problems. However, some reports have revealed that short- and long-span bridges can provide a similar prognosis. This clinical study aimed to investigate the technical complications associated with fixed dental prostheses (FDPs) of different span lengths.

Methods

All patients with previously cemented FDPs were clinically examined during their follow-up visits. Several data related to FDPs were registered, such as design, material type, location, and type of complication. The main clinical factors analyzed were technical complications. Life table survival analyses were performed to calculate the cumulative survival rate of FDPs when technical complications were detected.

Results

The study examined 229 patients with a total number of 258 prostheses and an average of 98 months of follow-up. Seventy-four prostheses suffered from technical complications, and the most common complication was ceramic fracture or chipping (n = 66), while loss of retention occurred in 11 prostheses. The long-term evaluation of long-span prostheses revealed a significantly higher technical complication rate compared to short-span prostheses (P = ,003). The cumulative survival rate for short-span FDPs was 91% in year 5, 68% in year 10, and 34% in year 15. For long-span FDPs, the cumulative survival rate was 85% in year 5, 50% in year 10, and 18% in year 15.

Conclusion

Long-span prostheses (5 units or more) can be associated with a higher technical complication rate compared to short-span prostheses after long-term evaluation.
Young Sca-1+ bone marrow stem cell-derived exosomes preserve visual function via the miR-150-5p/MEKK3/JNK/c-Jun pathway to reduce M1 microglial polarization
Authors: Wang Yuan , Qin Wan-yun , Wang Qi , Liu Xin-na , Li Xiang-hui , Ye Xin-qi , Bai Ying , Zhang Yan , Liu Pan , Wang Xin-lin , Zhou Yu-hang , Yuan Hui-ping , Shao Zheng-bo
Published: June 2023

Background

Polarization of microglia, the resident retinal immune cells, plays important roles in mediating both injury and repair responses post-retinal ischemia–reperfusion (I/R) injury, which is one of the main pathological mechanisms behind ganglion cell apoptosis. Aging could perturb microglial balances, resulting in lowered post-I/R retinal repair. Young bone marrow (BM) stem cell antigen 1-positive (Sca-1+) cells have been demonstrated to have higher reparative capabilities post-I/R retinal injury when transplanted into old mice, where they were able to home and differentiate into retinal microglia.

Methods

Exosomes were enriched from young Sca-1+ or Sca-1− cells, and injected into the vitreous humor of old mice post-retinal I/R. Bioinformatics analyses, including miRNA sequencing, was used to analyze exosome contents, which was confirmed by RT-qPCR. Western blot was then performed to examine expression levels of inflammatory factors and underlying signaling pathway proteins, while immunofluorescence staining was used to examine the extent of pro-inflammatory M1 microglial polarization. Fluoro-Gold labelling was then utilized to identify viable ganglion cells, while H&E staining was used to examine retinal morphology post-I/R and exosome treatment.

Results

Sca-1+ exosome-injected mice yielded better visual functional preservation and lowered inflammatory factors, compared to Sca-1−, at days 1, 3, and 7 days post-I/R. miRNA sequencing found that Sca-1+ exosomes had higher miR-150-5p levels, compared to Sca-1− exosomes, which was confirmed by RT-qPCR. Mechanistic analysis found that miR-150-5p from Sca-1+ exosomes repressed the mitogen-activated protein kinase kinase kinase 3 (MEKK3)/JNK/c-Jun axis, leading to IL-6 and TNF-α downregulation, and subsequently reduced microglial polarization, all of which contributes to reduced ganglion cell apoptosis and preservation of proper retinal morphology.

Conclusion

This study elucidates a potential new therapeutic approach for neuroprotection against I/R injury, via delivering miR-150-5p-enriched Sca-1+ exosomes, which targets the miR-150-5p/MEKK3/JNK/c-Jun axis, thereby serving as a cell-free remedy for treating retinal I/R injury and preserving visual functioning.
The effect of cinnamon supplementation on glycemic control in patients with type 2 diabetes or with polycystic ovary syndrome: an umbrella meta-analysis on interventional meta-analyses
Authors: Zarezadeh Meysam , Musazadeh Vali , Foroumandi Elaheh , Keramati Majid , Ostadrahimi Alireza , Mekary Rania A.
Published: June 2023

Background

Several meta-analyses reported glycemic-lowering effects of cinnamon, while others reported conflicting findings. In the present study, we aimed to perform an umbrella meta-analysis of previous interventional meta-analyses on the effects of cinnamon on glycemic control in patients with type 2 diabetes (T2D) or with polycystic ovary syndrome (PCOS).

Methods

Relevant studies were searched in PubMed, Scopus, EMBASE, Web of Science, and Google Scholar up to June 2022. Meta-analyses of randomized clinical trials (RCTs) investigating the effects of cinnamon on glycemic indices including fasting plasma glucose (FPG), homeostatic model assessment for insulin resistance (HOMA-IR), insulin, and hemoglobin A1C (HbA1c) were included. Random-effects models were used to perform the umbrella meta-analysis and pool the weighted mean difference (WMD) or standardized mean difference (SMD) and their 95% confidence intervals (CI).

Results

Overall, 11 meta-analyses of RCTs were included. Cinnamon supplementation was effective in reducing serum FPG (WMD: -10.93 mg/dL; 95%CI: -16.22, -5.65; SMD: -0.86; 95%CI: -1.19, -0.52), insulin (WMD: -2.01 IU/mL; 95%CI: -3.96, -0.07; SMD: -0.61; 95%CI: -0.93, -0.30), HOMA-IR levels (WMD: -0.61; 95%CI: -0.91, -0.31; SMD: -0.78; 95%CI: -1.26, -0.30), and HbA1c (WMD: -0.10%; 95%CI: -0.17, -0.03).

Conclusion

Cinnamon can be used as an anti-diabetic agent and an add-on treatment to control glycemic indices among patients with T2D or PCOS.
H∞ observer-based sliding mode control for uncertain discrete-time singularly perturbed systems
Authors: Liu Wei , Que Xuejie , Wang Yanyan
Published: June 2023

This paper studies the sliding mode control (SMC) problem of discrete-time singularly perturbed systems (DTSPSs) with external perturbations and nonlinear inputs. First, to estimate the state of the original system, a novel state observer is constructed. Under this condition, the observer error system is ensured to be input-to-state stable (ISS) and satisfies the givenH∞ performance index. Then, an appropriate sliding mode control law is proposed to satisfy the reachability condition. On this basis, the ISS criterion for the sliding mode dynamics (SMDs) is given, and the controller gain matrix is also obtained. In addition, a feasible algorithm is given to compute the upper bound for the small parameter. Finally, two numerical examples are given to demonstrate the effectiveness of the proposed method.
Gene expression dynamics of natural assemblages of heterotrophic flagellates during bacterivory
Authors: Obiol Aleix , López-Escardó David , Salomaki Eric D. , Wiśniewska Monika M. , Forn Irene , Sà Elisabet , Vaqué Dolors , Kolísko Martin , Massana Ramon
Published: June 2023

Background

Marine heterotrophic flagellates (HF) are dominant bacterivores in the ocean, where they represent the trophic link between bacteria and higher trophic levels and participate in the recycling of inorganic nutrients for regenerated primary production. Studying their activity and function in the ecosystem is challenging since most of the HFs in the ocean are still uncultured. In the present work, we investigated gene expression of natural HF communities during bacterivory in four unamended seawater incubations.

Results

The most abundant species growing in our incubations belonged to the taxonomic groups MAST-4, MAST-7, Chrysophyceae, and Telonemia. Gene expression dynamics were similar between incubations and could be divided into three states based on microbial counts, each state displaying distinct expression patterns. The analysis of samples where HF growth was highest revealed some highly expressed genes that could be related to bacterivory. Using available genomic and transcriptomic references, we identified 25 species growing in our incubations and used those to compare the expression levels of these specific genes.

Conclusions

Our results indicate that several peptidases, together with some glycoside hydrolases and glycosyltransferases, are more expressed in phagotrophic than in phototrophic species, and thus could be used to infer the process of bacterivory in natural assemblages.
Formation of lower fast-spread oceanic crust: a structural and geochemical study of troctolites in the Hess Deep Rift (East Pacific Rise)
Authors: Akizawa Norikatsu , Godard Marguerite , Ildefonse Benoît , Arai Shoji
Published: June 2023

Troctolites were recovered during Integrated Ocean Drilling Program Expedition 345 at the Hess Deep Rift, next to fast-spreading East Pacific Rise. These troctolites are divided into three groups based on textural differences: coarse-grained (1–10 mm in length) troctolite, fine-grained (~ 2 mm in length) troctolite, and skeletal olivine-bearing troctolite. All troctolites exhibit a magmatic fabric. The major-element compositions of olivine, plagioclase, and clinopyroxene in the troctolites are intermediate between those of Hess Deep gabbros and harzburgites. The trace-element compositions of olivine, plagioclase, and clinopyroxene in the troctolites overlap with those of troctolites from slow-spread crust, but they record no petrographic evidence indicating assimilation of mantle peridotite. Thermodynamic calculation for mineral chemistry showed that fractional crystallization of melt is the dominant process responsible for the formation of the troctolites. The fine-grained troctolite was crystallized with high crystallization rate resulting from hot melt injection into colder wall gabbro. In contrast, interactions between the unsolidified troctolite containing interstitial melt and newly injected melt resulted in the formation of the skeletal olivine-bearing troctolite. While our results demonstrate that the troctolites exhibit multiple melt injections and partial dissolution of a troctolite precursor, fractional crystallization is the dominant process for the creation of the lower crust in the Hess Deep Rift.
Muscle Architecture Adaptations to Static Stretching Training: A Systematic Review with Meta-Analysis
Authors: Panidi Ioli , Donti Olyvia , Konrad Andreas , Dinas Petros C. , Terzis Gerasimos , Mouratidis Athanasios , Gaspari Vasiliki , Donti Anastasia , Bogdanis Gregory C.
Published: June 2023

Background

Long-term stretching of human skeletal muscles increases joint range of motion through altered stretch perception and decreased resistance to stretch. There is also some evidence that stretching induces changes in muscle morphology. However, research is limited and inconclusive.

Objective

To examine the effect of static stretching training on muscle architecture (i.e., fascicle length and fascicle angle, muscle thickness and cross-sectional area) in healthy participants.

Design

Systematic review and meta-analysis.

Methods

PubMed Central, Web of Science, Scopus, and SPORTDiscus were searched. Randomized controlled trials and controlled trials without randomization were included. No restrictions on language or date of publication were applied. Risk of bias was assessed using Cochrane RoB2 and ROBINS-I tools. Subgroup analyses and random-effects meta-regressions were also performed using total stretching volume and intensity as covariates. Quality of evidence was determined by GRADE analysis.

Results

From the 2946 records retrieved, 19 studies were included in the systematic review and meta-analysis (n = 467 participants). Risk of bias was low in 83.9% of all criteria. Confidence in cumulative evidence was high. Stretching training induces trivial increases in fascicle length at rest (SMD = 0.17; 95% CI 0.01–0.33; p = 0.042) and small increases in fascicle length during stretching (SMD = 0.39; 95% CI 0.05 to 0.74; p = 0.026). No increases were observed in fascicle angle or muscle thickness (p = 0.30 and p = 0.18, respectively). Subgroup analyses showed that fascicle length increased when high stretching volumes were used (p < 0.004), while no changes were found for low stretching volumes (p = 0.60; subgroup difference: p = 0.025). High stretching intensities induced fascicle length increases (p < 0.006), while low stretching intensities did not have an effect (p = 0.72; subgroup difference: p = 0.042). Also, high intensity stretching resulted in increased muscle thickness (p = 0.021). Meta-regression analyses showed that longitudinal fascicle growth was positively associated with stretching volume (p < 0.02) and intensity (p < 0.04).

Conclusions

Static stretching training increases fascicle length at rest and during stretching in healthy participants. High, but not low, stretching volumes and intensities induce longitudinal fascicle growth, while high stretching intensities result in increased muscle thickness.

Registration

PROSPERO, registration number: CRD42021289884.
What are the core recommendations for gout management in first line and specialist care? Systematic review of clinical practice guidelines
Authors: Conley Brooke , Bunzli Samantha , Bullen Jonathan , O’Brien Penny , Persaud Jennifer , Gunatillake Tilini , Dowsey Michelle M , Choong Peter F , Nikpour Mandana , Grainger Rebecca , Lin Ivan
Published: June 2023

Background

Gout is the most common inflammatory arthritis, increasing in prevalence and burden. Of the rheumatic diseases, gout is the best-understood and potentially most manageable condition. However, it frequently remains untreated or poorly managed. The purpose of this systematic review is to identify Clinical Practice Guidelines (CPG) regarding gout management, evaluate their quality, and to provide a synthesis of consistent recommendations in the high-quality CPGs.

Methods

Gout management CPGs were eligible for inclusion if they were (1) written in English and published between January 2015-February 2022; focused on adults aged ≥ 18 years of age; and met the criteria of a CPG as defined by the Institute of Medicine; and (2) were rated as high quality on the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Gout CPGs were excluded if they required additional payment to access; only addressed recommendations for the system/organisation of care and did not include interventional management recommendations; and/or included other arthritic conditions. OvidSP MEDLINE, Cochrane, CINAHL, Embase and Physiotherapy Evidence Database (PEDro) and four online guideline repositories were searched.

Results

Six CPGs were appraised as high quality and included in the synthesis. Clinical practice guidelines consistently recommended education, commencement of non-steroidal anti-inflammatories, colchicine or corticosteroids (unless contraindicated), and assessment of cardiovascular risk factors, renal function, and co-morbid conditions for acute gout management. Consistent recommendations for chronic gout management were urate lowering therapy (ULT) and continued prophylaxis recommended based on individual patient characteristics. Clinical practice guideline recommendations were inconsistent on when to initiate ULT and length of ULT, vitamin C intake, and use of pegloticase, fenofibrate and losartan.

Conclusion

Management of acute gout was consistent across CPGs. Management of chronic gout was mostly consistent although there were inconsistent recommendations regarding ULT and other pharmacological therapies. This synthesis provides clear guidance that can assist health professionals to provide standardised, evidence-based gout care.

Trial registration

The protocol for this review was registered with Open Science Framework (DOI https://doi.org/10.17605/OSF.IO/UB3Y7).
Smallholder farmers’ knowledge, attitudes and practices towards biological control of papaya mealybug in Kenya
Authors: Constantine Kate , Makale Fernadis , Mugambi Idah , Rware Harrison , Chacha Duncan , Lowry Alyssa , Rwomushana Ivan , Williams Frances
Published: June 2023

Background

Farmer perceptions are highly important in influencing on-farm pest management decision-making. Biological control is extremely sustainable in the smallholder production context, but in Sub Saharan Africa (SSA) few attempts using this pest control method for arthropod pests have been successful, with one of the key reasons cited as poor involvement of farming communities and extension in the dissemination of information. Although farmers’ knowledge and attitudes are hugely important for the successful implementation of biological control, they are often disregarded. Papaya mealybug (Paracoccus marginatus) (PMB) has rapidly spread and established in suitable areas across Kenya becoming a serious pest. The objective of this study is to determine smallholder farmers’ knowledge, attitudes and practices towards biological control; farmers’ willingness to reduce their chemical pesticide use; and levels of support for a classical biological control initiative for PMB management.

Methods

Household surveys were conducted covering 383 farming households (148 women) in four papaya producing counties in Kenya alongside key informant interviews with eight extension agents and thirty agro-dealers, and eight focus group discussions.

Results

Although some farmers demonstrated awareness of the concept of biological control they lacked knowledge, experience and technical support from extension or agro-dealers. Reasons for not using biological control included inadequate awareness and concerns over efficacy and safety. Farmers expressed high levels of interest and willingness to support biological control, and were willing to reduce their chemical pesticide use to help conserve, and support the establishment of natural enemies. County, perception of biological as safe, training in IPM and gender were all highly significant factors determining farmers willingness to support biological control.

Conclusions

Previously, poor attention has been paid to farmer perceptions and participation in biological control, which has resulted in limited success in developing countries. With high levels of interest and willingness to support biological control, the next step is to engage with farming communities impacted by PMB. By building awareness and capacity, and developing a management plan with farmers that will support the release and establishment of the biological control agent, Acerophagus papayae, long-term, sustainable control of PMB in Kenya is possible.
Clinical Multigene Panel Testing Identifies Racial and Ethnic Differences in Germline Pathogenic Variants Among Patients With Early-Onset Colorectal Cancer
Authors: Seagle Hannah M. , Keller Samantha R. , Tavtigian Sean V. , Horton Carolyn , Holowatyj Andreana N.
Published: June 2023

PURPOSE

The early-onset colorectal cancer (EOCRC) burden differs across racial/ethnic groups, yet the role of germline genetic predisposition in EOCRC disparities remains uncharacterized. We defined the prevalence and spectrum of inherited colorectal cancer (CRC) susceptibility gene variations among patients with EOCRC by race and ethnicity.

PATIENTS AND METHODS

We included individuals diagnosed with a first primary CRC between age 15 and 49 years who identified as Ashkenazi Jewish, Asian, Black, Hispanic, or White and underwent germline genetic testing of 14 CRC susceptibility genes performed by a clinical testing laboratory. Variant comparisons by racial and ethnic groups were evaluated using chi-square tests and multivariable logistic regression adjusted for sex, age, CRC site, and number of primary colorectal tumors.

RESULTS

Among 3,980 patients with EOCRC, a total of 530 germline pathogenic or likely pathogenic variants were identified in 485 individuals (12.2%). By race/ethnicity, 12.7% of Ashkenazim patients, 9.5% of Asian patients, 10.3% of Black patients, 14.0% of Hispanic patients, and 12.4% of White patients carried a germline variant. The prevalence of Lynch syndrome ( P = .037), as well as APC, CHEK2, MLH1, monoallelic MUTYH, and PTEN variants, varied by race/ethnicity among patients with EOCRC (all P < .026). Ashkenazim and Hispanic patients had significantly higher odds of presenting with a pathogenic APC variant, which included p.I1307K (odds ratio [OR], 2.67; 95% CI, 1.30 to 5.49; P = .007) and MLH1 variant (OR, 8.69; 95% CI, 2.68 to 28.20; P = .0003), respectively, versus White patients in adjusted models.

CONCLUSION

Germline genetic features differed by race/ethnicity in young patients with CRC, suggesting that current multigene panel tests may not be representative of EOCRC risk in diverse populations. Further study is needed to optimize genes selected for genetic testing in EOCRC via ancestry-specific gene and variant discovery to yield equitable clinical benefits for all patients and to mitigate inequities in disease burden.
Ambedkar's Śūnyatā and the Impermanence of the Theologico-Political
Authors: Sperner Philipp
Published: June 2023

This article engages with B. R. Ambedkar as political philosopher and key contributor to debates on global democracy and the genealogy of democratic ideas outside the West. I focus specifically on Ambedkar's use of Buddhist philosophy and the concept of śūnyatā (emptiness/impermanence), which plays a central role in his search for a nontheological democratic politics. In order to explore the implications of such a politics, the article brings Ambedkar into conversation with Claude Lefort and his theorization of the relationships between politics, religion, and democracy. Through this reading, Ambedkar's political philosophy becomes legible not only as a profound challenge to what Lefort has called the “permanence of the theologico-political” but also as a radical way of combining everyday political practice with an emphatic notion of negative identity.
Concretion
Authors: Quigley Killian
Published: June 2023

The ruins of wrecked ships are often so thoroughly dispersed by their submarine environments as to practically vanish. Sometimes, however, the conditions of a wreck's submergence create complex modes of material endurance. Concretion, which names both a substance that forms on certain immersed surfaces and the phenomenon of that substance's formation, is one such mode. Inspired by maritime-archeological objects and practices, this article asks how concretion—from the Latin concrēscĕre for “to grow together”—marks and reworks imperial (and other) presences at the seabed. The article develops a hermeneutics of benthic becoming at intersections in literary studies, critical theory, cultural geography, and recent subsea turns in the oceanic (and more broadly environmental) humanities. Wrecky concretion, I argue, configures the thickening presences of empire's remains in the course of their underwater lives and in company with seawater, marine organisms, and inanimate beings. In this way, manifestly imperial presences actively coincide with others—and with the agencies, memories, and affects such presences may be understood to express (and not). Pivotally informed by Édouard Glissant's critical deeps, Derek Walcott's “The Sea Is History” (1978), and the politics of memory enacted by the Slave Wrecks Project and Diving with a Purpose, I observe a few of the ways that concretion may be punctuating and revising oceanic spaces, memories, and times. If the world ocean has long been unevenly composed by modernity, capitalism, and empire, it has also been reforming the wrecked stuff it receives into unanticipated configurations, growings-together that these pages provisionally ascertain.
Computational Mechanistic Study on Intramolecular Triple Cyclization of 1-Biphenylethynyl-2-phenylethynylbenzenes Giving Spiro Fluorene-Phenylenevinylenes by Dual Catalysis
Authors: Nagashima Yuki , Ouchi Seiya , Inoue Tomonori , Tanaka Ken
Published: June 2023

Cationic Au(I) complex-catalyzed double cyclizations of 1,2-dialkynylbenzene derivatives are valuable for the straightforward synthesis of ladder-type π-conjugated compounds. We have previously developed a method for synthesizing ladder-type π-conjugated molecules with spiro skeleton (spiro fluorene-phenylene vinylenes) by the triple cyclization of 1-biphenylethynyl-2-phenylethynylbenzenes using an AuCl(SMe2)/tBuXPhos/AgNTf2 catalyst system. Experimental mechanistic studies revealed that an Ag(I) complex or HNTf2, as well as a cationic Au(I) complex, catalyzes different reaction steps. However, detailed insight into which of the Ag(I) complex or HNTf2 functions as the actual cocatalyst and the origin of the selectivity of the reaction have not been elucidated. Here we report a detailed reaction mechanism for this triple cyclization by dual catalysis based on computational studies. A cationic Au(I) complex catalyzes the first and second cyclization steps, whose regioselectivity is thermodynamically and kinetically controlled. The third spirocyclization step to construct a spirocenter is catalyzed by in situ generated HNTf2 rather than an Au(I) or Ag(I) complex via a benzyl cation intermediate. The present Au(I)/Brønsted acid dual-catalyzed mechanism of the triple cyclization of 1-biphenylethynyl-2-phenylethynylbenzenes provides complimentary activation modes to the conventionally used single Au(I)-catalyzed one.